Quinapril Hydrochloride

Pronunciation

Pronunciation: KWIN-a-pril HYE-droe-KLOR-ide
Class: ACE inhibitor

Trade Names

Accupril
- Tablets, oral 5 mg
- Tablets, oral 10 mg
- Tablets, oral 20 mg
- Tablets, oral 40 mg

Pharmacology

Competitively inhibits angiotensin I–converting enzyme, resulting in prevention of angiotensin I conversion to angiotensin II, a potent vasoconstrictor that also stimulates aldosterone release. Clinical consequences are decrease in BP, reduced sodium resorption, and potassium retention.

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Pharmacokinetics

Absorption

The extent of absorption is at least 60%. T max is 1 h (quinapril) and 2 h (quinaprilat). Food decreases rate (25%) and extent of absorption (30%) when administered with a high-fat meal.

Distribution

Protein binding is about 97%.

Metabolism

Deesterified to major active metabolite quinaprilat (approximately 38% of dose).

Elimination

Renal (96% of quinaprilat [IV dose]). The elimination half-life is about 2 h for quinaprilat and half-life prolonged terminal phase is about 25 h.

Onset

Within 1 h.

Peak

2 to 4 h.

Duration

24 h.

Special Populations

Renal Function Impairment

When CrCl decreases, the elimination half-life increases for quinaprilat.

Hepatic Function Impairment

Quinaprilat concentrations are decreased in patients with alcoholic cirrhosis because of impaired deesterification of quinapril.

Elderly

Elimination of quinaprilat is decreased.

Indications and Usage

Treatment of hypertension; adjunctive therapy in the management of heart failure.

Contraindications

Hypersensitivity to any component of the product; history of angioedema related to previous treatment with an ACE inhibitor.

Dosage and Administration

Heart Failure
Adults

PO 5 mg twice daily initially; may increase dose weekly for clinical control, usually 20 to 40 mg daily in 2 equally divided doses.

Renal Function Impairment

Initial dosage is 5 mg daily with CrCl more than 30 mL/min or 2.5 mg daily with CrCl 10 to 30 mL/min. For CrCl less than 10 mL/min, there is insufficient data for dosage recommendations. If well tolerated, the initial dose may be given the following day as a twice-daily regimen. In the absence of excessive hypotension or significant deterioration of renal function, the dose may be increased at weekly intervals based on clinical and hemodynamic response.

Hypertension
Adults

PO 10 or 20 mg once daily initially in patients not on diuretics; adjust dosage at intervals of at least 2 wk. Usual dosage is 20, 40, or 80 mg/day as a single dose or 2 equally divided doses.

Elderly

PO 10 mg every day followed by titration to the optimal response.

Renal Function Impairment

Initial dose varies based on CrCl: more than 60 mL/min, 10 mg daily; 30 to 60 mL/min, 5 mg daily; 10 to 30 mL/min, 2.5 mg daily; less than 10 mL/min, there is insufficient data for dosage recommendation.

Concomitant Therapy

In patients currently treated with a diuretic, discontinue the diuretic, if possible, 2 to 3 days prior to starting quinapril to reduce the likelihood of hypotension. Resume the diuretic if BP is not controlled with quinapril alone.

General Advice

  • Observe heart failure patients for at least 2 h for the presence of hypotension or orthostasis following initial dose.
  • May administer with other antihypertensive agents.

Storage/Stability

Store between 59° and 89°F. Protect from light.

Drug Interactions

Aldosterone blockers (eg, eplerenone)

The risk of serious hyperkalemia may be increased, resulting in cardiac arrhythmias or arrest. Periodic monitoring of serum potassium concentrations is recommended until the effect of the aldosterone blocker is established. Dose reduction of the aldosterone blocker may be necessary to decrease potassium concentrations.

Aliskiren

The risk of hyperkalemia may be increased, particularly in diabetic patients. In addition, the risk of nonfatal stroke, renal complications, and hypotension may be increased. Coadministration is not recommended in diabetic patients.

Angiotensin II receptor antagonists (eg, losartan)

The risk of hypotension, hyperkalemia, syncope, and changes in renal function (including renal failure) may be increased. Close monitoring of BP, renal function, and electrolytes is warranted.

COX-2 inhibitors (eg, celecoxib), NSAIDs (eg, ibuprofen), salicylates (eg, aspirin)

May reduce hypotensive effects, especially in low-renin or volume-dependent hypertensive patients. Coadministration may result in deterioration of renal function; periodically monitor renal function.

Diuretics (eg, thiazides [eg, hydrochlorothiazide])

Increased risk of hypotension, syncope, and changes in renal function (including renal failure). Close monitoring of BP and renal function is warranted.

Food

Food (especially fat) reduces bioavailability of quinapril.

Gold salts (eg, sodium aurothiomalate)

During coadministration, nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) have been reported rarely with injectable gold.

Hypoglycemic agents (eg, insulin, oral hypoglycemic agents)

Coadministration may cause an increased blood glucose–lowering effect with risk of hypoglycemia. Monitor symptoms of hypoglycemia during initiation of therapy.

Lithium

May cause increased lithium levels and symptoms of lithium toxicity. Use with caution and frequently monitor lithium concentrations.

mTOR inhibitors (eg, everolimus, temsirolimus)

The risk of angioedema may be increased.

Potassium supplements and potassium-sparing diuretics (eg, spironolactone)

Coadministration may result in elevated serum potassium concentrations. If concomitant use is indicated, use with caution; monitor potassium concentrations and renal function frequently.

Tetracycline and other drugs that interact with magnesium

Decreased tetracycline absorption, possibly due to the magnesium content of quinapril. Consider this interaction when given concurrently.

Trimethoprim

Hyperkalemia, possibly with cardiac arrhythmias or cardiac arrest, may occur as a result of reduced aldosterone activity by both agents. Close monitoring of potassium concentrations and clinical response is warranted.

Adverse Reactions

Cardiovascular

Hypotension (3%); palpitation, syncope, tachycardia, vasodilation (1% or less).

CNS

Dizziness (8%); headache (6%); fatigue (3%); depression, insomnia, malaise, nervousness, paresthesia, somnolence, vertigo (1% or less).

Dermatologic

Pruritus, rash (1%); alopecia, increased sweating, pemphigus (1% or less).

GI

Diarrhea, nausea, vomiting (2%); abdominal pain; constipation, dry mouth or throat, flatulence (1% or less).

Genitourinary

Impotence, UTI (1% or less).

Hematologic

Agranulocytosis; neutropenia.

Lab Tests

BUN (11%); serum creatinine (8%).

Metabolic

Hyperkalemia (2%).

Musculoskeletal

Myalgia (2%); arthralgia, back pain (1% or less).

Respiratory

Cough (4%); dyspnea (2%); pharyngitis (1% or less).

Miscellaneous

Chest pain (2%); amblyopia, edema, viral infections (1% or less); anaphylactoid reactions.

Precautions

Warnings

Fetal toxicity

When pregnancy is detected, discontinue quinapril as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.


Monitor

Periodically monitor BP. Monitor renal function during the first few weeks of therapy in hypertensive patients with unilateral or bilateral renal artery stenosis. Evaluation of elderly patients and patients with hypertension or heart failure should always include assessment of renal function.


Pregnancy

Category D . Discontinue drug as soon as pregnancy is detected. Closely observe infants with history of in utero exposure.

Lactation

Excreted in breast-milk.

Children

Safety and efficacy not established.

Elderly

Use with caution; reduce dose if needed.

Hypersensitivity

Anaphylactoid reactions have occurred in patients taking ACE inhibitors undergoing desensitization, and in patients being dialyzed with high-flux membranes or undergoing LDL apheresis with dextran sulfate absorption.

Renal Function

In patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or BUN may occur. Dosage should be reduced to compensate for reduced drug elimination.

Hepatic Function

Use drug with caution; dosage reduction may be necessary because of impaired metabolism.

Angioedema

Angioedema involving the extremities, face, lips, tongue, glottis, or larynx may occur. Intestinal angioedema has also been reported. Risk of angioedema may be increased in patients with a history of angioedema unrelated to ACE inhibitor therapy.

Cough

A persistent nonproductive cough has been reported with all ACE inhibitors.

Hepatic failure

Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and sometimes death.

Hyperkalemia

Elevations in serum potassium have been observed; risk factors include renal insufficiency, diabetes, and concomitant use of potassium supplements or drugs known to increase serum potassium.

Hypotension/First-dose effect

Significant decreases in BP may occur after first dose, especially in severely salt- or volume-depleted patients (eg, patients on aggressive diuretic therapy) or in those with heart failure, hyponatremia, or on renal dialysis.

Neutropenia and agranulocytosis

Has occurred with other ACE inhibitors; risk appears greater with renal impairment, especially if they also have a collagen vascular disease.

Renal effects

Use with caution in patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe CHF); use may be associated with oliguria, progressive azotemia, acute renal failure, and/or death.

Surgery/Anesthesia

Risk of hypotension may be increased; if hypotension occurs, it can be corrected by volume expansion.

Overdosage

Symptoms

Severe hypotension.

Patient Information

  • Advise patients to take prescribed dose without regard to meals but to take with food if stomach upset occurs.
  • Advise patients to try to take each dose at about the same time each day
  • Inform hypertensive patients that drug controls, but does not cure, hypertension and to continue taking drug as prescribed even when BP is not elevated.
  • Instruct patients in BP and pulse measurement skills.
  • Advise patients to monitor and record BP and pulse at home and to inform their health care provider if abnormal measurements are noted. Also advise patients to take record of BP and pulse to each follow-up visit.
  • Caution patients to avoid sudden position changes to prevent orthostatic hypotension.
  • Instruct patients to lie or sit down if experiencing dizziness or light-headedness when standing.
  • Emphasize to hypertensive or heart failure patients the importance of the following other modalities that can help control BP and heart failure symptoms: weight control, progressive exercise program, smoking cessation, and moderate intake of alcohol and salt.
  • Advise heart failure patients to weigh themselves daily, keep a record of daily weights, and notify their health care provider if rapid weight gain (eg, 5 lb in 1 wk) is noted, or if edema or shortness of breath worsen.
  • Caution patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to excessive fall in BP, resulting in light-headedness or fainting.
  • Advise patients that medication may cause dizziness or light-headedness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Instruct patients to stop taking drug and immediately report any of the following symptoms to their health care provider: sore throat, fever, swelling of the hands or feet, irregular heartbeat, chest pains, fainting, swelling of the face, lips, eyelids, or tongue, difficulty breathing.
  • Instruct patients to inform their health care provider if a persistent cough develops while taking this medication.
  • Caution patients not to take any prescription or OTC medications, potassium-containing salt substitutes, potassium supplements, or dietary supplements unless advised by their health care provider.
  • Inform female patients of childbearing age about the consequences of exposure to quinapril during pregnancy. Tell patients to report pregnancies to their health care provider as soon as possible.

Copyright © 2009 Wolters Kluwer Health.

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