CADUET
Clinical safety rating
cautionComprehensive clinical and safety monograph for CADUET (CADUET).
Amlodipine: Dihydropyridine calcium channel blocker that inhibits calcium ion influx across cardiac and vascular smooth muscle cell membranes, causing vasodilation and reduced peripheral vascular resistance. Atorvastatin: HMG-CoA reductase inhibitor that competitively inhibits the conversion of HMG-CoA to mevalonate, reducing cholesterol synthesis in the liver.
| Metabolism | Amlodipine: Extensively metabolized in the liver via CYP3A4 to inactive metabolites. Atorvastatin: Metabolized in the liver primarily by CYP3A4 to active ortho- and para-hydroxylated metabolites. |
| Excretion | Amlodipine: 60% renal (metabolites), 20-25% biliary/fecal. Atorvastatin: 1% renal (unchanged), 90% biliary/fecal (≥70% as metabolites). |
| Half-life | Amlodipine: terminal half-life 30-50 h (enables once-daily dosing). Atorvastatin: terminal half-life ~14 h, but active metabolites (ortho- and para-hydroxy atorvastatin) have half-life 20-30 h; clinically, pharmacodynamic half-life (HMG-CoA reductase inhibition) is ~20-30 h. |
| Protein binding | Amlodipine: ~93% bound to plasma proteins. Atorvastatin: ≥98% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | Amlodipine: Vd ~21 L/kg (large, indicating extensive tissue distribution). Atorvastatin: Vd ~6.2 L/kg (moderately large, suggesting distribution into tissues). |
| Bioavailability | Oral: amlodipine 64-90%; atorvastatin ~14% (low due to first-pass metabolism); food reduces rate but not extent of absorption. |
| Onset of Action | Oral: amlodipine antihypertensive effect begins within 2-4 h; atorvastatin lipid-lowering effect detectable within 2 weeks, maximal at 4-6 weeks. |
| Duration of Action | Amlodipine: antihypertensive effect persists for 24 h (sustained once-daily). Atorvastatin: LDL reduction sustained for ≥24 h; duration of lipid-lowering effect is prolonged due to active metabolites. |
| Molecular Weight | Amlodipine besylate: 567.05 Da; atorvastatin calcium: 1209.42 Da |
| Brand Substitutes | A2 5mg/10mg Tablet, A2 5 mg/10 mg Tablet, AMAT 5MG/10MG TABLET, Amdepin Duo 5 mg/10 mg Tablet, Zivast-AM Tablet |
CADUET (amlodipine/atorvastatin) is available as tablets of 2.5/10, 2.5/20, 2.5/40, 5/10, 5/20, 5/40, 5/80, 10/10, 10/20, 10/40, and 10/80 mg amlodipine/atorvastatin. Initial dose depends on current antihypertensive and lipid-lowering therapy. Usual starting dose is 5/10 mg orally once daily; titrate at intervals of 2-4 weeks based on blood pressure and LDL-C goals. Maximum daily dose: amlodipine 10 mg; atorvastatin 80 mg.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). For severe renal impairment (CrCl <30 mL/min), use atorvastatin with caution; maximum atorvastatin dose is 20 mg daily. Amlodipine is not dialyzable. |
| Liver impairment | Contraindicated in active liver disease or unexplained persistent elevations of serum transaminases. For Child-Pugh Class A or B hepatic impairment: atorvastatin dose should be reduced; maximum atorvastatin dose is 20 mg daily. Amlodipine clearance is decreased; initial amlodipine dose should be 2.5 mg daily. No data for Child-Pugh Class C; use contraindicated. |
| Pediatric use | Not recommended for pediatric patients. Safety and efficacy in children <10 years have not been established. For patients 10-17 years with heterozygous familial hypercholesterolemia, atorvastatin monotherapy is used; CADUET is not indicated. |
| Geriatric use | Elderly patients (≥65 years) may have increased sensitivity to amlodipine; start at the lower end of dosing range (2.5 mg amlodipine component). Atorvastatin dose adjustment not required based on age alone. Monitor for hypotension and other adverse effects. |
| 1st trimester | Amlodipine: limited data; atorvastatin: contraindicated due to risk of fetal development interference (HMG-CoA reductase inhibition). |
| 2nd trimester | Amlodipine: possible use if benefit outweighs risk (potential fetal hypoxia); atorvastatin: contraindicated due to risk of fetal malformations. |
| 3rd trimester | Amlodipine: may cause fetal hypoxia and neonatal hypotension; atorvastatin: contraindicated (risk to fetus). |
Clinical note
Comprehensive clinical and safety monograph for CADUET (CADUET).
| Placental transfer | Amlodipine: crosses placenta in animals; atorvastatin: crosses placenta in humans (FDA Category X). |
| Breastfeeding | Amlodipine excreted in breast milk in small amounts; atorvastatin concentration unknown but statins generally contraindicated due to potential for serious adverse reactions in nursing infants. Use with caution, preferably avoid. |
| Lactation Rating | Avoid |
| Teratogenic Risk | FDA Pregnancy Category X. Amlodipine: No evidence of teratogenicity in animal studies, but limited human data; atorvastatin: contraindicated in pregnancy as HMG-CoA reductase inhibitors are associated with fetal abnormalities, including skeletal and CNS defects. First trimester: Atorvastatin is contraindicated; risk of congenital anomalies. Second/third trimester: Avoid exposure; potential for fetal toxicity. Effective contraception required for women of childbearing potential. |
| Fetal Monitoring | Pregnancy test prior to initiation and periodically as indicated. Monitor liver function tests (LFTs) in women of childbearing age. For unintended pregnancy, discontinue immediately and inform patient. Ultrasound for fetal assessment if exposure occurs. |
| Fertility Effects | Amlodipine: No significant impact on fertility in animal studies. Atorvastatin: No well-controlled human studies; animal studies showed no impairment of fertility. Overall, no established adverse effects on fertility in humans. |
■ FDA Black Box Warning
HMG-CoA reductase inhibitors (statins) can cause fetal harm; use in pregnant women is contraindicated. Caduet contains atorvastatin; therefore, it is contraindicated in pregnant women.
| Serious Effects |
Active liver diseaseUnexplained persistent elevations of serum transaminasesPregnancyBreastfeedingHypersensitivity to amlodipine, atorvastatin, or any component
| Precautions | Myopathy/Rhabdomyolysis: Risk increased with higher doses, age >65, renal impairment, hypothyroidism, and concurrent use of CYP3A4 inhibitors or other drugs that cause myopathy., Hepatic effects: Elevated liver enzymes; perform liver function tests before initiation and as clinically indicated., Fetal toxicity: May cause fetal harm; advise females of reproductive age to use effective contraception., Peripheral edema: More common with higher doses of amlodipine, especially in females., Hypotension: In patients with severe aortic stenosis. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they increase atorvastatin plasma concentrations and risk of adverse effects. No significant food interactions with amlodipine. |
| Clinical Pearls | CADUET is a fixed-dose combination of amlodipine (a calcium channel blocker) and atorvastatin (a statin) used for hypertension and dyslipidemia. Avoid concomitant use with strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole) due to increased statin exposure and risk of myopathy. Monitor liver enzymes before and during therapy, and for muscle symptoms. Use with caution in patients with severe renal impairment. Avoid grapefruit juice as it increases atorvastatin levels. |
| Patient Advice | Take this medication once daily at the same time, with or without food. · Avoid grapefruit and grapefruit juice while taking this medication. · Report unexplained muscle pain, tenderness, or weakness, especially if accompanied by fever or malaise. · Notify your doctor if you become pregnant, plan to become pregnant, or are breastfeeding. · Do not stop taking this medication without consulting your doctor, even if you feel well. |
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