Side Effects of Soriatane (acitretin)

Soriatane (acitretin) is a retinoid used to treat severe psoriasis in adults. Soriatane should be prescribed only by doctors who have experience in the systemic use of retinoids because it has serious side effects.

Common side effects of Soriatane include:

• inflammation of the lips,
• hair loss,
• increased triglyceride levels,
• skin peeling,
• dry skin,
• itching,
• cold symptoms,
• joint pain, and
• dry mouth.

Other side effects of Soriatane include:

• increased levels of liver enzymes;
• changes in phosphorus, potassium, sodium, and magnesium levels;
• nosebleeds,
• rash, and
• increased sun sensitivity.

Serious side effects of Soriatane include:

• birth defects,
• liver toxicity,
• dry eyes,
• pancreatitis,
• pseudotumor cerebri (increased pressure of the fluid in the brain), and
• skeletal abnormalities.

Drug interactions of Soriatane include alcohol, which increases conversion of acitretin to etretinate, which remains in the body much longer and is also harmful to a fetus. 

Soriatane may increase the effects of glyburide on blood glucose and potentially cause hypoglycemia. 

Soriatane reduces the effect of the microdose progestin minipill. 

Soriatane should not be combined with methotrexate due to increased risk of liver failure. 

Combining tetracycline with Soriatane increases intracranial pressure. 

Taking vitamin A supplements may increase side effects of Soriatane. 

If phototherapy also is being used as treatment, the doses of phototherapy should be reduced to avoid excessive burning of the skin. 

Soriatane is harmful to a fetus and it must not be used during pregnancy. Women must use 2 effective forms of birth control simultaneously for at least 1 month prior to starting Soriatane therapy, during therapy, and for at least 3 years after stopping treatment. 

Soriatane should not be used by women who are breastfeeding because it can pass into breast milk and harm the infant.

Common side effects of Soriatane include:

• Inflammation of the lips (cheilitis)
• Hair loss
• Increased triglyceride levels
• Skin peeling
• Dry skin (25%-50%)
• Itching
• Cold symptoms
• Joint pain
• Dry mouth

Other side effects of Soriatane include:

• Increased levels of liver enzymes
• Changes in phosphorus, potassium, sodium, and magnesium levels
• Nosebleeds
• Rash
• Increased sun sensitivity

Other less common side effects of Soriatane include:

• Water retention
• Headache
• Nausea
• Vomiting
• Insomnia
• Diarrhea
• Flushing
• Depression
• Fatigue
• Gingivitis
• Increased appetite
• Possible serious side effects include:
• Birth defects (Please see the pregnancy and breastfeeding safety section.)
• Liver toxicity
• Dry eyes (xerophthalmia)
• Pancreatitis
• Pseudotumor cerebri (increased pressure of the fluid in the brain)
• Skeletal abnormalities

Since acitretin can cause liver damage, liver function tests should be performed before treatment at 1- to 2-week intervals until stable, and thereafter at intervals as clinically needed

Hypervitaminosis A produces a wide spectrum of signs and symptoms primarily of the mucocutaneous, musculoskeletal, hepatic, neuropsychiatric, and central nervous systems. Many of the clinical adverse reactions reported to date with administration of Soriatane resemble those of the hypervitaminosis A syndrome.

Adverse Events/Postmarketing Reports

In addition to the events listed in the tables for the clinical trials, the following adverse events have been identified during postapproval use of Soriatane. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular: Acute myocardial infarction, thromboembolism, stroke.

Immune System Disorders: Hypersensitivity, including angioedema and urticaria.

Nervous System: Myopathy with peripheral neuropathy has been reported during therapy with Soriatane. Both conditions improved with discontinuation of the drug.

Psychiatric: Aggressive feelings and/or suicidal thoughts have been reported. These events, including self-injurious behavior, have been reported in patients taking other systemically administered retinoids, as well as in patients taking Soriatane. Since other factors may have contributed to these events, it is not known if they are related to Soriatane.

Reproductive: Vulvo-vaginitis due to Candida albicans.

Skin and Appendages: Thinning of the skin, skin fragility, and scaling may occur all over the body, particularly on the palms and soles; nail fragility is frequently observed. Madarosis and exfoliative dermatitis/erythroderma have been reported.

Vascular Disorders: Capillary leak syndrome.

Clinical Trials

During clinical trials with Soriatane, 513 of 525 (98%) subjects reported a total of 3,545 adverse events. One-hundred sixteen subjects (22%) left trials prematurely, primarily because of adverse experiences involving the mucous membranes and skin. Three subjects died. Two of the deaths were not drug-related (pancreatic adenocarcinoma and lung cancer); the other subject died of an acute myocardial infarction, considered remotely related to drug therapy.  In clinical trials, Soriatane was associated with elevations in liver function test results or triglyceride levels and hepatitis.

The tables below list by body system and frequency the adverse events reported during clinical trials of 525 subjects with psoriasis.

Table 3. Adverse Events Frequently Reported during Clinical Trials Percent of Subjects Reporting (N = 525)

Table 4. Adverse Events Less Frequently Reported during Clinical Trials (Some of Which May Bear No Relationship to Therapy) Percent of Subjects Reporting (N = 525)

Laboratory

Therapy with Soriatane induces changes in liver function tests in a significant number of patients. Elevations of AST (SGOT), ALT (SGPT) or LDH were experienced by approximately 1 in 3 subjects treated with Soriatane. In most subjects, elevations were slight to moderate and returned to normal either during continuation of therapy or after cessation of treatment. In subjects receiving Soriatane during clinical trials, 66% and 33% experienced elevation in triglycerides and cholesterol, respectively. Decreased high density lipoproteins (HDL) occurred in 40%. Transient, usually reversible elevations of alkaline phosphatase have been observed.

Table 5 lists the laboratory abnormalities reported during clinical trials.

Table 5. Abnormal Laboratory Test Results Reported during Clinical Trials Percent of Subjects Reporting

Ethanol

Clinical evidence has shown that etretinate can be formed with concurrent ingestion of acitretin and ethanol.

Glyburide

In a trial of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose-lowering effect of glyburide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the trial with 6 healthy male volunteers in the absence of glyburide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with Soriatane is recommended.

Hormonal Contraceptives

It has not been established if there is a pharmacokinetic interaction between acitretin and combined oral contraceptives. However, it has been established that acitretin interferes with the contraceptive effect of microdosed progestin “minipill” preparations. Microdosed “minipill” progestin preparations are not recommended for use with Soriatane. It is not known whether other progestin-only contraceptives, such as implants and injectables, are adequate methods of contraception during acitretin therapy.

Methotrexate

An increased risk of hepatitis has been reported to result from combined use of methotrexate and etretinate. Consequently, the combination of methotrexate with acitretin is also contraindicated.

Phenytoin

If acitretin is given concurrently with phenytoin, the protein binding of phenytoin may be reduced.

Tetracyclines

Since both acitretin and tetracyclines can cause increased intracranial pressure, their combined use is contraindicated.

Vitamin A And Oral Retinoids

Concomitant administration of vitamin A and/or other oral retinoids with acitretin must be avoided because of the risk of hypervitaminosis A.

Other

There appears to be no pharmacokinetic interaction between acitretin and cimetidine, digoxin, or glyburide. Investigations into the effect of acitretin on the protein binding of anticoagulants of the coumarin type (warfarin) revealed no interaction.