When pregnancy is detected, discontinue ramipril as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
Acute coronary syndrome (off-label use):
Non–ST-elevation acute coronary syndrome:
Note: Initiate in stable patients prior to hospital discharge as a component of an appropriate medical regimen, which may include antiplatelet agent(s), a beta-blocker, and a statin. Continue indefinitely for patients with concurrent diabetes, left ventricular ejection fraction ≤40%, hypertension, or stable chronic kidney disease (ACC/AHA [Amsterdam 2014]). Dosing recommendations are based on general dosing range in manufacturer's labeling.
Oral: Initial: 2.5 mg once daily; titrate slowly based on tolerability and response up to 20 mg/day in 1 or 2 divided doses.
ST-elevation acute coronary syndrome:
Note: In hemodynamically stable patients with large anterior ST-elevation myocardial infarction, consider starting within 24 hours of presentation as a component of an appropriate medical regimen, which may include antiplatelet agent(s), a beta-blocker, and a statin. Continue therapy indefinitely (ACCF/AHA [O'Gara 2013]). Dosing recommendations are based on general dosing range in manufacturer's labeling.
Oral: Initial: 2.5 mg once daily initiated within 24 hours of presentation; titrate slowly based on tolerability and response up to 20 mg/day in 1 or 2 divided doses.
Heart failure with reduced ejection fraction:
Note: If tolerated, an angiotensin II receptor-neprilysin inhibitor is generally preferred over an angiotensin-converting enzyme inhibitor (ACC [Maddox 2021]).
Oral: Initial: 1.25 mg once daily; as tolerated, may increase dose (eg, double) every ≥2 weeks to a target dose of 10 mg once daily (ACC [Maddox 2021]; ACC/AHA [Yancy 2017]; ACCF/AHA [Yancy 2013]). In closely monitored hospitalized patients, may titrate more rapidly as tolerated (Meyer 2021).
Hypertension, chronic:
Note: For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use with another appropriate agent (eg, long-acting dihydropyridine calcium channel blocker or thiazide diuretic) (ACC/AHA [Whelton 2018]).
Oral: Initial: 2.5 mg once daily; evaluate response after ~2 to 4 weeks and titrate dose (eg, increase the daily dose by doubling) as needed, up to 20 mg/day in 1 or 2 divided doses; if additional blood pressure control is needed, consider combination therapy. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (ACC/AHA [Whelton 2018]; Mann 2021).
Proteinuric chronic kidney disease (diabetic or nondiabetic) (off-label use):
Note: Dosing recommendations are based on clinical trials, expert opinion, and general dosing range in manufacturer's labeling.
Oral: Initial: 1.25 to 2.5 mg once daily depending on BP; titrate slowly based on tolerability and response up to 10 mg/day in 1 or 2 divided doses. Target to an appropriate BP goal and a proteinuria goal of <1 g/day (Agodoa 2001; KDIGO 2013; Mann 2021; GISEN 1997).
IgA nephropathy: In addition to an appropriate BP goal, a proteinuria goal of <1 g/day is also generally recommended (KDIGO 2012). Some experts treat to a proteinuria goal of <500 mg/day. If proteinuria goal is not met with monotherapy at the maximum tolerated dose, consider adding other modalities and/or agents (Cattran 2021).
Reduction in risk of myocardial infarction, 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/day in 1 or 2 divided doses.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl >40 mL/minute: No dosage adjustment necessary.
CrCl <40 mL/minute: Administer 25% of normal dose.
Heart failure with reduced ejection fraction: 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, chronic: 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.
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.
Refer to adult dosing; use with caution.
In the management of hypertension, consider lower initial doses and titrate to response (Aronow 2011).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
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
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Altace: 1.25 mg, 2.5 mg
Altace: 5 mg, 10 mg [contains fd&c blue #2 (indigotine)]
Altace: 15 mg [contains brilliant blue fcf (fd&c blue #1)]
Generic: 1.25 mg, 2.5 mg, 5 mg, 10 mg, 15 mg
Tablet, Oral:
Generic: 1.25 mg [DSC], 2.5 mg [DSC], 5 mg [DSC], 10 mg [DSC]
Oral: Swallow capsule whole; may open the capsule and the mix contents with 120 mL of water, apple juice, or applesauce.
Heart failure with reduced ejection fraction: Treatment of heart failure after myocardial infarction.
Hypertension, chronic: Management of hypertension.
Reduction in risk of myocardial infarction, stroke, and death from cardiovascular causes: To reduce the risk of MI, stroke, and death in patients ≥55 years of age at high risk of developing major cardiovascular events.
Non–ST-elevation acute coronary syndrome; Proteinuric chronic kidney disease (diabetic or nondiabetic); ST-elevation acute coronary syndrome
Ramipril may be confused with enalapril, Monopril, Amaryl
Altace may be confused with Altace HCT, alteplase, Amaryl, Amerge, Artane
Use may be associated with increased blood urea nitrogen and increased serum creatinine, resulting in oliguria and acute kidney injury (AKI). Increases in serum creatinine are expected due to pharmacologic mechanism and generally stabilize within 20% to 30% of the baseline; higher increases may indicate high efferent tone (such as with hypovolemia, congestive heart failure, or renal artery stenosis) (Ref).
Mechanism: Related to pharmacologic action; inhibits efferent arteriolar vasoconstriction, lowering glomerular filtration pressure, which can lead to a reduction in the glomerular filtration rate (GFR). Kidney hypoperfusion from systemic hypotension may also occur (Ref).
Onset: Intermediate; increases in serum creatinine generally occur within 2 weeks of initiation and stabilize within 2 to 4 weeks (Ref). However, more immediate increases can occur in patients with other risk factors for AKI (Ref).
Risk factors:
• Patients with low renal blood flow whose GFR is dependent on efferent arteriolar vasoconstriction by angiotensin II including (Ref):
- Low effective circulating volume (sodium or volume depletion)
- Congestive heart failure
- Hypotension or shock
- Renal artery stenosis
• High dose at initiation (Ref)
• Older patients (Ref)
• Preexisting kidney impairment (Ref)
• Concurrent diuretic and/or nonsteroidal anti-inflammatory drug use (Ref)
Angioedema may occur rarely; edema may manifest in the head and neck (potentially compromising the airway) or the intestine (presenting with abdominal pain). Use is contraindicated in patients with idiopathic or hereditary angioedema or previous angioedema associated with any angiotensin-converting enzyme inhibitors or neprilysin inhibitors (Ref).
Mechanism: Related to pharmacologic action (ie, increased bradykinin and substance P, vascular permeability, and vasodilation) (Ref).
Onset: Varied; may occur at any time during treatment. Most cases occur within the first week of therapy but may also occur years after therapy (Ref).
Risk factors:
• Black patients (estimated 4- to 5-fold higher risk); the mechanism for this is not completely understood but may be related to genetic variants (Ref)
• Females (Ref)
• Smoking history (Ref)
• Previous history of angioedema (Ref)
• Age >65 years (Ref)
• Seasonal allergies (Ref)
• Concurrent use of mechanistic target of rapamycin (mTOR) inhibitors (eg, everolimus) (Ref)
• Concurrent use of neprilysin inhibitor (contraindicated)
A dry, hacking, nonproductive cough that is typically associated with tickling or scratching in the throat may occur with angiotensin converting enzyme inhibitors (ACEI) in adult and pediatric patients (Ref). Recurrence is likely with rechallenge (Ref). Resolution of cough typically occurs 1 to 4 weeks after ACEI discontinuation but may persist for up to 3 months (Ref).
Mechanism: Various proposed mechanisms. May be related to pharmacologic action (ie, increased bradykinin and substance P, resulting in accumulation in the lungs and bronchoconstriction) (Ref).
Onset: Varied; within hours to 4 weeks after initiation but can be delayed for up to 6 months (Ref).
Risk factors:
• Females (Ref)
• Possibly certain genetic variants (some of which may be independent of the bradykinin pathway) (Ref).
Hyperkalemia (elevated serum potassium) may occur on therapy with angiotensin converting enzyme inhibitors (ACEI), including ramipril (Ref).
Mechanism: Related to pharmacologic action; inhibits formation of circulating angiotensin II, which leads to efferent arteriole vasodilation and subsequent lowering of glomerular filtration rate, which lowers potassium elimination. Additionally, interferes with the generation and release of aldosterone from the adrenal cortex, leading to an impairment of potassium excretion from the kidney (Ref).
Risk factors:
• Disease states associated with hyperkalemia (congestive heart failure, diabetes mellitus, chronic kidney disease) (Ref)
• Concurrent use of medications which cause hyperkalemia (ACEI, angiotensin receptor blockers, spironolactone, nonsteroidal anti-inflammatory drugs, beta blockers, heparin, tacrolimus, cyclosporine) (Ref)
• Acute kidney injury (elevated BUN and/or serum creatinine) (Ref)
• High dietary intake of potassium or concurrent use of potassium supplements (including potassium-containing salt substitutes) (Ref)
• Baseline elevated potassium level (≥5 mmol/L) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency ranges include data from hypertension and heart failure trials. Higher rates of adverse reactions have generally been noted in patients with heart failure. However, the frequency of adverse effects associated with placebo is also increased in this population.
>10%:
Cardiovascular: Hypotension (11%)
Respiratory: Cough (8% to 12%) (table 1)
Drug (Ramipril) |
Placebo |
Indication |
Number of Patients (Ramipril) |
Number of Patients (Placebo) |
---|---|---|---|---|
8% |
4% |
Cardiac failure post-myocardial infarction |
1,004 |
982 |
12% |
N/A |
Hypertension |
N/A |
N/A |
1% to 10%:
Cardiovascular: Angina pectoris (≤3%), orthostatic hypotension (2%), syncope (≤2%)
Endocrine & metabolic: Hyperkalemia (1%)
Gastrointestinal: Diarrhea (1%), nausea (≤2%), vomiting (≤2%)
Nervous system: Dizziness (2% to 4%), fatigue (≤2%), headache (5%), vertigo (2%)
Neuromuscular & skeletal: Asthenia (≤2%)
Renal: Increased serum creatinine (1%), renal insufficiency (1%)
<1%:
Cardiovascular: Edema, palpitations, symptomatic hypotension
Dermatologic: Diaphoresis, erythema multiforme, onycholysis, pemphigoid, pemphigus, skin photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis
Endocrine & metabolic: Weight gain
Gastrointestinal: Abdominal pain, anorexia, constipation, dysgeusia, dyspepsia, dysphagia, gastroenteritis, pancreatitis, sialorrhea, xerostomia
Genitourinary: Impotence
Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, hemolytic anemia, pancytopenia, purpuric disease, thrombocytopenia
Hepatic: Hepatic failure, hepatitis, jaundice
Hypersensitivity: Angioedema, nonimmune anaphylaxis
Nervous system: Amnesia, anxiety, depression, drowsiness, insomnia, malaise, nervousness, neuralgia, neuropathy, paresthesia, seizure
Neuromuscular & skeletal: Arthralgia, arthritis, myalgia, tremor
Ophthalmic: Visual disturbance
Otic: Hearing loss, tinnitus
Renal: Acute kidney injury, increased blood urea nitrogen
Respiratory: Dyspnea, epistaxis
Postmarketing:
Cardiovascular: Vasculitis
Dermatologic: Psoriasis (Song 2021)
Endocrine & metabolic: Hyponatremia, increased serum glucose, increased uric acid
Genitourinary: Proteinuria
Hematologic & oncologic: Agranulocytosis (Horowitz 2005), eosinophilia, increased erythrocyte sedimentation rate, leukopenia, positive ANA titer
Hepatic: Cholestatic jaundice (Yeung 2003), fulminant hepatic necrosis, increased serum bilirubin, increased serum transaminases
Nervous system: Visual hallucination (Doane 2013)
Respiratory: Eosinophilic pneumonitis
Miscellaneous: Fever
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).
Canadian labeling: Additional contraindications (not in US labeling): Hemodynamically relevant bilateral renal artery stenosis or unilateral in the single kidney; hypotensive or hemodynamically unstable states; concomitant use with aliskiren in patients with moderate to severe renal impairment (GFR <60 mL/minute/1.73 m2), hyperkalemia (>5 mMol/L) or congestive heart failure who are hypotensive; concomitant use with angiotensin II receptor blockers (ARBs) in patients with diabetes end organ damage, moderate to severe renal impairment (GFR <60 mL/minute/1.73 m2), hyperkalemia (>5 mMol/L) or congestive heart failure who are hypotensive; combination with extracorporeal treatments leading to contact of blood with negatively charged surfaces (dialysis or hemofiltration with certain high-flux [eg, polyacrylonitrile] membranes and low-density lipoprotein apheresis with dextran); pregnancy; breastfeeding.
Concerns related to adverse effects:
• Anemia: ACE inhibitors can suppress the production of erythropoietin. This is more likely to occur in the presence of chronic kidney disease.
• Hypersensitivity reactions: Anaphylactic reaction/nonimmune anaphylaxis can occur with ACE inhibitors. Severe nonimmune anaphylaxis 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 nonimmune anaphylaxis 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.
Disease-related concerns:
• Aortic stenosis: Use with caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.
• Ascites: 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 blood pressure and renal function carefully to avoid rapid development of renal failure (AASLD [Runyon 2012]).
• 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 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 2020]).
• 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.
Special populations:
• Race/Ethnicity: In Black patients, the BP-lowering effects of ACE inhibitors may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute (Brewster 2013; Helmer 2017).
• Surgical patients: 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). Based on current research and clinical guidelines in patients undergoing non-cardiac surgery, continuing ACE inhibitors is reasonable in the perioperative period. If ACE inhibitors are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible (ACC/AHA [Fleisher 2014]).
None known.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Aliskiren: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect 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 enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy
Alteplase: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Alteplase. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect 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 diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Angiotensin II: Angiotensin-Converting Enzyme Inhibitors may enhance the therapeutic effect of Angiotensin II. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the 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
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Aprotinin: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Drospirenone-Containing Products: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Eplerenone: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Everolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Risk C: Monitor therapy
Ferric Hydroxide Polymaltose Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Risk C: Monitor therapy
Finerenone: Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Finerenone. Risk C: Monitor therapy
Gelatin (Succinylated): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gelatin (Succinylated). Specifically, the risk of a paradoxical hypotensive reaction may be increased. Risk C: Monitor therapy
Gold Sodium Thiomalate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. This combination may increase the risk of developing a nitritoid reaction. Risk C: Monitor therapy
Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme 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). Risk X: Avoid combination
Heparin: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Icatibant: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Iron Dextran Complex: Angiotensin-Converting Enzyme 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. Risk D: Consider therapy modification
Lanthanum: May decrease the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: Administer angiotensin-converting enzyme inhibitors at least two hours before or after lanthanum. Risk D: Consider therapy modification
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lithium: Angiotensin-Converting Enzyme Inhibitors may increase the 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 enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: Angiotensin-Converting Enzyme 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 Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: 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. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Potassium Salts: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Pregabalin: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Racecadotril: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased with this combination. Risk C: Monitor therapy
Ranolazine: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Sacubitril: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Risk X: Avoid combination
Salicylates: May enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Sirolimus Products: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk for angioedema may be increased. Risk C: Monitor therapy
Sodium Phosphates: Angiotensin-Converting Enzyme 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. Risk D: Consider therapy modification
Tacrolimus (Systemic): Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
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. Risk X: Avoid combination
Temsirolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
TiZANidine: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Tolvaptan: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Trimethoprim: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
Urapidil: May interact via an unknown mechanism with Angiotensin-Converting Enzyme Inhibitors. Management: Avoid concomitant use of urapidil and angiotensin-converting enzyme (ACE) inhibitors. Risk D: Consider therapy modification
Urokinase: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Risk C: Monitor therapy
Avoid use of angiotensin-converting enzyme (ACE) inhibitor therapy in patients who may become pregnant and who are not using effective contraception (ADA 2021).
ACE inhibitors should generally be avoided for the treatment of hypertension in patients planning to become pregnant; use should only be considered for cases of hypertension refractory to other medications (ACOG 203 2019).
Ramipril crosses the placenta.
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 203 2019; ESC [Regitz-Zagrosek 2018]); however, outcomes observed may also be influenced by maternal disease (ACC/AHA [Whelton 2018]).
[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. 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. 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 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 duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 203 2019).
When treatment of hypertension in pregnancy is indicated, ACE inhibitors should generally be avoided due to their adverse fetal events; use in pregnant women should only be considered for cases of hypertension refractory to other medications (ACOG 203 2019). ACE inhibitors are not recommended for the treatment heart failure in pregnancy (Regitz-Zagrosek [ESC 2018]).
Ramipril and its metabolites were not detected in breast milk following a single oral dose of 10 mg. It is not known if multiple doses will produce detectable levels. Breastfeeding is not recommended by the manufacturer.
BP; BUN, serum creatinine and potassium (especially in patients on concomitant potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts); if patient has collagen vascular disease and/or renal impairment, periodically monitor CBC with differential. If angioedema is suspected, assess risk of airway obstruction (eg, involvement of tongue, glottis, larynx, and/or history of airway surgery).
In heart failure post-myocardial infarction patients, monitor for at least 2 hours after initial dose and for at least an additional hour after BP has stabilized.
Heart failure: 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]).
BP goals: May vary depending on clinical condition, different clinical practice guidelines, and expert opinion. Refer to clinical practice guidelines for specific treatment goals.
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
Onset of action: 1-2 hours
Duration: 24 hours
Absorption: Well absorbed (50% to 60%)
Distribution: 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
Protein binding: Ramipril: 73%; Ramiprilat: 56%
Metabolism: Hepatic to the active form, ramiprilat
Bioavailability: Ramipril: 28%; Ramiprilat: 44%
Half-life elimination: Ramiprilat: Effective: 13-17 hours; Terminal: >50 hours
Time to peak, serum: Ramipril: ~1 hour; Ramiprilat: 2-4 hours
Excretion: Urine (60%) and feces (40%) as parent drug and metabolites
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.
Hepatic function impairment: Slowed metabolism of ramiprilat. Ramipril plasma levels increase about 3-fold.
Capsules (Altace Oral)
1.25 mg (per each): $6.34
2.5 mg (per each): $7.48
5 mg (per each): $7.85
10 mg (per each): $9.18
Capsules (Ramipril Oral)
1.25 mg (per each): $1.18 - $1.53
2.5 mg (per each): $1.32 - $1.81
5 mg (per each): $1.41 - $1.89
10 mg (per each): $1.62 - $2.22
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