ISOTRETINOIN

Chemistry - A synthetic retinoid, isotretinoin occurs as a yellow-orange to orange, crystallinepowder. It is insoluble in both water and alcohol. Commercially, it is available in soft gelatincapsules as a suspension in soybean oil.

Storage, Stability, Compatibility

Capsules should be stored at room temperature in tight, lightresistant containers. The drug is photosensitive and will degrade with light exposure. Expirationdates of 2 years are assigned after manufacture.

Pharmacology - ISOTRETINOIN

A retinoid, isotretinoin's major pharmacologic effects appear to be regulation ofepithelial cell proliferation and differentiation. It also affects monocyte and lymphocyte functionwhich can cause changes in cellular immune responses. The effects on skin include reduction ofsebaceous gland size and activity, reducing sebum production. It also has anti-keratinization andanti-inflammatory activity. It may indirectly reduce bacterial populations in sebaceous pores.

Uses, Indications

Isotretinoin may be useful in treating a variety of dermatologic-related conditions, including canine lamellar ichthyosis, cutaneus T-cell lymphoma, intracutaneous cornifying epitheliomas, multiple epidermal inclusion cysts, comedo syndrome in Schnauzers, and sebaceous adenitis seen in standard poodles.

Pharmacokinetics - ISOTRETINOIN

Isotretinoin is rapidly absorbed from the gut once the capsule disintegratesand the drug is dispersed in the GI contents. This may require up to 2 hours after dosing. Animalstudies have shown that only about 25% of dose reaches the systemic circulation, but food or milkmay increase this amount. Isotretinoin is distributed into many tissues, but is not stored in the liver(unlike vitamin A). It crosses the placenta and is highly bound to plasma proteins. It is unknown ifit enters milk. Isotretinoin is metabolized in the liver and is excreted in the urine and feces. Inhumans, terminal half life is about 10-20 hours.

Contraindications, Precautions, Reproductive Safety

Isotretinoin should only be used whenthe potential benefits outweigh the risks when the following conditions exist: hypertriglyceridemiaor sensitivity to isotretinoin.
Isotretinoin is a known teratogen. Major anomalies have been reported in children of womentaking the medication. It should also be considered to be absolutely contraindicated in pregnantveterinary patients. At this time, it is not recommended to be used in nursing mothers. Isotretinoinalso appears to inhibit spermatogenesis.
Adverse Effects, Warnings -Although at the present time veterinary experience with this medication is minimal, there appears to be a low incidence of adverse effects, particularly in dogs.
Potential adverse effects include: GI effects (anorexia, vomiting, abdominal distention), CNS effects (lassitude, hyperactivity, collapse), pruritus, erythema of feet and mucocutaneous junctions, polydipsia, keratoconjunctivitis (KCS), swollen tongue.
Incidence of adverse effects may be higher in cats. Effects reported include: blepharospasm, periocular crusting, erythema, diarrhea and especially weight loss secondary to anorexia. If cats develop adverse effects, the time between doses may be prolonged (e.g., Every other week give every other day) to reduce the total dose given.

Overdosage, Acute Toxicity

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

Drug Interactions

Isotretinoin used with other retinoids (etretinate, tretinoin, or vitamin A) maycause additive toxic effects. Use with tetracyclines may increase the potential for the occurrence ofpseudotumor cerebri (cerebral edema and increased CSF pressure).
Laboratory Considerations - Increases in serum triglyceride and cholesterol levels may benoted which can be associated with corneal lipid deposits. Platelets may be increased. ALT(SGOT), AST (SGPT) and LDH levels may be increased.