ETRETINATE, ACITRETIN

Note: Etretinate has recently been withdrawn from the market by its manufacturer andreplaced with acitretin. Acitretin is an active metabolite of etritinate and has the sameindications, but acitretin is reportedly dosed at a rate of 2/3's that of etrinate. Forexample, if the dose for etrinate is 2 mg/kg, then acitretin would be dosed at 1.32 mg/kg.
Until a full monograph for acitretin can be written, use with extreme caution and refer toother current sources for information.

Pharmacology - ETRETINATE, ACITRETIN

Etretinate is a synthetic retinoid agent that may be useful in the treatment ofseveral disorders related to abnormal keratinization and/or sebaceous gland abnormalities in smallanimals. The drug apparently has some anti-inflammatory activity, but its exact mechanism of actionis not known.

Uses, Indications

Etretinate may be useful in the treatment of canine lamellar ichthyosis, solarinduced precancerous lesions in Dalmatians or in bull Terriers, actinic keratoses, squamous cellcarcinomas, and intracutaneous cornifying epitheliomas (multiple keratoacanthomas).
While the drugs has been effective in treating idiopathic seborrhea (particularly in cocker spaniels), it is not effective in treating the ceruminous otitis that may also be present. Results have been disappointing in treating idiopathic seborrheas seen in basset hounds and West Highland terriers.
Etretinate's usage in cats is very limited, but it has shown some usefulness in treating paraneoplastic actinic keratosis, solar-induced squamous cel carcinoma and Bowen's Disease in this species.

Pharmacokinetics - ETRETINATE, ACITRETIN

Etretinate absorption is enhanced by high lipid content in the gut. After absorption, a high first pass effect in the liver limits etretinate amounts available to the systemic circulation. However, the acid form metabolite formed from this first pass effect is pharmacologically active. Etretinate and the active metabolite are highly bound to plasma proteins. The drug issubsequently metabolized to conjugate forms that are excreted in the bile and urine. Terminal halflife can be very long probably due to storage in adipose tissue. In humans, terminal half life aftersix months of therapy is approximately 120 days.

Contraindications, Precautions, Reproductive Safety

Etretinate should only be used when thepotential benefits outweigh the risks when the following conditions exist: cardiovascular disease, hypertriglyceridemia or sensitivity to etretinate.
Etretinate is a known teratogen. Major anomalies have been reported in children of women takingthe medication. It should also be considered to be absolutely contraindicated in pregnant veterinarypatients. Etretinate is excreted in rat milk. At this time, it is not recommended to be used in nursingmothers.

Adverse Effects, Warnings

At the present time, veterinary experience with this medication islimited, but incidence of adverse effects appear to less in companion animals than in people. Mostanimals treated (thus far) do not exhibit adverse effects. Potential adverse effects include:anorexia/vomiting/diarrhea, cracking of foot pads, pruritus, ventral abdominal erythema, polydipsia, lassitude, joint pain/stiffness, eyelid abnormalities and conjunctivitis (KCS), swollen tongue, andbehavioral changes.
The most common adverse effect seen in cats is anorexia with resultant weight loss. If cats developadverse effects, the time between doses may be prolonged (e.g., Every other week give every otherday) to reduce the total dose given.
Do not confuse etretinate with etidronate disodium or etomidate.

Overdosage, Acute Toxicity

There appears to be very limited information on overdoses with thisagent. Because of the drug's potential adverse effects, gut emptying should be considered withacute overdoses when warranted.

Drug Interactions

Etretinate used with other retinoids (isotretinoin, tretinoin, or vitamin A) maycause additive toxic effects. There may be increased potential for hepatotoxicity when etretinate isused with methotrexate or other hepatotoxic drugs (e.g., anabolic steroids, androgens, asparaginase, erythromycins, estrogens, fluconazole, halothane, ketoconazole, sulfonamides orvalproic acid); use with caution and increase monitoring. Use with tetracyclines may increase thepotential for the occurrence of pseudotumor cerebri (cerebral edema and increased CSF pressure).
Laboratory Considerations - In humans, etretinate has caused significant increases in plasmatriglyceride, serum cholesterol, serum ALT (SGPT), serum AST (SGOT) and serum LDHconcentrations. Serum HDL (high density lipoprotein) concentrations may be decreased.
Veterinary significance of these effects are unclear.