Acitretin

Name: Acitretin

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

Acitretin Pharmacokinetics

Absorption

Bioavailability

Absorption from GI tract is linear with dose-proportional increases at doses of 25–100 mg.1 2

Following administration of a single 50-mg oral acitretin dose to healthy individuals, approximately 60–72% (range: 36–109%) of dose was absorbed.1 2 17

High interindividual and intraindividual variation in peak plasma concentrations;2 17 mean peak plasma concentration in healthy individuals was achieved in an average of 2.7 hours (range: 2–5 hours).1 17 Following multiple doses in healthy individuals, steady state achieved within approximately 1–3 weeks.1 2 15

In patients with psoriasis, mean steady-state trough concentrations demonstrated dose-dependent increases with daily dosages of 10–50 mg.1 Plasma concentrations were nonmeasurable 3–4 weeks after cessation of therapy.1 15 17

Onset

Improvement seen within first 8 weeks of treatment in clinical trials; full efficacy usually evident within 2–3 months.1 23

Food

Food enhances absorption and reduces the interindividual variability in absorption.1 2 3 6 8 9 15 16 17 19

Special Populations

In healthy geriatric individuals receiving multiple doses of acitretin, plasma concentrations increased twofold compared with those in younger individuals.1 (See Elimination: Special Populations, under Pharmacokinetics.)

In patients with end-stage renal failure receiving a single 50-mg oral acitretin dose, lower plasma concentrations (by 50–59%) were seen compared with healthy individuals; acitretin not removed by hemodialysis.1 17

Distribution

Extent

Distributes into skin with highest concentrations in stratum corneum.2 10 14 Penetrates adipose tissue but does not accumulate in tissues.10 13 14 16

Distributes into milk; crosses placenta.1 2 18

Small amounts of acitretin are distributed into semen; appear to pose little, if any, risk to an unborn child while a male patient is receiving the drug.1

Plasma Protein Binding

>99.9% (mainly albumin).1 9 13 15 16 17

Elimination

Metabolism

Extensively metabolized by simple isomerization in liver by interconversion to 13-cis-acitretin with subsequent oxidation into chain-shortened breakdown products and conjugation to glucuronides.1 2 9 11 13 14 16 17 18 Metabolized to etretinate if alcohol used concomitantly (see Specific Drugs under Interactions).1 9 Not metabolized by hepatic microsomal enzymes.23

Elimination Route

Excreted in urine (16–53%) and feces (34–54%) as metabolites.1 7 9 11

Half-life

Acitretin, following multiple doses: Estimated at about 49 hours but has been reported to range from 24–96 hours.1 3 4 6 7 8 11 12 13 14 15 16 17 18

13-cis-Acitretin, following multiple doses: About 63 hours (range: 28–157 hours).1 13 14 15 17 18

Special Populations

In healthy geriatric individuals, elimination half-life was similar to that in younger individuals.1

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 or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of low mood (depression), thoughts of killing yourself, 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.
  • Mean actions or thoughts of fighting.
  • Chest pain or pressure.
  • Very bad dizziness or passing out.
  • A burning, numbness, or tingling feeling that is not normal.
  • Swelling, warmth, numbness, change of color, or pain in a leg or arm.
  • 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.
  • Change in hearing.
  • Ringing in ears.
  • Fever.
  • Swelling.
  • Weight gain.
  • Stomach pain.
  • Very loose stools (diarrhea).
  • Bleeding from rectum or rectal pain.
  • Very bad and sometimes deadly pancreas problems (pancreatitis) have happened with acitretin. This could happen at any time during care. 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.
  • Lowered night eyesight may happen. This may be sudden. This may clear up after you stop the drug but sometimes it may not go away.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.

What are some other side effects of Acitretin?

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:

  • Runny nose.
  • Change in nails.
  • Itching.
  • Eye irritation.
  • Dry mouth.
  • Dry eyes.
  • Dry lips.
  • Hair loss.

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

If OVERDOSE is suspected

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.

Pharmacology

Binds to and activates all nuclear subtypes (alpha, beta, and gamma) of retinoid X receptors (RXR) and retinoic acid receptors (RAR) to inhibit the expression of the proinflammatory cytokines interleukin-6 (IL-6), migration inhibitory factor-related protein-8 (MRP-8), and interferon-gamma (markers of hyperproliferation and abnormal keratinocyte differentiation). Resulting actions are anti-inflammatory and antiproliferative, and keratinocyte differentiation is normalized in the epithelium.

Absorption

Oral: ~72% absorbed when given with food

Metabolism

Metabolized to cis-acitretin; both compounds are further metabolized. Concomitant ethanol use leads to the formation of etretinate (active).

Excretion

Feces (34% to 54%); urine (16% to 53%)

Dosing Geriatric

Refer to adult dosing.

Dosing Renal Impairment

There are no dosage adjustments provided in manufacturer's labeling; use is contraindicated in patients with severely impaired renal function.

Hemodialysis: Not removed by hemodialysis

Monitoring Parameters

Lipid profile (baseline and at 1- to 2-week intervals for 4 to 8 weeks, then as clinically indicated); liver function tests (baseline, and at 1- to 2-week intervals until stable, then as clinically indicated); blood glucose in patients with diabetes; evaluate for bone abnormalities (with long-term use); pregnancy tests (2 negative tests prior to therapy initiation, monthly during treatment, and every 3 months for ≥3 years after discontinuation of therapy)

The American Academy of Dermatology recommends: CBC and renal function tests (baseline and then every 12 weeks); liver function tests (every 2 weeks for the first 8 weeks, then every 6 to 12 weeks thereafter) (Menter, 2009)

Pregnancy Risk Factor X Pregnancy Considerations

[US Boxed Warning]: Acitretin is a known teratogen and use is contraindicated in females who are or may become pregnant. Birth defects (including facial, ear, central nervous system, cardiovascular, limb, bone, and joint) have been noted following acitretin exposure during pregnancy. Use only in women with severe psoriasis that is unresponsive to other therapies or with contraindications to the use of alternative treatments. Pregnancy must be avoided for at least 3 years after treatment discontinuation. Two reliable forms of contraception must be used simultaneously for 1 month prior to initiating therapy, during therapy, and for 3 years after discontinuation. Two negative pregnancy tests (sensitivity at least 25 milliunits/mL) are required prior to initiating therapy; pregnancy tests must be repeated every month during treatment. In addition, because ethanol forms a teratogenic metabolite and would increase the duration of teratogenic potential, ethanol should not be consumed during treatment or for 2 months after discontinuation.

Only physicians experienced with the diagnosis and treatment of severe psoriasis, including the use of retinoid treatment, and physicians who understand the risk of teratogenicity should prescribe acitretin. Females of childbearing potential must be able to fulfill all conditions for use prior to initiating therapy, including a Patient Agreement/Informed Consent (consult manufacturer's labeling for further detail). Prescriptions should be written for a monthly supply. The Do Your P.A.R.T. (Pregnancy Prevention Actively Required During and After Treatment) program explains teratogenic risks and requirements expected of females of childbearing potential to prevent pregnancies from occurring during use and 3 years following discontinuation; this should be used to educate patients and healthcare providers. Information for the Do Your P.A.R.T. program is available at www.soriatane.com/doyour-part-Program.html or by calling 1-888-784-3335.

Limited amounts of acitretin are found in seminal fluid; although it appears this poses little risk to a fetus, the actual risk of teratogenicity is not known.

Any pregnancy which occurs during treatment, or within 3 years after treatment is discontinued, should be reported to the manufacturer at 1-888-784-3335 or to the FDA at 1-800-FDA-1088.

Patient information

SORIATANE®

Patient Agreement/Informed Consent For Female Patients

To be completed by the patient* and signed by her prescriber

*Must also be initialed by the parent or guardian of a minor patient (under age 18)

Read each item below and initial in the space provided to show that you understand each item.

Do not sign this consent and do not take SORIATANE® (acitretin) if there is anything that you do not understand.

________________________________________________(Patient's name)

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 treatment with SORIATANE.

INITIAL: ___________

2. 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.

INITIAL: ___________

3. I know that I must avoid all alcohol, including drinks, food, medicines, and over-the-counter products that contain alcohol. I understand that the risk of birth defects may last longer than 3 years if I swallow any form of alcohol during therapy with SORIATANE, and for 2 months after I stop taking SORIATANE.

INITIAL: ___________

4. I understand that I must not have sexual intercourse, or I must use 2 separate, effective forms of birth control at the same time. The only exceptions are if I have had surgery to remove the womb (a hysterectomy) or my prescriber has told me I have gone completely through menopause.

INITIAL: ___________

5. I understand that I have to use 2 effective forms of birth control (contraception) at the same time for at least 1 month before starting SORIATANE, for the entire time of therapy with SORIATANE, and for at least 3 years after stopping SORIATANE.

INITIAL: ___________

6. I understand that any form of birth control can fail. Therefore, I must use 2 different methods at the same time, every time I have sexual intercourse.

INITIAL: ___________

7. I understand that the following are considered effective forms of birth control: Primary: Tubal ligation (having my tubes tied), partner's vasectomy, birth control pills (not progestin-only “minipills”), injectable/implantable/insertable/topical (patch) hormonal birth control products, and IUDs (intrauterine devices). Secondary: Condoms (with or without spermicide, which is a special cream or jelly that kills sperm), diaphragms and cervical caps (which must be used with a spermicide), and vaginal sponges (contains spermicide). I understand that at least 1 of my 2 methods of birth control must be a primary method.

INITIAL: ___________

8. I will talk with my prescriber about any medicines or dietary supplements I plan to take while taking SORIATANE because certain birth control methods may not work if I am taking certain medicines or herbal products (for example, St. John's wort).

INITIAL: ___________

9. 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 to start SORIATANE. I understand that if the second pregnancy test is negative, I must start taking my SORIATANE within 7 days of the specimen collection. I will then have pregnancy tests on a monthly basis during therapy with SORIATANE as instructed by my prescriber. In addition, for at least 3 years after I stop taking SORIATANE, I will have a pregnancy test every 3 months.

INITIAL: ___________

10. 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.

INITIAL: ___________

11. I have received information on emergency contraception (birth control).

INITIAL: ___________

12. I understand that my prescriber can give me a referral for a free contraception (birth control) counseling session and pregnancy testing.

INITIAL: ___________

13. I understand that on a monthly basis during therapy with SORIATANE and every 3 months for at least 3 years after stopping SORIATANE that I should receive counseling from my prescriber about contraception (birth control) and behaviors associated with an increased risk of pregnancy.

INITIAL: ___________

14. 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. INITIAL: ___________

15. 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 Stiefel at 1-888-784-3335 (1888-STIEFEL) or to the Food and Drug Administration (FDA) MedWatch program at 1-800FDA-1088. The information I share will be kept confidential (private) unless disclosure is legally required. This will help the company and the FDA evaluate the pregnancy prevention program to prevent birth defects.

INITIAL: ___________

I have received a copy of the Do Your P.A.R.T.™ brochure. My prescriber has answered all my questions about SORIATANE. I understand that it is my responsibility to follow my doctor's instructions, and not to get pregnant during treatment with SORIATANE 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: __________________

Revised 05/2015 SRN:XPI

SORIATANE®
(sor-RYE-uh-tane) (acitretin) Capsules

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 serious side effects, including:

1. 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?”

2. Liver problems, including abnormal liver function tests and inflammation of your liver (hepatitis). Your prescriber should do blood tests to check how your liver is working before you start taking and during treatment with SORIATANE. Stop taking SORIATANE and call your prescriber right away if you have any of the following signs or symptoms of a serious liver problem:

  • yellowing of your skin or the whites of your eyes
  • nausea and vomiting
  • loss of appetite
  • dark urine

What are the important warnings and instructions for females taking SORIATANE?

  • Before you receive your first prescription for SORIATANE, you should have discussed and signed a Patient Agreement/Informed Consent for Female Patients form with your prescriber. This is to help make sure you understand the risk of birth defects and how to avoid getting pregnant. If you did not talk to your prescriber about this and sign the form, contact your prescriber.

NOTE: If you are a female who can become pregnant:

  • You must not take SORIATANE if you are pregnant or might become pregnant during treatment or at any time for at least 3 years after you stop treatment because SORIATANE can cause severe birth defects.
  • During treatment with SORIATANE and for 2 months after you stop treatment with SORIATANE, you must avoid drinks, foods, and all medicines that contain alcohol. This includes over-the-counter products that contain alcohol. Avoiding alcohol is very important, because alcohol changes SORIATANE into a drug that may take longer than 3 years to leave your body. The chance of birth defects may last longer than 3 years if you swallow any form of alcohol during treatment with SORIATANE and for 2 months after you stop taking SORIATANE.
  • You and your prescriber must be sure you are not pregnant before you start therapy with SORIATANE. You must have negative results from 2 pregnancy tests before you start treatment with SORIATANE. A negative result shows you are not pregnant. Because it takes a few days after pregnancy begins for a test to show that you are pregnant, the first negative test may not ensure you are not pregnant. Do not start SORIATANE until you have negative results from 2 pregnancy tests.
    • The first pregnancy test (urine or blood) will be done at the time you and your prescriber decide if SORIATANE might be right for you.
    • The second pregnancy test will usually be done during the first 5 days of your menstrual period. You must start taking SORIATANE within 7 days of when the urine or blood for the second pregnancy test is collected.
  • After you start taking SORIATANE, you must have a pregnancy test repeated each month that you are taking SORIATANE. This is to be sure that you are not pregnant during treatment because SORIATANE can cause birth defects. In addition, your prescription of SORIATANE will be limited to a monthly supply.
  • For at least 3 years after stopping treatment with SORIATANE, you must have a pregnancy test repeated every 3 months to make sure that you are not pregnant.
  • Discuss effective birth control (contraception) with your prescriber. You must use 2 effective forms of birth control (contraception) at the same time during all of the following:
    • for at least 1 month before beginning treatment with SORIATANE
    • during treatment with SORIATANE
    • for at least 3 years after stopping treatment with SORIATANE
  • If you are sexually active, you must use 2 effective forms of birth control (contraception) at the same time even if you think you cannot become pregnant, unless 1 of the following is true for you:
    • You had your womb (uterus) removed during an operation (a hysterectomy).
    • Your prescriber said you have gone completely through menopause (the “change of life”).
  • You can get a free birth control counseling session and pregnancy testing from a prescriber or family planning expert. Your prescriber can give you a Contraception Counseling Referral Form for this free session.

The following are considered effective forms of birth control:

Primary Forms:

  • having your tubes tied (tubal ligation)
  • partner's vasectomy
  • IUD (Intrauterine device)
  • birth control pills that contain both estrogen and progestin (combination oral contraceptives); not progestin-only “minipills”
  • hormonal birth control products that are injected, implanted, or inserted in your body
  • birth control patch

Secondary Forms (use with a Primary Form):

  • diaphragms with spermicide
  • condoms (with or without spermicide)
  • cervical caps with spermicide
  • vaginal sponge (contains spermicide)

At least 1 of your 2 methods of birth control must be a primary form.

  • If you have sex at any time without using 2 effective forms of birth control (contraception) at the same time, or if you get pregnant or miss your period, stop using SORIATANE and call your prescriber right away.
  • Consider “Emergency Contraception” (EC) if you have sex with a male without correctly using 2 effective forms of birth control (contraception) at the same time. EC is also called “emergency birth control” or the “morning after” pill. Contact your prescriber as soon as possible if you have sex without using 2 effective forms of birth control (contraception) at the same time, because EC works best if it is used within 1 or 2 days after sex. EC is not a replacement for your usual 2 effective forms of birth control (contraception) because it is not as effective as regular birth control methods. You can get EC from private doctors or nurse practitioners, women's health centers, or hospital emergency rooms. You can get the name and phone number of EC providers nearest you by calling the free Emergency Contraception Hotline at 1-888-668-2528 (1-888-NOT-2-LATE).
  • Stop taking SORIATANE right away and contact your prescriber if you get pregnant while taking SORIATANE or at any time for at least 3 years after treatment has stopped. You need to discuss the possible effects on the unborn baby with your prescriber.
  • If you do become pregnant while taking SORIATANE or at any time for at least 3 years after stopping SORIATANE, you should report your pregnancy to Stiefel Laboratories, Inc. at 1-888-784-3335 (1-888STIEFEL) or directly to the Food and Drug Administration (FDA) MedWatch program at 1-800-FDA-1088. Your name will be kept in private (confidential). The information you share will help the FDA and the manufacturer evaluate the Pregnancy Prevention Program for SORIATANE.
  • Do not take SORIATANE if you are breastfeeding. 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.

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 possible benefits of SORIATANE 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 treatment with SORIATANE. 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 treatment with SORIATANE or at any time for at least 3 years after you stop treatment with SORIATANE (see “What are the important warnings and instructions for females taking SORIATANE?”).
  • Do NOT take SORIATANE if you are breastfeeding. 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:
    • methotrexate
    • tetracyclines

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 in SORIATANE (see the end of this Medication Guide for a list of all the ingredients in SORIATANE), or to any medicines that are like SORIATANE. Ask your prescriber or pharmacist if any medicines you are allergic to are like 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
  • depression
  • alcoholism
  • 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 over-the-counter 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:

  • methotrexate
  • tetracyclines
  • glyburide
  • phenytoin
  • 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 breastfeeding. See “What are the important warnings and instructions for females taking SORIATANE?”
  • Avoid alcohol. Females who are able to become pregnant 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 treatment with SORIATANE and for 2 months after stopping SORIATANE (see “What are the important warnings and instructions for females taking SORIATANE?”).
  • Avoid giving blood. Do not donate blood while you are taking SORIATANE and for at least 3 years after stopping treatment with SORIATANE. 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 (see “Serious side effects”).
  • 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 serious side effects. See “What is the most important information I should know about SORIATANE?” and “What are the important warnings and instructions for females taking SORIATANE?”

Stop taking SORIATANE and call your prescriber right away if you get the following signs or symptoms of possible serious side effects:

  • Bad headaches, nausea, vomiting, blurred vision. These symptoms can be signs of increased brain pressure that can lead to blindness or even death.
  • Vision problems. 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 treatment with SORIATANE stops. Stop taking SORIATANE and call your prescriber if you develop any vision problems or eye pain.
  • 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 patients taking SORIATANE. Since other things may have contributed to these problems, it is not known if they are related to SORIATANE.
  • Aches or pains in your bones, joints, muscles, or back, trouble moving, or 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.
  • Blood vessel problems. SORIATANE can cause fluid to leak out of your blood vessels into your body tissues. Call your prescriber right away if you have any of the following symptoms: sudden swelling in one part of your body or all over your body, weight gain, fever, lightheadedness or feeling faint, or muscle aches. If this happens, your prescriber will tell you to stop taking SORIATANE.
  • Serious allergic reactions. See “Who should not take SORIATANE?” Serious allergic reactions can happen during treatment with SORIATANE. Call your prescriber right away if you get any of the following symptoms of an allergic reaction: hives, itching, swelling of your face, mouth, or tongue, or problems breathing. If this happens, stop taking SORIATANE and do not take it again.
  • Serious skin problems. SORIATANE can cause skin problems that can begin in a small area and then spread over large areas of your body. Call your prescriber right away if your skin becomes red and swollen (inflamed), you have peeling of your skin, or your skin becomes itchy and painful. You should stop SORIATANE if this happens.

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 dose of SORIATANE 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. You may also lose your eyelashes.
  • 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 (see information under “Serious side effects”). You should have blood tests as directed by your prescriber.

Psoriasis gets worse for some patients when they first start treatment with SORIATANE. 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.

These are not all the possible side effects of SORIATANE. For more information, ask your prescriber or pharmacist.

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

How should I store SORIATANE?

  • Keep SORIATANE away from sunlight, high temperature, and humidity.
  • Keep SORIATANE and all medicines out of the reach of children.

What are the ingredients in SORIATANE?

Active ingredient: acitretin.

Inactive ingredients: black monogramming ink, gelatin, maltodextrin (a mixture of polysaccharides), microcrystalline cellulose, and sodium ascorbate. 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.

For more information about SORIATANE call 1-888-784-3335 or go to www.soriatane.com.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Uses of Acitretin

Acitretin is a prescription medication used to treat severe psoriasis.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Pregnancy & Lactation

Pregnancy Category: X

Major human fetal abnormalities have been reported including meningomyelocele, meningoencephalocele, multiple synostoses, facial dysmorphia, syndactyly, absence of terminal phalanges, malformations of bones (hip, ankle, forearm, skull, cerebral vertebrae), low-set ears, high palate, decreased cranial volume, and cardiovascular malformations

Lactation: enters breast milk/not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Where can i get more information?

Your pharmacist can provide more information about acitretin.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 4.02. Revision date: 12/15/2010.

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In Summary

Commonly reported side effects of acitretin include: increased gamma-glutamyl transferase and xerophthalmia. Other side effects include: eye irritation. See below for a comprehensive list of adverse effects.

Precautions

US BOXED WARNINGS:

-Acitretin must not be used by females who are pregnant, or who intend to become pregnant during therapy or at any time for at least 3 years following discontinuation of therapy. Acitretin also must not be used by females who may not use reliable contraception while undergoing treatment and for at least 3 years following discontinuation of treatment. Acitretin is a metabolite of etretinate and major human fetal abnormalities have been reported with the administration of acitretin and etretinate. Potentially, any fetus exposed can be affected.
-Ethanol must not be ingested by female patients either during treatment with acitretin or for 2 months after cessation of therapy.
-Because of the teratogenicity of acitretin, a program called T.A.P.P., Take Action to Prevent Pregnancy, has been developed to educate women of childbearing potential and their healthcare providers about the serious risks associated with acitretin and to help prevent pregnancies from occurring with the use of this drug and for 3 years after its discontinuation. The T.A.P.P. program requirements are described below and program materials are available at http://www.tevagenerics.com/acitretin or may be requested by calling 1-855-850-2138 Important Information for Women of Childbearing Potential
-Acitretin should be considered only for women with severe psoriasis unresponsive to other therapies or whose clinical condition contraindicates the use of other treatments.
-Females of reproductive potential must not be given a prescription for acitretin until pregnancy is excluded. Acitretin is contraindicated in females of reproductive potential unless the patient meets ALL of the following conditions:
-Must have had 2 negative urine or serum pregnancy tests with a sensitivity of at least 25 mInternational Units(mIU)/mL before receiving the initial prescription for acitretin. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue therapy with acitretin. The second pregnancy test (a confirmation test) should be done during the first 5 days of the menstrual period immediately preceding the beginning of therapy with acitretin. For patients with amenorrhea, the second test should be done at least 11 days after the last act of unprotected sexual intercourse (without using 2 effective forms of contraception [birth control] simultaneously).
-Must have a pregnancy test repeated every month during treatment with acitretin. The patient must have a negative result from a urine or serum pregnancy test before receiving a prescription for acitretin. To encourage compliance with this recommendation, a limited supply of the drug should be prescribed. For at least 3 years after discontinuing therapy with acitretin, a pregnancy test must be repeated every 3 months.
-Must have selected and have committed to use 2 effective forms of contraception (birth control) simultaneously, at least 1 of which must be a primary form, unless absolute abstinence is the chosen method, or the patient has undergone a hysterectomy or is clearly postmenopausal.
-Effective forms of contraception should be used for at least 1 month prior to initiation of therapy with acitretin, during therapy with acitretin, and for at least 3 years after discontinuing therapy with acitretin. An Acitretin Referral Form is available so that patients can receive an initial free contraceptive counseling session and pregnancy testing
-Effective forms of contraception include both primary and secondary forms of contraception. Primary forms of contraception include: tubal ligation, partner's vasectomy, intrauterine devices, birth control pills, and injectable/implantable/ insertable/topical hormonal birth control products. Secondary forms of contraception include latex condoms (with or without spermicide), diaphragms and cervical caps (which must be used with a spermicide).
-It has been established that acitretin interferes with the contraceptive effect of microdosed progestin preparations. 1 Microdosed "minipill" progestin preparations are not recommended for use with acitretin. It is not known whether other progestational contraceptives, such as implants and injectables, are adequate methods of contraception during acitretin therapy.
-Prescribers are advised to consult the package insert of any medication administered concomitantly with hormonal contraceptives, since some medications may decrease the effectiveness of these birth control products. Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John's wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives shortly after starting St. John's wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John's wort.
-Must have signed a Patient Agreement/Informed Consent for Female Patients that contains warnings about the risk of potential birth defects if the fetus is exposed to acitretin, about contraceptive failure, about the fact that they must not ingest beverages or products containing ethanol while taking acitretin and for 2 months after acitretin treatment has been discontinued, and about preventing pregnancy while taking acitretin and for at least 3 years after discontinuing acitretin.
-If pregnancy does occur during therapy with acitretin or at any time for at least 3 years following discontinuation of acitretin, the prescriber and patient should discuss the possible effects on the pregnancy.
-Acitretin, the active metabolite of etretinate, is teratogenic and is contraindicated during pregnancy. The risk of severe fetal malformations is well established when systemic retinoids are taken during pregnancy. Pregnancy must also be prevented after stopping acitretin therapy, while the drug is being eliminated to below a threshold blood concentration that would be associated with an increased incidence of birth defects.
-Severe birth defects have been reported where conception occurred during the time interval when the patient was being treated with acitretin and/or etretinate. In addition, severe birth defects have also been reported when conception occurred after the mother completed therapy.
-Females who have taken etretinate- must continue to follow the contraceptive recommendations for etrenitate. Etrenitate is no longer marketed in the U.S.; for information, call 1-888-838-2872.
-Patients should not donate blood during and for at least 3 years following the completion of therapy with acitretin because women of childbearing potential must not receive blood from patients being treated with acitretin.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Acitretin Levels and Effects while Breastfeeding

Summary of Use during Lactation

Limited information indicates that maternal doses of acitretin of 0.65 mg/kg daily produce low levels in milk. Because there is no published experience with acitretin during breastfeeding, opinions vary on the advisability of breastfeeding during acitretin therapy.[1][2][3] Various topical agents that are less likely to be absorbed by the mother may be preferred during breastfeeding, especially while nursing a newborn or preterm infant. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.[4]

Drug Levels

Maternal Levels. A woman who was 8 months postpartum discontinued breastfeeding and began acitretin 40 mg (0.65 mg/kg) once daily by mouth after breakfast. Milk was collected before starting the drug and then twice daily for 9 days. Acitretin and its 13-cis-metabolite were detected in milk 12 hours after the first dose and levels gradually increased over 4 to 5 days to steady-state levels between 30 and 40 mcg/L that did not fluctuate markedly during the day. Acitretin was the main component found in milk 10 to 12 hours after a dose while the metabolite was the primary component in milk 22 to 24 hours after the previous dose.[1] Assuming an average milk level of 35 mcg/L, an exclusively breastfed infant would receive an estimated 0.8% of the maternal weight-adjusted dosage as acitretin and its metabolite.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Depends on the severity of the psoriasis and its location on the body.

References

1. Rollman O, Pihl-Lundin I. Acitretin excretion into human breast milk. Acta Derm Venereol. 1990;70:487-90. PMID: 1981420

2. American Academy of Pediatrics Committee on Drugs. The transfer of drugs and other chemicals into human milk. Pediatrics. 2001;108:776-89. PMID: 11533352

3. Butler DC, Heller MM, Murase JE. Safety of dermatologic medications in pregnancy and lactation: Part II Lactation. J Am Acad Dermatol. 2014;70:417.e1-417.e10. PMID: 24528912

4. Noti A, Grob K, Biedermann M et al. Exposure of babies to C(15)-C(45) mineral paraffins from human milk and breast salves. Regul Toxicol Pharmacol. 2003;38:317-25. PMID: 14623482

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