LESCOL XL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LESCOL XL (LESCOL XL).
Competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, leading to increased LDL receptor expression and reduced plasma LDL-cholesterol.
| Metabolism | Primarily hepatic via CYP2C9 (major) and CYP3A4 (minor); undergoes extensive first-pass metabolism. |
| Excretion | Primarily hepatic metabolism with biliary/fecal elimination (approximately 90%); renal excretion accounts for approximately 10% of the dose. |
| Half-life | Terminal elimination half-life is approximately 1.3 to 2.5 hours for fluvastatin; clinical context: due to extended-release formulation, trough levels remain sufficient for once-daily dosing. |
| Protein binding | Highly protein bound (>98%), primarily to albumin. |
| Volume of Distribution | Apparent volume of distribution (Vd) approximately 0.42 L/kg (range 0.35-0.45 L/kg), indicating distribution into extracellular fluid and tissues. |
| Bioavailability | Fluvastatin immediate release: absolute bioavailability 24%; extended-release LESCOL XL: bioavailability approximately 60% relative to immediate release, due to reduced first-pass metabolism. |
| Onset of Action | Fluvastatin immediate release: within 2 weeks of initiation; extended-release (LESCOL XL): clinical effect seen after 2-4 weeks. |
| Duration of Action | Duration of lipid-lowering effect: 24 hours with once-daily dosing; sustained LDL reduction maintained with chronic therapy. |
80 mg orally once daily, at least 4 hours after a meal. The extended-release formulation (LESCOL XL) is not interchangeable with immediate-release fluvastatin.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), use with caution and limit dose to 40 mg immediate-release; LESCOL XL is not recommended. |
| Liver impairment | Contraindicated in active liver disease or unexplained persistent transaminase elevations. For Child-Pugh Class A, reduce to 20 mg immediate-release twice daily; LESCOL XL is not recommended. Contraindicated in Child-Pugh Class B or C. |
| Pediatric use | For heterozygous familial hypercholesterolemia in children (≥10 years): start with immediate-release 20 mg once daily; maximum 80 mg/day (40 mg twice daily). LESCOL XL is not indicated for pediatric use. |
| Geriatric use | No specific dose adjustment, but start at the lower end of the dosing range due to increased risk of adverse effects (e.g., myopathy). Use with caution in patients ≥65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LESCOL XL (LESCOL XL).
| Breastfeeding | Contraindicated in breastfeeding. No data on M/P ratio. Fluvastatin is lipophilic and likely excreted into breast milk. Risk of adverse effects in nursing infant; alternative agents recommended. |
| Teratogenic Risk | Pregnancy Category X. HMG-CoA reductase inhibitors are contraindicated in pregnancy. First trimester: No data show risk; however, cholesterol synthesis is essential for fetal development. Second and third trimesters: Potential for fetal harm based on animal data (skeletal malformations, reduced fetal weight). Limited human data; avoid use. |
■ FDA Black Box Warning
No FDA boxed warning exists for LESCOL XL.
| Serious Effects |
["Active liver disease or unexplained persistent elevations in serum transaminases","Hypersensitivity to any component of the product","Pregnancy and breastfeeding","Concomitant use with strong CYP2C9 inhibitors (e.g., amiodarone, fluconazole) due to increased risk of myopathy/rhabdomyolysis"]
| Precautions | ["Skeletal muscle effects: myalgia, myopathy, rhabdomyolysis; risk increased with concomitant use of CYP2C9 inhibitors or higher doses","Hepatic effects: persistent elevations in serum transaminases; liver function tests should be performed before initiation and periodically thereafter","Risk of diabetes mellitus: slight increase in fasting glucose and HbA1c","Use with caution in patients with predisposing factors for myopathy (e.g., renal impairment, hypothyroidism) and those consuming large quantities of grapefruit juice"] |
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| Fetal Monitoring |
| Monitor liver function tests (AST, ALT) at baseline and periodically. Monitor creatine kinase (CK) if muscle symptoms occur. No specific fetal monitoring required if used inadvertently; discontinue immediately upon pregnancy detection. |
| Fertility Effects | No evidence of impaired fertility in human studies. Animal studies showed no adverse effects on fertility. Theoretical concern due to cholesterol reduction may impact steroidogenesis; clinical significance unknown. |