Acetretin - General Information
An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of etretinate with the advantage of a much shorter half-life when compared with etretinate.
Pharmacology of Acetretin
Acetretin is a retinoid. Retinoids have a structure similar to vitamin A and are involved in the normal growth of skin cells. Acetretin works by inhibiting the excessive cell growth and keratinisation (process by which skin cells become thickened due to the deposition of a protein within them) seen in psoriasis. It therefore reduces the thickening of the skin, plaque formation and scaling.
Acetretin for patients
Medication Guide for Patients
Read this Medication Guide carefully before you start taking Soriatane and read it each time you get more Soriatane. There may be new information.
The first information in this Guide is about birth defects and how to avoid pregnancy. After this section there is important safety information about possible effects for any patient taking Soriatane. ALL patients should read this entire Medication Guide carefully.
This information does not take the place of talking with your prescriber about your medical condition or treatment.
What is the most important information I should know about Soriatane?
Soriatane can cause severe birth defects. If you are a female who can get pregnant, you should use Soriatane only if you are not pregnant now, can avoid becoming pregnant for at least 3 years, and other medicines do not work for your severe psoriasis or you cannot use other psoriasis medicines. Information about effects on unborn babies and about how to avoid pregnancy is found in the next section: "What are the important warnings and instructions for females taking Soriatane?".
What are the important warnings and instructions for females taking Soriatane?
What should males know before taking Soriatane?
Small amounts of Soriatane are found in the semen of males taking Soriatane. Based upon available information, it appears that these small amounts of Soriatane in semen pose little, if any, risk to an unborn child while a male patient is taking the drug or after it is discontinued. Discuss any concerns you have about this with your prescriber.
All patients should read the rest of this Medication Guide.
What is Soriatane?
Soriatane is a medicine used to treat severe forms of psoriasis in adults. Psoriasis is a skin disease that causes cells in the outer layer of the skin to grow faster than normal and pile up on the skin's surface. In the most common type of psoriasis, the skin becomes inflamed and produces red, thickened areas, often with silvery scales. Because Soriatane can have serious side effects, you should talk with your prescriber about whether Soriatane's possible benefits outweigh its possible risks.
Soriatane may not work right away. You may have to wait 2 to 3 months before you get the full benefit of Soriatane. Psoriasis gets worse for some patients when they first start Soriatane treatment.
Soriatane has not been studied in children.
Who should not take Soriatane?
• Do NOT take Soriatane if you can get pregnant. Do not take Soriatane if you are pregnant or might get pregnant during Soriatane treatment or at any time for at least 3 years after you stop Soriatane treatment.
• Do NOT take Soriatane if you are breast feeding. Soriatane can pass into your milk and may harm your baby. You will need to choose either to breast feed or take Soriatane, but not both.
• Do NOT take Soriatane if you have severe liver or kidney disease.
• Do NOT take Soriatane if you have repeated high blood lipids (fat in the blood).
• Do NOT take Soriatane if you take these medicines:
The use of these medicines with Soriatane may cause serious side effects.
• Do NOT take Soriatane if you are allergic to acitretin, the active ingredient in Soriatane, to any of the other ingredients, or to any similar drugs (ask your prescriber or pharmacist whether any drugs you are allergic to are related to Soriatane).
Tell your prescriber if you have or ever had:
• diabetes or high blood sugar
• liver problems
• kidney problems
• high cholesterol or high triglycerides (fat in the blood)
• heart disease
• an allergic reaction to a medication
Your prescriber needs this information to decide if Soriatane is right for you and to know what dose is best for you.
Tell your prescriber about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines can cause serious side effects if taken while you also take Soriatane. Some medicines may affect how Soriatane works, or Soriatane may affect how your other medicines work. Be especially sure to tell your prescriber if you are taking the following medicines:
• vitamin A supplements
• progestin-only oral contraceptives ("minipills")
•Tegison or Tigason (etretinate). Tell your prescriber if you have ever taken this medicine in the past.
• St. John's Wort herbal supplement
Tell your prescriber if you are getting phototherapy treatment. Your doses of phototherapy may need to be changed to prevent a burn.
How should I take Soriatane?
• Take Soriatane with food.
• Be sure to take your medicine as prescribed by your prescriber. The dose of Soriatane varies from patient to patient. The number of capsules you must take is chosen specially for you by your prescriber. This dose may change during treatment.
• If you miss a dose, do not double the next dose. Skip the missed dose and resume your normal schedule.
• If you take too much Soriatane (overdose), call your local poison control center or emergency room.
You should have blood tests for liver function, cholesterol and triglycerides before starting treatment and during treatment to check your body's response to Soriatane. Your prescriber may also do other tests.
Once you stop taking Soriatane, your psoriasis may return. Do not treat this new psoriasis with leftover Soriatane. It is important to see your prescriber again for treatment recommendations because your situation may have changed.
What should I avoid while taking Soriatane?
• Avoid pregnancy. See "What is the most important information I should know about Soriatane?", and "What are the important warnings and instructions for females taking Soriatane?".
• Avoid breast feeding. See "What are the important warnings and instructions for females taking Soriatane?".
• Avoid alcohol. Females must avoid drinks, foods, medicines, and over-the-counter products that contain alcohol. The risk of birth defects may continue for longer than 3 years if you swallow any form of alcohol during Soriatane treatment and for 2 months after stopping Soriatane.
• Avoid giving blood. Do not donate blood while you are taking Soriatane and for at least 3 years after stopping Soriatane treatment. Soriatane in your blood can harm an unborn baby if your blood is given to a pregnant woman. Soriatane does not affect your ability to receive a blood transfusion.
• Avoid progestin-only birth control pills ("minipills"). This type of birth control pill may not work while you take Soriatane. Ask your prescriber if you are not sure what type of pills you are using.
• Avoid night driving if you develop any sudden vision problems. Stop taking Soriatane and call your prescriber if this occurs.
• Avoid non-medical ultraviolet (UV) light. Soriatane can make your skin more sensitive to UV light. Do not use sunlamps, and avoid sunlight as much as possible. If you are taking light treatment (phototherapy), your prescriber may need to change your light dosages to avoid burns.
• Avoid dietary supplements containing vitamin A. Soriatane is related to vitamin A. Therefore, do not take supplements containing vitamin A, because they may add to the unwanted effects of Soriatane. Check with your prescriber or pharmacist if you have any questions about vitamin supplements.
• DO NOT SHARE Soriatane with anyone else, even if they have the same symptoms. Your medicine may harm them or their unborn child.
What are the possible side effects of Soriatane?
• Soriatane can cause birth defects. See "What is the most important information I should know about Soriatane?" and "What are the important warnings and instructions for females taking Soriatane?"
• Psoriasis gets worse for some patients when they first start Soriatane treatment. Some patients have more redness or itching. If this happens, tell your prescriber. These symptoms usually get better as treatment continues, but your prescriber may need to change the amount of your medicine.
Serious side effects. These do not happen often, but they can lead to permanent harm, or rarely, to death. Stop taking Soriatane and call your prescriber right away if you get the following signs or symptoms:
• Bad headaches, nausea, vomiting, blurred vision. These symptoms can be signs of increased brain pressure that can lead to blindness or even death.
• Decreased vision in the dark (night blindness). Since this can start suddenly, you should be very careful when driving at night. This problem usually goes away when Soriatane treatment stops. If you develop any vision problems or eye pain stop taking Soriatane and call your prescriber.
• Depression. There have been some reports of patients developing mental problems including a depressed mood, aggressive feelings, or thoughts of ending their own life (suicide). These events, including suicidal behavior, have been reported in patients taking other drugs similar to Soriatane as well as in patients taking Soriatane. Since other things may have contributed to these problems, it is not known if they are related to Soriatane. It is very important to stop taking Soriatane and call your prescriber right away if you develop such problems.
• Yellowing of your skin or the whites of your eyes, nausea and vomiting, loss of appetite, or dark urine. These can be signs of serious liver damage.
• Aches or pains in your bones, joints, muscles, or back; trouble moving; loss of feeling in your hands or feet. These can be signs of abnormal changes to your bones or muscles.
• Frequent urination, great thirst or hunger. Soriatane can affect blood sugar control, even if you do not already have diabetes. These are some of the signs of high blood sugar.
• Shortness of breath, dizziness, nausea, chest pain, weakness, trouble speaking, or swelling of a leg. These may be signs of a heart attack, blood clots, or stroke. Soriatane can cause serious changes in blood fats (lipids). It is possible for these changes to cause blood vessel blockages that lead to heart attacks, strokes, or blood clots.
Common side effects. If you develop any of these side effects or any unusual reaction, check with your prescriber to find out if you need to change the amount of Soriatane you take. These side effects usually get better if the Soriatane dose is reduced or Soriatane is stopped.
• Chapped lips; peeling fingertips, palms, and soles; itching; scaly skin all over; weak nails; sticky or fragile (weak) skin; runny or dry nose, or nosebleeds. Your prescriber or pharmacist can recommend a lotion or cream to help treat drying or chapping.
• Dry mouth
• Joint pain
• Tight muscles
• Hair loss. Most patients have some hair loss, but this condition varies among patients. No one can tell if you will lose hair, how much hair you may lose or if and when it may grow back.
• Dry eyes. Soriatane may dry your eyes. Wearing contact lenses may be uncomfortable during and after treatment with Soriatane because of the dry feeling in your eyes. If this happens, remove your contact lenses and call your prescriber. Also read the section about vision under "Serious side effects".
• Rise in blood fats (lipids). Soriatane can cause your blood fats (lipids) to rise. Most of the time this is not serious. But sometimes the increase can become a serious problem. You should have blood tests as directed by your prescriber.
These are not all the possible side effects of Soriatane. For more information, ask your prescriber or pharmacist.
How should I store Soriatane?
Keep Soriatane away from sunlight, high temperature, and humidity. Keep Soriatane away from children.
What are the ingredients in Soriatane?
Active ingredient: acitretin
Inactive ingredients: microcrystalline cellulose, sodium ascorbate, gelatin, black monogramming ink and maltodextrin (a mixture of polysaccharides). Gelatin capsule shells contain gelatin, iron oxide (yellow, black, and red), and titanium dioxide. They may also contain benzyl alcohol, carboxymethylcellulose sodium, edetate calcium disodium.
General information about the safe and effective use of Soriatane
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Soriatane for a condition for which it was not prescribed. Do not give Soriatane to other people, even if they have the same symptoms that you have.
This Medication Guide summarizes the most important information about Soriatane. If you would like more information, talk with your prescriber. You can ask your pharmacist or prescriber for information about Soriatane that is written for health professionals.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
PATIENT AGREEMENT/INFORMED CONSENT for FEMALE Patients
To be completed by the patient, her parent/guardian* and signed by her prescriber.
Read each item below and initial in the space provided to show that you understand each item and agree to follow your prescriber's instructions. Do not sign this consent and do not take Soriatane if there is anything that you do not understand.
*A parent or guardian of a minor patient (under age 18) must also read and initial each item before signing the consent.
1. I understand that there is a very high risk that my unborn baby could have severe birth defects if I am pregnant or become pregnant while taking Soriatane in any amount even for short periods of time. Birth defects have also happened in babies of women who became pregnant after stopping Soriatane treatment.
2. I understand that I must not take Soriatane if I am pregnant.
3. I understand that I must not become pregnant while taking Soriatane and for at least 3 years after the end of my treatment with Soriatane.
4. I know that I must avoid drinks, food, and medicines, including over-the-counter products, that contain alcohol. This is extremely important, because alcohol changes Soriatane in the blood into a drug that takes even longer to leave the body. This means the risk of birth defects may last longer than 3 years if I swallow any form of alcohol during Soriatane therapy or for 2 months after I stop taking Soriatane.
5. I understand that I must avoid sexual intercourse completely, or I must use 2 separate effective forms of birth control (contraception) at the same time. The only exception is if I have had surgery to remove the womb (a hysterectomy) or my prescriber has told me I have gone completely through menopause.
6. I have been told by my prescriber that 2 effective forms of birth control (contraception) must be used at the same time for at least 1 month before starting Soriatane, for the entire time of Soriatane therapy, and for at least 3 years after Soriatane treatment has stopped.
7. I understand that birth control pills and injectable/implantable/insertable/topical (patch) hormonal birth control products are among the most effective forms of birth control. However, any form of birth control can fail. Therefore, I must use 2 different methods at the same time, every time I have sexual intercourse, even if 1 of the methods I choose is birth control pills, injections, or tubal ligation (tube-tying).
8. I understand that the following are considered effective forms of birth control: Primary: Tubal ligation (tying my tubes), partner's vasectomy, birth control pills, injectable/implantable/insertable/topical (patch) hormonal birth control products, and an IUD (intrauterine device).
Secondary: Diaphragms, latex condoms, and cervical caps. Each must be used with a spermicide, which is a special cream or jelly that kills sperm.
I understand that at least 1 of my 2 methods of birth control must be a primary method.
9. I will talk with my prescriber about any medicines or dietary supplements I plan to take during my Soriatane treatment because hormonal birth control methods (for example, birth control pills) may not work if I am taking certain medicines or herbal products (for example, St. John's Wort).
10. I understand that if I have taken Tegison (etretinate), I must continue to follow the birth control (contraception) recommendations for Tegison.
11. Unless I have had a hysterectomy or my prescriber says I have gone completely through menopause, I understand that I must have 2 negative pregnancy test results before I can get a prescription for Soriatane. The first pregnancy test should be done when my prescriber decides to prescribe Soriatane. The second pregnancy test should be done during the first 5 days of my menstrual period right before starting Soriatane therapy, or as instructed by my prescriber. I will then have pregnancy tests on a regular basis as instructed by my prescriber during my Soriatane therapy.
12. I understand that I should not start taking Soriatane until I am sure that I am not pregnant and have negative results from 2 pregnancy tests.
13. I have read and understand the materials my prescriber has given to me, including the Soriatane Pregnancy Prevention Program. My prescriber gave me and asked me to watch the video about contraception (birth control). I was told about a confidential counseling line that I may call at Connetics for more information about birth control(1-888-500-DERM (3376)).
14. I have received information on emergency contraception (birth control).
15. I understand that I may receive a free contraceptive (birth control) counseling session and pregnancy testing. My prescriber can give me a Soriatane Patient Referral Form for this free consultation.
16. I understand that I should receive counseling from my prescriber, repeated on a regular basis, about contraception (birth control) and behaviors associated with an increased risk of pregnancy.
17. I understand that I must stop taking Soriatane right away and call my prescriber if I get pregnant, miss my menstrual period, stop using birth control, or have sexual intercourse without using my 2 birth control methods during and at least 3 years after stopping Soriatane treatment.
18. If I do become pregnant while on Soriatane or at any time within 3 years of stopping Soriatane, I understand that I should report my pregnancy to Connetics at 1-888-500-DERM (3376) or to the Food and Drug Administration (FDA) MedWatch program at 1-800-FDA-1088. The information I share will be kept confidential (private) and will help the company and the FDA evaluate the Pregnancy Prevention Program.
My prescriber has answered all my questions about Soriatane. I understand that it is my responsibility not to get pregnant during Soriatane treatment or for at least 3 years after I stop taking Soriatane. I now authorize my prescriber _____________________to begin my treatment with Soriatane.
Patient signature:________________________________ Date:____________________ Parent/guardian signature (if under age 18):____________________ Date:___________ Please print: Patient name and address________________________________________ ______________________________________ Telephone: _______________________
I have fully explained to the patient, __________________, the nature and purpose of the treatment described above and the risks to females of childbearing potential. I have asked the patient if she has any questions regarding her treatment with Soriatane and have answered those questions to the best of my ability.
Prescriber signature: ______________________________ Date:__________________
Ethanol:Clinical evidence has shown that etretinate can be formed with concurrent ingestion of acitretin and ethanol.
Glibenclamide: In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with Soriatane is recommended.
Hormonal Contraceptives: It has not been established if there is a pharmacokinetic interaction between acitretin and combined oral contraceptives. However, it has been established that acitretin interferes with the contraceptive effect of microdosed progestin "minipill" preparations. Microdosed "minipill" progestin preparations are not recommended for use with Soriatane. It is not known whether other progestational contraceptives, such as implants and injectables, are adequate methods of contraception during acitretin therapy.
Methotrexate: An increased risk of hepatitis has been reported to result from combined use of methotrexate and etretinate. Consequently, the combination of methotrexate with acitretin is also contraindicated.
Phenytoin: If acitretin is given concurrently with phenytoin, the protein binding of phenytoin may be reduced.
Tetracyclines: Since both acitretin and tetracyclines can cause increased intracranial pressure, their combined use is contraindicated.
Vitamin A and oral retinoids: Concomitant administration of vitamin A and/or other oral retinoids with acitretin must be avoided because of the risk of hypervitaminosis A.
Other: There appears to be no pharmacokinetic interaction between acitretin and cimetidine, digoxin, or glyburide. Investigations into the effect of acitretin on the protein binding of anticoagulants of the coumarin type (warfarin) revealed no interaction.
If significant abnormal laboratory results are obtained, either dosage reduction with careful monitoring or treatment discontinuation is recommended, depending on clinical judgement.
Blood Sugar: Some patients receiving retinoids have experienced problems with blood sugar control. In addition, new cases of diabetes have been diagnosed during retinoid therapy, including diabetic ketoacidosis. In diabetics, blood-sugar levels should be monitored very carefully.
Lipids: In clinical studies, the incidence of hypertriglyceridemia was 66%, hypercholesterolemia was 33% and that of decreased HDL was 40%. Pretreatment and follow-up measurements should be obtained under fasting conditions. It is recommended that these tests be performed weekly or every other week until the lipid response to Soriatane has stabilized.
Liver Function Tests: Elevations of AST (SGOT), ALT (SGPT) or LDH were experienced by approximately 1 in 3 patients treated with Soriatane. It is recommended that these tests be performed prior to initiation of Soriatane therapy, at 1- to 2-week intervals until stable and thereafter at intervals as clinically indicated.
Pregnancy Category X.
Soriatane is contraindicated in patients with severely impaired liver or kidney function and in patients with chronic abnormally elevated blood lipid values.
An increased risk of hepatitis has been reported to result from combined use of methotrexate and etretinate. Consequently, the combination of methotrexate with Soriatane is also contraindicated.
Since both Soriatane and tetracyclines can cause increased intracranial pressure, their combined use is contraindicated.
Soriatane is contraindicated in cases of hypersensitivity to the preparation (acitretin or excipients) or to other retinoids.
Additional information about Acetretin
Acetretin Indication: For the treatment of severe psoriasis in adults.
Mechanism Of Action: The mechanism of action of acitretin is unknown, however it is believed to work by targeting specific receptors (retinoid receptors) in the skin which help normalize the growth cycle of skin cells.
Drug Interactions: Demeclocycline Increased risk of intracranial hypertension
Doxycycline Increased risk of intracranial hypertension
Methacycline Increased risk of intracranial hypertension
Minocycline Increased risk of intracranial hypertension
Oxytetracycline Increased risk of intracranial hypertension
Tetracycline Increased risk of intracranial hypertension
Norethindrone Acetretine may cause a loss of contraceptive effect
Methotrexate Acetretin/etretinate increases the effect and toxicity of methotrexate
Rolitetracycline Increased risk of intracranial hypertension
Food Interactions: Not Available
Generic Name: Acitretin
Synonyms: Not Available
Drug Category: Keratolytic Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Acitretin: Acetretin; Soriatane;
Absorption: Oral absorption of acitretin is optimal when given with food, and is linear and proportional with increasing doses from 25 to 100 mg. Approximately 72% (range 47% to 109%) of the administered dose was absorbed after a single 50 mg dose of acitretin was given to 12 healthy subjects.
Toxicity (Overdose): Oral, rat: LD50 = >4000 mg/kg. Symptoms of overdose include headache and vertigo.
Protein Binding: Over 99.9% bound to plasma proteins, primarily albumin.
Biotransformation: Following oral absorption, acitretin undergoes extensive metabolism and interconversion by simple isomerization to its 13-cis form (cis-acitretin). Both parent compound and isomer are further metabolized into chain-shortened breakdown products and conjugates, which are excreted.
Half Life: 49 hours (range 33 to 96 hours)
Dosage Forms of Acetretin: Capsule Oral
Chemical IUPAC Name: (2Z,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid
Chemical Formula: C21H26O3
Acitretin on Wikipedia: http://en.wikipedia.org/wiki/Acitretin
Organisms Affected: Humans and other mammals