RAMIPRIL Drug Interactions: What You Need to Know

INTERACTIONS Diuretics: Possibility of excessive hypotension ( 7.1 ). Lithium: Use with caution (7.4). Gold: Nitritoid reactions have been reported (7.5). NSAIDS use may lead to increased risk of renal impairment and loss of antihypertensive effect (7.6). mTOR inhibitor or neprilysin inhibitor use may increase angioedema risk (7.7).

7.1 Diuretics Patients on diuretics, especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with ramipril. The possibility of hypotensive effects with ramipril can be minimized by either decreasing or discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with ramipril. If this is not possible, reduce the starting dose [ see Dosage and Administration ( 2 ) ].

7.2 Agents Increasing Serum Potassium Coadministration of ramipril with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.

7.3 Other Agents Affecting RAS In general, avoid combined use of RAS inhibitors. <span class="opacity-50 text-xs">[see Warnings and Precautions (5.7) ]</span> . Do not co-administer aliskiren with Ramipril in patients with diabetes <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .

7.4 Lithium Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium; therefore, frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be increased.

7.5 Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including ramipril.

7.6 Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including ramipril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving ramipril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including ramipril, may be attenuated by NSAIDs. 7.7 mTOR Inhibitors or Other Drugs Known to Cause Angioedema Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema. <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) ]</span>

7.1 Diuretics Patients on diuretics, especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with ramipril. The possibility of hypotensive effects with ramipril can be minimized by either decreasing or discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with ramipril. If this is not possible, reduce the starting dose [ see Dosage and Administration ( 2 ) ].

7.2 Agents Increasing Serum Potassium Coadministration of ramipril with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.

7.3 Other Agents Affecting RAS In general, avoid combined use of RAS inhibitors. <span class="opacity-50 text-xs">[see Warnings and Precautions (5.7) ]</span> . Do not co-administer aliskiren with Ramipril in patients with diabetes <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .

7.4 Lithium Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium; therefore, frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be increased.

7.5 Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including ramipril.

7.6 Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including ramipril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving ramipril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including ramipril, may be attenuated by NSAIDs.

7.7 mTOR Inhibitors or Other Drugs Known to Cause Angioedema Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema. [see Warnings and Precautions (5.1) ]

Ramipril capsules are contraindicated in patients who are hypersensitive to this product or any other ACE inhibitor (e.g., a patient who has experienced angioedema during therapy with any other ACE inhibitor). Ramipril capsules are contraindicated in combination with neprilysin inhibitor (e.g., sacubitril). Do not administer ramipril capsules within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor . Do not co-administer ramipril capsules with aliskiren: Ramipril capsules are contraindicated in patients who are hypersensitive to this product or any other ACE inhibitor (e.g., a patient who has experienced angioedema during therapy with any other ACE inhibitor). Ramipril capsules are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer ramipril capsules within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor [see Warnings and Precautions (5.1) ] . Do not co-administer ramipril capsules with aliskiren: in patients with diabetes Angioedema related to previous treatment with an ACE inhibitor, or a history of hereditary or idiopathic angioedema (4) . Ramipril capsules are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer ramipril capsules within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor ( 4 ). Do not co-administer aliskiren with ramipril capsules in patients with diabetes (4) .

AND PRECAUTIONS Angioedema, increased risk in patients with a prior history ( 5.1 ) Hypotension and hyperkalemia ( 5.5 , 5.8 ) Renal impairment: monitor renal function during therapy ( 5.3 ) Avoid concomitant use of an ACE inhibitor and angiotensin blocker ( 5.7 ) Rare cholestatic jaundice and hepatic failure ( 5.2 ) Rare neutropenia and agranulocytosis ( 5.4 )

5.1 Anaphylactoid and Possibly Related Reactions Presumably because drugs that act directly on the renin-angiotensin-aldosterone system (e.g., ACE inhibitors) affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving these drugs (including ramipril) may be subject to a variety of adverse reactions, some of them serious.

Angioedema

Head and Neck Angioedema Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor. Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, discontinue treatment with ramipril and institute appropriate therapy immediately. Where there is involvement of the tongue, glottis, or larynx likely to cause airway obstruction, administer appropriate therapy (e.g., subcutaneous epinephrine solution 1:1000 [0.3 mL to 0.5 mL]) promptly [see Adverse Reactions ( 6 )]. In considering the use of ramipril, note that in controlled clinical trials ACE inhibitors cause a higher rate of angioedema in Black patients than in non-Black patients. In a large U.S. post-marketing study, angioedema (defined as reports of angio, face, larynx, tongue, or throat edema) was reported in 3/1523 (0.20%) Black patients and in 8/8680 (0.09%) non-Black patients. These rates were not different statistically. Patients taking concomitant mammalian target of rapamycin (mTOR) inhibitor (e.g. temsirolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema [see Drug Interactions (7.7) ].

Intestinal Angioedema

Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Include intestinal angioedema in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Anaphylactoid Reactions During Desensitization

Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.

Anaphylactoid Reactions During Membrane Exposure

Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

5.2 Hepatic Failure and Impaired Liver Function Rarely, ACE inhibitors, including ramipril, have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death. The mechanism of this syndrome is not understood. Discontinue ramipril if patient develops jaundice or marked elevations of hepatic enzymes. As ramipril is primarily metabolized by hepatic esterases to its active moiety, ramiprilat, patients with impaired liver function could develop markedly elevated plasma levels of ramipril. No formal pharmacokinetic studies have been carried out in hypertensive patients with impaired liver function.

5.3 Renal Impairment As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors, including ramipril, may be associated with oliguria or progressive azotemia and rarely with acute renal failure or death. In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur. Experience with another ACE inhibitor suggests that these increases would be reversible upon discontinuation of ramipril and/or diuretic therapy. In such patients, monitor renal function during the first few weeks of therapy. Some hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when ramipril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction of ramipril and/or discontinuation of the diuretic may be required.

5.4 Neutropenia and Agranulocytosis In rare instances, treatment with ACE inhibitors may be associated with mild reductions in red blood cell count and hemoglobin content, blood cell or platelet counts. In isolated cases, agranulocytosis, pancytopenia, and bone marrow depression may occur. Hematological reactions to ACE inhibitors are more likely to occur in patients with collagen-vascular disease (e.g., systemic lupus erythematosus, scleroderma) and renal impairment. Consider monitoring white blood cell counts in patients with collagen-vascular disease, especially if the disease is associated with impaired renal function.

5.5 Hypotension General Considerations Ramipril can cause symptomatic hypotension, after either the initial dose or a later dose when the dosage has been increased. Like other ACE inhibitors, ramipril, has been only rarely associated with hypotension in uncomplicated hypertensive patients. Symptomatic hypotension is most likely to occur in patients who have been volume- and/or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Correct volume- and salt-depletion before initiating therapy with ramipril. If excessive hypotension occurs, place the patient in a supine position and, if necessary, treat with intravenous infusion of physiological saline. Ramipril treatment usually can be continued following restoration of blood pressure and volume.

Heart Failure

Post-Myocardial Infarction In patients with heart failure post-myocardial infarction who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of ramipril. If the initial dose of 2.5 mg ramipril cannot be tolerated, use an initial dose of 1.25 mg ramipril to avoid excessive hypotension. Consider reducing the dose of concomitant diuretic to decrease the incidence of hypotension.

Congestive Heart

Failure In patients with congestive heart failure, with or without associated renal insufficiency, ACE inhibitor therapy may cause excessive hypotension, which may be associated with oliguria or azotemia and rarely, with acute renal failure and death. In such patients, initiate ramipril therapy under close medical supervision and follow patients closely for the first 2 weeks of treatment and whenever the dose of ramipril or diuretic is increased. Surgery and Anesthesia In patients undergoing surgery or during anesthesia with agents that produce hypotension, ramipril may block angiotensin II formation that would otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion.

5.6 Fetal Toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue ramipril as soon as possible [ see Use in Specific Populations ( 8.1 ) ].

5.7 Dual Blockade of the Renin-Angiotensin System Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on ramipril and other agents that affect the RAS.

Telmisartan

The ONTARGET trial enrolled 25,620 patients >55 years old with atherosclerotic disease or diabetes with end-organ damage, randomized them to telmisartan only, ramipril only, or the combination, and followed them for a median of 56 months. Patients receiving the combination of telmisartan and ramipril did not obtain any benefit in the composite endpoint of cardiovascular death, MI, stroke and heart failure hospitalization compared to monotherapy, but experienced an increased incidence of clinically important renal dysfunction (death, doubling of serum creatinine, or dialysis) compared with groups receiving telmisartan alone or ramipril alone. Concomitant use of telmisartan and ramipril is not recommended. Aliskiren Do not co-administer aliskiren with ramipril in patients with diabetes. Avoid concomitant use of aliskiren with ramipril in patients with renal impairment (GFR <60 mL/min/1.73 m 2 ).

5.8 Hyperkalemia In clinical trials with ramipril, hyperkalemia (serum potassium &gt;5.7 mEq/L) occurred in approximately 1% of hypertensive patients receiving ramipril. In most cases, these were isolated values, which resolved despite continued therapy. None of these patients were discontinued from the trials because of hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of other drugs that raise serum potassium levels. Monitor serum potassium in such patients <span class="opacity-50 text-xs">[see Drug Interactions (7.2) ]</span> .

5.9 Cough Presumably caused by inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. Consider the possibility of angiotensin converting enzyme inhibitor induced-cough in the differential diagnosis of cough.

5.1 Anaphylactoid and Possibly Related Reactions Presumably because drugs that act directly on the renin-angiotensin-aldosterone system (e.g., ACE inhibitors) affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving these drugs (including ramipril) may be subject to a variety of adverse reactions, some of them serious.

Angioedema

Head and Neck Angioedema Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor. Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, discontinue treatment with ramipril and institute appropriate therapy immediately. Where there is involvement of the tongue, glottis, or larynx likely to cause airway obstruction, administer appropriate therapy (e.g., subcutaneous epinephrine solution 1:1000 [0.3 mL to 0.5 mL]) promptly [see Adverse Reactions ( 6 )]. In considering the use of ramipril, note that in controlled clinical trials ACE inhibitors cause a higher rate of angioedema in Black patients than in non-Black patients. In a large U.S. post-marketing study, angioedema (defined as reports of angio, face, larynx, tongue, or throat edema) was reported in 3/1523 (0.20%) Black patients and in 8/8680 (0.09%) non-Black patients. These rates were not different statistically. Patients taking concomitant mammalian target of rapamycin (mTOR) inhibitor (e.g. temsirolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema [see Drug Interactions (7.7) ].

Intestinal Angioedema

Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Include intestinal angioedema in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Anaphylactoid Reactions During Desensitization

Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.

Anaphylactoid Reactions During Membrane Exposure

Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.

5.2 Hepatic Failure and Impaired Liver Function Rarely, ACE inhibitors, including ramipril, have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death. The mechanism of this syndrome is not understood. Discontinue ramipril if patient develops jaundice or marked elevations of hepatic enzymes. As ramipril is primarily metabolized by hepatic esterases to its active moiety, ramiprilat, patients with impaired liver function could develop markedly elevated plasma levels of ramipril. No formal pharmacokinetic studies have been carried out in hypertensive patients with impaired liver function.

5.3 Renal Impairment As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors, including ramipril, may be associated with oliguria or progressive azotemia and rarely with acute renal failure or death. In hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine may occur. Experience with another ACE inhibitor suggests that these increases would be reversible upon discontinuation of ramipril and/or diuretic therapy. In such patients, monitor renal function during the first few weeks of therapy. Some hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when ramipril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction of ramipril and/or discontinuation of the diuretic may be required.

5.4 Neutropenia and Agranulocytosis In rare instances, treatment with ACE inhibitors may be associated with mild reductions in red blood cell count and hemoglobin content, blood cell or platelet counts. In isolated cases, agranulocytosis, pancytopenia, and bone marrow depression may occur. Hematological reactions to ACE inhibitors are more likely to occur in patients with collagen-vascular disease (e.g., systemic lupus erythematosus, scleroderma) and renal impairment. Consider monitoring white blood cell counts in patients with collagen-vascular disease, especially if the disease is associated with impaired renal function.

5.5 Hypotension General Considerations Ramipril can cause symptomatic hypotension, after either the initial dose or a later dose when the dosage has been increased. Like other ACE inhibitors, ramipril, has been only rarely associated with hypotension in uncomplicated hypertensive patients. Symptomatic hypotension is most likely to occur in patients who have been volume- and/or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Correct volume- and salt-depletion before initiating therapy with ramipril. If excessive hypotension occurs, place the patient in a supine position and, if necessary, treat with intravenous infusion of physiological saline. Ramipril treatment usually can be continued following restoration of blood pressure and volume.

Heart Failure

Post-Myocardial Infarction In patients with heart failure post-myocardial infarction who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of ramipril. If the initial dose of 2.5 mg ramipril cannot be tolerated, use an initial dose of 1.25 mg ramipril to avoid excessive hypotension. Consider reducing the dose of concomitant diuretic to decrease the incidence of hypotension.

Congestive Heart

Failure In patients with congestive heart failure, with or without associated renal insufficiency, ACE inhibitor therapy may cause excessive hypotension, which may be associated with oliguria or azotemia and rarely, with acute renal failure and death. In such patients, initiate ramipril therapy under close medical supervision and follow patients closely for the first 2 weeks of treatment and whenever the dose of ramipril or diuretic is increased. Surgery and Anesthesia In patients undergoing surgery or during anesthesia with agents that produce hypotension, ramipril may block angiotensin II formation that would otherwise occur secondary to compensatory renin release. Hypotension that occurs as a result of this mechanism can be corrected by volume expansion.

5.6 Fetal Toxicity Pregnancy Category D Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue ramipril as soon as possible [ see Use in Specific Populations ( 8.1 ) ].

5.7 Dual Blockade of the Renin-Angiotensin System Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on ramipril and other agents that affect the RAS.

Telmisartan

The ONTARGET trial enrolled 25,620 patients >55 years old with atherosclerotic disease or diabetes with end-organ damage, randomized them to telmisartan only, ramipril only, or the combination, and followed them for a median of 56 months. Patients receiving the combination of telmisartan and ramipril did not obtain any benefit in the composite endpoint of cardiovascular death, MI, stroke and heart failure hospitalization compared to monotherapy, but experienced an increased incidence of clinically important renal dysfunction (death, doubling of serum creatinine, or dialysis) compared with groups receiving telmisartan alone or ramipril alone. Concomitant use of telmisartan and ramipril is not recommended. Aliskiren Do not co-administer aliskiren with ramipril in patients with diabetes. Avoid concomitant use of aliskiren with ramipril in patients with renal impairment (GFR <60 mL/min/1.73 m 2 ).

5.8 Hyperkalemia In clinical trials with ramipril, hyperkalemia (serum potassium &gt;5.7 mEq/L) occurred in approximately 1% of hypertensive patients receiving ramipril. In most cases, these were isolated values, which resolved despite continued therapy. None of these patients were discontinued from the trials because of hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of other drugs that raise serum potassium levels. Monitor serum potassium in such patients <span class="opacity-50 text-xs">[see Drug Interactions (7.2) ]</span> .

5.9 Cough Presumably caused by inhibition of the degradation of endogenous bradykinin, persistent nonproductive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. Consider the possibility of angiotensin converting enzyme inhibitor induced-cough in the differential diagnosis of cough.