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Side effects of sulfamethoxazole-tmp: Sulfamethoxazole And Trimethoprim (Oral Route) Side Effects

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Sulfamethoxazole And Trimethoprim (Oral Route) Side Effects

Side Effects

Drug information provided by: IBM Micromedex

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

  1. Black, tarry stools

  2. blistering, peeling, or loosening of the skin

  3. changes in skin color

  4. chest pain or tightness

  5. chills

  6. clay-colored stools

  7. cough or hoarseness

  8. dark urine

  9. diarrhea

  10. dizziness

  11. fever

  12. general feeling of tiredness or weakness

  13. headache

  14. itching, skin rash

  15. joint or muscle pain

  16. light-colored stools

  17. loss of appetite

  18. lower back or side pain

  19. nausea

  20. pain, tenderness, or swelling of the foot or leg

  21. painful or difficult urination

  22. pale skin

  23. red skin lesions, often with a purple center

  24. red, irritated eyes

  25. sore throat

  26. sores, ulcers, or white spots in the mouth or on the lips

  27. stomach pain

  28. swollen or painful glands

  29. trouble breathing

  30. unpleasant breath odor

  31. unusual bleeding or bruising

  32. vomiting of blood

  33. yellow eyes or skin
Incidence not known

  1. Back, leg, or stomach pains

  2. bleeding gums

  3. blindness or vision changes

  4. bloating

  5. blood in the urine or stools

  6. bluish-colored lips, fingernails, or palms

  7. burning, crawling, itching, numbness, painful, prickling, “pins and needles”, or tingling feelings

  8. burning of the face or mouth

  9. cloudy urine

  10. clumsiness or unsteadiness

  11. confusion

  12. constipation

  13. continuing ringing or buzzing or other unexplained noise in the ears

  14. cracks in the skin

  15. decreased frequency or amount of urine

  16. difficulty with swallowing

  17. fainting spells

  18. fast, pounding, or irregular heartbeat or pulse

  19. general body swelling

  20. general feeling of discomfort or illness

  21. hair loss

  22. hearing loss

  23. hives

  24. increased thirst

  25. indigestion

  26. large, flat, blue, or purplish patches in the skin

  27. large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

  28. loss of heat from the body

  29. muscle or joint pain

  30. nosebleeds

  31. not able to pass urine

  32. numbness or tingling in the hands, feet, or lips

  33. pain or burning while urinating

  34. pinpoint red spots on the skin

  35. puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue

  36. raised red swellings on the skin, the buttocks, legs, or ankles

  37. redness of the white part of the eyes

  38. redness, swelling, or soreness of the tongue

  39. seizures

  40. soreness of the muscles

  41. stiff neck or back

  42. stomach tenderness

  43. swelling of the face, hands, legs, and feet

  44. unsteadiness, trembling, or other problems with muscle control or coordination

  45. weakness in the hands or feet

  46. weakness or heaviness of the legs

  47. weight gain or loss

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  1. Passing of gas
Incidence not known

  1. Discouragement

  2. feeling of constant movement of self or surroundings

  3. feeling sad or empty

  4. increased sensitivity of the skin to sunlight

  5. lack of feeling or emotion

  6. loss of interest or pleasure

  7. muscle pain, stiffness, cramps, or spasms

  8. nervousness

  9. redness or other discoloration of the skin

  10. seeing, hearing, or feeling things that are not there

  11. sensation of spinning

  12. severe sunburn

  13. trouble concentrating

  14. trouble sleeping

  15. uncaring

  16. weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

 

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Portions of this document last updated: June 01, 2021

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Sulfamethoxazole-TMP DS Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Nausea, vomiting, diarrhea, and loss of appetite may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: muscle weakness, mental/mood changes, signs of kidney problems (such as change in the amount of urine, blood in the urine), extreme drowsiness, signs of low blood sugar (such as sudden sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, or tingling hands/feet).

Get medical help right away if you have any very serious side effects, including: persistent headache, neck stiffness, seizures, slow/irregular heartbeat.

This medication may rarely cause serious (possibly fatal) allergic reactions and other side effects such as a severe peeling skin rash (such as Stevens-Johnson syndrome), blood disorders (such as agranulocytosis, aplastic anemia), liver damage, or lung injury. If you notice any of the following, get medical help right away: skin rash/blisters, itching/swelling (especially of the face/tongue/throat), persistent sore throat or fever, new or worsening lymph node swelling, paleness, joint pain/aches, persistent cough, trouble breathing, easy bleeding/bruising, yellowing eyes or skin, persistent nausea/vomiting, unusual fatigue, dark urine.

This medication may rarely cause a severe intestinal condition due to a bacteria called C. difficile. This condition may occur during treatment or weeks to months after treatment has stopped. Tell your doctor right away if you develop: diarrhea that doesn’t stop, abdominal or stomach pain/cramping, blood/mucus in your stool.

If you have these symptoms, do not use anti-diarrhea or opioid products because they may make symptoms worse.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new yeast infection. Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US –

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Sulfamethoxazole; Trimethoprim, SMX-TMP tablets

What is this medicine?

SULFAMETHOXAZOLE; TRIMETHOPRIM or SMX-TMP (suhl fuh meth OK suh zohl; trye METH oh prim) is a combination of a sulfonamide antibiotic and a second antibiotic, trimethoprim. It is used to treat or prevent certain kinds of bacterial infections. It will not work for colds, flu, or other viral infections.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

COMMON BRAND NAME(S): Bacter-Aid DS, Bactrim, Bactrim DS, Septra, Septra DS

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:

  • anemia
  • asthma
  • being treated with anticonvulsants
  • if you frequently drink alcohol containing drinks
  • kidney disease
  • liver disease
  • low level of folic acid or glucose-6-phosphate dehydrogenase
  • poor nutrition or malabsorption
  • porphyria
  • severe allergies
  • thyroid disorder
  • an unusual or allergic reaction to sulfamethoxazole, trimethoprim, sulfa drugs, other medicines, foods, dyes, or preservatives
  • pregnant or trying to get pregnant
  • breast-feeding

How should I use this medicine?

Take this medicine by mouth with a full glass of water. Follow the directions on the prescription label. Take your medicine at regular intervals. Do not take it more often than directed. Do not skip doses or stop your medicine early.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed. This medicine has been used in children as young as 2 months of age.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.

NOTE: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What may interact with this medicine?

Do not take this medicine with any of the following medications:

  • aminobenzoate potassium
  • dofetilide
  • metronidazole

This medicine may also interact with the following medications:

  • ACE inhibitors like benazepril, enalapril, lisinopril, and ramipril
  • birth control pills
  • cyclosporine
  • digoxin
  • diuretics
  • indomethacin
  • medicines for diabetes
  • methenamine
  • methotrexate
  • phenytoin
  • potassium supplements
  • pyrimethamine
  • sulfinpyrazone
  • tricyclic antidepressants
  • warfarin

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Tell your doctor or health care professional if your symptoms do not improve. Drink several glasses of water a day to reduce the risk of kidney problems.

Do not treat diarrhea with over the counter products. Contact your doctor if you have diarrhea that lasts more than 2 days or if it is severe and watery.

This medicine can make you more sensitive to the sun. Keep out of the sun. If you cannot avoid being in the sun, wear protective clothing and use a sunscreen. Do not use sun lamps or tanning beds/booths.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:

  • allergic reactions like skin rash or hives, swelling of the face, lips, or tongue
  • breathing problems
  • fever or chills, sore throat
  • irregular heartbeat, chest pain
  • joint or muscle pain
  • pain or difficulty passing urine
  • red pinpoint spots on skin
  • redness, blistering, peeling or loosening of the skin, including inside the mouth
  • unusual bleeding or bruising
  • unusually weak or tired
  • yellowing of the eyes or skin

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

  • diarrhea
  • dizziness
  • headache
  • loss of appetite
  • nausea, vomiting
  • nervousness

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 20 to 25 degrees C (68 to 77 degrees F). Protect from light. Throw away any unused medicine after the expiration date.

NOTE: This sheet is a summary. It may not cover all possible information. If you have questions about this medicine, talk to your doctor, pharmacist, or health care provider.

Sulfamethoxazole (SMZ-TMP) | Children’s Pittsburgh

SMZ-TPM Synonyms

Sulfamethoxazole with trimethoprim is also sometimes referred to as SMZ/TMP.

What Is SMZ-TPM?

Sulfamethoxazole with trimethoprim (Bactrim®, Septra®) is a combination antibiotic used to treat infections in children who have had liver transplants. It is also used to prevent and treat Pneumocystis carinii pneumonia.

SMZ-TPM Dosage

Sulfamethoxazole with trimethoprim is taken orally or given by injection, The oral form is available as single-strength (80/400-mg) or double-strength (160/800-mg) tablets, or as a liquid.

How to Properly Take SMZ-TPM

This medication can be taken with or without food. Your child’s doctor will usually recommend taking this medication with a glass of water. Your child should also drink several additional glasses of water daily, unless otherwise directed.

Missed Doses

If your child misses a dose, it should be taken as soon as you or your child remembers. If it is within two hours of the time for the next dose, however, skip the missed dose and resume your child’s usual dosing schedule. Do not double the dose to catch up.

SMZ-TPM Side Effects

If your child has an upset stomach when taking this medication, it may be helpful to give food or milk with each dose.

Limit your child’s exposure to the sun while he or she is taking this medication. Sulfamethoxazole with trimethoprim can also cause sensitivity to sunlight. If your child must be outside for a long period, he or she should wear protective clothing, such as a hat and sunglasses, and use a sunscreen with a sun protection factor (SPF) of at least 15. Make sure the sunscreen your child uses does not contain PABA oil. PABA can interfere with the action of sulfamethoxazole with trimethoprim.

You may notice that your child has less of an appetite than usual. Sometimes, people taking this medication experience headaches, nausea, or vomiting.

Tell your transplant doctor or transplant coordinator right away if your child develops any of these rare SMZ-TPM side effects:

  • Skin rash
  • Difficulty breathing
  • Itching
  • Hives
  • Chills
  • Fever
  • Sore throat
  • Aching of joints or muscles
  • Easy bleeding or bruising
  • Yellowing of the eyes or skin
  • Peeling skin
  • Tiredness

SMZ-TPM Drug Interactions

Tell your doctor or pharmacist about any prescription or over-the-counter medications that your child is taking, so you can be warned of interactions and prevent them.

Precautions for Children

Your child should not stop taking this medication unless advised to do so by a transplant surgeon or your coordinator. Notify your doctor if your child has an allergy to sulfa drugs.

SMZ-TPM Storage

Store at room temperature.

Sulfamethaxazole with Trimethoprim Availability

Most pharmacies stock sulfamethoxazole with trimethoprim.

Drug information changes periodically. For the most updated information on drugs, visit www.drugs.com.

Sulfamethoxazole and Trimethoprim: Pediatric Medication

This information from Lexicomp® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider.

Brand Names: US

Bactrim; Bactrim DS; Sulfatrim Pediatric

Brand Names: Canada

APO-Sulfatrim; Septra; Sulfatrim; Sulfatrim DS; Sulfatrim Pediatric; TEVA-Trimel; TEVA-Trimel DS

What is this drug used for?

  • It is used to treat or prevent bacterial infections.

What do I need to tell the doctor BEFORE my child takes this drug?

  • If your child is allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell the doctor about the allergy and what signs your child had.
  • If your child has anemia caused by a lack of folic acid.
  • If your child has any of these health problems: Kidney disease or liver disease.
  • If your child has any of these health problems: Asthma, porphyria, thyroid disease, not enough folate in the body, poor absorption, or poor nutrition.
  • If your child has been drinking alcohol for a long time or is taking a drug for seizures.
  • If your child has ever had a low platelet count when using trimethoprim or a sulfa (sulfonamide) drug.
  • If your child is taking any of these drugs: Amantadine, cyclosporine, dofetilide, indomethacin, leucovorin, methotrexate, pyrimethamine, or a water pill.
  • If your child is taking or has recently taken any of these drugs: Benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, or trandolapril.
  • If your child is younger than 2 months of age. Do not give this drug to an infant younger than 2 months of age.

This is not a list of all drugs or health problems that interact with this drug.

Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe to give this drug with all of your child’s other drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.

What are some things I need to know or do while my child takes this drug?

All products:

  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child’s blood work and other lab tests checked as you have been told by the doctor.
  • This drug may affect certain lab tests. Tell all of your child’s health care providers and lab workers that your child takes this drug.
  • Do not give to your child longer than you have been told. A second infection may happen.
  • Be careful if your child has G6PD deficiency. Anemia may happen.
  • If your child has high blood sugar (diabetes), you will need to watch your child’s blood sugar closely.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • This drug may make your child sunburn more easily. Use care if your child will be in the sun. Tell your child’s doctor if your child sunburns easily while taking this drug.
  • A severe and sometimes deadly reaction has happened. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. If you have questions, talk with the doctor.

If your child is pregnant or breast-feeding a baby:

  • This drug may cause harm to the unborn baby if your child takes it during pregnancy. If your child is pregnant or gets pregnant while taking this drug, call the doctor right away.
  • Tell the doctor if your child is breast-feeding a baby. You will need to talk about any risks to the baby.

Injection:

  • If your child is allergic to sulfites, talk with your child’s doctor. Some products have sulfites in them.
  • This drug has propylene glycol in it. Too much propylene glycol may lead to very bad health problems like nervous system problems, kidney problems, or other organ problems. If you have questions, talk with the doctor.
  • Some products have benzyl alcohol. Do not give a product that has benzyl alcohol in it to a newborn or infant. Talk with the doctor to see if this product has benzyl alcohol in it.

What are some side effects that I need to call my child’s doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:

All products:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of high potassium levels like a heartbeat that does not feel normal; feeling confused; feeling weak, lightheaded, or dizzy; feeling like passing out; numbness or tingling; or shortness of breath.
  • Signs of low blood sugar like dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of low sodium levels like headache, trouble focusing, memory problems, feeling confused, weakness, seizures, or change in balance.
  • Signs of lung or breathing problems like shortness of breath or other trouble breathing, cough, or fever.
  • Muscle or joint pain.
  • Purple patches on the skin or mouth.
  • Hallucinations (seeing or hearing things that are not there).
  • Depression or other mood changes.
  • A burning, numbness, or tingling feeling that is not normal.
  • Ringing in ears.
  • Swollen gland.
  • Chest pain.
  • Very bad dizziness or passing out.
  • Diarrhea is common with antibiotics. Rarely, a severe form called C diff–associated diarrhea (CDAD) may happen. Sometimes, this has led to a deadly bowel problem. CDAD may happen during or a few months after taking antibiotics. Call your child’s doctor right away if your child has stomach pain, cramps, or very loose, watery, or bloody stools. Check with your child’s doctor before treating diarrhea.
  • Rarely, very bad effects have happened with sulfa drugs. Sometimes, these have been deadly. These effects have included liver problems, blood problems, and very bad skin reactions (Stevens-Johnson syndrome/toxic epidermal necrolysis). Call the doctor right away if your child has a rash; red, swollen, blistered, or peeling skin; red or irritated eyes; sores in the mouth, throat, nose, or eyes; fever, chills, or sore throat; cough that is new or worse; feeling very tired or weak; any bruising or bleeding; or signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • This drug may raise the chance of a very bad brain problem called aseptic meningitis. Call the doctor right away if your child has a headache, fever, chills, very upset stomach or throwing up, stiff neck, rash, bright lights bother the eyes, feeling sleepy, or feeling confused.

Injection:

  • This drug may irritate the vein. If the drug leaks from the vein, it may also cause irritation around that area. Tell your child’s nurse if your child has any redness, burning, pain, swelling, or leaking of fluid where the drug is going into your child’s body.

What are some other side effects of this drug?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:

  • Diarrhea, upset stomach, or throwing up.
  • Not hungry.

These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.

You may report side effects to your national health agency.

How is this drug best given?

Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.

All oral products:

  • Give this drug with or without food. Give with food if it causes an upset stomach.
  • Give this drug with a full glass of water.
  • Give this drug at the same time of day.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
  • Have your child drink lots of noncaffeine liquids every day unless told to drink less liquid by your child’s doctor.

Liquid (suspension):

  • Shake well before use.
  • Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug.

Injection:

  • It is given as an infusion into a vein over a period of time.
  • Have your child drink lots of noncaffeine liquids every day unless told to drink less liquid by your child’s doctor.

What do I do if my child misses a dose?

All oral products:

  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.

Injection:

  • Call your child’s doctor to find out what to do.

How do I store and/or throw out this drug?

All oral products:

  • Store at room temperature protected from light. Store in a dry place. Do not store in a bathroom.

Injection:

  • If you need to store this drug at home, talk with your child’s doctor, nurse, or pharmacist about how to store it.

All products:

  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.

General drug facts

  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Consumer Information Use and Disclaimer

This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider’s examination and assessment of a patient’s specific and unique circumstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof. The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

Last Reviewed Date

2021-05-12

Copyright

© 2021 UpToDate, Inc. and its affiliates and/or licensors. All rights reserved.

Sulfamethoxazole and Trimethoprim | Memorial Sloan Kettering Cancer Center

This information from Lexicomp® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider.

Brand Names: US

Bactrim; Bactrim DS; Sulfatrim Pediatric

Brand Names: Canada

APO-Sulfatrim; Septra; Sulfatrim; Sulfatrim DS; Sulfatrim Pediatric; TEVA-Trimel; TEVA-Trimel DS

What is this drug used for?

  • It is used to treat or prevent bacterial infections.

What do I need to tell my doctor BEFORE I take this drug?

For all patients taking this drug:

  • If you are allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
  • If you have anemia caused by a lack of folic acid.
  • If you have any of these health problems: Kidney disease or liver disease.
  • If you have any of these health problems: Asthma, porphyria, thyroid disease, not enough folate in the body, poor absorption, or poor nutrition.
  • If you have been drinking alcohol for a long time or are taking a drug for seizures.
  • If you have ever had a low platelet count when using trimethoprim or a sulfa (sulfonamide) drug.
  • If you are taking any of these drugs: Amantadine, cyclosporine, dofetilide, indomethacin, leucovorin, methotrexate, or pyrimethamine.
  • If you are taking or have recently taken any of these drugs: Benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, or trandolapril.
  • If you are taking a water pill.

Children:

  • If your child is younger than 2 months of age. Do not give this drug to an infant younger than 2 months of age.

This is not a list of all drugs or health problems that interact with this drug.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take this drug?

All products:

  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Have your blood work and other lab tests checked as you have been told by your doctor.
  • This drug may affect certain lab tests. Tell all of your health care providers and lab workers that you take this drug.
  • Do not use longer than you have been told. A second infection may happen.
  • Be careful if you have G6PD deficiency. Anemia may happen.
  • If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
  • Talk with your doctor before you drink alcohol.
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  • Rarely, very bad effects have happened with sulfa drugs. Sometimes, these have been deadly. These effects have included liver problems, blood problems, and very bad skin reactions (Stevens-Johnson syndrome/toxic epidermal necrolysis). Call your doctor right away if you have a rash; red, swollen, blistered, or peeling skin; red or irritated eyes; sores in your mouth, throat, nose, or eyes; fever, chills, or sore throat; cough that is new or worse; feeling very tired or weak; any bruising or bleeding; or signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
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Injection:

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Injection:

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What are some other side effects of this drug?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

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These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

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General drug facts

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Trimethoprim-Sulfamethoxazole Revisited | Infectious Diseases | JAMA Internal Medicine

During the past 3 decades, the combination of trimethoprim and sulfamethoxazole has occupied a central role in the treatment of various commonly encountered infections and has also been particularly useful for several specific clinical conditions. However, changing resistance patterns and the introduction of newer broad-spectrum antibiotics have led to the need to carefully redefine the appropriate use of this agent in clinical practice. While trimethoprim-sulfamethoxazole’s traditional role as empirical therapy for several infections has been modified by increasing resistance, it remains a highly useful alternative to the new generation of expanded-spectrum agents if resistance patterns and other clinical variables are carefully considered. It also seems to have an increasing role as a cost-effective pathogen-directed therapy with the potential to decrease or delay development of resistance to newer antibiotics used for empirical treatment. In addition, trimethoprim-sulfamethoxazole continues to be the drug of choice for several clinical indications.

Many new antibiotics offer an expanded spectrum of in vitro antimicrobial susceptibility and an improved toxicity profile compared with older agents. However, the threat of development of resistant organisms from selection pressure and the high cost of these drugs raise significant concerns about their widespread use. Furthermore, in many instances, less expensive conventional antibiotics may be therapeutically equivalent in clinical practice. With a renewed interest in appropriate antibiotic use for common infections1 and the current focus on providing cost-conscious health care, this article examines the combination of trimethoprim and sulfamethoxazole to redefine its therapeutic role in relation to newer antimicrobial agents in the face of resistance trends and adverse effect profiles.

The concept of using the fixed combination of trimethoprim and sulfamethoxazole resulted from the recognition that bacteria are obligate folic acid synthesizers, while humans obtain folate through dietary sources.

Trimethoprim and sulfamethoxazole inhibit bacterial synthesis of tetrahydrofolic acid, the physiologically active form of folic acid and a necessary cofactor in the synthesis of thymidine, purines, and bacterial DNA (Figure 1). Sulfamethoxazole, a sulfonamide drug, is a structural analogue of para-aminobenzoic acid and inhibits synthesis of the intermediary dihydrofolic acid from its precursors. Trimethoprim is a structural analogue of the pteridine portion of dihydrofolic acid that competitively inhibits dihydrofolate reductase and, consequently, the production of tetrahydrofolic acid from dihydrofolic acid. This sequential blockade of 2 enzymes in one pathway results in an effective bactericidal action.

The drug was introduced in the late 1960s based on several potential advantages of the combination of these 2 components over each one individually. The sequential blockade of the bacterial folate synthesis pathway produces in vitro synergism,2-4 and it was postulated that such synergy would occur in vivo. It was also hoped that the use of 2 agents in a single pathway would prevent the development of bacterial resistance to either component alone.4

However, the clinical relevance of synergy has been questioned by studies5,6 of urinary tract infections (UTIs) and respiratory tract infections in which trimethoprim alone seems to be as efficacious as the combination product. In addition, emerging sulfonamide resistance and the finding that the activity of the trimethoprim component is the strongest determinant of efficacy of the antibiotic7 call into question the protection from resistance provided by the combination product.8

Despite these concerns, situations exist in which there is variable antimicrobial susceptibility to both components. In these cases, synergy and the ability of the combination product to potentially decrease the development of resistance may be important factors in determining the clinical efficacy of the drug.8


Pharmacological characteristics

The optimal ratio of the concentration of the 2 drugs for potential synergy has been determined to be 20 parts of sulfamethoxazole to 1 part of trimethoprim.3 Thus, available preparations are manufactured in a 1:5 fixed ratio of trimethoprim to sulfamethoxazole that results in peak serum concentrations of both drugs at levels in the desired synergistic ratio.

Trimethoprim-sulfamethoxazole is available in oral and intravenous preparations. The standard single-strength tablet contains 80 mg of trimethoprim and 400 mg of sulfamethoxazole, and the more clinically used double-strength tablet contains 160 mg of trimethoprim and 800 mg of sulfamethoxazole.

When taken orally, both components are well absorbed from the gastrointestinal (GI) tract and may be administered without regard to food or other medications. However, trimethoprim is absorbed more rapidly than sulfamethoxazole, and is more widely distributed throughout the body.9 Because of this unequal distribution, a wide range of concentrations is achieved in different tissues and body fluids. High concentrations of both drugs are found in the sputum, cerebrospinal fluid, prostatic fluid, and bile.

Trimethoprim is excreted mostly unchanged in the urine, with approximately 10% to 30% metabolized to an inactive form. Sulfamethoxazole is primarily metabolized in the liver, with approximately 30% excreted unchanged in the urine. In otherwise healthy individuals, the approximate half-lives of both agents in the 8- to 14-hour range require twice-daily dosing. Because most drug excretion occurs via the kidney, renal insufficiency may increase the half-lives of both agents up to 30 hours or more. Therefore, the dosage of trimethoprim-sulfamethoxazole should be adjusted for a creatinine clearance of less than 30 mL/min (<0.50 mL/s).10

Both components cross the placenta and appear in breast milk, with detectable concentrations found in fetal serum in patients undergoing therapy.11 Trimethoprim-sulfamethoxazole is listed in Pregnancy Category C by the US Food and Drug Administration.

Through various mechanisms, both components of the trimethoprim-sulfamethoxazole combination product may significantly influence the metabolism of several drugs frequently used concurrently with the antibiotic, requiring consideration of potential risks in treating patients taking these medications. The major drug interactions noted with trimethoprim-sulfamethoxazole and the proposed mechanisms are listed in Table 1.


Toxicity and adverse effects

Trimethoprim-sulfamethoxazole is a generally safe medication with a well-defined adverse effect profile in immunocompetent patients (Table 2). However, clinicians need to be aware of several uncommon, but potentially serious, adverse effects associated with trimethoprim and the sulfa-containing component of the combination product.

Gastrointestinal and cutaneous symptoms are the most commonly encountered adverse effects and have generally been attributed to the sulfonamide portion of the drug.6,32 These reactions tend to be mild, dose related, and reversible, and often do not require discontinuation of therapy.7,22,33 Although difficult to establish, rates of severe or life-threatening reactions seem to be low in immunocompetent patients.29,34

A quantitative comparison of overall adverse effect rates between different antibiotics is difficult; however, multiple studies35-37 suggest that trimethoprim-sulfamethoxazole has a 2 to 3 times increased incidence of adverse effects relative to newer antibiotics, such as the fluoroquinolones, for the treatment of similar infections.

Gastrointestinal intolerance occurs in approximately 3% to 8% of patients.22,23 Symptoms commonly include nausea, vomiting, and anorexia. Diarrhea, glossitis, and stomatitis are much less frequent. Hepatotoxicity, a known but rare complication of sulfonamide treatment, seems uncommon with trimethoprim-sulfamethoxazole treatment, and the risk is considered comparable to other antimicrobial agents.29

Skin reactions occur in 3% to 4% of the general population treated with trimethoprim-sulfamethoxazole.22-24 Multiple skin reactions have been described, including a maculopapular rash, urticaria, diffuse erythema, morbilliform lesions, erythema multiforme, purpura, and photosensitivity. Severe reactions, including the Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported and fortunately occur only rarely, although sulfonamides seem to impart a large increase in risk for these types of reactions relative to other antibiotics.38,39

Trimethoprim is known to decrease the tubular secretion of creatinine and may interfere with certain serum creatinine assays, leading to mild elevations of the serum creatinine level without true diminution of the glomerular filtration rate.25,40-42 These increases tend to be mild (approximately 10%), and reverse with drug discontinuation. Trimethoprim-sulfamethoxazole has only rarely been associated with direct nephrotoxicity.7

Recent observations25,26 of hyperkalemia occurring in patients treated with high-dose trimethoprim-sulfamethoxazole led to the elucidation of a mechanism whereby trimethoprim decreases potassium excretion by alteration of the transepithelial voltage in the distal renal tubule. Subsequent studies28 have documented that hyperkalemia may occur in association with the drug at lower doses used to treat routine infections, even in older patients with clinically normal renal function. Caution, thus, needs to be exercised when using trimethoprim-sulfamethoxazole in patients with preexisting renal dysfunction or in those taking concurrent medications (such as angiotensin-converting enzyme inhibitors and potassium-sparing diuretics) that may exacerbate this hyperkalemic effect to potentially dangerous levels.

Although trimethoprim inhibits dihydrofolate reductase in bacteria, it is estimated that an approximately 50 000 times increased concentration of the drug is required to inhibit the human form of this enzyme.43 Consequently, despite the theoretical potential to do so, trimethoprim does not seem to lead to megaloblastic changes when used in the treatment of routine infections, although patients with known low folate stores undergoing long-term treatment should be followed up for such changes.8

Sulfonamides have been associated with various other hematological disorders, including multiple forms of anemia, granulocytopenia, agranulocytosis, and thrombocytopenia. These reactions have also been reported with trimethoprim-sulfamethoxazole, although only rarely and at rates considered similar to other sulfonamides.7

Delirium and psychosis have been rarely reported with trimethoprim-sulfamethoxazole use, particularly in elderly persons.30,31


Adverse Reactions in Human Immunodeficiency Virus (HIV)–Infected Patients

Adverse reactions to trimethoprim-sulfamethoxazole seem to be particularly common in HIV-infected individuals, occurring in as many as 65% of those receiving the agent.44-46 These effects are seen when the medication is used for prophylaxis and treatment of Pneumocystis carinii pneumonia (PCP). Unfortunately, up to 50% of patients may require discontinuation of trimethoprim-sulfamethoxazole owing to its toxicity.

Adverse events generally are divided into hypersensitivity reactions and all others. Hypersensitivity reactions are most common, and include a rash and fever that develop 8 to 12 days after the initiation of therapy, usually at doses of trimethoprim-sulfamethoxazole used to treat acute PCP.47-49 The rash is commonly a generalized maculopapular eruption that becomes pruritic. Other reactions include nausea and vomiting, diarrhea, neutropenia, thrombocytopenia, anemia, transaminase elevations, cholestatic jaundice, and azotemia.44,46-49 Less common adverse reactions include hyperkalemia, hyponatremia, resting tremor, aseptic meningitis, rhabdomyolysis, the Stevens-Johnson syndrome, and toxic epidermal necrolysis.47,50-54 Some adverse reactions seem to be dose related (rash, fever, liver enzyme abnormalities, and GI disturbances), while others seem to be independent of dose (neutropenia, anemia, and azotemia).49

The treatment of HIV-infected patients with drug-associated hypersensitivity reactions remains controversial, with symptomatic treatment through the reaction45,55 and gradual reintroduction of the drug (desensitization)56,57 proving to be successful strategies.


Antimicrobial activity and clinical use in the era of emerging resistance

In the early 1970s, trimethoprim-sulfamethoxazole demonstrated a wide spectrum of activity against aerobic bacteria.3,58 Its antimicrobial efficacy and inexpensive cost rapidly garnered global popularity for its use in the treatment of UTIs, respiratory tract infections, and GI tract infections. However, increasing rates of resistance among clinically important pathogens have been reported worldwide during the past few decades.

Bacteria may become resistant to trimethoprim and sulfamethoxazole by several mechanisms, including the development of permeability barriers, efflux pumps, naturally insensitive target enzymes, and genetic alterations or dysregulation in the genes encoding target enzymes.59 Resistance to trimethoprim and sulfamethoxazole is transferable.59 A plasmid-encoded alteration in dihydrofolate reductase resulting in trimethoprim insensitivity against a background of high sulfonamide resistance is increasingly prevalent among bacterial pathogens.60

Certain organisms demonstrate marked geographic variation in resistance to trimethoprim-sulfamethoxazole, with a higher incidence typically found in developing countries. In addition, resistant gram-negative organisms are readily transmitted by person-to-person contact and spread by travelers.60

Trimethoprim-sulfamethoxazole is active against many Enterobacteriaceae, including Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, accounting for its widespread use in those with UTIs. In the United States, it has been the drug of choice for empirical therapy for uncomplicated UTIs in women.61

Unfortunately, the prevalence of resistant coliforms is increasing.59,62-70 In the 1980s, trimethoprim resistance in E coli isolates from outpatient urine samples often reached 15% to 20%.71 Trimethoprim resistance among enteric organisms is more prevalent in developing countries, with reported levels as high as 68% in South America, Asia, and Africa.60 In the United States and Europe, recent use of antibiotics, hospitalization, and immunosuppression have been implicated as factors contributing to trimethoprim-sulfamethoxazole resistance among urinary tract isolates.66-68 The San Francisco General Hospital, San Francisco, Calif, reported a sharp increase of trimethoprim-sulfamethoxazole resistance in clinical isolates of Staphylococcus aureus and 7 genera of Enterobacteriaceae, including E coli, from 1988 to 1995.65 Increases in resistance were most dramatic in isolates from HIV-infected patients and temporally associated with use of trimethoprim-sulfamethoxazole for prophylaxis against PCP.65 Furthermore, a recent study72 of a small number of resistant E coli isolates from women with community-acquired UTI in 3 separate US states suggested that a single clonal group accounted for nearly half of such strains. Such findings increase the concern for widespread transmission from a contaminated food source, leading to intestinal colonization.72

It is unclear if increased trimethoprim-sulfamethoxazole resistance among uropathogens correlates with treatment failure because a high urinary drug concentration may override in vitro insensitivity. A few studies73 limited by a small sample size suggest a higher rate of clinical failure with trimethoprim-sulfamethoxazole among resistant organisms. The Infectious Diseases Society of America74 has recommended that trimethoprim-sulfamethoxazole remain standard therapy for uncomplicated cystitis in women unless the prevalence of local resistance to the drug is greater than 10% to 20%. Patient factors favorable to the use of trimethoprim-sulfamethoxazole include no recent antimicrobial use, hospitalization, or recurrent UTI in the past year.73

Superior clinical success rates with fluoroquinolones have led to a preference for their use for acute and chronic prostate infections, although trimethoprim-sulfamethoxazole retains a role as an effective second-line treatment.75


Respiratory Tract Infections

Trimethoprim-sulfamethoxazole has been useful in the treatment of community-acquired upper and lower respiratory tract infections because of its activity against the major pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

Several studies76-78 in the 1980s showed trimethoprim-sulfamethoxazole to be an effective treatment for otitis media, including infections caused by ampicillin-resistant strains of H influenzae.79 It has also been a useful agent for acute bacterial sinusitis,80 short-term exacerbations of chronic bronchitis,81-85 and prophylaxis of recurrent otitis media.86,87 Until recently, trimethoprim-sulfamethoxazole has been considered a reasonable alternative to β-lactam antibiotics for the empirical treatment of mild to moderate severity community-acquired pneumonia.88

Emerging resistance among respiratory pathogens has raised serious concerns regarding the role of trimethoprim-sulfamethoxazole in the treatment of respiratory tract infections. The drug is not effective against most intermediate- and higher-level penicillin-resistant strains of S pneumoniae.89 The SENTRY Antimicrobial Surveillance Program89 recently reported a 15% to 20% frequency of trimethoprim-sulfamethoxazole resistance among S pneumoniae and H influenzae in the United States, Canada, and Europe. Higher rates of resistant respiratory pathogens were observed in Latin America and the Asian-Pacific region.89

Consequently, treatment guidelines by the Sinus and Allergy Health Partnership90 recommend trimethoprim-sulfamethoxazole only as an alternative in β-lactam–allergic patients for the treatment of mild acute bacterial sinusitis in adults and children who have not received antibiotics in the previous 4 to 6 weeks.

The American Thoracic Society’s recommendations for the empirical treatment of community-acquired pneumonia, released in 1993, considered trimethoprim-sulfamethoxazole an option for initial outpatient management in adults with a comorbidity or in those 60 years or older. However, the more recent treatment guidelines for community-acquired pneumonia by the American Thoracic Society91 and the Infectious Diseases Society of America92 do not include trimethoprim-sulfamethoxazole among recommendations for empirical therapy.

Thus, trimethoprim-sulfamethoxazole as a treatment for upper and lower respiratory tract infections requires consideration of local resistance patterns and individual patient factors, such as severity of disease, when deciding the appropriateness of use.

Salmonella and Shigella species and enterotoxigenic E coli were widely susceptible to trimethoprim-sulfamethoxazole in the 1970s. This agent was frequently used as successful therapy and prophylaxis for bacterial enteric infections.93

Resistant strains of Shigella species rapidly increased in developing countries and subsequently spread worldwide.59,94 Trimethoprim-sulfamethoxazole is no longer considered appropriate treatment of shigellosis in most parts of the world. Emerging resistance among Salmonella isolates has been slower and more geographically variable than with Shigella species.60 In the United States, the incidence of infections due to Salmonella typhi has been stable since the mid 1960s; however, the proportion of cases acquired abroad has increased steadily.95 Multidrug-resistant S typhi isolated in the United States from individuals with symptomatic typhoid fever was strongly associated with recent travel to the Indian subcontinent or to Vietnam.95 Most strains from apparent domestically acquired infections remained sensitive to trimethoprim-sulfamethoxazole.95

Trimethoprim-sulfamethoxazole seems to remain efficacious in the treatment of enterotoxigenic E coli in the interior of Mexico,96 but resistance levels are high in other parts of the world.97Yersinia enterocolitica,98Vibrio cholerae,99 and Aeromonas hydrophila100 are bacterial causes of diarrheal infections that are usually susceptible.

Among travelers to many developing countries, fluoroquinolones have replaced trimethoprim-sulfamethoxazole as chemoprophylaxis.93 The role of trimethoprim-sulfamethoxazole in the treatment and prevention of infectious diarrhea in travelers is restricted to certain locations (such as noncoastal Mexico)96,101 or when treatment is directed at specific pathogens.93


Skin-Associated Infections

Many isolates of S aureus and Staphylococcus epidermidis remain susceptible to trimethoprim-sulfamethoxazole. However, resistant strains have been widely reported among both species, especially methicillin sodium–resistant organisms.

In a surveillance102 of international strains, most methicillin-resistant coagulase-negative staphylococcal isolates were resistant to trimethoprim-sulfamethoxazole. Streptococcus pyogenes is variably susceptible.103 Several antimicrobial agents are more effective and reliable for the treatment of skin, soft tissue, and other staphylococcal infections.


Clinical Use in HIV-Infected Patients

Treatment of Active Infections. Because it was previously recognized as an effective agent for the treatment of PCP in immunosuppressed individuals,104 trimethoprim-sulfamethoxazole became the preferred treatment for PCP as the acquired immunodeficiency syndrome epidemic unfolded in the early 1980s. It was subsequently shown to be more effective and better tolerated than the other major parenterally active agent, pentamidine.45

It remains the treatment of choice for HIV-infected patients with severe PCP (PO2, <70 mm Hg; or alveolar to arterial gradient of oxygen, >35 mm Hg [at presentation]). In these patients, the drug is usually administered intravenously, with prednisone given as adjunctive therapy.

For mild to moderate PCP, orally administered trimethoprim-sulfamethoxazole is also considered the agent of choice, although other oral drug combinations (trimethoprim and dapsone and primaquine phosphate and clindamycin) are equally effective.47,105-107

Approximately 10% to 20% of patients with PCP fail to respond to trimethoprim-sulfamethoxazole as a first-line therapy. Although treatment failure is likely multifactorial, drug resistance likely plays a major role. Mutations in the P carinii dihydropteroate synthase gene have been identified more commonly in isolates from patients who have received trimethoprim-sulfamethoxazole or dapsone prophylaxis.108

Trimethoprim-sulfamethoxazole is an effective treatment for infections due to the coccidian protozoal parasites Isospora and Cyclospora.109,110

The drug has activity in the treatment of cerebral toxoplasmosis in patients with the acquired immunodeficiency syndrome,111,112 although its use for this infection is not recommended because of the improved efficacy of other regimens.

Prophylaxis. Trimethoprim-sulfamethoxazole is the recommended agent for the prevention of first-episode and recurrent PCP.113 Indications for primary prophylaxis include a CD4 cell count of less than 200/µL or the presence of oropharyngeal candidiasis.113 Doses as low as 1 double-strength tablet 3 times weekly have been highly effective in preventing PCP.114 Trimethoprim sulfamethoxazole has been superior to aerosolized pentamidine for the prevention of primary and recurrent episodes of PCP,115,116 and is equivalent overall when compared with dapsone-based regimens.116

One double-strength tablet daily has been effective for the primary prophylaxis of toxoplasmosis in patients with the acquired immunodeficiency syndrome,117 and is the agent of choice.113 When used prophylactically, trimethoprim-sulfamethoxazole also has been effective in preventing other concurrent bacterial infections.115,118-120

Trimethoprim-sulfamethoxazole has proved beneficial for prophylaxis against opportunistic infections and for reduction in the occurrence of routine infections in patients receiving immunosuppressive therapy for organ transplantation.121,122 It is also commonly used prophylactically in afebrile neutropenic individuals, although the effectiveness of this practice has been questioned.123 It is no longer considered an acceptable empirical treatment for febrile patients with neutropenia.124

Nonfermentative gram-negative bacilli are important infectious agents among hospitalized and immunocompromised patients. Stenotrophomonas (Xanthomonas) maltophilia is typically resistant to several classes of broad-spectrum antibiotics, but commonly is inhibited by trimethoprim-sulfamethoxazole.125,126 Other nonfermentative organisms, including Burkholderia (Pseudomonas) cepacia, Acinetobacter, and Alcaligenes, are frequently susceptible.125

Trimethoprim-sulfamethoxazole may have a place in therapy for meningitis caused by cephalosporin–resistant nonfermentative gram-negative bacilli and for Listeria monocytogenes infections in patients allergic to penicillin.127-129

Trimethoprim-sulfamethoxazole is frequently used to treat Nocardia infections,130 and is efficacious in the treatment of Whipple disease, a multisystem illness caused by the bacillus Tropheryma whippelii.131,132

Selected patients with Wegener granulomatosis may benefit from treatment with trimethoprim-sulfamethoxazole, although the mechanism of action and degree of clinical efficacy in patients with this disorder is uncertain.133

Since its introduction more than 3 decades ago, trimethoprim-sulfamethoxazole has played a key role in the treatment of a wide variety of clinical infections. However, worldwide changes in resistance patterns and the introduction of newer agents with different pharmacological and antimicrobial characteristics are rapidly changing the manner in which this agent is appropriately used.

Emerging resistance has required modification of trimethoprim-sulfamethoxazole’s role as empirical or first-line therapy for several infections for which it traditionally had widespread use. With attention to local, regional, and worldwide resistance patterns, trimethoprim-sulfamethoxazole may retain its usefulness as a primary agent for selected indications in carefully assessed patients (eg, for the prophylaxis and treatment of PCP and for the primary prophylaxis for Toxoplasma gondii in HIV-infected patients). It continues to be a second-line or alternative antibiotic for various infections, particularly in penicillin-allergic patients or other situations in which newer antibiotics cannot be used (eg, for uncomplicated UTIs, short-term exacerbations of chronic bronchitis, acute otitis media, acute sinusitis, and acute and chronic prostatitis).

A clearly emerging role for the drug seems to be its use as a pathogen-directed therapy for organisms identified as sensitive to trimethoprim-sulfamethoxazole (eg, organisms causing community-acquired and nosocomial pneumonia, GI tract infections, staphylococcal infections, and sexually transmitted diseases). Increasing resistance may require the use of newer expanded-spectrum agents and even multiple-antibiotic regimens for the empirical treatment of many infections. For those pathogens found to be sensitive, however, trimethoprim-sulfamethoxazole remains an efficacious and cost-effective alternative (Table 3) with a well-defined adverse effect profile that may help preserve the usefulness of the broader-spectrum drugs used for empirical therapy. Proper use in this manner requires greater diligence by the clinician in seeking a microbial diagnosis and a concerted effort at focusing treatment once a diagnosis has been made.

Trimethoprim-sulfamethoxazole certainly retains a special role in the prophylaxis and treatment of certain HIV-associated infections, and as first-line therapy for various less common infections (organisms affected include P carinii, S [X] maltophilia and other nonfermentative gram-negative bacilli, Isospora, Cyclospora, Nocardia, and T whippelii).

The judicious use of trimethoprim-sulfamethoxazole may ultimately serve as a model for the future appropriate use of broad-spectrum antibiotics in the setting of increasing antimicrobial resistance pressure and cost-conscious medical practice.

Corresponding author and reprints: Philip A. Masters, MD, Division of General Internal Medicine, The Pennsylvania State University College of Medicine, 500 University Dr, Suite 4100, Hershey, PA 17033 (e-mail: [email protected]).

Accepted for publication June 13, 2002.

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Not Available, Red Book Updates.  Montvale, NJ Medical Economics Books2001;

Diseptyl Forte – instructions for use, dosages, composition, analogs, side effects / Pillintrip

WARNINGS

Part of “PRECAUTIONS” Section

PRECAUTIONS

Embryo11 and

Fetal Toxicity that exposure to Diseptyl Forte during pregnancy may be associated with an increased risk of congenital malformations, especially neural tube defects, cardiovascular malformations, urinary tract defects, cleft mouth and clubfoot.If Disseptil Forte is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be warned of the potential hazard to the fetus.

Hypersensitivity And Other Fatal Reactions

Deaths associated with the intake of sulfonamides occurred due to severe reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant liver necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias.

Sulfonamides, including sulfonamide-containing drugs such as Diseptil Forte, should be discontinued at the first appearance of a skin rash or any sign of an adverse reaction. Clinical signs such as rash, sore throat, fever, arthralgia, cough, shortness of breath, pallor, purpura, or jaundice may be early signs of a serious reaction. A skin rash may be accompanied by more severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, liver necrosis, or severe circulatory problems.A complete blood count should be done frequently in patients receiving sulfonamides. Cough, dyspnea and pulmonary infiltrates are airway hypersensitivity reactions reported in connection with sulfonamide treatment

Thrombocytopenia

Diseptil Forte-induced thrombocytopenia may be an immune-mediated disorder. Severe cases of thrombocytopenia, which are fatal or life-threatening, have been reported. Observation of patients for hematologic toxicity.Thrombocytopenia usually goes away within a week after you stop taking Disseptil Forte.

Streptococcal Infections & Rheumatism

Avoid using Disseptil Forte when treating streptococcal pharyngitis. Clinical studies have shown that patients with group A β-hemolytic streptococcal tonsillopharyngitis have a higher incidence of bacteriological failure when treated with Diseptil Forte than those patients who received penicillin, as evidenced by the inability to eradicate this organism from the tonsils.Therefore, Disseptil Forte will not prevent consequences such as rheumatism.

Diarrhea associated with Clostridium Difficile

Clostridium difficile Associated diarrhea (CDAD) has been reported with almost all antibacterial agents, including Disseptil Forte, and can range in severity from mild diarrhea to fatal colitis. Antibacterial treatment alters the normal flora of the colon, resulting in an overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. Strains producing hypertoxin C. difficile cause increased morbidity and mortality, as these infections may be refractory to antimicrobial therapy and may require colectomy. CDAD should be considered in all patients who develop diarrhea after antibiotic use. A careful medical history is required, as it has been reported to occur within two months of the administration of antibacterial drugs.

If suspected or confirmed, chronic antibacterial use is not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment C. difficile , and surgical examination should be performed as clinically indicated.

Sulfite Sensitivity

Diseptil Forte contains sodium metabisulfite, a sulfite that can cause allergic reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in some susceptible individuals.The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity is more common in asthmatics than in non-asthmatics.

Benzyl Alcohol Toxicity In Pediatric Patients (“Choking Syndrome”)

Disseptil Forte contains benzyl alcohol as a preservative. Serious and fatal adverse reactions, including “choking syndrome”, can occur in infants and children with low birth weight who have received benzyl alcohol-preserved infusion solutions, including Disseptil Forte.“Choking syndrome” is characterized by central nervous system depression, metabolic acidosis, and shortness of breath. Disseptil Forte is contraindicated for use in pediatric practice less than two months of age.

When prescribing Diseptil Forte to pediatric patients (two months of age and older), the combined daily metabolic load of benzyl alcohol from all sources should be taken into account, including Diseptil Forte (contains 10 mg of benzyl alcohol per ml) and other drugs containing benzyl alcohol.

The minimum amount of benzyl alcohol at which serious adverse reactions can occur is not known.

Risk Associated With the Concomitant Use of Leucovorin In Pneumocystis Jirovecii Pneumonia

Treatment failure and excess mortality were observed with the concomitant use of Diseptil Forte with Leucovorin for the treatment of HIV-positive patients with Pneumocystis jirovecii Pneumocystis jirovecii pneumonia controlled pneumonia. 4 Avoid concomitant use of Disseptil Forte and leucovorin during treatment Pneumocystis jirovecii pneumonia.

Folic acid deficiency

Avoid the use of Disseptil Forte in patients with impaired renal or hepatic function, in those with possible folate deficiency (for example, the elderly, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome and patients with malnutrition), as well as in people with severe allergies or bronchial asthma.

Hematologic changes suggestive of folate deficiency may occur in elderly patients or in patients with pre-existing folate deficiency or renal impairment. These effects are reversible with folic acid therapy.

Hemolysis

People with glucose-6-phosphate dehydrogenase deficiency may experience hemolysis. This reaction is often dose related.

Infusion Reactions

When using Diseptil Forte, local irritation and inflammation were observed due to extravascular infiltration of the infusion.If they do occur, the infusion should be discontinued and resumed elsewhere.

Hypoglycemia

There have been cases of hypoglycemia in non-diabetic patients treated with Disseptil Forte, which usually occurs after several days of therapy. Patients with impaired renal function, liver disease, malnutrition or high doses of Disseptil Forte are especially at risk.

Disruption of Phenylalanine Metabolism

It has been noted that Trimethoprim, a component of Diseptil Forte, impairs phenylalanine metabolism, but this is of no consequence in PKU patients with appropriate dietary restriction.

Porphyria And Hypothyroidism

Like other drugs containing sulfonamides, Diseptil Forte can provoke a porphyria crisis and hypothyroidism. Avoid using Disseptil Forte in patients with porphyria or thyroid dysfunction.

Potential Risk In The Treatment Of Pneumocystis Pneumonia In Patients With Acquired Immunodeficiency Syndrome (AIDS)

AIDS patients may not tolerate or respond to Disseptil Forte in the same way as non-AIDS patients.The incidence of adverse reactions, especially rash, fever, leukopenia and elevated aminotransferase (transaminase) values, during therapy with Diseptil Forte in AIDS patients undergoing treatment Pneumocystis jirovecii , it has been reported that pneumonia is significantly increased compared to the frequency usually associated with the use of Diseptil Forte in non-AIDS patients. If the patient develops a skin rash or any signs of an adverse reaction, reconsider therapy with Diseptil Forte.

Avoid the simultaneous use of Disseptil Forte and leucovorin during treatment Pneumocystis jirovecii pneumonia.

Electrolyte disturbances

High dosage of trimethoprim used in patients with P. Jirovets pneumonia causes a progressive but reversible increase in serum potassium concentration in a significant number of patients. Even treatment with recommended doses can cause hyperkalemia if trimethoprim is prescribed to patients with major potassium metabolic disorders, renal insufficiency, or if drugs known to cause hyperkalemia are prescribed concurrently.These patients require careful monitoring of serum potassium levels.

Severe and symptomatic hyponatremia may occur in patients receiving Diseptil Forte, especially for the treatment of P. Jirovec pneumonia. Evaluation of hyponatremia and appropriate correction is necessary in symptomatic patients to prevent life-threatening complications.

During treatment, ensure adequate fluid intake and urination to prevent crystalluria.Patients who are “slow acetylators” may be more prone to idiosyncratic reactions to sulfonamides.

Laboratory Research Monitoring

A complete blood count should be performed frequently in patients receiving Disseptil Forte. Stop taking Disseptil Forte if there is a significant decrease in the amount of any formed blood element. During therapy, urine analysis is performed with a thorough microscopic examination and analysis of renal function, especially in patients with impaired renal function.

Development of Drug-Resistant Bacteria

Prescribing Diseptil Forte in the absence of proven or highly suspected bacterial infection or prophylactic indications is unlikely to benefit the patient and increase the risk of developing drug-resistant bacteria.

Non-clinical toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis

Sulfamethoxazole was not carcinogenic when evaluated in a 26-week study in tumor mice (tg-rash3) at doses up to 400 mg / kg / day, which is equivalent to 2 sulfamethoxazole – multiple systemic exposure to humans (with a daily dose of 800 mg sulfamethoxazole b.I. ( twice a day ).

Mutagenesis

Artificial Reverse mutation bacterial tests according to the standard protocol have not been performed with sulfamethoxazole and trimethoprim in combination. One artificial test for chromosomal aberration in human lymphocytes with sulfamethoxazole / trimethoprim was negative. At artificial and in vivo tests on animal species sulfamethoxazole / trimethoprim did not damage chromosomes. In vivo micronucleus assays were positive after oral administration of sulfamethoxazole / trimethoprim. Observations of leukocytes obtained from patients receiving sulfamethoxazole and trimethoprim did not reveal chromosomal abnormalities.

Sulfamethoxazole alone was positive in artificial reverse mutation bacterial assay and artificial micronucleus assay using cultured human lymphocytes.

Trimethoprim alone was negative in artificial bacterial reverse mutation assays and in artificial chromosomal aberration assays with Chinese hamster ovary or lung cells with or without C9 activation. At artificial Analysis of comets, micronuclei and chromosomal damage using cultured human lymphocytes showed a positive result for trimethoprim. In mice after oral administration of trimethoprim, no DNA damage was recorded in comet analysis of the liver, kidney, lungs, spleen, or bone marrow.

Impairment of Fertility

No adverse effects on fertility or general reproductive function in rats treated with oral doses up to 350 mg / kg / day of sulfamethoxazole plus 70 mg / kg / day of trimethoprim, doses approximately twice the recommended daily human dose based on body surface area was not observed.

Use In Specific Populations
Pregnancy
Risk Summary

Disseptil Forte may harm the fetus when administered to a pregnant woman.Some epidemiological studies indicate that exposure to Diseptyl Forte during pregnancy may be associated with an increased risk of congenital malformations, especially neural tube defects, cardiovascular abnormalities, urinary tract defects, clefts of the mouth, and clubfoot.

One of 3 studies in rats showed cleft palate at doses about 5 times the recommended human dose based on body surface area, the other 2 studies showed no teratogenicity at similar doses.Studies in pregnant rabbits have shown an increase in fetal loss of about 6 times the human dose on a body surface area basis.

The estimated background risk of serious birth defects and miscarriage for this population is unknown. In the general US population, the estimated background risk of serious birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Advise pregnant women about the potential harms of Disseptila Forte to the fetus.

Clinical considerations

Disease-related Risks to the mother and / or embryo / fetus

Urinary tract infection during pregnancy is associated with adverse perinatal outcomes such as preterm birth, low birth weight and preeclampsia, and increased mortality pregnant woman. P. Jirovets Pneumonia during pregnancy is associated with premature birth and increased morbidity and mortality in pregnant women.Disseptil Forte should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Data

Data

Despite the absence of large, prospective, well-controlled studies in pregnant women and their children, some retrospective epidemiological studies suggest an association between Diseptil Forte exposure in the first trimester of pregnancy with an increased risk of congenital malformations, especially birth defects neural tube, cardiovascular anomalies, urinary tract defects, clefts of the mouth and clubfoot.However, these studies were limited by the small number of case reports and lack of adjustment for multiple statistical comparisons and confusion. In addition, these studies are limited by biases about memorization, selection and information, as well as the limited generalizability of their results. Finally, outcome rates varied between studies, limiting cross-comparison

In addition, other epidemiological studies did not find statistically significant associations between Diseptyl Forte exposure and specific malformations.Available in: Kenya and Pursell, 10 A retrospective study reported the outcome of 186 pregnancies during which the mother received either placebo or oral trimethoprim and sulfamethoxazole. The incidence of congenital anomalies was 4.5% (3 of 66) in those receiving placebo and 3.3% (4 of 120) in those receiving trimethoprim and sulfamethoxazole. There were no abnormalities in 10 children whose mothers received the drug during the first trimester.

In a separate study, Brumfitt and Purcell also found no congenital anomalies in 35 babies whose mothers received oral trimethoprim and sulfamethoxazole at or shortly after conception.

Animal data

In rats, oral doses of 533 mg / kg sulfamethoxazole or 200 mg / kg trimethoprim produced teratological effects, manifested mainly as cleft palate. These doses are about 5 and 6 times the recommended total daily human dose based on body surface area. In two studies in rats, no teratology was observed with 512 mg / kg sulfamethoxazole in combination with 128 mg / kg trimethoprim. In some rabbit studies, an overall increase in fetal loss (dead and resorbed buds) has been associated with doses of trimethoprim 6 times the human therapeutic dose based on body surface area

Lactation period
Risk summary

Disseptil Forte level in breast milk is approximately 2-5% of the recommended daily dose for pediatric patients over two months of age.There is no information on the effect of Disseptil Forte on a nursing infant or on milk production. Due to the potential risk of displacement of bilirubin and cernicterus in a breastfed baby, it is recommended that women avoid breastfeeding during treatment with Disseptil Forte.

Pediatric use

Diseptil Forte is contraindicated in pediatric patients under 2 months of age due to the potential risk of displacement of bilirubin and cernicterus.

Serious adverse reactions, including fatal reactions and “choking syndrome”, have been observed in premature infants and low birth weight infants in the neonatal intensive care unit who received benzyl alcohol as a preservative in infusion solutions.In these cases, benzyl alcohol in doses from 99 to 234 mg / kg / day caused high levels of benzyl alcohol and its metabolites in the blood and urine (the level of benzyl alcohol in the blood was 0.61 to 1.378 mmol / L). Additional adverse reactions included gradual neurologic deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin destruction, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Premature infants with low birth weight may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol

When Diseptil Forte is prescribed to pediatric patients, the combined daily metabolic load of benzyl alcohol from all sources, including Diseptil Forte (Diseptil Forte contains 10 mg of benzyl alcohol per ml) and other preparations containing benzyl alcohol.The minimum amount of benzyl alcohol at which serious adverse reactions can occur is not known.

Geriatric Uses

Clinical studies of Diseptil Forte did not include sufficient numbers of subjects aged 65 and over to determine if they differ in response from younger subjects.

In elderly patients, the risk of developing severe adverse reactions may be increased, especially in the presence of complicating conditions such as impaired renal and / or liver function or the simultaneous use of other drugs.

Severe skin reactions, generalized bone marrow suppression, specific decreased platelet count (with or without purpura) and hyperkalemia are the most common severe adverse reactions in elderly patients.

In persons simultaneously receiving certain diuretics, primarily thiazides, there was an increased incidence of thrombocytopenia with purpura. An increased level of digoxin in the blood can be observed with concomitant therapy with Diseptil Forte, especially in elderly patients.Serum digoxin levels should be monitored.

Hematologic changes indicative of folic acid deficiency may occur in elderly patients. These effects are reversible with folic acid therapy. For patients with impaired renal function, appropriate dose adjustments should be made, and the duration of use should be as short as possible to minimize the risk of adverse reactions.

Trimethoprim component Diseptil Forte can cause hyperkalemia when administered to patients with major disorders of potassium metabolism, with renal failure, or when used simultaneously with drugs known to cause hyperkalemia, such as angiotensin-converting enzyme inhibitors.These patients require careful monitoring of serum potassium levels. To reduce the level of potassium in the blood serum, it is recommended to discontinue treatment with Diseptil Forte.

Pharmacokinetic parameters of sulfamethoxazole were similar for elderly patients and young adults. The mean maximum serum concentration of trimethoprim was higher and the mean renal clearance of trimethoprim was lower in older patients compared with younger patients.

RECOMMENDATIONS

4.Safrin S, Li BL, Sande MA. Supplemental folic acid with trimethoprim-sulfamethoxazole for Pneumocystis Pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death. J Infect Dis Oct 1994,170 (4): 912-7.

10. Available in: Kenya W, Pursell R. Trimethoprim / sulfamethoxazole in the treatment of bacteriuria in women. J Infect Dis. Nov 1973,128 (Suppl): S657-S663.

WARNINGS

Fetal toxicity

Several epidemiological studies indicate that exposure to sulfamethoxazole / trimethoprim during pregnancy may be associated with an increased risk of birth defects, especially neural tube defects, cardiovascular malformations, urinary tract defects, clefts and clubfoot.If sulfamethoxazole / trimethoprim is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be warned of the potential hazard to the fetus.

Hypersensitivity And Other Fatal Reactions

Deaths associated with the administration of sulfonamides, although rare, are due to severe reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant liver necrosis, agranulocytosis, aplastic anemia and other circulatory disorders …

Sulfonamides, including sulfonamide-containing drugs such as sulfamethoxazole / trimethoprim, should be discontinued at the first appearance of a skin rash or any sign of an adverse reaction. In rare cases, a skin rash may be accompanied by a more severe reaction such as Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatic necrosis, and serious blood disorders (see PRECAUTIONS Clinical signs such as rash, sore throat, fever, arthralgia, pallor, purpura, or jaundice may be early signs of a serious reaction.

Cough, dyspnea and pulmonary infiltrates are airway hypersensitivity reactions reported in association with sulfonamide treatment.

Thrombocytopenia

Sulfamethoxazole / trimethoprim-induced thrombocytopenia may be an immune-mediated disorder. Severe cases of thrombocytopenia, which are fatal or life-threatening, have been reported. Thrombocytopenia usually resolves within a week after stopping sulfamethoxazole / trimethoprim.

Streptococcal Infections And Rheumatism

Sulfonamides should not be used to treat group A beta-hemolytic streptococcal infections. If infected, they will not kill streptococcus and therefore will not prevent consequences such as rheumatism.

Diarrhea associated with Clostridium Difficile

Clostridium difficile Associated diarrhea (CDAD) has been reported with almost all antibacterial agents, including Disseptil Forte, and can range in severity from mild diarrhea to fatal colitis.Treatment with antibacterial agents alters the normal flora of the colon, resulting in an overgrowth of C. difficile .

C. difficile produces toxins A and B, which contribute to the development of CDAD. Strains producing hypertoxin C. difficile cause increased morbidity and mortality, as these infections may be refractory to antimicrobial therapy and may require colectomy. CDAD should be considered in all patients who develop diarrhea after antibiotic use.

A careful medical history is required as it has been reported to occur within two months of the administration of antibacterial drugs.

If suspected or confirmed, continued use of antibiotics other than C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment C. difficile , and surgical examination should be performed as clinically indicated.

Adjunctive treatment with Leucovorin for Pneumocystis pneumonia common surgical

Treatment failure and excess mortality have been observed with concomitant use of trimethoprim-sulfamethoxazole with leucovorin for the treatment of HIV-positive patients with Pneumocystis advanced surgical pneumonia in a randomized placebo controlled trial. 7 Concomitant use of trimethoprim-sulfamethoxazole and leucovorin in the treatment of Pneumocystis Common surgical pneumonia should be avoided.

PRECAUTIONS

Development of Drug-Resistant Bacteria

Prescribing Diseptil Forte in the absence of proven or highly suspected bacterial infection or prophylactic indications is unlikely to benefit the patient and increase the risk of developing drug-resistant bacteria.

Folic acid deficiency

Diseptil Forte should be used with caution in patients with impaired renal or liver function, people with possible folic acid deficiency (for example, the elderly, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome and patients with malnutrition), as well as those with severe allergies or bronchial asthma.

Hemolysis

People with glucose-6-phosphate dehydrogenase deficiency may experience hemolysis. This reaction is often dose related (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION ).

Hypoglycemia

Cases of hypoglycemia have been reported in non-diabetic patients treated with sulfamethoxazole / trimethoprim, usually occurring after several days of therapy. Patients with impaired renal function, liver disease, malnutrition or high doses of Disseptil Forte are especially at risk.

Phenylalanine metabolism

Trimethoprim has been observed to impair phenylalanine metabolism, but this is of no consequence in PKU patients with appropriate dietary restriction.

Porphyria & Hypothyroidism

As with all sulfonamide preparations, caution is advised in patients with porphyria or thyroid dysfunction.

Application In The Treatment And Prevention Of Pneumocystis Pneumonia In Patients With Acquired Immunodeficiency Syndrome (AIDS)

AIDS patients may not tolerate or react to Disseptil Forte as well as non-AIDS patients.In non-AIDS patients. Side effects are usually less pronounced in patients receiving Diseptil Forte for prophylaxis. A history of mild intolerance to Diseptyl Forte in AIDS patients, apparently, does not allow predicting intolerance to subsequent secondary prevention.However, if the patient develops a skin rash or any signs of an adverse reaction, therapy with Diseptil Forte should be reassessed (see WARNINGS ).

Simultaneous use of Disseptil Forte and leucovorin should be avoided. P. common surgical pneumonia (see WARNINGS ).

Electrolyte disturbances

High dosage of trimethoprim used in patients with P. common surgical pneumonia causes a progressive but reversible increase in serum potassium concentration in a significant number of patients.Even treatment with recommended doses can cause hyperkalemia if trimethoprim is prescribed to patients with major potassium metabolic disorders, renal insufficiency, or if drugs known to cause hyperkalemia are prescribed concurrently. These patients require careful monitoring of serum potassium levels.

Severe and symptomatic hyponatremia may occur in patients receiving sulfamethoxazole / trimethoprim, especially for the treatment of P. common surgical pneumonia .Evaluation of hyponatremia and appropriate correction is necessary in symptomatic patients to prevent life-threatening complications.

Adequate fluid intake and urination should be ensured during treatment to prevent crystalluria. Patients who are “slow acetylators” may be more prone to idiosyncratic reactions to sulfonamides.

Laboratory tests

A complete blood count should be performed frequently in patients receiving Diseptil Forte, if there is a significant decrease in the amount of any formed blood element, then Diseptil Forte should be discontinued.During therapy, urine analysis should be performed with careful microscopic examination and analysis of renal function, especially in patients with impaired renal function.

Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis

Sulfamethoxazole was not carcinogenic when evaluated in a 26-week study in tumor mice (tg-rash3) at doses up to 400 mg / kg / day of sulfamethoxazole, which is equivalent to 2.4 times systemic exposure to humans (with a daily dose of 800 mg sulfamethoxazole b.I.).

Mutagenesis

In vitro reverse mutation bacterial tests according to the standard protocol have not been performed with sulfamethoxazole and trimethoprim in combination. An in vitro chromosomal aberration test in human lymphocytes with sulfamethoxazole / trimethoprim was negative. In in vitro and in vivo animal tests, sulfamethoxazole / trimethoprim did not damage chromosomes. In vivo micronucleus assays were positive after oral administration of sulfamethoxazole / trimethoprim.Observations of leukocytes obtained from patients receiving sulfamethoxazole and trimethoprim did not reveal chromosomal abnormalities.

Sulfamethoxazole alone was positive in an in vitro bacterial reverse mutation assay and an in vitro micronucleus assay using cultured human lymphocytes.

Only trimethoprim was negative in in vitro bacterial reverse mutation assays and in vitro chromosomal aberration assays with Chinese hamster ovary or lung cells with or without S9 activation.In vitro analysis of comets, micronuclei and chromosomal damage using cultured human lymphocytes, trimethoprim was positive. In mice after oral administration of trimethoprim, no DNA damage was recorded in comet analysis of the liver, kidney, lungs, spleen, or bone marrow.

Impairment of Fertility

No adverse effects on fertility or general reproductive function in rats treated with oral doses up to 70 mg / kg / day of trimethoprim plus 350 mg / kg / day of sulfamethoxazole, doses approximately twice the recommended human daily dose based on body surface area was not observed.

Pregnancy

Despite the lack of large, well-controlled trials of trimethoprim and sulfamethoxazole in pregnant women, Brumfitt and Purcell, 9 , a retrospective study reported the outcome of 186 pregnancies during which the mother received either placebo or trimethoprim and sulfamethoxazole … The incidence of congenital anomalies was 4.5% (3 of 66) in those receiving placebo and 3.3% (4 of 120) in those receiving trimethoprim and sulfamethoxazole.There were no abnormalities in 10 children whose mothers received the drug during the first trimester. In a separate study, Brumfitt and Purcell also found no congenital anomalies in 35 babies whose mothers received oral trimethoprim and sulfamethoxazole at or shortly after conception.

Since trimethoprim and sulfamethoxazole can affect the metabolism of folic acid, Diseptil Forte should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Teratogenic effects

Pregnancy Category D

Data

Although there are no large prospective, well-controlled studies in pregnant women and their children, some retrospective epidemiological studies suggest an association between first trimester sulfamethoxazole / trimethoprim exposure to increased risk congenital malformations, especially neural tube defects, cardiovascular anomalies, urinary tract defects, cleft mouth and clubfoot.However, these studies were limited by the small number of case reports and lack of adjustment for multiple statistical comparisons and confusion. In addition, these studies are limited by biases about memorization, selection and information, as well as the limited generalizability of their results. Finally, outcome rates varied between studies, limiting cross-sectional comparisons. In addition, other epidemiological studies have not found statistically significant associations between exposure to sulfamethoxazole / trimethoprim and specific malformations

Animal data

In rats, oral doses of 533 mg / kg sulfamethoxazole or 200 mg / kg trimethoprim caused teratological effects, manifested mainly way in the form of a cleft palate.These doses are about 5 and 6 times the recommended total daily human dose based on body surface area. In two studies in rats, no teratology was observed with 512 mg / kg sulfamethoxazole in combination with 128 mg / kg trimethoprim. In some studies in rabbits, an overall increase in fetal loss (dead and resorbed primordia) was associated with doses of trimethoprim 6 times the therapeutic dose in humans, depending on body surface area

Non-teratogenic effects

See CONTRAINDICATIONS section.

Nursing Mothers

The level of trimethoprim / sulfamethoxazole in breast milk is approximately 2-5% of the RDA for infants over 2 months of age. Caution should be exercised when prescribing Disseptil Forte to a nursing woman, especially when breastfeeding icteric, sick, stressed or premature babies due to the potential risk of displacement of bilirubin and kernicterus.

Pediatric use

Disseptil Forte is contraindicated in pediatric patients younger than 2 months of age (see. INDICATIONS FOR USE and CONTRAINDICATIONS ).

Geriatric Uses

Clinical studies of Diseptil Forte did not include sufficient numbers of subjects aged 65 and over to determine if they differ in response from younger subjects.

In elderly patients, the risk of developing severe adverse reactions may be increased, especially in the presence of complicating conditions, such as impaired renal and / or liver function, possible deficiency of folic acid, or the simultaneous use of other drugs.Severe skin reactions, generalized bone marrow suppression (see WARNINGS and ADVERSE REACTIONS sections), specific platelet reduction (with or without purpura) and hyperkalemia are the most frequently reported severe adverse reactions in elderly patients. Individuals concurrently receiving certain diuretics, primarily thiazides, have an increased incidence of thrombocytopenia with purpura. An increased level of digoxin in the blood can be observed with concomitant therapy with Diseptil Forte, especially in elderly patients.Serum digoxin levels should be monitored. Hematologic changes indicative of folate deficiency can be observed in elderly patients. These effects are reversible with folic acid therapy. For patients with impaired renal function, appropriate dose adjustments should be made, and the duration of use should be as short as possible to minimize the risk of adverse reactions (see DOSAGE AND DOSAGE section). Trimethoprim component Diseptil Forte can cause hyperkalemia when administered to patients with major disorders of potassium metabolism, with renal failure, or when used simultaneously with drugs that are known to cause hyperkalemia, such as angiotensin-converting enzyme inhibitors. 8 These patients require careful monitoring of serum potassium levels. To reduce the level of potassium in the blood serum, it is recommended to discontinue treatment with Diseptil Forte. Disseptil Forte tablets contain 1.8 mg (0.08 meq) sodium per tablet. Disseptil Forte DS tablets contain 3.6 mg (0.16 meq) sodium per tablet.

Pharmacokinetic parameters of sulfamethoxazole were similar for elderly patients and young adults. The mean maximum serum concentration of trimethoprim was higher and the mean renal clearance of trimethoprim was lower in older patients compared with younger patients 3 (see. CLINICAL PHARMACOLOGY : Geriatric Pharmacokinetics :).

RECOMMENDATIONS

3. Varoqaux O, et al. Pharmacokinetics of trimethoprim-sulfamethoxazole combination in the elderly. Br J Clin Pharmacol. 1985, 20: 575-581.

7. Safrin S, Li BL, Sande MA. Folic acid supplementation with trimethoprim-sulfamethoxazole for Pneumocystis pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death.J Infect Dis. 1994 Oct 170 (4): 912-7.

8. Marinella MA. Trimethoprim – Induced Hyperkalemia: An Analysis of Reported Cases. Gerontology 45: 209-212, 1999.

9. Brumfitt U., Purcell R. Trimethoprim-sulfamethoxazole in the treatment of bacteriuria in women. J Infect Dis. 1973.128 (suppl): S657-S663.

Deaths, although very rare, have been due to severe reactions including fulminant liver necrosis, agranulocytosis, aplastic anemia, other blood dyscrasias, and airway hypersensitivity.

– Life-threatening skin reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with Septrin.

-Patients should be informed of signs and symptoms and closely monitored for skin reactions. The highest risk of SJS or TEN is observed during the first weeks of treatment.

-In the presence of symptoms or signs of SJS or TEN (for example, a progressive skin rash, often with blisters or lesions of the mucous membranes), treatment with Septrin should be discontinued (see.4.8 Adverse Effects).

-The best results in the treatment of SJS and TEN are achieved with early diagnosis and immediate discontinuation of any suspicious drug. Early withdrawal is associated with a better prognosis.

-If a patient develops SJS or TEN using Septrin, Septrin should not be restarted in that patient at any time.

Particular attention is paid to always is recommended when treating elderly patients, since as a group they are more susceptible to adverse reactions and are more prone to serious consequences as a result, especially in the presence of complicating conditions such as impaired renal and / or liver function and / or simultaneous use of other drugs.

Adequate urine output must be maintained at all times. Signs of crystalluria in vivo are rare, although sulfonamide crystals have been observed in chilled urine in treated patients. In patients who are malnourished, the risk may be increased.

Regular monthly blood tests are recommended for long-term use of Septrin, as well as in patients with folate deficiency or in the elderly, since there is a possibility of asymptomatic changes in hematological laboratory parameters due to the lack of available folic acid.These changes can be reversed by the administration of folic acid (5-10 mg / day) without disrupting the antibacterial activity.

In patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, hemolysis may occur.

Septrin should be used with caution in patients with severe allergies or bronchial asthma.

Septrin should not be used in the treatment of streptococcal pharyngitis caused by group A beta-hemolytic streptococci, the eradication of these organisms from the oropharynx is less effective than with the use of penicillin.

Trimethoprim has been observed to impair phenylalanine metabolism, but this is of no consequence in PKU patients with appropriate dietary restriction.

Avoid the appointment of Septrin to patients who are known or suspected of being at risk of developing acute porphyria. Both trimethoprim and sulfonamides (although not specifically sulfamethoxazole) have been associated with clinical exacerbation of porphyria.

Careful monitoring of serum potassium and sodium levels is warranted in patients at risk of developing hyperkalemia and hypopnatremia.

Except under close supervision, Septrin should not be prescribed to patients with serious hematological disorders (see 4.8 Adverse Effects). Septrin was prescribed to patients receiving cytotoxic therapy with little or no additional effect on the bone marrow or peripheral blood.

The combination of antibiotics in Septrin should be used only when, in the opinion of the physician, the benefits of treatment outweigh any possible risks, consideration should be given to using one effective antibacterial agent.

Patients with rare hereditary problems of fructose intolerance should not take this medication. See Section 2 Quantitative and Qualitative Composition.

This medicinal product contains methyl hydroxybenzoate, which may cause allergic reactions (possibly delayed).

This medicinal product contains a small amount of ethanol (alcohol), less than 100 mg per 5 ml.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose and therefore is substantially sodium free.

AZITROMYCIN EXPRESS 0.5 N3 TABL DISPERG / PHARMSTANDART /

Antacids

Antacids do not affect the bioavailability of azithromycin, but at least reduce the maximum concentration in the blood, therefore, the drug should be taken by at least 30%, therefore one hour before or two hours after taking these drugs and food.

Cetirizine

Simultaneous use of azithromycin with cetirizine (20 mg) in healthy volunteers for 5 days did not lead to pharmacokinetic interaction and a significant change in the QT interval.

Didanosine (dideoxyinosine)

The simultaneous use of azithromycin (1200 mg / day) and didanosine (400 mg / day) in 6 HIV-infected patients did not reveal changes in the pharmacokinetic indications of didanosine as compared with the placebo group.

Digoxin and colchicine (substrates of P-glycoprotein)

The simultaneous use of macrolide antibiotics, including azithromycin, with substrates of P-glycoprotein, such as digoxin and colchicine, leads to an increase in the concentration of P-glycoprotein in blood serum …Thus, with the simultaneous use of azithromycin and digoxin, it is necessary to take into account the possibility of increasing the concentration of digoxin in the blood serum.

Zidovudine

The simultaneous use of azithromycin (a single dose of 1000 mg and a multiple dose of 1200 mg or 600 mg) has little effect on pharmacokinetics, including the excretion of zidovudine or its glucuronide metabolite by the kidneys. However, the use of azithromycin caused an increase in the concentration of phosphorylated zidovudine, a clinically active metabolite, in peripheral blood mononuclear cells.The clinical significance of this finding is unclear.

Azithromycin weakly interacts with isoenzymes of the cytochrome P450 system. It was not revealed that azithromycin is involved in pharmacokinetic interactions similar to erythromycin and other macrolides. Azithromycin is not an inhibitor and inducer of cytochrome P450 isoenzymes.

Ergot alkaloids

Given the theoretical possibility of ergotism, the simultaneous use of azithromycin with ergot alkaloids is not recommended.

Pharmacokinetic studies were carried out for the simultaneous use of azithromycin and drugs, the metabolism of which occurs with the participation of isoenzymes of the cytochrome P450 system.

Atorvastatin

The simultaneous use of atorvastatin (10 mg daily) and azithromycin (500 mg daily) did not cause changes in atorvastatin concentrations in blood plasma (based on the analysis of inhibition of HMC-CoA reductase). However, in the post-registration period, there were separate reports of cases of rhabdomyolysis in patients receiving both azithromycin and statins.

Carbamazepine

In pharmacokinetic studies with healthy volunteers, no significant effect on the concentration of carbamazepine and its active metabolite in the blood plasma was found in patients receiving simultaneously azithromycin.

Cimetidine

In pharmacokinetic studies of the effect of a single dose of cimetidine on the pharmacokinetics of azithromycin, no changes in the pharmacokinetics of azithromycin were detected, provided that cimetidine was used 2 hours before azithromycin.

Indirect anticoagulants (coumarin derivatives)

In pharmacokinetic studies, azithromycin did not affect the anticoagulant effect of a single dose of 15 mg warfarin taken by healthy volunteers. It was reported about the potentiation of the anticoagulant effect after the simultaneous use of azithromycin and indirect anticoagulants (coumarin derivatives). Despite the fact that a causal relationship has not been established, one should take into account the need for frequent monitoring of prothrombin time when using azithromycin in patients who receive indirect oral anticoagulants (coumarin derivatives).

Cyclosporin

In a pharmacokinetic study involving healthy volunteers who took azithromycin (500 mg / day once) orally for 3 days, and then cyclosporin (10 mg / kg / day once), a significant increase in the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-5) of cyclosporine. Caution should be exercised with the simultaneous use of these drugs. If the simultaneous use of these drugs is necessary, it is necessary to monitor the concentration of cyclosporine in the blood plasma and adjust the dose accordingly.

Efavirenz

The simultaneous use of azithromycin (600 mg / day once) and efavirenz

(400 mg / day) daily for 7 days did not cause any clinically significant pharmacokinetic interaction.

Fluconazole

The simultaneous use of azithromycin (1200 mg once) did not change the pharmacokinetics of fluconazole (800 mg once). The total exposure and half-life of azithromycin did not change with the simultaneous use of fluconazole, however, a decrease in the Cmax of azithromycin (by 18%) was observed, which had no clinical significance.

Indinavir

The simultaneous use of azithromycin (1200 mg once) did not cause a statistically significant effect on the pharmacokinetics of indinavir (800 mg three times a day for 5 days).

Methylprednisolone

Azithromycin does not significantly affect the pharmacokinetics of methylprednisolone.

Nelfinavir

The simultaneous use of azithromycin (1200 mg) and nelfinavir (750 mg 3 times a day) causes an increase in the equilibrium concentrations of azithromycin in the blood serum.No clinically significant side effects were observed, and no dose adjustment of azithromycin is required when used simultaneously with nelfinavir.

Rifabutin

The simultaneous use of azithromycin and rifabutin does not affect the concentration of each drug in the blood serum. With the simultaneous use of azithromycin and rifabutin, neutropenia was sometimes observed. Despite the fact that neutropenia was associated with the use of rifabutin, a causal relationship between the use of a combination of azithromycin and rifabutin and neutropenia has not been established.

Sildenafil

When used in healthy volunteers, there was no evidence of the effect of azithromycin (500 mg / day daily for 3 days) on the AUC and Cmax of sildenafil or its main circulating metabolite.

Terfenadine

In pharmacokinetic studies, no evidence of an interaction between azithromycin and terfenadine was obtained. Isolated cases were reported where the possibility of such an interaction could not be completely ruled out, however, there was no concrete evidence that such an interaction took place.

It was found that the simultaneous use of terfenadine and macrolides can cause arrhythmias and prolongation of the QT interval.

Theophylline

No interaction was found between azithromycin and theophylline.

Triazolam / midazolam

Significant changes in pharmacokinetic parameters with the simultaneous use of azithromycin with triazolam or midazolam in therapeutic doses were not revealed.

Trimethoprim / sulfamethoxazole

The simultaneous use of trimethoprim / sulfamethoxazole with azithromycin did not reveal a significant effect on Cmax, total exposure or renal excretion of trimethoprim or sulfamethoxazole. Serum azithromycin concentrations were consistent with those found in other studies.

NOLIPREL A BI-FORTE 0.0025 + 0.01 N30 TABL P / PLEN / SHELL

General for perindopril and indapamide

Lithium preparations

Combination of inamidium with lithium preparations, usually perindopril not recommended (seesection “Interaction with other medicinal products”).

Renal impairment

Therapy with Noliprel A Bi-Forte is contraindicated in patients with moderate to severe renal impairment (CC below 60 ml / min). In some patients with arterial hypertension without previous obvious impairment of renal function, laboratory signs of functional renal failure may appear during therapy. In this case, treatment with Noliprel A Bi-forte should be discontinued.In the future, you can resume combination therapy using low doses of drugs, or use only one of the drugs.

Such patients need regular monitoring of the concentration of potassium and creatinine ions in the blood – 2 weeks after the start of therapy and then every 2 months during the period when the dose of the drug is selected. Renal failure is more common in patients with severe heart failure or underlying renal failure, including renal artery stenosis.

The drug Noliprel-A Bi-forte is not recommended for use in cases of bilateral renal artery stenosis or in the case of a single functioning kidney.

Hypotension and water-electrolyte imbalance

In case of initial hyponatremia, there is a risk of sudden development of arterial hypotension, in particular, in patients with renal artery stenosis. Therefore, a systematic assessment of the symptoms of dehydration and a decrease in plasma electrolytes is necessary, for example, after diarrhea or vomiting.Such patients need regular monitoring of the content of blood plasma electrolytes. With severe arterial hypotension, intravenous administration of isotonic saline may be required.

Transient arterial hypotension is not a contraindication for continued therapy.

After restoration of circulating blood volume and blood pressure, therapy can be resumed using low doses, or only one of the components of the drug can be used.

Potassium content

The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure.As with the use of any antihypertensive drug in combination with a diuretic, regular monitoring of the concentration of potassium ions in the blood plasma is necessary.

Excipients

The drug Noliprel® A Bi-forte is contraindicated in patients with hereditary galactose intolerance, complete lactase deficiency and glucose-galactose malabsorption.

Sodium content

Noliprel® A Bi-Forte contains less than 1 mmol sodium (23 mg) per tablet, that is, it practically does not contain sodium.

Childhood

The drug Noliprel® A Bi-Forte is contraindicated in children and adolescents under the age of 18 due to the lack of data on the efficacy and safety of perindopril and indapamide, both separately and together in patients of this age group.

Indapamide

Hepatic encephalopathy

In the presence of liver dysfunction, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy.In such a situation, you should immediately stop taking the diuretic.

Photosensitivity

Cases of photosensitivity reactions have been reported while taking thiazide and thiazide-like diuretics (see the Side Effects section). If a photosensitivity reaction develops while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays.

Water and electrolyte balance Concentration of sodium ions in blood plasma

The concentration of sodium ions in blood plasma must be determined before starting treatment, and then regularly monitored while taking the drug. A decrease in the concentration of sodium ions at the initial stage may not be accompanied by clinical symptoms, therefore, regular laboratory monitoring is necessary. More frequent monitoring of sodium ions is indicated in patients with cirrhosis of the liver and in elderly patients (see.Sections “Side effects” and “Overdose”). Treatment with any diuretic can cause hyponatremia, sometimes with very serious consequences. Hyponatremia accompanied by hypovolemia can lead to dehydration and orthostatic hypotension. A concomitant decrease in the content of chlorine ions can lead to the development of secondary compensatory metabolic alkalosis: the frequency of its occurrence and the degree of severity are insignificant.

Plasma potassium ion concentration

A decrease in potassium concentration with hypokalemia is the main risk associated with therapy with thiazide and thiazide-like diuretics.

It is necessary to prevent the risk of a decrease in the concentration of potassium ions (less than 3.4 mmol / l) in the following categories of high-risk patients: elderly patients and / or malnourished patients, both receiving and not receiving combined drug therapy, patients with cirrhosis of the liver with edema and ascites, ischemic heart disease, heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmias.

Patients with prolonged QT interval, both congenital and drug-induced, are also at increased risk.

Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially polymorphic ventricular tachycardia of the “pirouette” type, which can be fatal. In all the cases described above, more frequent monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of the concentration of potassium ions must be carried out within the first week from the start of therapy.If hypokalemia is detected, appropriate correction should be carried out.

Concentration of calcium ions in blood plasma

Thiazide and thiazide-like diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the content of calcium ions in blood plasma. A pronounced increase in the concentration of calcium ions may be associated with undiagnosed hyperparathyroidism. Before examining the function of the parathyroid glands, diuretics should be discontinued.

Blood glucose concentration

It is necessary to monitor the blood glucose concentration in patients with diabetes mellitus, especially when the concentration of potassium ions is low.

Uric acid

Patients with elevated plasma uric acid concentrations tend to have an increased incidence of gout attacks.

Diuretics and renal function

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (creatinine concentration in adult patients is below 25 mg / L or 220 μmol / L).In elderly patients, the plasma creatinine level should be assessed taking into account age, weight and sex, in accordance with the Cockcroft formula:

Creatinine clearance (CC) = (140 – age) x weight / 0.814 x plasma creatinine concentration where: age in years, weight in kg, plasma creatinine concentration in μmol / l

The formula is suitable for elderly men; for older women, the result should be multiplied by a factor of 0.85.

At the beginning of diuretic treatment in patients due to hypovolemia (due to the excretion of water and sodium ions), there may be a temporary decrease in the glomerular filtration rate and an increase in the concentration of urea and creatinine in the blood plasma.This transient functional renal failure does not have adverse consequences for patients with initially normal renal function, but may exacerbate pre-treatment renal impairment.

Athletes

Athletes should pay attention to the fact that the medicinal product contains an active substance that can give a positive result during a doping test.

Acute myopia and secondary angle-closure glaucoma

Sulfonamides and their derivatives can cause the development of idiosyncratic reactions leading to temporary myopia and acute angle-closure glaucoma.Without proper therapy, acute angle-closure glaucoma can lead to vision loss. First of all, it is necessary to stop taking the drug as soon as possible. If intraocular pressure continues to be high, immediate medical or surgical treatment may be required. Risk factors that can lead to the development of acute angle-closure glaucoma include an allergy to sulfonamide or penicillin.

Perindopril

Double blockade of the renin-angiotensin-aldosterone system (RAAS) There is evidence of an increased risk of arterial hypotension, hyperkalemia and a decrease in renal function (including acute renal failure) when combined with the use of inhibitors of AP II AP inhibitors …Therefore, double blockade of the RAAS by combining an ACE inhibitor with ARA II or aliskiren is not recommended (see sections “Pharmacodynamics” “Interaction with other drugs”). If double blockade is absolutely necessary, then this should be done under the strict supervision of a specialist with regular monitoring of renal function, plasma electrolytes and blood pressure.

The use of ACE inhibitors in combination with ARA II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see.section “Contraindications” and “Interaction with other medicinal products”).

Potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for table salt and food additives

Combined use of perindopril and potassium-sparing diuretics, as well as potassium preparations, potassium-containing substitutes for food salt and food additives is not recommended (see. medicines “).

Neutropenia / agranulocytosis / thrombocytopenia / anemia

There are reports of the development of neutropenia / agranulocytosis, thrombocytopenia and anemia while taking ACE inhibitors.In patients with normal renal function and no associated risk factors, neutropenia is rare. With extreme caution, perindopril should be used against the background of systemic diseases of the connective tissue, as well as while taking immunosuppressants, allopurinol, procainamide or a combination of these factors, especially in patients with initially impaired renal function.

Some patients developed severe infectious diseases, in some cases resistant to intensive antibiotic therapy.When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should inform their doctor about any signs of infectious diseases (for example, sore throat, fever) (see sections “Side effects” and “Interaction with other medicinal products”). Anemia can develop in patients after kidney transplantation or in patients on hemodialysis. In this case, the decrease in hemoglobin is the greater, the higher its initial value was.This effect, apparently, is not dose-dependent, but may be related to the mechanism of action of ACE inhibitors.

A slight decrease in hemoglobin occurs during the first 6 months, then it remains stable and fully recovers after discontinuation of the drug. In such patients, treatment can be continued, but hematological tests should be performed regularly. Renovascular hypertension

In patients with bilateral renal artery stenosis or stenosis of an artery of a single functioning kidney, the risk of hypotension and renal failure increases with the use of an ACE inhibitor.section “Contraindications”). Taking diuretics can be an additional risk factor (see section “Contraindications”). Deterioration of renal function can be observed even with a slight change in serum creatinine concentration, even in patients with unilateral renal artery stenosis. ” The treatment of renovascular hypertension is revascularization. Nevertheless, the use of ACE inhibitors can have a positive effect in this category of patients, both awaiting surgery and in the case when surgery is not possible.

Treatment with Noliprel® A Bi-forte is not indicated in patients with established or suspected renal artery stenosis, because therapy should be started in a hospital setting with lower doses of the combination of perindopril and indapamide.

Hypersensitivity / angioedema

When taking ACE inhibitors, including perindopril, in rare cases, there may be the development of angioedema of the face, limbs, lips, tongue, vocal folds and / or larynx (see.section “Side effects”). This can happen at any time during therapy. If symptoms appear, perindopril should be discontinued immediately, and the patient should be observed until the signs of edema disappear completely. If the swelling affects only the face and lips, then it usually goes away on its own, although antihistamines can be used as symptomatic therapy.

Angioedema accompanied by laryngeal edema can be fatal.Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. When such symptoms appear, appropriate therapy should be started immediately, for example, inject subcutaneously epinephrine (adrenaline) at a dilution of 1: 1000 (0.3 or 0.5 ml) and / or ensure airway patency.

A higher risk of angioedema has been reported in black patients.

In patients with a history of angioedema not associated with the use of ACE inhibitors, the risk of its development may be increased when taking drugs of this group (see.section “Contraindications”).

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors.

In this case, the patients had abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal activity of the enzyme C-1 esterase. Diagnosis is by abdominal computed tomography, ultrasound, or surgery.Symptoms resolved after discontinuation of ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when conducting differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

Combined use with combined medicinal products containing valsartan + sacubitril.

The combined use of perindopril with combined medicinal products containing valsartan + sacubitril is contraindicated, since the risk of developing angioedema is increased (see.section “Contraindications”). The use of a combined medicinal product containing valsartan + sacubitril is possible no earlier than 36 hours after the last dose of perindopril. The use of perindopril is possible no earlier than 36 hours after stopping the administration of the combined medicinal product containing valsartan + sacubitril (see the section “Contraindications” and “Interactions with other medicinal products”). When ACE inhibitors are used together with other neprilisin inhibitors (for example, racecadotril), the risk of developing angioedema may be increased (see.section “Interaction with other medicinal products”). In patients receiving therapy with perindopril, a careful assessment of the risk / benefit ratio should be performed before starting treatment with neprilisin inhibitors (for example, racecadotril).

mTOR inhibitors (mammalian rapamycin targets) (eg sirolimus, everolimus, temsirolimus)

When used together with mTOR inhibitors (eg sirolimus, everolimus from the respiratory tract, temsirolimus) or tongue, with or without respiratory impairment) (see.section “Interaction with other medicinal products”).

Anaphylactoid reactions during desensitization

There are isolated reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera venom) (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures.The use of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, in patients who require both the use of an ACE inhibitor and a desensitization procedure, anaphylactoid reaction can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the start of the procedure.

Anaphylactoid reactions during LDL apheresis

In rare cases, patients receiving ACE inhibitors have developed life-threatening anaphylactoid reactions during LDL apheresis using dextran sulfate.To prevent anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.

Hemodialysis patients

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high flow membranes (eg AN69®). Therefore, it is desirable to use a membrane of a different type or to use an antihypertensive agent of another pharmacotherapeutic group.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism, as a rule, are not susceptible to antihypertensive drugs, the action of which is based on inhibition of the RAAS. Therefore, the use of the drug in these patients is not recommended.

Cough

During therapy with an ACE inhibitor, a dry persistent cough may occur, which disappears after the drug is discontinued. When a dry cough appears in a patient, one should remember about the possible iatrogenic nature of this symptom.If the attending physician believes that therapy with an ACE inhibitor is necessary for the patient, it is possible to continue taking the drug.

Children

The efficacy and tolerability of perindopril in children and adolescents as monotherapy or in combination with other drugs has not been established.

Risk of arterial hypotension and / or renal failure (in patients with chronic heart failure, imbalance in water and electrolyte balance, etc.)

In some pathological conditions, there may be a significant activation of the renin-angiotensin-aldosterone system, especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (against the background of a salt-free diet or long-term use of diuretics), in patients with baseline low blood pressure, renal artery stenosis, congestive heart failure, or cirrhosis of the liver with edema and ascites.

The use of an ACE inhibitor causes a blockade of the RAAS and, therefore, may be accompanied by a sharp decrease in blood pressure and / or an increase in the concentration of creatinine in the blood plasma, indicating the development of functional renal failure.These phenomena are more often observed when taking the first dose of the drug and during the first two weeks of therapy. In rare cases, these conditions develop sharply and at other times of therapy. In such cases, when resuming therapy, it is recommended to use the drug at a lower dose and then gradually increase the dose.

Old age

Before starting perindopril, it is necessary to assess the functional activity of the kidneys and the content of potassium ions in the blood plasma.At the beginning of therapy, the dose of the drug is selected, taking into account the degree of decrease in blood pressure, especially in the case of dehydration and loss of electrolytes. Such measures allow you to avoid a sharp decrease in blood pressure.

Atherosclerosis

The risk of arterial hypotension exists in all patients, however, special care should be taken when using the drug in patients with coronary heart disease and cerebrovascular accident. In these patients, treatment should be started with low doses of the drug.

Heart failure / severe heart failure

In patients with severe heart failure (NYHA functional class IV), treatment with Noliprel A Bi-forte is not indicated, since therapy should be started with lower doses of the combination perindopril and indapamide and under close medical supervision.

Patients with arterial hypertension and coronary heart disease should not stop taking beta-blockers: ACE inhibitors should be used together with beta-blockers.Patients with diabetes mellitus

In patients with insulin-dependent diabetes mellitus (risk of spontaneous increase in the content), therapy with the drug Noliprel® A Bi-Forte is inappropriate, since treatment should begin with minimal doses and take place under constant medical supervision.

The level of glycemia should be carefully monitored in patients with diabetes mellitus who have previously received oral hypoglycemic drugs or insulin, namely during the first month of therapy with an ACE inhibitor (see.section “Interaction with other medicinal products”).

Ethnic differences

Perindopril, like other ACE inhibitors, has a clearly less pronounced antihypertensive effect in black patients compared to other races. Perhaps this difference is due to the fact that in patients with arterial hypertension of the Negroid race, low renin activity is more often observed.

Surgery / Anesthesia

The use of ACE inhibitors can lead to hypotension, especially when used together with antihypertensive anesthetics.Therefore, it is recommended that, if possible, stop taking long-acting ACE inhibitors such as perindopril one day before surgery.

Aortic or mitral valve stenosis / hypertrophic obstructive cardiomyopathy

ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction.

Liver failure

In rare cases, cholestatic jaundice occurs while taking ACE inhibitors.With the progression of this syndrome, fulminant necrosis of the liver may develop, sometimes with a fatal outcome. The mechanism for the development of this syndrome is unclear. If jaundice develops or if the activity of liver enzymes is significantly increased while taking ACE inhibitors, the patient should stop taking the ACE inhibitor and be under the appropriate supervision of a physician (see the “Side Effects” section).

Hyperkalemia

Hyperkalemia can develop during treatment with ACE inhibitors, including perindopril.Risk factors for hyperkalemia are renal failure, deterioration of renal function, age over 70, diabetes mellitus, some concomitant conditions, in particular dehydration, acute decompensation of cardiac activity, metabolic acidosis, concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride) , as well as preparations of potassium or potassium-containing substitutes for table salt, as well as the use of other drugs that increase the level of potassium in the blood plasma (for example, heparins, co-trimoxazole, also known as a combination of sulfamethoxazole + trimethoprim, other ACE inhibitors, angiotensin II receptor antagonists, acetylsalicylic acid (3 g / day or more), cyclooxygenase-2 (COX-2) inhibitors and non-selective NSAIDs, immunosuppressants such as cyclosporine or tacrolimus, and trimethoprim).The use of potassium preparations, potassium-sparing diuretics, potassium-containing substitutes for table salt can lead to a significant increase in the level of potassium in the blood, especially in patients with reduced kidney function. Hyperkalemia can lead to serious, sometimes fatal, heart rhythm disturbances. If the combined use of the above drugs is necessary, treatment should be carried out with caution against the background of regular monitoring of the content of potassium ions in the blood serum (see the section “Interaction with other drugs”).

Influence on the ability to drive vehicles, mechanisms

Both active ingredients, either individually or in combination with indapamide + perindopril, do not affect the ability to drive a car or other mechanisms. In some patients, especially at the beginning of therapy or in addition to the ongoing therapy of other antihypertensive drugs, individual reactions associated with a decrease in blood pressure may occur. As a result, the ability to drive a car and other mechanisms may be impaired.

Covid19 Clinical Study: Oral Co-trimoxazole – Clinical Trials Registry

Detailed Description

The coronavirus disease (COVID-19) caused by SARS-COV2 is a highly transmitted and potentially fatal disease that is currently a major public health concern. The pandemic situation in Bangladesh is also rapidly evolving with positive cases and deaths.increases every day. Epidemiological changes in COVID-19 infection should be monitored. take into account potential routes of transmission and subclinical infections, in addition to adaptation, evolution and spread of the virus among humans and possible intermediate animals and reservoirs, but there is still no specific guideline that deals with this deadly viral infection. However, there are several drugs that can provide positive impact on the patient’s recovery.Cotrimoxazole is a proven antibiotic that has been clinically tested. used for 60 years with antibacterial action against a wide range of organisms. With its antimicrobial effect, co-trimoxazole has anti-inflammatory and immunomodulatory effects. Co-trimoxazole has previously been shown to have an anticytokine effect by inhibiting interleukin 1, 6 (IL-1, IL-6) and tumor necrosis factor α (TNF α), which are the main cytokines identified in patients with severe COVID-19 …significant clinical improvement in ARDS, so there is a possibility that cotrimoxazole may also play a role in improving clinical outcome in patients with COVID-19, especially in moderate to severe cases. To date, there is no specific treatment for COVID-19 infections if cotrimoxazole if will be recognized as effective, will bring great benefit to the target In addition, cotrimoxazole, a very cheap drug compared to others, will also bring great economic benefits in caring for the general population.There are no published studies on the role of cotrimoxazole in COVID-19 patients, this study will generate new information that will be of great benefit in the fight against COVID-19 infectious disease. Investigate question: What are the results of taking cotrimoxazole in patients with severe COVID-19? Objectives: Overall objectives To assess the clinical outcome of cotrimoxazolein treatment in patients with severe disease. COVID-19 Specific Objectives: To assess the length of stay receiving co-trimoxazole in addition to standard treatment versus standard treatment alone.To find out side effects (rash, itching, dizziness, headache, nausea, vomiting, diarrhea, sore throat, unusual bruising or bleeding, yellowing of the skin or discoloration of the eyes, joints or muscle pain, red or purple skin, etc.) drugs that are additionally treated with co-trimoxazole to standard treatment versus standard treatment. To clarify the need for ventilator support (non-invasive and invasive ventilation) who are treated with co-trimoxazole in addition to standard treatment versus standard treatment alone.Estimate mortality in severe COVID-19 patients receiving co-trimoxazole. in addition to standard treatment versus standard treatment alone. Study design: open-label randomized controlled trial Study duration: six months. Study Population: Patients with symptoms of COVID-19 admitted to participating hospitals in Bangladesh will be assessed for eligibility. Inclusion criteria 1.Patients diagnosed with COVID-19 (positive RT-PCR for COVID-19) 2.age & gt; 18 years 3. hypoxic respiratory failure (saturation 50 mg / l Exclusion criterion 1. multiple organ failure 2. severe ARDS (requires ventilator support for invasive or invasive intervention). Non-invasive ventilation) 3. septic shock 4. severe liver disease 5. Acute renal failure (where GFR & lt; 15 and plasma sulfamethoxazole cannot be monitored) 6. Drug allergy / co-trimoxazole intolerance / sulfar sensitivity 7.pregnancy 8. already receiving tocilizumab or therapy during the recovery period. Sampling procedure: This RCT will consist of two groups, an experimental group and a control group. Random case (1: 1): control (non-blind) test. 1. the control group will receive standard treatment, 2. the experimental group will receive standard care and oral cotriamoxazole. (47) patients will be included in each group. Randomization will be done in a random table of numbers. Distributions will be numbered sequentially.Treatment Protocol Eligible patients will receive either oral co-trimoxazole + standard therapy or standard therapy only (per institution / national protocol). The following procedures are recommended as standard therapy: 1. Antibiotics for secondary bacterial infection according to facility instructions. 2. Supplemental oxygen (to maintain saturation between 90% and 96%) 3. IV hydration (to maintain euvolumia) 4.thromboprophylaxis according to local regulations. 5. paracetamol (orally or intravenously 1 gram of QDS as needed or regularly) 6. consider the use of steroids if indicated (for example, in exacerbation of COPD or in acute severe disease). asthma) NOTE: The dose of co-trimoxazole is 960 mg (trimethoprim 160 mg + sulfamethoxazole 800 mg) orally twice a day for 7 days. sample size: 94 Research instrument: 1. General questionnaire for assessing socio-demographic data.2. Clinical data checklist. 3. Checklist of the results of the investigation. Measure variable: Data collection is required for both groups (cotrimoxazole + standard therapy and standard therapy). only therapy) 1. age 2. sex 3. ethnicity 4. medical history – arterial hypertension, taking an ACE inhibitor or ARB, diabetes mellitus, coronary artery disease, COPD, CKD, obesity. (BMI) and cancer 5. Present symptoms (dry cough, productive cough, fever, sore throat, myalgia, lethargy, headache, shortness of breath, nausea, diarrhea, etc.)) 6.base observations on the day of initiation of treatment (day 0): oxygen saturation (SpO2), inhaled oxygen fraction (FiO2), SpO2 / FiO2 ratio, respiratory rate, body temperature, neutrophil to lymphocyte ratio, C-reactive protein and bilateral results infiltrates on a chest x-ray. 7. follow-up after randomization on days 1, 2, 3, 4 and 5 to determine the SpO2 / FiO2 ratio, respiratory rate, body temperature and C-reactive protein 8. Length of stay (in days) 9.Using ventilator support (invasive or non-invasive ventilation) 10. Side effects of drugs 11. Inpatient mortality. Primary endpoints. 1. Length of hospital stay (days) 2. Inpatient mortality Secondary endpoints 1.Change in observations after randomization at 1, 2, 3, 4 and 5 days for SpO2 / FiO2 ratio, respiratory rate, body temperature and C-reactive protein 2. Using ventilator support (invasive or non-invasive ventilation) 3.Side Effects of Co-Trimoxazole Drugs Data Collection Procedure: A Pre-Designed Case Record Form (CRF) will be used to collect data that will also contain the study result. The information gathered by the CRF will be reviewed and the inconsistencies will be investigated and clarified. the data from the case record forms will be anonymized and stored securely in a secure online portal. Statistical analysis: Statistical analysis will be performed using t-test or Mann-Whitney U test or Wilcoxon signed rank test for continuous variables and Chi-square test or Fisher’s test.exact test for categorical variables. Survival will be assessed using the Kaplan-Meier method. Comparison between the two groups will be made using a log rank test and hazard rating. regression test: a p value & lt; 0.05 will be considered significant. SPSS version 25 software will be used for the analysis.

Description CO-TRIMOXAZOLE indications, dosages, contraindications for the active substance CO-TRIMOXAZOLE

With the simultaneous use of co-trimoxazole, the effect of indirect anticoagulants is significantly enhanced due to the slowdown in the inactivation of the latter, as well as their release from the connection with plasma proteins.

With simultaneous use with some sulfonylurea derivatives, an increase in the hypoglycemic effect is possible, which is associated with an increase in the concentration of the free fraction of co-trimoxazole.

The simultaneous use of co-trimoxazole and methotrexate can lead to an increase in the toxicity of the latter (in particular, to the appearance of pancytopenia) due to its release from the bond with plasma proteins.

Under the influence of butadione, indomethacin, naproxen, salicylates and some other NSAIDs, the action of co-trimoxazole may increase with the development of undesirable effects, since the release of active substances from the connection with blood proteins and an increase in their concentration.

The simultaneous administration of diuretics and co-trimoxazole increases the likelihood of thrombocytopenia caused by the latter, especially in elderly patients.

In the case of the simultaneous administration of chloridine with co-trimoxazole, the antimicrobial effect is enhanced, since chloridine inhibits the formation of tetrahydrofolic acid, which is necessary for the synthesis of nucleic acids and proteins. In turn, sulfonamides inhibit the formation of dihydrofolic acid, which is a precursor of tetrahydrofolic acid.This combination is widely used in the treatment of toxoplasmosis.

The absorption of sulfamethoxazole and trimethoprim when taken together with cholestyramine decreases as a result of the formation of insoluble complexes, which leads to a decrease in their concentration in the blood.

Reduces the intensity of hepatic metabolism of phenytoin (lengthens its T 1/2 by 39%), increasing its effect and toxic effect.

With the simultaneous use of co-trimoxazole with pyrimethamine in doses exceeding 25 mg / week., the risk of developing megaloblastic anemia increases.

May increase serum digoxin concentrations, especially in elderly patients, monitor serum digoxin concentrations.

The effectiveness of tricyclic antidepressants when combined with co-trimoxazole may be reduced.

Patients receiving co-trimoxazole and cyclosporine after kidney transplantation may experience a reversible deterioration in renal function, manifested by an increase in creatinine levels.

With simultaneous use with ACE inhibitors, especially in elderly patients, hyperkalemia may develop.

Trimethoprim, inhibiting the transport system of the kidneys, increases the AUC of dofetilide by 103% and C max dofetilide by 93%. When the concentration is increased, dofetilide can cause ventricular arrhythmias with prolongation of the QT interval, including pirouette-type arrhythmias. Simultaneous use is contraindicated.

Tacrolimus (Systemic) | Memorial Sloan Kettering Cancer Center

This document, provided by Lexicomp ® , contains all the information you need to know about the drug, including the indications, route of administration, side effects, and when you should contact your healthcare provider.

Trade names: USA

Astagraf XL; Envarsus XR; Prograf

Trade names: Canada

Advagraf; Envarsus PA; Prograf; SANDOZ Tacrolimus

Warning

All forms of issue:

  • Taking this drug may increase the risk of cancer, such as lymphoma or skin cancer. Check with your doctor.
  • Get a skin examination.Tell your doctor if you have any skin changes, such as a new wart, a skin ulcer, or a reddish bleeding or non-healing swelling, or a change in the color or size of a mole.
  • Get immediate medical attention if you develop symptoms such as swollen lymph nodes, night sweats, shortness of breath, or unexplained weight loss.
  • This drug may increase the risk of very serious and sometimes deadly infections. Check with your doctor.
  • Any sign of infection, such as fever, chills, flu-like symptoms, very severe sore throat, ear or sinus pain, cough, increased or discolored sputum secretion, pain when urinating, ulceration in the mouth or non-healing wounds, see a doctor immediately.

Sustained-release capsules:

  • In one study, deaths were more common among women in patients using this drug after liver transplantation.This drug should not be used after liver transplantation.

What is this drug used for?

  • Used to prevent organ damage after transplantation.
  • This drug may also be used for other indications. Check with your doctor.

What do I need to tell my doctor BEFORE taking this drug?

  • If you are allergic to this drug, any of its ingredients, other drugs, foods or substances.Tell your doctor about your allergy and how it manifested itself.
  • With prolongation of the QT interval on the ECG.
  • If you are taking any of the following drugs: cyclosporine or sirolimus.

This list of drugs and diseases that may be adversely associated with this drug is not exhaustive.

Tell your doctor and pharmacist about all the medicines you take (prescription and over-the-counter, natural products and vitamins) and your health problems.You need to make sure that this drug is safe for your medical conditions and in combination with other drugs you are already taking. Do not start or stop taking any drug or change the dosage without your doctor’s approval.

What do I need to know or do while I am taking this drug?

  • Tell all healthcare providers that you are taking this drug.These are doctors, nurses, pharmacists and dentists.
  • You may be at increased risk of developing an infection. Wash your hands often. Try not to come into contact with carriers of the infection, incl. with people with colds or flu.
  • Perform blood tests as directed by your doctor. Please consult your doctor.
  • Many other drugs affect the amount of this drug in your body. This can increase the likelihood of organ rejection or side effects.If you are taking other drugs, talk to your doctor about taking blood samples for a more thorough test while taking this drug.
  • High blood pressure has happened with this drug. Monitor your blood pressure as directed by your doctor.
  • High blood sugar has happened with this drug. This includes the development or worsening of pre-existing diabetes mellitus.
  • Check your blood sugar as directed by your doctor.
  • Tell your doctor if you develop signs of high blood sugar, such as confusion, drowsiness, increased thirst and hunger, increased urination, facial flushing, rapid breathing, and fruity breath.
  • Do not consume grapefruit or grapefruit juice.
  • If you have not received all of the vaccines on schedule, talk to your doctor.You may need to get some vaccines before using this drug.
  • Consult a physician prior to any vaccination. Using some vaccines with this drug may increase the chance of infection or make the vaccine less effective.
  • You may need to refrain from consuming alcoholic beverages with certain medications. Ask your doctor or pharmacist to see if you should refrain from drinking alcoholic beverages with this drug.
  • Possibly increased risk of skin cancer. Avoid prolonged exposure to the sun, use of sun lamps and tanning beds. Use sunscreen, long clothing, and sunglasses.
  • Very bad and sometimes deadly gastrointestinal perforation has happened with this drug. Check with your doctor.
  • A very serious and sometimes deadly brain disorder called posterior reversible encephalopathy syndrome (PRES) has happened with this drug.If you have symptoms such as confused thinking, decreased concentration, change or loss of vision, seizures, or a very severe headache, contact your doctor immediately.
  • This drug may cause some type of heart rhythm disorder (prolonged QT interval). In this case, the risk of developing other unsafe, sometimes deadly, heart rhythm disturbances may be higher.
  • This drug may affect fertility.Fertility problems can lead to infertility in both men and women. If you plan to become pregnant or conceive a child, talk with your doctor before taking this drug.
  • Potentially harmful effects on the fetus if used during pregnancy. All people who will be treated with this drug should talk with their doctor about the use of contraception.
  • If you are pregnant or get pregnant while taking this drug, call your doctor right away.
  • If your sexual partner is pregnant or is planning a pregnancy during your course of treatment, consult your doctor.
  • Tell your doctor if you are breastfeeding. It is necessary to consult if the drug poses any risk to the child.

What side effects should I report to my doctor immediately?

WARNING. In rare cases, some people with this drug can cause serious and sometimes deadly side effects.Call your healthcare professional or get medical attention right away if you have any of the following signs or symptoms, which may be associated with serious side effects:

  • Signs of an allergic reaction such as rash, hives, itching, reddened and swollen skin with blistering or scaling, possibly associated with fever, wheezing or wheezing, tightness in the chest or throat, difficulty breathing, swallowing or speaking, unusual hoarseness, swelling in the mouth, face, lips, tongue, or throat.
  • Signs of kidney problems, including not urinating, change in urine volume, blood in the urine, or weight gain.
  • Signs of electrolyte imbalance, such as sudden changes in mood, confusion, muscle pain or weakness, a feeling of disturbed heartbeat, seizures, lack of appetite, severe stomach upset, or vomiting.
  • Signs of high blood pressure, such as very severe headache, or dizziness, or loss of consciousness, or blurred vision.
  • Symptoms of increased blood acidity (acidosis) such as confusion, rapid breathing, tachycardia, irregular heartbeat, very severe abdominal pain, nausea or vomiting, severe drowsiness, shortness of breath, increased fatigue or weakness.
  • Sensation of warmth, redness or soreness of the skin, or ulceration of the body.
  • Pain or pressure in the chest.
  • Shortness of breath, sudden weight gain, or swelling of the arms or legs.
  • Shiver.
  • Violation of motor functions.
  • Any unexplained bruising or bleeding.
  • Unusual burning, numbness, or tingling sensations.
  • Pale skin.
  • Black, tarry, or bloody stools.
  • Vomiting of blood or vomit in the form of coffee grounds.
  • A very bad brain disorder called progressive multifocal leukoencephalopathy (PML) has developed with this drug.It can lead to disability or death. If you develop signs such as confusion, memory problems, depressed mood (depression), movement disorders, changes in muscle strength on one side of the body, difficulty speaking or thinking, balance problems, or blurred vision, consult your doctor immediately.

What are some other side effects of this drug?

Any medicine can have side effects.However, many people have little or no side effects. Call your doctor or get medical help if these or any other side effects bother you or do not go away:

  • Feeling dizzy, tired or weak.
  • Headache.
  • Constipation, diarrhea, abdominal pain, nausea, vomiting, or decreased appetite.
  • Heartburn.
  • Sleep disorders.
  • Back pain.
  • Joint pain.
  • Irritation of nose or throat.

This list of potential side effects is not comprehensive. If you have any questions about side effects, please contact your doctor. Talk to your doctor about side effects.

You can report side effects to the National Health Office.

You can report side effects to the FDA at 1-800-332-1088. You can also report side effects at https: // www.fda.gov/medwatch.

What is the best way to take this drug?

Use this drug as directed by your healthcare practitioner. Read all the information provided to you. Follow all instructions strictly.

All oral preparations:

  • Continue taking this drug as directed by your doctor or other healthcare professional, even if you feel well.
  • Take this drug at about the same time of the day.
  • When you get a new prescription, check the drug to make sure you have the correct drug. If you have been given the wrong drug or are not sure what your drug should look like, contact your doctor right away.
  • If you are using a salt substitute containing potassium, a potassium-sparing diuretic, or a potassium supplement, consult your doctor.

Immediate-release capsules and granules:

  • Take with or without food, but do it the same way every time.Always take with food or only on an empty stomach.

Immediate release capsules:

  • Swallow whole. Do not chew, open, or crush.

Granules:

  • This drug must be used with extreme caution. Talk to your doctor or pharmacist on how to use this medication correctly.
  • Avoid breathing powder.
  • If this drug comes in contact with the skin, wash it off immediately with soap and water.
  • If this drug gets in your eyes, rinse your eyes with cold water.
  • Be sure to check the correct dose for this drug. Be sure to check the types of packs to be used to receive the dose. If in doubt, consult a doctor.
  • Use glass or metal objects when preparing a dose of the drug. Do not use plastic items.
  • Empty the contents of the container into a glass.Add 1-2 tablespoons (15-30 ml) of room temperature water to the glass and stir. The granules will not dissolve completely. After you take the drug, add the same volume of water to the glass, rinse and drink.
  • Take the dose immediately after mixing. Do not store for future use.
  • Do not add this drug to food.
  • If necessary, you can use the supplied oral syringe.
  • If you are giving this drug to your child whose weight changes, talk with your doctor.The dose of this drug may need to be changed.

All sustained-release preparations of the active substance:

  • Take in the morning on an empty stomach. Take no later than 1 hour before or no sooner than 2 hours after breakfast.
  • The drug should be swallowed completely with a glass of water.
  • Do not chew, break, or crush.
  • If you have difficulty swallowing, consult your doctor.

Infusion:

  • This drug is administered by intravenous infusion continuously over a period of time.
  • You will be closely monitored while you take this drug and for some time thereafter. Please consult your doctor.
  • If you are using a salt substitute containing potassium, a potassium-sparing diuretic, or a potassium supplement, consult your doctor.

What should I do if a dose of a drug is missed?

Immediate-release capsules and granules:

  • Take the missed dose as soon as you can.
  • If it is time for your next dose, do not take the missed dose and then return to your normal dose.
  • Do not take 2 doses at the same time or an additional dose.

Sustained-release capsules:

  • Take the missed dose as soon as you can.
  • If your dose is delayed by 14 hours or more, skip the forgotten dose and return to your normal dose schedule.
  • Do not take 2 doses at the same time or an additional dose.

Extended release tablets:

  • Take the missed dose as soon as you can.
  • If more than 15 hours have passed since the missed dose, do not take the missed dose and return to your normal dose schedule.
  • Do not take 2 doses at the same time or an additional dose.

Infusion:

  • See your doctor for further instructions.

How do I store and / or discard this drug?

All oral preparations:

  • Store at room temperature in a dry place. Do not store in the bathroom.

Infusion:

  • If you need to store this drug at home, ask your doctor, nurse, or pharmacist for information about how it is stored.

All forms of issue:

  • Store all medicines in a safe place.Keep all medicines out of the reach of children and pets.
  • Dispose of unused or expired drugs. Do not empty into toilet or drain unless directed to do so. If you have any questions about the disposal of your medicinal products, consult your pharmacist. There may be drug recycling programs in your area.

General information on medicinal products

  • If your health does not improve or even worsens, see your doctor.
  • Do not give your medicine to anyone or take other people’s medicines.
  • Some medicines may come with other patient information leaflets. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
  • Some medicines may come with other patient information leaflets. Check with your pharmacist. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
  • If you think there has been an overdose of a drug, call a Poison Control Center immediately or seek medical attention. Be prepared to tell or show which drug you took, how much and when it happened.

Use of information by the consumer and limitation of liability

This information should not be used to make decisions about taking this or any other drug. Only the attending physician has the necessary knowledge and experience to make decisions about which drugs are suitable for a particular patient.This information does not guarantee that the drug is safe, effective, or approved for the treatment of any disease or specific patient. Here are only brief general information about this drug. It does NOT contain all available information on the possible use of the drug with instructions for use, warnings, precautions, information about interactions, side effects and risks that may be associated with this drug. This information should not be construed as a treatment guide and does not replace information provided to you by your healthcare professional.Check with your doctor for complete information on the possible risks and benefits of taking this drug. Use of this information is governed by the Lexicomp End User License Agreement available at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

Copyright

© UpToDate, Inc. and its affiliates and / or licensors, 2021. All rights reserved.

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