HYDROXYUREA

Chemistry - Structurally similar to urea and acetohydroxamic acid, hydroxyurea occurs as white, crystalline powder that is freely soluble in water. It is moisture labile.

Storage, Stability, Compatibility

Capsules should be stored in tight containers at room temperature. Avoid excessive heat.

Pharmacology - HYDROXYUREA

While the exact mechanism of action for hydroxyurea has not been determined, itappears to interfere DNA synthesis without interfering with RNA or protein synthesis. It apparentlyinhibits thymidine incorporation into DNS and may also directly damage DNA. It is an S-phaseinhibitor, but may also arrest cells at the G1-S border.
Hydroxyurea also inhibits urease, but is less potent than acetohydroxamic acid. Hydroxyurea canalso stimulate production of fetal hemoglobin.

Uses, Indications

Hydroxyurea may be useful n the treatment of polycythemia vera, mastocytomas, and leukemias in dogs and cats. It potentially may be of benefit in the treatment of feline hypereosinophilic syndrome.

Pharmacokinetics - HYDROXYUREA

Hydroxyurea is well absorbed after oral administration and crosses theblood-brain barrier. Approximately 50% of an absorbed dose is excreted unchanged in the urineand about 50% is metabolized in the liver and then excreted in the urine.

Contraindications, Precautions, Reproductive Safety

Risk versus benefit should be considered before using hydroxyurea with the following conditions: anemia, bone marrow depression, history of urate stones, current infection, impaired renal function, or in patients who have received previous chemotherapy or radiotherapy.
Hydroxyurea is a teratogen. Use only during pregnancy when the benefits to the mother outweighthe risks to the offspring. Hydroxyurea can suppress gonadal function; arrest of spermatogenesishas been noted in dogs. Although hydroxyurea distribution into milk has not been documented, nursing puppies or kittens should receive milk replacer when the bitch or queen is receivinghydroxyurea.

Adverse Effects, Warnings

Potential adverse effects include GI effects (anorexia, vomiting, diarrhea), stomatitis, sloughing of nails, alopecia, and dysuria. The most serious adverse effectassociated with hydroxyurea is bone marrow depression (anemia, thrombocytopenia, leukopenia). Ifthese occur, it is recommended to halt therapy until values return to normal.

Overdosage, Acute Toxicity

No specific information located. Because of the potential toxicity ofthe drug, overdoses should be treated aggressively with gut emptying protocols employed whenpossible. For further information, refer to an animal poison center.

Drug Interactions

Other bone marrow depressant drugs (e.g., other neoplastics, chloramphenicol, flucytosine, amphotericin B or colchicine) may cause additive myelosuppression when used with hydroxyurea.
Laboratory Considerations - Hydroxyurea may raise serum uric acid levels. Drugs such as allopurinol may be required to control hyperuricemia.