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Side effects of acitretin: Acitretin (Oral Route) Side Effects

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Acitretin (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. Back pain

  2. bad, unusual, or unpleasant (after) taste

  3. bone or joint pain

  4. change in taste

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

  6. difficulty with moving or walking

  7. excessive muscle tone

  8. feeling of warmth

  9. headache (severe and continuing)

  10. hearing loss

  11. increased sensitivity to pain

  12. increased sensitivity to touch

  13. muscle stiffness, tension, or tightness

  14. nausea (severe and continuing)

  15. redness of the face, neck, arms, and occasionally, upper chest

  16. redness of the skin

  17. sleeplessness

  18. thinning of the skin with easy bruising

  19. tingling in the hands and feet

  20. tongue irritation

  21. trouble sleeping

  22. vomiting (severe and continuing)
Less common

  1. Abnormal sensation of burning or stinging

  2. blurred vision

  3. belching

  4. breast pain

  5. cracking, redness, skin irritation, or rash (including a rash that looks like psoriasis)

  6. eye pain

  7. general feeling of discomfort or illness

  8. heartburn

  9. increased hair growth on the forehead, back, arms, and legs

  10. indigestion

  11. infection, ulcers, unusual odor, or small red spots in the skin

  12. itching of the vagina or genital area

  13. loosening of the fingernails

  14. loss of eyebrows or eyelashes

  15. pain during sexual intercourse

  16. redness of the eyes

  17. redness or soreness around the fingernails

  18. redness or swelling of the eyelid

  19. sensitivity of the eyes to light

  20. sore mouth or tongue

  21. thick, white vaginal discharge with no odor or with a mild odor

  22. watery eyes

  23. white patches in the mouth or on the tongue
Rare

  1. Bleeding gums

  2. bleeding time increased

  3. chest pain

  4. coughing

  5. coughing up blood

  6. darkened urine

  7. diarrhea

  8. difficulty in breathing or swallowing

  9. double vision or other problems in seeing, including decreased night vision after sunset and before sunrise

  10. hoarseness

  11. increased menstrual flow or vaginal bleeding

  12. itchy or painful ears

  13. light-colored stools

  14. nosebleeds

  15. pale or cold hands or feet

  16. paralysis

  17. prolonged bleeding from cuts

  18. red or dark brown urine

  19. sore on the edge of the eyelid (stye)

  20. stomach pain

  21. thick, white, curd-like vaginal discharge

  22. unpleasant breath odor

  23. unusual tiredness or weakness

  24. vaginal itching or irritation

  25. vomiting of blood

  26. yellowing of the skin or eyes
Incidence not known

  1. Assault

  2. attack

  3. burning, numbness, tingling, or painful sensations

  4. chest discomfort

  5. confusion

  6. difficulty with speaking

  7. doing things to injure oneself

  8. inability to move the arms, legs, or facial muscles

  9. inability to speak

  10. pain in the chest, groin, or legs, especially calves

  11. pain or discomfort in the arms, jaw, back, or neck

  12. slow speech

  13. slurred speech

  14. sudden loss of coordination

  15. sudden, severe weakness or numbness in the arms or legs

  16. sweating

  17. thoughts of killing oneself

  18. unsteadiness or awkwardness

  19. vision changes

  20. weakness in the arms, hands, legs, or feet

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

  1. Dizziness or lightheadedness

  2. feeling of constant movement of self or surroundings

  3. sensation of spinning

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. Chapped, red, or swollen lips

  2. difficulty in wearing contact lenses

  3. dry or runny nose

  4. dryness of the eyes

  5. increased ability to sunburn

  6. increased amount of ear wax (unusual)

  7. irritation in the mouth or swollen gums

  8. itchy skin

  9. loss of hair (usually reversible)

  10. scaling and peeling of the eyelids, fingertips, palms, and soles of feet

  11. sticky skin

  12. unusual thirst
Less common

  1. Constipation

  2. increased sweating
Incidence not known

  1. Cracking fingernails or fingernails break easily

  2. muscular pain, tenderness, wasting, or weakness

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: July 01, 2021

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Acitretin: MedlinePlus Drug Information

For female patients:

Do not take acitretin if you are pregnant or plan to become pregnant within the next 3 years. Acitretin may harm the fetus. You should not begin taking acitretin until you have taken two pregnancy tests with negative results. You must use two acceptable forms of birth control for 1 month before you begin taking acitretin, during your treatment with acitretin, and for 3 years after treatment. Your doctor will tell you which methods of birth control are acceptable. You do not need to use two methods of birth control if you have had a hysterectomy (surgery to remove the womb), if your doctor tells you that you have finished menopause (change of life), or if you practice total sexual abstinence.

If you plan to use oral contraceptives (birth control pills) while taking acitretin, tell your doctor the name of the pill you will use. Acitretin interferes with the action of microdosed progestin (‘minipill’) oral contraceptives. Do not use this type of birth control while taking acitretin. If you plan to use hormonal contraceptives (birth control pills, patches, implants, injections, and intrauterine devices), be sure to tell your doctor about all the medications, vitamins, and herbal supplements you are taking. Many medications interfere with the action of hormonal contraceptives. Do not take St. John’s wort if you are using any type of hormonal contraceptive.

You will need to take pregnancy tests regularly during your treatment with acitretin and for at least 3 years after taking acitretin. Stop taking acitretin and call your doctor immediately if you become pregnant, miss a menstrual period, or have sex without using two forms of birth control. In some cases, your doctor can prescribe emergency contraception (‘the morning after pill’) to prevent pregnancy.

Do not consume foods, drinks, or prescription or nonprescription medications that contain alcohol while taking acitretin and for 2 months after treatment. Alcohol and acitretin combine to form a substance that remains in the blood for a long time and can harm the fetus. Read medication and food labels carefully and ask your doctor or pharmacist if you are not sure whether a medication contains alcohol.

Your doctor will give you a Patient Agreement/Informed Consent to read and sign before you begin treatment. Be sure to read this carefully and ask your doctor if you have any questions.

For male patients:

A small amount of acitretin is present in the semen of male patients who take this medication. It is not known whether this small amount of medication can harm the fetus. Talk to your doctor about the risks of taking this medication if your partner is pregnant or plans to become pregnant.

For male and female patients:

Do not donate blood while taking acitretin and for 3 years after treatment.

Acitretin may cause liver damage. Tell your doctor if you have or have ever had liver disease. If you experience any of the following symptoms, call your doctor immediately: nausea, vomiting, loss of appetite, pain in the upper right part of the stomach, yellowing of the skin or eyes, or dark urine.

Your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with acitretin and each time you fill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm388814.htm) or the manufacturer’s website to obtain the Medication Guide.

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

Soriatane

Brand Names: Canada

MINT-Acitretin; Soriatane; TARO-Acitretin

Warning

  • Do not take this drug if you are pregnant or want to get pregnant within 3 years after stopping this drug. The risk of severe and sometimes deadly birth defects is very high if you take this drug during pregnancy or if you get pregnant within 3 years after stopping this drug. The risk of losing an unborn baby is also raised, and premature births have happened. Your doctor will talk about the risks before you start this drug. You must use 2 kinds of birth control that you can trust 1 month before starting this drug, during treatment, and for 3 years after the last dose. Pregnancy tests will be done before you start this drug, while you take it, and for 3 years after the last dose. If you get pregnant while taking this drug or within 3 years after stopping it, call your doctor right away.
  • If you are able to get pregnant and you may not use 2 kinds of birth control during and after treatment with this drug, talk with your doctor. This drug may not be right for you.
  • If you are able to get pregnant, you must avoid alcohol while taking this drug and for 2 months after stopping it. This includes all drinks, food, drugs, or products that have alcohol in them. Alcohol will make this drug stay in the body longer and may raise the risk of birth defects for longer than 3 years after stopping this drug. If you have questions, talk with your doctor.
  • Small amounts of this drug are found in semen. It is not known if this may lead to any risk to the unborn baby. Talk with your doctor.
  • Do not donate blood while using this drug and for 3 years after stopping.
  • Very bad and sometimes deadly liver problems have happened with this drug. Call your doctor right away if you have 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.

What is this drug used for?

  • It is used to treat psoriasis.
  • It may be given to you for other reasons. Talk with the doctor.

What do I need to tell my doctor BEFORE I take 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 any of these health problems: High cholesterol, kidney disease, or liver disease.
  • If you are taking any of these drugs: Demeclocycline, doxycycline, minocycline, tetracycline, a product that has vitamin A in it, a product that is like vitamin A, or St. John’s wort.
  • If you are taking methotrexate.
  • If you are breast-feeding. Do not breast-feed while you take this drug. You will also need to avoid breast-feeding after you stop this drug until there is no more of this drug in your body. Talk with your doctor to see how long you need to avoid breast-feeding after you stop this drug.

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?

For all patients taking this drug:

  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how this drug affects you.
  • It may take a few months to see the full effect.
  • If you have high blood sugar (diabetes), this drug may sometimes raise blood sugar. Talk with your doctor about how to keep your blood sugar under control.
  • High cholesterol and triglyceride levels have happened with this drug. These changes may raise the chance of blood clots or heart and brain blood vessel disease like heart attack or stroke. If you have questions, talk with your doctor.
  • Call your doctor right away if you have signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Have a bone density test as you have been told by your doctor. Talk with your doctor.
  • Skin may look worse before it looks better.
  • You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
  • Trouble seeing at night has happened with this drug. This may be sudden. This may clear up after you stop the drug but sometimes it may not go away. Use care at night when driving or doing other tasks that call for clear eyesight. Keep work space well lit. If you have trouble seeing at night while taking this drug, call your doctor right away.
  • This drug may cause a severe and sometimes deadly problem called capillary leak syndrome (CLS). CLS may lead to low blood pressure, abnormal heartbeat, chest pain, or heart attack. It may also lead to lung or breathing problems, bleeding or lower blood flow in the stomach or bowel, kidney problems, swelling, or feeling confused. If you have questions, talk with the doctor.
  • Raised pressure in the brain has happened with this drug. This can cause long lasting loss of eyesight and sometimes death. Call your doctor right away if you have a bad headache, dizziness, upset stomach or throwing up, or seizures. Call your doctor right away if you have weakness on 1 side of the body, trouble speaking or thinking, change in balance, or change in eyesight.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • Do not use progestin-only birth control pills (minipills). They may not work well. Talk with your doctor.
  • If you have sex without using 2 kinds of birth control that you can trust, if you think you may be pregnant, or if you miss your period, call your doctor right away.

Males:

  • Talk with your doctor before you drink alcohol.

What are some side effects that I need to call my 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 doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • 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 depression, thoughts of suicide, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
  • Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
  • Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
  • Mean actions or thoughts of fighting.
  • Very bad dizziness or passing out.
  • A burning, numbness, or tingling feeling that is not normal.
  • Very bad muscle pain or weakness.
  • Bone or joint pain.
  • Change in eyesight, eye pain, or very bad eye irritation.
  • Change in how contact lenses feel in the eyes.
  • Fever, chills, or sore throat.
  • Swelling.
  • Weight gain.
  • Stomach pain.
  • Severe diarrhea.
  • Bleeding from rectum or rectal pain.
  • Blood in the urine.
  • Thinning of the skin.
  • Severe and sometimes deadly pancreas problems (pancreatitis) have happened with this drug. This could happen at any time during treatment. Signs of pancreatitis include very bad stomach pain, very bad back pain, or very upset stomach or throwing up. Call your doctor right away if you have any of these signs.

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:

  • Dry mouth, eyes, skin, or lips.
  • Hair loss.
  • Eye irritation.
  • It is common to have chapped lips; peeling fingertips, palms, and soles; itching; scaly skin; weak nails; sticky or fragile skin; runny or dry nose; or nosebleeds. Ask the doctor or pharmacist for a lotion or cream to help with drying or chapping. Call your doctor if any of these effects are severe, bother you, or do not go away.

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.

You may report side effects to your national health agency.

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

How is this drug best taken?

Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take this drug with food.
  • Take this drug at the same time of day.

What do I do if I miss a dose?

  • Skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

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

  • Store at room temperature in a dry place. Do not store in a bathroom.
  • Protect from heat and light.
  • 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 symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • This drug comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time this drug is refilled. If you have any questions about this drug, please talk with the doctor, 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

2021-01-13

Copyright

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

Acitretin capsules & psoriasis. Acitretin side-effects – Patient

About acitretin

Type of medicine A retinoid medicine (similar to vitamin A)
Used for Severe psoriasis and some other skin conditions
Also called Neotigason®
Available as Capsules

Acitretin is used to treat severe skin conditions where the surface of the skin has become thick and scaly. Normally, as new skin cells are produced, older ones are lost. If the skin cells in the outer layer of your skin multiply faster than normal, the old skin cells can build up on the surface of your skin, causing thick or scaly patches.

Acitretin is a retinoid medicine, which means simply that it is related to vitamin A. Our bodies use vitamin A to maintain a healthy skin. Acitretin helps to control conditions like psoriasis by making your skin grow more normally.

Acitretin is sometimes used as a treatment on its own but, more often, it is used alongside other preparations to help the skin’s condition.

Before taking acitretin

Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you start taking acitretin it is important that your doctor knows:

  • If you are pregnant, trying for a baby or breastfeeding. This is because you must not take acitretin if you think you are (or think you may be) pregnant.
  • If you have any problems with the way your liver works, or any problems with the way your kidneys work.
  • If you have high levels of fats (lipids) such as cholesterol in your blood.
  • If you have diabetes (diabetes mellitus).
  • If you are taking or using any other medicines. This includes any medicines you are taking which are available to buy without a prescription, as well as herbal and complementary medicines.
  • If you have ever had an allergic reaction to a medicine.

How to take acitretin

  • Before you start the treatment, read the manufacturer’s printed information leaflet from inside your pack and any other information that you are given by your doctor. The leaflets will give you more information about acitretin and will provide you with a full list of the side-effects which you could experience from taking it.
  • Take the capsules exactly as your doctor tells you to. Acitretin is taken once daily. Your doctor will tell you how many capsules to take and this will also be printed on the label of the pack to remind you about what the doctor said to you. Take each of your doses with a snack, or just after eating a meal. It is a good idea to swallow the capsules with a drink of water or milk.
  • Try to take your doses of acitretin at the same time of day each day, as this will help you to remember to take them regularly. If you forget to take a dose at the usual time, take it when you remember. If you do not remember until the following day, then miss out the forgotten dose. Do not take two doses together to make up for a missed dose. 

Getting the most from your treatment

  • It is important for you to keep your regular appointments with your doctor. This is so your doctor can check on your progress. You will need to have regular blood tests during the treatment. The tests will check that your lipid levels are normal and that your liver remains healthy. If you are a woman, you may also need to have regular tests to confirm that you are not pregnant.
  • It can take 2-4 weeks before you start to feel the benefit from the capsules and it may take up to four months before you feel the maximum benefit. A course of treatment is likely to last for up to six months but occasionally it can be for longer than this.
  • Acitretin is harmful to unborn babies, so it is very important that you do not become pregnant while you are taking it. Your doctor will advise you about suitable contraception and this may include using more than one method. You should continue to use suitable contraception for at least three years after you finish your course of treatment. If at any time during your treatment or the three years afterwards, you think you may be pregnant, contact your doctor for advice straightaway.
  • If you buy any medicines, vitamins, or herbal preparations, please check with your doctor or a pharmacist that they are suitable for you to take with acitretin. This is because you must not take any other preparation which contains vitamin A.
  • Acitretin can cause your skin to become more sensitive to sunlight than normal. Protect your skin from sunlight even on bright but cloudy days and do not use sunbeds.
  • If you normally drink alcohol, please ask your doctor for advice. Your doctor may recommend that you do not drink alcohol while you are on this medicine.
  • If you have diabetes you may need to check your blood sugar (glucose) more frequently, as acitretin can affect the levels of sugar in your blood. Your doctor will advise you about this.
  • You must not give blood while you are on acitretin and for at least three years after you finish taking it. This is because it could cause harm to other people.

Can acitretin cause problems?

Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains some of the most common ones associated with acitretin. You will find a full list in the manufacturer’s information leaflet supplied with the medicine. The unwanted effects often improve as your body adjusts to the new medicine but speak with your doctor or pharmacist if any of the following continue or become troublesome.

Common acitretin side-effects (these affect around 1 in 10 people)
What can I do if I experience this?
Dry mouth, feeling thirsty, sore mouth Try chewing sugar-free gum or sucking sugar-free sweets. If this continues, ask your doctor for advice
Dry or irritated eyes, blurred vision, and reduced night vision Take extra care when driving at night. If this becomes troublesome, speak with your doctor
Dry skin and lips, peeling Use a moisturising cream and lip balm regularly. After peeling, the new skin often appears more normal
Tummy (abdominal) pain, feeling sick (nausea), diarrhoea Stick to simple meals (avoid rich or spicy foods). Drink plenty of water to replace any lost fluids
Muscle and joint pain Let your doctor know about this so that it can be investigated
Headache Drink plenty of water and ask your pharmacist to recommend a suitable painkiller. If the headaches continue, let your doctor know
Dry or irritated nose, nosebleeds, weak nails, swollen feet and ankles, mood changes, loss of hair and changes in hair texture If any of these become troublesome, speak with your doctor

If you experience any other symptoms which you think may be due to the capsules, please speak with your doctor or pharmacist for further advice.

How to store acitretin

  • Keep all medicines out of the reach and sight of children.
  • Store in a cool, dry place, away from direct heat and light. 

Important information about all medicines

If you are having an operation or dental treatment, please tell the person carrying out the treatment which medicines you are taking or using.

Never take more than the prescribed dose. If you suspect that you or someone else might have taken an overdose of this medicine, go to the accident and emergency department of your local hospital. Take the container with you, even if it is empty.

This medicine is for you. Never give it to other people even if their condition appears to be the same as yours.

Do not keep out-of-date or unwanted medicines. Take them to your local pharmacy which will dispose of them for you.

If you have any questions about this medicine, ask your pharmacist.

Acitretin 10 mg Capsules – Summary of Product Characteristics (SmPC)

This information is intended for use by health professionals

 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section “Undesirable effects” for how to report adverse reactions.

Each capsule, hard of Acitretin 10 mg contains 10 mg acitretin.

Excipients with known effects

Each capsule, hard of Acitretin 10mg contains sodium.

For the full list of excipients, see section 6.1

Capsule, hard

Acitretin 10 mg consists of a white to off-white body and a brown cap, printed in black with “A10” on the capsule body and filled with a yellow powder.

• Extensive and severe refractory forms of psoriasis;

• Pustulous psoriasis of the hands and feet;

• Severe congenital ichthyosis and ichthyosiform dermatitis;

• Lichen ruber planus of skin and mucous membranes;

• Other severe and refractory forms of dermatitis characterised by dyskeratosis and/or hyperkeratosis.

Acitretin should only be prescribed by doctors, who have experience in treatment with systemic retinoids and who are aware of the teratogenic risk associated with acitretin (see sections 4.4 and 4.6).

The dosage is based on the clinical appearance of the disorder and the tolerability of the product. The treating physician must determine the dosage individually for each patient. The following information can serve as a guide.

This product is available in two strengths:

Acitretin 10 mg capsules

Acitretin 25 mg capsules

Adults

An initial daily dose of 25 or 30 mg acitretin (i.e. 1 capsule of Acitretin 25 mg or 3 capsules of Acitretin 10 mg) for 2 to 4 weeks is recommended. After this initial phase, it may be necessary in some cases to increase the dose up to a maximum of 75 mg acitretin per day (i.e. 3 capsules of Acitretin 25 mg). This maximum dose should not be exceeded.

In patients with Darier’s disease a starting dose of 10mg may be appropriate. The dose should be increased cautiously as isomorphic reactions may occur.

The maintenance dose must be adjusted to the therapeutic response and the tolerability. In general, a daily dose of 30 mg acitretin for a further 6 to 8 weeks allows an optimum therapeutic effect to be achieved in psoriasis. In keratinisation disorders, the maintenance dose should be kept as low as possible (possibly less than 10 mg acitretin per day). It should not on any account exceed 30 mg acitretin per day.

Therapy can generally be discontinued in patients with psoriasis whose lesions have improved sufficiently. Long-term therapy is not recommended in psoriasis patients. Relapses are treated in the same way.

Patients with severe congenital ichthyosis and severe Darier’s disease may require therapy beyond 3 months. The lowest effective dosage, not exceeding 50mg/day, should be given.

Elderly

Dosage recommendations are the same as for other adults.

Combination therapy:

If the administration of acitretin is combined with other forms of treatment, it may be possible to reduce the dose of acitretin according to the therapeutic result. Other dermatological therapy, particularly with keratolytics, should normally be stopped before administration of acitretin. However, the use of topical corticosteroids or bland emollient ointment may be continued if indicated.

Additional topical treatments, including purely skincare treatments, during the administration of acitretin must be discussed with the doctor.

Method of administration

Acitretin hard capsules are for oral administration.

The hard capsules are taken whole once daily with meals or with milk. It is absolutely essential to keep to the dose of acitretin calculated by the doctor.

PREGNANCY: Acitretin, the active substance of Acitretin, is highly teratogenic and must not be used during pregnancy. The same applies to all women of childbearing potential, unless strict contraception is practiced 4 weeks before, during and for 3 years after treatment (see sections 4.4 and 4.6).

LACTATION: Acitretin is contraindicated during the period of breast-feeding.

Acitretin is not indicated in hepatic and renal dysfunction (liver and kidney failure), severe hyperlipaemia, concurrent use of vitamin A or other retinoids and during co-medication with methotrexate. Since Acitretin and tetracyclines can cause an increase in intracranial pressure, they must not be given concurrently.

Acitretin must not be used concomitantly with low dose progesterone-only products (minipills) (see sections 4.5 and 4.6).

Acitretin must not be used in patients with hypersensitivity to the active substance “acitretin” or other retinoids or to any of the excipients.

Teratogenic effects

Acitretin is a powerful human teratogen inducing a high frequency of severe and life threatening birth defects.

Acitretin is strictly contraindicated in:

– Pregnant women

– Women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met


Pregnancy Prevention Programme

This medicinal product is TERATOGENIC.

Acitretin is contraindicated in women of childbearing potential unless all of the following conditions of the Pregnancy Prevention Programme are met:

• Acitretin is indicated for (see section 4.1 “Therapeutic indications”):

o Extensive and severe refractory forms of psoriasis;

o Pustulous psoriasis of the hands and feet;

o Sever congenital ichtyosisand ichthyosiform dermatitis;

o Lichten ruber planus of skin and mucous membranes;

o Other severe and refractory forms of dermatitis characterised by dyskeratosis and/or hyperkeratosis.

• The potential for pregnancy must be assessed for all female patients.

• She understands the teratogenic risk.

• She understands the need for rigorous follow-up on a monthly basis.

• She understands and accepts the need for effective contraception, without interruption, 1 month before starting treatment, throughout the entire duration of treatment and for 3 years after the end of treatment. At least one highly effective method of contraception (i.e. a user-independent form) or two complementary user-dependent forms of contraception should be used.

• Individual circumstances should be evaluated in each case, when choosing the contraception method, involving the patient in the discussion, to guarantee her engagement and compliance with the chosen measures.

• Even if she has amenorrhea she must follow all the advice on effective contraception.

• She is informed and understands the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy or if she might be pregnant.

• She understands the need and accepts to undergo regular pregnancy testing before, ideally monthly during treatment and periodically with 1-3 monthly intervals for a period of 3 years after stopping treatment.

• She has acknowledged that she has understood the hazards and necessary precautions associated with the use of acitretin.

These conditions also concern women who are not currently sexually active unless the prescriber considers that there are compelling reasons to indicate that there is no risk of pregnancy.

The prescriber must ensure that:

• The patient complies with the conditions for pregnancy prevention as listed above, including confirmation that she has an adequate level of understanding.

• The patient has acknowledged the aforementioned conditions.

• The patient understands that she must consistently and correctly use one highly effective method of contraception (i.e. a user-independent form) or two complementary user-dependent forms of contraception, for at least 1 month prior to starting treatment and is continuing to use effective contraception throughout the treatment period and for at least 3 years after cessation of treatment.

• Negative pregnancy test results have been obtained before, during and periodically with 1-3 monthly intervals for a period of 3 years after stopping treatment. The dates and results of pregnancy tests should be documented.

If pregnancy occurs in a woman treated with acitretin, treatment must be stopped and the patient should be referred to a physician specialised or experienced in teratology for evaluation and advice.

If pregnancy occurs after stopping treatment there remains a risk of severe and serious malformation of the foetus. This risk persists until the product has been completely eliminated, which is within 3 years following the end of treatment.


Contraception

Female patients must be provided with comprehensive information on pregnancy prevention and should be referred for contraceptive advice if they are not using effective contraception. If the prescribing physician is not in a position to provide such information the patient should be referred to the relevant healthcare professional

As a minimum requirement, female patients of childbearing potential must use at least one highly effective method of contraception (i. e. a user-independent form), or two complementary user-dependent forms of contraception. Contraception should be used for at least 1 month prior to starting treatment, throughout treatment and continue for at least 3 years after stopping treatment with acitretin, even in patients with amenorrhea.

Individual circumstances should be evaluated in each case, when choosing the contraception method involving the patient in the discussion, to guarantee her engagement and compliance with the chosen measures.


Pregnancy testing

According to local practice, medically supervised pregnancy tests with a minimum sensitivity of 25mUI/mL are recommended to be performed, as follows.

Prior to starting therapy

At least one month after the patient has started using contraception, and shortly (preferably a few days) prior to the first prescription, the patient should undergo a medically supervised pregnancy test. This test should ensure the patient is not pregnant when she starts treatment with acitretin.

Follow-up visits

Follow-up visits should be arranged at regular intervals, ideally monthly. The need for repeated medically supervised pregnancy tests every month should be determined according to local practice including consideration of the patient’s sexual activity, recent menstrual history (abnormal menses, missed periods or amenorrhea) and method of contraception. Where indicated, follow-up pregnancy tests should be performed on the day of the prescribing visit or in the 3 days prior to the visit to the prescriber.

End of treatment

Women should undergo pregnancy test periodically with 1-3 monthly intervals for a period of 3 years after stopping treatment.


Prescribing and dispensing restrictions

For women of childbearing potential, the prescription duration of this medicine should ideally be limited to 30 days in order to support regular follow up, including pregnancy testing and monitoring. Ideally, pregnancy testing, issuing a prescription and dispensing of this medicine should occur on the same day.

This monthly follow-up will allow ensuring that regular pregnancy testing and monitoring is performed and that the patient is not pregnant before receiving the next cycle of medication.


Male patients

The available data suggest that the level of maternal exposure from the semen of the patients receiving this medicine is not of a sufficient magnitude to be associated with the teratogenic effects of acitretin. Male patients should be reminded that they must not share their medication with anyone, particularly not females.


Additional precautions

Patients should be instructed never to give this medicinal product to another person and to return any unused capsules to their pharmacist at the end of treatment.

Patients should not donate blood during therapy and for 3 years following discontinuation of acitretin because of the potential risk to the foetus of a pregnant transfusion recipient.


Educational material

In order to assist prescribers, pharmacists and patients in avoiding foetal exposure to acitretin the Marketing Authorisation Holder will provide educational material to reinforce the warnings about the teratogenicity of acitretin, to provide advice on contraception before therapy is started and to provide guidance on the need for pregnancy testing.

Full patient information about the teratogenic risk and the strict pregnancy prevention measures as specified in the Pregnancy Prevention Programme should be given by the physician to all patients, both male and female.


Psychiatric disorders

Depression, depression aggravated, anxiety, and mood alterations have been reported in patients treated with systemic retinoids, including acitretin. Particular care should be taken in patients with a history of depression. Patients should be monitored for signs of depression and referred for appropriate treatment if necessary. Awareness by family or friends may be useful to detect mental health deterioration.


Other warnings

Clinical evidence has shown that etretinate can be formed with concurrent ingestion of acitretin and alcohol. Etretinate is highly teratogenic and has a longer half-life (approximately 120 days) than acitretin. Women of childbearing age must therefore not consume alcohol (in drinks, food or medicines) during treatment with acitretin and for 2 months after cessation of acitretin therapy. Contraceptive measures and pregnancy tests must also be taken for 3 years after completion of acitretin treatment (see section 4.6 and 5.2).

Women of childbearing potential must not receive blood from patients being treated with acitretin. Donation of blood by a patient being treated with acitretin is prohibited during and for 3 years after completion of treatment with acitretin.

Due to the risk of foetal malformations, the medicine must not be passed on to other people. Unused or expired products should be returned to a pharmacy for disposal.

In view of possible effects on liver function, this must be monitored regularly during treatment. Hepatic function should be checked before starting treatment with Acitretin, every 1 – 2 weeks for the first 2 months after commencement and then every 3 months during treatment. If abnormal results are obtained, weekly checks should be instituted. If hepatic function fails to return to normal or deteriorates further, Acitretin must be withdrawn. In such cases it is advisable to continue monitoring hepatic function for at least 3 months.

Serum cholesterol and serum triglycerides (fasting values) must be monitored before starting treatment, one month after the commencement and then every 3 months during treatment. Acitretin treatment should be discontinued in case of uncontrolled levels of hypertriglyceridemia or if symptoms of pancreatitis occur.

In diabetic patients, retinoids can alter glucose tolerance. Blood sugar levels should therefore be checked more frequently than usual at the beginning of the treatment period.

Before and during long-term therapy, x-rays (e.g. of the vertebral column, long bones, including ankles and wrists) must be taken at regular intervals (every year) in view of possible ossification abnormalities (see section 4.8). In the event of hyperostosis, the discontinuation of therapy must be discussed with the patient. The risks must be carefully weighed against the therapeutic benefit to be expected.

Since there have been occasional reports of bone changes in children, including premature epiphyseal closure, fractures, skeletal hyperostosis and extraosseous calcification after long-term treatment with etretinate, these effects may be expected with its active metabolite acitretin. Acitretin therapy in children is not, therefore, recommended unless, in the opinion of the physician, the benefits significantly outweigh the risks and all other alternative treatments have failed. If, in exceptional circumstances, such therapy is undertaken the child should be regularly monitored for any abnormalities of musculo-skeletal development and growth. Any symptoms that suggest possible bone changes (restricted mobility, bone pain) should be carefully investigated. As soon as the medical condition allows, the use of acitretin should be interrupted.

The dosage should be based on bodyweight (b.w.). An initial daily dose of 0.5 mg acitretin per kg b.w. is recommended. Higher doses up to 1 mg acitretin per kg b.w. per day may be necessary for a limited period in some cases. The maximum dose of 35 mg acitretin per day should not be exceeded.

The fixed-dose capsule formulations of 10 and 25 mg may not provide sufficient flexibility to cover the proposed paediatric dosing schedule per kg b.w. In this case preparation of a suitable dosage form (e.g. powders or capsules) made of the capsule content of Acitretin by qualified pharmaceutical personnel in a public or hospital pharmacy is suggested.

The mean maintenance dose lies at 0.1 mg acitretin per kg b.w. per day. The maintenance dose should be kept as low as possible and should generally not exceed 0.2 mg acitretin per kg b.w. per day (dosing every other day may be considered).

The effects of UV light are enhanced by retinoid therapy, therefore patients should avoid excessive exposure to sunlight and the unsupervised use of sun lamps.

Decreased night vision has been reported with acitretin therapy. Patients should be advised of this potential problem and warned to be cautious when driving or operating any vehicle at night. Visual problems should be carefully monitored (see sections 4.7 and 4.8).

Wearing of contact lenses might become impossible due to dryness of the eyes. Patients who wear contact lenses should be excluded from treatment or wear glasses throughout the treatment period.

Very rare cases of Capillary Leak Syndrome / retinoic acid syndrome have been reported from world-wide post marketing experience.

Very rare cases of Exfoliative dermatitis have been reported from world-wide post marketing experience.

Systemic treatment with retinoids may lead to an increase in intracranial pressure. Since tetracyclines can also cause such an increase in pressure, patients must not be treated concurrently with Acitretin and a tetracycline.

An increased risk of hepatitis has been reported during co-medication with etretinate and methotrexate. Consequently, the concomitant use of methotrexate and acitretin (metabolite of etretinate) should be avoided.

In concurrent treatment with phenytoin Acitretin, it must be remembered that Acitretin partially reduces the protein binding of phenytoin. In contrast, an influence of this kind on plasma binding with concurrent use of Acitretin and coumarin-type anticoagulants has not been observed.

The contraceptive effect of low-dose progesterone pills (“the mini-pill”) may be reduced by interaction with acitretin. These pills must therefore not be used for contraception during acitretin therapy. Interactions with combined oral oestrogen/progestogen oral contraceptives have not been observed (see section 4.6).

In a study with healthy volunteers, concurrent intake of a single dose of acitretin together with alcohol led to the formation of etretinate which is highly teratogenic. Women of childbearing age must therefore not consume alcohol (in drinks, food or medicines) during treatment with acitretin and for 2 months after cessation of acitretin therapy (see section 4.4 and 5.2). The mechanism of this metabolic process has not been defined, so it is not clear whether other interacting agents are also possible.

For interactions with alcohol in women of childbearing age and the effects on pregnancy: see section 4.6.

Patients are advised against taking vitamin A and other retinoids concurrently in view of the possible occurrence of hypervitaminosis A.

Interactions of Acitretin with other products (e.g. digoxin, cimetidine) have not been observed to date.

Acitretin is highly teratogenic. Its use is contraindicated in women who might become pregnant during or within 3 years of the cessation of treatment. The risk of giving birth to a deformed child (craniofacial, central nervous system, cardiovascular, skeleton, thymus) is exceptionally high if acitretin is taken before or during pregnancy, no matter for how long or at what dosage. Also after use of acitretin during pregnancy, a single case with similar deformations has been reported.

Acitretin in common with vitamin A and other retinoids may cause malformations in offspring of various animal species, even at the dose levels recommended for humans. As acitretin is teratogenic in animals at human dose levels, Acitretin is absolutely contraindicated during pregnancy and women of childbearing age must not be treated with Acitretin, if pregnancy cannot be excluded (see section 4.3).

At treatment of female patients of childbearing age with a very severe or disabling clinical picture, the treating physician may consider prescribing Acitretin, in case no alternative therapy, is available. Acitretin should only be prescribed by doctors, who have experience in treatment with systemic retinoids, preferably dermatologists, and who are aware of the teratogenic risk associated with acitretin if used during pregnancy.

Transformation of acitretin into etretinate is enhanced by alcohol. The formation, in vivo, of etretinate from acitretin with concomitant intake of alcohol, cannot be excluded. Etretinate is also teratogenic. As etretinate may be stored in fatty tissue and has a longer elimination half-time (approximately 120 days) than acitretin, women of childbearing age must not consume alcohol (in drinks, food or medicines) during treatment with acitretin and for 2 months after cessation of acitretin therapy (see section 4.4, 4.5 and 5.2). Also women of childbearing age should keep on practicing contraception for 3 years after stopping treatment.

Before Acitretin treatment is instituted, the potential risks must be weighed against the expected therapeutic effect. Furthermore, a number of precautionary measures must be STRICTLY followed:

Acitretin is contraindicated in every woman of childbearing potential unless each of the following conditions is met:

1) The patient is suffering from a severe disorder of keratinisation which is resistant to standard therapies.

2) She can be relied on to understand and follow the physician’s instructions.

3) She is capable of taking the stipulated contraceptive measures reliably and without fail.

4) It is absolutely essential that every woman of childbearing potential who is to undergo treatment with acitretin uses effective contraception (preferably 2 complementary methods) without interruption for four weeks before, during and for 3 years after the discontinuation of treatment with acitretin. The patient should be instructed to immediately contact a doctor in case of suspected pregnancy.

5) Therapy should not begin until the second or third day of the next normal menstrual period.

6) At the start of therapy, a negative pregnancy test result (minimum sensitivity of 25mIU/mL) must be obtained up to three days before the first dose is given. During therapy, pregnancy tests should be arranged at 28-day intervals. A negative pregnancy test not older than 3 days is mandatory before prescription is made at these visits. After stopping therapy, pregnancy tests should be performed at 1-3 monthly intervals for a period of 3 years after the last dose is given.

7) Before therapy with acitretin is instituted, the physician must give patients of childbearing potential detailed information about the precautions to be taken, the risk of very severe foetal malformation, and the possible consequences if pregnancy occurs during the course of treatment with acitretin or within 3 years of discontinuing therapy.

8) The same effective and uninterrupted contraceptive measures must be taken every time therapy is repeated, however long the intervening period may have been, and must be continued for 3 years afterwards.

9) Should pregnancy occur, in spite of these precautions, there is a high risk of severe malformation of the foetus (e.g. craniofacial defects, cardiac and vascular or CNS malformations, skeletal and thymic defects.) and the incidence of spontaneous abortion is increased. This risk applies especially during treatment with acitretin and 2 months after treatment. For up to 3 years after acitretin discontinuation, the risk is lower (particularly in women who have not consumed alcohol) but cannot be entirely excluded due to possible formation of etretinate.

10) She must avoid alcohol consumption (in drinks, food or medicines) during treatment and for 2 months after stopping treatment (see section 4.4, 4.5 and 5.2).

Primary contraceptive method is a combination hormonal contraceptive product or an intrauterine device and it is recommended that a condom or diaphragm (cap) is also used. Low dose progesterone-only products (minipills) are not recommended due to indications of possible interference with their contraceptive effect.

For male patients treated with acitretin, available data, based on the level of maternal exposure from the semen and seminal fluid indicate a minimal, if any, risk of teratogenic effects.

Pregnancy

Acitretin is contraindicated in pregnant women (see section 4.3).

Lactation

Acitretin is lipophilic and passes into the breast milk. Patients must not breast-feed during treatment with Acitretin (see section 4.3)

This medicine contains less than 1mmol sodium (23mg) per tablet, that is to say essentially “sodium-free”.

Acitretin has moderate influence on the ability to drive and use machines.

Decreased night vision has been reported with Acitretin therapy. In rare cases, this has continued after the treatment has stopped. Patients should be advised of this potential problem and warned to be cautious when driving or operating any vehicle at night or in a tunnel. Visual problems should be carefully monitored (see section 4. 8).

Possible side effects of Acitretin occur in varying degrees from patient to patient. Most of the side effects are dose-related and usually reversible with reduction of dosage or discontinuation of therapy.

At the start of treatment with Acitretin there may be a transient worsening of the psoriasis symptoms.

The skin and mucous membranes are most commonly affected, and it is recommended that patients should be so advised before treatment is commenced.

The reported adverse reactions are listed below by system organ class and by frequency.

Frequencies are defined as:

Very common (≥ 1/10)

Common (≥ 1/100 to < 1/10)

Uncommon (≥ 1/1,000 to < 1/100)

Rare (≥ 1/10,000 to < 1/1,000)

Very rare (<1/10,000)

Not known (frequency cannot be estimated from the available data)

Skin and subcutaneous tissue disorders:

Very common:

over 80% of patients experienced: hypervitaminosis A as e. g. dry lips and possibly inflamed lips (using moisturisers or ’emollients’ from the start of treatment can help to relieve dry skin problems.)

40 – 80% of patients experienced: dry mucous membranes of mouth and nose, peeling of skin, especially the palms of the hands and soles of the feet, rhinitis.10 – 40% of patients experienced: nose bleed, scaling and thinning of healthy skin with increased sensitivity, erythema, pruritus, sensation of “burning skin”, sensation of “sticky skin”, dermatitis, hair loss, inflammation of the nail wall, nail fragility.

Common:

up to 10% of patients experienced: development of rhagades, inflammation of oral mucosa and gingiva associated with taste disturbances, blistering of the skin, change in pigmentation of the skin and hair, change in growth rate of hair, change in hair structure.

Marked dose dependence has been observed especially with regard to

– dry skin and mucous membranes, especially of the lips and nose,

– increased sensitivity of the skin and mucous membranes and

– hair loss.

Side effects of the skin and mucous membranes occur rather soon (a few days) after start of treatment, hair loss cannot be expected until several weeks into the treatment.

These side effects are reversible after altering the dose or discontinuation of treatment. However, new growth of hair will take some months, due to the hair growth cycle.

Rare:

Increased sensitivity of the skin to light, as a result of which a sunburn can occur after only brief exposure to the sun. In these cases, care must be taken to wear adequate sun protection.

Not known:

Madarosis and exfoliative dermatitis.

Eye disorders

Common:

Conjunctivitis (10 to 40%), visual disturbances, e.g. xerophthalmia, blurred vision, impaired night vision (see also sections 4.4 and 4.7).

Wearing of contact lenses might become impossible. For this reason, patients should wear glasses during treatment with Acitretin.

Rare:

Inflammation or ulcers of the cornea.

Respiratory, thoracic and mediastinal disorders

Not known:

Dysphonia

Musculoskeletal and connective tissue disorders

Uncommon:

Myalgia, arthralgia and bone pain.

After long-term treatment (see section 4. 2) with acitretin, bone changes may occur (hyperostosis, thinning of bone, osteoporosis, premature epiphyseal closure) and soft-tissue calcification (extraosseous calcification).See section 4.4.

Gastrointestinal tract disorders

Rare:

Gastrointestinal symptoms (e.g. nausea, vomiting, abdominal pain, diarrhoea, dyspepsia).

Hepatobiliary disorders

Rare:

Hepatitis and jaundice.

Reproductive system and breast disorders

During treatment with Acitretin an increase in vulvovaginitis caused by Candida albicans has been observed.

General disorders

Common:

Thirst and feeling of cold (10 to 40%).

Uncommon:

Peripheral oedema, sensation of heat, dysgeusia, headache.

Investigations

In addition to a possible increase in liver function values, an elevation of blood lipids has also been observed during treatment with Acitretin.

The following changes in laboratory values occurred in patients during clinical trials:

– Elevation of triglycerides, total cholesterol, SGPT, creatine phosphokinase, SGOT, γ-GT, alkaline phosphatase, direct bilirubin, lactate dehydrogenase and uric acid

– Lowering of HDL cholesterol.

Occasionally an increase in creatinine, BUN and total bilirubin was observed.

Nervous system disorders

Rare:

An increase of intracranial pressure (pseudotumor cerebri) may occur, which may be accompanied by severe headache, lightheadedness, nausea, vomiting, dizziness or visual disturbances, but subsides after discontinuation of treatment. If these symptoms occur the treating physician should be consulted immediately.

Immune system disorders

Not known:

Type 1 hypersensitivity.

Vascular disorders

Not known:

Capillary Leak Syndrome / retinoic acid syndrome.

Not all the consequences of long-term therapy with Acitretin can be estimated as yet.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Health professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

Overdose of Acitretin leads to the signs and symptoms of acute hypervitaminosis A, with headache, nausea and/or vomiting, drowsiness, irritability and pruritus.

In the event of acute overdose, the use of Acitretin must be stopped. No further specific measures are necessary because of the low acute toxicity of the product.

Pharmacotherapeutic group: Antipsoriatics, retinoids for treatment of psoriasis

ATC code: D05BB02

Retinol (Vitamin A) is known to be essential for normal epithelial growth and differentiation, though the mode of this effect is not yet established. Both retinol and retinoic acid are capable of reversing hyperkeratotic and metaplastic skin changes. However, these effects are generally only obtained at dosages associated with considerable local or systemic toxicity.

Acitretin, the active ingredient of Acitretin, is a synthetic aromatic analogue of retinoic acid and the main metabolite of etretinate, which has been used with success for a number of years in the treatment of psoriasis and other disorders of keratinisation.

Clinical studies have confirmed that, in psoriasis and dyskeratosis, acitretin brings about a normalisation of epidermal cell proliferation, differentiation and keratinisation in doses at which the side effects are generally tolerable. The effect of Acitretin is purely symptomatic: the mechanism of action is still largely unknown.

In the case of keratinisation disorders, experience for up to 2 years is available.

Absorption

Acitretin reaches peak plasma concentration 1 – 4 hours after ingestion of the drug. Bioavailability of orally administered acitretin is enhanced by food. Bioavailability of a single dose is approximately 60%, but inter-patient variability is considerable (36 95%).

Distribution

Acitretin is highly lipophilic and penetrates readily into body tissues. Protein binding of acitretin exceeds 99%. In animal studies, acitretin passed the placental barrier in quantities sufficient to produce foetal malformations. Due to its lipophilic nature, it can be assumed that acitretin passes into breast milk in considerable quantities.

Metabolism

Acitretin is metabolised by isomerisation into its 13-cis isomer (cis acitretin), by glucuronidation and cleavage of the side chain.

Elimination

Multiple-dose studies in patients aged 21 – 70 years showed an elimination half-life of approximately 50 hours for acitretin and 60 hours for its main metabolite in plasma, cis acitretin, which is also a teratogen. From the longest elimination half-life observed in these patients for acitretin (96 hours) and cis acitretin (123 hours), and assuming linear kinetics, it can be predicted that more than 99% of the drug is eliminated within 36 days after cessation of long-term therapy. Furthermore, plasma concentrations of acitretin and cis acitretin dropped below the sensitivity limit of the assay (< 6ng/ml) within 36 days following cessation of treatment. Acitretin is excreted entirely in the form of its metabolites, in approximately equal parts via the kidneys and the bile.

Clinical evidence has shown that etretinate can be formed with concurrant ingestion of acitretin and alcohol. Etretinate is highly teratogenic and has a longer half-life (approximately 120 days) than acitretin (see section 4.4, 4.5 and 4.6).

Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxicity, and carcinogenic potential.

For teratogenic effects see section 4.6.

Capsule filling:

Maltodextrin

Sodium ascorbate

Microcrystalline cellulose

Capsule shell:

Gelatin

Propylene glycol (E1520)

Sodium laurilsulfate

Titanium dioxide (E171)

Iron oxide yellow (E172)

Iron oxide black (E172)

Iron oxide red (E172)

Purified water

Shellac

Do not store above 30 °C. Store in the original package, in order to protect from moisture.

PVC/PVDC aluminium blister packs

Pack sizes:

30 and 60 hard capsules

Not all pack sizes may be marketed.

Any unused product or waste material should be disposed of in accordance with local requirements.


Genus Pharmaceuticals

Linthwaite

Huddersfield

HD7 5QH

UK

Acitretin | DermNet NZ

Author: Dr Amanda Oakley, Department of Dermatology, Waikato Hospital, Hamilton, New Zealand, 1997. Updated February 2016. Updated May 2021


What is acitretin?

Acitretin is an oral retinoid (vitamin-A derivative) used to treat severe psoriasis, usually at a dose of 0.25–1 mg per kg body weight per day. It is best taken after a meal because it needs fat to be absorbed through the gut wall.

Acitretin is available as 10 mg and 25 mg capsules. Trade names include Neotigason™ and Novatretin®. Since March 2009, PHARMAC funding in New Zealand requires Special Authority application by a dermatologist or vocationally registered general practitioner. Restrictions apply.

What is acitretin used for?

Acitretin is particularly useful for pustular psoriasis, erythrodermic psoriasis and psoriasis affecting hands and feet. It is not effective for psoriatic arthritis.

It is occasionally used to treat other skin conditions including:

Risk of acitretin in pregnancy and during breastfeeding

Acitretin MUST NOT be taken in pregnancy; it can damage an unborn child and cause congenital disabilities. Strict birth control measures must be used during treatment and for three years after stopping acitretin. Therefore, acitretin is rarely prescribed to females of child-bearing potential. If it is, they will be asked to have a blood pregnancy test before treatment and regularly during treatment. People on acitretin should not donate blood during treatment or for three years afterwards. Acitretin is also contraindicated while breastfeeding.

It does not affect male sexual function or offspring, so males of all ages can take it.

What is the mechanism of action of acitretin?

Acitretin is a metabolite of an earlier antipsoriatic retinoid, etretinate. Etretinate (Tigason™) is no longer available in New Zealand.

Acitretin is thought to work in psoriasis by slowing down the proliferation of the skin cells. A response is noted in more than half of treated patients. Improvement begins about two weeks after starting treatment and is maximum after about twelve weeks. The affected skin either peels off or gradually clears.

Some patients are treated with acitretin for a few months, repeated from time to time, while others remain on the acitretin long term.

In resistant cases, acitretin can be combined with other antipsoriatic drugs and phototherapy.

What are the side effects and risks of acitretin?

Acitretin has side effects that may limit the dose that can be used.

  • Dryness of lips — apply lip salve frequently, especially when outdoors.
  • Dry nostrils that may crust and bleed: petroleum jelly can help.
  • Dry eyes — use artificial tear eye drops.
  • Dry reddened skin: apply moisturisers frequently.
  • Peeling skin, especially hands and feet; apply moisturisers frequently.
  • Fragile soft skin: protect it from injury.
  • With long-term use, thin, ridged, and brittle nails.
  • Generalised hair shedding and thinning may occur; this is usually temporary although permanent thinning has been reported.
  • Change in colour and texture of hair may occur.
  • Increased susceptibility to sunburn: protect your skin from the sun. Use a broad-spectrum sunscreen and dress up well. If you are receiving phototherapy, advise your therapist that you are taking acitretin. A reduction in dose may be necessary.
  • Skin infections, especially with Staphylococcus aureus (impetigo, boils or nail fold paronychia).
  • Aggravation of skin complaint: this is often temporary and followed by improvement, but if a severe flare occurs you should tell your dermatologist and stop taking the acitretin.
  • Headaches: if these are severe or accompanied by visual problems, inform your dermatologist and stop the acitretin; the symptoms could be caused by an increase in pressure on the brain.
  • Muscle, joint or bone aches, especially with exercise; reduce exercise if needed.
  • Hyperlipidaemia (raised blood fats — cholesterol and triglyceride), detected by blood tests, which are best taken when fasting (on an empty stomach). The level of the blood fats is compared with a pre-treatment test. High blood fats are more likely in people with diabetes and in those who drink a lot of alcohol. If the blood fats are too high, a particular low fat and low sugar diet may be recommended, a lipid-lowering medication may be prescribed, or the dose of acitretin may be reduced or stopped.
  • Rarely, acitretin may result in disturbed liver function (hepatitis). It should be discontinued if this occurs, and it would be unwise to retake it.
  • Mood changes; high dose retinoids can cause mood change including irritability, aggression and depression.

Side effects of acitretin

Interactions with other medications

Acitretin should not usually be taken at the same time as the following medications (there may be rare exceptions):

  • Vitamin A or any other retinoid (eg, isotretinoin)
  • Tetracycline or one of its derivatives is contraindicated as both tetracyclines and retinoids can increase intracranial pressure
  • Methotrexate
  • Phenytoin.

It is best to avoid alcohol when on acitretin, especially if triglyceride levels are high.

Soriatane – Uses, Side Effects, Interactions

How does this medication work? What will it do for me?

Acitretin is a derivative of vitamin A. It is used to treat severe psoriasis and other skin disorders. Acitretin reduces the speed at which the cells involved in psoriasis are formed. It may take 2 to 3 months before the full benefit of acitretin is seen.

Psoriasis is a skin condition that involves chronically occurring bright red patches covered with silvery scales. It cannot be passed from one person to another.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

10 mg
Each brown and white, hard gelatin capsule (No. 4) with “ACTAVIS” in black lettering contains acitretin 10 mg. Nonmedicinal ingredients: gelatin, glucose (liquid, spray-dried), microcrystalline cellulose, and sodium ascorbate; gelatin capsule shell: iron oxide (yellow, black, and red) and titanium dioxide.

25 mg
Each brown and yellow, hard gelatin capsule (No. 1) with “ACTAVIS” in black lettering contains acitretin 25 mg. Nonmedicinal ingredients: gelatin, glucose (liquid, spray-dried), microcrystalline cellulose, and sodium ascorbate; gelatin capsule shell: iron oxide (yellow, black, and red) and titanium dioxide.

How should I use this medication?

The recommended starting dose of acitretin is 25 mg once daily. If the desired effect has not been seen after 4 weeks and side effects have been tolerated, your doctor may increase the dose to 50 mg once daily. The maximum dose is 75 mg once a day.

Acitretin should be taken once daily with food or just after a meal.

Many things can affect the dose of medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

It is important to take this medication exactly as prescribed by your doctor. If you miss a dose, take it as soon as possible and continue with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take acitretin if you:

  • are allergic to acitretin, vitamin A, or any of the ingredients of the medication
  • have certain types of abnormal cholesterol levels
  • have excess vitamin A in the body
  • have severely reduced kidney or liver function
  • are taking methotrexate or tetracyclines

A woman capable of becoming pregnant must not take acitretin unless ALL of the following criteria are met:

  • She is able to use 2 effective birth control methods.
  • She is reliable in understanding and carrying out instructions.
  • She has had 2 negative pregnancy tests before the start of treatment (the first at the screening appointment and the second up to 3 days before the first dose of acitretin).
  • She will have pregnancy tests at 28-day intervals throughout treatment.
  • She has received and understands information regarding the risks of having babies with deformities associated with acitretin exposure.
  • She has severe psoriasis or other severe skin disease, as judged by the doctor.
  • She will have pregnancy tests every 1 to 3 months for at least 3 years after the last dose of acitretin.

Acitretin must not be taken by pregnant women. As well, women must not become pregnant while taking acitretin and should use effective birth control for at least 3years after stopping this medication. Women should not breast-feed while taking acitretin or for 3 years after stopping the medication.

Alcohol must not be consumed while taking acitretin and for 2 months after stopping the treatment.

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent. The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

When acitretin is first started, you may experience more redness, itching, skin scaling, peeling, and dry skin for the first month as your body adjusts to the medication. This will normally fade as treatment continues. It is important that you see your doctor regularly (preferably once a month) and report any side effects that become bothersome.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

  • abdominal pain
  • abnormal hair texture
  • back pain
  • change in appetite
  • cold or clammy skin
  • diarrhea
  • dry eyes
  • dry mouth, chapped lips (especially in the first few weeks)
  • dry skin
  • earache
  • fatigue
  • fluid retention
  • gum swelling or bleeding
  • hair loss (especially in the first few weeks)
  • headache
  • impotence
  • increased appetite
  • increased saliva
  • increased sweating
  • infection
  • inflammation around the fingernails
  • insomnia (difficulty sleeping)
  • itchiness (especially in the first few weeks)
  • mouth sores
  • muscle pain
  • nail disorders
  • nausea
  • nervousness
  • nosebleeds
  • numbness
  • rash
  • rhinitis (runny nose)
  • ringing in the ears
  • sensitivity of skin or eyes to light
  • skin peeling or scaling (especially in the first few weeks)
  • skin ulcers
  • sore joints
  • sticky skin
  • taste disturbances
  • thirst

Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not check with your doctor seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

  • abnormal vision
  • aches or pains in bones or joints
  • arthritis
  • bleeding or inflammation of the gums
  • blurred vision
  • dark urine
  • decrease in night vision
  • difficulty in moving
  • eye irritation
  • eye pain
  • eye sensitivity to light
  • flu-like symptoms
  • headaches
  • hearing problems
  • nausea (severe)
  • other visual problems
  • persistent feeling of dry eyes
  • signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
  • vomiting
  • yellowing of the skin or eyes

Stop taking the medication and seek immediate medical attention if any of the following occur:

  • signs of a blood clot in the arm or leg (tenderness, pain, swelling, warmth, or redness in the arm or leg) or lungs (difficulty breathing, sharp chest pain that is worst when breathing in, coughing, coughing up blood, sweating, or passing out)
  • signs of a heart attack (e.g., chest pain or pressure, pain extending through shoulder and arm, nausea and vomiting, sweating)
  • signs of a serious allergic reaction (e.g., abdominal cramps, difficulty breathing, nausea and vomiting, or swelling of the face and throat)
  • signs of a severe skin reaction such as blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort
  • signs of stroke (e.g., sudden headache, weakness or numbness in an arm or leg, difficulty speaking or understanding, sudden vision difficulty, dizziness)
  • signs of retinoic acid syndrome (e.g., fever, shortness of breath, swelling or puffiness of the arms, legs and feet, weight gain, difficulty in urination, yellowing of the skin or eyes)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin taking a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should take this medication.

Alcohol: Alcohol must not be consumed while taking acitretin and for 2 months after stopping the treatment. This includes alcohol in foods, drinks, and medicines.

Benign intracranial hypertension: Acitretin has been known to cause a condition called benign intracranial hypertension. Contact your doctor if you experience headaches, nausea and vomiting, or changes in vision.

Blood donation: Do not donate blood while taking acitretin and for at least 3 years after your last dose of acitretin, as your blood should not be given to pregnant women.

Cholesterol: Acitretin has been found to cause an increase in cholesterol and other lipids in the blood. You are more likely to experience this if you are already at an increased risk of developing high cholesterol, for example if you have diabetes or a family history of high cholesterol, are overweight, or have an increased alcohol intake.

If you are at any increased risk of developing increased blood lipids, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Contact lenses: If you wear contact lenses, you may find them uncomfortable during and after treatment with acitretin due to dry eyes.

Decreased night vision: Acitretin may cause decreased night vision. Do not drive or operate heavy machinery at night until you know how this medication affects you.

Depression and suicidal thoughts: Retinoid medications have been known to cause mood swings and symptoms of depression. If you have depression or a history of depression, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you experience symptoms of depression such as poor concentration, changes in weight, changes in sleep, or decreased interest in activities, or notice them in a family member who is taking this medication, contact your doctor as soon as possible.

Diabetes: Acitretin can cause changes in glucose tolerance for people with diabetes. If you have diabetes, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Excessive bone growth: Long-term use of acitretin may lead to excessive bone growth or unusual bone formation. Your doctor may request that you have yearly X-rays to monitor for bone changes.

Liver function: Retinoids like acitretin have been linked to inflammation of the liver in some cases. If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your liver function regularly with blood tests while you are taking this medication.

If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor as soon as possible.

Stomach and bowels: Other retinoid medications have occasionally caused inflammatory bowel disease (IBD). If you have inflammatory bowel disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience severe abdominal pain, rectal bleeding or severe diarrhea, you should stop using this medication and contact your doctor.

Sun sensitivity: Acitretin may make you more likely to burn in the sun. Use appropriate measures to prevent excessive exposure to the sun. Wear a hat and sunglasses when out in the sun, use a sunscreen with an SPF of 30 or higher, and avoid going out in the sun between 10 am and 2 pm when the sun is at its strongest. Avoid using sun lamps and tanning beds.

Women capable of becoming pregnant: See “Who should not take this medication?”

Pregnancy: Acitretin can cause birth defects. This medication must not be taken during pregnancy. If you become pregnant while taking acitretin, contact your doctor immediately.

Breast-feeding: This medication passes into breast milk. If you are a breast-feeding mother and are taking acitretin, it may affect your baby. Breast-feeding mothers must not take this medication.

Children: The safety and efficacy of using this medication have not been established for children.

What other drugs could interact with this medication?

There may be an interaction between acitretin and any of the following:

  • alcohol
  • any medications or products containing vitamin A (including multivitamins)
  • any medications or products related to vitamin A
  • carbamazepine
  • methotrexate
  • phenytoin
  • progestin-only birth control
  • sulfonylureas (e.g., glyburide)
  • tetracyclines (e.g., tetracycline, doxycycline, minocycline)

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

  • stop taking one of the medications,
  • change one of the medications to another,
  • change how you are taking one or both of the medications, or
  • leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2021. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Soriatane

Neotigason instructions for use: indications, contraindications, side effects – description of Neotigason caps. 25 mg: 30, 50 or 100 pcs. (19056)

📜 Instructions for use Neotigazon ®

💊 Composition of the preparation Neotigazone ®

✅ Application of the drug Neotigazone ®

📅 Storage conditions Neotigazon ®

⏳ Shelf life Neotigazon ®

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Description of the medicinal product

Neotigazone ®
(Neotigason)

Based on the officially approved instructions for use of the drug and prepared for the electronic edition of the Vidal Handbook 2009, update date: 2020.07.24

Marketing Authorization Holder:

Contacts for inquiries:

AKTAVIS GROUP AO
(Iceland)

Dosage forms

Neotigazone ®

Caps.10 mg: 30, 50 or 100 pcs.

reg. No .: P N016163 / 01
from 23.08.10
– Unlimited

Re-registration date: 05/07/14

Caps. 25 mg: 30, 50 or 100 pcs.

reg. No .: P N016163 / 01
from 23.08.10
– Unlimited

Re-registration date: 05/07/14

Release form, packaging and composition
the drug Neotigazone

®

Capsules gelatinous, No. 4, body – white or slightly yellowish, opaque; the lid is brown, opaque; with black lettering “10” on the body, with black lettering “actavis” on the lid; the contents of the capsules are powder with compact lumps from pale yellow to yellow.

1 caps.
acitretin (in the form of a dry spray containing 25% of the active substance) 10 mg

Excipients : microcrystalline cellulose – 50 mg; as part of a dry spray (per 1 g): gelatin – 270 mg, maltodextrin – 410 mg, sodium ascorbate – 70 mg.

5 pcs. – blisters (6) – cardboard packs.

Capsules gelatinous, No. 1, body – yellow, opaque; the lid is brown, opaque; with black lettering “25” on the body, with black lettering “actavis” on the lid; the contents of the capsules are powder with compact lumps from pale yellow to yellow.

1 caps.
acitretin (in the form of a dry spray containing 25% of the active substance) 25 mg

Excipients : microcrystalline cellulose – 125 mg; as part of a dry spray (per 1 g) : gelatin – 270 mg, maltodextrin – 410 mg, sodium ascorbate – 70 mg.

5 pcs. – blisters (6) – cardboard packs.

Pharmacological action

Systemic retinoid.

Acitretin, the active ingredient of Neotigazone, is a synthetic aromatic analogue of retinoic acid. In preclinical studies on the tolerability of acitretin, mutagenic or carcinogenic effects were not found; there were also no indications of its direct hepatotoxicity. Acitretin had a pronounced teratogenic effect on animals.

Clinical studies have confirmed that in psoriasis and keratinization disorders, acitretin normalizes the processes of proliferation, differentiation and keratinization of epidermal cells, and its side effects are generally quite tolerable.The action of the drug is purely symptomatic; its mechanism remains largely unknown.

Pharmacokinetics

Absorption

C max of acitretin in plasma are observed 1-4 hours after administration. The best bioavailability of acitretin is achieved when the drug is taken with food. The bioavailability of a single dose is about 60%, but it is subject to significant individual fluctuations (36-95%).

Distribution

Acitretin has a pronounced lipophilicity and easily penetrates into tissues. Its protein binding exceeds 99%. In animal studies, acitretin passed through the placental barrier in amounts that could cause fetal malformations. The lipophilic properties of acitretin suggest that significant amounts of it pass into breast milk.

Metabolism

Acitretin is metabolized by isomerization to the 13-cis isomer (cis-acitretin), as well as by the formation of glucuronides and cleavage of the side chain.

Excretion

Studies with repeated administration of the drug in patients aged 21 to 70 years showed that T 1/2 of acitretin is about 50 hours, and its main metabolite in plasma, cis-acitretin, which is also teratogenic , – 60 hours Considering the longest duration of T 1/2 acitretin (96 hours) and cis-acitretin (123 hours) in these patients, as well as based on their linear kinetics, it can be predicted that more than 99% of the drug will be excreted from the body within 36 days after stopping long-term treatment.Moreover, within 36 days after discontinuation of treatment, plasma concentrations of acitretin and cis-acitretin decreased below the detection limit (<6 ng / ml). Acitretin is excreted exclusively in the form of metabolites, in approximately equal amounts through the kidneys and biliary tract.

Indications of the drug

Neotigazone

®

  • severe forms of psoriasis, incl.including psoriatic erythroderma, localized or generalized pustular psoriasis;
  • severe dyskeratosis, such as congenital ichthyosis; red hair lichen; Daria’s disease; other severe keratinization disorders resistant to traditional therapies.

Dosing regimen

Due to individual differences in absorption and metabolic rate of acitretin, the dose must be selected individually.The capsules are best taken once a day with meals or with milk. The following are indicative recommendations.

Adults

Initial daily dose: 25 mg (i.e. 1 capsule of 25 mg) or 30 mg / day (3 capsules of 10 mg) for 2-4 weeks.

Maintenance dose depends on the clinical efficacy and tolerability of the drug. As a rule, the optimal therapeutic effect is achieved with a daily dose of 30 mg taken for another 6-8 weeks.In some cases, it may be necessary to increase the dose to a maximum of 75 mg / day (i.e. 3 capsules of 25 mg each).

After sufficient regression of psoriatic lesions, treatment of patients with psoriasis can be discontinued. Relapses are treated as described above.

With dyskeratosis , maintenance therapy is usually required, which is carried out in as small doses as possible. They can be below 20 mg / day and should not exceed 50 mg / day.

Children

Given the possibility of severe side effects, long-term treatment should carefully weigh the possible risk with the expected therapeutic effect.Acitretin should only be prescribed if all other treatments are ineffective.

The daily dose depends on body weight and is about 0.5 mg / kg. In some cases, for a limited time, higher doses may be required, up to I mg / kg / day (no more than 35 mg / day). The maintenance dose should be as small as possible, taking into account possible adverse reactions with long-term treatment.

Combination therapy

If Neotigazone is used in combination with other treatments, it may be possible to reduce its dose, depending on the patient’s individual response.

During treatment with Neotigazone, the usual external treatment can be continued; it does not affect the action of Neotigazone.

Side effects

Adverse reactions are observed in the majority of patients taking Neotigazone. However, they usually disappear after dose reduction or drug withdrawal. Sometimes at the beginning of treatment, there is an exacerbation of the symptoms of the disease.

The most common side effects are symptoms of hypervitamiasis A, for example, dry lips, which can be eliminated by applying a greasy cream; cheilitis and cracks in the corners of the mouth, dryness and inflammation of the mucous membranes and transitional epithelium; sometimes – nosebleeds, rhinitis and ophthalmic disorders (xerophthalmia, conjunctivitis), as well as intolerance to contact lenses; rarely – corneal ulcers.There were also cases of thirst and dry mouth, sometimes stomatitis, gingivitis and impaired taste, an increase in the frequency of vulvovaginitis caused by Candida albicans.

Thinning and flaking of the skin all over the body may occur, especially on the palms and soles. Frequent cases of skin “stickiness”, dermatitis, eczema and itching, hair loss, brittle nails and paronychia have been reported. There are isolated reports of the occurrence of bullous rashes and changes in the structure of the hair; photosensitivity reactions rarely develop.After discontinuation of Neotigazone, these side effects are usually reversible.

There are isolated reports of headaches, although an increase in intracranial pressure is rare. In the event of severe headaches, nausea, vomiting and visual impairment, Neotigazon should be immediately canceled, and the patient should be referred to a neurologist. Sometimes there was a violation of dark adaptation.

Muscle, bone and joint pain may occur. Supportive therapy can lead to an increase in the already existing hyperostoses of the spine, the appearance of new hyperostoses and calcification of soft tissues, as is observed with prolonged systemic use of other retinoids.

Cases of the appearance of peripheral edema and hot flashes are described, gastrointestinal disorders, hepatitis, jaundice, temporary and, as a rule, reversible increase in the activity of aminotransferases and alkaline phosphatase rarely develop.

During treatment with large doses of Neotigazone, a reversible increase in serum triglycerides and cholesterol occurred, especially in high-risk patients (with lipid metabolism disorders, diabetes mellitus, obesity, alcoholism). If these disorders persist, an increased risk of atherogenesis cannot be excluded.

Contraindications to use

  • severe hepatic and renal impairment;
  • severe chronic hyperlipidemia;
  • pregnancy. Neotigazone is highly teratogenic and should not be administered to pregnant women. The same applies to all women who are fertile, unless they are using reliable contraception 4 weeks before starting treatment, during treatment and for two years after it ends;
  • hypersensitivity to the drug (acitretin or excipients) or other retinoids.

Use during pregnancy and lactation

Pregnancy

Neotigazone is highly teratogenic. It is contraindicated not only for pregnant women who may become pregnant during treatment or within 2 years after its termination, but also for all women who are potentially fertile. The risk of having a baby with malformations is especially high if Neotigazone is taken before or during pregnancy, regardless of the dose and duration of therapy. The effect of Neotigazone on the fetus is always associated with the risk of congenital malformations.

Neotigazone is contraindicated in any woman capable of fertility, unless each of the following conditions is met:

1. The patient suffers from severe keratinization, resistant to standard treatments.

2. You can be sure that the patient understands and follows the doctor’s instructions.

3. The patient is able to carefully and continuously use the prescribed contraceptives.

4. It is imperative that every woman who is fertile should use effective contraception without interruption for 4 weeks before starting treatment, during treatment and for two years after completing treatment with Neotigazone.

5. Treatment should not begin earlier than the 2nd or 3rd day of the next normal menstrual cycle.

6. A negative pregnancy test must be obtained two weeks before the start of treatment. During treatment, it is recommended to carry out additional pregnancy tests at least 1 time / month.

7. Before starting treatment with Neotigazone, the doctor must inform women capable of childbearing in detail, orally and in writing, about the necessary precautions, the danger of very severe fetal malformations and the possible consequences of pregnancy during treatment with Neotigazone or within 2 years after it. endings.

8. The same effective and continuous contraceptive measures should be applied every time the course of treatment is repeated, regardless of its duration, and maintained for two years after the end of the course.

9. If, despite all precautions, pregnancy occurs during treatment with Neotigazone or within 2 years after its termination, there is a high risk of severe fetal malformations (eg, hernia of the brain).

Breastfeeding

Neotigazone should not be administered to nursing mothers.

Special instructions

Neotigazone can only be prescribed by physicians who have experience in the use of systemic retinoids and understand the risk of teratogenic effects of acitretin.

Women of childbearing age should not drink alcohol during treatment with Neotigazone, since there is clinical evidence that etretinate may be formed in the body when acitretin and alcohol are taken simultaneously.The mechanism of this metabolic transformation has not been established; therefore, it is unclear whether other substances can also participate in it. Ethanol should be avoided for 2 months after stopping acitretin therapy.

Women of childbearing age should not receive blood transfusions from patients receiving Neotigazone. Therefore, blood donation is prohibited during treatment with Neotigazone and for a year after its completion.

Liver function should be monitored before starting treatment with Neotigazoium, every 1-2 weeks during the first month after starting treatment, and then every 3 months.If the test results indicate pathology, control should be carried out weekly. If liver function does not return to normal or worsens further, Neotigazone should be discontinued. In this case, it is recommended to continue to monitor liver function for at least another 3 months.

It is necessary to control the level of cholesterol and serum triglycerides on an empty stomach, especially in patients at risk (lipid metabolism disorders, diabetes mellitus, obesity, alcoholism) and with long-term treatment.

In diabetic patients, retinoids can improve or worsen glucose tolerance, so blood glucose levels should be checked more frequently in the early stages of treatment.

Adults receiving long-term therapy with Neotigazone should regularly undergo appropriate examinations, taking into account the possibility of ossification anomalies (see “Side Effects”). If such violations occur, the patient should be discussed with the issue of continuing treatment, carefully weighing the possible risks and benefits of using the drug.

Children should be closely monitored for growth and bone development.

Due to the possibility of night vision impairment, patients should be warned about the need to exercise caution when driving a car or working with machines and mechanisms at night. Close monitoring of visual impairment is necessary.

Currently, not all the consequences of using Neotigazone that can occur throughout life are known.

Overdose

In case of acute overdose, Neotigazone should be discontinued immediately.No other special measures are required because the acute toxicity of the drug is low. Overdose symptoms are identical to those in acute hypervitaminosis A (headache, dizziness).

Drug interactions

Due to the risk of hypervitaminosis A, concomitant use of vitamin A and other retinoids should be avoided.

Since both Neotigazone and tetracyclines can cause an increase in intracranial pressure, their simultaneous use is contraindicated.

There are reports of an increased risk of developing hepatitis with the combined use of methotrexate and Tigason (etretinate), therefore, the appointment of methotrexate simultaneously with Neotigazone is also contraindicated.

Neotigazone does not affect the binding of coumarin anticoagulants (warfarin) to proteins.

If Neotigazone is administered concurrently with phenytoin, it should be noted that Neotigazone partially reduces the degree of phenytoin binding to proteins.

Acitretin may reduce the contraceptive effect of progesterone micropyls.Therefore, progesterone micropiles should not be used for contraception. No other interactions between Neotigazone and other drugs (for example, digoxin, cimetidine, combined estrogen / progestogenic oral contraceptives) have been found to date.

In a study in healthy volunteers, a single dose of acitretin together with ethyl alcohol led to the formation of etretinate (previously it was found in vitro). In recent studies, some patients taking Neotigazone also showed the formation of etretinate.Until this phenomenon is fully explained, it is necessary to take into account the pharmacokinetic features of etretinate: since its half-life is approximately 120 days, contraceptives must be used for two years after the completion of treatment.

Storage conditions of the drug Neotigazone

®

Store at a temperature not exceeding 25 ° C, protected from light and moisture, out of reach of children.

Shelf life of the drug Neotigazone

®

Shelf life is 3 years. The drug should not be used after the expiration date printed on the package.

Terms of sale

The drug is available with a prescription.

Contacts for inquiries

AKTAVIS GROUP JSC

Representative office in Russia LLC “Actavis”
115054 Moscow, Valovaya st.35
Tel .: (495) 644-44-14, 644-22-34
Fax: (495) 644-44-24, 644-22-35

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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

Soriatane

Trade names: Canada

MINT-Acitretin; Soriatane; TARO-Acitretin

Warning

  • Do not take this drug if you are pregnant or if you are planning to become pregnant within 3 years after you stop taking this drug. There is a very high risk of severe and sometimes deadly birth defects if you take this drug during pregnancy or if you become pregnant within 3 years of stopping it.There is also a high risk of fetal death and premature birth. Before you start using this drug, your doctor will advise you of all the risks. You must use 2 types of reliable contraception 1 month before you start using this drug, during treatment, and for 3 years after your last dose of the drug. You will have pregnancy tests before and during treatment with this drug, and for 3 years after your last dose of this drug.If you become pregnant while taking this drug or within 3 years after treatment ends, call your doctor right away.
  • If you can get pregnant and are unable to use 2 types of birth control during and after treatment with this drug, consult your doctor. This drug may not work for you.
  • If you are able to get pregnant, you must refrain from drinking alcohol while using this drug and for 2 months after treatment ends.This prohibition applies to all drinks, foods, medicines and other products containing alcohol. With the simultaneous use of alcohol, the drug will remain in the body for a longer period, which can lead to an increase in the risk of congenital malformations for more than 3 years after the end of drug treatment. If you have any questions, consult your doctor.
  • A small amount of this drug is found in semen. There is no information about whether this can lead to the risk of intrauterine death of the child.Consult your doctor.
  • Do not donate blood while taking this drug or for 3 years after you stop taking this drug.
  • Very bad and sometimes deadly liver problems have happened with this drug. Call your doctor right away if you have signs of liver problems, such as dark urine, tired feeling, lack of appetite, nausea or abdominal pain, light colored stools, vomiting, or yellow skin or eyes.

What is this drug used for?

  • Used to treat psoriasis.
  • This medicinal product may be used for other indications. Consult 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.
  • In one of the following: high cholesterol, kidney disease, or liver disease.
  • If you are taking any of these drugs: demeclocycline, doxycycline, minocycline, tetracycline, a drug containing vitamin A, a drug like vitamin A, or St. John’s wort.
  • If you are taking methotrexate.
  • If you are breastfeeding. Do not breast-feed a baby while taking this drug. You will also need to refrain from breastfeeding your baby after you stop taking this drug until it is completely cleared from the body.Talk to your doctor about how long you need to stop breastfeeding after you stop taking this drug.

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 (both 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 condition and in combination with other drugs you are already taking. Do not start or stop taking any medication or change the dosage without your doctor’s approval.

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

For all patients taking this drug:

  • Tell all healthcare providers that you are taking this drug.These are doctors, nurses, pharmacists and dentists.
  • Avoid driving or doing other tasks or work requiring attention or sharp eyesight until you know how this drug is affecting you.
  • It may take several months for the full result to be obtained.
  • If you have high blood sugar (diabetes mellitus), this drug can sometimes raise your blood sugar even further. Talk with your doctor about how you can keep your blood sugar under control.
  • Increases in cholesterol and triglyceride levels have happened with this drug. These changes can increase the risk of blood clots or the development of vascular diseases of the heart and brain, such as myocardial infarction and stroke. If you have any questions, please consult your doctor.
  • Call your doctor right away if you have signs of thrombosis, such as pain or tightness in your chest; coughing up blood; dyspnea; swelling, warmth, numbness, discoloration, or pain in your leg or arm; Difficulty speaking or swallowing.
  • Perform blood tests as directed by your healthcare practitioner. Please consult your doctor.
  • Get a bone density test as directed by your doctor. Consult your doctor.
  • The skin may look worse at first.
  • You can burn quickly. Avoid direct sunlight, sun lamps and tanning beds. Use sun umbrellas, long clothing, and sunglasses.
  • Night vision has happened with this drug.It can happen suddenly. These effects may disappear after discontinuation of the drug, but sometimes they persist. Be careful when driving at night or when performing other tasks that require clear vision. The workplace should be well lit. If you notice a decrease in night vision while using this drug, call your doctor right away.
  • This drug may cause a serious and sometimes fatal disorder called leaky capillary syndrome (PLE).SPEC can lead to low blood pressure, abnormal heart rhythms, chest pain, or myocardial infarction. This condition can also cause lung or breathing problems, bleeding or decreased blood flow to the stomach or intestines, kidney problems, swelling, or confusion. If you have any questions, please consult your doctor.
  • Increased intracranial pressure has happened with this drug. This can lead to permanent loss of vision and sometimes death.Call your doctor right away if you experience severe headache, dizziness, nausea, vomiting, or seizures. If you have weakness on one side of your body, difficulty speaking or thinking, balance or vision problems, see your doctor immediately.
  • If you are 65 years of age or older, use this drug with caution. You may have more side effects.
  • Do not use progestin-only birth control pills (low dose).They may be less effective. Consult your doctor.
  • If you have sex without using 2 types of reliable contraception, you suspect that you are pregnant, or you have a delay in your period, contact your doctor immediately.

Men:

  • Consult a physician before drinking alcohol.

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 doctor or get medical help 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.
  • Symptoms of depression, suicidal thoughts, nervousness, emotional ups and downs, distorted thinking, anxiety, or decreased interest in life.
  • Signs of high blood sugar, such as confusion, drowsiness, increased thirst and hunger, increased urination, facial flushing, rapid breathing, and fruity breath.
  • 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.
  • Aggressive behavior or thoughts of aggression.
  • Severe dizziness or fainting.
  • Unusual burning, numbness, or tingling sensations.
  • Severe muscle pain or weakness.
  • Pain in bones or joints.
  • Changes in vision, eye pain or very severe eye irritation.
  • Change in contact lens tolerance.
  • Fever, chills, or sore throat.
  • Inflammation.
  • Weight gain.
  • Pain in the intestines.
  • Severe diarrhea.
  • Pain in the rectum or rectal pain.
  • Blood in the urine.
  • Thinning of the skin.
  • A serious and sometimes deadly pancreas problem (pancreatitis) has happened with this drug. Such a violation can occur at any stage of treatment. Signs of pancreatitis include very severe abdominal pain, very severe back pain, very severe stomach upset, or vomiting.Call your doctor right away if any of these signs occur.

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:

  • Dry mouth, eyes, skin or lips.
  • Hair loss.
  • Eye irritation.
  • Chapped lips, flaky fingertips, palms and soles, itching, scaly skin, weak nails, clammy or brittle skin, runny or dry nose, and nosebleeds are common. Ask a doctor or pharmacist for a lotion or cream to help with dryness or cracking. If any of these effects are severe, bothersome, or persistent, see your doctor.

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.

  • Take this drug with food.
  • Take this drug at about the same time of the day.

What to do if a dose of a drug is missed?

  • Skip the forgotten dose and return to your normal schedule.
  • Do not take 2 doses at the same time or an additional dose.

How do I store and / or discard this drug?

  • Store at room temperature in a dry place.Do not store in the bathroom.
  • Do not expose to heat and light.
  • 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.Your area may have drug recycling programs.

General information about medicines

  • 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 have different patient information sheets. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
  • A separate patient instruction sheet is included with the product. Please read this information carefully. Reread it every time you replenish your supply. If you have questions about this drug, talk with your doctor, pharmacist, or other healthcare professional.
  • If you think an overdose has occurred, 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.

Consumer use of information 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 guide to treatment and does not replace the information provided to you by your healthcare professional. For complete information on the possible risks and benefits of taking this drug, consult your doctor.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.

90,000

Clinical Research Psoriasis: Acitretin 17.5 mg / day – Clinical Research Register

Intervention

Intervention type:

Drug, remedy, medication

Intervention name:
Acitretin 17.5 mg / day

Description:

reducing the dose of acitretin to 17.5 mg / day from 25 mg / day in patients with retinoid-related side effects

Arm Group label:

Low-dose acitretin (17.5 mg)

Another name:

soriatan, acitretin

Eligibility

Criteria:

Inclusion criteria: – Men or women aged 18 and over.- Surgically sterile females. Women who have undergone a hysterectomy or oophorectomy, or Completed menopause is allowed (postmenopausal period of at least 1 year). Men must agree to use 2 forms of birth control (eg, condoms, spermicide). – Stabilized on phototherapy for 4 weeks. – Corresponds to acitretin dosage of 25 mg / day and experiences side effects associated with retinoids. events that, in the clinical judgment of the investigator, benefit from a dose reduction to 17.5 mg / day.- Able to complete research and follow research instructions. – Abstinence from alcohol during acitretin therapy and for 2 months after it. abolition of acitretin. – Blood subjects must be prepared not to donate at the time of the study, as well as for 3 years. after the completion of this study. – Able to understand and willing to provide signed and dated voluntary informed (and any local or national authorization requirements) before any protocol specific procedures are followed.Exclusion criterion: – Uncontrolled hypertriglyceridemia. – Guttate, erythrodermic or pustular psoriasis. – Serious liver dysfunction,> 3 times the upper limit of normal, and the conclusion of a clinical investigator. – Use of systemic immunosuppressants (eg, methotrexate, cyclosporine, thioguanine, azathioprine, alephasept, egalizumab, corticosteroids) within 4 weeks of baseline and throughout the study continued. – Vitamin A, topical analogs or anthralin within 2 weeks of study start weeks.- A history of known or suspected intolerances to the ingredients of a research study product. – Use over-the-counter (over-the-counter) medications or herbs for 2 weeks. dosing unless agreed with the director as not clinically relevant by the investigator. – Participated in a previous study of the same educational product. – Any medications are currently being used that, in the opinion of the researcher, could interfere with the researcher’s evaluation of the research product or expose them to undue risk.- Is currently suffering from any disease or condition that, in the opinion of the researcher, may affect the evaluation of the investigational product or issue at excessive risk. – Any serious illness 30 days before the screening test. – Considered immunocompromised. – Clinically relevant history or current evidence of alcohol or evidence of drugs. – Use of investigational drugs or treatments during the study or within 4 weeks after the baseline visit.- Women of childbearing age (see Inclusion criteria).

Floor:

female

Minimum age:

18 years old

Maximum age:

N / A

Healthy volunteers:

No

Systemic therapy for psoriasis

In systemic therapy for the treatment of psoriasis, the following are used:

  • Retinoids
  • Methotrexate
  • Cyclosporine
  • Mycophenolate mofetil
  • Tacrolimus

Retinoids

Some retinoids, i.e.That is, metabolites derived from vitamin A have been used to treat psoriasis. Currently, Acitretin is used, which has favorable pharmacokinetic properties, the most important of which is its short half-life. When this drug is used alone, the daily dose is 25 to 50 mg; it is necessary to start treatment with a dose of 10 to 20 mg, and gradually increase (if necessary). Although complete remission is achieved only in 50% of cases, in most patients there is a sharp decrease in the number of scales, expansion or flaking.Higher doses of Acitretin (50 – 75 mg / day) are more effective in a shorter period of time, but are associated with major side effects. Like all retinoids, Acitretin is also teratogenic, so women of childbearing age need to use safe methods of contraception. They must adhere to them for three years after stopping treatment. Patients receiving this treatment cannot consume alcohol as it converts Acitretin to etretinate, which has a much longer half-life.The most easily observed side effects are dry lips, nose, eyes and thinning and fragility of the nail plate. Cases of tendon hyperostosis and calcification have also been reported. Acitretin is highly effective for pustular psoriasis and erythroderma.

Methotrexate

Methotrexate inhibits the deidrofolato reductase enzyme, which is essential for the synthesis of nucleotides and amino acids. Thus, the drug reduces DNA synthesis and inhibits mitosis, especially from rapidly proliferating cells.It is able to alter the behavior of lymphocytes, cytokine production and neutrophil activity. Methotrexate is contraindicated in patients with active infections, alcoholism, liver cirrhosis, viral hepatitis, immunological defects, renal failure, and women who do not use contraception. Side effects can range from simple nausea to cancer. The recommended starting dose is 7.5 mg once a week. Of course, today Methotrexate is used much less frequently for the treatment of psoriasis than in the past.

Cyclosporine

Cyclosporin is an immunosuppressant that suppresses the production of interleukin-2, which leads to inhibition of differentiation and proliferation of T – lymphocytes. The initial dose of the drug is 2.5 to 4 mg per kilogram / day, 2 times a day. Given the side effects of the drug, it is necessary to monitor blood pressure and kidney function, as well as bone marrow function. In fact, the main side effects are nephrotoxicity and hypertension, as well as hirsutism and gingival hyperplasia.Unfortunately, in addition to the side effects during treatment with cyclosporine, addiction to the drug occurs, and when the disease develops again, a worse and difficult response to other treatments occurs.

Mycophenolate mofetil

In addition to the fact that this drug is able to prevent graft rejection, it is an immunosuppressive agent and is used in the treatment of psoriasis. The recommended dose is 1 g up to 2 times a day or 500 mg up to 4 times a day.This drug is generally well tolerated and has a good safety profile. The main side effects are gastrointestinal upset, anemia, leukopenia, and infection.

Tacrolimus

Has a very similar mechanism of action to that used in cyclosporine. The recommended dose is 0.1 – 0.15 mg / kg / day. The most common side effects are limb pain and diarrhea. When taking this drug, you must follow the same principles as when taking cyclosporine.External use of the drug is not effective.

Neotigazon – instructions for use

Neotigazone can only be prescribed by doctors who have experience in the use of systemic retinoids and understand the risk of teratogenic action of acitretin.

The physician must provide all patients, both men and women, with complete information about the teratogenic effect of Neotigazone and measures to prevent pregnancy.

Women of childbearing age during treatment with Neotigazone and for 2 months after stopping treatment should not consume alcohol, as well as alcohol-containing drinks, foods and drugs, since there is clinical evidence that while taking acitretin and alcohol in the body can to form etretinate.Etretinate is highly teratogenic and has a longer T 1/2 (approximately 120 hours) compared to acitretin. Pregnancy protection measures and a pregnancy test must be performed within 2 years after the completion of treatment with Neotigazone (see section Use during pregnancy and during breastfeeding).

Women of childbearing age should not receive blood transfusions from patients receiving Neotigazone. Therefore, blood donation is prohibited during treatment with Neotigazone and for two years after its completion.

Due to the existing risk of developing congenital fetal abnormalities, the drug should not be passed on to other patients. Unused or expired drug should be destroyed in accordance with applicable law.

Liver function should be monitored before starting treatment with Neotigazone, every 1-2 weeks during the first two months after starting treatment, and then every 3 months. If the test results indicate pathology, control should be carried out weekly.If liver function does not return to normal or will deteriorate further, Neotigazone should be discontinued. In this case, it is recommended to continue to monitor liver function for at least another 3 months.

It is necessary to control the level of cholesterol and triglycerides of blood serum on an empty stomach, especially in patients at risk (lipid metabolism disorders, diabetes mellitus, obesity, alcoholism) before starting treatment, within a month after starting treatment, and then every 3 months.

Close monitoring of visual impairment is necessary.

Benign intracranial hypertension has been reported on rare occasions. If severe headaches, nausea, vomiting and visual impairment occur, Neotigazone should be immediately canceled and the patient should be referred to a neurologist.

Adults, especially elderly patients receiving long-term therapy with Neotigazone, should regularly undergo appropriate examinations, taking into account the possibility of ossification abnormalities (see the section on Side Effects).If these complications occur, follow-up treatment should be discussed with the patient based on a careful assessment of the benefit / risk ratio.

Children should be closely monitored for growth parameters and bone development. Currently, not all the consequences of using Neotigazone are known, which can occur throughout life with prolonged use of Neotigazone.

The effect of ultraviolet (UV) radiation on the body is enhanced by the intake of retinoids. Patients should avoid excessive sun exposure and limit the use of UV lamps (such as tanning beds).

If necessary, sunscreens with a high protection factor (at least SPF 15) should be used. Treatment with high doses of retinoids can cause mood changes, including irritability, aggression, and depression.

Risk groups for pumping patients :

In patients with diabetes mellitus, alcoholism, obesity, with risk factors from the cardiovascular system or lipid metabolism, taking Neotigazone, it is necessary to monitor cholesterol levels and / or glucose concentration more often or to observe symptoms indicating the possible development of complications with side of the cardiovascular system (for example, to measure blood pressure).

In diabetic patients, retinoids can improve or worsen glucose tolerance, so blood glucose levels should be checked more frequently in the early stages of treatment.

For all at-risk patients in whom the observed complications from the cardiovascular system do not normalize or worsen further, the dose of Neotigazone should be reduced or the decision to be discontinued.

The preparation contains maltodextrin, which contains glucose, therefore Neotigazone should not be used in patients with a rare hereditary disease – glucose-galactose malabsorption.

Based on the available data on the degree of influence on the incidence of birth defects during fertilization of women with sperm and seminal fluid of male patients taking acitretin, it can be concluded that the risk of teratogenic effects is minimal.

Four roads to one destination

What are these methods and how do they work

There are many different therapeutic options available to control and relieve psoriasis symptoms. A doctor can help find the right remedy for you.

Generally, the various therapeutic agents are divided into four categories.

  • Medicines for external use: Includes products applied to the skin, such as creams, gels or ointments.
  • Phototherapy and climatic therapy: Treatment with light – ultraviolet or sunlight.
  • Medicines for systemic use: Medicines for oral administration or injection. Systemic therapies get their name because they affect the body as a whole, not just the local area of ​​the skin.
  • Biologics: Biologics are a special type of systemic medications (usually given by injection) that target specific components of the immune system.

Topical remedies

Includes various medications such as creams, ointments and gels that are applied directly to the skin

Medicines for external use

Topical medications are therapeutic agents applied directly to the skin — usually a cream, gel, or ointment.Usually, for mild to moderate psoriasis, the doctor begins treatment with drugs for external use. Topical medications, when used correctly, help many patients and are usually associated with fewer side effects than other treatments.

Prescription drugs for external use

The most common topical preparations contain a so-called corticosteroid or a vitamin D derivative. A combination of vitamin D with a corticosteroid is also often used.Some hospitals use dithranol or coal tar.

  • Topical corticosteroids (or simply steroids): Corticosteroid hormones are produced by the adrenal glands. Steroids can help remove scales, reduce swelling, irritation, redness, and itching. There are a number of brands available that contain different types and concentrations of corticosteroids. They are marketed in many different dosage forms. The more potent a remedy is, the more careful you need to be with it during long-term treatment.Common side effects include skin thinning, pigmentation changes, mild superficial trauma, stretch marks, redness, and dilated superficial blood vessels. Typically, high concentrations of steroids on a daily basis should not be used for an extended period. If this does happen, you should consult your doctor before the end of treatment. Abrupt discontinuation of treatment may lead to withdrawal symptoms with severe exacerbation of psoriasis 90 180
  • Vitamin D3 Analogs: Vitamin D3, such as calcitriol or a synthetic vitamin D3 called calcipotriol, can help slow the growth of skin cells, smooth out lesions, and remove scales.Skin irritation, tingling and burning sensations are common side effects. The use of calcitriol also increases sensitivity to sunlight.
  • Combination of a steroid and a vitamin D3 analogue: Patients with psoriasis are often prescribed combination preparations containing both a corticosteroid and a vitamin D analogue. Combination products are available in the form of gels and ointments. This combination helps to slow down the development of skin cells, evens out lesions, removes scales and reduces swelling, irritation, redness and itching.Side effects include itching, rashes, and a burning sensation of the skin.
  • Salicylic acid
    This active ingredient is called “keratolytic”. This means that it dissolves or destroys the outer layer of the skin (keratins). It is often used in combination with other therapies. Keratolytic products can help soften skin and remove scales. However, they can also irritate the skin.
  • Coal tar: Shampoos and solutions containing coal tar can help slow the rapid growth of skin cells and reduce inflammation, itching, and flaking.However, coal tar products can cause redness and irritation of the skin and stain clothing, bedding and blond hair. Coal tar products also increase the sensitivity of the skin to sunlight, so it is very important to use sunscreen and be careful about sun exposure. In some clinics, coal tar is used in combination with phototherapy (Heckermann’s method).
  • Dithranol: The active ingredient derived from the bark of the Araroba tree has been used for over a century in the fight against psoriasis.It helps slow down the growth of skin cells, but it can irritate the skin and stain hair, unaffected skin, clothing, and bedding. It can cause irritation when it comes in contact with healthy skin around the lesion, and is therefore usually only used in hospitals where a nurse can help with correct application.

In addition to prescription topical products, there are many over the counter products available.

You can buy OTC drugs in pharmacies, pharmacies

It is important for all psoriasis patients to keep their skin hydrated.Therefore, good moisturizing lotions and creams should be part of your daily routine. They will help keep your skin hydrated and reduce cracking, soreness, and itching caused by dryness.

It is not known exactly how phototherapy works, but it is known that treatment with natural light and some forms of ultraviolet radiation can significantly improve psoriasis.

Phototherapy

Therapy using rays of light, of various lengths and shapes, from ultraviolet to sunlight

Phototherapy and climatic therapy

Sunlight has a positive effect on many psoriasis patients.Therefore, treatment may include systematic exposure to sunlight (climate therapy) or artificially produced ultraviolet light. Light therapy (sometimes called phototherapy) is used to treat moderate to severe psoriasis. It is not known exactly how phototherapy works, but it is known that treatment with natural light and some forms of ultraviolet radiation can significantly improve psoriasis in many patients. It reduces skin metabolism and has a positive effect on inflammation.There are 2 types of phototherapy:

  • Ultraviolet B (UVB): This type of ultraviolet is also present in normal sunlight. It penetrates the skin and helps slow the growth of affected skin cells. In UVB treatment, the patient is exposed for a specified period of time and on a regular basis.
  • PUVA (psoralen + UVA): Phototherapy can also be based on the use of ultraviolet spectrum A. This type of ultraviolet is effective only in combination with the light sensitizing drug psoralen.It enhances the effect of phototherapy and helps slow the overgrowth of skin cells and reduce or eliminate psoriasis symptoms. Common short-term side effects of PUVA are nausea, itching and redness of the skin. It is important to avoid sunlight after taking psoralen as it can damage your eyes and lead to severe sunburn.

Common side effects of phototherapy are redness, itching, or dryness of the skin after exposure to ultraviolet light. Some people develop a sunburn-like reaction; in addition, patients may experience a temporary worsening of psoriasis before cleansing the skin.It is important to avoid sunburn and be aware that excessive sun exposure can lead to skin aging and increase the risk of skin cancer.

Systemic therapy

These are medications taken by mouth or by injection into the body. They affect the human body as a whole, and not a specific affected area.

Medicines for systemic use

Systemic therapies get their name because they affect the body as a whole, not just the local area of ​​the skin.They are taken by mouth or injected, and because they affect the entire body, they are generally used only for severe psoriasis and psoriatic arthritis.

  • Cyclosporine: This active drug suppresses the body’s immune response. Therefore, it is known as an immunosuppressant. It helps slow the growth of certain cells in the immune system. It has a number of potential side effects, including hypertension and nephrotoxicity; it is only used for very severe cases of psoriasis.
  • Methotrexate: This substance acts by binding and inhibiting an enzyme involved in the rapid growth of cells. Thus, it slows down the rate of growth of skin cells. Methotrexate can potentially harm the liver. Therefore, it is very important that patients follow the instructions exactly. Patients are generally advised to avoid alcohol and other liver-damaging substances. In addition, methotrexate can interact with some medications, so it is important to see your doctor if you need to use another drug (for example, some anti-inflammatory drugs) or if you experience side effects.
  • Acitretin: This is a synthetic analogue of vitamin A that normalizes cell growth and is often used for erythrodermic and pustular psoriasis. It can help reduce scaling and thickness of lesions and reduce inflammation. It is sometimes used in combination with phototherapy. Acitretin also has a number of possible side effects; women are advised to avoid pregnancy for at least two years after the end of treatment, as it can cause serious birth defects in the fetus.

Biological therapy

Biological therapy is a separate line of therapy for psoriasis. Most often these are injections that act on a specific part of the human immune system.

Biological products

Biological therapies are a newer class of drugs that target specific components of the immune system. They are protein-based therapeutics that are administered by injection or intravenous infusion directly into the bloodstream.They work by blocking certain proteins of the immune system, such as tumor necrosis factor alpha (antibodies against TNF) or interleukins 12 and 23 (antibodies against IL 12-23).

Three different types of anti-TNF antibodies are currently available for use in psoriasis. Each contains a different active ingredient: etanercept, adalimumab, and infliximab. They are administered by injection or infusion. The only anti-IL 12-23 antibody product available on the market is based on the active ingredient ustekinumab and is intended to be administered by injection.

Biological therapies are very expensive and are usually used only for moderate to severe psoriasis. Major side effects include an increased risk of infection due to a weakened immune system. In addition, it is important to know that certain vaccines should not be used during treatment. Always tell your doctor that you are taking biological therapies if you need vaccinations.

Other common side effects are injection side effects; in some cases, more severe side effects may appear.If you are experiencing a side effect of the medication, do not hesitate to see your doctor.

Russian analogues of imported drugs with prices

Pharmacological action

Systemic retinoid.

Acitretin, the active ingredient of Neotigazone, is a synthetic aromatic analogue of retinoic acid. In preclinical studies on the tolerability of acitretin, mutagenic or carcinogenic effects were not found; there were also no indications of its direct hepatotoxicity.Acitretin had a pronounced teratogenic effect on animals.

Clinical studies have confirmed that in psoriasis and keratinization disorders, acitretin normalizes the processes of proliferation, differentiation and keratinization of epidermal cells, and its side effects are generally quite tolerable. The action of the drug is purely symptomatic; its mechanism remains largely unknown.

Pharmacokinetics

Absorption

C max Acitretin in plasma are observed 1-4 hours after administration.The best bioavailability of acitretin is achieved when the drug is taken with food. The bioavailability of a single dose is about 60%, but it is subject to significant individual fluctuations (36-95%).

Distribution

Acitretin has a pronounced lipophilicity and easily penetrates into tissues. Its protein binding exceeds 99%. In animal studies, acitretin passed through the placental barrier in amounts that could cause fetal malformations.The lipophilic properties of acitretin suggest that significant amounts of it pass into breast milk.

Metabolism

Acitretin is metabolized by isomerization to the 13-cis isomer (cis-acitretin), as well as by the formation of glucuronides and cleavage of the side chain.

Excretion

Studies with repeated administration of the drug in patients aged 21 to 70 years showed that T 1/2 of acitretin is about 50 hours, and its main metabolite in plasma, cis-acitretin, which is also teratogenic , – 60 hoursConsidering the longest duration of T 1/2 acitretin (96 hours) and cis-acitretin (123 hours) in these patients, as well as based on their linear kinetics, it can be predicted that more than 99% of the drug will be excreted from the body within 36 days after stopping long-term treatment. Moreover, within 36 days after discontinuation of treatment, plasma concentrations of acitretin and cis-acitretin decreased below the detection limit (<6 ng / ml). Acitretin is excreted exclusively in the form of metabolites, in approximately equal amounts through the kidneys and biliary tract.

Indications

– severe forms of psoriasis, including psoriatic erythroderma, localized or generalized pustular psoriasis;

– severe dyskeratosis, such as congenital ichthyosis; red hair lichen; Daria’s disease; other severe keratinization disorders resistant to traditional therapies.

Dosing regimen

Due to individual differences in absorption and metabolic rate of acitretin, the dose must be selected individually.The capsules are best taken once a day with meals or with milk. The following are indicative recommendations.

Adults

Initial daily dose: 25 mg (i.e. 1 capsule of 25 mg) or 30 mg / day (3 capsules of 10 mg) for 2-4 weeks.

Maintenance dose depends on the clinical efficacy and tolerability of the drug. As a rule, the optimal therapeutic effect is achieved with a daily dose of 30 mg taken for another 6-8 weeks.In some cases, it may be necessary to increase the dose to a maximum of 75 mg / day (i.e. 3 capsules of 25 mg each).

After sufficient regression of psoriatic lesions, treatment of patients with psoriasis can be discontinued. Relapses are treated as described above.

With dyskeratosis , maintenance therapy is usually required, which is carried out in as small doses as possible. They can be below 20 mg / day and should not exceed 50 mg / day.

Children

Given the possibility of severe side effects, long-term treatment should carefully weigh the possible risk with the expected therapeutic effect.Acitretin should only be prescribed if all other treatments are ineffective.

The daily dose depends on body weight and is about 0.5 mg / kg. In some cases, for a limited time, higher doses may be required, up to I mg / kg / day (no more than 35 mg / day). The maintenance dose should be as small as possible, taking into account possible adverse reactions with long-term treatment.

Combination therapy

If Neotigazone is used in combination with other treatments, it may be possible to reduce its dose, depending on the patient’s individual response.

During treatment with Neotigazone, the usual external treatment can be continued; it does not affect the action of Neotigazone.

Side effects

Side effects are observed in most patients taking Neotigazone. However, they usually disappear after dose reduction or drug withdrawal. Sometimes at the beginning of treatment, there is an exacerbation of the symptoms of the disease.

The most common side effects are symptoms of hypervitamiasis A, for example, dry lips, which can be eliminated by applying a greasy cream; cheilitis and cracks in the corners of the mouth, dryness and inflammation of the mucous membranes and transitional epithelium; sometimes – nosebleeds, rhinitis and ophthalmic disorders (xerophthalmia, conjunctivitis), as well as intolerance to contact lenses; rarely – corneal ulcers.There were also cases of thirst and dry mouth, sometimes stomatitis, gingivitis and impaired taste, an increase in the frequency of vulvovaginitis caused by Candida albicans.

Thinning and flaking of the skin all over the body may occur, especially on the palms and soles. Frequent cases of skin “stickiness”, dermatitis, eczema and itching, hair loss, brittle nails and paronychia have been reported. There are isolated reports of the occurrence of bullous rashes and changes in the structure of the hair; photosensitivity reactions rarely develop.After discontinuation of Neotigazone, these side effects are usually reversible.

There are isolated reports of headaches, although an increase in intracranial pressure is rare. In the event of severe headaches, nausea, vomiting and visual impairment, Neotigazon should be immediately canceled, and the patient should be referred to a neurologist. Sometimes there was a violation of dark adaptation.

Muscle, bone and joint pain may occur. Supportive therapy can lead to an increase in the already existing hyperostoses of the spine, the appearance of new hyperostoses and calcification of soft tissues, as is observed with prolonged systemic use of other retinoids.

Cases of the appearance of peripheral edema and hot flashes are described, gastrointestinal disorders, hepatitis, jaundice, temporary and, as a rule, reversible increase in the activity of aminotransferases and alkaline phosphatase rarely develop.

During treatment with large doses of Neotigazone, a reversible increase in serum triglycerides and cholesterol occurred, especially in high-risk patients (with lipid metabolism disorders, diabetes mellitus, obesity, alcoholism). If these disorders persist, an increased risk of atherogenesis cannot be excluded.

Contraindications for use

– severe hepatic and renal failure;

– severe chronic hyperlipidemia;

– pregnancy. Neotigazone has a strong teratogenic effect and should not be administered to pregnant women. The same applies to all women who are fertile, unless they are using reliable contraception 4 weeks before starting treatment, during treatment and for two years after it ends;

– hypersensitivity to the drug (acitretin or fillers) or to other retinoids.

Application during pregnancy and lactation

Pregnancy

Neotigazone is highly teratogenic. It is contraindicated not only for pregnant women who may become pregnant during treatment or within 2 years after its termination, but also for all women who are potentially fertile. The risk of having a baby with malformations is especially high if Neotigazone is taken before or during pregnancy, regardless of the dose and duration of therapy. The effect of Neotigazone on the fetus is always associated with the risk of congenital malformations.

Neotigazone is contraindicated in any woman capable of fertility, unless each of the following conditions is met:

1. The patient suffers from severe keratinization, resistant to standard treatments.

2. You can be sure that the patient understands and follows the doctor’s instructions.

3. The patient is able to carefully and continuously use the prescribed contraceptives.

4. It is imperative that every woman who is fertile should use effective contraception without interruption for 4 weeks before starting treatment, during treatment and for two years after completing treatment with Neotigazone.

5. Treatment should not begin earlier than the 2nd or 3rd day of the next normal menstrual cycle.

6. A negative pregnancy test must be obtained two weeks before the start of treatment. During treatment, it is recommended to carry out additional pregnancy tests at least 1 time / month.

7. Before starting treatment with Neotigazone, the doctor must inform women capable of childbearing in detail, orally and in writing, about the necessary precautions, the danger of very severe fetal malformations and the possible
consequences of pregnancy during treatment with Neotigazone or within 2 years after its ending.

8. The same effective and continuous contraceptive measures should be applied every time the course of treatment is repeated, regardless of its duration, and maintained for two years after the end of the course.

9. If, despite all precautions, pregnancy occurs during treatment with Neotigazone or within 2 years after its termination, there is a high risk of severe fetal malformations (eg, hernia of the brain).

Breastfeeding

Neotigazone should not be administered to nursing mothers.

Overdose

In case of acute overdose, Neotygazone should be discontinued immediately. No other special measures are required because the acute toxicity of the drug is low. Overdose symptoms are identical to those in acute hypervitaminosis A (headache, dizziness).

Drug interactions

Due to the risk of hypervitaminosis A, the simultaneous use of vitamin A and other retinoids should be avoided.

Since both Neotigazone and tetracyclines can cause an increase in intracranial pressure, their simultaneous use is contraindicated.

There are reports of an increased risk of developing hepatitis with the combined use of methotrexate and Tigason (etretinate), therefore, the appointment of methotrexate simultaneously with Neotigazone is also contraindicated.

Neotigazone does not affect the binding of coumarin anticoagulants (warfarin) to proteins.

If Neotigazone is administered concurrently with phenytoin, it should be noted that Neotigazone partially reduces the degree of phenytoin binding to proteins.

Acitretin may reduce the contraceptive effect of progesterone micropyls.Therefore, progesterone micropiles should not be used for contraception. No other interactions between Neotigazone and other drugs (for example, digoxin, cimetidine, combined estrogen / progestogenic oral contraceptives) have been found to date.

In a study in healthy volunteers, a single dose of acitretin together with ethyl alcohol led to the formation of etretinate (previously it was found in vitro). In recent studies, some patients taking Neotigazone also showed the formation of etretinate.Until this phenomenon is fully explained, it is necessary to take into account the pharmacokinetic features of etretinate: since its half-life is approximately 120 days, contraceptives must be used for two years after the completion of treatment.

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

Store at a temperature not exceeding 25 ° C, protected from light and moisture, out of reach of children.Shelf life is 3 years. The drug should not be used after the expiration date printed on the package.

Special instructions

Neotigazone can only be prescribed by doctors who have experience in the use of systemic retinoids and understand the risk of teratogenic action of acitretin.

Women of childbearing age should not drink alcohol during treatment with Neotigazone, since there is clinical evidence that etretinate may be formed in the body when acitretin and alcohol are taken simultaneously.The mechanism of this metabolic transformation has not been established; therefore, it is unclear whether other substances can also participate in it. Ethanol should be avoided for 2 months after stopping acitretin therapy.

Women of childbearing age should not receive blood transfusions from patients receiving Neotigazone. Therefore, blood donation is prohibited during treatment with Neotigazone and for a year after its completion.

Liver function should be monitored before starting treatment with Neotigazoium, every 1-2 weeks during the first month after starting treatment, and then every 3 months.If the test results indicate pathology, control should be carried out weekly. If liver function does not return to normal or worsens further, Neotigazone should be discontinued. In this case, it is recommended to continue to monitor liver function for at least another 3 months.

It is necessary to control the level of cholesterol and serum triglycerides on an empty stomach, especially in patients at risk (lipid metabolism disorders, diabetes mellitus, obesity, alcoholism) and with long-term treatment.

In diabetic patients, retinoids can improve or worsen glucose tolerance, so blood glucose levels should be checked more frequently in the early stages of treatment.