ENALAPRIL MALEATE AND, HYDROCHLOROTHIAZIDE, TABLETS, USP

USE IN PREGNANCY

id: 0e2dc6a9-6b48-4d63-9c42-3a1c861f580a
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, enalapril maleate/hydrochlorothiazide tablets should be discontinued as soon as possible. See WARNINGS, Pregnancy, Enalapril Maleate, Fetal/Neonatal Morbidity and Mortality.

DESCRIPTION

id: abda6d33-806d-42b3-aea3-dacfa6e063e7
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Enalapril Maleate/Hydrochlorothiazide combines an angiotensin converting enzyme inhibitor, enalapril maleate, and a diuretic, hydrochlorothiazide. Enalapril maleate is the maleate salt of enalapril, the ethyl ester of a long-acting angiotensin converting enzyme inhibitor, enalaprilat. Enalapril maleate is chemically described as (S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline, (Z)-2-butenedioate salt (1:1). Its empirical formula is C₂₀H₂₈N₂O₅•C₄H₄O₄, and its structural formula is: Enalapril maleate is a white to off-white crystalline powder with a molecular weight of 492.53. It is sparingly soluble in water, soluble in ethanol, and freely soluble in methanol. Enalapril is a pro-drug; following oral administration, it is bioactivated by hydrolysis of the ethyl ester to enalaprilat, which is the active angiotensin converting enzyme inhibitor. Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C₇H₈ClN₃O₄S₂ and its structural formula is: It is a white, or practically white, crystalline powder with a molecular weight of 297.74, which is slightly soluble in water but freely soluble in sodium hydroxide solution. Enalapril maleate/hydrochlorothiazide is available in two tablet combinations of enalapril maleate with hydrochlorothiazide: enalapril maleate/hydrochlorothiazide 5/12.5, containing 5 mg enalapril maleate and 12.5 mg hydrochlorothiazide and enalapril maleate/hydrochlorothiazide 10/25, containing 10 mg enalapril maleate and 25 mg hydrochlorothiazide. Inactive ingredients are: lactose, corn starch, sodium bicarbonate, pregelatinized starch, magnesium stearate and iron oxide.

CLINICAL PHARMACOLOGY

id: 2353db25-f7ca-47b1-99d3-8d196c757668
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

As a result of its diuretic effects, hydrochlorothiazide increases plasma renin activity, increases aldosterone secretion, and decreases serum potassium. Administration of enalapril maleate blocks the renin-angiotensin-aldosterone axis and tends to reverse the potassium loss associated with the diuretic. In clinical studies, the extent of blood pressure reduction seen with the combination of enalapril maleate and hydrochlorothiazide was approximately additive. The antihypertensive effect of enalapril maleate/hydrochlorothiazide was usually sustained for at least 24 hours. Concomitant administration of enalapril maleate and hydrochlorothiazide has little, or no effect on the bioavailability of either drug. The combination tablet is bio-equivalent to concomitant administration of the separate entities.

INDICATIONS AND USAGE

id: 4e60996b-9c29-4f72-ae91-4930bf94adca
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Enalapril maleate/hydrochlorothiazide is indicated for the treatment of hypertension. These fixed dose combinations are not indicated for initial treatment (see DOSAGE AND ADMINISTRATION ). In using enalapril maleate/hydrochlorothiazide, 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 does not have a similar risk. (See WARNINGS .) In considering use of enalapril maleate/hydrochlorothiazide, 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 .)

CONTRAINDICATIONS

id: 499738f9-9b24-44b2-bf60-b3294beffbc8
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Enalapril maleate/hydrochlorothiazide is contraindicated in patients who are hypersensitive to any component of this product and in patients with a history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

ADVERSE REACTIONS

id: b9797e60-9939-4515-bde7-8c01a8d7e43a
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Enalapril maleate/hydrochlorothiazide has been evaluated for safety in more than 1500 patients, including over 300 patients treated for one year or more. In clinical trials with enalapril maleate/hydrochlorothiazide no adverse experiences peculiar to this combination drug have been observed. Adverse experiences that have occurred, have been limited to those that have been previously reported with enalapril or hydrochlorothiazide. The most frequent clinical adverse experiences in controlled trials were: dizziness (8.6 percent), headache (5.5 percent), fatigue (3.9 percent) and cough (3.5 percent). Generally, adverse experiences were mild and transient in nature. Adverse experiences occurring in greater than two percent of patients treated with enalapril maleate/hydrochlorothiazide in controlled clinical trials are shown below.

OVERDOSAGE

id: b1b97f59-319f-4077-9e63-344d72d8e9af
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

No specific information is available on the treatment of overdosage with enalapril maleate/hydrochlorothiazide. Treatment is symptomatic and supportive. Therapy with enalapril maleate/hydrochlorothiazide should be discontinued and the patient observed closely. Suggested measures include the induction of emesis and/or gastric lavage, and correction of dehydration, electrolyte imbalance and hypotension by established procedures.

DOSAGE AND ADMINISTRATION

id: 6f687f86-0928-412b-9819-d11255a0eba0
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Enalapril and hydrochlorothiazide are effective treatments for hypertension. The usual dosage range of enalapril is 10 to 40 mg per day administered in a single or two divided doses; hydrochlorothiazide is effective in doses of 12.5 to 50 mg daily. The side effects (see WARNINGS ) of enalapril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of enalapril and hydrochlorothiazide will be associated with both sets of dose-independent side effects but the addition of enalapril in clinical trials blunted the hypokalemia normally seen with diuretics. To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

HOW SUPPLIED

id: 350f4975-be04-4d4e-91a8-086e3a4afc18
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Enalapril Maleate and Hydrochlorothiazide Tablets USP, 10/25 mg, are peach, caplet-shaped, compressed tablets, engraved on one side with T3. Each tablet contains 10 mg of enalapril maleate and 25 mg of hydrochlorothiazide. They are supplied as follows: NDC 21695-780-30 bottles of 30

Principal Display Panel

id: 2bf8a177-c1c1-4112-84e2-2dc0041b15dd
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4