"The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended the marketing of selexipag (Uptravi, Actelion Registration Ltd) for the treatment of adults with pulmonary arterial hypertension (PAH)./"...
EPANED is indicated for the treatment of hypertension, to lower blood pressure in adults and children older than one month.
Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including this drug.
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.
EPANED is effective alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. The blood pressure lowering effects of EPANED and thiazides are approximately additive.
EPANED is indicated for the treatment of symptomatic heart failure, usually in combination with diuretics and digitalis. In these patients, EPANED increases survival and decreases the frequency of hospitalization.
Asymptomatic Left Ventricular Dysfunction
In clinically stable asymptomatic patients with left ventricular dysfunction (ejection fraction ≤ 35 percent), EPANED decreases the rate of development of overt heart failure and decreases the incidence of hospitalization for heart failure.
DOSAGE AND ADMINISTRATION
The recommended initial dose in adults is 5 mg once a day. Titrate upward to maximum of 40 mg daily as needed to help achieve blood pressure goals. The dose may be divided and administered twice daily if the antihypertensive effect diminishes at the end of the dosing interval.
Use with Diuretics
If additional blood pressure reduction is needed, EPANED may be administered with a low dose of diuretic. The recommended initial dose in patients taking diuretics is 2.5 mg daily.
Dosage Adjustment for Renal Impairment
See table below. The dosage may be titrated upward as needed to a maximum of 40 mg daily.
|Renal Status||Creatinine-Clearance mL/min||Initial Dose mg/day|
|Normal or Mild Impairment of Renal Function||> 30 mL/min||5 mg|
|Moderate to Severe Impairment||≤ 30 mL/min||2.5 mg|
|Dialysis Patients*||-||2.5 mg on dialysis days†|
|* =[See WARNINGS AND PRECAUTIONS].
† = Dosage on nondialysis days should be adjusted depending on the blood pressure response.
Children > 1 Month
The usual recommended starting dose is 0.08 mg/kg (up to 5 mg) once daily. Dosage should be adjusted according to blood pressure response. Doses above 0.58 mg/kg (or in excess of 40 mg) have not been studied in pediatric patients [see CLINICAL PHARMACOLOGY].
EPANED is not recommended in neonates and in pediatric patients with glomerular filtration rate < 30 mL/min/1.73 m², as no data are available.
The recommended initial dose is 2.5 mg twice a day titrated up to a maximum of 20 mg twice a day, as tolerated. Doses are usually given in combination with diuretics and digitalis.
In patients with hyponatremia (serum sodium less than 130 mEq/L) or serum creatinine greater than 1.6 mg/dL, the recommended initial dose is 2.5 mg once daily.
Diuretic dose may need to be adjusted to minimize hypovolemia and hypotension. The appearance of hypotension after the initial dose of EPANED does not preclude subsequent careful dose titration with the drug, following effective management of the hypotension.
Asymptomatic Left Ventricular Dysfunction
The recommended initial dose is 2.5 mg twice a day titrated up to a maximum of 10 mg twice a day, as tolerated. Diuretic dose may need to be adjusted [see Hypertension section above].
Preparation Of EPANED (for 150 mL, 1 mg/mL Enalapril Solution)
EPANED Powder for Oral Solution is a kit containing 1 bottle of enalapril powder and 1 bottle of Ora-Sweet SF diluent to be added to the enalapril powder prior to dispensing to the patient.
Firmly tap the EPANED Powder for Oral Solution bottle on a hard surface 5 times. Add approximately one-half (75 mL) of the Ora-Sweet SF diluent to the 150 mL EPANED Powder for Oral Solution bottle. Replace the child-resistant cap. Shake well for 30 seconds. Reopen. Add the remainder of the Ora-Sweet SF diluent to the EPANED Powder for Oral Solution bottle, replace the child-resistant cap and shake well for an additional 30 seconds. Calculate 60 days from the date of reconstitution. Write this date as the discard date on the front of the label. Affix a “Do Not Use After” or a “Discard After” label with the calculated date added to the reconstituted EPANED bottle.
Dosage Forms And Strengths
EPANED Powder for Oral Solution is a kit that contains 150 mg of enalapril maleate in a 150-mL bottle and Ora-Sweet SF diluent. Reconstitution with 150 mL of the provided Ora-Sweet SF diluent results in a 1 mg/mL EPANED oral solution.
Storage And Handling
EPANED is supplied as a kit.
- One bottle containing EPANED Powder (150 mg enalapril maleate) for Oral Solution in an HDPE bottle with child-resistant cap to provide 1 mg/mL final concentration after reconstitution.
- One bottle containing 150 mL of Ora-Sweet SF provided as the diluent for reconstitution.
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].
Do not freeze.
Keep container tightly closed.
Protect from moisture.
Manufactured For: Silvergate Pharmaceuticals, Inc. 6251 Greenwood Plaza Blvd., Suite 101 Greenwood Village, CO 80111. Revised: Sep 2014This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 1/6/2016
Additional Epaned Information
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