PLATINOL-AQ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PLATINOL-AQ (PLATINOL-AQ).

How it works

Platinol-AQ (cisplatin) exerts its cytotoxic effects by forming intrastrand and interstrand DNA crosslinks, thereby inhibiting DNA replication and transcription, leading to apoptosis.

What the body does with it

Metabolism	Cisplatin is metabolized via aquation to reactive species, primarily in the liver and kidneys, involving glutathione conjugation and subsequent enzymatic degradation.
Excretion	Renal excretion of unchanged cisplatin; 15-50% of total platinum is excreted within 24 hours, and 20-80% within 72 hours. Biliary/fecal excretion is minimal (<5%).
Half-life	Terminal elimination half-life of total platinum is 20-30 hours (mean ~24 hours) in patients with normal renal function; ultrafilterable (active) cisplatin has an initial half-life of 20-30 minutes and a terminal half-life of 48-72 hours due to prolonged tissue binding.
Protein binding	>90% bound to plasma proteins (primarily albumin, but also globulins and tissue proteins); binding is irreversible and time-dependent.
Volume of Distribution	Vd of total platinum: 0.5-1.0 L/kg (mean 0.7 L/kg) indicating extensive tissue distribution (especially liver, kidneys, and spleen). Ultrafilterable platinum Vd: 0.1-0.2 L/kg.
Bioavailability	Not applicable; administered exclusively by intravenous route.
Onset of Action	Intravenous: Clinical effect (e.g., antitumor activity) is typically observed within 2-4 weeks after initiation of therapy; however, intracellular binding and DNA crosslinking occur within hours.
Duration of Action	Duration of cytotoxic effect persists for several weeks due to slow removal of DNA adducts. Dose-limiting nephrotoxicity may be delayed (3-7 days) and prolonged (weeks to months).

Classification & Brands

Dosing & administration

50-100 mg/m² intravenously every 3-4 weeks, or 15-20 mg/m² intravenously daily for 5 days every 3-4 weeks.

Dosage form	INJECTABLE
Renal impairment	For CrCl 10-50 mL/min: administer 75% of dose; for CrCl <10 mL/min: administer 50% of dose.
Liver impairment	No specific dose adjustment recommended; monitor hepatic function and consider dose reduction in severe impairment.
Pediatric use	30-60 mg/m² intravenously every 3-4 weeks; adjust for renal function as in adults.
Geriatric use	No specific dose adjustment; monitor renal function closely and dose according to CrCl.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PLATINOL-AQ (PLATINOL-AQ).

Breastfeeding	Cisplatin is excreted in human breast milk. M/P ratio unknown. Due to potential adverse effects in the nursing infant (e.g., myelosuppression, renal toxicity), breastfeeding is contraindicated during therapy and for at least 2 weeks after the last dose.
Teratogenic Risk	Platinol-AQ (cisplatin) is pregnancy category D. First trimester: Associated with major congenital malformations including neural tube defects, skeletal abnormalities, and cardiovascular defects. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and neonatal myelosuppression.

Warnings & precautions

■ FDA Black Box Warning

Cisplatin is a highly emetogenic chemotherapeutic agent. It can cause cumulative nephrotoxicity, neurotoxicity, ototoxicity, and anaphylactic reactions. Acute leukemia has been reported with prolonged use.

Side Effect Profile

Serious Effects

Absolute Contraindications

Pre-existing renal impairment (creatinine clearance < 60 mL/min), myelosuppression, hearing impairment, history of hypersensitivity to cisplatin or other platinum-containing compounds, pregnancy, breastfeeding.

Clinical Precautions

Precautions

Nephrotoxicity: Risk increases with dose and cumulative exposure; ensure adequate hydration. Ototoxicity: Irreversible high-frequency hearing loss; monitor audiometry. Neurotoxicity: Peripheral neuropathy; risk increases with prolonged therapy. Myelosuppression: Leukopenia, thrombocytopenia, anemia. Anaphylactic reactions: Have epinephrine and resuscitation equipment available. Electrolyte disturbances: Hypomagnesemia, hypokalemia, hypocalcemia. Hemolytic uremic syndrome. Hepatotoxicity. Vomiting: Severe and intractable; aggressive antiemetic therapy required.

Clinical Tips & Counseling

Drug interactions

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PLATINOL-AQ

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PLATINOL-AQ (PLATINOL-AQ).

How it works

Platinol-AQ (cisplatin) exerts its cytotoxic effects by forming intrastrand and interstrand DNA crosslinks, thereby inhibiting DNA replication and transcription, leading to apoptosis.

What the body does with it

Metabolism	Cisplatin is metabolized via aquation to reactive species, primarily in the liver and kidneys, involving glutathione conjugation and subsequent enzymatic degradation.
Excretion	Renal excretion of unchanged cisplatin; 15-50% of total platinum is excreted within 24 hours, and 20-80% within 72 hours. Biliary/fecal excretion is minimal (<5%).
Half-life	Terminal elimination half-life of total platinum is 20-30 hours (mean ~24 hours) in patients with normal renal function; ultrafilterable (active) cisplatin has an initial half-life of 20-30 minutes and a terminal half-life of 48-72 hours due to prolonged tissue binding.
Protein binding	>90% bound to plasma proteins (primarily albumin, but also globulins and tissue proteins); binding is irreversible and time-dependent.
Volume of Distribution	Vd of total platinum: 0.5-1.0 L/kg (mean 0.7 L/kg) indicating extensive tissue distribution (especially liver, kidneys, and spleen). Ultrafilterable platinum Vd: 0.1-0.2 L/kg.
Bioavailability	Not applicable; administered exclusively by intravenous route.
Onset of Action	Intravenous: Clinical effect (e.g., antitumor activity) is typically observed within 2-4 weeks after initiation of therapy; however, intracellular binding and DNA crosslinking occur within hours.
Duration of Action	Duration of cytotoxic effect persists for several weeks due to slow removal of DNA adducts. Dose-limiting nephrotoxicity may be delayed (3-7 days) and prolonged (weeks to months).

Classification & Brands

Dosing & administration

50-100 mg/m² intravenously every 3-4 weeks, or 15-20 mg/m² intravenously daily for 5 days every 3-4 weeks.

Dosage form	INJECTABLE
Renal impairment	For CrCl 10-50 mL/min: administer 75% of dose; for CrCl <10 mL/min: administer 50% of dose.
Liver impairment	No specific dose adjustment recommended; monitor hepatic function and consider dose reduction in severe impairment.
Pediatric use	30-60 mg/m² intravenously every 3-4 weeks; adjust for renal function as in adults.
Geriatric use	No specific dose adjustment; monitor renal function closely and dose according to CrCl.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PLATINOL-AQ (PLATINOL-AQ).

Breastfeeding	Cisplatin is excreted in human breast milk. M/P ratio unknown. Due to potential adverse effects in the nursing infant (e.g., myelosuppression, renal toxicity), breastfeeding is contraindicated during therapy and for at least 2 weeks after the last dose.
Teratogenic Risk	Platinol-AQ (cisplatin) is pregnancy category D. First trimester: Associated with major congenital malformations including neural tube defects, skeletal abnormalities, and cardiovascular defects. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and neonatal myelosuppression.