Quinapril Hydrochloride

Class: Angiotensin-Converting Enzyme 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
Brands: Accupril, Accuretic

• 
  

  May cause fetal and neonatal morbidity and mortality if used during pregnancy.^{1 47 65 66} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  If pregnancy is detected, discontinue quinapril as soon as possible.^{1 47 66}

  
  

Introduction

Nonsulfhydryl ACE inhibitor.^{1 2 3 47}

Uses for Quinapril Hydrochloride

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).^{1 2 4 11 28 47}

One of several preferred initial therapies in hypertensive patients with heart failure, postmyocardial infarction, high coronary disease risk, diabetes mellitus, chronic renal failure, and/or cerebrovascular disease.⁵⁰

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.⁵⁰

CHF

Management of symptomatic CHF, usually in conjunction with cardiac glycosides, diuretics, and β-adrenergic blocking agents.¹

Diabetic Nephropathy

A first-line agent in the treatment of diabetic nephropathy† in hypertensive patients with type 2 diabetes mellitus.^{42 54 55 56 57 58 59 60 61}

Quinapril Hydrochloride Dosage and Administration

General

Hypertension

• 
  

  Quinapril/hydrochlorothiazide fixed combinations should not be used for initial treatment of hypertension.⁴⁷

  
  

Administration

Oral Administration

Administer orally once or twice daily.^{1 47}

Manufacturer makes no specific recommendation regarding administration of quinapril with meals;^{1 47} administer quinapril/hydrochlorothiazide fixed combinations without regard to meals.⁴⁷ (See Food under Pharmacokinetics.)

Dosage

Available as quinapril hydrochloride; dosage expressed in terms of quinapril.^{1 47}

Pediatric Patients

Hypertension†

Oral

Some experts recommend an initial dosage of 5–10 mg once daily.⁶² Increase dosage as necessary to a maximum dosage of 80 mg once daily.⁶²

Adults

Hypertension

Oral

Initially, 10 or 20 mg once daily as monotherapy.^{1 2 3 11 28 50} Adjust dosage at ≥2-week intervals to achieve BP control.¹

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating quinapril.¹ May cautiously resume diuretic therapy if BP not controlled adequately with quinapril alone.¹ If diuretic cannot be discontinued, increase sodium intake and initiate quinapril at 5 mg daily under close medical supervision for several hours and until BP has stabilized.¹

Usual dosage: 20–80 mg daily, given in 1 dose or 2 divided doses.^{1 28 50}

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in 2 divided doses.^{1 28}

Quinapril/Hydrochlorothiazide Combination Therapy

Oral

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.⁴⁷ Adjust dosage of either or both drugs according to patient’s response.⁴⁷

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.⁴⁷

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.⁴⁷

CHF

Oral

Initially, 5 mg twice daily.¹ Monitor closely for ≥2 hours until BP has stabilized.¹ To minimize risk of hypotension, reduce diuretic dosage, if possible.¹

Adjust dosage at weekly intervals to reach usual dosage.¹

Usual dosage: 20–40 mg daily, given in 2 equally divided doses.¹

Prescribing Limits

Pediatric Patients

Hypertension†

Oral

Maximum 80 mg daily.⁶²

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.¹ Titrate at 2-week intervals until BP is controlled.¹ (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).⁴⁷

CHF

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.¹ If well tolerated, administer as twice-daily regimen on subsequent days.¹ Titrate at weekly intervals based on clinical and hemodynamic response.¹

Geriatric Patients

Hypertension

Oral

Initially, 10 mg once daily as monotherapy.¹ Adjust dosage at ≥2-week intervals to achieve BP control.¹

Cautions for Quinapril Hydrochloride

Contraindications

• 
  

  Known hypersensitivity (e.g., history of angioedema) to quinapril or another ACE inhibitor.^{1 47}

  
  

Warnings/Precautions

Warnings

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.^{1 47}

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.^{1 47}

Hypotension

Possible symptomatic hypotension, sometimes associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death.^{1 47} Patients at particular risk include those with intensive diuretic therapy or recent increase in diuretic dose, dialysis, or severe volume and/or salt depletion.^{1 47}

Risk of marked hypotension in patients with CHF.^{1 47} Potential for MI or stroke in patients with ischemic cardiovascular or cerebrovascular disease.^{1 47}

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.^{1 47}

To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical conditions.^{1 47} May minimize potential for hypotension by withholding diuretic therapy (except in patients with CHF), reducing diuretic dosage, and/or increasing sodium intake (except in patients with CHF) prior to initiation of quinapril.^{1 47} (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.^{1 47}

If excessive hypotension occurs, immediately place patient in supine position and, if necessary, administer IV infusion of 0.9% sodium chloride solution.^{1 47} Quinapril therapy usually can be continued following restoration of volume and BP.^{1 47} If symptomatic hypotension develops, dosage reduction or discontinuance of quinapril or diuretic may be necessary.^{1 47}

Hematologic Effects

Neutropenia and agranulocytosis reported with captopril; risk appears to depend principally on presence of renal impairment and/or presence of collagen vascular disease.^{1 47} Data insufficient to rule out similar incidence of agranulocytosis with quinapril.^{1 47}

Consider monitoring leukocytes in patients with collagen vascular disease and/or renal disease.^{1 47}

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.^{1 47 65 66} (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.⁶⁶

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.^{65 66}

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.⁶⁶ Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.^{1 47}

Sensitivity Reactions

Anaphylactoid reactions and/or head and neck angioedema possible; if associated with laryngeal edema, may be fatal.^{1 47 b} Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.^{1 47}

Intestinal angioedema reported; sometimes occurs in patients with no prior history of facial angioedema.^{1 b} Manifestations include abdominal pain (with or without nausea or vomiting).^{1 b} Consider intestinal angioedema in the differential diagnosis of patients receiving ACE inhibitors presenting with abdominal pain.^{1 b}

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.^{1 47}

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.^{1 47}

Contraindicated in patients with a history of angioedema associated with ACE inhibitors.^{1 47}

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.^{1 47} 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.^{1 47}

Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe CHF.^{1 47}

Closely monitor renal function for the first few weeks of therapy in hypertensive patients with unilateral or bilateral renal-artery stenosis.^{1 47} Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic.^{1 47}

Hyperkalemia

Possible hyperkalemia, especially in patients 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).^{1 47} (See Specific Drugs under Interactions.)

Monitor serum potassium concentration carefully in these patients.^{1 47}

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.^{1 47}

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.⁴⁷

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).^{1 47} (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)

Lactation

Distributed into milk.^{1 47} Caution if used in nursing women.^{47 3 4}

Pediatric Use

Safety and efficacy remain to be fully established in children;^{1 47} however, some experts have recommended dosages for hypertension based on current limited clinical experience.⁶²

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.^{1 47} 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.^{1 47}

Renal Impairment

Deterioration of renal function may occur. (See Renal Effects under Cautions.)^{1 47}

Initial dosage adjustment recommended in patients with renal impairment.¹ (See Renal Impairment under Dosage and Administration.) Safety and efficacy not established in patients with Cl_cr <10 mL/minute.^{1 47}

Quinapril/hydrochlorothiazide fixed combinations are not recommended in patients with severe renal impairment (Cl_cr ≤30 mL/minute or S_cr >3 mg/dL).⁴⁷

Hepatic Impairment

Use with caution in patients with hepatic impairment or progressive liver disease.⁴⁷

Blacks

BP reduction may be smaller in black patients compared with nonblack patients;^{1 24 25 47 48 49} however, no apparent population difference during combined therapy with ACE inhibitor and thiazide diuretic.^{11 24 26 27 28 47} Use in combination with a diuretic.^{11 42}

Higher incidence of angioedema reported with ACE inhibitors in blacks compared with other races.^{1 47 49 50}

Common Adverse Effects

Patients with hypertension: Headache, dizziness, fatigue, cough, nausea, vomiting, abdominal pain.^{1 47} 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.⁴⁷

Patients with CHF: Dizziness, cough, fatigue, nausea, vomiting, chest pain, hypotension, dyspnea, diarrhea, headache, myalgia, rash, back pain, increased serum creatinine concentration, increased BUN.¹

Interactions for Quinapril Hydrochloride

Drugs That Interact with Magnesium

Possible decreased absorption of drugs that interact with magnesium, possibly due to high magnesium content in quinapril-containing preparations.^{1 47}

Specific Drugs

Drug	Interaction	Comments
Atorvastatin	Pharmacokinetic interaction unlikely1
Cimetidine	Pharmacokinetic interaction unlikely1 47
Digoxin	Pharmacokinetic interaction unlikely1 47
Diuretics	Increased hypotensive effect1 47	If possible, discontinue diuretic before initiating quinapril1 47 (See Dosage under Dosage and Administration)
Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)	Enhanced hyperkalemic effect1 47	Use with caution; monitor serum potassium concentrations frequently1 47
Lithium	Increased serum lithium concentrations; possible toxicity1 47	Monitor serum lithium concentrations frequently1 47
Potassium supplements or potassium-containing salt substitutes	Enhanced hyperkalemic effect1 47	Use with caution; monitor serum potassium concentrations frequently1 47
Propranolol	Pharmacokinetic interaction unlikely1 47
Tetracycline	Decreased tetracycline absorption1 47
Warfarin	Pharmacologic interaction unlikely1 47

Quinapril Hydrochloride Pharmacokinetics

Absorption

Bioavailability

About 60% of oral dose is absorbed.^{1 47}

Peak plasma concentrations of quinapril and quinaprilat are achieved within 1 and 2 hours, respectively.^{1 47}

Onset

Following a single oral dose, antihypertensive effects are observed within 1 hour, with peak BP reduction at 2–4 hours.^{1 47}

During chronic therapy, maximum antihypertensive effect is achieved after 1–2 weeks.^{1 47}

Duration

Inhibition of >80% of ACE activity persists for about 24 hours.^{1 47} Inhibition of 75% of the pressor response to angiotensin I persists for about 4 hours.^{1 47}

Food

High-fat meals result in moderate (25–30%) reductions in rate and extent of absorption of quinapril.^{1 47} When quinapril/hydrochlorothiazide combination is administered with high-fat meals, rate of quinapril absorption is reduced by 14%, but extent of absorption is unaffected.⁴⁷

Special Populations

Decreased quinaprilat concentrations in patients with alcoholic cirrhosis.^{1 47}

Distribution

Extent

Quinapril and quinaprilat do not cross the blood-brain barrier.^{1 47}

Crosses the placenta in rats.^{1 47} Distributed into human milk.^{1 47}

Plasma Protein Binding

97% for both quinapril and quinaprilat.^{1 47}

Elimination

Metabolism

Metabolized principally to an active metabolite, quinaprilat (approximately 38% of oral dose).^{1 47}

Elimination Route

Eliminated principally in urine (as metabolites).^{1 47}

Not removed by hemodialysis or peritoneal dialysis.^{1 47}

Half-life

Quinaprilat: Elimination: 2 hours; prolonged terminal phase of 25 hours.^{1 47}

Special Populations

In patients with renal impairment, elimination half-life increases with decreasing Cl_cr.^{1 47}

Decreased elimination of quinaprilat in patients ≥65 years of age.^{1 47}

Stability

Storage

Oral

Tablets

Conventional tablets: 15–30°C.¹ Protect from light.¹

Fixed combination tablets: 20–25°C.⁴⁷

ActionsActions

• 
  

  Prodrug; not pharmacologically active until hydrolyzed in the liver to quinaprilat.^{1 2 3 47}

  
  


• 
  

  Suppresses the renin-angiotensin-aldosterone system.^{1 47}

  
  

Advice to Patients

• 
  

  Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions.^{1 47} 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.^{1 47}

  
  


• 
  

  Importance of reporting signs of infection (e.g., sore throat, fever).^{1 47}

  
  


• 
  

  Risk of hypotension.^{1 47} Importance of informing clinicians promptly if lightheadedness or fainting occurs.^{1 47}

  
  


• 
  

  Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.^{1 47}

  
  


• 
  

  Risks of use during pregnancy.^{1 47 65 66} (See Boxed Warning.)

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).^{1 47}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 47}

  
  


• 
  

  Importance of advising patients of other important precautionary information.^{1 47} (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

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

Quinapril Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	5 mg (of quinapril)*	Accupril (scored)	Pfizer
			Quinapril Hydrochloride Tablets	Ranbaxy
		10 mg (of quinapril)*	Accupril	Pfizer
			Quinapril Hydrochloride Tablets	Ranbaxy
		20 mg (of quinapril)*	Accupril	Pfizer
			Quinapril Hydrochloride Tablets	Ranbaxy
		40 mg (of quinapril)*	Accupril	Pfizer
			Quinapril Hydrochloride Tablets	Ranbaxy

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

Quinapril Hydrochloride Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	10 mg (of quinapril) with Hydrochlorothiazide 12.5 mg*	Accuretic (with povidone; scored)	Pfizer
			Quinapril Hydrochloride and Hydrochlorothiazide Tablets	Mylan
			Quinaretic	Amide
		20 mg (of quinapril) with Hydrochlorothiazide 12.5 mg*	Accuretic (with povidone)	Pfizer
			Quinapril Hydrochloride and Hydrochlorothiazide Tablets	Mylan
			Quinaretic	Amide
		20 mg (of quinapril) with Hydrochlorithiazide 25 mg*	Accuretic (with povidone)	Pfizer
			Quinapril Hydrochloride and Hydrochlorothiazide Tablets	Mylan
			Quinaretic	Amide

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Accupril 10MG Tablets (PFIZER U.S.): 30/$66.99 or 90/$175.98

Accupril 20MG Tablets (PFIZER U.S.): 30/$66.99 or 90/$176.97

Accupril 40MG Tablets (PFIZER U.S.): 30/$66.99 or 90/$176.97

Accupril 5MG Tablets (PFIZER U.S.): 30/$65.97 or 90/$167.84

Accuretic 10-12.5MG Tablets (PFIZER U.S.): 30/$59.99 or 90/$179.98

Accuretic 20-12.5MG Tablets (PFIZER U.S.): 30/$64.2 or 90/$166.24

Accuretic 20-25MG Tablets (PFIZER U.S.): 30/$60.99 or 90/$182.97

Quinapril HCl 10MG Tablets (GREENSTONE): 30/$19.99 or 90/$50.97

Quinapril HCl 20MG Tablets (LUPIN PHARMACEUTICALS): 30/$26.97 or 90/$59.97

Quinapril HCl 40MG Tablets (LUPIN PHARMACEUTICALS): 30/$21.99 or 90/$50.97

Quinapril HCl 5MG Tablets (GREENSTONE): 30/$21.99 or 90/$50.97

Quinapril-Hydrochlorothiazide 10-12.5MG Tablets (MYLAN): 30/$35.99 or 90/$89.97

Quinapril-Hydrochlorothiazide 20-25MG Tablets (MYLAN): 90/$86.99 or 100/$95.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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