Etretinate

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.^[2] 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.

Etretinate

Clinical data
Trade names	Tigason, formerly Tegison
AHFS/Drugs.com	Drugs.com archive
MedlinePlus	a601010
Routes of administration	Oral
ATC code	D05BB01 (WHO)
Legal status
Legal status	BR: Class F4 (Other prohibited substances)[1] US: Withdrawn
Pharmacokinetic data
Protein binding	>99%
Metabolites	Free acid, Z-form, chain shortening
Elimination half-life	120 days
Identifiers
IUPAC name Ethyl (2E,4E,6E,8E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoate
CAS Number	54350-48-0 N
PubChem CID	5282375
IUPHAR/BPS	7599
DrugBank	DB00926 Y
ChemSpider	4445538 Y
UNII	65M2UDR9AG
KEGG	D00316 Y
ChEBI	CHEBI:4913 Y
ChEMBL	ChEMBL464 Y
CompTox Dashboard (EPA)	DTXSID0023036
ECHA InfoCard	100.053.727
Chemical and physical data
Formula	C23H30O3
Molar mass	354.490 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(OCC)\C=C(\C=C\C=C(\C=C\c1c(cc(OC)c(c1C)C)C)C)C
InChI InChI=1S/C23H30O3/c1-8-26-23(24)14-17(3)11-9-10-16(2)12-13-21-18(4)15-22(25-7)20(6)19(21)5/h9-15H,8H2,1-7H3/b11-9+,13-12+,16-10+,17-14+ Y Key:HQMNCQVAMBCHCO-DJRRULDNSA-N Y
NY (what is this?)  (verify)

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 (t_1/2) of 120 days,^[2] 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Etretinate has been replaced by acitretin, the free acid (without the ethyl ester).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,^[2] so that it is still a long-acting teratogen and pregnancy is prohibited for two years after therapy.^[3]

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.^[4]
• Etretinate should be avoided in children, as it may interfere with bone growth.^[4]
• If a patient has ever taken etretinate, they are not eligible to donate blood in the United States, the United Kingdom, Australia, Ireland or Québec, due to the risk of birth defects.^[5][6][7] In Japan, people may not donate blood for two years after ceasing to use the medication.^[8]

Side effects

Side effects are those typical of hypervitaminosis A, most commonly^[4]

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

History

The drug was approved by 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.^[4][9][10]

In Japan, the drug remains on market branded Tigason.^[8]

See also

• Isotretinoin
• List of withdrawn drugs