Amdopril

Approved Indications:

• Hypertension:
  Indicated in adult patients whose blood pressure is not adequately controlled by monotherapy with either perindopril arginine or amlodipine. This fixed-dose combination is used to improve blood pressure control.
• Stable Coronary Artery Disease (CAD):
  To reduce the risk of cardiovascular events in adult patients with stable CAD already controlled with perindopril and amlodipine given separately.

Route of Administration: Oral
Available Strengths:

• Perindopril Arginine 3.5 mg / Amlodipine 2.5 mg
• Perindopril Arginine 7 mg / Amlodipine 5 mg
• Perindopril Arginine 14 mg / Amlodipine 10 mg

Adults:

• Initial dose: 3.5 mg / 2.5 mg once daily, preferably in the morning before meals.
• Titrate based on response to:
• 7 mg / 5 mg once daily, then
• 14 mg / 10 mg once daily if needed.

Elderly:

• Begin at the lowest available dose.
• Monitor blood pressure and renal function regularly.

Renal Impairment:

• Mild to Moderate (eGFR ≥30 mL/min): Use with caution; initiate at low doses.
• Severe impairment (eGFR <30 mL/min): Contraindicated.

Hepatic Impairment:

• Amlodipine clearance may be reduced. Start at a lower dose and monitor carefully.
• Avoid in severe hepatic impairment.

Pediatric Use:

• Not recommended in children or adolescents under 18 years due to lack of safety and efficacy data.

Perindopril arginine is an angiotensin-converting enzyme (ACE) inhibitor that is hydrolyzed to its active metabolite, perindoprilat. It inhibits the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, leading to vasodilation, reduced aldosterone secretion, decreased sodium and water retention, and reduced blood pressure. Amlodipine is a long-acting dihydropyridine calcium channel blocker that inhibits the influx of calcium ions into vascular smooth muscle and cardiac cells, promoting vasodilation and reducing peripheral vascular resistance. Together, these actions result in effective and sustained blood pressure reduction with added cardiovascular protection.

Perindopril Arginine:

• Absorption: Rapidly absorbed; converted to perindoprilat
• Bioavailability (as perindoprilat): ~20%
• Tmax (perindoprilat): 3–4 hours
• Half-life: ~25–30 hours
• Metabolism: Hepatic hydrolysis to active form
• Excretion: Primarily renal (up to 70%)

Amlodipine:

• Absorption: Slowly but completely absorbed
• Bioavailability: 64–90%
• Tmax: 6–12 hours
• Half-life: 30–50 hours
• Metabolism: Hepatic via CYP3A4
• Excretion: Renal (~60%) and fecal (~20%)

• Pregnancy:
  FDA Category D (2nd and 3rd trimesters): Perindopril may cause fetal injury or death (e.g., renal dysfunction, skull hypoplasia, oligohydramnios). Discontinue immediately upon pregnancy detection.
• Lactation:
  Amlodipine is excreted into breast milk in low amounts. Data on perindopril are limited. Use is not recommended during breastfeeding due to possible adverse effects in the infant.

• Primary Class: Antihypertensive Combination
• Subclasses:
• Perindopril Arginine: ACE Inhibitor
• Amlodipine: Dihydropyridine Calcium Channel Blocker

• Hypersensitivity to perindopril, amlodipine, ACE inhibitors, dihydropyridines, or excipients
• History of angioedema (with ACE inhibitors or idiopathic)
• Severe renal impairment (eGFR <30 mL/min/1.73 m²)
• Severe hepatic impairment
• Pregnancy or lactation
• Cardiogenic shock or unstable angina
• Concomitant use with aliskiren in diabetic or renally impaired patients

• Angioedema: Can occur any time during therapy. Discontinue immediately if it occurs.
• Hypotension: More likely in volume-depleted or sodium-depleted patients.
• Hyperkalemia: Monitor serum potassium levels regularly, especially in renal impairment.
• Cough: Nonproductive cough may occur due to ACE inhibition.
• Hepatic Impairment: May reduce amlodipine metabolism; careful monitoring required.
• Renal Function: Monitor creatinine and eGFR regularly, especially in high-risk patients.
• Perioperative Risk: May increase risk of hypotension during surgery or anesthesia.
• Peripheral Edema: A known adverse effect of amlodipine.

Common Side Effects (≥1%):

• Cardiovascular: Edema (especially ankles), flushing, palpitations, hypotension
• CNS: Headache, dizziness, fatigue
• Respiratory: Dry cough (due to ACE inhibition), dyspnea
• Gastrointestinal: Nausea, abdominal discomfort
• Musculoskeletal: Muscle cramps

Serious or Rare Side Effects:

• Angioedema (face, lips, tongue, or larynx)
• Hepatitis, jaundice
• Agranulocytosis, neutropenia, thrombocytopenia
• Stevens-Johnson syndrome
• Acute renal failure
• Arrhythmias

• Potassium supplements or potassium-sparing diuretics: May increase risk of hyperkalemia
• NSAIDs: May reduce antihypertensive effect and impair renal function
• Lithium: Increased risk of lithium toxicity
• Other antihypertensives or diuretics: Additive hypotensive effect
• Alcohol: May enhance hypotensive effect
• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): May increase amlodipine levels
• CYP3A4 inducers (e.g., carbamazepine, rifampin): May decrease amlodipine levels

• ESC/ESH 2023 Guidelines for Hypertension:
  Recommends fixed-dose combinations of an ACE inhibitor and a calcium channel blocker as first-line therapy for most hypertensive patients, especially those with cardiovascular comorbidities.
• EMA/FDA Label Updates:
  Reinforced contraindication in pregnancy and need for renal monitoring in patients on dual renin-angiotensin system (RAS) blockade.

• Temperature: Store below 25°C (77°F)
• Humidity & Light: Protect from moisture and light
• Handling: Store in original packaging; keep out of reach of children
• Reconstitution: Not applicable; tablets are ready to use
• Shelf Life: Use before the expiry date on the pack