Usage
Acitretin is prescribed for severe recalcitrant psoriasis, Darier’s disease (keratosis follicularis), and severe congenital ichthyosis. It falls under the pharmacological classification of retinoids, specifically, a synthetic retinoid. Acitretin modulates cell proliferation and differentiation, normalizing epidermal cell growth.
Alternate Names
The International Nonproprietary Name (INN) is acitretin. Brand names include Neotigason and Soriatane.
How It Works
Pharmacodynamics: Acitretin is a metabolite of etretinate, which is stored in adipose tissue and slowly releases acitretin. It binds to retinoic acid receptors (RARs) and retinoid X receptors (RXRs) in the nucleus, influencing gene expression related to cell differentiation, proliferation, and inflammation in the skin.
Pharmacokinetics: Acitretin is well-absorbed orally, enhanced by food. It’s metabolized in the liver, with some enterohepatic recirculation. Elimination is primarily via hepatic metabolism and biliary excretion, with a small amount in urine. The terminal elimination half-life is about 50 hours for acitretin and two days for its major metabolite.
Dosage
Standard Dosage
Adults:
Initial: 25 to 50 mg orally once daily with the main meal.
Maintenance: 25 to 50 mg orally daily, adjusted based on individual response and tolerability. Maximum dose: 75 mg/day.
Children:
Not recommended unless alternative treatments have failed. If used, dose is weight-based, starting at 0.5 mg/kg/day, up to a maximum of 1 mg/kg/day (not to exceed 35 mg/day). Close monitoring of musculoskeletal development and growth is essential. Maintenance doses are kept as low as possible.
Special Cases:
- Elderly Patients: Start at the lower end of the dosing range (25 mg/day), increasing cautiously due to potential decreased hepatic, renal, or cardiac function.
- Patients with Renal Impairment: Contraindicated in severe renal impairment. Dose adjustments needed in moderate renal impairment.
- Patients with Hepatic Dysfunction: Contraindicated in severe hepatic dysfunction. Careful consideration and potential dose reduction in mild to moderate hepatic dysfunction.
- Patients with Comorbid Conditions: Monitor closely, especially those with diabetes, cardiovascular disease, or hyperlipidemia. Dose adjustment may be necessary.
Clinical Use Cases
Acitretin is not indicated for use in the context of intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations. Its primary indication is for chronic dermatological conditions.
Side Effects
Common Side Effects:
Dry lips, skin, eyes, and mucous membranes; cheilitis; hair thinning; nail fragility; itching; increased photosensitivity; headache; myalgia; elevated triglycerides and cholesterol.
Rare but Serious Side Effects:
Hepatotoxicity; pseudotumor cerebri (benign intracranial hypertension); skeletal hyperostosis; premature epiphyseal closure in children; depression; suicidal ideation; pancreatitis; hyperlipidemia.
Long-Term Effects:
Bone changes (hyperostosis, premature epiphyseal closure in children); liver damage; vision changes.
Contraindications
Absolute: Pregnancy; breastfeeding; severe hepatic or renal impairment; concomitant use of methotrexate, tetracyclines, or other retinoids; hypersensitivity to acitretin.
Relative: Women of childbearing potential not adhering to strict contraception; pre-existing hyperlipidemia; diabetes; alcoholism.
Drug Interactions
- Vitamin A: Increased risk of hypervitaminosis A.
- Methotrexate, Tetracyclines: Increased risk of hepatotoxicity and pseudotumor cerebri.
- Minipills (progestin-only birth control): Reduced efficacy of contraception.
- Phenytoin: Increased phenytoin side effects.
- Alcohol: Women of childbearing age must not consume alcohol during treatment or for two months after stopping, as it can convert acitretin to etretinate, which has a much longer half-life.
Pregnancy and Breastfeeding
Pregnancy Category X. Acitretin is highly teratogenic. Women of childbearing potential must use effective contraception for 4 weeks before, during, and for 3 years after treatment. Contraindicated during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Regulates epidermal cell growth through RAR and RXR binding, normalizing keratinization.
- Side Effects: Common: dryness of skin and mucous membranes, hair loss. Serious: hepatotoxicity, pseudotumor cerebri, teratogenicity.
- Contraindications: Pregnancy, breastfeeding, severe hepatic/renal impairment, concomitant use of methotrexate/tetracyclines.
- Drug Interactions: Vitamin A, methotrexate, tetracyclines, minipills, phenytoin, alcohol.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 25-50 mg/day. Children: 0.5-1 mg/kg/day (max 35 mg/day). Elderly: start low and titrate cautiously.
- Monitoring Parameters: Liver function tests, lipid profile, bone health (in children).
Popular Combinations
Acitretin is often used as monotherapy. Combination with phototherapy (UVB or PUVA) is possible but requires careful dose adjustments for both therapies.
Precautions
- General Precautions: Liver function tests, lipid profile, and blood glucose should be monitored before, during, and periodically after treatment.
- Specific Populations: Women of childbearing potential must adhere to the T.A.P.P. (Take Action to Prevent Pregnancy) program. Not recommended for children unless other options fail. Caution in elderly.
- Lifestyle Considerations: Alcohol should be avoided in women of childbearing age. Avoid excessive sun exposure due to photosensitivity.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Acitretin?
A: Adults: Initial 25-50mg daily with main meal. Maintenance: 25-50 mg daily adjusted based on response. Max 75 mg/day. Children: 0.5-1 mg/kg/day, max 35 mg/day. Elderly: Start low and titrate carefully.
Q2: What is the most serious side effect of Acitretin?
A: Teratogenicity is the most serious side effect. Other serious side effects include hepatotoxicity and pseudotumor cerebri.
Q3: How long does it take for Acitretin to work?
A: Initial improvement may be seen within 2-4 weeks, with full effect taking up to 3 months.
Q4: Can Acitretin be used during pregnancy?
A: No, Acitretin is absolutely contraindicated during pregnancy due to its high teratogenic potential.
Q5: What are the main drug interactions with Acitretin?
A: Vitamin A, methotrexate, tetracyclines, mini-pills, phenytoin, and alcohol.
Q6: What should be monitored in patients taking Acitretin?
A: Liver function tests, lipid profile, and bone health (especially in children).
Q7: What are the contraindications for Acitretin?
A: Pregnancy, breastfeeding, severe hepatic/renal impairment, and concomitant use of methotrexate, tetracyclines, other retinoids, or vitamin A supplements.
Q8: Can Acitretin be combined with other psoriasis treatments?
A: Yes, acitretin can be used in combination with phototherapy, but careful dosage adjustments of both are necessary.
Q9: What precautions are necessary for women of childbearing potential taking Acitretin?
A: They must adhere to strict contraception for 4 weeks before, during, and for 3 years after treatment with Acitretin and must not consume alcohol during treatment or for 2 months after cessation of therapy. They must also be enrolled in a pregnancy prevention program (like T.A.P.P).
Q10: What is the mechanism of action of Acitretin?
A: Acitretin modulates cell proliferation, differentiation, and inflammation in the skin through binding to retinoid receptors, thereby normalizing epidermal cell growth.
