Anapril

Approved Indications:

• Hypertension (High Blood Pressure):
  First-line treatment for mild to moderate hypertension, alone or in combination with other antihypertensives.
• Heart Failure (NYHA Class II–IV):
  Used to improve symptoms, reduce hospitalization, and improve survival.
• Asymptomatic Left Ventricular Dysfunction:
  Delays the onset of symptomatic heart failure and reduces hospitalization risk.
• Diabetic Nephropathy (Type 1 Diabetes with proteinuria):
  Slows the progression of renal disease and reduces proteinuria.

Clinically Accepted Off-Label Uses:

• Hypertensive crisis (non-emergency):
  May be used in step-down therapy following IV control.
• Scleroderma Renal Crisis:
  Used cautiously to manage hypertension and protect renal function.

Route of Administration: Oral (Tablet)

Adults:

• Hypertension:
  Initial: 5 mg once daily (2.5 mg if on diuretics);
  Maintenance: 10–40 mg/day in 1–2 divided doses.
• Heart Failure:
  Initial: 2.5 mg twice daily;
  Target: 20 mg/day in divided doses, titrated over 2–4 weeks.
• Asymptomatic Left Ventricular Dysfunction:
  Initial: 2.5 mg twice daily;
  Target: 20 mg/day in divided doses.

Pediatric (≥1 month, for Hypertension):

• Initial: 0.08 mg/kg once daily (max 5 mg/day);
  Max dose: 0.58 mg/kg/day or 40 mg/day.

Elderly:

• Start with lower dose (2.5 mg/day); titrate cautiously.

Renal Impairment:

• Creatinine Clearance (CrCl) 30–80 mL/min: Start with 2.5–5 mg/day
• CrCl <30 mL/min or on dialysis: Start with 2.5 mg every other day or daily; dose titration must be slow.

Hepatic Impairment:
No specific adjustments; monitor closely.

Enalapril is a prodrug that is converted in the liver to its active form, enalaprilat. Enalaprilat inhibits angiotensin-converting enzyme (ACE), which is responsible for the conversion of angiotensin I to angiotensin II—a potent vasoconstrictor. By inhibiting ACE, enalapril reduces levels of angiotensin II, leading to vasodilation, reduced aldosterone secretion, decreased sodium and water retention, and reduced blood pressure. In heart failure, this mechanism reduces preload and afterload, improving cardiac output and ventricular remodeling.

• Absorption: ~60% oral bioavailability; food does not affect absorption.
• Distribution: Volume of distribution ~0.8 L/kg; not extensively protein-bound.
• Metabolism: Hepatic conversion of enalapril (prodrug) to enalaprilat (active).
• Onset of Action: 1 hour; peak effect in 4–6 hours.
• Half-life: Enalapril ~1.3 hours; enalaprilat ~11 hours.
• Excretion: Primarily renal (~60% as enalaprilat); remainder in feces.
• Steady State: Achieved in ~3 days with regular dosing.

• Pregnancy:
  Category D (2nd and 3rd trimesters): Contraindicated due to risk of fetal toxicity, including renal failure, oligohydramnios, and death.
  1st Trimester: Use only if absolutely necessary.
• Lactation:
  Enalapril and enalaprilat are excreted in breast milk in low levels.
  Caution is advised, especially in neonates or preterm infants.
  Consider alternatives if clinically justified.

• Primary Class: Angiotensin-Converting Enzyme (ACE) Inhibitor
• Subclass: Long-acting ACE inhibitor
• Generation: Second generation

• Known hypersensitivity to enalapril, enalaprilat, or any ACE inhibitors
• History of angioedema related to previous ACE inhibitor use
• Hereditary or idiopathic angioedema
• Concomitant use with aliskiren in patients with diabetes mellitus
• Pregnancy (especially 2nd and 3rd trimesters)
• Severe renal impairment without monitoring
• Bilateral renal artery stenosis or stenosis of a solitary functioning kidney

• Black Box Warning:
  Discontinue immediately if pregnancy is detected due to fetal toxicity.
• High-Risk Populations:
  Patients with renal dysfunction, volume depletion, or on diuretics are at higher risk of hypotension.
  Use cautiously in patients with collagen vascular disease (e.g., lupus).
• Angioedema Risk:
  Monitor for facial, tongue, or airway swelling, especially in Black patients.
• Renal Function Monitoring:
  Monitor serum creatinine and potassium during treatment, especially in the elderly or those with kidney disease.
• Hyperkalemia:
  Use with caution in patients receiving potassium supplements, potassium-sparing diuretics, or NSAIDs.
• Cough:
  Persistent dry cough is a common reason for discontinuation.

Common Side Effects:

• Cardiovascular: Hypotension, dizziness, orthostatic hypotension
• Respiratory: Dry, persistent cough
• Renal: Increased serum creatinine, renal impairment
• GI: Nausea, abdominal pain, diarrhea
• Neurologic: Headache, fatigue

Serious Adverse Effects:

• Angioedema (face, lips, tongue, airway)
• Hyperkalemia
• Hepatotoxicity (rare)
• Neutropenia/agranulocytosis (especially in renal impairment or autoimmune disease)
• Stevens-Johnson syndrome (very rare)

Timing:
Adverse effects like hypotension may occur after the first dose, especially in volume-depleted patients.

Major Interactions:

• Potassium-Sparing Diuretics & Supplements: Risk of hyperkalemia
• NSAIDs: May reduce antihypertensive efficacy and worsen renal function
• Diuretics: Potentiate hypotension with first dose
• Lithium: Increased lithium levels and toxicity risk
• Aliskiren: Avoid in diabetics or patients with renal impairment
• Loop/Thiazide Diuretics: May increase risk of electrolyte imbalance

Metabolism/Enzymes:
No significant involvement of CYP450 isoenzymes; minimal risk of CYP-mediated interactions.

• Hypertension Guidelines (AHA/ACC): Enalapril remains a first-line option, especially for patients with heart failure, diabetes, or proteinuric CKD.
• Heart Failure Guidelines (ESC & AHA 2023): Reconfirmed use in HFrEF (with reduced EF); may be replaced with ARNi in eligible patients but still widely recommended where ARNi not feasible.
• Safety Alerts:
  Continued caution advised for use in pregnancy and for monitoring hyperkalemia and renal function in high-risk patients.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C.
• Humidity & Light: Store in a dry place, protected from moisture and light.
• Handling: Do not freeze. Keep tablets in the original container.
• Special Instructions: No reconstitution or refrigeration required.