Systemic retinoid (severe psoriasis)
Acitretin is an oral retinoid used for severe psoriasis in adults. It normalises the growth and maturation of skin cells, reducing plaques. It has important adverse effects and, like other retinoids, is highly teratogenic: it cannot be used in pregnancy nor for 3 years after stopping treatment.
Also known as: Acitretina, Neotigason
Acitretin + Methotrexate is CONTRAINDICATED: increased risk of hepatitis with the combination.
The acitretin label is explicit: an increased risk of hepatitis has been reported with the combined use of methotrexate and etretinate (the precursor of acitretin) and, consequently, the combination of methotrexate with acitretin is contraindicated. Both drugs are potentially hepatotoxic and the risk of liver injury is additive. In severe psoriasis, if methotrexate is an option, acitretin should not be used together; consider monotherapy or an alternative (e.g., phototherapy, biologics) and monitor liver function after any accidental exposure.
Acitretin + methotrexate: CONTRAINDICATED — increased risk of hepatitis with the combination.
An increased risk of hepatitis has been reported with the combined use of methotrexate and etretinate (a precursor of acitretin); consequently, the combination of methotrexate with acitretin is contraindicated.
Monitor liver function if there is accidental exposure.
Jaundice, elevated transaminases or signs of hepatitis.
Do not use the combination. Choose an alternative psoriasis therapy.
DailyMed/FDA (NIH/NLM) — approved Acitretin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6546625-acb8-460e-b34e-f795bfb3680a ; approved Methotrexate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=04a95db9-a124-4b97-bd71-1c37a6b3b0c8
Acitretin + tetracyclines (Doxycycline) is CONTRAINDICATED: both may cause increased intracranial pressure.
The acitretin label states that, since both acitretin and tetracyclines can cause increased intracranial pressure (pseudotumor cerebri), their combined use is contraindicated. Doxycycline is the most commonly used tetracycline in dermatology, making this the most relevant pair of the class. In psoriasis requiring acitretin and an infection requiring a tetracycline, choose an alternative antibiotic class and monitor persistent headache, nausea and visual disturbances after accidental exposure.
Acitretin + doxycycline: CONTRAINDICATED — both may cause increased intracranial pressure.
Since both acitretin and tetracyclines can cause increased intracranial pressure (pseudotumor cerebri), their combined use is contraindicated.
Monitor for headache, visual disturbances and papilledema in case of exposure.
Persistent headache, visual disturbances, papilledema.
Do not use the combination.
DailyMed/FDA (NIH/NLM) — approved Acitretin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6546625-acb8-460e-b34e-f795bfb3680a ; approved Doxycycline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f0fbf63a-e75c-40cf-b2e9-429deaac899d
Acitretin + Phenytoin: acitretin may reduce the protein binding of phenytoin, possibly increasing the free fraction.
When acitretin is given with phenytoin, the protein binding of phenytoin may be reduced, increasing the pharmacologically active free fraction and the potential for toxicity. Phenytoin has a narrow therapeutic index, so an increase in the free fraction may cause nystagmus, ataxia and drowsiness even with apparently normal total levels. Use with caution, consider monitoring free phenytoin and watch for clinical signs of toxicity, especially when starting the combination.
Acitretin + phenytoin: acitretin may reduce phenytoin protein binding, increasing the free fraction.
When acitretin is given with phenytoin, the protein binding of phenytoin may be reduced, increasing the pharmacologically active free fraction.
Monitor for signs of phenytoin toxicity (nystagmus, ataxia, drowsiness).
Nystagmus, ataxia, drowsiness or other signs of phenytoin toxicity.
Use with caution; consider monitoring phenytoin levels and signs of toxicity.
DailyMed/FDA (NIH/NLM) — approved Acitretin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6546625-acb8-460e-b34e-f795bfb3680a ; approved Phenytoin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3580e6a8-f7c3-44a0-a1eb-2a84ae589d21
Oral acitretin absorption is optimal when taken with food — "Oral absorption of acitretin is optimal when given with food".
Take with meals to optimise absorption.
DailyMed/FDA (NIH/NLM) — approved Acitretin label (USP): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6546625-acb8-460e-b34e-f795bfb3680a
Alcohol converts acitretin into etretinate, a metabolite with a very long half-life (about 120 days), extending the teratogenic risk well beyond the expected 3 years and increasing hepatotoxicity.
Do not drink alcohol (including wine and beer) during treatment and for 2 weeks after stopping; also avoid alcohol-containing medicines.
DailyMed/FDA (NIH/NLM) — approved Acitretin label (USP): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6546625-acb8-460e-b34e-f795bfb3680a
Acitretin may raise triglycerides and cholesterol; risk of pancreatitis in patients with severe hypertriglyceridaemia.
Monitor fasting lipid profile before and during treatment.
DailyMed/FDA (NIH/NLM) — approved Acitretin label (USP): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6546625-acb8-460e-b34e-f795bfb3680a
Risk of hepatotoxicity (transaminase elevation) associated with acitretin; use with caution in hepatic disease and monitor liver function.
Monitor transaminases before and during treatment; caution in hepatic disease and with alcohol or hepatotoxic drugs.
DailyMed/FDA (NIH/NLM) — approved Acitretin label (USP): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6546625-acb8-460e-b34e-f795bfb3680a
Teratogenic — "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" (label); alcohol extends the risk (etretinate formation).
Contraindicated in pregnancy; reliable contraception during and for at least 3 years after stopping; exclude pregnancy before starting.
DailyMed/FDA (NIH/NLM) — approved Acitretin label (USP): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6546625-acb8-460e-b34e-f795bfb3680a
Teratogenic — "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".
Contraindicated in any trimester; never use during pregnancy.
Contraindicated during breastfeeding ("do not breast feed or take acitretin capsules, but not both") — excretion in milk.
Reliable contraception mandatory during and for at least 3 years after stopping; exclude pregnancy before starting.
DailyMed/FDA (NIH/NLM) — approved Acitretin label (USP): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a6546625-acb8-460e-b34e-f795bfb3680a
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Normalises epidermal keratinocyte proliferation and differentiation (psoriatic hyperproliferation) and modulates cutaneous inflammatory response; induces terminal differentiation of epidermal cells.
Aromatic retinoid that binds to retinoic acid nuclear receptors (RAR), regulating transcription of genes involved in cell growth, differentiation and keratinisation; reduces keratinocyte proliferation and inflammation.
Oral absorption is optimal with food ("Oral absorption of acitretin is optimal when given with food") and is linear and proportional for doses of 25 to 100 mg; bioavailability is about 60–70%.
Metabolised by simple isomerisation to 13-cis-acitretin ("metabolism and interconversion by simple isomerization to its 13-cis form (cis-acitretin)"); etretinate (a very long-lived metabolite — 120 days) may form with alcohol — hence the prohibition of alcohol during treatment.
Elimination half-life of about 49 hours ("elimination half-life of 49 hours"); the cis-acitretin metabolite has a similar half-life, and etretinate (when formed) of 120 days ("half-life of 120 days").
