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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ATORVASTATIN CALCIUM (ATORVASTATIN CALCIUM).
| Breastfeeding | Atorvastatin is excreted into human milk. The milk-to-plasma ratio is not well characterized. Due to potential for serious adverse reactions in nursing infants, breastfeeding is contraindicated during atorvastatin therapy. |
| 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. |
■ FDA Black Box Warning
None
| Common Effects | Increased bleeding tendency Abdominal pain Indigestion Bruise Nosebleeds Gastrointestinal bleeding Diarrhea |
| Serious Effects |
["Active liver disease or unexplained persistent elevations in serum transaminases","Pregnancy (Category X)","Breastfeeding (use not recommended)","Hypersensitivity to atorvastatin or any component of the formulation","Concurrent use with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, clarithromycin, telithromycin, nefazodone, cobicistat-containing products, and large quantities of grapefruit juice intended to be consumed with the drug)"]
| 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…
| 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. |