Zithromax Tri-Pak Advanced Patient Information

Generic name: azithromycin [ ay-zith-roe-MYE-sin ]
Drug class: Macrolides

Medically reviewed by Drugs.com. Last updated on Aug 18, 2022.

Uses for Zithromax Tri-Pak

Azithromycin is used to treat certain bacterial infections in many different parts of the body. This medicine may mask or delay the symptoms of syphilis. It is not effective against syphilis infections.

Azithromycin belongs to the class of drugs known as macrolide antibiotics. It works by killing bacteria or preventing their growth. However, this medicine will not work for colds, flu, or other virus infections.

This medicine is available only with your doctor’s prescription.

Before using Zithromax Tri-Pak

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of azithromycin to treat sinusitis in children or to treat pneumonia in children younger than 6 months of age. Safety and efficacy have not been established.

Appropriate studies have not been performed on the relationship of age to the effects of azithromycin oral suspension and tablets to treat pharyngitis or tonsillitis in children younger than 2 years of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of azithromycin in the elderly. However, elderly patients are more likely to have heart rhythm problems (eg, torsades de pointes) which may require caution in patients receiving azithromycin.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Bepridil
• Cisapride
• Dihydroergotamine
• Dronedarone
• Ergoloid Mesylates
• Ergonovine
• Ergotamine
• Levoketoconazole
• Methylergonovine
• Methysergide
• Pimozide
• Piperaquine
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide
• Adagrasib
• Alfuzosin
• Amiodarone
• Amisulpride
• Amitriptyline
• Amoxapine
• Anagrelide
• Apomorphine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Azimilide
• Bretylium
• Buprenorphine
• Buserelin
• Ceritinib
• Chloroquine
• Chlorpromazine
• Cholera Vaccine, Live
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clofazimine
• Clomipramine
• Clothiapine
• Clozapine
• Crizotinib
• Dabrafenib
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Deutetrabenazine
• Dexmedetomidine
• Digoxin
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Droperidol
• Edoxaban
• Efavirenz
• Encorafenib
• Entrectinib
• Erythromycin
• Escitalopram
• Fexinidazole
• Fingolimod
• Flecainide
• Fluconazole
• Fluoxetine
• Formoterol
• Foscarnet
• Fostemsavir
• Gatifloxacin
• Gemifloxacin
• Glasdegib
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Histrelin
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Inotuzumab Ozogamicin
• Ivabradine
• Ivosidenib
• Ketoconazole
• Lapatinib
• Lefamulin
• Lenvatinib
• Leuprolide
• Levofloxacin
• Lofexidine
• Lopinavir
• Lumefantrine
• Macimorelin
• Mefloquine
• Methadone
• Methotrexate
• Metronidazole
• Mifepristone
• Mirtazapine
• Mobocertinib
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nafarelin
• Nilotinib
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Ondansetron
• Osilodrostat
• Osimertinib
• Oxaliplatin
• Ozanimod
• Pacritinib
• Paliperidone
• Panobinostat
• Pasireotide
• Pazopanib
• Pentamidine
• Phenobarbital
• Pimavanserin
• Pitolisant
• Pixantrone
• Ponesimod
• Posaconazole
• Primidone
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Ranolazine
• Ribociclib
• Risperidone
• Selpercatinib
• Sematilide
• Sertraline
• Sevoflurane
• Simvastatin
• Siponimod
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• Sulpiride
• Sunitinib
• Tacrolimus
• Tedisamil
• Telithromycin
• Tetrabenazine
• Toremifene
• Trazodone
• Triclabendazole
• Trifluoperazine
• Trimipramine
• Triptorelin
• Vandetanib
• Vardenafil
• Vemurafenib
• Vilanterol
• Vinflunine
• Voclosporin
• Voriconazole
• Warfarin
• Zuclopenthixol

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Atorvastatin
• Lovastatin
• Nelfinavir
• Rifabutin
• Theophylline

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to any macrolide and ketolide antibiotic (eg, clarithromycin, erythromycin, telithromycin, Biaxin®, Ery-tab®, or Ketek®) or
• Liver disease with prior azithromycin use, history of—Should not be used in patients with this condition.

• Bacteremia (blood infection) or
• Cystic fibrosis or
• Infections, nosocomial or hospital-acquired or
• Weak immune system or
• Weakened physical condition—Should not be used in patients with these conditions to treat pneumonia.

• Bradycardia (slow heartbeat) or
• Congestive heart failure or
• Diarrhea or
• Heart disease or
• Heart rhythm problems (eg, QT prolongation, torsades de pointes, bradyarrhythmias), history of or
• Hypokalemia (low potassium in the blood), uncorrected or
• Hypomagnesemia (low magnesium in the blood), uncorrected or
• Myasthenia gravis (severe muscle weakness)—Use with caution. May make these conditions worse.

• Kidney disease, severe or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper use of Zithromax Tri-Pak

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

You may take Zithromax® oral liquid or tablets with or without food.

Shake well the bottle of Zithromax® oral liquid before each use. Measure your dose correctly with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.

Measure the Zmax® extended-release oral suspension with a marked measuring spoon, syringe, or cup. You or your child must take this medicine within 12 hours after it has been mixed with water. It is best to take the Zmax® extended-release oral suspension on an empty stomach or at least 1 hour before or 2 hours after a meal. If your child does not use all of the medicine in the bottle, throw it away after you give the dose.

If you or your child vomits within one hour of taking the Zmax® extended-release oral suspension, call your doctor right away to see if more medicine is needed.

Keep using this medicine for the full treatment time, even if you or your child feel better after the first few doses. Your infection may not clear up if you stop using the medicine too soon.

If you are taking aluminum or magnesium-containing antacids, do not take them at the same time that you take Zithromax®. These medicines may keep azithromycin from working properly. However, you can take antacids with Zmax®.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release suspension):
  • For treatment of pneumonia:
    • Adults—2 grams (g) once as a single dose.
    • Children weighing 34 kilograms (kg) or more—Dose is based on body weight and must be determined by your doctor. The dose is usually 2 grams once a day, taken as a single dose.
    • Children 6 months of age and older weighing less than 34 kg—Dose is based on body weight and must be determined by your doctor. The dose is usually 60 milligrams (mg) per kilogram (kg) of body weight once a day, taken as a single dose.
  • For treatment of sinusitis:
    • Adults—2 grams (g) once a day as a single dose.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage forms (suspension or tablets):
  • For treatment of infections:
    • Adults—500 to 2000 milligrams (mg) once a day, taken as a single dose. Depending on the type of infection, this may be followed with doses of 250 to 500 mg once a day for several days.
    • Children 6 months of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 10 to 30 milligrams (mg) per kilogram (kg) of body weight once a day, taken as a single dose. Depending on the type of infection, this may be followed with doses of 5 to 10 mg per kg of body weight once a day for several days.
    • Children younger than 6 months of age—Use and dose must be determined by your doctor.
  • For treatment of pharyngitis or tonsillitis:
    • Adults—500 milligrams (mg) on Day 1 (the first day), taken as a single dose. Then, 250 mg on Day 2 through Day 5.
    • Children 2 years of age and older—Dose is based on body weight and must be determined by your doctor. The dose is usually 12 milligrams (mg) per kilogram (kg) of body weight once a day for 5 days.
    • Children younger than 2 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Do not refrigerate or freeze the Zmax® extended-release oral suspension. After water has been added to the powder, use the dose within 12 hours and throw away any unused liquid after your dose.

You may store the Zithromax® oral liquid at room temperature or in the refrigerator. Do not freeze the bottle. Do not keep the oral liquid for more than 10 days. Throw away any unused liquid after all doses are completed.

Precautions while using Zithromax Tri-Pak

It is very important that your doctor check the progress of you or your child at regular visits to make sure this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

If you or your child’s symptoms do not improve within a few days, or if they become worse, check with your doctor.

This medicine may cause serious allergic reactions, including anaphylaxis and angioedema, which can be life-threatening and require immediate medical attention. Call your doctor right away if you or your child have a rash, itching, hives, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth after you take this medicine.

Serious skin reactions, including Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) can occur with this medicine. Check with your doctor right away if you or your child have black, tarry stools, blistering, peeling, or loosening of the skin, chest pain, chills, cough, diarrhea, itching, joint or muscle pain, painful or difficult urination, red irritated eyes, red skin lesions, often with a purple center, sore throat, sores, ulcers, or white spots in the mouth or on the lips, swollen glands, unusual bleeding or bruising or unusual tiredness or weakness while you are using this medicine.

Check with your doctor right away if you or your child have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Call your child’s doctor right away if your child feels irritable or vomits after feeding. These may be symptoms of a condition called infantile hypertrophic pyloric stenosis.

Azithromycin may cause diarrhea, and in some cases it can be severe. It may occur 2 months or more after you stop using this medicine. Do not take any medicine to treat diarrhea without first checking with your doctor. Diarrhea medicines may make the diarrhea worse or make it last longer. If you or your child have any questions about this or if mild diarrhea continues or gets worse, check with your doctor.

This medicine can cause changes in heart rhythms, including QT prolongation. It may change the way your heart beats and cause fainting or serious side effects in some patients. Contact your doctor right away if you or your child have any symptoms of heart rhythm problems, including fast, pounding, or irregular heartbeats.

This medicine may increase the risk of serious heart or blood vessel problems. Call your doctor right away if you have blurred vision, chest pain, confusion, lightheadedness, dizziness, fainting, fast or irregular heartbeat, trouble breathing, or unusual tiredness or weakness.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of Zithromax Tri-Pak

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

• Diarrhea
• loose stools

Less common

• Blistering, crusting, irritation, itching, or reddening of the skin
• cracked, dry, or scaly skin
• fever
• swelling

Rare

• Blistering, peeling, or loosening of the skin
• bloody or cloudy urine
• bloody, black, or tarry stools
• body aches or pain
• burning while urinating
• chest pain or tightness
• chills
• congestion
• cough increased
• cough producing mucus
• dark urine
• difficult or labored breathing
• difficult or painful urination
• dizziness
• drowsiness
• dryness or soreness of the throat
• earache
• fainting
• fast, irregular, pounding, or racing heartbeat or pulse
• general feeling of discomfort or illness
• headache
• indigestion
• irregular or slow heart rate
• itching or rash
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• loss of appetite
• muscle aches and pains
• nausea or vomiting
• noisy breathing
• passing of gas
• red skin lesions, often with a purple center
• red, irritated eyes
• redness or swelling in the ear
• runny nose
• shivering
• sneezing
• sores, ulcers, or white spots on the lips or in the mouth
• stomach pain, continuing
• stomach pain, fullness, or discomfort
• stuffy nose
• sweating
• swelling of the face, ankles, hands, feet, or lower legs
• tender, swollen glands in the neck
• trouble with sleeping
• trouble with swallowing
• unpleasant breath odor
• unusual bleeding or bruising
• unusual tiredness or weakness
• upper right abdominal or stomach pain
• voice changes
• vomiting of blood
• yellow eyes or skin

Incidence not known

• Bleeding gums
• bloating
• blood in the urine or stools
• blurred vision
• change in hearing
• clay-colored stools
• coma
• confusion
• constipation
• continuing ringing or buzzing or other unexplained noise in the ears
• decreased urine output
• depression
• diarrhea, watery and severe, which may also be bloody
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• greatly decreased frequency of urination or amount of urine
• hives
• hostility
• increased thirst
• irritability
• lethargy
• loss of hearing
• lower back or side pain
• muscle twitching
• no blood pressure or pulse
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pale skin
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid weight gain
• seizures
• stomach cramps or tenderness
• stopping of heart
• stupor
• unconsciousness
• unusual weight 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:

Rare

• Acid or sour stomach
• aggressive or angry
• bad, unusual, or unpleasant (after) taste
• belching
• burning feeling in the chest or stomach
• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
• change in taste
• changes in the color of the tongue
• crying
• depersonalization
• dry mouth
• dysphoria
• euphoria
• excess air or gas in the stomach or intestines
• feeling of constant movement of self or surroundings
• full feeling
• heartburn
• hyperventilation
• increase in body movements
• itching of the vagina or genital area
• lack or loss of strength
• mental depression
• nervousness
• pain during sexual intercourse
• paranoia
• quick to react or overreact emotionally
• rapidly changing moods
• rash with flat lesions or small raised lesions on the skin
• redness of the skin
• restlessness
• sensation of spinning
• shaking
• sleepiness or unusual drowsiness
• stomach upset
• thick, white vaginal discharge with no odor or with a mild odor
• white patches in the mouth, tongue, or throat

Incidence not known

• Difficulty with moving
• increased sensitivity of the skin to sunlight
• muscle pain or stiffness
• pain in the joints
• redness or other discoloration of the skin
• severe sunburn
• trouble sitting still

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.

Frequently asked questions

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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Azithromycin Tri-Pak Oral Tablet 500 mg

Uses

For treating bacterial infection.

Instructions

This medicine may be taken with or without food.

You may take with food to prevent stomach upset.

Keep the medicine at room temperature. Avoid heat and direct light.

Do not take this medicine with antacids.

It is important that you keep taking each dose of this medicine on time even if you are feeling well.

If you forget to take a dose on time, take it as soon as you remember. If it is almost time for the next dose, do not take the missed dose. Return to your normal dosing schedule. Do not take 2 doses of this medicine at one time.

Please tell your doctor and pharmacist about all the medicines you take. Include both prescription and over-the-counter medicines. Also tell them about any vitamins, herbal medicines, or anything else you take for your health.

It is very important that you continue using this medicine for the full number of days that it is prescribed. Please do not stop the medicine even if you start to feel better after the first few days.

Cautions

Tell your doctor and pharmacist if you ever had an allergic reaction to a medicine. Symptoms of an allergic reaction can include trouble breathing, skin rash, itching, swelling, or severe dizziness.

Do not use the medication any more than instructed.

Please tell your doctor if you have moderate to severe diarrhea while on this medicine. Do not treat the diarrhea with over-the-counter diarrhea medicine.

Tell the doctor or pharmacist if you are pregnant, planning to be pregnant, or breastfeeding.

Ask your pharmacist if this medicine can interact with any of your other medicines. Be sure to tell them about all the medicines you take.

Please tell all your doctors and dentists that you are on this medicine before they provide care.

Do not start or stop any other medicines without first speaking to your doctor or pharmacist.

Do not share this medicine with anyone who has not been prescribed this medicine.

Side Effects

The following is a list of some common side effects from this medicine. Please speak with your doctor about what you should do if you experience these or other side effects.

• diarrhea
• nausea
• stomach upset or abdominal pain
• yeast infection of mouth
• vaginal itching or yeast infection
• vomiting

Call your doctor or get medical help right away if you notice any of these more serious side effects:

• severe, watery or bloody diarrhea
• ear problems (ringing in the ears, hearing loss)
• fainting
• swelling in the neck or throat
• fast or irregular heart beats
• symptoms of liver damage (such as yellowing of skin or eyes, dark urine, unusual tiredness or weakness; severe stomach or back pain)
• muscle weakness
• skin irritation such as redness, itching, rash, or burning
• severe stomach or bowel pain
• blurring or changes of vision
• severe or persistent vomiting

A few people may have an allergic reaction to this medicine. Symptoms can include difficulty breathing, skin rash, itching, swelling, or severe dizziness. If you notice any of these symptoms, seek medical help quickly.

Extra

Please speak with your doctor, nurse, or pharmacist if you have any questions about this medicine.

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IMPORTANT NOTE: This document tells you briefly how to take your medicine, but it does not tell you all
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Please talk to them if you have any questions.Always follow their advice. There is a more complete
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AZITHROMYCIN AVEXIMA | OJSC Aveksima

Azithromycin is a broad-spectrum bacteriostatic antibiotic from the group of azalide macrolides. It has a wide spectrum of antimicrobial activity. The mechanism of action of azithromycin is associated with the suppression of protein synthesis of microbial cells. By binding to the 50S-sybunit of the ribosome, it inhibits the peptide translocase at the translation stage and inhibits protein synthesis, slowing down the growth and reproduction of bacteria. In high concentrations, it has a bactericidal effect.

It has activity against a number of gram-positive, gram-negative, anaerobic, intracellular and other microorganisms. Microorganisms may initially be resistant to the action of an antibiotic or may acquire resistance to it.

Azithromycin Susceptibility Scale (Minimum Inhibitory Concentration [MIC], mg/mL)

Mostly sensitive organisms

1. Gram-positive aerobes

Staphylococcus aureus methicillin-sensitive

Streptococcus pneumoniae penicillin-susceptible

Streptococcus pyogenes

2 . Gram-negative aerobes

Haemophilus influenzae

Haemophilus parainfluenzae

Legionella pneumophila

Moraxella catarrhalis

Pasteurella multocida

Neisseria gonorrhoeae

3. Anaerobes

Clostridium perfringens

Fusobacterium spp.

Prevotella spp.

Porphyriomonas spp.

4. Other microorganisms

Chlamydia trachomatis

Chlamydia pneumonia

Chlamydia psittaci

Mycoplasma pneumoniae

Mycoplasma hominis

Mycoplasma genitalium

Borrelia burgdorferi

Microorganisms capable of developing resistance to azithromycin

1. Gram-positive aerobes

Streptococcus pneumoniae penicillin-resistant

Inherently resistant microorganisms

1. Gram-positive aerobes

Enterococcus faecalis

Staphylococcus spp . (methicillin-resistant staphylococci have acquired resistance to macrolides with a very high frequency)

Gram-positive bacteria resistant to erythromycin

2. Anaerobes

Bacteroides fragilis

Azithromycin: instruction, price, analogues | Compendium – a guide to medicines

The year is 1980. Dr. Slobodan Rokeach and his research team at Pliva (a pharmaceutical company in Croatia) have discovered Azithromycin. A patent for it was obtained a year later. And then, using the Pliva license, Pfizer brings the drug to the pharmaceutical markets and already under a completely different trade name. And this happens in 10 years. A few more years passed. And they approved a new formulation of azithromycin for the treatment of eye infections.

Azithromycin is practically insoluble in water and freely soluble in anhydrous ethanol and methylene chloride. Azithromycin is a macrolide antibiotic. It is a semi-synthetic derivative of erythromycin. Azithromycin differs from erythromycin by the addition of a methyl-substituted nitrogen atom to the lactone ring. This structural modification increased the acid resistance of the compound and improved the penetration of the drug molecule into tissues, expanding its spectrum of action. Macrolides are generally distinguished by their activity, covering a wide range of Gram-positive and Gram-negative bacterial species, including intracellular pathogens such as Chlamydia and Legionella. They exhibit their antibiotic activity by binding to the 50S ribosome (its subunit) and inhibiting protein synthesis. Modern antibacterial drugs are intended not only for inpatient treatment, but also for outpatient use. But at the same time, patients often do not comply with the drug regimen or the total duration of the course of treatment. In turn, this can lead to chronic bacterial inflammation or to the development of antibiotic resistance in bacteria. That is why preference is given to drugs with a simple regimen (1 r / day) with a long T _½ , which reduces the duration of the course of treatment. Such drugs make it possible to achieve the complete elimination of the bacterial pathogen and are even able to prevent the exacerbation of chronic diseases. Azithromycin meets all these requirements.

Compared with other macrolide drugs, azithromycin has a number of advantages in terms of pharmacokinetics, pharmacodynamics, as well as safety and tolerability in both adult and pediatric practice. It demonstrates time-dependent bacteriostatic or bactericidal activity, and at the same time shows concentration-dependent bactericidal activity and a pronounced post-antibacterial effect (Matzneller P. , 2013). After oral administration, the drug is distributed throughout the body, with C _max is reached in 2–3 hours, and the tissue concentration exceeds the serum concentration by 50 times (instruction of the Ministry of Health of Ukraine). At the same time, azithromycin accumulates mainly in the extracellular space of muscle tissue and subcutaneous adipose tissue, as well as in fibroblasts and tissue phagocytes. The concentration of azithromycin in the lung tissue can be characterized as high or very high, which ensures the effectiveness of the drug against most respiratory bacterial infections (Leophonte P., 1995). The post-antibacterial effect of azithromycin lies in the fact that its molecules strongly bind to tissue proteins and T _½ is 5 days after the completion of the course of treatment, and in some patients it reached 10 days (Matzneller P., 2013).

The spectrum of antibacterial activity of azithromycin covers methicillin-susceptible strains of staphylococcus, penicillin-susceptible strains of streptococcus, hemophilic infection, moraxella and pasteurella, as well as intracellular pathogens such as chlamydia and legionella (Neu H. C., 1991). In addition, azithromycin is active against anaerobic bacteria such as clostridia and fusobacteria.

The group of bacteria resistant to azithromycin is represented by penicillin-resistant streptococci, methicillin-resistant Staphylococcus aureus, bacteroids and the overwhelming majority of gram-negative bacteria. Cross-resistance to azithromycin is observed in pathogens resistant to erythromycin, other macrolides and lincosamides (instruction of the Ministry of Health of Ukraine).

Azithromycin pharmacology and therapy

Azithromycin has been found to be less active than erythromycin against Gram-positive bacteria, but more effective against some Gram-negative organisms such as Haemophilus influenzae, Moraxella catarrhalis, and also has activity against some enterobacteria, such as Escherichia coli and Salmonella and Shigella species, as well as against Legionella pneumophila, B. burgdorferi, Mycoplasma pneumoniae. He (azithromycin) has increased activity against Mycobacterium avium-intracellulare, as well as some protozoa (for example, Cryptosporidium and Plasmodium species), excellent action against Toxoplasma gondii, kills cysts. It is more active than erythromycin against Chlamydia trachomatis and Ureaplasma urealyticum.

Mechanism of action. It is a bacteriostatic agent that inhibits protein synthesis by reversibly binding to the 50S ribosomal subunits of susceptible microorganisms. The cells of the body are much more permeable to the dosage form of the drug, which is likely to exhibit increased antimicrobial activity at an alkaline pH.

Macrolide resistance. Generally, resistance to macrolides is due to the following mechanisms:

• ribosomal protection by inducible or constitutive production of methylase enzymes mediated by the expression of (ermA), (ermB), and (ermC), which modify the ribosomal target and reduce drug binding;
• hydrolysis by esterases produced by Enterobacteriaceae;
• chromosomal mutations that alter the 50S ribosome subunit protein (noted in B. subtilis, Campylobacter species, mycobacteria, and Gram-positive cocci).

Action other than antimicrobial effects. Studies have indicated the activity of Azithromycin as a promising drug for the treatment of gastroparesis and gastrointestinal motility disorders.

• One study showed that azithromycin may be effective against asthma (late onset).
• Information has been obtained on the effectiveness of azithromycin against malaria when used in combination with artemisinin or quinine sulfate. Azithromycin-artemisinin, even if taken only once a day (3 days), and azithromycin-quinine sulfate – 3 times a day. These drug combinations have been relatively safe and effective in uncomplicated malaria and deserve further study in specific patient populations.
• Ischemic heart disease: macrolide antibacterial agents, including Azithromycin.

Clarithromycin, roxithromycin, azithromycin have been investigated for the prevention of coronary artery disease based on the proposed association between atherosclerosis and Chlamydophila pneumoniae (Chlamydia) infection. Although the preliminary results of some experimental studies have been promising, long-term studies in a large number of patients have been disappointing, and none of the three macrolides reduced ischemic outcomes or provided a clinical benefit. In one study, an unexpected increase in cardiovascular mortality was observed with clarithromycin.

• Gingival hyperplasia: Azithromycin has a positive effect on the treatment of gingival hyperplasia, which was caused by cyclosporine, especially when it (azithromycin) is introduced early in the inflammation process.
• Cystic fibrosis: Azithromycin is widely used in cystic fibrosis, with evidence demonstrating decreased lung function and exacerbation rates. This immunomodulatory therapy likely interferes with Pseudomonas aeruginosa biofilm growth.

ADME (absorption, distribution, metabolism, and excretion) profile. Orally administered azithromycin is rapidly absorbed and widely distributed throughout the body except the brain and cerebrospinal fluid. Peak plasma concentrations are reached 2-3 hours after oral administration. A loading dose of 500 mg will give a peak plasma drug concentration of 0.4 g/mL. When the loading dose is 250 mg 1 time per day for 4 days, then in a stationary state, the peak concentration of the drug is 0. 24 g / ml. Azithromycin can also be administered intravenously, producing plasma concentrations of 3–4 g/mL following a 1-hour infusion of 500 mg. Absorption from capsules decreases with food. The unique pharmacokinetic properties of the drug are extensive redistribution in tissues and high concentrations of the drug in cells (including phagocytes). This leads to an increase in the concentration of the drug in the tissues, when compared with simultaneous concentrations in the blood serum. Tissue fibroblasts act as a natural drug reservoir in vivo.

Animal data show that azithromycin crosses the placenta. At very low plasma concentrations, this represents 50% of the amount of protein. Azithromycin undergoes demethylation in the liver to an inactive metabolite, but excretion is carried out by the biliary tract – the main route. Only 12% of the drug is excreted unchanged in the urine. Half-life (T _½ ) – 40-68 hours

Adverse reactions. Anorexia, dyspepsia, flatulence, dizziness, headache, drowsiness, convulsions, arthralgia and taste and smell disorders; rarely – constipation, hepatitis, liver failure, syncope, insomnia, agitation, restlessness, asthenia, paresthesia, hyperactivity, thrombocytopenia, hemolytic anemia, interstitial nephritis, acute renal failure, photosensitivity, discoloration of the lips and tongue.

Drug interactions. It is not recommended to use Azithromycin in combination with antacids containing aluminum or magnesium. Salts can reduce the rate, but not the extent of its absorption;

Azithromycin should be given at least 1 hour before or 2 hours after the antacid.

• Serum concentrations of azithromycin are markedly increased when given with nelfinavir.
• Azithromycin capsules should not be administered with food because this reduces the availability of the drug itself.
• Azithromycin possibly enhances the anticoagulant effect of coumarins.
• Azithromycin possibly increases the concentration of theophylline in blood plasma (Bakheit A.H., 2014).

Clinical experience with azithromycin

Clinical use and dosing (see instructions of the Ministry of Health of Ukraine).

1. respiratory infections;

2. skin and soft tissue infections;

3. chlamydial infections;

4. mild or moderate non-gonococcal urethritis;

5. otitis media;

6. typhoid fever due to multiple antibacterial resistant organisms;

7. prophylaxis of group A streptococcal infection;

8. as a prophylactic treatment for bacterial endocarditis in patients undergoing dental procedures at high risk of developing endocarditis;

whooping cough;

10. mycobacterial infections.

• Treatment or prophylaxis of Mycobacterium avium intracellular infection in AIDS patients requiring higher doses: 600 mg per day in combination with one or more other drugs for treatment or 1200 mg once a week for primary prevention.
• Azithromycin is prescribed for the treatment of sexually transmitted diseases, especially during pregnancy, when tetracyclines are contraindicated. Treatment for uncomplicated nongonococcal urethritis suspected to be C. trachomatis is a single dose (1 g) of azithromycin. This dose is also effective in chancroid.
• Azithromycin (1 g/week for 3 weeks) is an alternative regimen for the treatment of inguinal or venous lymphogranuloma.
• Uncomplicated genital chlamydial infections and non-gonococcal urethritis, 1 g as a single dose.
• Typhoid fever, 500 mg once a day (total number of days of taking the drug – 7).

Systematic reviews contain a wealth of information on the use and safety of Azithromycin in various therapeutic areas.

Here is information on several studies that, in our opinion, may be of interest.

Long-term therapy with azithromycin has been shown to reduce exacerbations of chronic obstructive pulmonary disease (COPD) and is indicated according to the latest recommendations for patients with COPD who are at risk of recurrent exacerbations. However, concerns about adverse effects limit its widespread use. Physicians deciding whether to use long-term azithromycin therapy should evaluate each patient’s individual risk of cardiovascular events and the individual and population impact of macrolide resistance versus expected benefit. This review will summarize data on the efficacy and safety of chronic azithromycin for the prevention of COPD exacerbations (Taylor S. P., 2015).

The FDA has updated the packaging labeling of azithromycin to include the risk of prolonged cardiac repolarization and prolongation of the QT interval, which increases the risk of cardiac dysrhythmias, especially in the elderly. The update was initiated by a study that found an increased risk of death in patients taking azithromycin compared to patients taking amoxicillin. However, the cardiovascular results of other studies of azithromycin have been inconsistent, so more research is needed. At the same time, specialists should recognize that azithromycin plays a role in the treatment of bacterial infections, and should prescribe an antibiotic if necessary (Sutton S.S., 2017).

Azithromycin is widely used as a first-line drug for the treatment of children with mycoplasmal pneumonia, although children often vomit in the pediatric ward as a result of oral administration. It is believed that drugs that are administered rectally enter the circulatory system without first passing through the liver. Therefore, 5 healthy volunteers were included in the study. All participants gave written informed consent to participate in the study. Either oral administration of a 500 mg Azithromycin tablet or rectal administration of a suppository of the same preparation 125 was randomly assigned; 250 or 500 mg. Blood samples for serum preparation were taken before and after 1; 2; 3; 4; 6; 12 and 24 hours after the first rectal dose. Serum azithromycin concentrations were determined by high performance liquid chromatography (HPLC) with electrochemical detection.

Thus, the bioavailability of the suppository when administered rectally was 20.3% compared to oral administration. It is assumed that the surface area where the active substance is absorbed also affects the absorption when administered rectally. Although further research is needed to improve rectal absorption and child safety, azithromycin suppositories may already be effective in cases where oral administration is not allowed (Maeda M. et al., 2016).

Antibacterial therapy with azithromycin is widely used in modern medical practice: the drug is effective for middle ear infections, tonsillitis, pneumonia, typhoid, bronchitis and sinusitis. In addition, it is effective against some STDs – it is included in the treatment regimens for non-gonococcal urethritis, cervicitis and chlamydia (Bakheit A., 2014). Azithromycin is successfully used for the treatment of chlamydial cervicitis and urethritis, and its single dose is comparable in its effectiveness to a 7-day course of doxycycline treatment (Katanani M.S., 1994).

According to a prospective study, it was found that a 5-day course of azithromycin can be considered quite sufficient for the treatment of erythema migrans in tick-borne borreliosis (Arnez M., 2015).

Interestingly, azithromycin has been shown to be effective against typhus in 5 clinical trials, with activity comparable to that of other anti-rickettsial drugs. Azithromycin is an effective alternative to doxycycline, which is contraindicated, for example, in pregnant women or young children (Lee S. C., 2017).

Azithromycin is recommended for the treatment of obstructive bronchiolitis, obstructive airway injury associated with lung or allogeneic stem cell transplantation. Meta-analysis data suggest that when it is included in the treatment regimen, there is a small but statistically significant increase in such an indicator as forced expiratory volume in the first second. The therapeutic effect is associated with the fact that under the influence of azithromycin, the secretion of interleukin-8 by alveolar macrophages decreases, the activity of fibroblast matrix metalloproteases decreases, the survival of neutrophils and the general microbial contamination of the lungs decrease (Yadav H., 2016). In addition, studies of in vitro and in animals it was found that azithromycin acts like an inhibitor of nuclear factor κβ and inhibits the maturation of dendritic cells, thereby reducing the severity of the graft-versus-host reaction (Iwamoto S., 2013).

In a randomized, double-blind, placebo-controlled trial (3 years), it was found that the use of azithromycin as an antibiotic prophylaxis helps to reduce the number of chronic lung infections in patients with primary antibody deficiency (Milito C. , 2019).

Azithromycin is also recommended for the prevention of exacerbations in patients with fibrous bronchiectasis – its systematic use improves the quality of life in patients who have experienced at least one exacerbation per year without therapy (Wong C., 2012).

The effectiveness of azithromycin for the treatment and prevention of whooping cough has been proven (Devasia R., 2009) – it is recommended as an alternative first-line drug. The high efficacy of azithromycin in the treatment of legionella pneumonia has also been established – it has been proven not only in animal models, but also in clinical studies (Plouffe J.F., 2003).

According to a systematic review, it was found that azithromycin can be prescribed to premature babies – the antibiotic significantly reduces the risk of developing bronchopulmonary dysplasia in them (Smith C., 2015). The ability of azithromycin to prevent the development of chronic pulmonary pathology during intrauterine infection with ureaplasma has been proven (Turner M. A., 2012). Azithromycin is also used in pediatric practice for the treatment of mycoplasmal pneumonia (Wang J., 2018). It is very important that azithromycin therapy is well combined with probiotic preparations based on Saccharomyces boulardii – with this combination, the cure for mycoplasma pneumonia is accelerated and the frequency of intestinal dysbacteriosis is reduced (Chen Q.F., 2018).

Azithromycin has proven itself in dermatological practice. For the treatment of chronic furunculosis – recurrent staphylococcal abscesses of hair follicles – it is recommended to use the drug for a 12-week course at a dosage of 500 mg / week. This treatment regimen makes it possible to achieve stable remission after 3 months in 79 patients..2% of patients (Amynzadeh A., 2007).

The literature describes the successful treatment of cutaneous leishmaniasis with azithromycin. At the same time, the drug was prescribed in the regimen of 500 mg/day for 10 days (Minodier P.