Brand name: Accupril
Drug class: Angiotensin-Converting Enzyme Inhibitors
- ACE Inhibitors
VA class: CV800
Chemical name: [3S-[2[R*(R)],3R*]]-2-[2-[[1-Ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2 ,3,4-tetrahydro-3-isoquinolinecarboxylic acid monohydrochloride
Molecular formula: C₂₅H₃₀N₂O₅•HCl
CAS number: 82586-55-8

Medically reviewed by Drugs.com on Feb 23, 2024. Written by ASHP.

Introduction

Nonsulfhydryl ACE inhibitor.

Uses for Quinapril

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).

ACE inhibitors are recommended as one of several preferred agents 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. 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.

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).

A 2017 ACC/AHA multidisciplinary hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension. (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP. However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) of <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk. In addition, an SBP goal of <130 mm Hg is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg. These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.

Other hypertension guidelines generally have based target BP goals on age and comorbidities. Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients compared with those recommended by the 2017 ACC/AHA hypertension guideline.

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors. ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg. Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP. Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to ACE inhibitors. However, the combination of an ACE inhibitor or an angiotensin II receptor antagonist with a calcium-channel blocker or thiazide diuretic produces similar BP lowering in black patients as in other racial groups.

ACE inhibitors may be preferred in hypertensive patients with heart failure, ischemic heart disease, diabetes mellitus, CKD, or cerebrovascular disease or post-MI.

Heart Failure

Management of heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-adrenergic blocking agents (β-blockers).

Some evidence indicates that therapy with an ACE inhibitor (enalapril) may be less effective than angiotensin receptor-neprilysin inhibitor (ARNI) therapy (e.g., sacubitril/valsartan) in reducing cardiovascular death and heart failure-related hospitalization.

ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend that patients with chronic symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (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.

Diabetic Nephropathy

A recommended agent in the management of patients with diabetes mellitus and persistent albuminuria^{† [off-label]} who have modestly elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours) levels of urinary albumin excretion; slows rate of progression of renal disease in such patients.

Quinapril Dosage and Administration

General

BP Monitoring and Treatment Goals

• Monitor BP regularly (i.e., monthly) during therapy and adjust dosage of the antihypertensive drug until BP controlled.

• If unacceptable adverse effects occur, discontinue drug and initiate another antihypertensive agent from a different pharmacologic class.

• If adequate BP response not achieved with a single antihypertensive agent, either increase dosage of single drug or add a second drug with demonstrated benefit and preferably a complementary mechanism of action (e.g., calcium-channel blocker, thiazide diuretic). Many patients will require ≥2 drugs from different pharmacologic classes to achieve BP goal; if goal BP still not achieved, add a third drug.

Administration

Oral Administration

Administer orally once or twice daily.

Manufacturer makes no specific recommendation regarding administration of quinapril with meals; administer quinapril/hydrochlorothiazide fixed combinations without regard to meals. (See Food under Pharmacokinetics.)

Dosage

Available as quinapril hydrochloride; dosage expressed in terms of quinapril.

May minimize risk of hypotension in patients currently receiving diuretic therapy by discontinuing the diuretic, reducing diuretic dosage, or cautiously increasing salt intake prior to initiating quinapril; if diuretic therapy cannot be discontinued, initiate quinapril at a reduced dosage. (See Hypotension under Cautions and see the individual dosage sections in Dosage and Administration.)

Pediatric Patients

Hypertension† [off-label]

Oral

Some experts recommend an initial dosage of 5 mg once daily. These experts state dosage should be increased every 2–4 weeks until BP controlled, maximum dosage reached (80 mg once daily), or adverse effects occur.

Adults

Hypertension

Quinapril Therapy

Oral

Initially, 10 or 20 mg once daily in patients not receiving a diuretic. Adjust dosage at ≥2-week intervals to achieve BP control.

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating quinapril. May resume diuretic therapy if BP not controlled adequately with quinapril alone. If diuretic cannot be discontinued, initiate quinapril at a dose of 5 mg under close medical supervision for several hours until BP has stabilized.

Usual maintenance dosage: Manufacturers state 20–80 mg daily, given in 1 dose or 2 divided doses. Some experts state 10–80 mg daily, given in 1 dose or 2 divided doses.

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in 2 divided doses.

Quinapril/Hydrochlorothiazide Fixed-combination Therapy

Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.

If BP is not adequately controlled by monotherapy with quinapril or hydrochlorothiazide, can switch to the fixed-combination preparation containing quinapril 10 mg and hydrochlorothiazide 12.5 mg or, alternatively, quinapril 20 mg and hydrochlorothiazide 12.5 mg. Adjust dosage of either or both drugs according to patient’s response.

If BP is controlled by monotherapy with hydrochlorothiazide 25 mg daily but potassium loss is problematic, can switch to fixed-combination preparation containing quinapril 10 mg and hydrochlorothiazide 12.5 mg or, alternatively, quinapril 20 mg and hydrochlorothiazide 12.5 mg.

If BP is controlled with quinapril 20 mg and hydrochlorothiazide 25 mg (administered separately) and if no clinically important electrolyte disturbance is observed, can switch to the fixed-combination preparation containing these corresponding doses for convenience.

Heart Failure

Oral

Initially, 5 mg twice daily. Monitor closely for ≥2 hours until BP has stabilized. To minimize risk of hypotension, reduce diuretic dosage, if possible.

Adjust dosage at weekly intervals to reach usual dosage.

Usual dosage: 20–40 mg daily, given in 2 equally divided doses.

Prescribing Limits

Pediatric Patients

Hypertension† [off-label]

Oral

Maximum 80 mg daily.

Special Populations

Renal Impairment

Hypertension

Oral

Initially, 10 mg once daily in adults with Cl_cr >60 mL/minute; 5 mg once daily in those with Cl_cr 30–60 mL/minute; or 2.5 mg once daily in those with Cl_cr 10–30 mL/minute. Titrate at 2-week intervals until BP is controlled. (See Renal Impairment under Cautions.)

Quinapril/hydrochlorothiazide fixed combinations are not recommended in patients with severe renal impairment (Cl_cr ≤30 mL/minute or S_cr >3 mg/dL).

Heart Failure

Oral

Initially (first day), 5 mg in patients with moderate renal impairment (Cl_cr >30 mL/minute) or 2.5 mg in patients with severe renal impairment (Cl_cr 10–30 mL/minute) under close medical supervision. If well tolerated, administer as twice-daily regimen on subsequent days. Titrate at weekly intervals based on clinical and hemodynamic response.

Geriatric Patients

Hypertension

Oral: Initially, 10 mg once daily as monotherapy. Adjust dosage at ≥2-week intervals to achieve BP control.

Cautions for Quinapril

Contraindications

• Known hypersensitivity to quinapril or another ACE inhibitor.

  History of angioedema with prior ACE inhibitor treatment.

• Concomitant aliskiren therapy in patients with diabetes mellitus.

• Concomitant use (within 36 hours) of a neprilysin inhibitor (e.g., sacubitril).

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Possible reduction in fetal renal function and increase in fetal and neonatal morbidity and mortality when used during pregnancy. (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.

Discontinue ACE inhibitors (e.g., quinapril) as soon as possible when pregnancy is detected, unless continued use is considered lifesaving. Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.

Potential neonatal effects include skull hypoplasia, anuria, hypotension, renal failure, and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.

Hepatic Effects

Clinical syndrome that usually is manifested initially by cholestatic jaundice and may progress to fulminant hepatic necrosis (occasionally fatal) reported rarely with ACE inhibitors.

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.

Hypotension

Possible symptomatic hypotension. Risk of marked hypotension, sometimes associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death, in patients with heart failure, hyponatremia, or severe volume and/or salt depletion; patients undergoing dialysis; and those receiving higher-dose diuretic therapy, recent increase in diuretic dosage, or recent intensive diuresis. Potential for MI or stroke in patients with ischemic cardiovascular or cerebrovascular disease.

To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical conditions. May minimize potential for hypotension in patients at risk of excessive hypotension by withholding diuretic therapy (except in patients with heart failure), reducing diuretic dosage, and/or cautiously increasing sodium intake (except in patients with heart failure) prior to initiation of quinapril. (See Dosage under Dosage and Administration.)

In patients at risk of excessive hypotension, initiate therapy under close medical supervision; monitor closely for first 2 weeks following initiation of quinapril or any increase in quinapril or diuretic dosage.

If excessive hypotension occurs, immediately place patient in supine position and, if necessary, administer IV infusion of 0.9% sodium chloride solution. Quinapril therapy usually can be continued following restoration of volume and BP. If symptomatic hypotension develops, dosage reduction or discontinuance of quinapril or diuretic may be necessary.

Neutropenia/Agranulocytosis

Neutropenia and agranulocytosis reported with other ACE inhibitors; risk appears to depend principally on presence of renal impairment and/or presence of collagen vascular disease. Agranulocytosis reported with quinapril therapy in at least one patient with history of captopril-associated agranulocytosis. Data insufficient to rule out similar incidence of agranulocytosis with quinapril in patients without prior reactions to other ACE inhibitors.

Consider monitoring leukocytes in patients with collagen vascular disease and/or renal disease.

Sensitivity Reactions

Anaphylactoid reactions and/or head and neck angioedema possible; if associated with laryngeal edema, may be fatal. Head and neck angioedema reported in patients receiving an ACE inhibitor and at a higher rate in black patients compared with patients of other races. Concomitant use of an ACE inhibitor and a mammalian target of rapamycin (mTOR) inhibitor may increase the risk of angioedema. Immediate medical intervention (e.g., epinephrine) required for involvement of tongue, glottis, or larynx.

Intestinal angioedema reported; sometimes occurs in patients with no prior history of facial angioedema. Manifestations include abdominal pain (with or without nausea or vomiting). Consider intestinal angioedema in the differential diagnosis of patients receiving ACE inhibitors presenting with abdominal pain.

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption or following initiation of hemodialysis that utilized high-flux membrane.

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.

Contraindicated in patients with a history of angioedema associated with ACE inhibitors.

General Precautions

Renal Effects

Transient increases in BUN and S_cr possible, especially in patients with preexisting renal impairment or those receiving concomitant diuretic therapy. Possible increases in BUN and S_cr in patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of ACE inhibitor and/or diuretic.

Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe heart failure.

Closely monitor renal function for the first few weeks of therapy in hypertensive patients with unilateral or bilateral renal-artery stenosis. Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic.

Effects on Potassium

Possible hyperkalemia, especially in patients with renal impairment or diabetes mellitus and those receiving agents that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes). (See Specific Drugs under Interactions.)

Monitor serum potassium concentration in these patients.

Initiate ACE inhibitor therapy with caution in patients with elevated serum potassium concentrations (>5 mEq/L).

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.

Surgery/Anesthesia

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.

Use of Fixed Combinations

When quinapril is used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.

Specific Populations

Pregnancy

Can cause fetal and neonatal morbidity and mortality when administered to a pregnant woman. (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)

Lactation

Distributed into milk. Caution if used in nursing women.

Pediatric Use

If oliguria or hypotension occurs in neonates with a history of in utero exposure to quinapril, support BP and renal function; exchange transfusions or dialysis may be required. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Safety and efficacy remain to be fully established in children; however, some experts have recommended quinapril dosages for hypertension based on clinical experience.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults. However, cautious dosing recommended due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.

Renal Impairment

Deterioration of renal function may occur. (See Renal Effects under Cautions.)

Initial dosage adjustment recommended in patients with renal impairment. (See Renal Impairment under Dosage and Administration.) Safety and efficacy not established in patients with Cl_cr <10 mL/minute.

Quinapril/hydrochlorothiazide fixed combinations not recommended in patients with severe renal impairment (Cl_cr ≤30 mL/minute or S_cr >3 mg/dL).

Hepatic Impairment

Use with caution in patients with hepatic impairment or progressive liver disease.

Black Patients

BP reduction may be smaller in black patients compared with patients of other races. (See Hypertension under Uses.)

Higher incidence of angioedema reported with ACE inhibitors in black patients compared with other races.

Common Adverse Effects

Patients with hypertension: Headache, dizziness, fatigue, cough, nausea and/or vomiting, abdominal pain. With fixed-combination preparation, myalgia, virus infection, rhinitis, back pain, diarrhea, upper respiratory tract infection, insomnia, somnolence, bronchitis, dyspepsia, asthenia, pharyngitis, vasodilation, vertigo, chest pain.

Patients with heart failure: Dizziness, cough, fatigue, nausea and/or vomiting, chest pain, hypotension, dyspnea, diarrhea, headache, myalgia, rash, back pain, increased serum creatinine concentration, increased BUN.

Drug Interactions

Drugs That Interact with Magnesium

Possible decreased absorption of drugs that interact with magnesium, possibly due to high magnesium content in quinapril-containing preparations.

Specific Drugs

Quinapril Pharmacokinetics

Absorption

Bioavailability

About 60% of oral dose is absorbed.

Peak plasma concentrations of quinapril and quinaprilat are achieved within 1 and 2 hours, respectively.

Onset

Following a single oral dose, antihypertensive effects are observed within 1 hour, with peak BP reduction at 2–4 hours.

During chronic therapy, maximum antihypertensive effect is achieved after 1–2 weeks.

Duration

Inhibition of >80% of ACE activity persists for about 24 hours. Inhibition of 75% of the pressor response to angiotensin I persists for about 4 hours.

Food

High-fat meals result in moderate (25–30%) reductions in rate and extent of absorption of quinapril. When quinapril/hydrochlorothiazide combination is administered with high-fat meals, rate of quinapril absorption is reduced by 14%, but extent of absorption is unaffected.

Special Populations

Decreased quinaprilat concentrations in patients with alcoholic cirrhosis.

Distribution

Extent

Quinapril and quinaprilat do not cross the blood-brain barrier.

Crosses the placenta in rats. Distributed into human milk.

Plasma Protein Binding

97% for both quinapril and quinaprilat.

Elimination

Metabolism

Metabolized principally to an active metabolite, quinaprilat (approximately 38% of oral dose).

Elimination Route

Eliminated principally in urine (as metabolites).

Not removed by hemodialysis or peritoneal dialysis.

Half-life

Quinaprilat: Elimination: 2 hours; prolonged terminal phase of 25 hours.

Special Populations

In patients with renal impairment, elimination half-life increases with decreasing Cl_cr.

Decreased elimination of quinaprilat in patients ≥65 years of age.

Stability

Storage

Oral

Tablets

Conventional tablets: 15–30°C. Protect from light.

Fixed-combination tablets: 20–25°C.

Actions

• Prodrug; not pharmacologically active until hydrolyzed in the liver to quinaprilat.

• Suppresses the renin-angiotensin-aldosterone (RAA) system.

Advice to Patients

• Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions. Importance of reporting sensitivity reactions (e.g., edema of face, eyes, lips, tongue, or extremities; hoarseness; swallowing or breathing with difficulty) immediately to clinician and of discontinuing the drug.

• Risk of hypotension. Importance of temporarily discontinuing drug until clinician can be contacted if symptoms of syncope (e.g., lightheadedness, fainting) occur. Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.

• Importance of reporting signs of infection (e.g., sore throat, fever).

• Risk of hyperkalemia. Importance of avoiding use of potassium supplements or salt substitutes containing potassium without consulting a clinician.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Risks of use during pregnancy; importance of discussing other options for hypertension treatment if pregnancy occurs.

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• Do ACE inhibitors make COVID-19 worse?

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