Cisplatin Side Effects

Not all side effects for cisplatin may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to cisplatin: intravenous powder for solution, intravenous solution

In addition to its needed effects, some unwanted effects may be caused by cisplatin. In the event that any of these side effects do occur, they may require medical attention.

Also, because of the way cancer medicines act on the body, there is a chance that they might cause other unwanted effects that may not occur until months or years after the medicine is used. These delayed effects may include certain types of cancer, such as leukemia. Discuss these possible effects with your doctor.

You should check with your doctor immediately if any of these side effects occur when taking cisplatin:

Less common
  • Black, tarry stools
  • blood in urine or stools
  • cough or hoarseness accompanied by fever or chills
  • dizziness or faintness (during or shortly after a dose)
  • fast heartbeat (during or shortly after a dose)
  • fever or chills
  • lower back or side pain accompanied by fever or chills
  • painful or difficult urination accompanied by fever or chills
  • pain or redness at place of injection
  • pinpoint red spots on skin
  • swelling of face (during or shortly after a dose)
  • unusual bleeding or bruising
  • wheezing (during or shortly after a dose)

If any of the following side effects occur while taking cisplatin, check with your doctor or nurse as soon as possible:

More common
  • Joint pain
  • loss of balance
  • ringing in ears
  • swelling of feet or lower legs
  • trouble in hearing
  • unusual tiredness or weakness
Less common
  • Convulsions (seizures)
  • loss of reflexes
  • loss of taste
  • numbness or tingling in fingers or toes
  • trouble in walking
Rare
  • Agitation or confusion
  • blurred vision
  • change in ability to see colors (especially blue or yellow)
  • muscle cramps
  • sores in mouth and on lips

Some of the side effects that can occur with cisplatin may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Nausea and vomiting (severe)
Less common
  • Loss of appetite

After you stop taking this drug, it is possible that you may still experience side effects that need medical attention. If you notice any of the following side effects check with your doctor immediately:

  • Black, tarry stools
  • blood in urine or stools
  • convulsions (seizures)
  • cough or hoarseness
  • decrease in urination
  • fever or chills
  • loss of balance
  • loss of reflexes
  • loss of taste
  • lower back or side pain
  • numbness or tingling in fingers or toes
  • painful or difficult urination
  • pinpoint red spots on skin
  • ringing in ears
  • swelling of feet or lower legs
  • trouble in hearing
  • trouble in walking
  • unusual bleeding or bruising

For Healthcare Professionals

Applies to cisplatin: compounding powder, intravenous powder for injection, intravenous solution

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.[Ref]

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.[Ref]

Gastrointestinal

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.[Ref]

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.)[Ref]

Nervous system

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.[Ref]

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.[Ref]

Hematologic

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

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

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.[Ref]

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.[Ref]

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

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.[Ref]

Endocrine

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

Dermatologic

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

Metabolic

Metabolic side effects have included chronic lipid abnormalities.

References

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