Vaseretic Information
Vaseretic (Enalapril/hctz)
Vaseretic (Enalapril/hctz) Use In Pregnancy
Vaseretic (Enalapril/hctz) Description
Vaseretic (Enalapril/hctz) (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 ()-1-[-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline, ()-2-butenedioate salt (1:1). Its empirical formula is CHNO•CHO, 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-2-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is CHClNOS 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.
Vaseretic (Enalapril/hctz) is available in the tablet combination of enalapril maleate with hydrochlorothiazide: Vaseretic (Enalapril/hctz) 10-25, containing 10 mg enalapril maleate and 25 mg hydrochlorothiazide. Inactive ingredients are: iron oxide, lactose, magnesium stearate, sodium bicarbonate, and starch.
Vaseretic (Enalapril/hctz) Clinical Pharmacology
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 Vaseretic (Enalapril/hctz) 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 bioequivalent to concomitant administration of the separate entities.
Vaseretic (Enalapril/hctz) Indications And Usage
Vaseretic (Enalapril/hctz) is indicated for the treatment of hypertension.
This fixed dose combination is not indicated for initial treatment (see ).
In using Vaseretic (Enalapril/hctz) , 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 ).
In considering use of Vaseretic (Enalapril/hctz) , 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 ).
Vaseretic (Enalapril/hctz) Contraindications
Vaseretic (Enalapril/hctz) 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.
Vaseretic (Enalapril/hctz) Precautions
General
Information for Patients
Drug Interactions
Carcinogenesis, Mutagenesis, Impairment of Fertility
Enalapril in combination with hydrochlorothiazide was not mutagenic in the Ames microbial mutagen test with or without metabolic activation. Enalapril-hydrochlorothiazide did not produce DNA single strand breaks in an alkaline elution assay in rat hepatocytes or chromosomal aberrations in an mouse bone marrow assay.
Pregnancy
Nursing Mothers
Enalapril, enalaprilat, and hydrochlorothiazide have been detected in human breast milk. Because of the potential for serious reactions in nursing infants from either drug, a decision should be made whether to discontinue nursing or to discontinue Vaseretic (Enalapril/hctz) , taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Clinical studies of Vaseretic (Enalapril/hctz) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Evaluation of the hypertensive patient should always include assessment of renal function (see ).
Vaseretic (Enalapril/hctz) Adverse Reactions
Vaseretic (Enalapril/hctz) has been evaluated for safety in more than 1500 patients, including over 300 patients treated for one year or more. In clinical trials with Vaseretic (Enalapril/hctz) 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 Vaseretic (Enalapril/hctz) in controlled clinical trials are shown below.
Clinical adverse experiences occurring in 0.5 to 2.0 percent of patients in controlled trials included: Syncope, chest pain, abdominal pain; Orthostatic hypotension, palpitation, tachycardia; Vomiting, dyspepsia, constipation, flatulence, dry mouth; Insomnia, nervousness, paresthesia, somnolence, vertigo; Pruritus, rash; Dyspnea, gout, back pain, arthralgia, diaphoresis, decreased libido, tinnitus, urinary tract infection.
Vaseretic (Enalapril/hctz) Overdosage
No specific information is available on the treatment of overdosage with Vaseretic (Enalapril/hctz) . Treatment is symptomatic and supportive. Therapy with Vaseretic (Enalapril/hctz) should be discontinued and the patient observed closely. Suggested measures include induction of emesis and/or gastric lavage, and correction of dehydration, electrolyte imbalance and hypotension by established procedures.
Enalapril Maleate
Hydrochlorothiazide
Vaseretic (Enalapril/hctz) Dosage And Administration
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 ) 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.
Dose Titration Guided by Clinical Effect:
Replacement Therapy:
Use in Renal Impairment:
2
Vaseretic (Enalapril/hctz) How Supplied
Vaseretic (Enalapril/hctz) Tablets 10-25 mg, are rust, oval shaped tablets, with one side "VASE 10-25" and scored and the other side scored. Each tablet contains 10 mg of enalapril maleate and 25 mg of hydrochlorothiazide. They are supplied as follows:
Vaseretic (Enalapril/hctz)
Vaseretic (Enalapril/hctz) Principal Display Panel - Tablet Bottle
