This combination is indicated for the management of hypertension. However, it is not recommended as an initial treatment for patients newly diagnosed with hypertension.

The combination of amlodipine and benazepril is used for controlling high blood pressure through complementary mechanisms. Benazepril and its active metabolite benazeprilat inhibit the angiotensin-converting enzyme (ACE), thereby reducing the formation of angiotensin II. This leads to decreased vasoconstriction and reduced aldosterone secretion. Although its primary effect is through suppression of the renin-angiotensin-aldosterone system, benazepril can also lower blood pressure in patients with low-renin hypertension. Amlodipine is a dihydropyridine calcium channel blocker that prevents calcium ions from entering vascular smooth muscle and cardiac muscle cells. It acts predominantly on vascular smooth muscle, causing peripheral arterial dilation and reducing vascular resistance, which results in decreased blood pressure.

The absorption of benazepril and amlodipine from the combined formulation is comparable to that from individual preparations. After oral administration, peak plasma levels of benazepril are reached within approximately 0.5–2 hours, while amlodipine reaches peak levels within 6–12 hours, with an absorption rate of about 64–90%. Clinical studies have shown that once-daily administration of this combination produces a significant reduction in blood pressure, beginning within one hour, with maximum effects observed between 2 to 8 hours after dosing. The antihypertensive effect is sustained for up to 24 hours.

Amlodipine is an effective treatment of hypertension in once-daily doses of 2.5-10 mg while Benazepril is effective in doses of 10-80 mg.

It is usually appropriate to begin therapy with this capsule only after a patient has either

• Failed to achieve the desired antihypertensive effect with one or the other monotherapy, or
• Demonstrated inability to achieve adequate antihypertensive effect with Amlodipine therapy without developing edema.

Dose Titration Guided by Clinical Effect: A patient whose blood pressure is not adequately controlled with Amlodipine (or another dihydropyridine) alone or with Benazepril (or another ACE inhibitor) alone may be switched to combination therapy with this capsule. All patient groups benefit from the reduction in Amlodipine-induced edema. Dosage must be guided by clinical response; steady-state levels of Benazepril an Amlodipine will be reached after approximately 2 and 7 days of dosing respectively.

In patients whose blood pressures are adequately controlled with Amlodipine but who experience unacceptable edema, combination therapy may achieve similar (or better) blood-pressure control without edema. Especially in nonblacks, it may be prudent to minimize the risk of excessive response by reducing the dose of Amlodipine as Benazepril is added to the regimen.

Replacement Therapy: For convenience, patients receiving Amlodipine and Benazepril from separate tablets may instead wish to receive this capsule containing the same component doses. In small, elderly, or hepatically impaired patients, the recommended initial dose of Amlodipine, as monotherapy or as a component of combination therapy, is 2.5 mg.

Diuretics: Patients receiving diuretics, particularly those recently started on such therapy, may experience an excessive drop in blood pressure when treatment with Benazepril/Amlodipine is initiated.

Potassium supplements & potassium-sparing diuretics: Benazepril may reduce potassium loss caused by thiazide diuretics. However, potassium-sparing diuretics (such as spironolactone, amiloride, triamterene) or potassium supplements may increase the risk of hyperkalemia. If used together, careful monitoring of serum potassium is required.

Others: Benazepril has been used safely with oral anticoagulants, beta-blockers, calcium channel blockers, cimetidine, diuretics, digoxin, hydralazine, and naproxen without clinically significant interactions.

Amlodipine has also been safely co-administered with thiazide diuretics, beta-blockers, ACE inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, NSAIDs, antibiotics, and oral antidiabetic agents.

This combination is contraindicated in patients with hypersensitivity to benazepril, other ACE inhibitors, or amlodipine.

Benazepril/Amlodipine has been evaluated in hypertensive patients for both short-term and long-term use. Most reported adverse effects are mild and transient, with no significant relation to age, gender, race, or duration of therapy. Discontinuation due to side effects occurred in a small percentage of patients, mainly due to cough and edema. Common side effects include cough, headache, dizziness, and peripheral edema.

Edema is more commonly associated with amlodipine alone and may occur more frequently in women. The addition of benazepril appears to reduce the incidence of edema.

Rare side effects include angioedema, weakness, fatigue, insomnia, anxiety, tremor, decreased libido, flushing, skin rash, dermatitis, dry mouth, nausea, abdominal discomfort, constipation, diarrhea, indigestion, esophagitis, hypokalemia, and pharyngitis.

This combination falls under Pregnancy Category C during the first trimester and Category D during the second and third trimesters. ACE inhibitors may cause serious fetal and neonatal complications, including death, when used during pregnancy. Numerous cases have been reported worldwide. If pregnancy is detected, the medication should be discontinued immediately.

Small amounts of unchanged benazepril and its active metabolite benazeprilat are excreted into breast milk. However, the amount ingested by an infant is estimated to be less than 0.1% of the maternal dose. It is not known whether amlodipine is excreted into human breast milk. Due to insufficient data, breastfeeding should be discontinued while taking this medication.

Impaired Renal Function: Use cautiously in patients with severe renal impairment.

Hyperkalemia: Elevated potassium levels may occur, although usually reversible.

Hepatic Impairment: Amlodipine is extensively metabolized in the liver, and its elimination half-life may be prolonged in patients with liver dysfunction. Therefore, caution is required in patients with severe hepatic disease.

Cough: Persistent cough associated with ACE inhibitors should be considered during diagnosis.

Surgery/Anesthesia: During surgery or anesthesia, benazepril may block angiotensin II formation, leading to hypotension. This condition can usually be corrected by fluid administration.

Carcinogenesis, Mutagenesis, Fertility: No evidence of carcinogenic, mutagenic, or fertility-impairing effects has been observed with this combination.

Geriatric Use: No significant differences in response have been observed between elderly and younger patients, although some older individuals may be more sensitive.

Pediatric Use: Safety and effectiveness in children have not been established.

There are no reported cases of overdose with this specific combination. Reports of benazepril or other ACE inhibitor overdose rarely indicate fatal outcomes.

Combined antihypertensive preparations

Store below 25°C, protected from light and moisture. Keep out of reach of children.