LOVASTATIN
Clinical safety rating: avoid
Contraindicated (not allowed)
Competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Reduces hepatic cholesterol synthesis, leading to increased LDL receptor expression and enhanced clearance of LDL from plasma.
| Metabolism | Extensively metabolized in the liver via CYP3A4 isoenzyme. Undergoes first-pass metabolism to active beta-hydroxy acid metabolites. Also metabolized by CYP2C8 and glucuronidation. |
| Excretion | Renal: 10% (as metabolites); Fecal: 83% (primarily as metabolites); Biliary: minor; <5% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life: 1.5–2 hours for lovastatin acid; clinical context: short half-life supports evening dosing to maximize HMG-CoA reductase inhibition during peak cholesterol synthesis. |
| Protein binding | >95% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 0.3–0.4 L/kg; indicates distribution mainly in extracellular fluid and tissues, with extensive hepatic extraction. |
| Bioavailability | Oral: <5% due to extensive first-pass hepatic metabolism; prodrug (lovastatin lactone) converted to active hydroxy acid in the liver. |
| Onset of Action | Oral: reduction in LDL-C begins within 2 weeks of initiation; full effect observed by 4–6 weeks. |
| Duration of Action | Duration: Effect on LDL-C persists for 24 hours with once-daily dosing; clinical note: maximal effect at trough concentration, sustained with chronic dosing due to inhibition of cholesterol synthesis. |
10-80 mg orally once daily in the evening, starting at 10-20 mg once daily; maximum dose 80 mg/day.
| Dosage form | TABLET |
| Renal impairment | For severe renal impairment (CrCl <30 mL/min), doses should be limited to 20 mg/day; avoid doses exceeding 20 mg/day. |
| Liver impairment | Contraindicated in active liver disease or unexplained persistent transaminase elevations. For Child-Pugh class A, caution with dose titration; class B or C, avoid use. |
| Pediatric use | For heterozygous familial hypercholesterolemia in patients 10-17 years: start 10 mg orally once daily in the evening, maximum 40 mg/day (dose based on response and tolerability, adjusted at 4-week intervals). |
| Geriatric use | Start at lower end of dosing range (10-20 mg once daily) due to increased risk of myopathy; monitor renal function and adjust if CrCl <30 mL/min (limit to 20 mg/day). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors (eg itraconazole) can significantly increase levels and risk of myopathy Can cause myopathy and rhabdomyolysis.
| Breastfeeding | Lovastatin is excreted into human breast milk in small amounts (M/P ratio not reported). Potential for serious adverse reactions in nursing infants (e.g., disruption of lipid metabolism). Manufacturer recommends discontinuing nursing or drug, considering importance to mother. Use only if clearly needed. |
| Teratogenic Risk | Lovastatin is contraindicated in pregnancy due to risk of fetal harm. Statins inhibit HMG-CoA reductase, potentially disrupting fetal cholesterol synthesis necessary for development. First trimester: retrospective data show congenital anomalies (CNS, limb defects) but not significantly elevated; risk may be low. Second/third trimester: theoretical risk persists; no adequate studies. FDA Category X: avoid in pregnant women or those planning pregnancy. |
■ FDA Black Box Warning
None
| Common Effects | Headache |
| Serious Effects |
["Active liver disease or unexplained persistent elevations of transaminases","Hypersensitivity to lovastatin or any component","Concomitant use with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, cobicistat-containing products)","Concomitant use with gemfibrozil","Pregnancy and breastfeeding"]
| Precautions | ["Skeletal muscle effects: myopathy, rhabdomyolysis; risk increased with high doses, concomitant use of CYP3A4 inhibitors, fibrates, niacin, or renal impairment.","Hepatic effects: elevated transaminases; monitor liver function before initiation and periodically.","May increase HbA1c and fasting glucose levels.","Avoid use with grapefruit juice due to increased systemic exposure.","Use caution in patients with predisposing factors for myopathy (e.g., renal impairment, hypothyroidism, alcohol abuse)."] |
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| Fetal Monitoring | Monitor hepatic function (ALT, AST) before and during therapy, as statins can elevate liver enzymes. Monitor creatine kinase (CK) if muscle symptoms occur, due to risk of myopathy/rhabdomyolysis. In pregnancy if inadvertent exposure, fetal ultrasound to exclude major anomalies. |
| Fertility Effects | No specific human data on fertility effects. In animal studies, no impairment of fertility at clinically relevant doses. However, statins may theoretically alter steroid hormone synthesis; clinical significance unknown. |