CADUET vs AFEDITAB CR Comparison

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-Co A reductase inhibitor that competitively inhibits the conversion of HMG-Co A to mevalonate, reducing cholesterol synthesis in the liver.

Hypertension,Coronary artery disease,Hyperlipidemia (as adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels, and to increase HDL-C),Prevention of cardiovascular events in patients with multiple risk factors

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.

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-Co A reductase inhibition) is ~20-30 h.

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.

Amlodipine: 60% renal (metabolites), 20-25% biliary/fecal. Atorvastatin: 1% renal (unchanged), 90% biliary/fecal (≥70% as metabolites).

Amlodipine: ~93% bound to plasma proteins. Atorvastatin: ≥98% bound to plasma proteins (mainly albumin).

Amlodipine: Vd ~21 L/kg (large, indicating extensive tissue distribution). Atorvastatin: Vd ~6.2 L/kg (moderately large, suggesting distribution into tissues).

Oral: amlodipine 64-90%; atorvastatin ~14% (low due to first-pass metabolism); food reduces rate but not extent of absorption.

No dosage adjustment required for mild to moderate renal impairment (Cr Cl ≥30 m L/min). For severe renal impairment (Cr Cl <30 m L/min), use atorvastatin with caution; maximum atorvastatin dose is 20 mg daily. Amlodipine is not dialyzable.

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.

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.

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.

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.

Active liver disease or unexplained persistent elevations of hepatic transaminases,Pregnancy,Breastfeeding (due to potential for serious adverse reactions in nursing infants),Hypersensitivity to amlodipine, atorvastatin, or any component of the formulation

Avoid grapefruit and grapefruit juice as they increase atorvastatin plasma concentrations and risk of adverse effects. No significant food interactions with amlodipine.

FDA Pregnancy Category X. Amlodipine: No evidence of teratogenicity in animal studies, but limited human data; atorvastatin: contraindicated in pregnancy as HMG-Co A 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.

Excreted in human milk: Amlodipine: present in low levels (M/P ratio approximately 1.0); atorvastatin: unknown. Due to potential for serious adverse reactions in nursing infants (e.g., skeletal muscle toxicity from statins), breastfeeding is contraindicated during therapy. Alternative agents preferred.

Contraindicated during pregnancy; therefore, no dosing adjustments recommended. Discontinue therapy immediately if pregnancy is suspected or confirmed. Pharmacokinetic changes during pregnancy may alter drug metabolism, but no dose adjustments are justified due to teratogenic risk.

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.

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.