Vaseretic (enalapril maleate/hydrochlorothiazide)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Hydrochlorothiazide is a thiazide diuretic and antihypertensive agent.
Enalapril is an angiotensin-converting enzyme (ACE) inhibitor; enalaprilat is the active metabolite of the orally administered prodrug, enalapril maleate. .
Enalapril maleate is a prodrug that undergoes bioactivation to its active form, enalaprilat. Enalaprilat prevents the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) through inhibition of angiotensin-converting enzyme (ACE). Inhibition of ACE results in decreased plasma angiotensin II concentrations and, consequently, blood pressure may be reduced in part through decreased vasoconstriction.
Because of decreased plasma angiotensin II concentrations, plasma renin activity (PRA) increases. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. With decreased plasma angiotensin II concentrations, small increases in serum potassium can be observed (mean of 0.2 mEq/L), although with concomitant use of a thiazide diuretic there are essentially no changes in serum potassium.
While the mechanism by which enalapril lowers blood pressure is thought to be from suppression of the renin-angiotensin-aldosterone system, enalapril may also lower blood pressure in patients with low-renin hypertension. Although enalapril has lowered blood pressure in all races studied, the drug was less effective in Black hypertensive patients, a population associated with low renin hypertension. Because ACE is identical to 'kininase,' enalapril may also interfere with degradation of the vasodepressor peptide bradykinin.
Whether increased concentrations of bradykinin play a role in the therapeutic efficacy of enalapril remains to be elucidated.
Following oral administration of enalapril maleate, peak plasma concentrations occur in about 1 hour. Although enalaprilat is a more potent ACE inhibitor than enalapril, it is poorly absorbed from the GI tract. Approximately 60% of an oral dose of enalapril maleate is absorbed from the GI tract.
Food does not appear to substantially affect the rate or extent of absorption of enalapril maleate. Peak plasma concentrations of enalaprilat occur 3-4 hours after oral administration of enalapril maleate. Following oral administration, the onset of hypotensive effects occurs after 1 hour, with peak hypotensive effects observed at 4-6 hours.
The hypotensive effect of usual doses of the drug generally persists for at least 24 hours but may diminish toward the end of the dosing interval in some patients. The reduction in blood pressure may be gradual, and several weeks of therapy may be required before the full effect is achieved. Following IV administration of enalaprilat, the hypotensive effect is usually apparent within 15 minutes with maximal effect occurring within 1-4 hours; the duration of hypotensive effect appears to be dose related, but with the recommended doses, the duration of action in most patients is approximately 6 hours.
After withdrawal of enalapril or enalaprilat, blood pressure gradually returns to pretreatment levels; rebound hypertension following abrupt withdrawal of the drug has not been reported to date.
Information on distribution into the CNS is limited, but enalapril appears to cross the blood-brain barrier poorly, if at all, and enalaprilat does not appear to distribute into the CNS. The drug did not accumulate in any tissue following multiple dose administration in animals. The drug crosses the placenta.
Enalapril and enalaprilat are distributed into breastmilk.
About 60% of an absorbed dose of enalapril is extensively hydrolyzed to enalaprilat, principally in the liver. There is no evidence of other metabolites of enalapril. Following oral administration, enalapril and enalaprilat are excreted in urine and feces.
Approximately 94% of an enalapril dose is excreted in urine or feces (40% of the dose excreted as enalaprilat and the remainder as intact enalapril in the urine). In a multiple dose study (0.07-0.14 mg/kg of enalapril maleate daily) in hypertensive pediatric patients (2 months to 16 years of age), 68% (63-76% as enalaprilat and the remainder as unchanged drug) of the administered dose is recovered in urine within 24 hours. Enalaprilat is removed by hemodialysis.
The effective half-life for accumulation of enalaprilat has been reported to average about 11 hours in adults with normal renal function. At steady state, the mean effective half-life for accumulation of enalaprilat was 14 hours in pediatric patients. In patients with a creatinine clearance <30 mL/minute, the effective half-life for accumulation of enalaprilat following multiple doses of enalapril maleate is prolonged.
USES: This medication is used to treat high blood pressure. Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. This product contains 2 medications, enalapril and hydrochlorothiazide.
Enalapril belongs to a class of drugs known as ACE inhibitors. It works by relaxing blood vessels so blood can flow more easily. Hydrochlorothiazide is a "water pill" (diuretic) that causes you to make more urine.
This helps your body get rid of extra water and salt.
Generic name: enalapril maleate/hydrochlorothiazide
Pronunciation: (e-NAL-a-pril/HYE-droe-KLOR-oh-THYE-a-zide)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Vaseretic
Indications
The following indications are listed for Vaseretic:
- Hypertension
Also known as: Elevated Blood Pressure, Essential Hypertension, Hyperpiesia, Hyperpiesis, Hypertensive Disorder, Systemic Arterial Hypertension.
Dosing
Dosage of hydrochlorothiazide should be individualized according to the patient's requirements and response. The lowest dosage necessary to produce the desired clinical effect should be used. If hydrochlorothiazide is added to the regimen of a patient stabilized on a potent hypotensive agent, dosage of the hypotensive agent should initially be reduced to avoid the possibility of severe hypotension.
Dosage of enalapril maleate (oral tablets or solution) is expressed in terms of the salt. Dosage of enalaprilat (IV injection) is expressed in terms of enalaprilat.
Dosage of enalapril maleate and enalaprilat must be adjusted according to the patient's tolerance and response.
Since enalapril maleate is a prodrug of enalaprilat and is well absorbed following oral administration, dosage of the two drugs is not identical and clinicians must give careful attention to the dosage when converting from oral to IV therapy or vice versa.
Because of the risk of inducing hypotension, initiation of enalapril maleate or enalaprilat therapy requires consideration of recent antihypertensive therapy, the extent of blood pressure elevation, sodium intake, fluid status, and other clinical circumstances. If therapy is initiated in patients already receiving a diuretic, symptomatic hypotension may occur following the initial dose of the angiotensin-converting enzyme (ACE) inhibitor. The possibility of hypotension may be minimized by discontinuing the diuretic, reducing the diuretic dosage, or cautiously increasing salt intake prior to initiation of oral enalapril maleate or IV enalaprilat therapy.
Hydrochlorothiazide is administered orally.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
When enalapril is used in fixed combination with hydrochlorothiazide, consider the drug interactions associated with hydrochlorothiazide in addition to those associated with enalapril. Consult the full prescribing information for the fixed-combination preparation for specific information.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*History of angioedema related to angiotensin-converting enzyme (ACE) inhibitor therapy and those with hereditary or idiopathic angioedema.
*Known hypersensitivity to enalapril, enalaprilat, or any ingredient in the formulation.
*Concomitant aliskiren therapy in patients with diabetes mellitus.
*Concomitant use (within 36 hours) of a neprilysin inhibitor (e.g., sacubitril).
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effect reported in >=3% of patients receiving enalapril for hypertension was fatigue. In patients receiving enalapril for heart failure, the most common adverse effects reported in >6% of patients were hypotension and dizziness. The most common adverse effect reported in 3.4% of patients receiving enalaprilat was hypotension.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Antihypertensive effects of enalapril maleate have been established in hypertensive pediatric patients 1 month to 16 years of age. Enalapril maleate is not recommended for neonates or for pediatric patients with a glomerular filtration rate of <30 mL/minute per 1.73 m2; no data are available. The adverse effect profile of enalapril maleate in pediatric patients is similar to that in adults. Safety and efficacy of enalaprilat injection in pediatric patients have not been established.
Infants exposed in utero to ACE inhibitors should be observed closely for hypotension, oliguria, and hyperkalemia. If oliguria occurs, supportive measures (e.g., administration of fluids and pressor agents) to correct hypotension and renal perfusion should be considered. Exchange transfusion or dialysis may be required to reverse hypotension and/or substitute for impaired renal function. Enalapril, which crosses the placenta, has been removed from neonatal circulation by peritoneal dialysis with some clinical benefit. The manufacturer states that the drug theoretically may be removed by exchange transfusion; however, this latter procedure has not been used to date.
Drugs that act on the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce fetal renal function and increase fetal and neonatal morbidity and mortality when used in pregnancy during the second and third trimesters. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death. Most epidemiologic data evaluating antihypertensive use in the first trimester and the development of fetal abnormalities have not differentiated a risk between medications affecting the renin-angiotensin system and other antihypertensive agents.
Appropriate management of maternal hypertension during pregnancy is necessary to optimize outcomes for the mother and fetus. Discontinue enalapril as soon as possible when pregnancy is detected. In the rare situation that use of enalapril is deemed necessary, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intraamniotic environment. Fetal testing may be appropriate, based on the week of pregnancy; however, oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, discontinue enalapril unless it is considered lifesaving for the mother. Closely observe infants with histories of in utero exposure to enalapril for hypotension, oliguria, and hyperkalemia.
Enalapril and enalaprilat are excreted into human milk.
Because exposure may cause serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or enalapril, taking into account the importance of the drug to the woman.
The manufacturer provides no specific dosage recommendations in geriatric patients.
Enalapril is substantially eliminated by the kidneys; because geriatric patients have a greater likelihood of decreased renal function and therefore an increased risk of toxicity, renal function should be monitored and dosage should be selected carefully.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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