LIPITOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LIPITOR (LIPITOR).
Competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, leading to increased hepatic LDL receptor expression and reduced plasma LDL cholesterol.
| Metabolism | Extensively metabolized by CYP3A4 to active ortho-hydroxy and para-hydroxy metabolites; primarily excreted in bile. |
| Excretion | Biliary/fecal (90%); renal (10% as metabolites) |
| Half-life | 14 hours; prolonged in hepatic impairment |
| Protein binding | ≥98% bound to albumin and other plasma proteins |
| Volume of Distribution | Approximately 0.7 L/kg; extensive extravascular distribution |
| Bioavailability | Oral: 30% (first-pass effect; active metabolites contribute) |
| Onset of Action | 2-4 weeks (oral) for lipid-lowering effect; maximal effect at 4-6 weeks |
| Duration of Action | About 24 hours (oral); supports once-daily dosing |
| Action Class | HMG CoA inhibitors (statins) |
| Brand Substitutes | Atorast 10mg Tablet, Zivast 10 Tablet, Storvas 10 Tablet, Tonact 10 Tablet, Atorlip 10 Tablet, Drlipid 40mg Tablet, Atchol 40 Tablet, Caditor 40mg Tablet, Lipikind 40 Tablet, Eltor 40mg Tablet |
Atorvastatin 10-80 mg orally once daily; initial dose 10-20 mg; titrate at 2-4 week intervals based on LDL-C response.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment. Hemodialysis does not significantly remove atorvastatin. |
| Liver impairment | Contraindicated in active liver disease or unexplained persistent transaminase elevations. For Child-Pugh class A, reduce dose; no data for Child-Pugh B/C; avoid use in severe hepatic impairment. |
| Pediatric use | Heterozygous familial hypercholesterolemia (10-17 years): 10 mg orally once daily; maximum 20 mg. Homozygous familial hypercholesterolemia (≥10 years): 10-80 mg orally once daily. |
| Geriatric use | No specific dose adjustment required; use the lowest effective dose due to increased risk of adverse effects (e.g., myopathy, cognitive impairment). Monitor renal and hepatic function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LIPITOR (LIPITOR).
| Breastfeeding | Contraindicated in breastfeeding. Endogenous cholesterol in breast milk is critical for infant development. Atorvastatin and its metabolites are excreted into human milk; M/P ratio not established but likely significant based on physicochemical properties. Alternative agents with lower risk should be considered. |
| Teratogenic Risk | Pregnancy Category X. Atorvastatin is contraindicated in pregnancy. First trimester: potential for fetal developmental toxicity based on animal studies and case reports. Second and third trimesters: significant risk of fetal malformations due to inhibition of HMG-CoA reductase essential for fetal cholesterol synthesis. Significant fetal adverse effects include skeletal anomalies, CNS defects, and growth restriction. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Active liver disease or unexplained persistent transaminase elevations","Pregnancy and breastfeeding","Concomitant use with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, protease inhibitors, erythromycin, clarithromycin, nefazodone)"]
| Precautions | ["Myopathy/rhabdomyolysis risk increased with high doses, concomitant CYP3A4 inhibitors, or in predisposed patients","Hepatic enzyme elevation; monitor liver function before and during therapy","New-onset diabetes mellitus risk reported with statins","Use caution in patients with renal impairment"] |
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| Fetal Monitoring | Monitor hepatic function (LFTs) prior to and during therapy. Assess for muscle symptoms (CPK if myopathy suspected). Inadvertent exposure in pregnancy requires fetal ultrasound for structural anomalies, particularly skeletal and CNS. Discontinue immediately upon pregnancy detection. |
| Fertility Effects | No evidence of direct impairment of fertility in humans. Animal studies show no adverse effects on fertility or reproductive performance. However, underlying conditions requiring statin use (e.g., hyperlipidemia, PCOS) may indirectly affect fertility. |