Cisplatin Side Effects

Brand Names: Platinol

Please note - some side effects for Cisplatin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Cisplatin - for the Consumer

Cisplatin

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Cisplatin:

Diarrhea; loss of appetite; nausea; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur when using Cisplatin:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; wheezing); blood in the urine; bloody, black, or tarry stools; burning, numbness, or tingling of the arms, hands, legs, or feet; chest pain; confusion; decreased urine volume or frequency; dizziness; fainting; fast or irregular heartbeat; hearing problems (eg, loss of hearing); joint pain; lightheadedness; loss of balance; loss of motor function; loss of taste; mental or mood changes; muscle pain, weakness, or cramping; numbness of an arm or leg; one-sided weakness; pain, redness, or swelling at the injection site; ringing in the ears; seizures; severe or persistent diarrhea, nausea, or vomiting; slurred speech; stomach or back pain; sudden, severe headache; symptoms of infection (eg, fever, chills, cough, sore throat); uncontrolled muscle movements; unusual bruising or bleeding; unusual tiredness or weakness; vision changes (eg, blindness, blurred vision, inability to distinguish colors); yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Cisplatin Side Effects - for the Professional

Cisplatin

Nephrotoxicity

Dose-related and cumulative renal insufficiency, including acute renal failure, is the major dose-limiting toxicity of Cisplatin. Renal toxicity has been noted in 28% to 36% of patients treated with a single dose of 50 mg/m2. It is first noted during the second week after a dose and is manifested by elevations in BUN and creatinine, serum uric acid and/or a decrease in creatinine clearance. Renal toxicity becomes more prolonged and severe with repeated courses of the drug. Renal function must return to normal before another dose of Cisplatin can be given. Elderly patients may be more susceptible to nephrotoxicity.

Impairment of renal function has been associated with renal tubular damage. The administration of Cisplatin using a 6- to 8-hour infusion with intravenous hydration, and mannitol has been used to reduce nephrotoxicity. However, renal toxicity still can occur after utilization of these procedures.

Ototoxicity

Ototoxicity has been observed in up to 31% of patients treated with a single dose of Cisplatin 50 mg/m2, and is manifested by tinnitus and/or hearing loss in the high frequency range (4000 to 8000 Hz). Decreased ability to hear normal conversational tones may occur. Deafness after the initial dose of Cisplatin has been reported. Ototoxic effects may be more severe in children receiving Cisplatin. Hearing loss can be unilateral or bilateral and tends to become more frequent and severe with repeated doses. Ototoxicity may be enhanced with prior or simultaneous cranial irradiation. It is unclear whether Cisplatin-induced ototoxicity is reversible. Ototoxic effects may be related to the peak plasma concentration of Cisplatin. Careful monitoring of audiometry should be performed prior to initiation of therapy and prior to subsequent doses of Cisplatin.

Vestibular toxicity has also been reported.

Ototoxicity may become more severe in patients being treated with other drugs with nephrotoxic potential.

Hematologic

Myelosuppression occurs in 25% to 30% of patients treated with Cisplatin. The nadirs in circulating platelets and leukocytes occur between days 18 to 23 (range 7.5 to 45) with most patients recovering by day 39 (range 13 to 62). Leukopenia and thrombocytopenia are more pronounced at higher doses (>50 mg/m2). Anemia (decrease of 2 g hemoglobin/100 mL) occurs at approximately the same frequency and with the same timing as leukopenia and thrombocytopenia. Fever and infection have also been reported in patients with neutropenia. Potential fatalities due to infection (secondary to myelosuppression) have been reported. Elderly patients may be more susceptible to myelosuppression.

In addition to anemia secondary to myelosuppression, a Coombs' positive hemolytic anemia has been reported. In the presence of Cisplatin hemolytic anemia, a further course of treatment may be accompanied by increased hemolysis and this risk should be weighed by the treating physician.

The development of acute leukemia coincident with the use of Cisplatin has been reported. In these reports, Cisplatin was generally given in combination with other leukemogenic agents.

Gastrointestinal

Marked nausea and vomiting occur in almost all patients treated with Cisplatin, and may be so severe that the drug must be discontinued. Nausea and vomiting may begin within 1 to 4 hours after treatment and last up to 24 hours. Various degrees of vomiting, nausea and/or anorexia may persist for up to 1 week after treatment.

Delayed nausea and vomiting (begins or persists 24 hours or more after chemotherapy) has occurred in patients attaining complete emetic control on the day of Cisplatin therapy.

Diarrhea has also been reported.

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Side Effects by Body System - for Healthcare Professionals

Renal

A study of 12 patients who received recommended doses of cisplatin incurred moderate loss of renal function 12 and 24 months after therapy was discontinued. The renal dysfunction was not progressive. However, glomerular filtration rate (GFR) and effective renal plasma flow (EPRF) were decreased by 23% and 19%, respectively. Other studies have shown moderate and permanent reduction in GFR up to 52 months after cisplatin therapy.

Elderly patients may be more susceptible to nephrotoxicity.

The risk of renal toxicity may be decreased with appropriate monitoring of renal function tests as well as aggressive hydration with chloride-containing fluids and appropriate electrolyte replacement. Amifostine, a thiol chemoprotectant, is approved to reduce cisplatin nephrotoxicity and does not interfere with antitumor activity.

Renal side effects have been reported to present during the second week after a dose of cisplatin and become more prolonged and severe with repeated courses of cisplatin therapy. Nephrotoxicity is the most important dose-limiting side effect of cisplatin, which is dose-related, cumulative, and occurs in 36% of patients after single doses of 50 mg/m2. Renal function should return to baseline before subsequent doses are administered.

Cisplatin-induced renal tubule damage can result in clinically significant hypomagnesemia and hypokalemia as well as hypocalcemia, hyponatremia, hypophosphatemia, and hyperuricemia.

Gastrointestinal

Acute cisplatin-induced emesis occurs one to four hours after cisplatin administration and is primarily serotonin mediated. Appropriate antiemetics are essential. A serotonin-receptor antagonist in combination with a steroid generally controls this emesis effectively.

Delayed emesis occurs two to seven days after cisplatin administration and is more difficult to control. Oral steroid therapy, if tolerated, with or without metoclopramide may be useful in the prevention of delayed emesis. (Serotonin antagonists provide limited benefits for delayed emesis.)

Gastrointestinal side effects have included nausea and vomiting which can be dose-limiting in some patients. Nausea and vomiting usually begin one to four hours after treatment and may last up to five days. Diarrhea, hiccups, and elevated serum amylase have also been reported.

Nervous system

Nervous system side effects can be dose limiting for patients receiving cisplatin. The most common form of nerve damage from cisplatin is a sensory polyneuropathy. Other forms of nerve damage from cisplatin include autonomic neuropathies, seizures, encephalopathy, myasthenic syndrome, cortical blindness, Lhermitte's sign, and dorsal column myelopathy. Ototoxicity, headache, loss of taste, strokes, leukoencephalopathy, and reversible posterior leukoencephalopathy syndrome (RPLS) have also been reported.

Symptoms of the sensory polyneuropathy typically begin in toes and feet and, later, affect the fingers and hands in a stocking-and-glove distribution. The neuropathies typically occur after prolonged therapy (4 to 7 months). However, symptoms have been reported after a single dose. Cisplatin neuropathies generally occur with higher dosage regimens and may be irreversible.

Elderly patients may be more susceptible to peripheral neuropathy.

Tinnitus and/or high-frequency (4000 to 8000 Hz) hearing loss occurs first, is unilateral or bilateral and may appear 3 to 4 days after initial treatment; however, deafness after the initial dose of cisplatin is rare. Cisplatin-induced ototoxicity is related to the loss of outer hair cells in the cochlea. Ototoxicity is associated with both high cisplatin doses and high cumulative doses. Hearing impairment is generally irreversible; however, hearing aids may help.

Hematologic

Hematologic side effects including myelosuppression have been reported. Cisplatin causes moderate and transient myelosuppression in 25% to 30% of patients. Coombs' positive hemolytic anemia has also been reported.

Myelosuppression is a dose-related effect and usually occurs with doses greater than 50 mg/m2. Cisplatin-based therapy may result in a cumulative, clinically significant anemia which is disproportionate to the drugs effects on other blood cells.

Elderly patients may be more susceptible to myelosuppression.

Frequent anemia was reported in one study with 28 patients receiving six cycles of cisplatin in combination with 3 other chemotherapeutic agents. Thirteen patients became severely anemic, 12 became moderately anemic, and three became mildly anemic. The anemia was progressive and 66.7% of the patients became severely anemic during the third and fourth months of therapy.

Treatment of anemia with recombinant erythropoietin is generally helpful. Epoetin alfa has been approved for use in the treatment of anemia in patients with nonmyeloid malignancies where anemia is the result of concomitantly administered chemotherapy.

The nadirs in circulating erythrocytes, platelets, and leukocytes occur between days 18 to 23 (range 7.5 to 45), with most patients recovering by day 39 (range 13 to 62). Leukocytes usually recover after 14 to 21 days. Most patients are able to be retreated at 21 day intervals.

Ocular

Ocular side effects including optic neuritis, papilledema, cortical blindness, focal deficits, and cerebral blindness have been infrequently reported in patients receiving standard doses of cisplatin. Improvement and/or total recovery usually occurs after discontinuation of cisplatin. Blurred vision and altered color perception have been reported after the use of regimens with higher doses or greater dose frequencies than those recommended by the manufacturer.

Hypersensitivity

Hypersensitivity side effects including anaphylactic-like reactions have been occasionally reported in patients previously exposed to cisplatin. The reactions consist of facial edema, wheezing, tachycardia, and hypotension within a few minutes of drug administration.

Reactions may be treated with intravenous epinephrine, corticosteroids and/or antihistamines. Supportive equipment and medications should be available for possible anaphylactic-like reactions.

Hepatic

Hepatic side effects including transient elevations of liver enzymes, especially SGOT, as well as bilirubin, have been reported. However, the incidence and clinical importance is relatively low.

Local

Severity of the local tissue toxicity appears to be related to the concentration of the cisplatin solution. Infusions of solutions with a cisplatin concentration greater than 0.5 mg/mL may rarely result in tissue inflammation and fibrosis.

Local side effects including soft tissue toxicity have rarely been reported following extravasation of cisplatin.

Cardiovascular

Cardiovascular side effects including myocardial infarction, cerebrovascular accident, deep vein thrombosis, pulmonary embolism, transient ischemic attack, thrombotic microangiopathy (hemolytic uremic syndrome), cerebral arteritis, and blood pressure abnormalities have been reported. Raynaud's phenomenon has been reported in patients receiving bleomycin and vinblastine, with or without cisplatin. Distal ischemic changes have been reported in patients receiving combination chemotherapy with cisplatin and gemcitabine. Possible cardiotoxicity (ST-T wave abnormalities and bundle branch block) have rarely been reported. Atrial fibrillation, supraventricular tachycardia, and bradycardia have also been reported.

Endocrine

Endocrine side effects including the syndrome of inappropriate antidiuretic hormone have been reported.

Dermatologic

Dermatologic side effects including rash and alopecia have been reported. A case of digital necrosis has also been reported.

Metabolic

Metabolic side effects have included chronic lipid abnormalities.

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