Cisplatin Prescribing Information
- 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 () and Warnings and Precautions (
2.1 Hydration and Anti-Emetic TreatmentPatients 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 ].)].5.1 NephrotoxicityCisplatin 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 NeuropathyCisplatin 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 () and Warnings and Precautions (
2.1 Hydration and Anti-Emetic TreatmentPatients 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 ].)].5.3 Nausea and VomitingCisplatin 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 MyelosuppressionMyelosuppression 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.
• Administer pre-treatment hydration and pre- and post-treatment antiemetics. (
Patients treated with cisplatin injection must receive appropriate pre-treatment hydration. Maintain adequate hydration and urinary output for 24 hours after cisplatin injection administration
• Cisplatin injection has been administered intravenously at:
- o Advanced testicular cancer: 20 mg/m2 daily for 5 days per cycle ()
2.2 Advanced Testicular CancerCisplatin injection has been administered at 20 mg/m2intravenously daily for 5 days per cycle. Other doses and combination regimens have been used.
- o Advanced ovarian cancer: 75 mg/m2 to 100 mg/m2 per cycle once every 3 to 4 weeks ()
2.3 Advanced Ovarian CancerCisplatin 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.
- o Advanced bladder cancer: 50 mg/m2 to 70 mg/m2 intravenously per cycle once every 3 to 4 weeks ()
2.4 Advanced Bladder CancerCisplatin 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. (
Do not use needles or intravenous sets containing aluminum parts that can come in contact with cisplatin injection during preparation or administration. Aluminum reacts with cisplatin injection, causing precipitate formation and a loss of potency.
Cisplatin injection is a cytotoxic drug. Follow applicable special handling and disposable procedures.1
The aqueous solution should be used intravenously only and should be administered by IV infusion over a 6- to 8-hour period (see
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Administer cisplatin injection by slow intravenous infusion.
Cisplatin injection, USP, is a clear, colorless to pale yellow, sterile aqueous solution available in sterilie 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 LactationRisk SummaryLimited 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 PotentialPregnancy TestingVerify the pregnancy status of females of reproductive potential prior to initiation of cisplatin injection.
ContraceptionFemalesCisplatin 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.MalesAdvise 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.
InfertilityFemalesThe use of cisplatin has been associated with cumulative dose-dependent ovarian failure, premature menopause, and reduced fertility.
MalesThe use of cisplatin has been associated with a cumulative dose-dependent impairment of spermatogenesis (oligospermia, azoospermia; possibly irreversible) and reduced fertility.
Cisplatin injection is contraindicated in patients with severe hypersensitivity to cisplatin
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
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.
- Hypersensitivity reactions: Anaphylaxis and death may occur; monitor for and treat accordingly ()
5.5 Hypersensitivity ReactionsCisplatin injection can cause severe hypersensitivity reactions, including anaphylaxis and death. Manifestations have included facial edema, wheezing, tachycardia, and hypotension. Hypersensitivity reactions have occurred within minutes of administration to patients with prior exposure tocisplatin injection.
Monitor patients receiving cisplatin injection for possible hypersensitivity reactions. Ensure supportive equipment and medications are available to treat severe hypersensitivity reactions. Severe hypersensitivity reactions require immediate discontinuation of cisplatin injection and aggressive therapy. Patients with a history of severe hypersensitivity reactions should not be rechallenged with cisplatin injection
[see Contraindications ]. Cross-reactivity between platinum-based antineoplastic agents has been reported. Cases of severe hypersensitivity reactions have recurred after rechallenging patients with a different platinum agent. - Ototoxicity: Cumulative toxicity may be severe particularly in pediatric patients; consider audiometric and vestibular function monitoring (,
5.6 OtotoxicityCisplatin injection can cause ototoxicity, which is cumulative and may be severe. Consider audiometric and vestibular function monitoring.
Ototoxicity is manifested by tinnitus, hearing loss in the high frequency range (4,000 to 8,000 Hz) and/or decreased ability to hear normal conversational tones. Ototoxicity can occur during or after treatment and can be unilateral or bilateral. Deafness after the initial dose of cisplatin injection has been reported. Vestibular toxicity has also been reported.
Ototoxic effects can be more severe and detrimental in pediatric patients, particularly in patients less than 5 years of age. The prevalence of hearing loss in pediatric patients is estimated to be 40-60%. Additional risk factors for ototoxicity include simultaneous cranial irradiation, treatment with other ototoxic drugs and renal impairment. Consider audiometric and vestibular testing in all pediatric patients receiving cisplatin
[see Use in Specific Populations ].Genetic factors (e.g. variants in the thiopurine S-methyltransferase [TPMT] gene) may also contribute to the cisplatin-induced ototoxicity; although this association has not been consistent across populations and study designs.
)8.4 Pediatric UseOtotoxic effects may be more severe and detrimental in pediatric patients receiving cisplatin injection, particularly in patients less than 5 years of age. Consider audiometric and vestibular function monitoring in all patients receiving cisplatin injection. The prevalence of hearing loss in pediatric patients is particularly high and is estimated to be 40% to 60%.
Earlier detection of hearing loss can limit the potential impact of hearing impairment on a pediatric patient’s cognitive and social development
[see Warnings and Precautions ]. - Ocular toxicity: Optic neuritis, papilledema, and cortical blindness may occur ()
5.7 Ocular ToxicityOptic neuritis, papilledema, and cortical blindness have been reported in patients receiving standard recommended doses of cisplatin injection. Blurred vision and altered color perception have been reported after the use of regimens with higher doses and dose frequencies of cisplatin injection. The altered color perception manifests as a loss of color discrimination, particularly in the blue-yellow axis and irregular retinal pigmentation of the macular area on fundoscopic exam. Improvement and/or total recovery usually occurs after discontinuing cisplatin injection but can be delayed.
- Secondary leukemia: Secondary acute leukemia may occur ()
5.8 Secondary MalignanciesThe development of acute leukemia secondary to the use of cisplatin injection has been reported. In these reports, cisplatin injection was generally given in combination with other leukemogenic agents.
- Embryo-fetal toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception. (,
5.9 Embryo-Fetal ToxicityBased on human data, cisplatin injection can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 14 months after the last dose of cisplatin injection. 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
[see Use in Specific Populations ].,8.1 PregnancyRisk SummaryBased on human data from published literature, cisplatin injection can cause fetal harm when administered to pregnant women. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Data demonstrates transplacental transfer of cisplatin. Exposure of pregnant women to cisplatin-containing chemotherapy has been associated with oligohydramnios, intrauterine growth restriction, and preterm birth. Cases of neonatal acute respiratory distress syndrome, cytopenias, and hearing loss have been reported. Cisplatin injection administration to animals during and after organogenesis resulted in teratogenicity. A published study in mice showed placental transfer of cisplatin increased with placenta maturation.
The background risk of major birth defects and miscarriage for the indicated populations are unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.
)8.3 Females and Males of Reproductive PotentialPregnancy TestingVerify the pregnancy status of females of reproductive potential prior to initiation of cisplatin injection.
ContraceptionFemalesCisplatin 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.MalesAdvise 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.
InfertilityFemalesThe use of cisplatin has been associated with cumulative dose-dependent ovarian failure, premature menopause, and reduced fertility.
MalesThe use of cisplatin has been associated with a cumulative dose-dependent impairment of spermatogenesis (oligospermia, azoospermia; possibly irreversible) and reduced fertility.