Amdova

Approved Indications:

• Hypertension with Hyperlipidemia or Dyslipidemia: For patients with coexisting high blood pressure and elevated cholesterol or triglycerides, to reduce cardiovascular risk.
• Stable Coronary Artery Disease (CAD): In patients with established atherosclerotic disease or multiple risk factors where both blood pressure and LDL-C need to be targeted.
• Primary Prevention of Cardiovascular Disease: In individuals at high risk (e.g., diabetics, smokers, obese patients) with elevated LDL and borderline hypertension.
• Secondary Prevention: In patients post-MI, PCI, or with documented coronary heart disease requiring both antihypertensive and lipid-lowering therapy.
• Mixed Dyslipidemia with Elevated BP: In patients with combined cholesterol abnormalities and hypertension.
• Angina (Chronic Stable or Vasospastic): Amlodipine component provides antianginal benefit, especially in patients also requiring statin therapy.

Important Off-label/Clinically Accepted Uses:

• Carotid Atherosclerosis: For reduction of atherosclerotic progression in high-risk individuals.
• Post-stroke Vascular Risk Reduction: In selected patients with elevated BP and dyslipidemia.

General Considerations:

• Administer once daily orally, with or without food.
• Swallow tablet whole with water; do not chew or crush.

Adults:

• Initial Dose: Amlodipine 5 mg + Atorvastatin 10 mg once daily.
• Titration: Adjust every 2–4 weeks based on BP and lipid response.
• Maintenance Dose Range: Amlodipine 5–10 mg + Atorvastatin 10–80 mg once daily.

Elderly (≥65 years):

• Start with lower end of dose range (e.g., Amlodipine 2.5–5 mg + Atorvastatin 10 mg).
• Monitor for hypotension, myopathy, or liver enzyme elevations.

Pediatrics (<18 years):

• Safety and efficacy of the combination not established.

Renal Impairment:

• Mild to Moderate: No dose adjustment needed.
• Severe (CrCl <30 mL/min): Use with caution; initiate at lower dose and monitor.

Hepatic Impairment:

• Mild (Child-Pugh A): Start at lower dose; monitor LFTs.
• Moderate to Severe (Child-Pugh B or C): Contraindicated due to risk of statin-related hepatotoxicity.

Amlodipine is a dihydropyridine calcium channel blocker that inhibits L-type calcium channels in vascular smooth muscle and myocardium, leading to vasodilation and reduced peripheral vascular resistance, which lowers blood pressure and reduces myocardial oxygen demand.
Atorvastatin is a selective HMG-CoA reductase inhibitor that blocks the conversion of HMG-CoA to mevalonate, a rate-limiting step in cholesterol biosynthesis. This leads to decreased intrahepatic cholesterol, upregulation of LDL receptors, and enhanced clearance of circulating LDL-C, thereby lowering plasma LDL, total cholesterol, and triglyceride levels while modestly raising HDL-C.

Amlodipine:

• Absorption: ~60–80%, peak plasma levels in 6–12 hours.
• Bioavailability: 64–90%
• Distribution: Widely distributed; ~93% protein-bound.
• Metabolism: Hepatic via CYP3A4 to inactive metabolites.
• Elimination: Renal and fecal; terminal half-life ~30–50 hours.
• Onset of action: Gradual, within 24–48 hours.

Atorvastatin:

• Absorption: Rapid but variable; peak levels in 1–2 hours.
• Bioavailability: ~14% (due to first-pass metabolism).
• Distribution: >98% protein-bound.
• Metabolism: Liver via CYP3A4; active ortho- and para-hydroxylated metabolites.
• Elimination: Primarily via bile (feces); minimal renal excretion.
• Half-life: ~14 hours (metabolites: ~20–30 hours).
• Lipid-lowering effect duration: 24–30 hours.

• Pregnancy: Contraindicated. Atorvastatin is Category X; may cause fetal harm by interfering with cholesterol biosynthesis vital for fetal development.
• Lactation: Contraindicated. Atorvastatin may be excreted into human milk and affect lipid metabolism in the infant.
• Recommendation: Discontinue combination if pregnancy is detected. Do not use while breastfeeding.

• Primary Class: Antihypertensive and Lipid-Lowering Agent
• Subclasses:
• Amlodipine – Calcium Channel Blocker (Dihydropyridine)
• Atorvastatin – HMG-CoA Reductase Inhibitor (Statin)

• Known hypersensitivity to amlodipine, atorvastatin, or any component of the product
• Active liver disease or unexplained persistent elevations in liver transaminases
• Pregnancy and lactation
• Severe hepatic impairment (Child-Pugh Class B or C)
• Concurrent use of strong CYP3A4 inhibitors (e.g., cyclosporine, clarithromycin) with high-dose atorvastatin
• History of statin-induced myopathy or rhabdomyolysis

• Hepatic Monitoring: Regular liver function tests required before and during treatment due to atorvastatin’s hepatotoxic potential.
• Myopathy/Rhabdomyolysis: Risk increased with high-dose atorvastatin, advanced age, hypothyroidism, or concurrent use of interacting drugs. Monitor for muscle pain, weakness, or CK elevation.
• Hypotension Risk: Especially in patients with severe aortic stenosis or volume depletion (amlodipine).
• CYP3A4 Interactions: Atorvastatin levels may rise with concurrent use of CYP3A4 inhibitors.
• Alcohol Use: May exacerbate hepatic toxicity; use cautiously in chronic alcohol users.
• Diabetogenic Effect: Statins may slightly increase HbA1c and fasting glucose in predisposed patients.
• Elderly: Use lowest effective dose due to increased susceptibility to side effects.

Common:

• Cardiovascular: Peripheral edema, flushing, palpitations (amlodipine)
• Musculoskeletal: Myalgia, joint pain, muscle cramps (atorvastatin)
• GI: Nausea, constipation, abdominal pain
• CNS: Dizziness, fatigue, headache
• Hepatic: Elevated liver enzymes

Less Common:

• Sleep disturbances, rash, erectile dysfunction

Serious (Rare):

• Rhabdomyolysis with acute renal failure
• Severe hepatotoxicity
• Anaphylaxis or angioedema
• Exacerbation of pre-existing diabetes
• Pancreatitis

Major Drug-Drug Interactions:

• CYP3A4 Inhibitors (e.g., itraconazole, ritonavir, clarithromycin): Increase atorvastatin concentration; may require dose reduction.
• CYP3A4 Inducers (e.g., rifampin, phenytoin): Reduce atorvastatin efficacy.
• Other Lipid-Lowering Agents (e.g., fibrates, niacin): Increase risk of myopathy/rhabdomyolysis.
• Calcium Channel Blocker Interactions: Grapefruit juice inhibits CYP3A4, may elevate both drug levels.
• Cyclosporine & Gemfibrozil: Contraindicated or require extreme caution.

Drug-Food Interactions:

• Grapefruit Juice: Avoid due to CYP3A4 inhibition leading to statin toxicity.
• High-fat meals: Slight delay in absorption, but no clinically significant effect.

Drug-Alcohol Interactions:

• Increased risk of hepatic toxicity with excessive alcohol consumption.

• NICE and AHA Guidelines: Continue to support combination therapy in patients with coexisting hypertension and dyslipidemia to reduce overall CV risk.
• 2022 ACC/AHA Updates: Recommend individualized risk-based statin dosing alongside BP control in patients with ASCVD risk >10%.
• EMA Safety Notice (recent years): Statins may slightly increase blood glucose and diabetes risk in some populations; monitor accordingly.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Humidity/Light: Protect from excessive moisture and direct light.
• Handling: Store in original container. Keep tightly closed.
• Reconstitution: Not applicable (oral solid formulation).
• Keep out of reach of children.