Etretinate

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Etretinate
Skeletal formula of etretinate
Space-filling model of the etretinate molecule
Systematic (IUPAC) name
Ethyl (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate
Clinical data
Trade names Tigason, formerly Tegison
AHFS/Drugs.com Drugs.com archive
MedlinePlus a601010
Pregnancy
category
  • US: X (Contraindicated)
Routes of
administration
Oral
Legal status
Legal status
  • US: Withdrawn
Pharmacokinetic data
Protein binding >99%
Metabolites Free acid, Z-form, chain shortening
Biological half-life 120 days
Identifiers
CAS Number 54350-48-0 N
ATC code D05BB01 (WHO)
PubChem CID 5282375
IUPHAR/BPS 7599
DrugBank DB00926 YesY
ChemSpider 4445538 YesY
UNII 65M2UDR9AG YesY
KEGG D00316 YesY
ChEBI CHEBI:4913 YesY
ChEMBL CHEMBL464 YesY
Chemical data
Formula C23H30O3
Molar mass 354.483 g/mol
 NYesY (what is this?)  (verify)

Etretinate (trade name Tegison) is a medication developed by Hoffmann–La Roche that was approved by the FDA in 1986 to treat severe psoriasis. It is a second-generation retinoid.[1] It was subsequently removed from the Canadian market in 1996 and the United States market in 1998 due to the high risk of birth defects. It remains on the market in Japan as Tigason.

Pharmacology[edit]

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,[1] 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Etretinate has been replaced by acitretin, the free acid (without the ethyl ester).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,[1] so that it is still a long-acting teratogen and pregnancy is prohibited for two years after therapy.[2]

Precautions[edit]

  • 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.[3]
  • Etretinate should be avoided in children, as it may interfere with bone growth.[3]
  • If a patient has ever taken etretinate, he or she is not eligible to donate blood in the United States or the United Kingdom, due to the risk of birth defects.[4] In Japan, people may not donate blood for two years after ceasing to use the medication.[5]

Side effects[edit]

Side effects are those typical of hypervitaminosis A, most commonly[3]

History[edit]

The drug was approved by the FDA in 1986 to treat severe psoriasis. It was subsequently removed from the Canadian market in 1996 and the United States market in 1998 due to the high risk of birth defects.[3][6][7]

In Japan, the drug remains on market branded Tigason.[5]

See also[edit]

References[edit]

  1. ^ a b c Mutschler, Ernst; Schäfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 728f. ISBN 3-8047-1763-2. 
  2. ^ Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. p. 5669. ISBN 978-3-85200-181-4. 
  3. ^ a b c d Drugs.com archive for etretinate
  4. ^ UK Blood Transfusion and Tissue Transplantation Services
  5. ^ a b Drug information sheet: Tigason
  6. ^ Qureshi, ZP; Seoane-Vazquez, E; Rodriguez-Monguio, R; Stevenson, KB; Szeinbach, SL (July 2011). "Market withdrawal of new molecular entities approved in the United States from 1980 to 2009.". Pharmacoepidemiology and drug safety 20 (7): 772–7. doi:10.1002/pds.2155. PMID 21574210. 
  7. ^ Fung, M.; Thornton, A.; Mybeck, K.; Wu, J. H.-h.; Hornbuckle, K.; Muniz, E. (1 January 2001). "Evaluation of the Characteristics of Safety Withdrawal of Prescription Drugs from Worldwide Pharmaceutical Markets-1960 to 1999". Therapeutic Innovation & Regulatory Science 35 (1): 293–317. doi:10.1177/009286150103500134.