Enalapril-Akri^® H (Tablets) Instructions for Use

ATC Code

C09BA02 (Enalapril and diuretics)

Active Substances

Hydrochlorothiazide (Rec.INN registered by WHO)

Enalapril (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antihypertensive drug

Pharmacotherapeutic Group

Antihypertensive combination agent (ACE inhibitor + diuretic)

Indications

• Arterial Hypertension: This fixed-dose combination is indicated for the treatment of hypertension in patients for whom combination therapy is appropriate. It is not indicated for initial therapy.
• Heart Failure (as adjunctive therapy): Enalapril-Akri H may be used in the management of heart failure in patients who require the specific effects of both an ACE inhibitor and a thiazide diuretic, typically to reduce edema and afterload.

The use of this combination should be individualized. It may be more convenient than administering the two components separately, but dose titration is best achieved by first establishing the effective doses of the individual components.

Contraindications

• Hypersensitivity: Known hypersensitivity to enalapril, hydrochlorothiazide, any other sulfonamide-derived drugs, or any of the excipients.
• Angioedema: A history of angioedema related to previous ACE inhibitor therapy. Hereditary or idiopathic angioedema.
• Anuria and Severe Renal Impairment: Patients with anuria or severe renal impairment (creatinine clearance less than 30 mL/min).
• Refractory Hypokalemia and Hypercalcemia: Pre-existing severe refractory hypokalemia, hyponatremia, or hypercalcemia.
• Pregnancy and Lactation: The drug is contraindicated during the second and third trimesters of pregnancy and is not recommended during the first trimester. It is also contraindicated in breastfeeding mothers.
• Concomitant Use with Aliskiren: In patients with diabetes mellitus or renal impairment (GFR < 60 mL/min/1.73 m²), the concomitant use with aliskiren is contraindicated.
• Bilateral Renal Artery Stenosis: Or stenosis in a solitary kidney.

Dosage Regimen

The dosage of Enalapril-Akri H must be individualized based on the patient’s blood pressure response and clinical status. The fixed-dose combination is not for initial therapy. The patient’s condition should be stabilized on the individual components first.

For Hypertension: The usual recommended dosage is one tablet once daily. The strength (10 mg+12.5 mg or 10 mg+25 mg) is determined by the patient’s previous therapeutic regimen. The dosage may be titrated up to a maximum of two tablets of the 10 mg+25 mg strength per day, administered as a single dose or in two divided doses. Dosage adjustment is required in patients with renal impairment. In patients with a creatinine clearance below 30 mL/min, loop diuretics are preferred over thiazides, and thus, this combination is not recommended.

For Heart Failure (adjunctive therapy): Therapy should be initiated under close medical supervision. The usual starting dose is one tablet of the 10 mg+12.5 mg strength once daily. The dose may be increased gradually, based on tolerance and clinical response. The maximum daily dose is two tablets of the 10 mg+25 mg strength.

The tablets should be taken orally, with or without food, at approximately the same time each day. It is important to maintain adequate hydration unless otherwise directed by a physician.

Adverse Reactions

Adverse reactions are generally mild and transient, but serious reactions can occur. The most frequently reported reactions are associated with the ACE inhibitor class and the diuretic component.

Common Adverse Reactions: These may include dizziness, headache, fatigue, persistent dry cough, orthostatic hypotension, nausea, and diarrhea. Hypokalemia, hyperuricemia, and slight increases in blood urea nitrogen and serum creatinine may also occur.

Serious Adverse Reactions:Angioedema of the face, extremities, lips, tongue, glottis, and/or larynx has been reported and requires immediate discontinuation and emergency treatment. Symptomatic hypotension may occur, especially in volume-depleted patients. Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported. Other serious reactions include neutropenia/agranulocytosis, pancreatitis, hepatic dysfunction, and acute renal failure.

Electrolyte Imbalances: Hydrochlorothiazide can cause electrolyte disturbances such as hypokalemia, hyponatremia, hypochloremic alkalosis, and hypomagnesemia. Regular monitoring of serum electrolytes is recommended.

Drug Interactions

Concomitant use of Enalapril-Akri H with other agents requires caution due to the potential for significant interactions.

Diuretics and Other Antihypertensives: Concomitant use may have an additive hypotensive effect. A severe hypotensive reaction is possible, particularly after the first dose, if the patient is already taking high-dose diuretics. It is recommended to discontinue the diuretic or increase salt intake 2-3 days before starting enalapril, or to initiate enalapril at a lower dose.

Lithium: Thiazide diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity. Concurrent use is not recommended; if necessary, monitor lithium serum levels closely.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): NSAIDs, including selective COX-2 inhibitors, may reduce the antihypertensive effect of ACE inhibitors and increase the risk of renal impairment, especially in dehydrated or elderly patients.

Potassium-Sparing Diuretics and Potassium Supplements: Concomitant use can lead to significant hyperkalemia. Such combinations should be used with extreme caution and with frequent monitoring of serum potassium.

Antidiabetic Agents: Thiazide diuretics may decrease glucose tolerance, potentially necessitating an adjustment in the dose of insulin or oral hypoglycemic agents.

Alcohol, Barbiturates, and Narcotics: May potentiate orthostatic hypotension.

Overdose

Symptoms: The most likely manifestation of overdose is hypotension, which can be severe. Other symptoms may include bradycardia, circulatory shock, electrolyte disturbances (hypokalemia, hyponatremia), dehydration, and acute renal failure. Lethargy and other signs of central nervous system depression may occur.

Management: Treatment is primarily supportive and symptomatic. Place the patient in a supine position and elevate the legs. Volume repletion with intravenous normal saline is the treatment of choice for hypotension. Gastric lavage or activated charcoal may be considered if ingestion was recent. Enalapril can be removed from the body by hemodialysis. Serum electrolyte levels and renal function should be monitored closely, and appropriate corrective measures taken for any imbalances. Bradycardia or profound hypotension may require administration of atropine or catecholamines.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.