Amlodipine and Benazepril capsules for hypertension not controlled by single agents

Amlodipine and benazepril hydrochloride capsules combine a calcium channel blocker and an ACE inhibitor to treat high blood pressure in adults who do not achieve adequate control with either medication alone. This oral capsule is designed for once-daily use and helps lower blood pressure by relaxing blood vessels and reducing the workload on the heart.

This medication is indicated for the treatment of hypertension in patients whose blood pressure is not adequately controlled by either amlodipine or benazepril alone. It is intended as an add-on therapy to improve blood pressure management in adults.

Amlodipine besylate and benazepril hydrochloride

Amlodipine is a dihydropyridine calcium channel blocker that relaxes blood vessel muscles, helping to lower blood pressure. Benazepril is an angiotensin-converting enzyme (ACE) inhibitor that reduces the production of angiotensin II, a substance that narrows blood vessels. Together, they dilate blood vessels and decrease blood pressure, improving blood flow and reducing strain on the heart.

The recommended starting dose is one capsule containing amlodipine 2.5 mg and benazepril 10 mg taken orally once daily. Therapy should begin only after a patient has demonstrated insufficient blood pressure control with either amlodipine or benazepril monotherapy or cannot tolerate amlodipine due to edema. The antihypertensive effect generally develops within two weeks.

If blood pressure remains uncontrolled, the dose may be increased gradually up to amlodipine 10 mg and benazepril 40 mg once daily, with adjustment based on individual response. Patients who develop edema on amlodipine alone may benefit from switching to this combination with a lower amlodipine dose.

This medication may replace titrated doses of the individual components when used together.

• History of angioedema related to previous ACE inhibitor therapy.
• Hypersensitivity to benazepril, amlodipine, or any excipients.
• Concomitant use with neprilysin inhibitors (e.g., sacubitril) or within 36 hours before or after such therapy.
• Coadministration with aliskiren in diabetic patients.

Fetal toxicity

Drugs acting on the renin-angiotensin system, including this combination, can cause injury or death to the developing fetus if used during the second or third trimester of pregnancy. Discontinue immediately if pregnancy is detected.

Angioedema and anaphylactoid reactions

Severe swelling of the face, lips, tongue, glottis, or larynx, which can block the airway and be fatal, has been reported at any time during treatment. Discontinue and treat promptly if these symptoms occur. Patients with a history of angioedema or black patients may be at increased risk. Combination with mTOR inhibitors or neprilysin inhibitors increases risk of angioedema.

Hypotension

Symptomatic low blood pressure can occur, especially in patients with heart failure, salt or volume depletion, or severe valve stenosis. Correct volume depletion before starting therapy. If hypotension occurs, place the patient supine and provide intravenous saline if needed. Continue therapy once stable.

Worsening angina or myocardial infarction

May occur after starting or increasing amlodipine dose, particularly in patients with severe coronary artery disease.

Renal impairment

Monitor kidney function regularly. Patients at risk (renal artery stenosis, heart failure, volume depletion, concurrent NSAIDs) may develop acute renal failure. Consider stopping therapy if significant decline occurs.

Hyperkalemia

Monitor serum potassium periodically. Risk increases with renal insufficiency, diabetes, potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes.

Hepatic effects

Rare cases of serious liver injury including cholestatic hepatitis and acute liver failure have been reported. Discontinue if jaundice or marked enzyme elevation occurs.

In clinical trials, treatment discontinuation due to side effects occurred in about 4% of patients taking this combination and 3% on placebo, commonly due to cough and edema.

The incidence of edema was lower with amlodipine and benazepril hydrochloride (2.1%) than with amlodipine alone (5.1%).

Common side effects (>1% incidence) possibly related to treatment include:

• Cough (3.3%)
• Headache (2.2%)
• Dizziness (1.3%)
• Edema (2.1%, including peripheral and facial edema)

Other reported adverse effects include asthenia, fatigue, insomnia, nervousness, anxiety, tremor, decreased libido, flushing, rash, dry mouth, nausea, abdominal pain, dyspepsia, neutropenia, cramps, sexual dysfunction, and polyuria.

Rare postmarketing reports include Stevens-Johnson syndrome, pancreatitis, hemolytic anemia, pruritus, photosensitivity, arthralgia, myalgia, renal impairment, and allergic reactions.

Contraindicated with aliskiren in patients with diabetes. Avoid coadministration with neprilysin inhibitors (e.g., sacubitril) and do not administer within 36 hours of switching.

Coadministration with mTOR inhibitors (temsirolimus, sirolimus, everolimus) increases angioedema risk.

Pregnancy

Amlodipine and benazepril hydrochloride can cause fetal harm when taken during the second or third trimesters, including kidney dysfunction, lung underdevelopment, and death. Discontinue immediately upon pregnancy detection.

Contraception/Fetal risk

Use effective contraception to avoid pregnancy while taking this medication.

Lactation

No specific information provided regarding breastfeeding; consult healthcare provider.