Cisplatin Pfizer Adverse Reactions

Gastrointestinal Disorders: Stomatitis, vomiting, nausea, anorexia, hiccups, diarrhoea.
Cisplatin induces severe nausea and vomiting in almost all patients. Severe nausea and vomiting usually begin 1-4 hours after treatment and may persist for up to a week. This may necessitate stopping treatment. These side effects are only partially relieved by standard antiemetics. The severity of these symptoms may be reduced by dividing the total dose per cycle into smaller doses given once daily for five days. Reported toxicity includes gingival platinum line.
Renal and Urinary Disorders: Acute renal toxicity, which was highly frequent in the past and represented the major dose-limiting toxicity of cisplatin, has been greatly reduced by the use of 6 to 8 hour infusions as well as by concomitant intravenous hydration and forced diuresis. Cumulative toxicity, however, remains a problem and may be severe. Renal impairment, which is associated with tubular damage, may first be noted during the second week after a dose and is manifested by an increase in serum creatinine, BUN, serum uric acid and/or decrease in creatinine clearance. Renal insufficiency is generally mild to moderate and reversible at the usual doses of the drug, however, high or repeated doses can increase the severity and duration of renal impairment and may produce irreversible renal insufficiency (sometimes fatal). Renal failure has been reported following intraperitoneal instillation of the drug.
Blood and Lymphatic System Disorders: Thrombotic microangiopathy (haemolytic uraemic syndrome), bone marrow failure, neutropenia, Coombs positive haemolytic anaemia.
Myelosuppression often occurs during cisplatin therapy. Mild bone marrow toxicity may occur with both leucopenia and thrombocytopenia. These effects are usually reversible after ceasing treatment. Cisplatin may also induce anaemia: this is not clearly dose related and is occasionally caused by haemolysis. Leucopenia and thrombocytopenia are dose-related and more pronounced at doses greater than 50 mg/m². Leucocyte and platelet nadirs generally occur between days 18 and 23 of treatment, with recovery in most patients by day 39. Anaemia occurs at approximately the same frequency.
There have been rare reports of acute myelogenous leukemias and myelodysplastic syndromes arising in patients who have been treated with cisplatin, mostly when given in combination with other potentially leukemogenic agents.
Infections and Infestations: Infection (infectious complications have led to death), sepsis.
Immune System Disorders: Anaphylactic and anaphylactic like reactions such as flushing, facial oedema, wheezing, tachycardia, and hypotension have been reported in patients previously exposed to cisplatin. The reactions usually occur within a few minutes of cisplatin administration and may be controlled with IV adrenaline, corticosteroids and/or antihistamines.
Ear and Labyrinth Disorders: Unilateral or bilateral tinnitus and/or hearing loss in high frequencies (>4000 Hz) may occur in 10% of patients and is usually reversible. The damage to the hearing system appears to be dose related and cumulative, and it is reported more frequently in very young or very old patients. Auditory function should be monitored more closely during treatment.
Nervous System Disorders: Convulsion, leukoencephalopathy, reversible posterior leukoencephalopathy syndrome, haemorrhagic stroke, ischaemic stroke, ageusia, cerebral arteritis, myelopathy.
Peripheral neuropathies occur infrequently with usual doses of the drug. They are generally sensory in nature (e.g., paraesthesia of the upper and lower extremities), but can also include motor difficulties, reduced or absent reflexes and leg weakness. Autonomic neuropathy, seizures, slurred speech, loss of taste and memory loss have also been reported. These neuropathies usually appear after prolonged therapy, but have also developed after a single drug dose. Areflexia and loss of proprioception and vibratory sensation may be seen, especially if cisplatin is given at higher doses or more frequently than recommended. In some patients they may be irreversible however, they have been partially or completely reversible in others following discontinuance of cisplatin therapy. Cerebrovascular accident has been reported in patients treated with cisplatin. Lhermitte's sign has been reported.
Eye Disorders: Retinal toxicity manifests as blurred vision and altered colour perception. Optic neuritis, papilloedema and cortical blindness have been reported rarely following the administration of cisplatin. These events are usually reversible after drug withdrawal. Retinal pigmentation has also been reported.
Cardiac Disorders: Cardiovascular abnormalities (coronary disease, congestive heart failure, arrhythmias, postural hypotension, thrombotic microangiopathy, bradycardia, tachycardia, cardiac arrest, cardiac disorder etc.).
Vascular Disorders: Raynaud's phenomenon. Venous thromboembolism.
A significant increase in the risk of venous thromboembolic events has been reported in patients with advanced solid tumours and treated with cisplatin compared with non-cisplatin-based chemotherapy.
Vascular toxicity coincident with the use of cisplatin in combination with other antineoplastic agents have been reported rarely. The events are clinically heterogeneous and may include myocardial infarction, cerebrovascular accident (haemorrhagic and ischaemic stroke), thrombotic microangiopathy (haemolytic uremic syndrome) or cerebral arteritis. Various mechanisms have been proposed for these vascular complications.
Respiratory, Thoracic and Mediastinal Disorders: Pulmonary embolism.
Pulmonary toxicity has been reported in patients treated with cisplatin in combination with bleomycin or 5-fluorouracil.
Hepatobiliary Disorders: Mild and transient elevations of serum AST and ALT levels may occur infrequently.
Skin and Subcutaneous Tissue Disorders: Mild alopecia. Rarely, urticarial or maculopapular skin rashes have also been observed.
Musculoskeletal and Connective Tissue Disorders: Myalgia, muscle spasm.
Reproductive System and Breast Disorders: Impairment of spermatogenesis and azoospermia have been reported (see Use in Pregnancy & Lactation).
Metabolism and Nutrition Disorders: Cisplatin may cause dehydration in patients. Cisplatin may also cause serious electrolyte disturbances, mainly represented by hypomagnesaemia, hypocalcaemia, and hypokalaemia, and associated with renal tubular dysfunction. Hypomagnesaemia and/or hypocalcaemia may become symptomatic, with muscle irritability or cramps, clonus, tremor, carpopedal spasm and/or tetany. Hypomagnesaemia and hypocalcaemia may develop during cisplatin therapy or following discontinuance of the drug. Other reported toxicities are hyperuricaemia, hyponatremia hypophosphataemia and syndrome of inappropriate antidiuretic hormone (SIADH). Hyperuricaemia may occur in patients receiving cisplatin, principally as a result of drug-induced nephrotoxicity. Hyperuricaemia is more pronounced with doses greater than 50 mg/m², with peak levels occurring between 3-5 days after administration of the drug. Allopurinol may be administered to reduce serum uric acid levels. Regular monitoring of serum electrolyte levels and replacement where necessary are advisable.
General Disorders and Administration Site Conditions: Pyrexia, asthenia, malaise. Local effects such as pain, oedema, erythema, phlebitis, tissue cellulitis, fibrosis and skin necrosis (following extravasation of the drug) may also occur. Extravasation may result from infusion of solutions greater than 0.5 mg/mL cisplatin.