AHFS/Drugs.com Monograph Routes of
administration Topical, oral Molar mass 300.435 g/mol | MedlinePlus a601012 CAS ID 5300-03-8 | |
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Trade names Panretin (gel), Toctino (oral) License data EU EMA: Panretin
US FDA: Alitretinoin Pregnancy
category US: D (Evidence of risk) | ||
What does alitretinoin mean
Alitretinoin, or 9-cis-retinoic acid, is a form of vitamin A. It is also used in medicine as an antineoplastic (anti-cancer) agent developed by Ligand Pharmaceuticals. It is a first generation retinoid. Ligand gained Food and Drug Administration (FDA) approval for alitretinoin in February 1999.
Contents
10um alitretinoin
Kaposi’s sarcoma
In the United States, topical alitretinoin (in the form of a gel; trade name Panretin) is indicated for the treatment of skin lesions in AIDS-related Kaposi's sarcoma. Alitretinoin is not indicated when systemic therapy against Kaposi's sarcoma is required. It has received EMA (11 October 2000) and FDA (2 March 1999) approval for this indication.
Chronic hand eczema
Under the trade name Toctino (marketed by GSK, UK) it has been granted prescription rights in the UK (08/09/2008) for oral use in chronic hand eczema. In May 2009 the National Institute for Health and Clinical Excellence (NICE) issued preliminary guidance on the use of Alitretinoin for the treatment of severe chronic hand eczema in adults. The recommendation stated that only patients with severe chronic hand eczema who are unresponsive to potent topical corticosteroids, oral immunosuppressants or phototherapy should receive the drug. Final NICE guidance is expected in August 2009.
Adverse effects by frequency
Systemic use, when being used to treat chronic hand eczema
Very common (>10% frequency):
Common (1-10% frequency):
Uncommon (0.1-1% frequency):
Rare (<0.1% frequency):
Unknown frequency:
Topical use for Kaposi's sarcoma
Very common (>10% frequency):
Common (1-10% frequency):
Contraindications
Pregnancy is an absolute contraindication as with most other vitamin A products, it should also be avoided when it comes to systemic use in any women that is of childbearing potential and not taking precautions to prevent pregnancy. Toctino (the oral capsule formulation of alitretinoin) contains soya oil and sorbitol. Patients who are allergic to peanut, soya or with rare hereditary fructose intolerance should not take this medicine. It is also contraindicated in nursing mothers. The oral formulation of alitretinoin is contraindicated in patients with:
Interactions
It is a CYP3A4 substrate and hence any inhibitor or inducer of this enzyme may alter plasma levels of alitretinoin. It should not be given to patients with excess vitamin A in their system as there is a potential for its actions on the retinoid X receptor to be exacerbated. It may also interact with tetracyclines to cause benign intracranial hypertension.
Overdose
Alitretinoin is a form of vitamin A. Alitretinoin has been administered in oncological clinical studies at dosages of more than 10-times of the therapeutic dosage given for chronic hand eczema. The adverse effects observed were consistent with retinoid toxicity, and included severe headache, diarrhoea, facial flushing and hypertriglyceridemia. These effects were reversible.
Mechanism of action
Alitretinoin is believed to be the endogenous ligand (a substance that naturally occurs in the body that activates this receptor) for retinoid X receptor, but it also activates the retinoic acid receptor.