AMLODIPINE BESYLATE AND ATORVASTATIN CALCIUM
Clinical safety rating: safe
Weak CYP3A4 inhibitors may increase levels but no dosage adjustment is typically needed Monitor for hypotension and peripheral edema dose-related side effects.
Amlodipine is a dihydropyridine calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle, causing vasodilation and reduced peripheral vascular resistance. Atorvastatin is an HMG-CoA reductase inhibitor that competitively inhibits the conversion of HMG-CoA to mevalonate, reducing cholesterol biosynthesis in the liver.
| Metabolism | Amlodipine is extensively metabolized in the liver via CYP3A4 to inactive metabolites. Atorvastatin is metabolized primarily by CYP3A4 to active ortho- and para-hydroxylated metabolites. |
| Excretion | Amlodipine: ~60% renal (10% unchanged), 20-25% biliary/fecal. Atorvastatin: ~70% biliary/fecal as metabolites, <2% renal. |
| Half-life | Amlodipine: 30-50 hours (terminal), allowing once-daily dosing. Atorvastatin: 14 hours (parent), active metabolites up to 20-30 hours. |
| Protein binding | Amlodipine: ~93% bound, primarily to albumin. Atorvastatin: ≥98% bound, mainly to albumin and α1-acid glycoprotein. |
| Volume of Distribution | Amlodipine: 21 L/kg (extensive tissue distribution). Atorvastatin: 381 L (large Vd due to lipophilicity; 5.4 L/kg for 70 kg). |
| Bioavailability | Amlodipine: 64-90% (oral). Atorvastatin: 14% (oral, due to first-pass metabolism); absolute bioavailability ~12%. |
| Onset of Action | Oral: Amlodipine 2-4 hours (peak antihypertensive effect), Atorvastatin 1-2 weeks (max lipid reduction). |
| Duration of Action | Amlodipine: 24 hours; steady-state by 7-8 days. Atorvastatin: 24 hours; continuous use for sustained lipid lowering. |
Oral, one tablet daily. Initial dose based on individual components: amlodipine 2.5-10 mg and atorvastatin 10-80 mg. Titrate at intervals of 2-4 weeks.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR >30 mL/min). For GFR <30 mL/min, use with caution; no specific guidelines, monitor for adverse effects. |
| Liver impairment | Child-Pugh Class A or B: Atorvastatin maximum 20 mg daily; amlodipine dose not specified but use caution. Child-Pugh Class C: contraindicated for atorvastatin; amlodipine use with caution. |
| Pediatric use | Not approved in pediatric patients; safety and efficacy not established. |
| Geriatric use | Start at lowest dose (amlodipine 2.5 mg) due to increased sensitivity and reduced clearance; titrate slowly. Monitor for hypotension and dizziness. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Weak CYP3A4 inhibitors may increase levels but no dosage adjustment is typically needed Monitor for hypotension and peripheral edema dose-related side effects.
| FDA category | Animal |
| Breastfeeding | Amlodipine: Excreted in breast milk; M/P ratio unknown; use with caution. Atorvastatin: Excreted in breast milk; contraindicated due to potential adverse effects on infant lipid metabolism. Combination: Discontinue breastfeeding or drug. |
| Teratogenic Risk |
■ FDA Black Box Warning
None.
| Common Effects | angina |
| Serious Effects |
["Hypersensitivity to amlodipine, atorvastatin, or any component of the formulation","Active liver disease or unexplained persistent elevations of serum transaminases (atorvastatin)","Pregnancy (atorvastatin)","Lactation (atorvastatin)"]
| Precautions | ["Risk of myopathy/rhabdomyolysis: Atorvastatin may cause myopathy or rhabdomyolysis; risk increased with higher doses, advanced age, renal impairment, hypothyroidism, and concomitant use of CYP3A4 inhibitors or other statins.","Hepatic effects: Atorvastatin may cause persistent elevations in serum transaminases; liver function tests should be performed before initiation and as clinically indicated.","Peripheral edema: Amlodipine may cause peripheral edema, particularly dose-dependent.","Worsening angina/acute myocardial infarction: Rarely, amlodipine may precipitate angina or MI, especially in patients with severe obstructive coronary artery disease.","Symptomatic hypotension: Amlodipine may cause hypotension, especially in patients with severe aortic stenosis.","Increased angina on beta-blocker withdrawal: Do not abruptly withdraw beta-blockers; taper dose to avoid increased angina."] |
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| Pregnancy Category X. Amlodipine: No teratogenic effects in animal studies but may cause fetal cardiovascular effects in third trimester. Atorvastatin: Contraindicated due to inhibition of HMG-CoA reductase necessary for fetal cholesterol synthesis; first trimester exposure associated with congenital anomalies, second/third trimester exposure may impair fetal development. Combination risk: Avoid in pregnancy. |
| Fetal Monitoring | Pregnancy test before initiation; monitor liver function tests (LFTs) and creatine kinase (CK) for atorvastatin; monitor blood pressure and fetal growth/well-being if inadvertently used in pregnancy. |
| Fertility Effects | Amlodipine: No known effect on fertility. Atorvastatin: No known effect on fertility in animal studies; human data limited. Combination: Unlikely significant effect. |
| Food/Dietary | Grapefruit and grapefruit juice: avoid large quantities as they inhibit CYP3A4 and increase atorvastatin levels, raising risk of myopathy. Alcohol: limit intake as excessive alcohol may increase hepatotoxic risk of atorvastatin. High-fat meals: may slightly reduce absorption of atorvastatin but clinical significance is minimal; take consistently with regard to meals. |
| Clinical Pearls | This fixed-dose combination is indicated for patients who require both amlodipine (calcium channel blocker) and atorvastatin (HMG-CoA reductase inhibitor). Amlodipine may cause peripheral edema, especially at higher doses; consider dose adjustment or add ACE inhibitor. Atorvastatin may increase risk of new-onset diabetes, myopathy, and hepatotoxicity; monitor LFTs and CK. Avoid use with strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole) due to increased atorvastatin exposure. Amlodipine can be taken with or without food; atorvastatin may be more effective if taken in the evening (though not required). |
| Patient Advice | Take this medication exactly as prescribed, usually once daily with or without food. Try to take it at the same time each day. · Avoid consuming large amounts of grapefruit or grapefruit juice while taking this medication, as it can increase the risk of side effects from atorvastatin. · Report any unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever or dark urine, as this may indicate a rare but serious muscle problem. · Avoid alcohol; limit alcohol intake as it can increase the risk of liver damage. · This medication may cause dizziness or swelling in the ankles/feet; rise slowly from sitting or lying down. Contact your doctor if swelling becomes bothersome. · Do not take other medications, including over-the-counter products, without consulting your doctor, especially antifungal drugs, antibiotics, or HIV medications. · If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and resume your regular schedule. Do not double the dose. |