Biovinate Special Precautions

General: Since carboplatin is a highly toxic drug with a narrow therapeutic index, therapeutic effect is unlikely to occur without some evidence of toxicity. Carboplatin should only be administered under the supervision of a qualified physician experienced in cancer chemotherapeutic drugs. Blood counts as well as renal and hepatic function tests must be monitored closely. Diagnostic and treatment facilities should be readily available for appropriate management of therapy and possible complications.
Generally, carboplatin courses should not be administered more frequently than every 4 weeks to ensure that the nadir in blood counts has occurred and that there has been recovery to a satisfactory level.
Discontinue carboplatin therapy if severe myelosuppression or abnormal renal or hepatic function is observed.
Myelosuppression: Myelosuppression, especially thrombocytopenia, may be more severe and prolonged in patients with abnormal renal function and who are receiving concomitant therapy with nephrotoxic drugs.
The occurrence, severity and protraction of myelosuppression is likely to be greater in older patients, those who have received extensive prior treatment with carboplatin for their disease or with cisplatin and have poor performance status. Renal function parameters of patients should be assessed prior, during and after carboplatin therapy. Dosage of carboplatin should be appropriately reduced in these groups and the effects carefully monitored through frequent blood counts between courses.
Combination therapy with other myelosuppressive drugs may require dosage and timing schedule modification in order to minimize additive effects. Peripheral blood counts (including platelets, white blood cells and hemoglobin) should be assessed during and after therapy.
Hypersensitivity/Allergic reactions: Observe patients carefully. Like with other platinum-based drugs, allergic reactions appear most often during administration that may necessitate discontinuation of infusion. In such cases, appropriate symptomatic treatment that includes antihistamine, adrenaline and/or glucocorticoids must also be initiated.
Hematologic Toxicity: Bone marrow suppression (leukopenia, neutropenia and thrombocytopenia) is dose-dependent and dose-limiting toxicity. Frequently monitor peripheral blood counts during carboplatin therapy, and when appropriate, until recovery is achieved because this will monitor toxicity and help determine the nadir and recovery of hematological parameters. This will also assist in subsequent adjustment of dosage of the drug. Median nadir occurs at day 21 in patients receiving single agent carboplatin and at day 15 in patients receiving combination therapy with other chemotherapeutic drugs. Do not repeat intermittent courses of carboplatin until leukocyte, neutrophil, and platelet counts have normalized that usually takes 5 to 6 weeks. Lowest levels of platelets and white cells are seen between days 14 to 21 and 14 to 28, respectively.
Since anemia is cumulative, transfusions may be needed during treatment with carboplatin, particularly in patients receiving prolonged therapy (i.e., more than 6 cycles).
Nephrotoxicity: Carboplatin is excreted mainly in the urine and renal function must be monitored in patients receiving the drug. The incidence and severity of nephrotoxicity may increase in patients with impaired renal function prior to carboplatin therapy. It is unclear if appropriate hydration programme might overcome such an effect but dosage reduction or discontinuation of therapy is required when there is severe alteration in renal function test. Impairment of renal function is more likely in patients who have experienced nephrotoxicity with cisplatin use.
Neurotoxicity: Patients older than 65 years and/or previously treated with cisplatin have an increased risk of peripheral neurologic toxicity (limited to paresthesia and decrease in osteotendinous reflexes). Monitoring and neurological examinations should be carried out at regular intervals.
There have been reports of visual disturbances, including loss of vision, in post-carboplatin use in doses higher than those recommended in patients with renal impairment. Vision appears to recover totally or to a significant extent within weeks of stopping these high doses.
Ototoxicity: Cases of auditory defects have been reported with carboplatin use. Ototoxicity may be more pronounced when used in children and more likely seen in patients previously treated with cisplatin. Since delayed onset hearing loss have also been reported in pediatric patients, long-term audiometric follow-up in this population is recommended.
Gastrointestinal: Carboplatin can induce emesis, which can be more severe in patients previously receiving emetogenic therapy. Nausea and/or vomiting, which are generally mild to moderate in severity may occur within 6 to 12 hours after carboplatin administration and may persist up to 24 hours or longer. Incidence and intensity of emesis have been reduced by using premedication with antiemetics. Although no conclusive efficacy data exist with carboplatin's schedules, lengthening the duration of single IV administration to 24 hours or dividing the total dose over 5 consecutives daily pulse doses has resulted in reduced emesis.
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 (see Interactions).
Carcinogenicity, Mutagenicity, Impairment of Fertility: Carboplatin is mutagenic in both in vitro and in vivo experimental models. The carcinogenic potential of carboplatin has not been fully established. However, drugs with similar mechanisms of action and evidence of mutagenic effects have been reported to be carcinogenic.
Patients receiving antineoplastic therapy may experience gonadal suppression resulting in amenorrhea or azospermia depending on the dose and length of therapy and may be irreversible. Men are advised not to father a child during and six months post treatment with carboplatin. These patients should seek advice regarding sperm preservation prior to initiation of therapy because of the possibility of irreversible infertility due to carboplatin therapy.
Effects on ability to drive and use machines: Carboplatin may cause nausea, vomiting, vision abnormalities and ototoxicity; therefore, patients should be warned of the potential effect of the drug on the ability to drive and use machines.
Use in Children: The safety and efficacy of carboplatin in children have not been established.
Use in Elderly: The safety and efficacy of carboplatin when used in geriatric patients have not been established. Geriatric patients experienced severe thrombocytopenia more frequently than in younger patients. Also, carboplatin-induced peripheral neuropathy appears to be more common in adults older than 65 years of age than in younger patients. Among a total of 1942 patients (21% of whom were ≥65 years old) receiving carboplatin monotherapy in different tumor types, a similar incidence of adverse effects was observed in younger and older patients. Other reported clinical experience has not identified differences between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Renal function and decreased hematopoietic function should be considered when determining dosage.