Hypersensitivity Reactions: As in the case of other platinum complexed compounds, allergic reactions to carboplatin have been reported. Patients should be monitored for possible anaphylactoid reactions and appropriate equipment and medication should be readily available to treat such reactions (e.g., antihistamines, corticosteroids, adrenaline, oxygen) whenever carboplatin is administered.
Carboplatin should be administered only under constant supervision by physicians experienced in therapy with cytotoxic agents and only when potential benefits of carboplatin therapy outweigh the possible risks. Appropriate facilities should be available for adequate management of complications should they arise.
Myelosuppression: Myelosuppression associated with carboplatin is closely related to the renal clearance of the drug; therefore patients with impaired renal function are more susceptible.
Myelosuppression, particularly thrombocytopenia (reduction in platelet count), will also be more severe in patients receiving concomitant therapy with other nephrotoxic drugs such as aminoglycoside antibiotics. Toxicity is more likely to be prolonged and more severe in patients who have undergone previous chemotherapy, are more advanced in age, or who are debilitated. Dosage reductions may be necessary in these cases.
The nadir for platelets (peak detrimental effect) is usually between days 14-21 following initial treatment and days 14-28 for white blood cells. Minimum counts should be 50,000/mm3 for platelets and 2,000/mm3 for white blood cells. If counts fall below this level, therapy should be suspended until recovery is complete, usually five to six weeks. Supportive transfusional therapy may be necessary in severe cases.
It is important, therefore, that the assessment of renal function and peripheral blood counts (including white blood cells, platelets and haemoglobin) be made prior to, during and following treatment with carboplatin. In order to ensure that the peak detrimental effect on blood cells has occurred, repeat courses of treatment with carboplatin should not be given more frequently than monthly under normal circumstances.
Nephrotoxicity: Renal toxicity is not usually dose-limiting. Unlike cisplatin therapy, pre-treatment and post-treatment hydration is not necessary, although some patients may show a decrease in creatinine clearance. Renal impairment is more likely to be seen in patients who have previously experienced nephrotoxicity as a result of chemotherapy.
Neurotoxicity: Neurological evaluations and auditory monitoring should be performed regularly during and after carboplatin therapy.
Ototoxicity: Ototoxicity is cumulative, and frequency and severity of hearing disorder increases with high dose regimens and repeated doses, or prior treatment with cisplatin (also ototoxic). Auditory function should be monitored during treatment.
Gastrointestinal: Carboplatin can induce emesis. The incidence and severity of emesis may be reduced by pretreatment with antiemetics or by carboplatin administration as a continuous IV infusion over 24 hours, or as IV administration of divided doses over 5 consecutive days rather than as a single infusion. Selective inhibitors of type 3 (5-HT3), serotonergic receptors (e.g., ondansetron) or substituted benzamides (e.g., metoclopramide) may be particularly effective antiemetics and combination therapy may be considered for patients experiencing severe or refractory emetogenic effects.
Immunosuppressant Effects / Increased Susceptibility to Infections: Administration of live or live-attenuated vaccines in patients immunocompromised by chemotherapeutic agents, including carboplatin, may result in serious or fatal infections. Vaccination with a live vaccine should be avoided in patients receiving carboplatin. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.
Mutagenicity and Carcinogenicity: Animal studies demonstrate that carboplatin is mutagenic and teratogenic. The carcinogenic potential of carboplatin has not been studied; however, compounds with a similar mechanism of action have been reported to be carcinogenic.
Effects on ability to drive or operate machinery: The effect of carboplatin on the ability to drive or use machinery has not been systematically evaluated.
Use in Pregnancy: Category D: Carboplatin has been shown to be embryo-toxic and mutagenic, and its use in pregnant women is not recommended. Women of child-bearing potential should use adequate contraception and carboplatin should only be used in women of child-bearing potential if the expected benefits outweigh the risks of such therapy. If the patient becomes pregnant whilst receiving the drug she should be advised of the potential hazard to the foetus.
Use in Lactation: It is not known whether or not carboplatin is excreted in breast milk so breast feeding should be discontinued during carboplatin therapy in lactating women.