What is the dosage and administration of Enalaprilat (Angiotensin-Converting Enzyme (ACE) inhibitor) for treating hypertension and heart failure?

Enalaprilat Dosing and Administration

For hypertension, initiate enalaprilat at 1.25 mg IV every 6 hours (or 0.625 mg every 6 hours if on diuretics), administered over 5 minutes, with doses up to 5 mg every 6 hours well-tolerated but rarely exceeding 20 mg total daily dose. 1

Standard Dosing for Hypertension

Initial Dosing

• Standard patients: 1.25 mg IV every 6 hours, administered as a slow infusion over 5 minutes 1
• Patients on diuretic therapy: Start at 0.625 mg IV over 5 minutes due to increased hypotension risk 1
• Clinical response typically occurs within 15 minutes, though peak effects may take up to 4 hours after the first dose 1

Dose Titration

• If inadequate response after 1 hour, the 0.625 mg dose may be repeated 1
• Additional doses of 1.25 mg can be administered at 6-hour intervals 1
• Doses up to 5 mg every 6 hours have been well-tolerated for up to 36 hours in controlled studies 1
• Total daily doses should rarely exceed 20 mg 1

Renal Impairment Adjustments

Dosing must be reduced in renal dysfunction to prevent drug accumulation and excessive hypotension:

• CrCl >30 mL/min (serum creatinine ≤3 mg/dL): Standard dose of 1.25 mg every 6 hours 1
• CrCl ≤30 mL/min (serum creatinine ≥3 mg/dL): Initial dose 0.625 mg IV 1
  • May repeat 0.625 mg after 1 hour if inadequate response 1
  • Subsequent doses of 1.25 mg at 6-hour intervals as needed 1

High-Risk Patients Requiring Lower Initial Doses

Patients at risk of excessive hypotension require starting doses no greater than 0.625 mg administered over at least 5 minutes (preferably up to 1 hour) under close medical supervision. 1

High-Risk Characteristics:

• Heart failure 1
• Hyponatremia 1
• High-dose diuretic therapy or recent intensive diuresis 1
• Renal dialysis 1
• Severe volume or salt depletion of any etiology 1

Critical caveat: Single doses as low as 0.2 mg have produced excessive hypotension in normotensive patients with these conditions 1

Administration Technique

• Administer as slow IV infusion over at least 5 minutes 1
• May be given undiluted or diluted in up to 50 mL of compatible diluent 1
• Compatible diluents include: 5% dextrose, 0.9% sodium chloride, 0.9% sodium chloride in 5% dextrose, 5% dextrose in lactated Ringer's, or ISOLYTE E 1
• Mixed solutions maintain full activity for 24 hours at room temperature 1

Duration of IV Therapy

• Enalaprilat has been studied for up to 48 hours in hypertension trials, though some patients received it for up to 7 days 1
• Conversion to oral enalapril: 5 mg once daily for most patients, or 2.5 mg once daily for those on 0.625 mg IV every 6 hours or with renal impairment (CrCl ≤30 mL/min) 1

Monitoring Requirements

• Observe patients for at least 2 hours after initial dose and until blood pressure stabilizes for an additional hour 2
• Monitor blood pressure closely, especially during dose adjustments 1
• Check renal function and serum potassium within 1-2 weeks of initiation 3
• Ensure appropriate diuretic dosing before and during ACE inhibitor therapy, as fluid retention blunts therapeutic effects while fluid depletion potentiates adverse effects 3

Heart Failure Context

While the evidence provided focuses primarily on oral enalapril for heart failure (target dose 10-20 mg twice daily orally) 3, enalaprilat IV is not the preferred route for chronic heart failure management 4. The IV formulation is primarily indicated for acute hypertensive situations where oral therapy is not feasible 1.