Benazepril

BRAND NAMES

Benazepril is sold under several brand names. The most common include:

Lotensin – the primary brand name for benazepril tablets. 

Lotensin HCT – a combination of benazepril and hydrochlorothiazide (a diuretic) for enhanced blood pressure control.

MECHANISM OF ACTION

Benazepril is an ACE inhibitor that lowers blood pressure by blocking the formation of angiotensin II, a substance that narrows blood vessels. This causes vessels to relax, reduces heart workload, and promotes mild fluid loss. It also helps protect the kidneys by lowering pressure inside them, especially in patients with diabetes or kidney disease.

PHARMACOKINETICS

Absorption

Benazepril is well absorbed orally, but its bioavailability is about 37%, meaning only a portion reaches systemic circulation in active form. After absorption, it is rapidly converted in the liver to its active metabolite, benazeprilat, which is responsible for its therapeutic effects.. Peak plasma levels of benazeprilat are typically reached 1–2 hours after oral administration.

Distribution

Benazepril is widely distributed throughout the body after absorption. It is moderately bound to plasma proteins (approximately 96%), mainly albumin. The active metabolite, benazeprilat, also distributes into tissues, including the kidneys, where it exerts protective effects. Its volume of distribution (Vd) is about 0.3 L/kg, indicating that it remains largely within the extracellular fluid rather than accumulating extensively in fat or other tissues.

Metabolism

Benazepril is a prodrug that is rapidly metabolized in the liver to its active form, benazeprilat, primarily by hepatic esterases. This conversion is essential because benazepril itself has minimal ACE-inhibiting activity. The metabolic process is not significantly affected by liver enzymes like CYP450, and the active metabolite is responsible for the drug’s antihypertensive and renal-protective effects.

Excretion

Benazeprilat, the active form of benazepril, is primarily excreted by the kidneys. Approximately 95% of the drug is eliminated in the urine, with only a small portion excreted in feces. The elimination half-life of benazeprilat is about 10–11 hours, allowing for once-daily dosing in most patients. Renal function significantly affects clearance, so dose adjustments may be needed in patients with impaired kidney function.

PHARMACODYNAMICS

Benazepril is an ACE inhibitor that lowers blood pressure by blocking the formation of angiotensin II, causing blood vessels to relax and reducing fluid retention. This decreases heart workload and provides kidney protection, especially in patients with diabetes or kidney disease. Its effects begin within an hour and increase with continued use.

ADMINISTRATION

Benazepril is administered orally in tablet form, usually once daily, with or without food. The dose may be adjusted based on blood pressure response and kidney function. For patients with renal impairment, lower starting doses are recommended to reduce the risk of excessive blood pressure lowering or kidney-related side effects.

DOSAGE AND STRENGTH

Benazepril is available in oral tablet form with the following common strengths: 5, 10 mg, 20 mg, and 40 mg.

• Typical adult dose for hypertension: 10–40 mg once daily, depending on blood pressure response.

• Starting dose: Usually 10 mg once daily; lower doses (5 mg) may be used in patients at risk of hypotension or with kidney impairment.

• Maximum dose: 40 mg per day.

• Combination therapy: It can be combined with diuretics like hydrochlorothiazide (as in Lotensin HCT) for additional blood pressure control.

FOOD INTERACTIONS

Benazepril can be taken with or without food, as meals do not affect its absorption. Patients should avoid excessive potassium or salt substitutes, which can increase the risk of high potassium levels, and be cautious with alcohol, which may enhance blood pressure lowering.

DRUG INTERACTIONS

• Potassium-sparing diuretics, potassium supplements, or salt substitutes – May cause hyperkalemia.

• Other antihypertensives – Can enhance blood pressure–lowering effects, increasing risk of hypotension.

• NSAIDs (e.g., ibuprofen, naproxen) – May reduce the blood pressure–lowering effect and increase the risk of kidney problems.

• Lithium – ACE inhibitors can increase lithium levels, raising the risk of toxicity.

• Diuretics – May intensify blood pressure reduction, especially with initial doses.

CONTRAINDICATIONS

• History of angioedema related to previous ACE inhibitor use.

• Pregnancy, especially during the second and third trimesters, due to risk of fetal injury or death.

• Bilateral renal artery stenosis or severe kidney impairment, as it can worsen renal function.

• Hypersensitivity to benazepril or any other ACE inhibitor.

SIDE EFFECTS

Common side effects:

• Cough (dry, persistent)

• Dizziness or lightheadedness, especially when standing

• Fatigue or headache

• Nausea

Serious but less common side effects:

• Angioedema (swelling of face, lips, tongue, or throat)

• Hyperkalemia (high potassium levels)

• Low blood pressure (hypotension)

• Kidney dysfunction or worsening renal failure

• Liver dysfunction (rare)

TOXICITY

Benazepril toxicity usually results from overdose or impaired kidney function and can cause severe low blood pressure, high potassium levels, kidney damage, or rare life-threatening swelling (angioedema). Treatment involves stopping the drug, supportive care, correcting electrolytes, and in severe cases, dialysis.