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.

CARBOPLATIN

Chemistry - Carboplatin, like cisplatin is a platinum-containing antineoplastic agent. It occurs aswhite to off-white crystalline powder having a solubility of 14 mg/ml in water and is insoluble inalcohol. The commercially available powder for injection contains equal parts of mannitol andcarboplatin. After reconstitution with sterile water for injection, a resulting solution of 10 mg/ml ofcarboplatin has a pH of 5-7 and an osmolality of 94 mOsm/kg.

Storage, Stability, Compatibility

The powder for injection should kept stored at room temperature and protected from light.
After reconstitution, solutions containing 10 mg/ml are stable for at least 8 hours. Some sourcessay that the solution is stable for up to 24 hours and can be refrigerated, but because there are nopreservatives in the solution, the manufacturer recommends discarding unused portions after 8hours. Previous recommendations to avoid the use of solutions containing sodium chloride to dilutecarboplatin, are no longer warranted as only a minimal amount of carboplatin is converted tocisplatin in these solutions.
Because aluminum can displace platinum from carboplatin, the solution should not be prepared, stored or administered where aluminum-containing items can come into contact with the solution.
Should carboplatin come into contact with aluminum, a black precipitate will form and the productshould not be used.

Pharmacology - CARBOPLATIN

Carboplatin's exact mechanism of action is not fully understood. Both carboplatin's and cisplatin's properties are analogous to those of bifunctional alkylating agents producing inter- and intrastrand crosslinks in DNA, thereby inhibiting DNA replication, RNA transcription, and protein synthesis. Carboplatin is cell-cycle nonspecific.
Uses, Indications -Like cisplatin, carboplatin may be useful in a variety of veterinary neoplasticdiseases including squamous cel carcinomas, ovarian carcinomas, mediastinal carcinomas, pleuraladenocarcinomas, nasal carcinomas and thyroid adenocarcinomas. Carboplatin's primary usecurrently in small animal medicine is in the adjunctive treatment (post amputation) of osteogenicsarcomas. It's effectiveness in treating transitional cel carcinoma of the bladder has been disappointing thus far. However, carboplatin may have more efficacy against melanomas than does cisplatin.
Carboplatin, unlike cisplatin, appears to be relatively safe to use in cats.
Whether carboplatin is more efficacious than cisplatin for certain cancers does not appear to bedecided at this point, but the drug does appear to have fewer adverse effects (less renal toxicity andreduced vomiting) in dogs than does cisplatin. However, it does cost significantly more thancisplatin.

Pharmacokinetics - CARBOPLATIN

After IV administration, carboplatin is well distributed throughout the body;highest concentrations are found in the liver, kidney, skin and tumor tissue. The metabolic fate andelimination of carboplatin are complex and the discussion of this aspect of the drugs pharmacokinetics is beyond the scope of this reference. Suffice it to say that the parent drug degradesinto platinum and platinum-complexed compounds that are primarily eliminated by kidneys. Indogs, approximately 70% of the platinum administered is secreted in the urine after 72 hours.

Contraindications, Precautions, Reproductive Safety

Carboplatin is contraindicated in patients hypersensitive to it or other platinum-containing compounds. It is also contraindicated inpatients with severe bone marrow suppression. Patients with severe carboplatin-induced myelosuppression should be allowed to recover their counts before additional therapy.
Caution is advised in patients with active infections, hearing impairment or preexisting renal orhepatic disease. Dosage may need adjustment in patients with reduced renal function.
Do not give carboplatin IM or SubQ.
Carboplatin is fetotoxic and embryotoxic in rats and the risks of its use during pregnancy shouldbe weighed with its potential benefits. It is unknown whether carboplatin enters maternal milk. Inhumans, it is recommended to discontinue nursing if the mother is receiving the drug.

Adverse Effects, Warnings

Established adverse effects in dogs include, anorexia, vomiting andbone marrow suppression which is exhibited primarily as thrombocytopenia and/or neutropenia.
The nadir of platelet and neutrophil counts generally occur about 14 days post treatment.
Hepatotoxicity (increased serum bilirubin & liver enzymes) is seen in about 15% of human patients treated with carboplatin. Other potential adverse effects include: nephrotoxicity, neuropathiesand ototoxicity. These effects occur with carboplatin therapy much less frequently than withcisplatin therapy. Anaphylactoid reactions have been reported rarely in humans that have receivedplatinum-containing compounds (e.g., cisplatin). Hyperuricemia may occur after therapy in a smallpercentage of patients.
Overdosage - There is limited information available. An overdose of carboplatin would be expectedto cause aggravated effects associated with the drug's bone marrow and liver toxicity. Monitor forneurotoxicity, ototoxicity and nephrotoxicity..
Treatment is basically supportive; no specific antidote is available. Plasmapheresis or hemodialysiscould potentially be of benefit in removing the drug.

Drug Interactions

The leukopenic or thrombocytopenic effects secondary to carboplatin may beenhanced by other myelosuppressive medications. Human patients previously treated withcisplatin have an increased risk of developing neurotoxicity or ototoxicity after receiving carboplatin. Live or killed virus vaccines administered after carboplatin therapy may not be as effective as the immune-response to these vaccines may be modified by carboplatin therapy. Carboplatin may also potentiate live virus vaccines replication and increase the adverse effects associated with these vaccines.
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