Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

LOMUSTINE (CCNU)

Chemistry - A nitrosourea derivative alkylating agent, lomustine occurs as a yellow powder that ispractically insoluble in water and soluble in alcohol.

Storage, Stability, Compatibility

Store capsules in well-closed containers at room temperature.
Expiration dates of two years are assigned after manufacture.

Pharmacology - LOMUSTINE (CCNU)

While lomustine's mechanism of action is not totally understood, it is believed itacts as an alkylating agent. However, other mechanisms such as carbamoylation and cellular proteinmodification may be involved. The net effects are of DNA and RNA synthesis inhibition.
Lomustine is cell cycle-phase nonspecific.

Uses, Indications

Lomustine may be useful in the adjunctive treatment of CNS neoplasms indogs. It potentially could be of benefit in the adjunctive therapy of other neoplastic diseases in smallanimals as well.

Pharmacokinetics - LOMUSTINE (CCNU)

Lomustine is absorbed rapidly and extensively from the GI tract and someabsorption occurs after topical administration. Lomustine or its active metabolites are widelydistributed in the body. While lomustine is not detected in the CSF, its active metabolites aredetected in substantial concentrations. Lomustine is metabolized extensively in the liver to bothactive and inactive metabolites which are then eliminated primarily in the urine. Lomustine half lifein humans is very short (about 15 minutes), but its biologic activity is significantly longer due to thelonger elimination times of active metabolites.

Contraindications, Precautions, Reproductive Safety

Lomustine should be used only when itspotential benefits outweigh its risks with the following conditions: anemia, bone marrow depression, pulmonary function impairment, current infection, impaired renal function, sensitivity to lomustineor patients who have received previous chemotherapy or radiotherapy.
Lomustine is a teratogen in lab animals. Use only during pregnancy when the benefits to themother outweigh the risks to the offspring. Lomustine can suppress gonadal function. Lomustineand its metabolites have been detected in maternal milk, nursing puppies or kittens should receivemilk replacer when the bitch or queen is receiving lomustine.

Adverse Effects, Warnings

Potential adverse effects include GI effects (anorexia, vomiting, diarrhea), stomatitis, alopecia, and rarely, hepatotoxicity and pulmonary infiltrates or fibrosis. Themost serious adverse effect likely is bone marrow depression (anemia, thrombocytopenia, leukopenia). Nadirs in dogs generally occur about 1-3 weeks after treatment has begun.
Cross-resistance may occur between lomustine and carmustine.

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

The principal concern with lomustine is with its concurrent use with otherdrugs that are also myelosuppressive, including many of the other antineoplastics and otherbone marrow depressant drugs (e.g., chloramphenicol, flucytosine, amphotericin B, orcolchicine). Bone marrow depression may be additive. Use with other immunosuppressantdrugs (e.g., azathioprine, cyclophosphamide, corticosteroids) may increase the risk of infection. Live virus vaccines should be used with caution if at all during lomustine therapy.

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