Version July 2025
When pregnancy is detected, discontinue enalaprilat as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Note: Use lower listed initial dose in patients with hyponatremia, hypovolemia, severe congestive heart failure, or decreased renal function, or in those receiving diuretics.
Hypertension: IV: 1.25 mg/dose, given over 5 minutes every 6 hours; may titrate as needed to a maximum dose of 5 mg/dose every 6 hours. Note: If patients are concomitantly receiving diuretic therapy, begin with 0.625 mg IV over 5 minutes every 6 hours; if the effect is not adequate after 1 hour, repeat the dose and administer 1.25 mg at 6-hour intervals thereafter.
Conversion from IV enalaprilat to oral enalapril therapy: If not concurrently receiving diuretics, initiate enalapril 5 mg once daily; if concurrently receiving diuretics and responding to enalaprilat 0.625 mg IV every 6 hours, initiate with enalapril 2.5 mg once daily; subsequent titration as needed.
Manufacturer's labeling:
CrCl >30 mL/minute: No dosage adjustment necessary
CrCl ≤30 mL/minute: Initiate with 0.625 mg; if after 1 hour clinical response is unsatisfactory, may repeat. May then administer 1.25 mg every 6 hours.
Intermittent hemodialysis (IHD): Moderately dialyzable (20% to 50%): Initial: 0.625 mg IV over a period of 5 to 60 minutes (60-minute infusion duration preferred)
Conversion from IV enalaprilat to oral enalapril therapy:
CrCl >30 mL/minute: May initiate enalapril 5 mg once daily.
CrCl ≤30 mL/minute: May initiate enalapril 2.5 mg once daily.
Alternate recommendations (Ref):
CrCl >50 mL/minute: No dosage adjustment necessary
CrCl 10 to 50 mL/minute: Administer 50% to 100% of usual dose
CrCl <10 mL/minute: Administer 25% to 50% of usual dose
Peritoneal dialysis: Administer 25% to 50% of usual dose; supplemental dose is not necessary, although some removal of drug occurs.
No dosage adjustment necessary for patients with hepatic impairment; enalaprilat does not undergo hepatic metabolism. Use with caution, particularly in patients with ascites due to cirrhosis (Ref).
Refer to adult dosing.
(For additional information see "Enalaprilat (intravenous): Pediatric drug information")
Hypertension: Limited data available, optimal dose not defined: Note: Enalaprilat is not included in the 2017 Clinical Practice Guidelines for Screening and Management of High Blood Pressure in Children and Adolescents (Ref).
Infants, Children, and Adolescents: IV: Usual range: 0.005 to 0.01 mg/kg/dose every 8 to 24 hours; higher doses of 0.06 mg/kg/dose have also been described; maximum dose: 1.25 mg/dose; frequency determined by clinical response; monitor patients carefully and individualize dose based on etiology of hypertension and patient response (Ref). Note: Based on experience in adults, if patients are concomitantly receiving diuretic therapy, begin with a lower initial dose; if the effect is not adequate after 1 hour, repeat the dose and administer subsequent doses at a higher dose.
Infants, Children, and Adolescents: There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; based on pharmacokinetic information in adult patients, CrCl <30 mL/minute is associated with increased peak, trough, and half-life; some experts have suggested the following:
Aronoff 2007:
GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 10 to 50 mL/minute/1.73 m2: Administer 75% of usual dose.
GFR <10 mL/minute/1.73 m2: Administer 50% of usual dose.
Hemodialysis: Administer 50% of usual dose.
Peritoneal dialysis: Administer 50% of usual dose.
Continuous renal replacement therapy: Administer 75% of usual dose.
No dosage adjustment necessary for patients with hepatic impairment; enalaprilat does not undergo hepatic metabolism.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Since enalapril is converted to enalaprilat, adverse reactions associated with enalapril may also occur with enalaprilat (also refer to Enalapril monograph). Frequency ranges include data from hypertension and cardiac failure trials. Higher rates of adverse reactions have generally been noted in patients with cardiac failure. However, the frequency of adverse effects associated with placebo is also increased in this population.
1% to 10%:
Cardiovascular: Hypotension (2% to 5%)
Central nervous system: Headache (3%)
Gastrointestinal: Nausea (1%)
<1%, postmarketing, and/or case reports: Angioedema, constipation, cough, dizziness, fatigue, fever, myocardial infarction, psoriasis (Song 2021), skin rash
Hypersensitivity to enalapril, enalaprilat, or any component of the formulation; angioedema related to previous treatment with an ACE inhibitor; idiopathic or hereditary angioedema; concomitant use with aliskiren in patients with diabetes mellitus.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Angioedema: At any time during treatment (especially following first dose) angioedema may occur rarely with ACE inhibitors; it may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain). African-Americans may be at an increased risk. Risk may also be increased with concomitant use of mTOR inhibitor (eg, everolimus) therapy. Prolonged frequent monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Aggressive early and appropriate management is critical. Use in patients with idiopathic or hereditary angioedema or previous angioedema associated with ACE inhibitor therapy is contraindicated.
• Cholestatic jaundice: A rare toxicity associated with ACE inhibitors includes cholestatic jaundice, which may progress to fulminant hepatic necrosis; discontinue if marked elevation of hepatic transaminases or jaundice occurs.
• Cough: An ACE inhibitor cough is a dry, hacking, nonproductive one that usually occurs within the first few months of treatment and should generally resolve within 1 to 4 weeks after discontinuation of the ACE inhibitor. Other causes of cough should be considered (eg, pulmonary congestion in patients with heart failure) and excluded prior to discontinuation.
• Hyperkalemia: May occur with ACE inhibitors; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely.
• Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors. Severe anaphylactoid reactions may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of anaphylactoid reactions have been reported in patients undergoing sensitization treatment with hymenoptera (bee, wasp) venom while receiving ACE inhibitors.
• Hypotension/syncope: Symptomatic hypotension with or without syncope can occur with ACE inhibitors (usually with the first several doses); effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation; close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use especially in patients with heart failure where a reduction in systolic blood pressure is a desirable observation.
• Neutropenia/agranulocytosis: Another ACE inhibitor, captopril, has been associated with rare cases of agranulocytosis, neutropenia, or leukopenia with myeloid hypoplasia. Patients with renal impairment are at high risk of developing neutropenia. Patients with both renal impairment and collagen vascular disease (eg, systemic lupus erythematosus) are at an even higher risk of developing neutropenia. Periodically monitor CBC with differential in these patients.
• Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function.
Disease-related concerns:
• Aortic stenosis: Use with caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.
• Ascites: Generally, avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor BP and renal function carefully to avoid rapid development of renal failure (AASLD [Runyon 2013]).
• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences posed by falling blood pressure (eg, MI, stroke). Fluid replacement, if needed, may restore blood pressure; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs.
• Collagen vascular disease: Use with caution in patients with collagen vascular disease especially with concomitant renal impairment; may be at increased risk for hematologic toxicity.
• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (AHA/ACC [Ommen 2024]).
• Renal artery stenosis: Use with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks.
• Renal impairment: Use with caution in preexisting renal insufficiency; dosage adjustment may be needed. Avoid rapid dosage escalation which may lead to further renal impairment.
Concurrent drug therapy issues:
• Angiotensin receptor blockers (ARBs) and renin inhibitors: Concomitant use of an ARB or renin inhibitor (eg, aliskiren) is associated with an increased risk of hypotension, hyperkalemia, and renal dysfunction. Concomitant use with aliskiren should be avoided in patients with GFR <60 mL/minute and is contraindicated in patients with diabetes mellitus (regardless of GFR).
Special populations:
• Pregnancy: [US Boxed Warning]: Based on human data, ACEIs can cause injury and death to the developing fetus when used in the second and third trimesters. ACEIs should be discontinued as soon as possible once pregnancy is detected.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.
Other warnings/precautions:
• Surgery: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011).
A large, multicenter, retrospective trial reported on the safety of enalapril/at in neonates and infants who were exposed to enalapril/at within the first 120 days of life; of 662 neonates/infants exposed to enalapril/at, adverse effects were reported in 21% (n=142); the most frequently reported events were: Hyperkalemia (13%), increased serum creatinine (5%), hypotension requiring pressors (4%), and death (0.5%). Patients who were PNA <30 days for first exposure had significantly increased risk of hyperkalemia, elevated serum creatinine, and hypotension. A longer duration of exposure was associated with increased odds of hyperkalemia and death; however, causality with the drug not determined and underlying patient condition likely a key factor (ie, when congenital heart defect/disease excluded from data, the odds were not higher) (Ku 2017); consider alternate therapeutic options for management of neonatal hypertension (Dionne 2017).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 1.25 mg/mL (1 mL, 2 mL)
Yes
Solution (Enalaprilat Intravenous)
1.25 mg/mL (per mL): $6.37
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Vasotec IV: 1.25 mg/mL (2 mL) [contains benzyl alcohol]
Generic: 1.25 mg/mL (2 mL)
IV: Administer IV push undiluted over at least 5 minutes or as an infusion with a diluted solution.
Administer as IV infusion over 5 minutes (undiluted or diluted).
Hypertension: Management of hypertension when oral therapy is not practical
Significant differences exist between oral and IV dosing. Use caution when converting from one route of administration to another.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Aliskiren: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may increase hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Risk D: Consider Therapy Modification
Allopurinol: Angiotensin-Converting Enzyme Inhibitors may increase hypersensitivity effects of Allopurinol. Risk C: Monitor
Alteplase: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Alteplase. Specifically, the risk for angioedema may be increased. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Amphetamines: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Angiotensin II Receptor Blockers: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives when possible. Monitor blood pressure, renal function, and potassium if combined. Risk D: Consider Therapy Modification
Angiotensin II: Angiotensin-Converting Enzyme Inhibitors may increase therapeutic effects of Angiotensin II. Risk C: Monitor
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Aprotinin: May decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may increase myelosuppressive effects of AzaTHIOprine. Risk C: Monitor
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Brigatinib: May decrease antihypertensive effects of Antihypertensive Agents. Brigatinib may increase bradycardic effects of Antihypertensive Agents. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Dapoxetine: May increase orthostatic hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Dexmethylphenidate: May decrease therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Dipeptidyl Peptidase-IV Inhibitors: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor
Drospirenone-Containing Products: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
Everolimus: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor
Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Ferric Gluconate. Risk C: Monitor
Ferric Hydroxide Polymaltose Complex: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Risk C: Monitor
Finerenone: Angiotensin-Converting Enzyme Inhibitors may increase hyperkalemic effects of Finerenone. Risk C: Monitor
Flunarizine: May increase therapeutic effects of Antihypertensive Agents. Risk C: Monitor
Gelatin (Succinylated): Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Gelatin (Succinylated). Specifically, the risk of a paradoxical hypotensive reaction may be increased. Risk C: Monitor
Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors may increase the risk of severe allergic reaction to Grass Pollen Allergen Extract (5 Grass Extract). Risk X: Avoid
Heparin: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Heparins (Low Molecular Weight): May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Herbal Products with Blood Pressure Increasing Effects: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Icatibant: May decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Indoramin: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Iron Dextran Complex: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Risk C: Monitor
Isocarboxazid: May increase antihypertensive effects of Antihypertensive Agents. Risk X: Avoid
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Lithium: Angiotensin-Converting Enzyme Inhibitors may increase serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor for increased concentrations/toxic effects of lithium if an ACE inhibitor is initiated/dose increased, or if switching between ACE inhibitors. Risk D: Consider Therapy Modification
Loop Diuretics: May increase hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Methylphenidate: May decrease antihypertensive effects of Antihypertensive Agents. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Topical): May decrease therapeutic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents: May decrease antihypertensive effects of Angiotensin-Converting Enzyme Inhibitors. Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Risk C: Monitor
Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perazine: May increase hypotensive effects of Antihypertensive Agents. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Angiotensin-Converting Enzyme Inhibitors may increase nephrotoxic effects of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor
Potassium Salts: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Potassium-Sparing Diuretics: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Prazosin: Antihypertensive Agents may increase hypotensive effects of Prazosin. Risk C: Monitor
Pregabalin: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Racecadotril: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased with this combination. Risk C: Monitor
Ranolazine: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Sacubitril: Angiotensin-Converting Enzyme Inhibitors may increase adverse/toxic effects of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Risk X: Avoid
Salicylates: May decrease therapeutic effects of Angiotensin-Converting Enzyme Inhibitors. Salicylates may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Sirolimus Products: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased. Risk C: Monitor
Sodium Phosphates: Angiotensin-Converting Enzyme Inhibitors may increase nephrotoxic effects of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor
Sparsentan: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk X: Avoid
Tacrolimus (Systemic): Angiotensin-Converting Enzyme Inhibitors may increase hyperkalemic effects of Tacrolimus (Systemic). Risk C: Monitor
Temsirolimus: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor
Terazosin: Antihypertensive Agents may increase hypotensive effects of Terazosin. Risk C: Monitor
Thiazide and Thiazide-Like Diuretics: May increase hypotensive effects of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may increase nephrotoxic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Tolvaptan: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor
Trimethoprim: May increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Management: Consider avoiding coadministration if possible. If combined, monitor serum potassium closely, particularly for patients with other risk factors (eg, renal impairment, older age, and other medications that increase potassium. Risk X: Avoid
Urapidil: And Angiotensin-Converting Enzyme Inhibitors may interact via an unclear mechanism. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. Risk D: Consider Therapy Modification
Urokinase: May increase adverse/toxic effects of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor
Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be used in patients trying to conceive. Angiotensin-converting enzyme (ACE) inhibitors are fetotoxic. Transition patients prior to conception to an agent preferred for use during pregnancy unless treatment with an ACE inhibitor is absolutely necessary (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019).
Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Exposure to an angiotensin-converting enzyme (ACE) inhibitor during the first trimester of pregnancy may be associated with an increased risk of fetal malformations (ACOG 2019; ESC [Regitz-Zagrosek 2018]). Following exposure during the second or third trimesters, drugs that act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. Oligohydramnios may not appear until after an irreversible fetal injury has occurred. ACE inhibitor use during pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. Monitor infants exposed to an ACE inhibitor in utero for hyperkalemia, hypotension, and oliguria. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function.
Chronic maternal hypertension is also associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, pre-eclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019).
Discontinue ACE inhibitors as soon as possible once pregnancy is detected. Agents other than ACE inhibitors are recommended for the treatment of chronic hypertension during pregnancy (ACOG 2019; ESC [Cífková 2020]; SOGC [Magee 2022]). Consider the use of ACE inhibitors only for pregnant patients with hypertension refractory to other medications (ACOG 2019). Closely monitor pregnant patients on ACE inhibitors with serial ultrasounds.
Enalapril and enalaprilat are present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother.
Enalaprilat is the active metabolite of enalapril. Refer to the Enalapril monograph for additional information.
Limit salt substitutes or potassium-rich diet.
BP, BUN; serum creatinine; electrolytes (eg, potassium [especially in patients on concomitant potassium-sparing diuretics, potassium supplements and/or potassium containing salts]); if patient has collagen vascular disease and/or kidney impairment, periodically monitor CBC with differential.
Competitive inhibitor of angiotensin-converting enzyme (ACE); prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion
Onset of action: IV: ≤15 minutes
Peak effect: IV: 1-4 hours
Duration: IV: ~6 hours (dose-dependent)
Protein binding: ~50% (Davies, 1984)
Half-life elimination: CHF: Neonates (n=3; PNA: 10-19 days): 11.9 hours (range: 5.9-15.6 hours) (Nakamura, 1994); CHF: Infants and Children ≤6.5 years of age (n=11): 11.1 hours (range: 5.1-20.8 hours) (Nakamura, 1994); Infants 6 weeks to 8 months of age: 6-10 hours (Lloyd, 1989); Adults: ~35 hours (Till, 1984; Ulm, 1982)
Excretion: Urine (>90% as unchanged drug); Feces (small amount)
Altered kidney function: When GFR is ≤30 mL/minute, peak, trough, and time to peak concentrations are increased, half-life is prolonged, and time to steady-state may be delayed.
