LESCOL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LESCOL (LESCOL).

How it works

Competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, leading to increased LDL receptor expression and reduced plasma LDL cholesterol.

What the body does with it

Metabolism	Hepatic; primarily via CYP2C9 isoenzyme; minor contributions from CYP3A4.
Excretion	Primarily biliary, with approximately 90% recovered in feces as parent drug and metabolites; renal excretion accounts for less than 10%.
Half-life	Terminal elimination half-life is 2.5 to 4.0 hours; clinical context: effective for once-daily dosing due to prolonged HMG-CoA reductase inhibition despite short half-life.
Protein binding	Approximately 99% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Approximately 0.3 L/kg; clinical meaning: limited distribution into extravascular tissues, consistent with extensive protein binding.
Bioavailability	Oral bioavailability is approximately 30% due to extensive first-pass metabolism.
Onset of Action	Oral: Onset of lipid-lowering effect occurs within 1–2 weeks; maximal effect seen after 4 weeks.
Duration of Action	Duration of lipid-lowering effect persists for at least 24 hours with once-daily dosing; clinical note: sustained reduction in LDL-C maintained throughout dosing interval.

Classification & Brands

Dosing & administration

For primary hypercholesterolemia: starting dose 20 mg orally once daily, titrated to a maximum of 80 mg once daily. For patients requiring LDL-C reduction >25%, start at 40 mg once daily. For prevention of cardiovascular events: 40 mg orally once daily.

Dosage form	CAPSULE
Renal impairment	For GFR 30-80 mL/min: no adjustment required. For GFR <30 mL/min: use with caution, maximum dose 20 mg daily. For hemodialysis: not recommended.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: maximum dose 20 mg daily. Child-Pugh Class C: contraindicated.
Pediatric use	Children ≥10 years: starting dose 20 mg orally once daily, titrated to 40 mg once daily after 4 weeks; maximum 80 mg daily. For adolescents with homozygous familial hypercholesterolemia: 40 mg once daily.
Geriatric use	No specific dose adjustment required for elderly patients; however, increased risk of myopathy, rhabdomyolysis, and hepatic impairment; initiate at lower end of dosing range and titrate slowly.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LESCOL (LESCOL).

Breastfeeding	Excretion in human milk unknown; not recommended due to potential for serious adverse reactions in nursing infants. M/P ratio not established.
Teratogenic Risk	Pregnancy Category X. HMG-CoA reductase inhibitors are contraindicated in pregnancy. First trimester: potential for fetal developmental toxicity based on animal studies; second and third trimesters: risk of fetal skeletal and organ malformations due to inhibition of cholesterol synthesis essential for fetal development. Use only in women of childbearing potential with reliable contraception.

Warnings & precautions

■ FDA Black Box Warning

No black box warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Active hepatic disease or unexplained persistent transaminase elevations","Concurrent use with gemfibrozil","Pregnancy","Lactation"]

Clinical Precautions

Precautions

["Myopathy/rhabdomyolysis risk, especially with concurrent use of gemfibrozil, cyclosporine, or niacin","Hepatic enzyme elevation","Use with caution in patients with renal impairment","Avoid during pregnancy and breastfeeding"]

Clinical Tips & Counseling

Drug interactions

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LESCOL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LESCOL (LESCOL).

How it works

Competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, leading to increased LDL receptor expression and reduced plasma LDL cholesterol.

What the body does with it

Metabolism	Hepatic; primarily via CYP2C9 isoenzyme; minor contributions from CYP3A4.
Excretion	Primarily biliary, with approximately 90% recovered in feces as parent drug and metabolites; renal excretion accounts for less than 10%.
Half-life	Terminal elimination half-life is 2.5 to 4.0 hours; clinical context: effective for once-daily dosing due to prolonged HMG-CoA reductase inhibition despite short half-life.
Protein binding	Approximately 99% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Approximately 0.3 L/kg; clinical meaning: limited distribution into extravascular tissues, consistent with extensive protein binding.
Bioavailability	Oral bioavailability is approximately 30% due to extensive first-pass metabolism.
Onset of Action	Oral: Onset of lipid-lowering effect occurs within 1–2 weeks; maximal effect seen after 4 weeks.
Duration of Action	Duration of lipid-lowering effect persists for at least 24 hours with once-daily dosing; clinical note: sustained reduction in LDL-C maintained throughout dosing interval.

Classification & Brands

Dosing & administration

Dosage form	CAPSULE
Renal impairment	For GFR 30-80 mL/min: no adjustment required. For GFR <30 mL/min: use with caution, maximum dose 20 mg daily. For hemodialysis: not recommended.
Liver impairment	Child-Pugh Class A: no adjustment. Child-Pugh Class B: maximum dose 20 mg daily. Child-Pugh Class C: contraindicated.
Pediatric use	Children ≥10 years: starting dose 20 mg orally once daily, titrated to 40 mg once daily after 4 weeks; maximum 80 mg daily. For adolescents with homozygous familial hypercholesterolemia: 40 mg once daily.
Geriatric use	No specific dose adjustment required for elderly patients; however, increased risk of myopathy, rhabdomyolysis, and hepatic impairment; initiate at lower end of dosing range and titrate slowly.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for LESCOL (LESCOL).

Breastfeeding	Excretion in human milk unknown; not recommended due to potential for serious adverse reactions in nursing infants. M/P ratio not established.
Teratogenic Risk	Pregnancy Category X. HMG-CoA reductase inhibitors are contraindicated in pregnancy. First trimester: potential for fetal developmental toxicity based on animal studies; second and third trimesters: risk of fetal skeletal and organ malformations due to inhibition of cholesterol synthesis essential for fetal development. Use only in women of childbearing potential with reliable contraception.

Warnings & precautions

■ FDA Black Box Warning

No black box warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Active hepatic disease or unexplained persistent transaminase elevations","Concurrent use with gemfibrozil","Pregnancy","Lactation"]