The frequency of adverse reactions reported is based on a cumulative database of 1,893 patients receiving single agent carboplatin and post-marketing experience. The list is presented by system organ class, MedDRA preferred term, and frequency using the following frequency categories: very common (≥1/10), common (≥1/100 to < 1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (< 1/10,000), and not known (cannot be estimated from the available data).
System Organ Class Frequency MedDRA Term Common Infections*Infections and infestations Not known Pneumonia Neoplasms, benign, malignant and unspecified (incl. cysts and polyps) Not known Treatment related secondary malignancy Very common Thrombocytopenia, neutropenia, leukopenia, anaemia Common Haemorrhage* Blood and lymphatic system disorders Not known Bone marrow failure, febrile neutropenia, hemolytic-uraemic syndrome Immune system disorders Common Hypersensitivity, anaphylactoid type reaction Metabolism and nutrition disorders Not known Dehydration, anorexia, hyponatraemia, tumor lysis syndrome Common Neuropathy peripheral, paraesthesia, decrease of osteotendinous reflexes, sensory disturbance, dysgeusia Nervous system disorders Not known Cerebrovascular accident*, Reversible Posterior Leukoencephalopathy Syndrome (RPLS)# Eye disorders Common Visual disturbance, rare cases of loss of vision Ear and labyrinth disorders Common Ototoxicity Common Cardiovascular disorder*Cardiac disorders Not known Cardiac failure*, Kounis syndrome Vascular disorders Not known Embolism*, hypertension, hypotension Respiratory, thoracic and mediastinal disorders Common Respiratory disorder, interstitial lung disease, bronchospasm Very common Vomiting, nausea, abdominal pain Common Diarrhoea, constipation, mucous membrane disorder Gastrointestinal disorders Not known Stomatitis, pancreatitis# Common Alopecia, skin disorderSkin and subcutaneous tissue disorders Not known Urticaria, rash, erythema, pruritus Musculoskeletal and connective tissue disorders Common Musculoskeletal disorder Renal and urinary disorders Common Urogenital disorder General disorders and Common Asthenia System Organ Class Frequency MedDRA Term administration site conditions Not known Injection site necrosis, injection site reaction, injection site extravasation, injection site erythema, malaise Very common Creatinine renal clearance decreased, blood urea increased, blood alkaline phosphatase increased, aspartate aminotransferase increased, liver function test abnormal, blood sodium decreased, blood potassium decreased, blood calcium decreased, blood magnesium decreased.
Investigation Common Blood bilirubin increased, blood creatinine increased, blood uric acid increased * Fatal in <1%, fatal cardiovascular events in <1% included cardiac failure, embolism, and cerebrovascular accident combined. # based on the post-marketing experience Description of selected adverse reactions Blood and lymphatic system disorders Myelosuppression is the dose-limiting toxicity of carboplatin.
In patients with normal baseline values, thrombocytopenia with platelet counts below 50,000/mm3 occurs in 25% of patients, neutropenia with granulocyte counts below 1,000/mm3 in 18% of patients, and leukopenia with WBC counts below 2,000/mm3 in 14% of patients.
The nadir usually occurs on day 21. Myelosuppression can be worsened by combination of carboplatin with other myelosuppressive compounds or forms of treatment. Myelotoxicity is more severe in previously treated patients, in particular in patients previously treated with cisplatin and in patients with impaired kidney function.
Patients with poor performance status have also experienced increased leukopenia and thrombocytopenia. These effects, although usually reversible, have resulted in infectious and hemorrhagic complications in 4% and 5% of patients given carboplatin, respectively.
These complications have led to death in less than 1% of patients. Anaemia with haemoglobin values below 8 g/dL has been observed in 15% of patients with normal baseline values. The incidence of anaemia is increased with increasing exposure to carboplatin.
Gastrointestinal disorders Vomiting occurs in 65% of patients, in one-third of whom it is severe. Nausea occurs in an additional 15%. Previously treated patients (in particular patients previously treated with cisplatin) appear to be more prone to vomiting.
These effects usually disappear within 24 hours after treatment and are generally responsive to or prevented by antiemetic medication. Vomiting is more likely when carboplatin is given in combination with other emetogenic compounds.
The other gastro-intestinal complaints corresponded to pain in 8% of patients, diarrhoea, and constipation in 6 % of patients. Nervous system disorders Peripheral neuropathy (mainly paresthesias and decrease of osteotendinous reflexes) has occurred in 4% of patients administered carboplatin.
Patients older than 65 years and patients previously treated with cisplatin, as well as those receiving prolonged treatment with carboplatin, appear to be at increased risk. , visual disturbances and taste modifications) have occurred in 1% of patients.
The overall frequency of neurologic side effects seems to be increased in patients receiving carboplatin in combination. This may also be related to longer cumulative exposure. Ear and labyrinth disorders Auditory defects out of the speech range with impairments in the high-frequency range (4,000-8,000 Hz) were found in serial audiometric investigations with a frequency of 15%.
Very rare cases of hypoacusia have been reported. In patients with a hearing organ predamaged due to cisplatin, a further exacerbation in the hearing function sometimes occurs during treatment with carboplatin. Renal and urinary disorders When given in usual doses, development of abnormal renal function has been uncommon, despite the fact that carboplatin has been […]