Etretinate

Pharmacology

Etretinate is a highly lipophilic, aromatic retinoid. It is stored and released from adipose tissue, so its effects can continue long after dosage stops. It is detectable in the plasma for up to three years following therapy. Etretinate has a low therapeutic index and a long elimination half-life (t1/2) of 120 days, which make dosing difficult.

Etretinate has been replaced by acitretin, the free acid (without the ethyl ester). While acitretin is less lipophilic and has a half-life of only 50 hours, it is partly metabolized to etretinate in the body, so that it is still a long-acting teratogen and pregnancy is prohibited for two years after therapy.

Precautions

• Etretinate is a teratogen, and may cause birth defects long after use. Therefore, birth control is advised during therapy, and for at least three years after therapy has stopped.
• Etretinate should be avoided in children, as it may interfere with bone growth.
• If a patient has ever taken etretinate, they are not eligible to donate blood in the United States, the United Kingdom, the United Arab Emirates, Australia, Ireland or Québec, due to the risk of birth defects. In Japan, people may not donate blood for two years after ceasing to use the medication.

Side effects

Side effects are those typical of hypervitaminosis A, most commonly

• bone or joint pain, stiffness; in long-term treatment diffuse idiopathic skeletal hyperostosis
• muscular or abdominal cramps
• dry, burning, itching eyelids
• unusual bruising

History

Etretinate received FDA approval in 1986 for the treatment of severe psoriasis. However, it was voluntarily withdrawn from the Canadian market in 1996 and the United States market in 1998 due to its prolonged elimination half-life and significant teratogenic potential. Because the drug accumulates in adipose tissue, it can pose a high risk of birth defects for several years following the cessation of therapy. Etretinate was largely succeeded by its active metabolite, acitretin, which has a much shorter half-life and was approved by the FDA in 1996.

In Japan, the drug remains on market branded Tigason.

References

References

1. Anvisa. (2023-07-24). "RDC Nº 804 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial". [[Diário Oficial da União]].
2. (2001). "Arzneimittelwirkungen". Wissenschaftliche Verlagsgesellschaft.
3. (2007). "Austria-Codex". Österreichischer Apothekerverlag.
4. "Donor Selection Guidelines: Etretinate". UK Blood Transfusion and Tissue Transplantation Services.
5. "Medications taken on a regular basis that exclude you from donating blood". Héma-Québec.
6. "Health FAQs".
7. {{drugs.com. MMX. etretinate for etretinate
8. (July 2011). "Market withdrawal of new molecular entities approved in the United States from 1980 to 2009". Pharmacoepidemiology and Drug Safety.
9. (1 January 2001). "Evaluation of the Characteristics of Safety Withdrawal of Prescription Drugs from Worldwide Pharmaceutical Markets-1960 to 1999". Therapeutic Innovation & Regulatory Science.
10. (28 February 2024). "Acitretin". StatPearls Publishing.
11. "Tigason Drug information sheet". RAD-AR Council Japan.