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Uses

Quinapril hydrochloride is used alone or in combination with other classes of antihypertensive agents (e.g., thiazide diuretics) in the management of hypertension. 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.

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) or in patients receiving immunosuppressive therapy, the possibility that similar adverse effects may occur with quinapril should be considered since current evidence is insufficient to rule out such risk.

Hypertension

Quinapril hydrochloride is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. ACE inhibitors are considered one of several preferred antihypertensive drugs for the initial management of hypertension; other options include angiotensin II receptor antagonists, calcium-channel blockers, and thiazide diuretics. While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes. 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, or cerebrovascular disease or following myocardial infarction. (See Uses: Hypertension in and in )

In general, black hypertensive patients tend to respond better to monotherapy with thiazide diuretics or calcium-channel blockers than to monotherapy with ACE inhibitors. 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; however, this population difference in response does not appear to occur during combined therapy with an ACE inhibitor and a thiazide diuretic or calcium-channel blocker. In addition, ACE inhibitors appear to produce a higher incidence of angioedema in black patients than in other races studied. (See Race under Hypertension: Other Special Considerations for Antihypertensive Therapy, in Uses in and in )

For additional information on the role of ACE inhibitors in the management of hypertension, and in . For information on overall principles and expert recommendations for treatment of hypertension,

Heart Failure

Quinapril is used in the management of symptomatic heart failure, usually in conjunction with other agents such as cardiac glycosides, diuretics, and β-blockers.

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. 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. 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. 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. 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, 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. 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. 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. In patients in whom an ARNI or ACE inhibitor is not appropriate, an angiotensin II receptor antagonist may be used. For additional information on the use of ACE inhibitors in the management of heart failure, see Uses: Heart Failure, and in .

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. In some studies, improvement in cardiac function indexes and exercise tolerance were sustained for up to 6 months. In some patients, beneficial effects have been sustained for up to 12-24 months. 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. 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. 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. and

Diabetic Nephropathy

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, 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. The usual precautions of ACE inhibitor or angiotensin II receptor antagonist therapy in patients with substantial renal impairment should be observed. For additional information on the use of ACE inhibitors in the treatment of diabetic nephropathy, see

Dosage and Administration

Administration

Quinapril hydrochloride alone or in fixed combination with hydrochlorothiazide is administered orally. The rate and extent of GI absorption of quinapril reportedly are reduced by about 25-30% by concomitant administration with a high-fat meal. 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. Therefore, the fixed-combination formulation may be administered without regard to food.

Dosage

Dosage of quinapril hydrochloride is expressed in terms of quinapril.

Dosage of quinapril must be adjusted according to patient tolerance and response. 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. 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. 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. If diuretic therapy cannot be discontinued, the initial dosage of quinapril should be reduced.(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.

Hypertension

Quinapril Therapy

For the management of hypertension in adults not receiving a diuretic, the usual initial dosage of quinapril is 10 or 20 mg once daily. 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. In patients currently receiving a diuretic, it is recommended that the diuretic be discontinued, if possible, 2-3 days before initiating quinapril. If blood pressure is not controlled adequately with the ACE inhibitor alone, diuretic therapy may be resumed. 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.

Dosage of quinapril should be adjusted according to the patient's peak (2-6 hours after dosing) and trough blood pressure responses. 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. Dosage generally should be adjusted no more rapidly than at 2-week intervals. The usual maintenance dosage in adults is 20-80 mg daily, given as a single dose or in 2 divided doses daily. Generally, quinapril doses of 40 or 80 mg or divided daily doses provide an increased response toward the end of the dosing interval. If blood pressure is not controlled with quinapril alone, a second antihypertensive agent (e.g., a diuretic) may be added.

If quinapril is used for the management of hypertension in children, some experts recommend a usual initial dosage of 5-10 mg once daily. Dosage may be increased as necessary to a maximum dosage of 80 mg once daily. For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients,

The panel members appointed to the Eighth Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8 expert panel) state that evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) should be used when available to determine target dosages of antihypertensive agents. Target dosages generally can be achieved within 2-4 weeks, but it may take up to several months.

Antihypertensive therapy should be titrated until goal blood pressure is achieved. If an adequate blood pressure response is not achieved with quinapril monotherapy, another antihypertensive agent with demonstrated benefit may be added; if goal blood pressure is still not achieved with the use of 2 antihypertensive agents at optimal dosages, a third drug may be added. In patients who experience intolerable adverse effects with quinapril, dosage reduction should be considered; if adverse effects worsen or fail to resolve, it may be necessary to discontinue the ACE inhibitor and initiate another class of antihypertensive agent.

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. 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. Volume and/or salt depletion should be corrected before initiating therapy with quinapril in fixed combination with hydrochlorothiazide. 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. 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. Such fixed combinations also may be used to prevent hydrochlorothiazide-induced potassium loss. 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. 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. 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.

Blood Pressure Monitoring and Treatment Goals

Careful monitoring of blood pressure during initial titration or subsequent upward adjustment in dosage of quinapril is recommended.

The goal of hypertension management and prevention is to achieve and maintain optimal control of blood pressure; specific target levels of blood pressure should be individualized based on consideration of multiple factors, including patient age and comorbidities, and the currently available evidence from clinical studies.

For additional information on initiating and adjusting quinapril dosage in the management of hypertension, see Blood Pressure Monitoring and Treatment Goals under Dosage: Hypertension, in Dosage and Administration in the .

Heart Failure

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. 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. 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). 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.

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. 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.

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. 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. After the initial dose, the patient should be monitored closely for at least 2 hours until blood pressure has stabilized. 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. To minimize the likelihood of hypotension, the dosage of any diuretic given concomitantly with quinapril should be reduced, if possible. This initial dosage of quinapril may improve symptoms of heart failure, but higher dosages of the drug usually are required to increase exercise duration. 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. The American College of Cardiology (ACC) and American Heart Association (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. 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.

Special Populations

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. 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. Subsequent dosage should be titrated according to individual tolerance and blood pressure response generally no more rapidly than at 2-week intervals.

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 m. 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.

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. 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.

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). If the initial dosage of quinapril is well tolerated the first day, quinapril may be administered the following day as a twice-daily regimen. 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. There are insufficient data to recommend specific dosages for patients with creatinine clearances less than 10 mL/minute.

Cautions

Contraindications

History of angioedema related to previous angiotensin-converting enzyme (ACE) inhibitor treatment.

Known hypersensitivity to quinapril, other ACE inhibitors, or any ingredient in the formulation.

Warnings/Precautions

Warnings

When hydrochlorothiazide is used in fixed combination with quinapril, the usual cautions, precautions, and contraindications associated with hydrochlorothiazide must be considered in addition to those associated with quinapril.

Cardiovascular Effects

Like other ACE inhibitors, quinapril rarely is associated with excessive hypotension in patients with uncomplicated hypertension. Volume and/or salt depletion should be corrected before starting quinapril therapy. 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).

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 diuretic therapy with high dosages, a recent increase in diuretic dosage, or recent intensive diuresis. 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. 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. 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. (See Dosage and Administration: Dosage.)

If 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. Transient hypotension is not a contraindication to further quinapril therapy. 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.

Hematologic Effects

Neutropenia/agranulocytosis, particularly in patients with renal impairment (especially with concomitant collagen vascular disease [e.g., systemic lupus erythematosus, scleroderma]), have been reported with another ACE inhibitor (i.e., captopril). Data are insufficient to rule out similar incidence of agranulocytosis with quinapril in patients without prior reactions to other ACE inhibitors. Monitoring of leukocytes in patients with collagen vascular disease, especially if renal impairment exists, should be considered.

Fetal/Neonatal Morbidity and Mortality

ACE inhibitors can cause fetal and neonatal morbidity and mortality when used during the second and third trimesters of pregnancy. ACE inhibitors also increase the risk of major congenital malformations when administered during the first trimester of pregnancy. Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving for the mother. Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy. For additional information on the risk of ACE inhibitors during pregnancy, and in .

Hepatic Effects

Rare ACE inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice; may progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including quinapril, who develop jaundice or marked elevations of hepatic enzymes should discontinue the drug and receive appropriate monitoring.

Sensitivity Reactions

Sensitivity reactions, including anaphylactoid reactions and angioedema (including laryngeal edema), are potentially fatal. Head and neck angioedema involving the tongue, glottis, or larynx may cause airway obstruction. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, quinapril should be discontinued and appropriate therapy (e.g., ensure airway, epinephrine) should be initiated immediately. Angioedema reported in 0.1% of patients receiving quinapril in clinical trials. Caution in patients with history of angioedema unrelated to ACE inhibitor therapy.

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. Intestinal angioedema, which frequently presents as abdominal pain (with or without nausea or vomiting) usually is diagnosed by abdominal CT scan, ultrasound, or surgery; manifestations usually have resolved after discontinuance of the ACE inhibitor. Intestinal angioedema should be considered in the differential diagnosis of patients who develop abdominal pain during therapy with an ACE inhibitor.

Life-threatening anaphylactoid reactions have been reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization with hymenoptera venom. In these patients, such reactions did not occur when ACE inhibitors were temporarily discontinued before desensitization but recurred following inadvertent rechallenge. Anaphylactoid reactions also have been reported following initiation of hemodialysis that used a high-flux membrane in patients receiving an ACE inhibitor. In addition, anaphylactoid reactions have been reported in patients undergoing low-density lipoprotein (LDL) apheresis with dextran sulfate absorption.

General Precautions

Aortic Stenosis/Hypertrophic Cardiomyopathy

Like other vasodilators, quinapril should be administered with caution in patients with obstruction in the outflow tract of the left ventricle (e.g., aortic stenosis, hypertrophic cardiomyopathy).

Renal Effects

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).

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. This effect usually was reversible following discontinuance of ACE inhibitor and/or diuretic therapy. 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.

Effects on Potassium

Hyperkalemia can develop, especially in those with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes). ACE inhibitor therapy should be initiated with caution in patients with elevated serum potassium concentrations (exceeding 5 mEq/L).

Cough

Persistent and nonproductive reported with all ACE inhibitors; resolves after drug discontinuance.

Surgery/Anesthesia

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension.

Specific Populations

Pregnancy

Category C (first trimester); Category D (second and third trimesters).(See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.)

Lactation

Quinapril and hydrochlorothiazide are distributed into milk in humans. 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.

Pediatric Use

Although safety and efficacy remain to be fully established in children, some experts have recommended pediatric dosages for hypertension based on currently limited clinical experience.(See Quinapril Therapy under Dosage: Hypertension, in Dosage and Administration.) For information on overall principles and expert recommendations for treatment of hypertension in pediatric patients,

Geriatric Use

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. 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 with renal impairment compared with values observed in younger patients, but 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.

Renal Impairment

Renal function may decrease with ACE inhibitor therapy in susceptible patients. Safety and efficacy not established in patients with creatinine clearance less than 10 mL/minute. Use with caution in those with moderate to mild renal impairment.(See Dosage and Administration: Special Populations and also see Renal Effects under Warnings/Precautions: General Precautions, in Cautions.)

Hepatic Impairment

Use with caution.(See Dosage and Administration: Special Populations.)

Black Patients

ACE inhibitors generally are not as effective in black patients compared with other races. (See Uses: Hypertension).

Common Adverse Effects

Adverse effects reported 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, vomiting, or abdominal pain. 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, or chest pain.

Adverse effects reported in at least 1% of patients receiving quinapril for the management of heart failure include dizziness, cough, fatigue, nausea, vomiting, chest pain, hypotension, dyspnea, diarrhea, headache, myalgia, rash, back pain, increased serum creatinine concentration, and increased BUN.

Drug Interactions

Diuretics

Potential pharmacokinetic and pharmacologic interaction (hypotensive effect).

Drugs Increasing Serum Potassium Concentration

Potential pharmacologic interaction (additive hyperkalemic effect). Includes potassium-sparing diuretics, potassium supplements, and other drugs that can increase serum potassium.

Lithium

Potential pharmacokinetic interaction (increased lithium concentrations and clinical toxicity).

Drugs that Interact with Magnesium

Potential pharmacokinetic interaction (decreased absorption of tetracyclines or other interacting drug), possibly because of high magnesium content in commercial quinapril hydrochloride tablets alone or in fixed combination with hydrochlorothiazide.