PLATINOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PLATINOL (PLATINOL).
Cisplatin forms intrastrand crosslinks with DNA, inhibiting DNA replication and transcription, leading to cell cycle arrest and apoptosis.
| Metabolism | Cisplatin undergoes nonenzymatic conversion to inactive metabolites; limited hepatic metabolism. |
| Excretion | Renal: >90% unchanged; biliary/fecal <10% |
| Half-life | Terminal elimination half-life: 20-30 hours (biphasic: initial t1/2 20-30 min; post-distribution t1/2 5-10 days for protein-bound platinum). Prolonged in renal impairment. |
| Protein binding | >90% primarily to albumin; irreversible binding to plasma proteins. |
| Volume of Distribution | Vd: 0.25-0.5 L/kg (total body water); extensive tissue distribution, high concentrations in kidneys, liver, skin. |
| Bioavailability | IV: 100% (not administered orally due to severe GI toxicity and poor absorption). |
| Onset of Action | IV: 2-4 hours (earliest clinical effect); peak effect 2-4 weeks. |
| Duration of Action | Duration: 2-4 weeks. Cumulative toxicity (nephrotoxicity, neurotoxicity) may persist for months. |
50-100 mg/m² IV every 3-4 weeks as a single dose or 15-20 mg/m² IV daily for 5 days every 3-4 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 10-50 mL/min: Reduce dose by 25%; CrCl <10 mL/min: Administer 25% of normal dose after dialysis. |
| Liver impairment | Child-Pugh Class B or C: Decrease initial dose by 50% and titrate based on tolerance. |
| Pediatric use | 30-60 mg/m² IV every 3-4 weeks, adjusted based on renal function and myelosuppression. |
| Geriatric use | No specific dose adjustment; monitor renal function closely due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PLATINOL (PLATINOL).
| Breastfeeding | Excreted into human milk; M/P ratio not established. Potential for severe adverse reactions in nursing infants (e.g., nephrotoxicity, ototoxicity). Breastfeeding is contraindicated during therapy and for at least 2 weeks after last dose. |
| Teratogenic Risk | First trimester: High risk of fetal malformations including skeletal, neural tube, and cardiovascular defects based on animal studies and human case reports. Second and third trimesters: Associated with intrauterine growth restriction, oligohydramnios, and fetal nephrotoxicity. Risk of myelosuppression and ototoxicity in the neonate if administered near delivery. |
■ FDA Black Box Warning
Cisplatin is associated with cumulative nephrotoxicity, neurotoxicity, and ototoxicity. Myelosuppression may occur. Anaphylactic-like reactions have been reported.
| Serious Effects |
Pre-existing renal impairment; hearing impairment; history of hypersensitivity to cisplatin or platinum-containing compounds; myelosuppression; concurrent live vaccines.
| Precautions | Renal toxicity (dose-dependent and cumulative); neurotoxicity including peripheral neuropathy; ototoxicity, especially high-frequency hearing loss; myelosuppression; electrolyte disturbances; nausea/vomiting; hypersensitivity reactions; need for adequate hydration and monitoring of renal function. |
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| Fetal Monitoring | Baseline and serial complete blood counts, renal function tests (serum creatinine, BUN), and electrolytes. Auditory testing (audiogram) before and during therapy. Fetal ultrasound to assess growth and amniotic fluid volume. Newborn auditory screening. |
| Fertility Effects | Causes amenorrhea and ovarian failure in females (premature menopause). In males, may cause azoospermia or oligospermia with potential for permanent infertility. Reversibility is variable. |