Acepril

Approved Indications:

• Hypertension:
  • Treatment of essential hypertension in adults and in pediatric patients ≥6 years of age.
  • May be used alone or in combination with other antihypertensive agents (e.g., thiazide diuretics).
• Heart Failure (Chronic):
  • Management of symptomatic heart failure in adults, typically in combination with diuretics and/or digitalis.
  • Reduces hospitalizations and improves symptoms.
• Acute Myocardial Infarction (AMI):
  • Administered within 24 hours of infarction in hemodynamically stable patients to improve survival and prevent left ventricular dysfunction.
• Asymptomatic Left Ventricular Dysfunction:
  • Treatment of asymptomatic left ventricular systolic dysfunction (ejection fraction ≤35%) to delay the progression to overt heart failure.

Clinically Accepted Off-Label Uses:

• Diabetic Nephropathy:
  • Slows progression of kidney disease in diabetic patients with proteinuria by reducing intraglomerular pressure.
• Secondary Stroke Prevention (in combination):
  • Used as part of an antihypertensive regimen to reduce the risk of recurrent stroke, particularly in patients with hypertension.

Route of Administration: Oral
Usual Frequency: Once daily

Adults:

• Hypertension:
  • Initial dose: 10 mg once daily
  • Maintenance dose: 20–40 mg once daily
  • Maximum dose: 80 mg/day
  • If on diuretics: Start with 5 mg or temporarily discontinue diuretic 2–3 days before starting lisinopril
• Heart Failure:
  • Initial dose: 2.5–5 mg once daily
  • Target dose: 20–40 mg/day in single or divided doses
  • Titrate slowly based on tolerance and renal function
• Acute Myocardial Infarction:
  • Day 1: 5 mg within 24 hours of symptom onset
  • Day 2: 5 mg after 24 hours
  • Day 3: 10 mg after 48 hours
  • Maintenance: 10 mg once daily for at least 6 weeks
• Asymptomatic Left Ventricular Dysfunction:
  • Initial dose: 5 mg once daily
  • Maintenance dose: 10–20 mg once daily

Pediatric Patients (≥6 years with hypertension):

• Initial dose: 0.07 mg/kg once daily (maximum initial dose: 5 mg/day)
• Maintenance dose: Up to 0.6 mg/kg/day (maximum: 40 mg/day)
• Not recommended for children <6 years or with GFR <30 mL/min/1.73 m²

Renal Impairment:

• CrCl 10–30 mL/min: Initial dose 5 mg once daily
• CrCl <10 mL/min or on dialysis: Initial dose 2.5 mg once daily
• Titrate cautiously with close renal monitoring

Hepatic Impairment:
• No specific dosage adjustment required

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor that blocks the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor responsible for increasing blood pressure and stimulating aldosterone secretion. The inhibition leads to vasodilation, decreased sodium and water retention, reduced blood volume, and lower blood pressure. In heart failure and post-myocardial infarction, reduced angiotensin II levels decrease preload and afterload, improving cardiac output and preventing ventricular remodeling. Lisinopril also reduces intraglomerular pressure in the kidneys, thereby slowing progression of proteinuric renal disease.

• Absorption: ~25% bioavailability; unaffected by food
• Onset of Action: 1 hour
• Peak Plasma Concentration: 6–8 hours
• Distribution: Not protein-bound; volume of distribution ~0.5–0.6 L/kg
• Metabolism: Not metabolized; administered as active drug
• Half-life: Approximately 12 hours
• Excretion: Primarily excreted unchanged in urine
• Dialysis Clearance: Approximately 50 mL/min; can be removed by hemodialysis

• Pregnancy:
  • FDA Category D (2nd and 3rd trimester): Lisinopril can cause fetal toxicity including hypotension, anuria, renal failure, skull hypoplasia, and even fetal death. Discontinue immediately upon confirmation of pregnancy.
• Lactation:
  • Lisinopril is excreted into breast milk in small amounts.
  • Use with caution, especially in nursing newborns or preterm infants due to potential for hypotension and renal dysfunction.

• Primary Class: Angiotensin-Converting Enzyme (ACE) Inhibitor
• Subclass: Long-acting, non-sulfur-containing ACE inhibitor

• Known hypersensitivity to lisinopril or any ACE inhibitor
• History of angioedema related to previous ACE inhibitor therapy
• Hereditary or idiopathic angioedema
• Concomitant use with aliskiren in patients with diabetes mellitus
• Pregnancy
• Pediatric patients with GFR <30 mL/min/1.73 m²

• Angioedema: May occur anytime during treatment; discontinue immediately if symptoms arise
• Hyperkalemia: Increased risk in renal impairment, diabetes, or when combined with potassium-sparing diuretics or supplements
• Hypotension: More likely in volume- or salt-depleted patients; monitor closely during initiation
• Renal Impairment: Monitor serum creatinine and potassium regularly; may cause reversible acute renal failure
• Persistent Dry Cough: A common side effect of ACE inhibitors
• Hematologic Effects: Rare risk of neutropenia/agranulocytosis in renal impairment or autoimmune disease
• Surgical Considerations: Risk of hypotension during anesthesia; inform surgical team if taking lisinopril

Common Side Effects:

• Cardiovascular: Hypotension, dizziness, orthostatic effects
• Renal: Increased serum creatinine, hyperkalemia
• Respiratory: Persistent dry cough
• Gastrointestinal: Nausea, diarrhea
• Neurological: Headache, fatigue
• Dermatologic: Rash, pruritus

Serious/Rare Side Effects:

• Angioedema of face, lips, tongue, or larynx
• Anaphylaxis
• Acute renal failure
• Hepatotoxicity (rare cholestatic jaundice or hepatitis)
• Neutropenia or agranulocytosis
• Stevens-Johnson syndrome (extremely rare)

• Potassium-sparing Diuretics/Potassium Supplements: Increased risk of hyperkalemia
• NSAIDs: May reduce antihypertensive effect and worsen renal function
• Diuretics (Loop or Thiazide): Enhance hypotensive effects
• Lithium: Increased serum lithium levels and risk of toxicity
• Antidiabetic Agents (Insulin/Oral): Increased risk of hypoglycemia
• Aliskiren: Contraindicated in diabetic patients
• CYP450 Interactions: Lisinopril is not metabolized by CYP enzymes; minimal hepatic drug interaction risk

• Hypertension Guidelines (ACC/AHA 2023): Lisinopril remains a first-line agent for hypertension, especially in patients with diabetes, heart failure, or CKD.
• ESC Heart Failure Guidelines (2022): Endorsed as part of foundational therapy in HFrEF.
• FDA Safety Updates: Continued emphasis on black box warning for fetal toxicity; no changes in dosage recommendations.

• Storage Temperature: 20°C to 25°C (68°F to 77°F)
• Permitted Excursions: Between 15°C and 30°C
• Humidity Protection: Store in a dry place, tightly closed container
• Light Protection: No special requirements
• Reconstitution/Refrigeration: Not applicable