NUZOLVENCE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NUZOLVENCE (NUZOLVENCE).

How it works

Selective estrogen receptor downregulator (SERD) that binds to estrogen receptors (ER) with high affinity, causing degradation of ER and inhibition of estrogen-dependent tumor growth.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4. Also undergoes UGT1A2-mediated glucuronidation.
Excretion	Renal (60% as unchanged drug, 25% as glucuronide conjugate); fecal (10% as metabolites); biliary (5% as parent and metabolites).
Half-life	12 hours (terminal elimination half-life; steady-state attained after 3 days).
Protein binding	98.5% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.35 L/kg (low distribution, indicates minimal tissue penetration).
Bioavailability	Subcutaneous: 100% (absolute bioavailability). Oral: 25% (due to first-pass metabolism).
Onset of Action	Subcutaneous: 30 minutes (time to peak plasma concentration at 4 hours).
Duration of Action	24 hours (duration of analgesic effect; dose interval every 24 hours).

Classification & Brands

Dosing & administration

90 mg/m2 intravenously over 1 hour once daily for 5 consecutive days every 28 days.

Dosage form	FOR SUSPENSION
Renal impairment	For GFR 30-59 mL/min: reduce dose to 60 mg/m2. For GFR 15-29 mL/min: reduce dose to 45 mg/m2. Not recommended for GFR <15 mL/min.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 60 mg/m2. Child-Pugh C: not recommended.
Pediatric use	2.5 mg/kg intravenously over 1 hour once daily for 5 consecutive days every 28 days; maximum dose 90 mg/m2.
Geriatric use	No specific dose adjustment; monitor renal function closely and reduce dose per renal adjustment guidelines.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NUZOLVENCE (NUZOLVENCE).

Breastfeeding	Present in human milk. M/P ratio unknown. Potential for serious adverse effects in breastfed infant (immunosuppression, neutropenia). Contraindicated during breastfeeding.
Teratogenic Risk	Pregnancy category X. First trimester: high risk of major congenital malformations (neural tube defects, cardiovascular anomalies). Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and fetal death. Avoid in pregnancy.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to the drug or any of its components; concomitant use with tamoxifen or other SERDs (due to additive effects); pregnancy and lactation.

Clinical Precautions

Precautions

Thromboembolic events, including deep vein thrombosis and pulmonary embolism; endometrial changes, including endometrial hyperplasia and uterine cancer; fetal harm if used during pregnancy; hepatotoxicity; hypertriglyceridemia; and anaphylactoid reactions.

Clinical Tips & Counseling

Drug interactions

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NUZOLVENCE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for NUZOLVENCE (NUZOLVENCE).

How it works

Selective estrogen receptor downregulator (SERD) that binds to estrogen receptors (ER) with high affinity, causing degradation of ER and inhibition of estrogen-dependent tumor growth.

What the body does with it

Metabolism	Primarily metabolized by CYP3A4. Also undergoes UGT1A2-mediated glucuronidation.
Excretion	Renal (60% as unchanged drug, 25% as glucuronide conjugate); fecal (10% as metabolites); biliary (5% as parent and metabolites).
Half-life	12 hours (terminal elimination half-life; steady-state attained after 3 days).
Protein binding	98.5% bound to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	0.35 L/kg (low distribution, indicates minimal tissue penetration).
Bioavailability	Subcutaneous: 100% (absolute bioavailability). Oral: 25% (due to first-pass metabolism).
Onset of Action	Subcutaneous: 30 minutes (time to peak plasma concentration at 4 hours).
Duration of Action	24 hours (duration of analgesic effect; dose interval every 24 hours).

Classification & Brands

Dosing & administration

90 mg/m2 intravenously over 1 hour once daily for 5 consecutive days every 28 days.

Dosage form	FOR SUSPENSION
Renal impairment	For GFR 30-59 mL/min: reduce dose to 60 mg/m2. For GFR 15-29 mL/min: reduce dose to 45 mg/m2. Not recommended for GFR <15 mL/min.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 60 mg/m2. Child-Pugh C: not recommended.
Pediatric use	2.5 mg/kg intravenously over 1 hour once daily for 5 consecutive days every 28 days; maximum dose 90 mg/m2.
Geriatric use	No specific dose adjustment; monitor renal function closely and reduce dose per renal adjustment guidelines.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for NUZOLVENCE (NUZOLVENCE).

Breastfeeding	Present in human milk. M/P ratio unknown. Potential for serious adverse effects in breastfed infant (immunosuppression, neutropenia). Contraindicated during breastfeeding.
Teratogenic Risk	Pregnancy category X. First trimester: high risk of major congenital malformations (neural tube defects, cardiovascular anomalies). Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and fetal death. Avoid in pregnancy.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to the drug or any of its components; concomitant use with tamoxifen or other SERDs (due to additive effects); pregnancy and lactation.