Lexxel Indications, Dosage, Storage, Stability - Enalapril Maleate-Felodipine

Lexxel Indications, Dosage, Storage, Stability - Enalapril Maleate-Felodipine

INDICATIONS AND USAGE

LEXXEL 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 LEXXEL, consideration should be given to the fact that another angiotensin converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease, and that available data are insufficient to show that enalapril (a component of LEXXEL) does not have a similar risk. (See WARNINGS, Neutropenia/Agranulocytosis.)

In considering use of LEXXEL, it should be noted that black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to non-blacks. (See WARNINGS, Angioedema.)

LEXXEL is an effective treatment for hypertension. This fixed combination drug is not indicated for initial therapy of hypertension.

The recommended initial dose of enalapril maleate for hypertension in patients not receiving diuretics is 5 mg once a day. The usual dosage range of enalapril maleate for hypertension is 10-40 mg per day administered in a single dose or two divided doses. In some patients treated once daily with enalapril, the antihypertensive effect may diminish toward the end of the dosing interval. In such patients, an increase in dosage or twice daily administration should be considered. The recommended initial dose of felodipine ER is 5 mg once a day with a usual dosage range of 2.5 mg-10 mg once a day. In elderly or hepatically impaired patients, the recommended initial dose of felodipine is 2.5 mg. When LEXXEL is taken with food, the peak concentration of felodipine is almost doubled, and the trough (24-hour) concentration is approximately halved (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism).

In clinical trials of enalapril-felodipine ER combination therapy using enalapril doses of 5-20 mg and felodipine ER doses of 2.5-10 mg once daily, the antihypertensive effects increased with increasing doses of each component in all patient groups.

The hazards (see WARNINGS and ADVERSE REACTIONS) of enalapril are generally independent of dose; those of felodipine are a mixture of dose-dependent phenomena (primarily peripheral edema) and dose-independent phenomena, the former much more common than the latter. Therapy with any combination of enalapril and felodipine will thus be associated with both sets of dose-independent hazards.

Rarely, the dose-independent hazards associated with enalapril or felodipine are serious. To minimize dose-independent hazards, it is usually appropriate to begin therapy with LEXXEL only after a patient has failed to achieve the desired antihypertensive effect with one or the other monotherapy.

Although the felodipine component of LEXXEL has not been shown to be bioequivalent to the available extended-release felodipine (PLENDIL), patients receiving enalapril and felodipine from separate tablets once a day may instead wish to receive the tablets of LEXXEL containing the same component doses.

A patient whose blood pressure is not adequately controlled with felodipine (or another dihydropyridine) or enalapril (or another ACE inhibitor) alone may be switched to combination therapy with LEXXEL, initially one tablet daily, usually LEXXEL 5-5. If blood pressure control is inadequate after a week or two, the dose may be increased to 2 tablets LEXXEL 5-5 administered once daily. The next incremental effect can be achieved with 4 tablets LEXXEL 5-2.5 administered once daily. If control remains unsatisfactory, consider addition of a thiazide diuretic.

Regimens of therapy with LEXXEL need not be adjusted for renal function as long as the patient’s creatinine clearance is >30 mL/min/1.73m² (serum creatinine roughly £3 mg/dL or 265 mmol/L). In patients with more severe renal impairment, the recommended initial dose of enalapril is 2.5 mg.

LEXXEL should regularly be taken either without food or with a light meal (see CLINICAL PHARMACOLOGY, Pharmacokinetics and Metabolism). LEXXEL should be swallowed whole and not divided, crushed or chewed.

No. 3771 — Tablets LEXXEL, 5-2.5 are white. round/biconvex-shaped, film-coated tablets, coded LEXXEL 2, 5-2.5 on one side and no markings on the other. Each tablet contains 5 mg of enalapril maleate and 2.5 mg of felodipine as an extended-release formulation. They are supplied as follows:

NDC 0186-0002-31 unit of use bottles of 30 (with desiccants)

No. 3661 — Tablets LEXXEL, 5-5 are white, round/biconvex-shaped, film-coated tablets, coded LEXXEL 1, 5-5 on one side and no markings on the other. Each tablet contains 5 mg of enalapril maleate and 5 mg of felodipine as an extended-release formulation. They are supplied as follows:

NDC 0186-0001-31 unit of use bottles of 30 (with desiccants)

NDC 0186-0001-68 bottles of 100 (with desiccants)

Store at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature]. Keep container tightly closed. Protect from moisture and light. Dispense in a tight container, if product package is subdivided.

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*Registered trademark of Merck & Co., Inc.

**Trademark of the AstraZeneca Group

† Based on patient weight of 50 kg

Revised 11/03, LEXXEL is a trademark of the AstraZeneca group © AstraZeneca 2002,2003, Manufactured for: AstraZeneca LP Wilmington, DE 19850 By: Merck & Co., Inc., Whitehouse Station, NJ 08889, USA, 9176508 620008-08