Carboplatin Pharmachemie Adverse Reactions

Hematologic: Myelosuppression is the dose-limiting toxicity of carboplatin. It is usually reversible and is not cumulative when carboplatin is used as a single agent and at the recommended dosage regimens.
Thrombocytopenia, with nadir platelet counts occurs in about a third of the patients. The nadir usually occurs between days 14 and 21, with recovery within 35 days from the start of therapy.
Leukopenia has also occurred in approximately a fifth of patients but its recovery from the day of nadir (day 14-28) may be slower and usually occurs within 42 days from the start of therapy. A hemoglobin decrease may also be observed.
The hematologic effects, although usually reversible, have resulted in infectious or hemorrhagic complications in patients treated with carboplatin, with drug-related death occurring rarely.
Gastrointestinal: Although carboplatin is significantly less emetogenic than cisplatin, vomiting (65% of the patients and about 33% of these patients is severe) and nausea without vomiting (quarter of the patients) were reported. Nausea and vomiting usually occur 6 to 12 hours after administration of carboplatin and disappear within 24 hours. They are readily controlled (or may be prevented) by antiemetic medication. Emesis was increased when carboplatin was used in combination with other emetogenic compounds.
Other gastrointestinal effects observed frequently were plain, diarrhea and constipation.
Renal: Renal toxicity is usually not dose-limiting in patients receiving carboplatin, nor does it require preventive measures such as high volume fluid hydration or forced diuresis. Nevertheless, increasing blood urea or serum creatinine levels can occur. Renal function impairment, as defined by decrease in the creatinine clearance below 60 ml/min, may also be observed. The incidence and severity of nephrotoxicity may increase in patients who have impaired kidney function before carboplatin treatment.
Creatinine clearance has proven to be the most sensitive measure of kidney function in patients receiving carboplatin, and it appears to be the most useful test for correlating drug clearance and bone marrow suppression.
Decreases in serum magnesium, potassium and calcium have occurred after treatment with carboplatin but have not been reported to be severe enough to cause the appearance of clinical signs or symptoms.
Neurologic: In the majority of patients, neurotoxicity is limited to parasthesias and decreased deep tendon reflexes. Peripheral neuropathies have been observed infrequently, however its incidence is increased in patients older than 65 years and in patients previously treated with cisplatin. Parasthesias present before commencing therapy with carboplatin, particularly if related to prior cisplatin treatment, may persist or worsen during treatment with carboplatin.
Special Senses: Transient visual disturbances, sometimes including transient sight loss, have been reported rarely with carboplatin therapy. This is usually associated with high dose therapy in renally-impaired patients.
Ototoxicity, usually manifested as tinnitus, has been reported. In patients who developed hearing loss as a result of cisplatin therapy, the impairment may persist or worsen. Dysgeusia has been rarely reported.
Other: Abnormalities of liver function tests (usually mild to moderate) have been reported with carboplatin in about one-third of the patients with normal baseline values. The alkaline phosphatase level is increased more frequently than SGOT, SGPT or total bilirubin. The majority of these abnormalities regress spontaneously during the course of treatment. Hypersensitivity reactions, similar to those seen after cisplatin treatment, have been observed.
They included: erythematous rash, fever, pruritus, bronchospasm and hypotension. These reactions have been successfully managed with standard epinephrine, corticosteroid and antihistamine therapy.
Pain, asthenia, alopecia, cardiovascular, respiratory, genitourinary and mucosal side effects, were also reported.