DOXORUBICIN HYDROCHLORIDE (LIPOSOMAL)

Clinical safety rating: avoid

Other cardiotoxic drugs (eg trastuzumab) increase risk Can cause severe and irreversible cardiotoxicity and myelosuppression.

How it works

Topoisomerase II inhibitor; intercalates DNA, inhibits DNA and RNA synthesis, and generates free radicals; liposomal formulation enhances accumulation in tumor tissue.

What the body does with it

Metabolism	Hepatic metabolism via aldo-keto reductases (e.g., AKR1A1, AKR1C3) and carbonyl reductases to doxorubicinol; also undergoes deglycosylation; biliary excretion.
Excretion	Predominantly biliary/fecal; <5% renal excretion as unchanged drug and metabolites.
Half-life	Terminal half-life ranges from 30 to 60 hours (mean ~45 h), with a prolonged distribution phase. Encapsulation in liposomes extends circulation time compared to conventional doxorubicin.
Protein binding	Approximately 70% bound to plasma proteins, primarily albumin.
Volume of Distribution	Vd is small, approximately 0.05 L/kg (about 3–4 L in adults), limited largely to plasma volume due to liposomal encapsulation.
Bioavailability	Bioavailability is 100% via intravenous administration; no oral formulation available.
Onset of Action	Clinical effect onset is variable, typically within 1–3 weeks after first dose due to cumulative drug exposure.
Duration of Action	Duration of action (antitumor effect) persists for the remainder of the treatment cycle, with repeated dosing every 2–4 weeks.

Classification & Brands

Dosing & administration

Liposomal doxorubicin 20 mg/m2 IV over 60 minutes every 3 weeks.

Dosage form	INJECTABLE, LIPOSOMAL
Renal impairment	No dose adjustment required for mild-to-moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min).
Liver impairment	Child-Pugh A: Reduce dose by 50% to 10 mg/m2 every 3 weeks. Child-Pugh B: Reduce dose by 75% to 5 mg/m2 every 3 weeks. Child-Pugh C: Contraindicated.
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	No specific dose adjustment, but monitor for increased toxicity (cardiac, myelosuppression). Start at lower end of dosing range (e.g., 20 mg/m2) and titrate based on tolerance.

Use during pregnancy

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

Clinical note

Other cardiotoxic drugs (eg trastuzumab) increase risk Can cause severe and irreversible cardiotoxicity and myelosuppression.

FDA category	Contraindicated
Breastfeeding	No data on M/P ratio. Liposomal doxorubicin is likely excreted in human milk due to its molecular weight and lipophilicity. Potential for severe adverse reactions in nursing infants (e.g., cardiotoxicity, immunosuppression). Discontinue breastfeeding during therapy and for at least 10-14 days after last dose.
Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Cardiotoxicity (may lead to heart failure); extravasation (tissue necrosis); myelosuppression (severe, with liposomal formulation).

Side Effect Profile

Common Effects	Myelosuppression
Serious Effects

Absolute Contraindications

Hypersensitivity to doxorubicin or any component; severe hepatic impairment; severe myelosuppression; pre-existing cardiac disease (e.g., cardiomyopathy).

Clinical Precautions

Precautions

Cardiotoxicity: cumulative dose limit (400-450 mg/m2 for liposomal); myelosuppression; hand-foot syndrome (palmar-plantar erythrodysesthesia); infusion-related reactions; hepatic impairment; secondary malignancies.

Clinical Tips & Counseling

Drug interactions

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DOXORUBICIN HYDROCHLORIDE (LIPOSOMAL)

Clinical safety rating: avoid

Other cardiotoxic drugs (eg trastuzumab) increase risk Can cause severe and irreversible cardiotoxicity and myelosuppression.

How it works

Topoisomerase II inhibitor; intercalates DNA, inhibits DNA and RNA synthesis, and generates free radicals; liposomal formulation enhances accumulation in tumor tissue.

What the body does with it

Metabolism	Hepatic metabolism via aldo-keto reductases (e.g., AKR1A1, AKR1C3) and carbonyl reductases to doxorubicinol; also undergoes deglycosylation; biliary excretion.
Excretion	Predominantly biliary/fecal; <5% renal excretion as unchanged drug and metabolites.
Half-life	Terminal half-life ranges from 30 to 60 hours (mean ~45 h), with a prolonged distribution phase. Encapsulation in liposomes extends circulation time compared to conventional doxorubicin.
Protein binding	Approximately 70% bound to plasma proteins, primarily albumin.
Volume of Distribution	Vd is small, approximately 0.05 L/kg (about 3–4 L in adults), limited largely to plasma volume due to liposomal encapsulation.
Bioavailability	Bioavailability is 100% via intravenous administration; no oral formulation available.
Onset of Action	Clinical effect onset is variable, typically within 1–3 weeks after first dose due to cumulative drug exposure.
Duration of Action	Duration of action (antitumor effect) persists for the remainder of the treatment cycle, with repeated dosing every 2–4 weeks.

Classification & Brands

Dosing & administration

Liposomal doxorubicin 20 mg/m2 IV over 60 minutes every 3 weeks.

Dosage form	INJECTABLE, LIPOSOMAL
Renal impairment	No dose adjustment required for mild-to-moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min).
Liver impairment	Child-Pugh A: Reduce dose by 50% to 10 mg/m2 every 3 weeks. Child-Pugh B: Reduce dose by 75% to 5 mg/m2 every 3 weeks. Child-Pugh C: Contraindicated.
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	No specific dose adjustment, but monitor for increased toxicity (cardiac, myelosuppression). Start at lower end of dosing range (e.g., 20 mg/m2) and titrate based on tolerance.

Use during pregnancy

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

Clinical note

Other cardiotoxic drugs (eg trastuzumab) increase risk Can cause severe and irreversible cardiotoxicity and myelosuppression.

FDA category	Contraindicated
Breastfeeding	No data on M/P ratio. Liposomal doxorubicin is likely excreted in human milk due to its molecular weight and lipophilicity. Potential for severe adverse reactions in nursing infants (e.g., cardiotoxicity, immunosuppression). Discontinue breastfeeding during therapy and for at least 10-14 days after last dose.
Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Cardiotoxicity (may lead to heart failure); extravasation (tissue necrosis); myelosuppression (severe, with liposomal formulation).

Side Effect Profile

Common Effects	Myelosuppression
Serious Effects

Absolute Contraindications

Hypersensitivity to doxorubicin or any component; severe hepatic impairment; severe myelosuppression; pre-existing cardiac disease (e.g., cardiomyopathy).