VA Class:CV800
Quinapril is a nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor.1, 2, 3
Quinapril hydrochloride is used alone or in combination with other classes of antihypertensive agents (e.g., thiazide diuretics) in the management of hypertension.1, 2, 4, 47, 1200 Quinapril also may be used in conjunction with agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers) in the management of heart failure.1, 2, 12, 18, 524, 800
Because captopril, another angiotensin-converting enzyme (ACE) inhibitor, may cause serious adverse effects (e.g., neutropenia, agranulocytosis), particularly in patients with renal impairment (especially those with collagen vascular disease)1, 47 or in patients receiving immunosuppressive therapy,5, 6 the possibility that similar adverse effects may occur with quinapril should be considered since current evidence is insufficient to rule out such risk.1, 47 (See Cautions: Hematologic Effects, in Captopril 24:32.04.)
Quinapril hydrochloride is used alone or in combination with other classes of antihypertensive agents in the management of hypertension.1, 2, 4, 47, 1200 ACE inhibitors are considered one of several preferred antihypertensive drugs for the initial management of hypertension according to current evidence-based hypertension guidelines; other preferred options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics.501, 502, 503, 504, 1200 While there may be individual differences with respect to recommendations for initial drug selection and use in specific patient populations, current evidence indicates that these antihypertensive drug classes all generally produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.501, 502, 504, 1200, 1213 (See Uses: Hypertension, in Captopril 24:32.04.) ACE inhibitors may be particularly useful in the management of hypertension in patients with certain coexisting conditions such as heart failure, ischemic heart disease, diabetes mellitus, chronic kidney disease (CKD), or cerebrovascular disease or following myocardial infarction.501, 502, 504, 523, 524, 525, 526, 527, 534, 535, 536, 543, 1200, 1214, 1215 (See Uses: Hypertension, in Captopril 24:32.04 and in Enalaprilat/Enalapril 24:32.04.)
In patients with hypertension and compelling indications (e.g., CKD with albuminuria [urine albumin 300 mg/day or greater, or urine albumin:creatinine ratio of 300 mg/g or equivalent in the first morning void]), angiotensin II receptor antagonists are usually considered an alternative for ACE inhibitor-intolerant patients.1218 However, data indicate no difference in efficacy between ACE inhibitors and angiotensin II receptor antagonists with regard to blood pressure lowering and clinical outcomes (i.e., all-cause mortality, cardiovascular mortality, MI, heart failure, stroke, and end-stage renal disease).1200, 1218 Adverse events (e.g., cough, angioedema) leading to drug discontinuance occur more frequently with ACE inhibitor therapy than with angiotensin II receptor antagonist therapy.1218 Because of similar efficacy and a lower frequency of adverse effects, some experts believe that angiotensin II receptor antagonists should be used instead of an ACE inhibitor for the treatment of hypertension or hypertension with certain compelling indications.1218
Most patients with hypertension, especially black patients, will require at least 2 antihypertensive drugs to achieve adequate blood pressure control.1200 In general, black hypertensive patients tend to respond better to monotherapy with thiazide diuretics or calcium-channel blockers than to monotherapy with ACE inhibitors.24, 63, 64, 501, 504, 1200 Although ACE inhibitors have lowered blood pressure in all races studied, monotherapy with these agents has produced a smaller reduction in blood pressure in black hypertensive patients, a population associated with low-renin hypertension.1, 24, 25, 47, 48, 49 However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar blood pressure lowering in black patients as in other racial groups.1200 In addition, ACE inhibitors appear to produce a higher incidence of angioedema in black patients than in other races studied.1, 47, 49, 1200 (See Race under Hypertension: Other Special Considerations for Antihypertensive Drug Therapy, in Uses in Captopril 24:32.04 and in Enalaprilat/Enalapril 24:32.04.)
For additional information on the role of ACE inhibitors in the management of hypertension, see Uses in Captopril 24:32.04 and in Enalaprilat/Enalapril 24:32.04. For information on overall principles and expert recommendations for treatment of hypertension, see Uses: Hypertension in Adults and also see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Quinapril is used in the management of symptomatic heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-blockers.1, 2, 12, 18, 524, 800
Current guidelines for the management of heart failure in adults generally recommend a combination of drug therapies to reduce morbidity and mortality, including neurohormonal antagonists (e.g., ACE inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors [ARNIs], β-blockers, aldosterone receptor antagonists) that inhibit the detrimental compensatory mechanisms in heart failure.524, 701, 703, 800 Additional agents (e.g., cardiac glycosides, diuretics, sinoatrial modulators [i.e., ivabradine]) added to a heart failure treatment regimen in selected patients have been associated with symptomatic improvement and/or reduction in heart failure-related hospitalizations.524, 800 Experts recommend that all asymptomatic patients with reduced left ventricular ejection fraction (LVEF) (American College of Cardiology Foundation [ACCF]/American Heart Association [AHA] stage B heart failure) receive therapy with an ACE inhibitor and β-blocker to prevent symptomatic heart failure and to reduce morbidity and mortality.524 In patients with prior or current symptoms of chronic heart failure and reduced LVEF (ACCF/AHA stage C heart failure), ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend inhibition of the renin-angiotensin-aldosterone (RAA) system with an ACE inhibitor, angiotensin II receptor antagonist, or ARNI in conjunction with a β-blocker, and an aldosterone antagonist in selected patients, to reduce morbidity and mortality.800 While ACE inhibitors have been the preferred drugs for inhibition of the RAA system because of their established benefits in patients with heart failure and reduced ejection fraction,524 some evidence indicates that therapy with sacubitril/valsartan, an ARNI, may be more effective than ACE inhibitor therapy (enalapril) in reducing cardiovascular death and heart failure-related hospitalization.702, 800 ACCF, AHA, and HFSA recommend that patients with chronic symptomatic heart failure and reduced LVEF (New York Heart Association [NYHA] class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality.800 However, in patients in whom an ARNI is not appropriate, continued use of an ACE inhibitor for all classes of heart failure with reduced ejection fraction remains strongly advised.800 In patients in whom an ARNI or ACE inhibitor is not appropriate, an angiotensin II receptor antagonist may be used.800 For additional information on the use of ACE inhibitors in the management of heart failure, see Uses: Heart Failure, in Captopril 24:32.04 and in Enalaprilat/Enalapril 24:32.04. For further information on the use of ARNIs in patients with heart failure, see Uses: Heart Failure, in Sacubitril and Valsartan 24:32.92.
Many patients with heart failure respond to quinapril with improvement in cardiac function indexes, symptomatic (e.g., dyspnea, fatigue) relief, improved functional capacity, and increased exercise tolerance.1, 2, 12, 18 In some studies, improvement in cardiac function indexes1, 2 and exercise tolerance 2, 18, 20 were sustained for up to 6 months.1, 2 In some patients, beneficial effects have been sustained for up to 12-24 months.1, 2, 18 Although additional studies are needed to determine the specific role of quinapril in the management of heart failure and its long-term efficacy, preliminary data indicate that the efficacy of the drug appears to be similar to that of enalapril and lisinopril.12 Because the renin-angiotensin system appears to substantially contribute to preservation of glomerular filtration in patients with heart failure in whom renal function is severely compromised, therapy with an ACE inhibitor may adversely affect renal function.1, 13, 14, 15, 16, 17, 19 However, at least one study appears to indicate that poor renal function may not increase the risk of renal deterioration in heart failure patients receiving quinapril.17 (See Cautions: Renal Effects in Captopril 24:32.04 and in Enalapril 24:32.04.)
Both ACE inhibitors and angiotensin II receptor antagonists have been shown to slow the rate of progression of renal disease in patients with diabetes mellitus and persistent albuminuria†, 57, 58, 59, 60, 61, 1232 and use of a drug from either class is recommended in such patients with modestly elevated (30-300 mg/24 hours) or higher (exceeding 300 mg/24 hours) levels of urinary albumin excretion.535, 536, 1232 The usual precautions of ACE inhibitor or angiotensin II receptor antagonist therapy in patients with substantial renal impairment should be observed.53 For additional information on the use of ACE inhibitors in the treatment of diabetic nephropathy, see Diabetic Nephropathy under Uses: Nephropathy, in Captopril 24:32.04.
Quinapril hydrochloride alone or in fixed combination with hydrochlorothiazide is administered orally.1, 47 The rate and extent of GI absorption of quinapril reportedly are reduced by about 25-30% by concomitant administration with a high-fat meal.1 When the fixed combination of quinapril hydrochloride and hydrochlorothiazide is administered with a high-fat meal, the rate of quinapril and hydrochlorothiazide absorption is reduced by 14 and 12%, respectively, compared with fasting administration; the extent of absorption is not appreciably affected.47 Therefore, the fixed-combination formulation may be administered without regard to food.47
Dosage of quinapril hydrochloride is expressed in terms of quinapril.1
Dosage of quinapril must be adjusted according to patient tolerance and response.1 Because of the risk of inducing hypotension, initiation of quinapril therapy requires consideration of recent antihypertensive therapy, the extent of blood pressure elevation, sodium intake, fluid status, and other clinical circumstances.1 If therapy is initiated in a patient already receiving a diuretic, symptomatic hypotension may occur following the initial dose of the angiotensin-converting enzyme (ACE) inhibitor.1 The possibility of hypotension may be minimized by discontinuing the diuretic, reducing the diuretic dosage, or cautiously increasing salt intake prior to initiation of quinapril therapy.1 If diuretic therapy cannot be discontinued, the initial dosage of quinapril should be reduced.1 (See Cardiovascular Effects under Warnings/Precautions: Warnings, in Cautions.) For additional information on initiating quinapril in patients receiving diuretic therapy, see the disease-specific dosage sections in Dosage and Administration.
For the management of hypertension in adults not receiving a diuretic, the usual initial dosage of quinapril is 10 or 20 mg once daily.1, 2, 3 In geriatric patients 65 years of age or older, the usual initial dosage of quinapril for the management of hypertension is 10 mg once daily.1 In patients currently receiving a diuretic, it is recommended that the diuretic be discontinued, if possible, 2-3 days before initiating quinapril.1 If blood pressure is not controlled adequately with the ACE inhibitor alone, diuretic therapy may be resumed.1 If diuretic therapy cannot be discontinued, an initial quinapril dose of 5 mg should be given under close medical supervision for several hours until blood pressure has stabilized.1
Dosage of quinapril should be adjusted according to the patient's peak (2-6 hours after dosing) and trough blood pressure responses.1 If the blood pressure response diminishes toward the end of the dosing interval during once-daily administration, increasing the dosage or giving the drug in 2 divided doses daily should be considered.1 Dosage generally should be adjusted no more rapidly than at 2-week intervals.1 The manufacturer states that the usual maintenance dosage in adults is 20-80 mg daily, given as a single dose or in 2 divided doses.1 Some experts state that the usual maintenance dosage is 10-80 mg daily, given as a single dose or in 2 divided doses.1200 Generally, quinapril doses of 40 or 80 mg or divided daily doses provide an increased response toward the end of the dosing interval.1 If blood pressure is not controlled with quinapril alone, a second antihypertensive agent (e.g., a diuretic1 ) may be added.
If quinapril is used for the management of hypertension in children†, some experts recommend a usual initial dosage of 5 mg once daily.1150 Some experts state that the dosage should be increased every 2-4 weeks until blood pressure is controlled, the maximum dosage is reached (80 mg once daily), or adverse effects occur.1150 For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Quinapril/Hydrochlorothiazide Fixed-combination Therapy
The manufacturer recommends that therapy with the commercially available preparation containing quinapril in fixed combination with hydrochlorothiazide should only be initiated in adults after an adequate response is not achieved with quinapril or hydrochlorothiazide monotherapy.47 Alternatively, the fixed combination containing quinapril with hydrochlorothiazide may be used in patients who have been receiving the drugs separately and in whom dosage of the individual drugs has been adjusted to the ratio in a commercial combination preparation. 47 Volume and/or salt depletion should be corrected before initiating therapy with quinapril in fixed combination with hydrochlorothiazide.47 Patients whose blood pressure is not adequately controlled with quinapril monotherapy may receive the fixed combination containing 10 mg of quinapril and 12.5 mg of hydrochlorothiazide or, alternatively, the preparation containing 20 mg of quinapril and 12.5 mg of hydrochlorothiazide.47 Further increases in the dosage of either or both drugs depend on clinical response; however, the dosage of hydrochlorothiazide generally should not be increased for about 2-3 weeks after initiation of therapy.47 Such fixed combinations also may be used to prevent hydrochlorothiazide-induced potassium loss.47 Patients whose blood pressure has been adequately controlled with a hydrochlorothiazide dosage of 25 mg daily, but who experienced potassium loss, may achieve a similar response but less electrolyte disturbance if they are switched to therapy with the fixed-combination preparation containing 10 or 20 mg of quinapril and 12.5 mg of hydrochlorothiazide.47 In clinical trials of quinapril hydrochloride and hydrochlorothiazide as combination therapy using a quinapril dosage of 2.5-40 mg and a hydrochlorothiazide dosage of 6.25-25 mg, the antihypertensive effects increased with increasing dosages of either component.47 For convenience, patients whose hypertension is adequately controlled with 20 mg of quinapril and 25 mg of hydrochlorothiazide administered separately and who experience no clinically important electrolyte disturbance at this combined dosage may be switched to the fixed combination containing these corresponding doses.47
Blood Pressure Monitoring and Treatment Goals
Blood pressure should be monitored regularly (i.e., monthly) during therapy and dosage of the antihypertensive drug adjusted until blood pressure is controlled.1200 If an adequate blood pressure response is not achieved with ACE inhibitor monotherapy, the dosage may be increased or another antihypertensive agent with demonstrated benefit and preferably with a complementary mechanism of action (e.g., calcium-channel blocker, thiazide diuretic) may be added; if target blood pressure is still not achieved with the use of 2 antihypertensive agents, a third drug may be added.1200, 1216 (See Uses: Hypertension.) In patients who develop unacceptable adverse effects with quinapril, the drug should be discontinued and another antihypertensive agent from a different pharmacologic class should be initiated.1216
The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure.1200 However, the optimum blood pressure threshold for initiating antihypertensive drug therapy and specific treatment goals remain controversial.505, 506, 507, 508, 515, 523, 530, 1201, 1207, 1209, 1222 While other hypertension guidelines have based target blood pressure goals on age and comorbidities,501, 504, 536 a 2017 multidisciplinary hypertension guideline from the American College of Cardiology (ACC), American Heart Association (AHA), and a number of other professional organizations incorporates underlying cardiovascular risk into decision making regarding treatment and generally recommends the same target blood pressure (i.e., less than 130/80 mm Hg) in all adults.1200 Many patients will require at least 2 drugs from different pharmacologic classes to achieve this blood pressure goal; the potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs also should be considered when deciding a patient's blood pressure treatment goal.1200, 1220
For additional information on target levels of blood pressure and on monitoring therapy in the management of hypertension, see Blood Pressure Monitoring and Treatment Goals under Dosage: Hypertension, in Dosage and Administration in the Thiazides General Statement 40:28.20.
Because of the risk of severe hypotension, quinapril therapy for heart failure should be initiated under very close medical supervision (e.g., in a hospital setting) with consideration given to recent diuretic therapy and the possibility of severe sodium and/or fluid depletion.1 Patients with heart failure, with or without renal impairment, should be monitored closely for the first 2 weeks of quinapril therapy and whenever dosage of the drug and/or concomitantly administered diuretic is increased.1 ACE inhibitor therapy should be initiated with caution in patients with very low systemic blood pressure (systolic blood pressure less than 80 mm Hg), markedly increased serum creatinine concentrations (exceeding 3 mg/dL), bilateral renal artery stenosis, or elevated serum potassium concentrations (exceeding 5 mEq/L).524 Experts recommend that patients receiving an ACE inhibitor be monitored (i.e., renal function and serum potassium) within 1-2 weeks of initiation of therapy and periodically thereafter, especially patients with preexisting hypotension, hyponatremia, diabetes mellitus, or azotemia, or those taking potassium supplements.524
Although symptoms of heart failure may improve within 48 hours after initiating ACE inhibitor therapy in some patients, such improvement usually is not evident for several weeks or months after initiating ACE inhibitor therapy. In addition, such therapy may reduce the risk of disease progression even if symptomatic improvement is not evident.38 Therefore, dosages generally should be titrated to a prespecified target or highest tolerated dosage (maximum dosage 20 mg twice daily) rather than according to response.524
The usual initial quinapril dosage for the management of heart failure in adults with normal renal function and serum sodium concentration is 5 mg twice daily.1 Quinapril often is administered in conjunction with other agents such as a cardiac glycoside, diuretic, and a β-adrenergic blocking agent (β-blocker) in patients with heart failure.1, 2, 12, 18, 524 After the initial dose, the patient should be monitored closely for at least 2 hours until blood pressure has stabilized.1 Hypotension occurring after the initial dose does not preclude the administration of subsequent doses of the drug, provided caution is exercised and the hypotension has been managed effectively.1 To minimize the likelihood of hypotension, the dosage of any diuretic given concomitantly with quinapril should be reduced, if possible.1 This initial dosage of quinapril may improve symptoms of heart failure, but higher dosages of the drug usually are required to increase exercise duration.1 If the initial dosage is tolerated, dosage generally should be adjusted at weekly intervals to the usual effective dosage of 20-40 mg daily administered in 2 equally divided doses, unless adverse effects (e.g., hypotension, orthostatic hypotension, azotemia) occur.1 The ACC and AHA recommend that therapy with ACE inhibitors be titrated upwards to dosages that have been shown to reduce the risk of cardiovascular events in clinical trials rather than titrating based on a patient's therapeutic response.524 Renal function and serum potassium should be assessed within 1-2 weeks of initiation of therapy and periodically thereafter, especially in patients with preexisting hypotension, hyponatremia, diabetes mellitus, or azotemia, or in those taking potassium supplements.524
If quinapril is used in hypertensive patients with impaired renal function, dosage must be modified in response to the degree of renal impairment, and as with other ACE inhibitors, the theoretical risk of neutropenia must be considered.1, 2, 3 In hypertensive adults with creatinine clearances exceeding 60 mL/minute, the usual initial dosage of quinapril is 10 mg daily. In hypertensive adults with creatinine clearances of 30-60 mL/minute, the usual initial dosage of quinapril is 5 mg daily, whereas in those with creatinine clearances of 10-30 mL/minute, the usual initial dosage is 2.5 mg daily.1 Subsequent dosage should be titrated according to individual tolerance and blood pressure response generally no more rapidly than at 2-week intervals.1
Modification of the usual dosage of quinapril hydrochloride in fixed combination with hydrochlorothiazide does not appear to be necessary in patients with creatinine clearances exceeding 30 mL/minute per 1.73 m2.47 In patients with more severe renal impairment, loop-type diuretics are preferred to thiazide diuretics, and use of quinapril hydrochloride in fixed combination with hydrochlorothiazide is not recommended in such patients.47
Since metabolism of quinapril to quinaprilat normally depends on hepatic esterases, markedly elevated plasma concentrations of quinapril could occur in patients with impaired hepatic function.47 Quinapril hydrochloride in fixed combination with hydrochlorothiazide should be used with caution in patients with hepatic impairment or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.47
The manufacturer states that adults with heart failure and moderate renal impairment (i.e., creatinine clearances greater than 30 mL/minute) and those with severe renal impairment (i.e., creatinine clearances of 10-30 mL/minute) should receive an initial quinapril dosage of 5 and 2.5 mg the first day, respectively, under close monitoring (see Heart Failure under Dosage and Administration: Dosage).1 If the initial dosage of quinapril is well tolerated the first day, quinapril may be administered the following day as a twice-daily regimen.1 If excessive hypotension or substantial deterioration of renal function does not occur, quinapril dosage may be increased at weekly intervals based on clinical and hemodynamic response.1 There are insufficient data to recommend specific dosages for patients with creatinine clearances less than 10 mL/minute.1
Known hypersensitivity to quinapril, other angiotensin-converting enzyme (ACE) inhibitors, or any ingredient in the formulation.1, 47
History of angioedema related to previous ACE inhibitor treatment.1, 47
Concomitant aliskiren therapy in patients with diabetes mellitus.1, 47
Concomitant use (within 36 hours) of a neprilysin inhibitor (e.g., sacubitril).1, 47 (See Drug Interactions: Neprilysin Inhibitors.)
Fetal/Neonatal Morbidity and Mortality
Drugs that act on the renin-angiotensin system (e.g., ACE inhibitors, angiotensin II receptor antagonists) reduce fetal renal function and increase fetal and neonatal morbidity and mortality when used in pregnancy during the second and third trimesters.1, 47, 65, 66 ACE inhibitors also increase the risk of major congenital malformations when administered during the first trimester of pregnancy.65, 66 Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.1, 47 Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death.1, 47 ACE inhibitors (e.g., quinapril) should be discontinued as soon as possible when pregnancy is detected, unless continued use is considered lifesaving for the mother.1, 47, 66 Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.1, 47 For additional information on the risk of ACE inhibitors during pregnancy, see Cautions: Pregnancy, Fertility, and Lactation, in Captopril 24:32.04 and in Enalaprilat/Enalapril 24:32.04.
An ACE inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice has occurred rarely; the syndrome may progress to fulminant hepatic necrosis and is potentially fatal.1, 47 Patients receiving an ACE inhibitor, including quinapril, who develop jaundice or marked elevations of hepatic enzymes should discontinue the drug and receive appropriate monitoring.1, 47
Quinapril may rarely be associated with excessive hypotension in patients with uncomplicated hypertension.1, 47 Volume and/or salt depletion should be corrected before starting quinapril therapy.1 The American College of Cardiology (ACC) and American Heart Association (AHA) recommend that ACE inhibitor therapy be initiated with caution in patients with very low systemic blood pressure (systolic blood pressure less than 80 mm Hg).524
Marked hypotension, which may be associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death, may occur in patients with heart failure, hyponatremia, or severe volume and/or salt depletion of any etiology; patients undergoing dialysis; and those receiving high-dose diuretic therapy, a recent increase in diuretic dosage, or recent intensive diuresis.1, 47 In patients at risk for excessive hypotension, quinapril therapy should be started under close medical supervision, and patients should be followed closely for at least 2 weeks after initiation of quinapril or diuretic therapy or dosage adjustment of either drug.1, 47 In such patients, it may be advisable to discontinue diuretic therapy (except in patients with heart failure), reduce the diuretic dosage, or cautiously increase salt intake (except in patients with heart failure), if possible, prior to initiation of quinapril.1, 47 In addition, it should be considered that in patients with ischemic heart disease, aortic stenosis, or cerebrovascular disease, an excessive decrease in blood pressure may result in myocardial infarction or stroke.1, 47 (See Dosage and Administration: Dosage.)
If excessive hypotension occurs, the patient should be placed in the supine position, and if necessary, an IV infusion of 0.9% sodium chloride injection should be administered to expand fluid volume.1, 47 Transient hypotension is not a contraindication to further quinapril therapy.1, 47 The drug usually may be continued following restoration of blood pressure and volume; however, a reduction in dosage of quinapril or concomitant diuretic therapy may be necessary.1, 47
Neutropenia/agranulocytosis, particularly in patients with renal impairment (especially those with a concomitant collagen vascular disease such as systemic lupus erythematosus or scleroderma), have been reported with other ACE inhibitors (e.g., captopril).1, 47 (See Cautions: Hematologic Effects, in Captopril 24:32.04.) Agranulocytosis also has been reported in at least one patient receiving quinapril who had a history of captopril-associated agranulocytosis.1, 47 Data are insufficient to rule out a similar incidence of agranulocytosis with quinapril in patients without prior reactions to other ACE inhibitors.1, 47 Periodic monitoring of leukocytes in patients with collagen vascular disease, especially if renal impairment exists, should be considered.1, 47
Sensitivity reactions, including anaphylactoid reactions and angioedema (including laryngeal edema), are potentially fatal.1, 47 Head and neck angioedema have occurred in patients receiving an ACE inhibitor and have been reported at a higher rate in black patients compared with patients of other races.1, 47 In addition, concomitant use of an ACE inhibitor and a mammalian target of rapamycin (mTOR) inhibitor may increase the risk of angioedema.1, 47 Head and neck angioedema involving the tongue, glottis, or larynx may cause airway obstruction.1 If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, ACE inhibitors (e.g., quinapril) should be discontinued and appropriate therapy (e.g., ensure airway, epinephrine) initiated immediately.1, 47 Angioedema was reported in 0.1% of patients receiving quinapril in clinical trials.1 Caution should be used in patients with a history of angioedema unrelated to ACE inhibitor therapy.1, 47
Intestinal angioedema (occasionally without a prior history of facial angioedema or elevated serum levels of complement 1 [C1]) esterase inhibitor) also has been reported in patients receiving ACE inhibitors.1, 47 Intestinal angioedema, which frequently presents as abdominal pain (with or without nausea or vomiting) usually is diagnosed by abdominal CT scan, ultrasound, or surgery;1, 47 manifestations usually have resolved after discontinuance of the ACE inhibitor.1 Intestinal angioedema should be considered in the differential diagnosis of patients who develop abdominal pain during therapy with an ACE inhibitor.1, 47
Life-threatening anaphylactoid reactions have been reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization with hymenoptera venom.1, 47 In these patients, such reactions did not occur when ACE inhibitors were temporarily discontinued before desensitization but recurred following inadvertent rechallenge.1, 47 Anaphylactoid reactions also have been reported following initiation of hemodialysis that used a high-flux membrane in patients receiving an ACE inhibitor.1, 47 In addition, anaphylactoid reactions have been reported in patients undergoing low-density lipoprotein (LDL) apheresis with dextran sulfate absorption.1, 47
Inhibition of the renin-angiotensin-aldosterone (RAA) system may cause renal impairment and rarely renal failure and/or death in susceptible patients (e.g., those whose renal function depends on the activity of the RAA system, such as patients with severe heart failure).1, 47
Deterioration of renal function, manifested as transient increases in BUN and serum creatinine concentrations, may occur following administration of ACE inhibitor therapy, particularly in hypertensive patients with unilateral or bilateral renal artery stenosis, preexisting renal impairment (e.g., serum creatinine exceeding 3 mg/dL), or concomitant diuretic therapy.1, 47, 524 This effect usually was reversible following discontinuance of ACE inhibitor and/or diuretic therapy.1 Renal function should be monitored during the first few weeks of therapy in such patients; dosage reduction and/or discontinuance of quinapril and/or the diuretic may be required.1, 47
Hyperkalemia can develop, especially in patients with renal impairment or diabetes mellitus and those receiving drugs or other agents that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes); serum potassium concentrations should be monitored in such patients.1, 47 ACE inhibitor therapy should be initiated with caution in patients with elevated serum potassium concentrations (exceeding 5 mEq/L).524
Persistent and nonproductive cough has been reported with all ACE inhibitors and resolves after drug discontinuance.1, 47
Because quinapril blocks the formation of angiotensin II that would otherwise occur as a result of compensatory renin due to hypotension, hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension.1, 47
When quinapril is used in fixed combination with hydrochlorothiazide, the usual cautions, precautions, and contraindications associated with hydrochlorothiazide must be considered in addition to those associated with quinapril.47 (See Cautions, in the Thiazides General Statement 40:28.20.)
Category D.1, 47 (See Users Guide.)
Quinapril can cause fetal and neonatal morbidity and mortality when administered to a pregnant woman.1, 47 (See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.)
Quinapril and hydrochlorothiazide are distributed into milk in humans.1, 47 Because of the potential for serious adverse reactions to ACE inhibitors (e.g., quinapril) in nursing infants, a decision should be made whether to discontinue nursing or quinapril (either alone or in fixed combination with hydrochlorothiazide), taking into account the importance of the drug(s) to the mother.
If oliguria or hypotension occurs in neonates with a history of in utero exposure to quinapril, blood pressure and renal function should be supported; exchange transfusions or dialysis may be required.1, 47 (See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.)
Although safety and efficacy remain to be fully established in children,1, 47 some experts have recommended pediatric dosages of quinapril for hypertension based on clinical experience.1150 (See Quinapril Therapy under Dosage: Hypertension, in Dosage and Administration.) Safety and efficacy of the fixed combination of quinapril and hydrochlorothiazide have not been established in children.47 For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients, see Uses: Hypertension in Pediatric Patients, in the Thiazides General Statement 40:28.20.
Data from clinical studies evaluating quinapril alone or in combination with hydrochlorothiazide in those 65 years of age and older are insufficient to determine whether they respond differently than younger adults.1, 47 Other reported clinical experience has not identified differences in responses between geriatric and younger patients. Area under the plasma concentration-time curve (AUC) and peak plasma concentrations of quinaprilat, a major metabolite of quinapril, were increased in geriatric patients compared with values observed in younger patients, but these differences appeared to be related to decreased renal function in geriatric patients; no pharmacokinetic differences related solely to age were observed. Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in geriatric patients, dosages of quinapril alone or in combination with hydrochlorothiazide should be initiated at the lower end of the usual dosage range in such patients.1, 47
Renal function may decrease with ACE inhibitor therapy in susceptible patients.1, 47 Safety and efficacy not established in patients with creatinine clearance less than 10 mL/minute.1, 47 Use with caution in those with moderate to mild renal impairment.1, 47 (See Dosage and Administration: Special Populations and also see Renal Effects under Warnings/Precautions: General Precautions, in Cautions.)
Use with caution.1, 47 (See Dosage and Administration: Special Populations.)
ACE inhibitors generally are not as effective in black patients compared with other races.1, 47, 1200 (See Uses: Hypertension).
Adverse effects reported in clinical trials in at least 1% of patients receiving quinapril or quinapril in fixed combination with hydrochlorothiazide for the management of hypertension include headache, dizziness, fatigue, cough, nausea and/or vomiting, and abdominal pain.1, 47 Additional adverse effects reported in at least 1% of patients receiving quinapril in fixed combination with hydrochlorothiazide include myalgia, virus infection, rhinitis, back pain, diarrhea, upper respiratory tract infection, insomnia, somnolence, bronchitis, dyspepsia, asthenia, pharyngitis, vasodilation, vertigo, and chest pain.47
Adverse effects reported in at least 1% of patients receiving quinapril for the management of heart failure include dizziness, cough, fatigue, nausea and/or vomiting, chest pain, hypotension, dyspnea, diarrhea, headache, myalgia, rash, back pain, increased serum creatinine concentration, and increased BUN.1
Agents that Increase Serum Potassium Concentration
Potential pharmacologic interaction (additive hyperkalemic effect)1, 47 with potassium-sparing diuretics, potassium supplements, salt substitutes, and other agents that can increase serum potassium.1, 47 Serum potassium concentrations should be monitored in patients receiving such concomitant therapy.1, 47
Quinapril (80 mg) did not substantially alter the steady-state pharmacokinetics of atorvastatin (multiple doses of 10 mg). 1
Multiple-dose therapy with cimetidine had no effect on the pharmacokinetics of single-dose quinapril.1
The pharmacokinetics of digoxin are not affected by concurrent administration of quinapril.1
Potential pharmacokinetic and pharmacologic interaction (hypotensive effect).1, 47 No pharmacokinetic interactions observed with concomitant single-dose quinapril and hydrochlorothiazide.1, 47
Drugs that Block the Renin-Angiotensin System
Dual blockade of the renin-angiotensin system with angiotensin receptor blocking agents, angiotensin-converting enzyme (ACE) inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared with monotherapy.1, 47 Most patients receiving the combination of 2 renin-angiotensin system blocking agents do not obtain any additional benefit compared with monotherapy.1, 47 Concomitant use of 2 renin-angiotensin system blocking agents generally should be avoided.1, 47 Blood pressure, renal function, and electrolytes should be closely monitored in patients receiving quinapril and other agents that affect the renin-angiotensin system.1, 47
Drugs that Interact with Magnesium
Potential pharmacokinetic interaction (decreased absorption of tetracyclines or other interacting drugs), possibly because of high magnesium content in commercially available tablets containing quinapril hydrochloride alone or in fixed combination with hydrochlorothiazide.1, 47
Nitroid reactions (manifestations include facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients receiving concomitant therapy with injectable gold (sodium aurothiomalate) and an ACE inhibitor.1, 47
Potential pharmacokinetic interaction (increased lithium concentrations and clinical toxicity).1, 47
Mammalian Target of Rapamycin Inhibitors
Concomitant use of an ACE inhibitor and a mammalian target of rapamycin (mTOR) inhibitor may increase the risk of angioedema.1, 47
Increased risk of angioedema.1, 47 Quinapril should not be administered within 36 hours of switching to or from a neprilysin inhibitor.1, 47 (See Contraindications.)
Nonsteroidal Anti-inflammatory Agents
In geriatric patients, patients who are volume depleted (including those who are receiving diuretic therapy), or patients with compromised renal function, concomitant use of nonsteroidal anti-inflammatory agents (NSAIAs), including cyclooxygenase-2 (COX-2) inhibitors, and ACE inhibitors may result in the deterioration of renal function, including possible renal failure.1, 47 These effects are usually reversible.1, 47 Renal function should be monitored periodically in patients receiving concomitant quinapril and NSAIA therapy.1, 47
Multiple-dose therapy with propranolol had no effect on the pharmacokinetics of single-dose quinapril.1
Anticoagulant effect of a single dose of warfarin (i.e., prothrombin time [PT]) was not affected by concurrent administration of twice-daily quinapril.1
Quinapril is an angiotensin-converting enzyme (ACE, bradykininase, kininase II) inhibitor.1, 2, 3, 47 Quinapril, the ethylester of quinaprilat, is a prodrug and has little pharmacologic activity until hydrolyzed to quinaprilat.1, 2, 3, 47 Like benazepril, enalapril, fosinopril, lisinopril, and ramipril but unlike captopril, quinapril does not contain a sulfhydryl group.1, 2, 47 Quinapril is structurally and pharmacologically similar to moexipril.67
Risk of angioedema, anaphylactoid, and other sensitivity reactions; importance of discontinuing the drug and immediately reporting suggestive manifestations (e.g., edema of face, eyes, lips, or tongue; swallowing or breathing with difficulty) to a clinician.1, 47
Risk of hypotension (e.g., lightheadedness, syncope), especially during initial therapy and with volume depletion secondary to excessive perspiration or dehydration, vomiting, or diarrhea.1, 47 Importance of adequate fluid intake.1, 47 Importance of advising patient to temporarily discontinue drug until clinician can be contacted if symptoms of syncope occur.1, 47
Importance of contacting a clinician promptly if manifestations of infection (e.g., sore throat, fever) or neutropenia develop.1, 47
Risk of hyperkalemia; importance of avoiding use of potassium supplements or potassium-containing salt substitutes without consulting a clinician.1, 47
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1, 47
Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed.1, 47, 66 Risk of use during first, second, and third trimesters of pregnancy; importance of discussing other options for hypertension treatment if pregnancy occurs.1, 47, 65, 66
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 5 mg (of quinapril)* | Accupril® (scored) | |
10 mg (of quinapril)* | Accupril® | Pfizer | ||
Quinapril Hydrochloride Tablets | ||||
20 mg (of quinapril)* | Accupril® | Pfizer | ||
Quinapril Hydrochloride Tablets | ||||
40 mg (of quinapril)* | Accupril® | Pfizer | ||
Quinapril Hydrochloride Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 10 mg (of quinapril) with Hydrochlorothiazide 12.5 mg* | Accuretic® (scored) | Pfizer |
20 mg (of quinapril) with Hydrochlorothiazide 12.5 mg* | Accuretic® | Pfizer | ||
Quinapril Hydrochloride and Hydrochlorothiazide Tablets | ||||
Quinaretic® | Amide | |||
20 mg (of quinapril) with Hydrochlorothiazide 25 mg* | Accuretic® | Pfizer | ||
Quinapril Hydrochloride and Hydrochlorothiazide Tablets | ||||
Quinaretic® | Amide |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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