LORELCO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LORELCO (LORELCO).
Probucol lowers serum cholesterol by increasing hepatic clearance of LDL and decreasing cholesterol absorption, but its exact molecular mechanism is unclear; it also acts as an antioxidant and inhibits cholesterol synthesis via HMG-CoA reductase.
| Metabolism | Metabolized in liver via glucuronidation and oxidative pathways; metabolites excreted in bile and urine. |
| Excretion | Primarily biliary excretion (90%) as unchanged drug and glucuronide conjugates; renal excretion accounts for <5%. |
| Half-life | Terminal elimination half-life is 19-27 hours; prolonged in cholestasis (up to 50 hours) and chronic liver disease. |
| Protein binding | 95% bound primarily to albumin; minor binding to LDL and VLDL. |
| Volume of Distribution | 6.5 L/kg; extensive distribution into tissues, with high concentrations in liver and adipose tissue. |
| Bioavailability | Oral bioavailability is 20-30% due to first-pass metabolism. |
| Onset of Action | Oral: 2-4 hours for initial reduction in serum cholesterol; maximal effect seen after 4-6 weeks. |
| Duration of Action | The hypolipidemic effect persists for several weeks after discontinuation; rebound hypercholesterolemia may occur. |
500 mg orally twice daily with meals.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for renal impairment. However, use with caution in severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | Contraindicated in patients with significant hepatic impairment (Child-Pugh class B or C). Use with caution in mild hepatic impairment (Child-Pugh class A) with no dose adjustment specified. |
| Pediatric use | Not approved for pediatric patients. Safety and efficacy have not been established. |
| Geriatric use | No specific dosage adjustment recommended for elderly patients; select dose with caution due to potential for decreased organ function and concomitant disease or drug therapy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LORELCO (LORELCO).
| Breastfeeding | Probucol is excreted in human milk; M/P ratio approximately 0.5. Breastfeeding is not recommended due to potential adverse effects on the nursing infant, including prolonged QT interval and lipid metabolism alterations. Consider alternative treatments or discontinue breastfeeding. |
| Teratogenic Risk | Lorelco (probucol) is contraindicated in pregnancy due to known teratogenicity in animal studies. First trimester: Increased risk of major congenital malformations including cardiac and skeletal anomalies. Second and third trimesters: Fetal growth restriction, delayed ossification, and increased perinatal mortality observed in animal models. Human data insufficient but risk extrapolated from animal findings. |
■ FDA Black Box Warning
Warning: QT interval prolongation and risk of serious ventricular arrhythmias (e.g., torsade de pointes) especially when used with other drugs that prolong QT or in patients with electrolyte imbalances.
| Serious Effects |
["Hypersensitivity to probucol","known QT prolongation or ventricular arrhythmia","recent MI or unstable angina","electrolyte imbalance","concomitant use of other QT-prolonging drugs"]
| Precautions | ["QT interval prolongation risk","electrolyte disturbances (hypokalemia, hypomagnesemia)","bradycardia","hepatic impairment","renal impairment","myopathy risk with statins","discontinue if unexplained syncope or arrhythmia"] |
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| Fetal Monitoring | Maternal: Baseline ECG and periodic monitoring for QT prolongation, electrolyte disturbances. Fetal: Detailed ultrasound for growth and anatomy if inadvertent exposure. Postnatally, monitor infant for signs of arrhythmia or lipid abnormalities. |
| Fertility Effects | Reproductive toxicity studies in animals show reduced fertility and impaired spermatogenesis at high doses. Human data limited; potential for reversible effects on fertility in both males and females. Caution in patients planning conception. |