ATORVASTATIN CALCIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ATORVASTATIN CALCIUM (ATORVASTATIN CALCIUM).
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 | Primarily hepatic via CYP3A4; metabolites include ortho- and para-hydroxylated derivatives and beta-oxidation products. Subject to enterorecirculation. |
| Excretion | Primarily biliary excretion (approx. 70%) as metabolites; renal excretion accounts for <2% of the administered dose; fecal elimination of metabolites and parent drug (approx. 90%). |
| Half-life | Terminal elimination half-life: 14 hours (range 11–24 h); the active metabolite half-life is 20–30 h; clinical context: supports once-daily dosing despite shorter HMG-CoA reductase inhibitory half-life due to prolonged pharmacodynamic effect. |
| Protein binding | ≥98% bound to plasma proteins (primarily albumin); binding is independent of concentration. |
| Volume of Distribution | Approximately 0.33 L/kg (range 0.25–0.50 L/kg); indicates limited tissue distribution, primarily in liver where active drug is present. |
| Bioavailability | Oral bioavailability: 12–14% (range 6–20%); low due to extensive first-pass hepatic metabolism; food reduces rate but not extent of absorption; no other routes relevant. |
| Onset of Action | Oral: Reduction in LDL-C observed within 2 weeks; maximal effect at 4 weeks; no other routes clinically relevant. |
| Duration of Action | Duration of LDL-C reduction persists for the dosing interval; clinical effect maintained with daily dosing; no significant rebound upon discontinuation. |
| Molecular Weight | 558.64 |
10-80 mg orally once daily, starting at 10-20 mg; maximum dose 80 mg/day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for any degree of renal impairment; use caution in severe impairment due to limited data. |
| Liver impairment | Contraindicated in active liver disease or unexplained persistent transaminase elevations (Child-Pugh class A, B, C); use not recommended. |
| Pediatric use | 10-20 mg orally once daily for ages 10-17 years (postmenarchal females); maximum 20 mg/day. |
| Geriatric use | Start at lower end of dosing range (10 mg daily) due to increased risk of myopathy; titrate cautiously. |
| 1st trimester | Contraindicated due to risk of fetal malformations; use only if clearly needed and no alternative. |
| 2nd trimester | Contraindicated; may cause fetal harm; use only if clearly needed. |
| 3rd trimester | Contraindicated; may cause fetal harm; use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for ATORVASTATIN CALCIUM (ATORVASTATIN CALCIUM).
| Placental transfer | Crosses placenta; animal studies show fetal harm; no adequate human studies. |
| Breastfeeding | Excreted into human milk in low levels; however, due to potential for serious adverse reactions in nursing infants, decision should be made to discontinue nursing or discontinue drug, taking into account importance of drug to mother. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Common Effects | Increased bleeding tendency Abdominal pain Indigestion Bruise Nosebleeds Gastrointestinal bleeding Diarrhea |
| Serious Effects |
Active liver diseaseUnexplained persistent elevations of serum transaminasesHypersensitivity to atorvastatin or any componentPregnancyBreastfeedingConcomitant use with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, telithromycin, clarithromycin, delayirdine, nefazodone, and protease inhibitors including ritonavir, lopinavir/ritonavir, atazanavir/ritonavir, indinavir/ritonavir, saquinavir/ritonavir, tipranavir/ritonavir, darunavir/ritonavir, cobicistat-containing products)
| Precautions | Myopathy/rhabdomyolysis risk (increased with high doses, renal impairment, drug interactions including CYP3A4 inhibitors, gemfibrozil, cyclosporine), Hepatic enzyme elevations (monitor liver function before initiation and as needed), Hemorrhagic stroke (minor increased risk in patients with prior stroke/TIA), New-onset diabetes (small increased risk; monitor glucose in predisposed patients), Use caution in patients with predisposing factors for renal impairment (e.g., sepsis, hypotension, major surgery, trauma, electrolyte disorders) |
Loading safety data…
| L4 (Contraindicated) |
| Teratogenic Risk | Atorvastatin is contraindicated in pregnancy. HMG-CoA reductase inhibitors decrease synthesis of cholesterol and possibly other biologically active substances derived from cholesterol, which are essential for fetal development. First trimester exposure may be associated with congenital anomalies; second and third trimester exposure poses risk of fetal toxicity and should be avoided. |
| Fetal Monitoring | Monitor maternal liver function tests (ALT, AST) and creatine kinase (CK) levels. Assess for signs of myopathy or rhabdomyolysis. Fetal monitoring via ultrasound for growth and development if inadvertent exposure occurs. |
| Fertility Effects | No significant impact on fertility has been reported in human studies. Animal studies showed no impairment of fertility at clinically relevant doses. |
| Food/Dietary | Grapefruit juice (>1 quart/day) increases systemic exposure via CYP3A4 inhibition. Red yeast rice containing monacolin K may potentiate adverse effects. Avoid alcohol consumption if hepatic impairment is present. |
| Clinical Pearls | Atorvastatin is a potent statin with a long half-life (14 hours), allowing once-daily dosing at any time. Monitor liver transaminases at baseline and as clinically indicated; myopathy risk increases with concurrent use of CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, grapefruit juice >1 quart/day). Avoid use in active liver disease or unexplained persistent transaminase elevations. |
| Patient Advice | Take exactly as prescribed, usually once daily at the same time, with or without food. · Avoid grapefruit juice intake greater than 1 quart per day. · Report unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever or dark urine. · Maintain a heart-healthy diet and exercise regimen as adjunct therapy. · Do not stop without consulting your doctor; cholesterol lowering is a long-term therapy. |