Lotrel is indicated for the treatment of hypertension.

This fixed combination drug is not indicated for the initial therapy of hypertension (see DOSAGE AND ADMINISTRATION).

In using Lotrel, consideration should be given to the fact that an ACE inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that benazepril does not have a similar risk (see WARNINGS, Neutropenia/Agranulocytosis).

Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to nonblacks.

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. In clinical trials of amlodipine/benazepril combination therapy using amlodipine doses of 2.5-10 mg and benazepril doses of 10-40 mg, the antihypertensive effects increased with increasing dose of amlodipine in all patient groups, and the effects increased with increasing dose of benazepril in nonblack groups. All patient groups benefited from the reduction in amlodipine-induced edema (see below).

The hazards (see WARNINGS) of benazepril are generally independent of dose; those of amlodipine are a mixture of dose-dependent phenomena (primarily peripheral edema) and dose- independent phenomena, the former much more common than the latter. When benazepril is added to a regimen of amlodipine, the incidence of edema is substantially reduced. Therapy with any combination of amlodipine and benazepril will thus be associated with both sets of dose-independent hazards, but the incidence of edema will generally be less than that seen with similar (or higher) doses of amlodipine monotherapy.

Rarely, the dose-independent hazards of benazepril are serious. To minimize dose-independent hazards, it is usually appropriate to begin therapy with Lotrel only after a patient has either (a) failed to achieve the desired antihypertensive effect with one or the other monotherapy, or (b) 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 Lotrel. The addition of benazepril to a regimen of amlodipine should not be expected to provide additional antihypertensive effect in African- Americans. However, all patient groups benefit from the reduction in amlodipine-induced edema. Dosage must be guided by clinical response; steady-state levels of benazepril and 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 capsules of Lotrel containing the same component doses.

Use in Patients With Metabolic Impairments: Regimens of therapy with Lotrel need not take account of renal function as long as the patient's creatinine clearance is > 30 mL/min/1.73m² (serum creatinine roughly ≤ 3 mg/dL or 265 µmol/L). In patients with more severe renal impairment, the recommended initial dose of benazepril is 5 mg. Lotrel is not recommended in these patients.

In small, elderly, frail, or hepatically impaired patients, the recommended initial dose of amlodipine, as monotherapy or as a component of combination therapy, is 2.5 mg.

Lotrel is available as capsules containing amlodipine besylate equivalent to 2.5 mg, 5 mg or 10 mg of amlodipine, with 10 mg, 20 mg or 40 mg of benazepril hydrochloride providing for the following available combinations: 2.5/10 mg, 5/10 mg, 5/20 mg, 5/40 mg, 10/20 mg and 10/40 mg. All six strengths are packaged in bottles of 100 capsules.

Capsules are imprinted with “Lotrel” and appropriate code.

Storage: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).

[See USP controlled room temperature.] Protect from moisture. Dispense in tight container (USP).

** Trademark of Thomson Healthcare, Inc.
REV: January 2007. Distributed by: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936. FDA Rev date: 8/31/2007

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