(RA mi pril)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Altace: 1.25 mg
Altace: 2.5 mg [contains fd&c red #40, fd&c yellow #10 (quinoline yellow)]
Altace: 5 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]
Altace: 10 mg [contains brilliant blue fcf (fd&c blue #1)]
Generic: 1.25 mg, 2.5 mg, 5 mg, 10 mg
Brand Names: U.S.
- Angiotensin-Converting Enzyme (ACE) Inhibitor
Ramipril is an ACE inhibitor which prevents the formation of angiotensin II from angiotensin I and exhibits pharmacologic effects that are similar to captopril. Ramipril must undergo enzymatic saponification by esterases in the liver to its biologically active metabolite, ramiprilat. The pharmacodynamic effects of ramipril result from the high-affinity, competitive, reversible binding of ramiprilat to angiotensin-converting enzyme, thus preventing the formation of the potent vasoconstrictor angiotensin II. This isomerized enzyme-inhibitor complex has a slow rate of dissociation, which results in high potency and a long duration of action; a CNS mechanism may also be involved in the hypotensive effect as angiotensin II increases adrenergic outflow from CNS; vasoactive kallikreins may be decreased in conversion to active hormones by ACE inhibitors, thus reducing blood pressure
Well absorbed (50% to 60%)
Plasma levels decline in a triphasic fashion; rapid decline is a distribution phase to peripheral compartment, plasma protein and tissue ACE (half-life: 2-4 hours); second phase is an apparent elimination phase representing the clearance of free ramiprilat (half-life: 9-18 hours); and final phase is the terminal elimination phase representing the equilibrium phase between tissue binding and dissociation
Hepatic to the active form, ramiprilat
Urine (60%) and feces (40%) as parent drug and metabolites
Onset of Action
Time to Peak
Serum: Ramipril: ~1 hour; Ramiprilat: 2-4 hours
Duration of Action
Ramiprilat: Effective: 13-17 hours; Terminal: >50 hours
Ramipril: 73%; Ramiprilat: 56%
Special Populations: Renal Function Impairment
In patients with CrCl <40 mL/minute, peak levels of metabolite approximately doubled. AUC was 3 to 4 times larger. Urinary excretion of metabolite is reduced. Higher peak and trough ramiprilat levels.
Special Populations: Hepatic Function Impairment
Slowed metabolism of ramiprilat. Ramipril plasma levels increase about 3-fold.
Use: Labeled Indications
Heart failure post-myocardial infarction: Treatment of heart failure (HF) after myocardial infarction (MI).
Hypertension: Management of hypertension (monotherapy or in combination with thiazide diuretics).
Reduction in risk of MI, stroke, and death from cardiovascular causes: To reduce the risk of MI, stroke, and death in patients ≥55 years at high risk of developing major cardiovascular events.
Heart failure: The 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) heart failure guidelines recommend the use of ACE inhibitors, along with other guideline-directed medical therapies, to prevent HF in patients with a reduced ejection fraction who have a history of MI (stage B HF), to prevent HF in any patient with a reduced ejection fraction (stage B HF), or to treat those with HF and reduced ejection fraction (stage C HFrEF) (Yancy 2013)
Hypertension: The 2014 guideline for the management of high blood pressure in adults (Eighth Joint National Committee [JNC 8]) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients:
• Patients ≥60 years of age with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥ 90 mm Hg.
• Patients <60 years of age with SBP ≥140 mm Hg or DBP is ≥90 mm Hg.
• Patients ≥18 years of age with diabetes and SBP ≥140 mm Hg or DBP ≥90 mm Hg.
• Patients ≥18 years of age with chronic kidney disease (CKD) and SBP ≥140 mm Hg or DBP ≥90 mm Hg.
Coronary artery disease (CAD) and hypertension: The American Heart Association, American College of Cardiology and American Society of Hypertension (AHA/ACC/ASH) 2015 scientific statement for the treatment of hypertension in patients with CAD recommends the use of an ACE inhibitor (or an ARB) as part of a regimen in patients with hypertension and chronic stable angina if there is prior MI, LV systolic dysfunction, diabetes mellitus, or CKD. A BP target of <140/90 mm Hg is reasonable for the secondary prevention of cardiovascular events. A lower target BP (<130/80 mm Hg) may be appropriate in some individuals with CAD, previous MI, stroke or transient ischemic attack, or CAD risk equivalents (AHA/ACC/ASH [Rosendorff 2015]).
Diabetes and hypertension: The American Diabetes Association (ADA) guidelines recommend an ACE inhibitor (or an ARB) for patients with HTN and diabetes with albuminuria (urinary albumin-to-creatinine ratio [UACR] ≥30 mg/g). For patients with hypertension and diabetes without albuminuria, any of the 4 classes of blood pressure medications (eg, ACE inhibitors, ARBs, thiazide-like diuretics, or dihydropyridine calcium channel blockers) may be used and have shown beneficial cardiovascular outcomes (ADA 2017a).
STEMI: The 2013 ACCF/AHA guidelines for the management of patients with ST-elevation myocardial infarction (STEMI) state that an ACE inhibitor should be initiated within the first 24 hours after STEMI in patients with anterior MI, heart failure, or left ventricular ejection fraction (LVEF) ≤0.4. It is also reasonable to initiate an ACE inhibitor in all patients with STEMI (O'Gara 2013).
Off Label Uses
Heart failure with reduced ejection fraction
Based on the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Guideline for the Management of Heart Failure, ACE inhibitors, including ramipril, are effective and recommended in reducing morbidity and mortality in heart failure patients with reduced ejection fraction and current or prior symptoms even if they do not have a history of myocardial infarction.
Improve kidney outcomes in hypertensive patients with chronic kidney disease (CKD) (diabetic and nondiabetic population)
Based on the Eighth Joint National Committee (JNC 8) guidelines for the management of high blood pressure in adults, an ACE inhibitor (eg, ramipril) or an ARB is effective and recommended to improve kidney outcomes in adult patients with CKD and hypertension. This recommendation applies to hypertensive CKD patients, with and without proteinuria, and regardless of race and diabetes status.
Based on the American Diabetes Association Standards of Medical Care in Diabetes, in CKD patients with diabetes and hypertension, an ACE inhibitor (eg, ramipril) or an ARB is effective and strongly recommended in patients with an eGFR <60 mL/min/1.73 m2 and/or a UACR ≥300 mg/g for the prevention of CKD progression. In patients with modestly elevated UACR (30 to 299 mg/g), ACE inhibitors or ARBs are also recommended to reduce the progression to more advanced albuminuria.
Non–ST-elevation acute coronary syndrome
Based on the American Heart Association/American College of Cardiology (AHA/ACC) guidelines for the management of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS), an ACE inhibitor (eg, ramipril) should be initiated and continued indefinitely after NSTE-ACS in patients with an LVEF ≤0.4 and in those with hypertension, diabetes mellitus, or stable CKD unless contraindicated. Use of an ACE inhibitor may also be useful in all other patients with cardiac or other vascular disease. In patients with stress (Takotsubo) cardiomyopathy, the use of ACE inhibitors (in combination with beta blockers, aspirin and diuretics) is recommended.
Hypersensitivity to ramipril, other ACE inhibitors, or any component of the formulation; hereditary/idiopathic angioedema or history of angioedema related to previous treatment with an ACE inhibitor; concomitant use with aliskiren in patients with diabetes mellitus; concomitant use or within 36 hours of switching to or from a neprilysin inhibitor (eg, sacubitril).
Note: Consider discontinuation or dose reduction of concomitant diuretic when initiating ramipril. If diuretic cannot be discontinued or dose reduced, consider reduced initial ramipril dose. Monitor blood pressure closely until stabilized.
Heart failure post-myocardial infarction: Oral: Initial: 2.5 mg twice daily; may reduce dose to 1.25 mg twice daily for hypotension. Continue initial dose for one week then titrate upward every 3 weeks as tolerated to target dose of 5 mg twice daily.
Hypertension: Oral: Initial: 2.5 mg once daily in patients not receiving a diuretic; adjust dose according to blood pressure response after 2 to 4 weeks. Usual maintenance dosage (per the manufacturer): 2.5 to 20 mg daily in 1 or 2 divided doses (consider twice daily administration for patients unable to maintain adequate blood pressure control with once daily administration). Usual dosage range (ASH/ISH [Weber 2014]): 5 to 10 mg daily.
Reduction in risk of MI, stroke, and death from cardiovascular causes: Oral: Initial: 2.5 mg once daily for 1 week, then 5 mg once daily for the next 3 weeks, then increase as tolerated to maintenance dose of 10 mg once daily (may administer in divided doses in hypertensive or recently post-MI patients).
Heart failure with reduced ejection fraction (off-label use): Oral: Initial: 1.25 to 2.5 mg once daily; target dose: 10 mg once daily (ACCF/AHA [Yancy 2013])
Dosage adjustment for patients with volume depletion: Initial: 1.25 mg once daily; titrate as tolerated to effect.
Refer to adult dosing; use with caution.
In the management of hypertension, consider lower initial doses and titrate to response (Aronow 2011).
Dosing: Renal Impairment
CrCl >40 mL/minute: No dosage adjustment necessary.
CrCl <40 mL/minute: Administer 25% of normal dose.
Heart failure post-MI: Initial: 1.25 mg once daily, may increase to 1.25 mg twice daily and then up to a maximum of 2.5 mg twice daily as tolerated.
Hypertension: Initial: 1.25 mg once daily, titrated as tolerated to effect; maximum: 5 mg/day.
Renal artery stenosis: Initial: 1.25 mg once daily; titrate as tolerated to effect.
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling, however ramipril is primarily metabolized by hepatic esterases; patients with hepatic impairment could develop markedly elevated plasma levels of ramipril.
Swallow capsule whole; may open the capsule and the mix contents with 120 mL of water, apple juice, or applesauce.
Store at 15°C to 30°C (59°F to 86°F). Ramipril mixed with applesauce, apple juice, or water may be stored at room temperature for up to 24 hours or for up to 48 hours under refrigeration.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Aliskiren: May enhance the hyperkalemic effect of ACE Inhibitors. Aliskiren may enhance the hypotensive effect of ACE Inhibitors. Aliskiren may enhance the nephrotoxic effect of ACE 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. Consider therapy modification
Allopurinol: ACE Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Consider therapy modification
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of ACE Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of ACE Inhibitors. Management: In US labeling, 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 to the combination when possible. Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Aprotinin: May diminish the antihypertensive effect of ACE Inhibitors. Monitor therapy
AzaTHIOprine: ACE Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Canagliflozin: May enhance the hyperkalemic effect of ACE Inhibitors. Canagliflozin may enhance the hypotensive effect of ACE Inhibitors. Monitor therapy
Ciprofloxacin (Systemic): ACE Inhibitors may enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Monitor therapy
Dapoxetine: May enhance the orthostatic hypotensive effect of ACE Inhibitors. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
DPP-IV Inhibitors: May enhance the adverse/toxic effect of ACE Inhibitors. Specifically, the risk of angioedema may be increased. Monitor therapy
Drospirenone: ACE Inhibitors may enhance the hyperkalemic effect of Drospirenone. Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Everolimus: May enhance the adverse/toxic effect of ACE Inhibitors. Specifically, the risk of angioedema may be increased. Monitor therapy
Ferric Gluconate: ACE Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Monitor therapy
Ferric Hydroxide Polymaltose Complex: ACE Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Monitor therapy
Gold Sodium Thiomalate: ACE Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. An increased risk of nitritoid reactions has been appreciated. Monitor therapy
Grass Pollen Allergen Extract (5 Grass Extract): ACE Inhibitors may enhance the adverse/toxic effect 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). Consider therapy modification
Heparin: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Heparin (Low Molecular Weight): May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Icatibant: May diminish the antihypertensive effect of ACE Inhibitors. Monitor therapy
Iron Dextran Complex: ACE Inhibitors may enhance the adverse/toxic effect of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Management: Follow iron dextran recommendations closely regarding both having resuscitation equipment and trained personnel on-hand prior to iron dextran administration and the use of a test dose prior to the first therapeutic dose. Consider therapy modification
Lanthanum: May decrease the serum concentration of ACE Inhibitors. Management: Administer angiotensin-converting enzyme inhibitors at least two hours before or after lanthanum. Consider therapy modification
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Lithium: ACE Inhibitors may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor patient response to lithium closely following addition or discontinuation of concurrent ACE inhibitor treatment. Consider therapy modification
Loop Diuretics: May enhance the hypotensive effect of ACE Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: ACE Inhibitors may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of ACE Inhibitors. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect 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. Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Pregabalin: ACE Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Sacubitril: ACE Inhibitors may enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Avoid combination
Salicylates: May enhance the nephrotoxic effect of ACE Inhibitors. Salicylates may diminish the therapeutic effect of ACE Inhibitors. Monitor therapy
Sirolimus: May enhance the adverse/toxic effect of ACE Inhibitors. Monitor therapy
Sodium Phosphates: ACE Inhibitors may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ACEIs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Consider therapy modification
Telmisartan: May enhance the adverse/toxic effect of Ramipril. Telmisartan may increase the serum concentration of Ramipril. Concentrations of the active metabolite, ramiprilat, may also be increased. Avoid combination
Temsirolimus: May enhance the adverse/toxic effect of ACE Inhibitors. Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of ACE Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Monitor therapy
TiZANidine: May enhance the hypotensive effect of ACE Inhibitors. Monitor therapy
Tolvaptan: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Trimethoprim: May enhance the hyperkalemic effect of ACE Inhibitors. Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Positive Coombs' [direct]; may cause false-positive results in urine acetone determinations using sodium nitroprusside reagent; may lead to false-negative aldosterone/renin ratio (ARR) (Funder 2016)
Frequency ranges include data from hypertension and heart 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.
Cardiovascular: Hypotension (11%)
Respiratory: Increased cough (7% to 12%)
1% to 10%:
Cardiovascular: Angina pectoris (≤3%), orthostatic hypotension (2%), syncope (≤2%)
Central nervous system: Headache (1% to 5%), dizziness (2% to 4%), fatigue (2%), vertigo (≤2%), noncardiac chest pain (1%)
Endocrine & metabolic: Hyperkalemia (1% to 10%)
Gastrointestinal: Nausea (≤2%), vomiting (≤2%)
Renal: Increased blood urea nitrogen (≤3%; transient increases may occur more frequently), increased serum creatinine (1% to 2%; transient increases may occur more frequently), renal insufficiency (1%)
Respiratory: Cough (1% to 10%)
<1% (Limited to important or life-threatening): Agranulocytosis, amnesia, anaphylactoid reaction, angioedema, auditory impairment, bone marrow depression, cardiac arrhythmia, depression, dysphagia, eosinophilia, erythema multiforme, hemolytic anemia, hepatitis, hypersensitivity reaction (fever, skin rash, urticaria), impotence, insomnia, myocardial infarction, neuropathy, onycholysis, pancreatitis, pancytopenia, pemphigoid, pemphigus, proteinuria, seizure, skin photosensitivity, Stevens-Johnson syndrome, symptomatic hypotension, thrombocytopenia, toxic epidermal necrolysis, visual hallucination (Doane 2013)
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). Black patients and patients with idiopathic or hereditary angioedema or previous angioedema associated with ACE inhibitor therapy may be at an increased risk. Risk may also be increased with concomitant use of mTOR inhibitor (eg, everolimus) or neprilysin inhibitor (eg, sacubitril) 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 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 (some fatal); 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.
• Hematologic effects: Another ACE inhibitor, captopril, has been associated with neutropenia with myeloid hypoplasia and agranulocytosis; anemia and thrombocytopenia have also occurred. 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.
• Hyperkalemia: May occur with ACE inhibitors; risk factors include renal impairment, 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 (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.
• 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 glomerular filtration rate (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 (Bakris 2000).
• Aortic stenosis: Use with caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.
• 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.
• Hepatic impairment: Use with caution in patients with hepatic impairment (ramipril is primarily metabolized by hepatic esterases and these patients could develop markedly elevated plasma levels of ramipril).
• Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (ACCF/AHA [Gersh 2011]).
• Renal artery stenosis: Use with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented unilateral or bilateral renal artery stenosis is present or suspected, 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 patients with renal impairment; dosage adjustment may be needed. Avoid rapid dosage escalation which may lead to further renal impairment.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Black patients: Effectiveness of ACE inhibitors is less in black patients than in non-blacks. In addition, ACE inhibitors cause a higher rate of angioedema in black than in non-black patients.
• Pregnancy: [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
• 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).
Blood pressure; BUN, serum creatinine and potassium; if patient has collagen vascular disease and/or renal impairment, periodically monitor CBC with differential.
In heart failure post-myocardial infarction patients, monitor for at least 2 hours after initial dose and for at least an additional hour after blood pressure has stabilized.
2013 ACCF/AHA Heart Failure guideline recommendations: Within 1 to 2 weeks after initiation and periodically thereafter, reassess renal function and serum potassium especially in patients with preexisting hypotension, hyponatremia, diabetes mellitus, azotemia, or those taking potassium supplements (ACCF/AHA [Yancy 2013]).
Pregnancy Risk Factor
[US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. Ramipril crosses the placenta. 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. The use of these drugs in pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. Teratogenic effects may occur following maternal use of an ACE inhibitor during the first trimester, although this finding may be confounded by maternal disease. Because adverse fetal events are well documented with exposure later in pregnancy, ACE inhibitor use in pregnant women is not recommended (Seely 2014; Weber 2014). Infants exposed to an ACE inhibitor in utero should be monitored for hyperkalemia, hypotension, and oliguria. Oligohydramnios may not appear until after irreversible fetal injury has occurred. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function, although data related to the effectiveness in neonates is limited.
Chronic maternal hypertension itself is also associated with adverse events in the fetus/infant and mother. ACE inhibitors are not recommended for the treatment of uncomplicated hypertension in pregnancy (ACOG 2013) and they are specifically contraindicated for the treatment of hypertension and chronic heart failure during pregnancy by some guidelines (Regitz-Zagrosek 2011). In addition, ACE inhibitors should generally be avoided in women of reproductive age (ACOG 2013). If treatment for hypertension or chronic heart failure in pregnancy is needed, other agents should be used (ACOG 2013; Regitz-Zagrosek 2011).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, cough, or loss of strength and energy. Have patient report immediately to prescriber signs of infection, signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling), severe dizziness, passing out, persistent cough, severe abdominal pain, severe nausea, or vomiting (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
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- Drug class: Angiotensin Converting Enzyme Inhibitors
Other brands: Altace