LEQVIO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LEQVIO (LEQVIO).

How it works

Leqvio (inclisiran) is a small interfering RNA (siRNA) that targets proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA. It inhibits PCSK9 synthesis in hepatocytes, leading to increased LDL receptor expression and reduced plasma LDL-C levels.

What the body does with it

Metabolism	Inclisiran is metabolized by nucleases to shorter inactive oligonucleotides. It is not a substrate for CYP450 enzymes or drug transporters.
Excretion	Renal: negligible intact drug; primarily eliminated via binding to target and subsequent intracellular degradation. Biliary/fecal: not quantified; expected minimal.
Half-life	Terminal half-life approximately 4 weeks (26 days), supporting monthly subcutaneous dosing.
Protein binding	Extensively bound to PCSK9; not albumin-bound; free fraction <1% when bound to target.
Volume of Distribution	47 L (approx 0.6 L/kg), indicating limited extravascular distribution.
Bioavailability	Subcutaneous: 80-90%.
Onset of Action	Subcutaneous: LDL-C reduction observed by week 4, maximal effect by 8-12 weeks.
Duration of Action	Sustained LDL-C reduction for up to 6 months after single dose; monthly injections maintain effect.

Classification & Brands

Dosing & administration

284 mg subcutaneously once, then at 3 months, then every 6 months.

Dosage form	SOLUTION
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m^2).
Liver impairment	No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate or severe hepatic impairment (Child-Pugh B or C).
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	No specific dose adjustments recommended; clinical studies included patients ≥65 years with no overall differences in safety or efficacy.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LEQVIO (LEQVIO).

Breastfeeding	Unknown if distributed into human breast milk; no available M/P ratio. Given low bioavailability, risk to nursing infant is likely low, but caution advised.
Teratogenic Risk	Insufficient human data; animal studies show no evidence of fetal harm. As an siRNA, systemic exposure is low, but administration during pregnancy should only be considered if clearly needed.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reaction to inclisiran or any excipient in Leqvio."]

Clinical Precautions

Precautions	["Hypersensitivity reactions including angioedema and urticaria have been reported.","Injection-site reactions (e.g., erythema, pain, pruritus) are common."]
Food/Dietary	No specific food interactions. Take with or without food. Avoid grapefruit juice if also taking statins; however, inclisiran itself has no dietary restrictions.

Clinical Tips & Counseling

Clinical Pearls

Drug interactions

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LEQVIO

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LEQVIO (LEQVIO).

How it works

What the body does with it

Metabolism	Inclisiran is metabolized by nucleases to shorter inactive oligonucleotides. It is not a substrate for CYP450 enzymes or drug transporters.
Excretion	Renal: negligible intact drug; primarily eliminated via binding to target and subsequent intracellular degradation. Biliary/fecal: not quantified; expected minimal.
Half-life	Terminal half-life approximately 4 weeks (26 days), supporting monthly subcutaneous dosing.
Protein binding	Extensively bound to PCSK9; not albumin-bound; free fraction <1% when bound to target.
Volume of Distribution	47 L (approx 0.6 L/kg), indicating limited extravascular distribution.
Bioavailability	Subcutaneous: 80-90%.
Onset of Action	Subcutaneous: LDL-C reduction observed by week 4, maximal effect by 8-12 weeks.
Duration of Action	Sustained LDL-C reduction for up to 6 months after single dose; monthly injections maintain effect.

Classification & Brands

Dosing & administration

284 mg subcutaneously once, then at 3 months, then every 6 months.

Dosage form	SOLUTION
Renal impairment	No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m^2).
Liver impairment	No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate or severe hepatic impairment (Child-Pugh B or C).
Pediatric use	Safety and efficacy not established in pediatric patients.
Geriatric use	No specific dose adjustments recommended; clinical studies included patients ≥65 years with no overall differences in safety or efficacy.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LEQVIO (LEQVIO).

Breastfeeding	Unknown if distributed into human breast milk; no available M/P ratio. Given low bioavailability, risk to nursing infant is likely low, but caution advised.
Teratogenic Risk	Insufficient human data; animal studies show no evidence of fetal harm. As an siRNA, systemic exposure is low, but administration during pregnancy should only be considered if clearly needed.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of serious hypersensitivity reaction to inclisiran or any excipient in Leqvio."]

Clinical Precautions

Precautions	["Hypersensitivity reactions including angioedema and urticaria have been reported.","Injection-site reactions (e.g., erythema, pain, pruritus) are common."]
Food/Dietary	No specific food interactions. Take with or without food. Avoid grapefruit juice if also taking statins; however, inclisiran itself has no dietary restrictions.

Clinical Tips & Counseling

Clinical Pearls

Drug interactions

Loading safety data…