Anapril5 mg

Anapril is an angiotensin-converting enzyme (ACE) inhibitor indicated for the following:

Established/FDA-approved uses

• Hypertension: Anapril is indicated for the treatment of high blood pressure, alone or in combination with other antihypertensive agents (e.g. thiazide diuretics), to lower blood pressure and reduce the risk of fatal and non-fatal cardiovascular events, primarily stroke and myocardial infarction.
• Heart failure: Anapril is indicated as adjunct therapy, together with diuretics and, when indicated, digitalis, in the management of symptomatic heart failure, to improve survival and reduce the frequency of hospitalization.
• Asymptomatic left ventricular dysfunction: Anapril is indicated in clinically stable, asymptomatic patients with left ventricular ejection fraction ≤35% to decrease the rate of development of overt heart failure and reduce the incidence of hospitalization for heart failure.

Guideline-supported / off-label uses

• Diabetic and non-diabetic nephropathy: Anapril is commonly used, per clinical guidelines, to slow the progression of renal disease in patients with proteinuria, based on the renoprotective, blood-pressure-independent effects of ACE inhibition.
• Post-myocardial infarction left ventricular dysfunction: used in some patients to reduce the risk of subsequent heart failure, as an alternative when other ACE inhibitors with formal post-MI labeling are not suitable; this is not a primary FDA-labeled indication for Anapril.

Use of Anapril for any indication should be individualized and directed by a physician.

Enalapril Maleate is available as oral tablets, commonly in strengths of 2.5 mg, 5 mg, 10 mg, and 20 mg. Each tablet contains Enalapril Maleate as the active pharmaceutical ingredient, along with standard pharmaceutical excipients such as diluents, binders, and lubricants used in tablet manufacturing.

Anapril is a synthetic angiotensin-converting enzyme (ACE) inhibitor used to manage high blood pressure and certain forms of heart failure. Chemically, Anapril is a prodrug: after oral absorption it is hydrolyzed in the liver to enalaprilat, its active metabolite, which is responsible for its pharmacological effect.

Anapril has been used clinically for several decades and is one of the most extensively studied members of the ACE inhibitor class, with a well-characterized efficacy and safety profile in adults and children.

Anapril belongs to the therapeutic class of Angiotensin-Converting Enzyme (ACE) Inhibitors, a group of antihypertensive and cardioprotective agents.

Enalapril Maleate is a prodrug that is de-esterified in the liver to its active diacid metabolite, enalaprilat. Enalaprilat competitively inhibits angiotensin-converting enzyme (ACE), which is responsible for converting angiotensin I to the potent vasoconstrictor angiotensin II.

By blocking this conversion, Enalapril Maleate produces the following effects:

• Decreased plasma angiotensin II, leading to reduced systemic vascular resistance and lower blood pressure.
• Decreased aldosterone secretion, which reduces sodium and water retention and can raise serum potassium slightly.
• Reduced bradykinin degradation (since ACE also breaks down bradykinin), which contributes to vasodilation but is also implicated in the cough and angioedema associated with this drug class.
• In heart failure, reduced afterload and preload, improving cardiac output and reducing symptoms of congestion.

Onset of antihypertensive effect typically occurs within an hour, with peak effect at 4-6 hours after oral dosing of Enalapril Maleate; the antihypertensive effect generally persists for 24 hours, supporting once- or twice-daily dosing.

Anapril tablets may be taken with or without food, at approximately the same time each day to maintain consistent blood levels. Tablets should be swallowed with a glass of water. Anapril should not be stopped abruptly without medical advice, and any dose changes should be made only under a physician's guidance.

The following clinically significant interactions have been reported with Anapril:

• Potassium-sparing diuretics, potassium supplements, and salt substitutes: may increase the risk of hyperkalemia when combined with Anapril; concurrent use requires monitoring of serum potassium.
• Lithium: Anapril can reduce lithium excretion, increasing serum lithium levels and the risk of lithium toxicity; lithium levels should be monitored closely.
• NSAIDs (including selective COX-2 inhibitors): may reduce the antihypertensive effect of Anapril and increase the risk of renal impairment, particularly in patients who are elderly, volume-depleted, or have pre-existing renal disease.
• Dual blockade of the renin-angiotensin system (ARBs or aliskiren): combining Anapril with an angiotensin receptor blocker or with aliskiren (especially in patients with diabetes or renal impairment) increases the risk of hypotension, hyperkalemia, and renal impairment, and is generally not recommended; concomitant use with aliskiren in diabetic patients is contraindicated.
• Sacubitril/valsartan: Anapril must not be co-administered with sacubitril/valsartan due to an increased risk of angioedema; a washout period of at least 36 hours is required when switching between the two agents (see Contraindications).
• Diuretics and other antihypertensives: may cause additive or excessive hypotension, particularly the first dose after diuretic initiation.

Side effects reported with Anapril include:

Common

• Dizziness, headache, fatigue
• Persistent dry cough
• Hypotension, particularly after the first dose
• Nausea, diarrhea
• Mild elevations in serum potassium and creatinine

Less common but serious

• Angioedema of the face, lips, tongue, or throat (see Contraindications and Precautions and Warnings)
• Significant hyperkalemia
• Acute renal failure, particularly in patients with renal artery stenosis or volume depletion
• Neutropenia/agranulocytosis (rare, more common with renal impairment or collagen vascular disease)
• Hepatic injury, including rare cases of cholestatic jaundice progressing to hepatic necrosis

Patients should seek prompt medical attention for swelling of the face/tongue/throat, difficulty breathing, or signs of liver problems while taking Anapril.

Pregnancy: Anapril is contraindicated in pregnancy. Drugs that act directly on the renin-angiotensin system, including Anapril, can cause fetal and neonatal morbidity and death when used in the second and third trimesters, including oligohydramnios, fetal growth restriction, renal failure, and skull hypoplasia. When pregnancy is detected, Anapril should be discontinued as soon as possible and the patient switched to an alternative antihypertensive under physician guidance, unless continued use is considered lifesaving.

Lactation: Anapril and its active metabolite pass into breast milk in small amounts. Because of the potential for adverse effects in a nursing infant, Anapril should be used during breastfeeding only if clearly needed and the potential benefit justifies the potential risk to the infant; caution is advised particularly when nursing a newborn or premature infant, and a physician should be consulted.

The following precautions apply to the use of Anapril:

• Angioedema: Anapril can cause angioedema of the face, extremities, lips, tongue, glottis, and/or larynx, which can occur at any time during treatment and may be life-threatening if it involves the airway. Anapril should be discontinued immediately and emergency treatment given if angioedema occurs (see Contraindications).
• Hypotension: symptomatic hypotension, especially after the first dose, can occur, particularly in patients who are volume- or salt-depleted (e.g. from diuretics, dietary salt restriction, dialysis, vomiting, or diarrhea). Volume depletion should be corrected before starting Anapril where possible.
• Hyperkalemia: Anapril can raise serum potassium; risk is increased with renal impairment, diabetes, concomitant potassium-sparing diuretics/supplements, or other RAAS-acting drugs.
• Renal impairment / renal artery stenosis: Anapril can cause acute renal failure in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney; renal function should be monitored, especially early in treatment.
• Cough: a persistent, dry, non-productive cough is a recognized class effect of ACE inhibitors, including Anapril, and typically resolves after discontinuation.
• Hepatic failure: rarely, ACE inhibitors including Anapril have been associated with a syndrome starting with cholestatic jaundice that can progress to fulminant hepatic necrosis; Anapril should be discontinued if marked elevation of liver enzymes or jaundice occurs.
• Neutropenia/agranulocytosis: rare, with higher risk in patients with renal impairment, especially those with collagen vascular disease; periodic monitoring of white blood cell counts may be considered in such patients.
• Anaphylactoid reactions: reported during desensitization with hymenoptera venom and during low-density lipoprotein apheresis with dextran sulfate in patients taking ACE inhibitors; temporary discontinuation before such procedures may be advised by the treating physician.

The most likely manifestation of Anapril overdose is significant hypotension, which may present as dizziness, lightheadedness, or fainting; other features may include electrolyte disturbances and renal impairment.

If overdose is suspected, seek immediate medical attention or contact a poison control center/emergency services without delay. Management is supportive and should be provided in a medical facility; it may include intravenous normal saline for volume expansion and close monitoring of blood pressure, renal function, and electrolytes. Enalaprilat, the active metabolite of Anapril, can be removed by hemodialysis in severe cases. Do not attempt to manage a suspected overdose of Anapril at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal impairment: lower starting doses and careful titration of Anapril are recommended, with monitoring of renal function and serum potassium (see Dosage and Administration).

Hepatic impairment: Anapril should be used with caution, as conversion of the prodrug to its active metabolite may be reduced; patients should be monitored for reduced efficacy and for hepatic adverse effects (see Precautions and Warnings).

Elderly: no overall differences in safety or effectiveness have been observed compared to younger patients, but elderly patients, who often have reduced renal function, may be more sensitive to hypotension and hyperkalemia; dose titration should be cautious.

Black patients: ACE inhibitors, including Anapril, have been associated with a higher rate of angioedema in Black patients compared with non-Black patients, and antihypertensive response as monotherapy may be reduced in this population.

Pediatric and pregnant/lactating patients: see Pediatric Uses and Pregnancy and Lactation.

Anapril is generally used as a long-term, often lifelong, maintenance therapy for chronic conditions such as hypertension and heart failure, since these conditions typically require ongoing blood pressure and cardiac support rather than short courses of treatment. The duration of therapy should be determined by the prescribing physician based on the patient's condition, response, and tolerability, with periodic clinical review. Anapril should not be stopped abruptly without medical advice.

Angiotensin-Converting Enzyme (ACE) Inhibitor; Antihypertensive agent

Enalapril Maleate is hydrolyzed to enalaprilat, which inhibits angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. This lowers circulating angiotensin II and aldosterone, reduces vasoconstriction and sodium/water retention, and increases bradykinin-mediated vasodilation, resulting in lowered blood pressure and reduced cardiac workload.

D

Anapril is approved for the treatment of hypertension in pediatric patients 1 month of age and older. It is not recommended for neonates (infants younger than 1 month), particularly premature neonates, because of insufficient data on safety in this age group and their vulnerability to profound and unpredictable decreases in blood pressure and urine output.

Anapril has not been studied in pediatric patients with a glomerular filtration rate less than 30 mL/min/1.73 m², and is not recommended in this population.

Safety and effectiveness of Anapril for indications other than hypertension (such as heart failure) have not been established in pediatric patients.

Pediatric dosing (hypertension), when used, is weight-based and initiated at a low dose with careful titration by a physician experienced in treating pediatric hypertension; oral solutions or crushed-tablet suspensions of Anapril may be used where an appropriate pediatric strength or formulation is not commercially available, under pharmacist/physician guidance.