Etretinate (trade name Tegison) is a
medication
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...
developed by
Hoffmann–La Roche
F. Hoffmann-La Roche AG, commonly known as Roche (), is a Swiss multinational holding healthcare company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on ...
that was approved by the FDA in 1986 to treat severe
psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...
. It is a second-generation
retinoid
The retinoids are a class of chemical compounds that are natural derivatives of vitamin A or are chemically related to it. Synthetic retinoids are utilized in cosmetic formulations, clinical dermatology, and the treatment of some forms of cancer ...
.
It was subsequently removed from the
Canadian
Canadians () are people identified with the country of Canada. This connection may be residential, legal, historical or cultural. For most Canadians, many (or all) of these connections exist and are collectively the source of their being ''C ...
market in 1996 and the
United States
The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
market in 1998 due to the high risk of birth defects. It remains on the market in Japan as Tigason.
Pharmacology
Etretinate is a highly
lipophilic
Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...
,
aromatic
In organic chemistry, aromaticity is a chemical property describing the way in which a conjugated system, conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibits a stabilization stronger than would be expected from conjugati ...
retinoid. It is stored and released from
adipose tissue
Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...
, 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
The therapeutic index (TI; also referred to as therapeutic ratio) is a quantitative measurement of the relative safety of a drug with regard to risk of overdose. It is a comparison of the amount of a therapeutic agent that causes toxicity to the ...
and a long
elimination half-life
Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...
(''t''
1/2) of 120 days,
which make dosing difficult.
Etretinate has been replaced by
acitretin
Acitretin, sold under the brand names Neotigason and Soriatane, is a second-generation retinoid. It is taken orally, and is typically used for psoriasis.
Acitretin is an oral retinoid used in the treatment of severe resistant psoriasis. Becaus ...
, 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 defect
A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth de ...
s 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
A child () is a human being between the stages of childbirth, birth and puberty, or between the Development of the human body, developmental period of infancy and puberty. The term may also refer to an unborn human being. In English-speaking ...
, as it may interfere with
bone growth
Ossification (also called osteogenesis or bone mineralization) in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in the ...
.
* 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.
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
Hypervitaminosis A refers to the toxic effects of ingesting too much preformed vitamin A (retinyl esters, retinol, and retinal). Symptoms arise as a result of altered bone metabolism and altered metabolism of other fat-soluble vitamins. Hype ...
, most commonlydiffuse idiopathic skeletal hyperostosis
Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by abnormal calcification/bone formation (hyperostosis) of the soft tissues surrounding the joints of the spine, and also of the peripheral or appendicular skeleton. In ...
* muscular or abdominal
The abdomen (colloquially called the gut, belly, tummy, midriff, tucky, or stomach) is the front part of the torso between the thorax (chest) and pelvis in humans and in other vertebrates. The area occupied by the abdomen is called the abdominal ...
cramps
* dry, burning, itching eyelids
* unusual bruising
History
The drug was approved by FDA in 1986 to treat severe psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete b ...
. It was subsequently removed from the Canadian
Canadians () are people identified with the country of Canada. This connection may be residential, legal, historical or cultural. For most Canadians, many (or all) of these connections exist and are collectively the source of their being ''C ...
market in 1996 and the United States
The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
market in 1998 due to the high risk of birth defects.[ for etretinate]
See also
* Isotretinoin
Isotretinoin, also known as 13-''cis''-retinoic acid and sold under the brand name Accutane among others, is a medication used to treat skin diseases like harlequin-type ichthyosis, and lamellar ichthyosis, and severe cystic acne or moderat ...
* List of withdrawn drugs
Medication, Drugs or medicines may be withdrawn from commercial markets because of risks to patients, but also because of commercial reasons (e.g. lack of demand and relatively high production costs) or because it turns out that they are less effe ...
References
{{Retinoid receptor modulators
Retinoids
Withdrawn drugs
Ethyl esters
Phenol ethers
Polyenes