Acitretin

Name: Acitretin

What should I discuss with my healthcare provider before taking acitretin?

You should not take this medicine if you are allergic to acitretin or similar medications (such as Accutane, Altinac, Avita, Renova, Retin-A, and others), or if you have:

  • severe liver or kidney disease;

  • high levels of triglycerides (a type of fat) in your blood;

  • if you are pregnant or breast-feeding;

  • if you are also using methotrexate (Rheumatrex, Trexall); or

  • if you are also using a tetracycline antibiotic, including demeclocycline (Declomycin), doxycycline (Adoxa, Doryx, Oracea, Vibramycin), minocycline (Dynacin, Minocin, Solodyn, Vectrin), tetracycline (Brodspec, Panmycin, Sumycin, Tetracap), and others.

Acitretin is available only under an agreement that you will use birth control and undergo required pregnancy testing, and that you will not consume alcohol while you are taking acitretin and for 2 months after you stop taking it.

To make sure acitretin is safe for you, tell your doctor if you have:

  • kidney or liver disease;

  • heart disease;

  • high cholesterol;

  • diabetes (you may need to check your blood sugar more often);

  • depression;

  • if you receive phototherapy;

  • if you drink large amounts of alcohol; or

  • if you have ever taken etretinate (Tegison or Tigason).

Acitretin can cause birth defects. Do not use if you are pregnant or plan to become pregnant within 3 years after you stop taking acitretin. You must use 2 effective forms of birth control starting at least 1 month before treatment with acitretin, and for at least 3 years after you stop taking this medication. Use both forms of birth control together every time you have sex.

The first birth control method should include one of the following forms: birth control pills (but not the "mini-pill"), an intrauterine device (IUD), birth control shots, inserts, skin patches, or implants, a tubal ligation, or your male partner's vasectomy.

The second birth control method should include one of the following forms: a latex condom, or a diaphragm or cervical cap used together with a spermicide cream or gel.

For women taking acitretin: Before using acitretin, you must have 2 negative pregnancy tests. The first test is given when your doctor prescribes acitretin. The second test must be given during the first 5 days of your menstrual period just before you start taking acitretin. No testing is needed if you have had a hysterectomy or have gone completely through menopause.

You will need monthly pregnancy tests while you are taking acitretin. If you are not menstruating, your pregnancy test should be done at least 11 days after you last had sex without using 2 effective forms of birth control.

Do not miss a scheduled pregnancy test or you may not be able to continue taking acitretin.

You will also need pregnancy tests every 3 months for at least 3 years after you stop taking this medication.

Call your doctor right away if you think you might be pregnant, if you miss a period, or if you have had sex without using the 2 recommended forms of birth control within 3 years of taking acitretin.

Acitretin can pass into breast milk and harm a nursing baby. Do not take acitretin if you are breast-feeding a baby.

Uses For acitretin

Acitretin is used to treat severe skin disorders, such as psoriasis. It works by allowing normal growth and development of the skin. Acitretin will continue to work after you stop taking it, but after a time, the skin condition returns and you may need to take it again.

Acitretin must not be used to treat women who are able to bear children unless other forms of treatment have been tried first and have failed. Acitretin must not be taken during pregnancy because it causes birth defects in humans. If you are able to bear children, it is very important that you read, understand, and follow the pregnancy warnings for acitretin.

acitretin is available only with your doctor's prescription.

Precautions While Using acitretin

It is important that your doctor check your progress at regular visits to make sure that acitretin is working properly. Blood tests may be needed to check for unwanted effects.

Using acitretin while you are pregnant can cause very serious birth defects. You must use 2 forms of birth control together for 1 month before starting acitretin, for the entire time that you are being treated with acitretin, and for 3 years after you take your last dose of acitretin. You will need to have 2 negative pregnancy tests to be sure that you are not pregnant before you start using acitretin. You will also need to have pregnancy tests every month during treatment, and every 3 months for 3 years after you stop taking the medicine. If you think you have become pregnant while using acitretin, stop taking it and call your doctor right away.

Do not use methotrexate (Rheumatrex®, Trexall®) or a tetracycline medicine to treat an infection (such as doxycycline, minocycline, tetracycline, Minocin®, or Vibramycin®) while you are using acitretin. Using these medicines together may cause unwanted side effects.

Do not take other medicines without checking first with your doctor. This includes vitamins, herbal products, prescription or nonprescription (over-the-counter [OTC]) medicines. Some of these medicines or nutritional supplements (eg, St. John's wort) may make your birth control pills not work.

Do not take vitamin A or any supplement containing vitamin A while you are using acitretin, unless otherwise directed by your doctor. To do so may increase the chance of side effects.

Your skin condition may improve or get worse during the first few weeks of treatment and you also may notice some skin irritation from the medicine. With continued use, the expected skin irritation will lessen after a few weeks. Check with your doctor if the skin irritation becomes worse or if your skin condition does not improve within 8 to 12 weeks.

Women who are able to bear children must avoid all forms of alcohol while they are taking acitretin and for 2 months after they stop. Do not eat foods, drink beverages, or take medicines that contain alcohol. Drinking alcohol will make the medicine remain in the body for an extended period of time and will increase the chance for side effects. If a woman consumes alcohol during acitretin treatment, she should consider delaying a pregnancy for longer than 2 to 3 years. Talk to your doctor if you have any questions about this.

Do not donate blood during treatment with acitretin, for 3 years following treatment, or as otherwise directed by your doctor. Women who are able to bear children must not receive blood containing the medicine.

Liver problems may occur while you are using acitretin. Check with your doctor right away if you are having more than one of these symptoms: abdominal or stomach pain or tenderness, clay-colored stools, dark urine, decreased appetite, fever, headache, itching, loss of appetite, nausea and vomiting, skin rash, swelling of the feet or lower legs, unusual tiredness or weakness, or yellow eyes or skin.

Acitretin may cause bone or muscle problems, including joint pain, muscle pain or stiffness, or difficulty moving. You may get hurt more easily during rough sports. You may heal more slowly.

Acitretin may cause blurred vision or a decrease in night vision (night blindness). The night blindness may occur suddenly. Do not drive, use machines, or do anything else that could be dangerous if you are not able to see well. Check with your doctor right away if you have vision changes.

Acitretin may cause dry eyes. Wearing contact lenses may become uncomfortable while using acitretin. To help relieve dry eyes, check with your doctor about using a lubricating solution, such as artificial tears. If severe eye irritation or inflammation occurs, check with your doctor.

Acitretin may cause dryness of the mouth, nose, and throat. For temporary relief of mouth dryness, use sugarless candy or gum, melt bits of ice in your mouth, or use a saliva substitute. However, if dry mouth continues for more than 2 weeks, check with your medical doctor or dentist. Continuing dryness of the mouth may increase the chance of developing dental disease, including tooth decay, gum disease, and fungus infections.

Avoid exposing your skin to wind, cold weather, and sunlight, even on cloudy days. Your skin will be more prone to sunburn, dryness, or irritation, especially during the first 2 or 3 weeks. You should not stop taking acitretin, unless the skin irritation becomes too severe. Do not use a sunlamp or tanning bed. Use sunscreen or sunblock lotions with a sun protection factor (SPF) of at least 15 on a regular basis. Wear protective clothing and hats and stay out of direct sunlight, especially between the hours of 10 a.m. and 3 p.m.

Unless your doctor tells you otherwise, you should avoid skin products that can irritate the skin. Some examples are:

  • Any topical acne product or skin product containing a peeling agent (eg, benzoyl peroxide, resorcinol, salicylic acid, or sulfur).
  • Hair products that are irritating, such as permanents or hair removal products.
  • Skin products that cause sensitivity to the sun, such as those containing spices or limes.
  • Skin products containing a large amount of alcohol, such as astringents, shaving creams, or after-shave lotions.
  • Skin products that are too drying or abrasive, such as some cosmetics, soaps, or skin cleansers.

For diabetic patients:

  • acitretin may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests or if you have any questions, check with your doctor.

Pancreatitis may occur while you are using acitretin. Tell your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

Acitretin may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you or your caregiver notice any of these side effects, check with you doctor right away.

Call your doctor right away if you have a fever, cloudy urine, decrease or increase in the amount of urine, fainting or lightheadedness, nausea, stomach pain, or swelling of hands, ankles, feet, or lower legs. These may be symptoms of a rare but serious condition called capillary leak syndrome.

acitretin Side Effects

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
  • Back pain
  • bad, unusual, or unpleasant (after) taste
  • bone or joint pain
  • change in taste
  • continuing ringing or buzzing or other unexplained noise in the ears
  • difficulty with moving or walking
  • excessive muscle tone
  • feeling of warmth
  • headache (severe and continuing)
  • hearing loss
  • increased sensitivity to pain
  • increased sensitivity to touch
  • muscle stiffness
  • muscle tension or tightness
  • nausea or vomiting (severe and continuing)
  • redness of the face, neck, arms, and occasionally, upper chest
  • redness of the skin
  • sleeplessness
  • stiff, painful muscles
  • thinning of the skin with easy bruising
  • tingling in the hands and feet
  • tongue irritation
  • trouble sleeping
  • unable to sleep
Less common
  • Acid or sour stomach
  • blurred vision
  • belching
  • breast pain
  • eye pain
  • eye problems, such as loss of eyebrows or eyelashes, redness or swelling of the eyelid, redness of the eyes, sensitivity of the eyes to light, or watery eyes
  • general feeling of discomfort or illness
  • heartburn
  • increased hair growth on the forehead, back, arms, and legs
  • indigestion
  • itching of the vagina or genital area
  • loosening of the fingernails
  • pain during sexual intercourse
  • redness or soreness around the fingernails
  • sore mouth or tongue
  • thick, white vaginal discharge with no odor or with a mild odor
  • white patches in the mouth or on the tongue
Rare
  • Abdominal or stomach pain
  • bleeding gums
  • bleeding time increased
  • chest pain
  • coughing, hoarseness, trouble in speaking, or flu-like symptoms
  • coughing up blood
  • darkened urine
  • diarrhea
  • difficulty in breathing or swallowing
  • double vision or other problems in seeing, including decreased night vision after sunset and before sunrise
  • increased menstrual flow or vaginal bleeding
  • itchy or painful ears
  • light-colored stools
  • nosebleeds
  • pale or cold hands or feet
  • paralysis
  • prolonged bleeding from cuts
  • red or dark brown urine
  • shortness of breath
  • skin problems, such as abnormal sensation of burning or stinging, cracking, redness, skin irritation or rash (including a rash that looks like psoriasis), infection, ulcers, unusual odor, or small red spots in the skin
  • sore on the edge of the eyelid (stye)
  • thick, white, curd-like vaginal discharge
  • unpleasant breath odor
  • unusual tiredness or weakness
  • vaginal itching or irritation
  • vomiting of blood
  • yellowing of the skin or eyes
Incidence not known
  • Assault
  • attack
  • burning, numbness, tingling, or painful sensations
  • chest pain or discomfort
  • confusion
  • difficulty with breathing
  • difficulty with speaking
  • doing things to injure oneself
  • force
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • pain in the chest, groin, or legs, especially calves
  • pain or discomfort in the arms, jaw, back, or neck
  • shortness of breath
  • slow speech
  • slurred speech
  • sudden loss of coordination
  • sudden, severe weakness or numbness in the arms or legs
  • sudden, unexplained shortness of breath
  • sweating
  • thoughts of killing oneself
  • unsteadiness or awkwardness
  • vision changes
  • weakness in the arms, hands, legs, or feet

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

Symptoms of overdose
  • Dizziness or lightheadedness
  • feeling of constant movement of self or surroundings
  • 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
  • Chapped, red, or swollen lips
  • difficulty in wearing contact lenses
  • dry or runny nose
  • dryness of the eyes
  • increased ability to sunburn
  • increased amount of ear wax (unusual)
  • irritation in the mouth or swollen gums
  • itchy skin
  • loss of hair (usually reversible)
  • nosebleeds
  • scaling and peeling of the eyelids, fingertips, palms, and soles of feet
  • sticky skin
  • unusual thirst
Less common
  • Constipation
  • diarrhea
  • increased sweating
Incidence not known
  • Cracking fingernails or fingernails break easily
  • 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.

Use Labeled Indications

Psoriasis: Treatment of severe psoriasis in adults.

Limitations of use: Not for the treatment of acne.

Canadian labeling: Additional uses (not in U.S. labeling): Other disorders of keratinization

Administration

Administer with food, preferably with the main meal of the day.

Dietary Considerations

Take with food. Avoid ingestion of additional sources of exogenous vitamin A (in excess of RDA); use of ethanol and ethanol-containing products is contraindicated.

Drug Interactions

Alcohol (Ethyl): May enhance the teratogenic effect of Acitretin. Avoid combination

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy

Contraceptives (Estrogens): Retinoic Acid Derivatives may diminish the therapeutic effect of Contraceptives (Estrogens). Two forms of contraception are recommended in females of child-bearing potential during retinoic acid derivative therapy. Monitor therapy

Contraceptives (Progestins): Acitretin may diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Given the potential for progestin-only preparations to fail to prevent pregnancy during acitretin therapy, such products should not be relied upon. Alternative, nonhormonal forms of contraception must be employed during acitretin therapy. Consider therapy modification

Methotrexate: Acitretin may enhance the hepatotoxic effect of Methotrexate. Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination

Multivitamins/Minerals (with AE, No Iron): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Tetracycline Derivatives: May enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Avoid combination

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vitamin A: May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination

Adverse Reactions

>10%:

Central nervous system: Hyperesthesia (10% to 25%), paresthesia (10% to 25%), rigors (10% to 25%)

Dermatologic: Cheilitis (>75%), alopecia (50% to 75%), exfoliation of skin (50% to 75%), xeroderma (25% to 50%), nail disease (25% to 50%), pruritus (25% to 50%), erythematous rash (10% to 25%), paronychia (10% to 25%), skin atrophy (10% to 25%), acquired cutaneous adherence (10% to 25%)

Endocrine & metabolic: Hypertriglyceridemia (50% to 75%), increased serum glucose (fasting; 25% to 50%), decreased HDL cholesterol (25% to 50%), hypercholesterolemia (25% to 50%), acetonuria (10% to 25%), decreased serum glucose (fasting; 10% to 25%), decreased serum magnesium (10% to 25%), hypermagnesemia (10% to 25%), hyperphospheremia (10% to 25%), increased gamma-glutamyl transferase (10% to 25%), increased serum potassium (10% to 25%), increased serum sodium (10% to 25%), increased uric acid (10% to 25%)

Gastrointestinal: Xerostomia (10% to 25%)

Genitourinary: Erythrocyturia (10% to 25%), hematuria (10% to 25%)

Hematologic & oncologic: Leukocyturia (25% to 50%), reticulocytosis (25% to 50%), increased haptoglobin (10% to 25%), decreased hematocrit (10% to 25%), decreased hemoglobin (10% to 25%), increased neutrophils (10% to 25%), change in WBC count (10% to 25%)

Hepatic: Increased liver enzymes (25% to 50%), increased serum alkaline phosphatase (10% to 25%), increased direct serum bilirubin (10% to 25%)

Neuromuscular & skeletal: Increased creatine phosphokinase (25% to 50%), arthralgia (10% to 25%), spinal hyperostosis (progression; 10% to 25%)

Ophthalmic: Xerophthalmia (10% to 25%)

Respiratory: Rhinitis (25% to 50%), epistaxis (10% to 25%)

1% to 10%:

Cardiovascular: Edema, flushing

Central nervous system: Bell's palsy, depression, drowsiness, fatigue, headache, hypertonia, insomnia, pain

Dermatologic: Abnormal hair texture, abnormal skin odor, Bullous skin disease, cold and clammy skin, dermatitis, diaphoresis (increased), madarosis, psoriasiform eruption, pyogenic granuloma, seborrhea, skin fissure, skin rash, sunburn

Endocrine & metabolic: Decreased haptoglobins, decreased serum albumin, decreased serum calcium, decreased serum iron, decreased serum potassium, decreased serum sodium, diaphoresis (increased), glycosuria, hot flash, hyperchloremia, hypochloremia, hypophosphatemia, increased serum albumin, increased serum calcium, increased serum iron, increased thirst

Gastrointestinal: Abdominal pain, anorexia, aphthous stomatitis, diarrhea, dysgeusia, gingival hemorrhage, gingivitis, increased appetite, nausea, sialorrhea, stomatitis, tongue disease

Genitourinary: Proteinuria

Hematologic & oncologic: Change in RBC count, decreased neutrophils, increased hematocrit, increased hemoglobin, reticulocytopenia, purpura

Hepatic: Increased serum bilirubin

Neuromuscular & skeletal: Arthritis, back pain, myalgia, ostealgia, osteoarthritis, peripheral joint hyperostosis

Ophthalmic: Blepharitis, blurred vision, cataract, conjunctivitis, diplopia, epithelial keratopathy, eye pain, nocturnal amblyopia, photophobia

Otic: Otalgia, tinnitus

Renal: Increased blood urea nitrogen, increased serum creatinine

Respiratory: Sinusitis

Miscellaneous: Ulcer

<1% (Limited to important or life-threatening): Abnormal gait, abnormal lacrimation, acne vulgaris, ageusia, aggressive behavior, alcohol intolerance, anal disease, bone disease, bursitis (olecranon), candidiasis, capillary leak syndrome, cerebrovascular accident, chalazion, conjunctival hemorrhage, constipation, corneal lesion, corneal ulcer, cutaneous nodule, cyanosis, cyst, deafness, decreased libido, dyspepsia, dysuria, ectropion, epidermal thinning, exfoliative dermatitis, flu-like symptoms, fungal infection, furunculosis, gastritis, gingival hyperplasia, glossitis, hair discoloration, hepatic cirrhosis, hepatic dysfunction, hepatitis, herpes simplex infection, hordeolum (recurrent), hyperkeratosis, hypersensitivity reaction, hypertrichosis, hypoesthesia, increased bronchial secretions, increased cerumen production, intermittent claudication, laryngitis, leukorrhea, mastalgia, melena, migraine, myasthenia, myocardial infarction, myopathy (with peripheral neuropathy), nail disease (fragility), neuritis, otitis media, pancreatitis, papilledema, peripheral ischemia, pharyngitis, prolonged bleeding time, pseudotumor cerebri, skin hypertrophy, skin photosensitivity, spinal hyperostosis (new lesion), suicidal ideation, tendonitis, tenesmus, thromboembolism, tongue ulcer, vaginitis, voice disorder, warts, weight gain, wound healing impairment

ALERT U.S. Boxed Warning

Pregnancy:

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 etretinate and acitretin. Potentially, any fetus exposed can be affected.

Clinical evidence has shown that concurrent ingestion of acitretin and ethanol has been associated with the formation of etretinate, which has a significantly longer elimination half-life than acitretin. Because the longer elimination half-life of etretinate would increase the duration of teratogenic potential for female patients, ethanol must not be ingested by female patients of childbearing potential either during treatment with acitretin or for 2 months after cessation of therapy. This allows for elimination of acitretin, thus removing the substrate for transesterification to etretinate. The mechanism of the metabolic process for conversion of acitretin to etretinate has not been fully defined. It is not known whether substances other than ethanol are associated with transesterification.

Acitretin has been shown to be embryotoxic and/or teratogenic in rabbits, mice, and rats at doses of 0.6, 3, and 15 mg/kg, respectively. These doses are approximately 0.2, 0.3, and 3 times the maximum recommended therapeutic dose, respectively, based on a mg/m2 comparison.

Major human fetal abnormalities associated with acitretin and/or etretinate administration have been reported, including meningomyelocele, meningoencephalocele, multiple synostoses, facial dysmorphia, syndactyly, absence of terminal phalanges, malformations of hip, ankle and forearm, low-set ears, high palate, decreased cranial volume, cardiovascular malformation, and alterations of the skull and cervical vertebrae.

Acitretin should be prescribed only by those who have special competence in the diagnosis and treatment of severe psoriasis, are experienced in the use of systemic retinoids, and understand the risk of teratogenicity.

Because of the teratogenicity of acitretin, a program called the Do Your P.A.R.T program (Pregnancy Prevention Actively Required During and After Treatment), has been developed to educate women of childbearing potential and their health care 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 Do Your P.A.R.T. program requirements and program materials are available at http://www.soriatane.com/doyour-part-Program.html or may be requested by calling 1-888-784- 3335 (1-888-STIEFEL).

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 milliunits/mL before receiving the initial acitretin prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue acitretin therapy. The second pregnancy test (a confirmation test) should be done during the first 5 days of the menstrual period immediately preceding the beginning of acitretin therapy. 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). If the second pregnancy test is negative, initiation of treatment should begin within 7 days of the specimen collection. Acitretin should be limited to a monthly supply.

Must have a pregnancy test with a sensitivity of at least 25 milliunits/mL 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 monthly supply of the drug should be prescribed. For at least 3 years after discontinuing therapy, 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.

Patients must use 2 effective forms of contraception (birth control) simultaneously for at least 1 month prior to initiation of acitretin therapy, during acitretin therapy, and for at least 3 years after discontinuing acitretin therapy. A contraception counseling referral form is available so that patients can receive an initial free contraception counseling session and pregnancy testing. Counseling about contraception and behaviors associated with an increased risk of pregnancy must be repeated on a monthly basis by the prescriber during acitretin therapy and every 3 months for at least 3 years following discontinuation of acitretin. Effective forms of contraception include both primary and secondary forms of contraception. Primary forms of contraception include the following: 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) and vaginal sponges (contains spermicide). Any birth control method can fail. Therefore, it is critically important that women of childbearing potential use 2 effective forms of contraception (birth control) simultaneously. 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 preparations. Microdosed “minipill” progestin preparations are not recommended for use with acitretin. It is not known whether other progestin-only 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 because 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, and 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 treatment.

If pregnancy does occur during acitretin therapy or at any time for at least 3 years following discontinuation of acitretin therapy, the prescriber and patient should discuss the possible effects on the pregnancy. The available information is as follows:

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. Because this threshold has not been established for acitretin in humans and because elimination rates vary among patients, the duration of posttherapy contraception to achieve adequate elimination cannot be calculated precisely. It is strongly recommended that contraception be continued for at least 3 years after stopping treatment with acitretin, based on the following considerations:

In the absence of transesterification to form etretinate, greater than 98% of the acitretin would be eliminated within 2 months, assuming a mean elimination half-life of 49 hours.

In cases where etretinate is formed, as has been demonstrated with concomitant administration of acitretin and ethanol, greater than 98% of the etretinate formed would be eliminated in 2 years, assuming a mean elimination half-life of 120 days, and greater than 98% of the etretinate formed would be eliminated in 3 years, based on the longest demonstrated elimination half-life of 168 days. However, etretinate was found in plasma and subcutaneous fat in 1 patient reported to have had sporadic alcohol intake, 52 months after she stopped acitretin therapy.

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. These cases have been reported both prospectively (before the outcome was known) and retrospectively (after the outcome was known). The events below are listed without distinction as to whether the reported birth defects are consistent with retinoid-induced embryopathy or not.

There have been 318 prospectively reported cases involving pregnancies and the use of etretinate, acitretin, or both. In 238 of these cases, the conception occurred after the last dose of etretinate (103 cases), acitretin (126), or both (9). Fetal outcome remained unknown in approximately one-half of these cases, of which 62 were terminated and 14 were spontaneous abortions. Fetal outcome is known for the other 118 cases and 15 of the outcomes were abnormal (including cases of absent hand/wrist, clubfoot, GI malformation, hypocalcemia, hypotonia, limb malformation, neonatal apnea/anemia, neonatal ichthyosis, placental disorder/death, undescended testicle, and 5 cases of premature birth). In the 126 prospectively reported cases where conception occurred after the last dose of acitretin only, 43 cases involved conception at least 1 year but less than 2 years after the last dose. There were 3 reports of abnormal outcomes out of these 43 cases (involving limb malformation, GI tract malformations, and premature birth). There were only 4 cases where conception occurred at least 2 years after the last dose but there were no reports of birth defects in these cases.

There is also a total of 35 retrospectively reported cases where conception occurred at least 1 year after the last dose of etretinate, acitretin, or both. From these cases, there are 3 reports of birth defects when the conception occurred at least 1 year but less than 2 years after the last dose of acitretin (including heart malformations, Turner syndrome, and unspecified congenital malformations) and 4 reports of birth defects when conception occurred 2 or more years after the last dose of acitretin (including foot malformation, cardiac malformations [2 cases], and unspecified neonatal and infancy disorder). There were 3 additional abnormal outcomes in cases where conception occurred 2 or more years after the last dose of etretinate (including chromosome disorder, forearm aplasia, and stillbirth).

Females who have taken etretinate must continue to follow the contraceptive recommendations for etretinate. Etretinate is no longer marketed in the United States; for information, call the manufacturer at 1-888-784-3335 (1-888-STIEFEL).

Patients should not donate blood during and for at least 3 years following the completion of acitretin therapy because women of childbearing potential must not receive blood from patients being treated with acitretin.

Important information for males taking acitretin:

Patients should not donate blood during and for at least 3 years following acitretin therapy because women of childbearing potential must not receive blood from patients being treated with acitretin.

Samples of seminal fluid from 3 male patients treated with acitretin and 6 male patients treated with etretinate have been assayed for the presence of acitretin. The maximum concentration of acitretin observed in the seminal fluid of these men was 12.5 ng/mL. Assuming an ejaculate volume of 10 mL, the amount of drug transferred in semen would be 125 ng, which is 1/200,000 of a single 25 mg capsule. Thus, although it appears that residual acitretin in seminal fluid poses little, if any, risk to a fetus while a male patient is taking the drug or after it is discontinued, the no-effect limit for teratogenicity is unknown and there is no registry for birth defects associated with acitretin. The available data are as follows:

There have been 25 cases of reported conception when the male partner was taking acitretin. The pregnancy outcome is known in 13 of these 25 cases. Of these, 9 reports were retrospective and 4 were prospective (meaning the pregnancy was reported prior to knowledge of the outcome).

When acitretin treatment was given at time of conception, there were 5 deliveries of healthy neonates (4 of 5 cases were prospective), 5 spontaneous abortions, and 1 induced abortion.

When acitretin was discontinued approximately 4 weeks prior to conception, there was 1 induced abortion (with malformation pattern not typical of retinoid embryopathy [bilateral cystic hygromas of neck, hypoplasia of lungs bilateral, pulmonary atresia, ventricular septal defect with overriding truncus arteriosus]).

When acitretin was discontinued approximately 6 to 8 months prior to conception, there was 1 spontaneous abortion.

Medication guide (for all patients):

An acitretin Medication Guide must be given to the patient each time acitretin is dispensed, as required by law.

Hepatotoxicity:

Of the 525 patients treated in US clinical trials, 2 had clinical jaundice with elevated serum bilirubin and transaminases considered related to acitretin treatment. Liver function test results in these patients returned to normal after acitretin was discontinued. Two of the 1,289 patients treated in European clinical trials developed biopsy-confirmed toxic hepatitis. A second biopsy in 1 of these patients revealed nodule formation suggestive of cirrhosis. One patient in a Canadian clinical trial of 63 patients developed a 3-fold increase of transaminases. A liver biopsy of this patient showed mild lobular disarray, multifocal hepatocyte loss, and mild triaditis of the portal tracts compatible with acute reversible hepatic injury. The patient's transaminase levels returned to normal 2 months after acitretin was discontinued.

The potential of acitretin therapy to induce hepatotoxicity was prospectively evaluated using liver biopsies in an open-label study of 128 patients. Pretreatment and posttreatment biopsies were available for 87 patients. A comparison of liver biopsy findings before and after therapy revealed 58% of patients showed no change, 25% improved, and 17% of patients had a worsening of their liver biopsy status. For 6 patients, the classification changed from class 0 (no pathology) to class I (normal fatty infiltration; nuclear variability and portal inflammation; both mild); for 7 patients, the change was from class I to class II (fatty infiltration, nuclear variability, portal inflammation and focal necrosis; all moderate to severe); and for 1 patient, the change was from class II to class IIIb (fibrosis, moderate to severe). No correlation could be found between liver function test result abnormalities and the change in liver biopsy status, and no cumulative dose relationship was found.

Elevations of AST, ALT, gamma-glutamyl transpeptidase (GGT; GGTP), or lactate dehydrogenase (LDH) have occurred in approximately 1 in 3 patients treated with acitretin. Of the 525 patients treated in clinical trials in the United States, treatment was discontinued in 3.8% of patients due to elevated liver function test results. If hepatotoxicity is suspected during treatment with acitretin, the drug should be discontinued and the etiology further investigated.

Ten of 652 patients treated in US clinical trials of etretinate, of which acitretin is the active metabolite, had clinical or histologic hepatitis considered to be possibly or probably related to etretinate treatment. There have been reports of hepatitis-related deaths worldwide; a few of these patients had received etretinate for 1 month or less before presenting with hepatic symptoms or signs.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience rhinorrhea, nail changes, dry mouth, dry lips, dry eyes, itching, or hair loss. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of capillary leak syndrome (abnormal heartbeat; angina; shortness of breath; weight gain; vomiting blood or vomit that looks like coffee grounds; black, tarry, or bloody stools; urinary retention or change in amount of urine passed; or hematuria), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of high blood sugar (confusion, fatigue, increased thirst, hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), anger, behavioral changes, angina, severe dizziness, passing out, severe headache, nausea, vomiting, seizures, burning or numbness feeling, severe muscle pain, severe muscle weakness, bone pain, joint pain, vision changes, eye pain, severe eye irritation, contact lens discomfort, hearing impairment, tinnitus, edema, weight gain, severe diarrhea, rectal bleeding, rectal pain, poor night vision, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Indications

SORIATANE is indicated for the treatment of severe psoriasis in adults. Because of significant adverse effects associated with its use, SORIATANE should be prescribed only by those knowledgeable in the systemic use of retinoids. In females of reproductive potential, SORIATANE should be reserved for non-pregnant patients who are unresponsive to other therapies or whose clinical condition contraindicates the use of other treatments (see BOXED CONTRAINDICATIONS AND WARNINGSSORIATANE can cause severe birth defects).

Most patients experience relapse of psoriasis after discontinuing therapy. Subsequent courses, when clinically indicated, have produced efficacy results similar to the initial course of therapy.

Overdose

In the event of acute overdosage, SORIATANE must be withdrawn at once. Symptoms of overdose are identical to acute hypervitaminosis A (e.g., headache and vertigo). The acute oral toxicity (LD50) of acitretin in both mice and rats was greater than 4,000 mg per kg.

In one reported case of overdose, a 32-year-old male with Darier's disease took 21 x 25-mg capsules (525-mg single dose). He vomited several hours later but experienced no other ill effects.

All female patients of childbearing potential who have taken an overdose of SORIATANE must: 1) Have a pregnancy test at the time of overdose; 2) Be counseled as per the boxed CONTRAINDICATIONS AND WARNINGS AND PRECAUTIONS sections regarding birth defects and contraceptive use for at least 3 years' duration after the overdose.

Acitretin Brand Names

Acitretin may be found in some form under the following brand names:

  • Soriatane

Usual Adult Dose for Psoriasis

Initial dose: 25 to 50 mg orally once a day, administered as a single dose with main meal
Maintenance dose: 25 to 50 mg orally once a day, administered upon an individual patient's response to initial treatment

Comments: When used with phototherapy, the healthcare provider should decrease the phototherapy dose, dependent on the patient's individual response.

Use: Treatment of severe psoriasis in adults

Administrative Information

LactMed Record Number

490

Last Revision Date

20140515

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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