Cisplatin

• Nephrotoxicity: cisplatin injection can cause severe renal toxicity, including acute renal failure. Severe renal toxicities are dose-related and cumulative. Ensure adequate hydration and monitor renal function and electrolytes. Consider dose reductions or alternative treatments in patients with renal impairment
  
  

  [see Dosage and Administration (
  
  

  2.1 Hydration and Anti-Emetic Treatment

  Patients treated with cisplatin injection must receive appropriate pre-treatment hydration. Maintain adequate hydration and urinary output for 24 hours after cisplatin injection administration

  [see Warnings and Precautions ]

  . Administer pre-treatment and post-treatment antiemetics as appropriate

  [see Warnings and Precautions ]

  .

  ) and Warnings and Precautions (
  
  

  5.1 Nephrotoxicity

  Cisplatin injection can cause dose-related nephrotoxicity, including acute renal failure that becomes more prolonged and severe with repeated courses of the drug. Renal toxicity typically begins during the second week after a dose of cisplatin injection. Patients with baseline renal impairment, geriatric patients, patients who are taking other nephrotoxic drugs, or patients who are not well hydrated may be more susceptible to nephrotoxicity

  [see Use in Specific Populations ]

  .

  Ensure adequate hydration before, during, and after cisplatin injection administration

  [see Dosage and Administration ]

  . Measure serum creatinine, blood urea nitrogen, creatinine clearance, and serum electrolytes including magnesium prior to initiating therapy, and as clinically indicated. Consider magnesium supplementation as clinically needed.

  Consider alternative treatments or reduce the dose of cisplatin injection for patients with baseline renal impairment or who develop significant reductions in creatinine clearance during treatment with cisplatin injection according to clinical treatment guidelines

  [see Dosage and Administration].

  )].
  
  
• Peripheral Neuropathy: cisplatin injection can cause dose-related peripheral neuropathy that becomes more severe with repeated courses of the drug
  
  

  [see Warnings and Precautions (
  
  

  5.2 Peripheral Neuropathy

  Cisplatin injection can cause dose-related peripheral neuropathy that becomes more severe with repeated courses of the drug. Neurologic symptoms have been reported to occur after a single dose. Neuropathy can also have a delayed onset from 3 to 8 weeks after the last dose of cisplatin injection. Manifestations include paresthesias in a stocking-glove distribution, areflexia, and loss of proprioception and vibratory sensation. The neuropathy may progress further even after stopping treatment. Peripheral neuropathy may be irreversible in some patients.

  Perform a neurological examination before initiating cisplatin injection, at appropriate intervals during therapy, and after completion of therapy. Consider discontinuation of cisplatin injection for patients who develop symptomatic peripheral neuropathy. Geriatric patients may be more susceptible to peripheral neuropathy

  [see Use in Specific Populations ]

  .

  )].
  
  
• Nausea and Vomiting: cisplatin injection can cause severe nausea and vomiting. Use highly effective antiemetic premedication
  
  

  [see Dosage and Administration (
  
  

  2.1 Hydration and Anti-Emetic Treatment

  Patients treated with cisplatin injection must receive appropriate pre-treatment hydration. Maintain adequate hydration and urinary output for 24 hours after cisplatin injection administration

  [see Warnings and Precautions ]

  . Administer pre-treatment and post-treatment antiemetics as appropriate

  [see Warnings and Precautions ]

  .

  ) and Warnings and Precautions (
  
  

  5.3 Nausea and Vomiting

  Cisplatin injection is a highly emetogenic antineoplastic agent. Premedicate with anti-emetic agents

  [see Dosage and Administration ]

  . Without antiemetic therapy, marked nausea and vomiting occur in almost all patients treated with cisplatin injection 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 72 hours. Maximal intensity occurs 48 to 72 hours after administration. 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 injection therapy. Consider the use of additional anti-emetics following infusion.

  )].
  
  
• Myelosuppression: cisplatin injection can cause severe myelosuppression with fatalities due to infections. Monitor blood counts accordingly. Interruption of therapy may be required
  
  

  [see Warnings and Precautions (
  
  

  5.4 Myelosuppression

  Myelosuppression suppression occurs in 25% to 30% of patients treated with cisplatin injection. Fever and infection have been reported in patients with neutropenia. Potential fatalities due to infection (secondary to myelosuppression) have been reported. Geriatric patients may be more susceptible to myelosuppression

  [see Use in Specific Populations ]

  .

  Perform standard hematologic tests before initiating cisplatin injection, before each subsequent course, and as clinically indicated. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with cisplatin injection. For patients who develop severe myelosuppression during treatment with cisplatin injection, consider dose modifications and manage according to clinical treatment guidelines.

  )].
  
  

Cisplatin injection is a platinum-based drug indicated for the treatment of:

• Advanced testicular cancer (

• Advanced ovarian cancer (

• Advanced bladder cancer (

• Administer pre-treatment hydration and pre- and post-treatment antiemetics. (

• Cisplatin injection has been administered intravenously at:

• Advanced testicular cancer: 20 mg/m2 daily for 5 days per cycle (
  
  
  2.2 Advanced Testicular Cancer

  Cisplatin injection has been administered at 20 mg/m²intravenously daily for 5 days per cycle. Other doses and combination regimens have been used.
  )
  
• Advanced ovarian cancer: 75 mg/m2 to 100 mg/m2 per cycle once every 3 to 4 weeks (
  
  
  2.3 Advanced Ovarian Cancer

  Cisplatin injection has been administered at 75 mg/m²to 100 mg/m²intravenously per cycle once every 3 to 4 weeks on Day 1. Other doses and combination regimens have been used.
  )
  
• Advanced bladder cancer: 50 mg/m2 to 70 mg/m2 intravenously per cycle once every 3 to 4 weeks (
  
  
  2.4 Advanced Bladder Cancer

  Cisplatin injection has been administered at 50 mg/m²to 70 mg/m²intravenously per cycle once every 3 to 4 weeks. For heavily pretreated patients, an initial dose of 50 mg/m²per cycle repeated every 4 weeks is recommended. Other doses and combination in regimens have been used.
  )
  
• Refer to current treatment guidelines for specific dosing information.

• Administer by slow intravenous infusion. Avoid contact of cisplatin injection with aluminum parts. (

Cisplatin injection USP, is a clear, colorless to pale yellow, sterile aqueous solution available in sterile multiple-dose vials containing

• 50 mg/50 mL (1 mg/mL)
• 100 mg/100 mL (1 mg/mL)

• Lactation: Advise not to breastfeed. (
  
  
  8.2 Lactation

  Risk Summary

  Limited data from published literature report the presence of cisplatin in human milk in low amounts. Because of the potential for serious adverse reactions from cisplatin injection in a breastfed child and because of the potential for tumorigenicity shown for cisplatin injection, advise lactating women not to breastfeed during treatment with cisplatin injection.
  )
  
• Females and Males of Reproductive Potential: Verify pregnancy status prior to initiation of cisplatin injection. Can impair fertility. (
  
  
  8.3 Females and Males of Reproductive Potential

  Pregnancy Testing

  Verify the pregnancy status of females of reproductive potential prior to initiation of cisplatin injection.

  Contraception

  Females

  Cisplatin injection can cause fetal harm when administered to a pregnant woman

  [see Use in Specific Populations ]

  . Advise females of reproductive potential to use effective contraception during treatment and for 14 months following the last dose of cisplatin injection.

  Males

  Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 11 months after the last dose of cisplatin injection.

  Infertility

  Females

  The use of cisplatin has been associated with cumulative dose-dependent ovarian failure, premature menopause, and reduced fertility.

  Males

  The use of cisplatin has been associated with a cumulative dose-dependent impairment of spermatogenesis (oligospermia, azoospermia; possibly irreversible) and reduced fertility.
  )