LOCHOLEST
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOCHOLEST (LOCHOLEST).
Locholest is a bile acid sequestrant that binds bile acids in the intestine, preventing their reabsorption and promoting fecal excretion. This leads to increased hepatic conversion of cholesterol to bile acids, reducing serum LDL cholesterol.
| Metabolism | Not absorbed systemically; acts locally in gastrointestinal tract. No hepatic metabolism. |
| Excretion | Primarily fecal (biliary) as unchanged drug; renal excretion <5%. |
| Half-life | Terminal elimination half-life is approximately 19 hours (range 14-47 hours) for patients with normal renal function; accumulation occurs with once-daily dosing. |
| Protein binding | >95% bound to plasma proteins. |
| Volume of Distribution | Vd approximately 5.4 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is 30% (range 12-60%) due to extensive first-pass metabolism. |
| Onset of Action | Oral: 2 weeks for initial reduction in LDL-C; maximal effect by 4-6 weeks. |
| Duration of Action | Duration of effect is sustained with continued therapy; after discontinuation, lipid levels return to baseline within 6 weeks. |
| Molecular Weight | 404.54 Da |
Initial dose: 10-20 mg orally once daily, taken in the evening. Titrate as tolerated every 4 weeks to a maximum of 80 mg once daily.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl >30 mL/min). In severe renal impairment (CrCl <30 mL/min), not on dialysis: maximum dose 20 mg daily; on dialysis: maximum dose 20 mg daily (administer after dialysis). |
| Liver impairment | Contraindicated in active liver disease or unexplained persistent transaminase elevations. For Child-Pugh Class A: reduce dose; maximum 20 mg daily. Child-Pugh Class B: maximum 10 mg daily. Child-Pugh Class C: use not recommended. |
| Pediatric use | For heterozygous familial hypercholesterolemia (HeFH) in children ≥10 years: initial dose 10 mg once daily; titrate to 20 mg after 4 weeks; maximum 40 mg daily. For children <10 years: safety and efficacy not established. |
| Geriatric use | Elderly patients (≥65 years) may be more susceptible to myopathy; start at lower end of dosing range (10 mg daily) and titrate cautiously. No specific dose adjustment required based on age alone, but monitor renal function and drug interactions. |
| 1st trimester | Contraindicated due to risk of teratogenicity; inhibits cholesterol synthesis essential for fetal development. |
| 2nd trimester | Contraindicated; may cause fetal harm. |
| 3rd trimester | Contraindicated; may cause fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for LOCHOLEST (LOCHOLEST).
| Placental transfer | Crosses placenta; inhibits HMG-CoA reductase in fetal tissues, reducing cholesterol synthesis. |
| Breastfeeding | Excreted in human milk in low amounts; potential for serious adverse reactions in nursing infants. Decision to discontinue nursing or drug should be based on importance of drug to mother. |
| Lactation Rating |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Active liver diseasePersistent elevations of serum transaminases (ALT/AST >3x ULN)PregnancyBreastfeedingHypersensitivity to any component
| Precautions | May cause hypertriglyceridemia, especially in patients with pre-existing hypertriglyceridemia, Risk of vitamin K deficiency and bleeding due to fat malabsorption, May impair absorption of fat-soluble vitamins (A, D, E, K), Chronic use may lead to hyperchloremic metabolic acidosis, especially in children and smaller adults, May bind other drugs; administer other drugs at least 1 hour before or 4-6 hours after Locholest |
| Food/Dietary | Avoid grapefruit juice and grapefruit products due to increased risk of simvastatin myopathy. No specific restrictions with ezetimibe. |
Loading safety data…
| L4 - Possibly Hazardous |
| Teratogenic Risk | Locholest (cholestyramine) is a non-absorbable bile acid sequestrant. No known teratogenic risk; reduced absorption of fat-soluble vitamins may occur, potentially affecting fetal development if deficiency arises. No specific fetal risks reported from direct drug exposure. |
| Fetal Monitoring | Monitor maternal prothrombin time and INR for vitamin K deficiency; assess for signs of fat-soluble vitamin deficiency (A, D, E, K). Periodic fetal growth assessment with ultrasound. Monitor maternal lipid levels and gastrointestinal tolerability. |
| Fertility Effects | No direct effects on fertility reported. Chronic use may lead to vitamin deficiencies (e.g., folate), which could indirectly affect reproductive outcomes. No adverse impact on male or female fertility in humans. |
| Clinical Pearls | LOCHOLEST is a combination of ezetimibe and simvastatin. Monitor for myopathy, especially in patients on concurrent CYP3A4 inhibitors (e.g., azole antifungals, macrolides). Use with caution in renal impairment; adjust simvastatin dose if eGFR <30 mL/min. Start with 10 mg simvastatin in patients on verapamil, diltiazem, or amiodarone. Check LFTs at baseline and as clinically indicated. |
| Patient Advice | Take this medication once daily in the evening with or without food. · Avoid grapefruit juice or grapefruit products while taking this medication. · Report unexplained muscle pain, tenderness, or weakness, especially with dark urine. · Limit alcohol consumption as it may increase liver risk. · Notify your doctor of any new medications, especially antibiotics or antifungals. |