TOPOTECAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TOPOTECAN (TOPOTECAN).

How it works

Topotecan is a topoisomerase I inhibitor that binds to the topoisomerase I-DNA complex and prevents religation of single-strand breaks, leading to DNA damage and apoptosis.

What the body does with it

Metabolism	Topotecan undergoes reversible hydrolysis to inactive lactone ring-opened form. Metabolism is primarily hepatic via CYP3A4 and to a lesser extent by CYP1A2, with renal excretion of unchanged drug and metabolites.
Excretion	Renal excretion accounts for approximately 50-60% of total clearance as unchanged drug. Biliary/fecal elimination is minor, around 20-30% as metabolites. The lactone form is predominantly excreted renally.
Half-life	Terminal elimination half-life is approximately 2-3 hours in patients with normal renal function. In patients with creatinine clearance <20 mL/min, half-life may extend to 4-5 hours.
Protein binding	Approximately 35% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution is approximately 100-200 L/m² (or about 2-4 L/kg), indicating extensive tissue distribution.
Bioavailability	Not administered orally; bioavailability by intravenous route is 100%. Oral bioavailability is less than 40% and not clinically used.
Onset of Action	Intravenous: Antitumor effect onset is variable, typically within days to weeks; myelosuppression (neutropenia) occurs within 7-10 days after dosing.
Duration of Action	Myelosuppression (neutrophil nadir) occurs approximately 7-10 days post-dose, with recovery by day 21. Antitumor effect duration is cycle-dependent, typically 21-day cycles.

Classification & Brands

Dosing & administration

1.5 mg/m² intravenously over 30 minutes daily for 5 consecutive days, repeated every 21 days.

Dosage form	SOLUTION
Renal impairment	For creatinine clearance (CrCl) 20-39 mL/min: 0.75 mg/m²/day. CrCl <20 mL/min: insufficient data, avoid use.
Liver impairment	Child-Pugh Class B: reduce dose by 25% (e.g., 1.1 mg/m²/day). Child-Pugh Class C: avoid use.
Pediatric use	2.4 mg/m² intravenously over 30 minutes daily for 5 days, repeated every 21 days (based on limited data).
Geriatric use	No specific dose adjustment, but monitor for increased myelosuppression, especially at standard dose.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TOPOTECAN (TOPOTECAN).

Breastfeeding	Topotecan is excreted into breast milk in animal studies; no human data. Milk-to-plasma ratio unknown. Due to potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 2 weeks after last dose.
Teratogenic Risk	Topotecan is embryotoxic and fetotoxic in animals. In humans, first trimester exposure is associated with spontaneous abortion and congenital malformations (neural tube, skeletal, visceral). Second and third trimester exposure increases risk of intrauterine growth restriction, fetal myelosuppression, and neonatal pancytopenia. Avoid use in pregnancy unless no alternative.

Warnings & precautions

■ FDA Black Box Warning

Topotecan can cause severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Treatment should not be initiated unless baseline neutrophil count is ≥1,500 cells/mm³ and platelet count ≥100,000 cells/mm³.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Severe hypersensitivity to topotecan or any excipient","Severe bone marrow suppression (neutrophils <1,500 cells/mm³, platelets <100,000 cells/mm³)","Breastfeeding"]

Clinical Precautions

Precautions

["Myelosuppression: Monitor blood counts frequently","Renal impairment: Dose adjustment required for moderate to severe impairment (CrCl <40 mL/min)","Interstitial lung disease: May occur, monitor for pulmonary symptoms","Hepatic impairment: Not recommended in severe impairment (total bilirubin >10 mg/dL)","Pregnancy: Can cause fetal harm"]

Clinical Tips & Counseling

Drug interactions

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TOPOTECAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TOPOTECAN (TOPOTECAN).

How it works

Topotecan is a topoisomerase I inhibitor that binds to the topoisomerase I-DNA complex and prevents religation of single-strand breaks, leading to DNA damage and apoptosis.

What the body does with it

Metabolism	Topotecan undergoes reversible hydrolysis to inactive lactone ring-opened form. Metabolism is primarily hepatic via CYP3A4 and to a lesser extent by CYP1A2, with renal excretion of unchanged drug and metabolites.
Excretion	Renal excretion accounts for approximately 50-60% of total clearance as unchanged drug. Biliary/fecal elimination is minor, around 20-30% as metabolites. The lactone form is predominantly excreted renally.
Half-life	Terminal elimination half-life is approximately 2-3 hours in patients with normal renal function. In patients with creatinine clearance <20 mL/min, half-life may extend to 4-5 hours.
Protein binding	Approximately 35% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution is approximately 100-200 L/m² (or about 2-4 L/kg), indicating extensive tissue distribution.
Bioavailability	Not administered orally; bioavailability by intravenous route is 100%. Oral bioavailability is less than 40% and not clinically used.
Onset of Action	Intravenous: Antitumor effect onset is variable, typically within days to weeks; myelosuppression (neutropenia) occurs within 7-10 days after dosing.
Duration of Action	Myelosuppression (neutrophil nadir) occurs approximately 7-10 days post-dose, with recovery by day 21. Antitumor effect duration is cycle-dependent, typically 21-day cycles.

Classification & Brands

Dosing & administration

1.5 mg/m² intravenously over 30 minutes daily for 5 consecutive days, repeated every 21 days.

Dosage form	SOLUTION
Renal impairment	For creatinine clearance (CrCl) 20-39 mL/min: 0.75 mg/m²/day. CrCl <20 mL/min: insufficient data, avoid use.
Liver impairment	Child-Pugh Class B: reduce dose by 25% (e.g., 1.1 mg/m²/day). Child-Pugh Class C: avoid use.
Pediatric use	2.4 mg/m² intravenously over 30 minutes daily for 5 days, repeated every 21 days (based on limited data).
Geriatric use	No specific dose adjustment, but monitor for increased myelosuppression, especially at standard dose.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for TOPOTECAN (TOPOTECAN).

Breastfeeding	Topotecan is excreted into breast milk in animal studies; no human data. Milk-to-plasma ratio unknown. Due to potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 2 weeks after last dose.
Teratogenic Risk	Topotecan is embryotoxic and fetotoxic in animals. In humans, first trimester exposure is associated with spontaneous abortion and congenital malformations (neural tube, skeletal, visceral). Second and third trimester exposure increases risk of intrauterine growth restriction, fetal myelosuppression, and neonatal pancytopenia. Avoid use in pregnancy unless no alternative.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Severe hypersensitivity to topotecan or any excipient","Severe bone marrow suppression (neutrophils <1,500 cells/mm³, platelets <100,000 cells/mm³)","Breastfeeding"]