Pendoril

Approved Indications:

• Essential Hypertension:
  Indicated for the treatment of mild to moderate high blood pressure in adults. Reduces the risk of stroke, myocardial infarction, and cardiovascular mortality.
• Stable Coronary Artery Disease (CAD):
  Indicated to reduce the risk of cardiovascular events in patients with a history of myocardial infarction and/or revascularization, especially with preserved left ventricular function.
• Heart Failure (Symptomatic):
  Indicated in chronic heart failure (NYHA class II to IV) as part of combination therapy with diuretics and/or other medications (e.g., beta-blockers, aldosterone antagonists).

Clinically Accepted Off-Label Uses:

• Diabetic Nephropathy:
  For renal protection in diabetic patients with proteinuria or hypertension.
• Post-Myocardial Infarction:
  To reduce cardiovascular remodeling and prevent reinfarction in appropriate patients.

Route of Administration: Oral
Available Formulations: Tablets containing Perindopril Arginine 2.5 mg, 5 mg, or 10 mg (equivalent to Perindopril Erbumine 2 mg, 4 mg, or 8 mg)

Adults:

• Hypertension:
  Initial dose: 5 mg once daily before meals.
  Maintenance: 5–10 mg once daily.
  Maximum dose: 10 mg/day.
• Stable CAD:
  Start with 5 mg once daily for 2 weeks, then increase to 10 mg once daily if tolerated.
• Heart Failure:
  Start with 2.5 mg once daily. Titrate to 5 mg once daily after 2 weeks, depending on tolerance.

Elderly:

• Start at a lower dose (2.5 mg once daily). Titrate slowly based on renal function and blood pressure response.

Renal Impairment:

• Mild (CrCl ≥60 mL/min): No dose adjustment.
• Moderate (CrCl 30–60 mL/min): Start with 2.5 mg once daily.
• Severe (CrCl <30 mL/min): Not recommended.

Hepatic Impairment:

• Use with caution. No dose adjustment required, but clinical monitoring is advised.

Pediatrics:

• Not recommended. Safety and efficacy in children have not been established.

Perindopril Arginine is a long-acting angiotensin-converting enzyme (ACE) inhibitor. After oral administration, it is hydrolyzed to its active metabolite, perindoprilat, which inhibits ACE and thus prevents the conversion of angiotensin I to angiotensin II. Angiotensin II is a vasoconstrictor that also stimulates aldosterone secretion. Blocking its formation results in vasodilation, reduced sodium and water retention, and a decrease in blood pressure. In heart failure and coronary artery disease, this leads to reduced preload and afterload, improved cardiac output, and protection against ventricular remodeling.

• Absorption: Rapidly absorbed; peak plasma levels in 1 hour (perindopril), 3–4 hours (perindoprilat).
• Bioavailability: ~65% (perindopril); ~20% (perindoprilat)
• Protein Binding: Low (10–30%), mainly to ACE
• Metabolism: Hepatic hydrolysis of perindopril to active perindoprilat
• Half-life: Terminal half-life of perindoprilat ~25–30 hours
• Elimination: Primarily renal (70%) as perindoprilat

• Pregnancy:
  Category D (2nd and 3rd trimesters): Use of ACE inhibitors can result in fetal toxicity, including renal dysfunction, skull hypoplasia, and fetal death. Discontinue immediately upon detection of pregnancy.
• Lactation:
  Use is not recommended during breastfeeding. It is unknown whether perindopril is excreted in breast milk; potential adverse effects on the infant cannot be excluded.

• Primary Class: Antihypertensive Agent
• Subclass: Angiotensin-Converting Enzyme (ACE) Inhibitor
• Generation: Long-acting, tissue-penetrating ACE inhibitor

• Known hypersensitivity to perindopril or any component of the formulation
• History of angioedema associated with previous ACE inhibitor therapy
• Hereditary or idiopathic angioedema
• Pregnancy and breastfeeding
• Severe renal impairment (eGFR <30 mL/min/1.73 m²)
• Bilateral renal artery stenosis
• Concomitant use with aliskiren in diabetic patients or those with renal impairment

• Angioedema: Can occur at any time during treatment; discontinue immediately if symptoms occur.
• Hypotension: Especially in sodium-depleted, dehydrated, or heart failure patients.
• Hyperkalemia: Monitor serum potassium in patients on potassium-sparing drugs or supplements.
• Renal Impairment: Risk of deterioration; monitor renal function, especially with diuretics or renal artery stenosis.
• Cough: Dry, persistent cough may occur; consider discontinuation if bothersome.
• Surgery/Anesthesia: Risk of hypotension; inform anesthesiologist before procedure.
• Liver Function: Use with caution in patients with hepatic impairment.

Common Side Effects (≥1%):

• Cardiovascular: Hypotension, dizziness, flushing
• CNS: Headache, fatigue, somnolence
• Respiratory: Dry cough, dyspnea
• Gastrointestinal: Nausea, abdominal discomfort, taste changes
• Renal: Elevated serum creatinine, hyperkalemia
• Dermatologic: Rash, pruritus

Serious or Rare Adverse Effects:

• Angioedema (life-threatening)
• Anaphylactoid reactions
• Hepatitis, cholestatic jaundice
• Agranulocytosis, thrombocytopenia
• Stevens-Johnson syndrome (very rare)

• Potassium-sparing diuretics or supplements: ↑ Risk of hyperkalemia
• Diuretics: May enhance hypotensive effect, especially during initiation
• NSAIDs: May reduce antihypertensive effect and worsen renal function
• Lithium: Increased lithium levels and toxicity risk
• Aliskiren: Contraindicated in patients with diabetes or impaired renal function
• General anesthetics: May enhance hypotensive effects

• ESC/ESH 2023 Guidelines: Perindopril remains a recommended first-line ACE inhibitor for hypertension, particularly in high-risk cardiovascular patients.
• EMA/FDA: Reinforced warning regarding fetal toxicity; emphasize discontinuation in pregnancy.
• Recent Trials: Continued evidence supports cardiovascular benefits in patients with stable coronary disease, including mortality reduction.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Excursions: Permitted between 15°C and 30°C
• Humidity/Light: Protect from moisture and direct sunlight
• Handling: Keep in original packaging; do not remove tablets until use
• Reconstitution: Not applicable
• Precaution: Keep out of reach of children; do not use after expiry date