No

Angiotensin-Converting Enzyme (ACE) Inhibitors

Management of hypertension; treatment of congestive heart failure, left ventricular dysfunction after myocardial infarction

C/D (2nd and 3rd trimesters)

Hypersensitivity to quinapril or any component; angioedema related to previous treatment with an ACE inhibitor; bilateral renal artery stenosis; primary hyperaldosteronism; patients with idiopathic or hereditary angioedema; pregnancy (2nd and 3rd trimesters)

Anaphylactic reactions can occur. Angioedema can occur at any time during treatment (especially following first dose). Careful blood pressure monitoring with first dose (hypotension can occur especially in volume depleted patients). Dosage adjustment needed in renal impairment. Use with caution in hypovolemia; collagen vascular diseases; valvular stenosis (particularly aortic stenosis); hyperkalemia; or before, during, or immediately after anesthesia. Avoid rapid dosage escalation, which may lead to renal insufficiency. Neutropenia/agranulocytosis with myeloid hyperplasia can rarely occur. If patient has renal impairment, a baseline WBC with differential and serum creatinine should be evaluated and monitored closely during the first 3 months of therapy. Hypersensitivity reactions may be seen during hemodialysis with high-flux dialysis membranes (eg, AN69). Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency. Deterioration in renal function can occur with initiation.

Note: Frequency ranges include data from hypertension and heart failure trials. Higher rates of adverse reactions have generally been noted in patients with congestive heart failure. However, the frequency of adverse effects associated with placebo is also increased in this population.

Cardiovascular: Hypotension (2.9%), chest pain (2.4%), first-dose hypotension (up to 2.5%)

Central nervous system: Dizziness (3.9 to 7.7%), headache (1.7% to 5.6%), fatigue (2.6%)

Dermatologic: Rash (1.2%)

Endocrine and metabolic: Hyperkalemia (2%)

Gastrointestinal: Vomiting/nausea (1.4% to 2.4%), diarrhea (1.7%)

Neuromuscular and Skeletal: Myalgias (1.5% to 5%), back pain (1.2%)

Renal: Increased BUN/serum creatinine (2% - transient elevations may occur with a higher frequency), worsening of renal function (in patients with bilateral renal artery stenosis or hypovolemia)

Respiratory: Upper respiratory symptoms, cough (2% to 4.3%; up to 13% in some studies), dyspnea (1.9%)

<1% (Limited to important or life-threatening symptoms): Angioedema, back pain, malaise, viral infection, palpitation, vasodilation, tachycardia, heart failure, hyperkalemia, myocardial infarction, cerebrovascular accident, hypertensive crisis, angina, orthostatic hypotension, arrhythmia, shock, hemolytic anemia, xerostomia, constipation, gastrointestinal hemorrhage, pancreatitis, abnormal liver function tests, somnolence, vertigo, syncope, nervousness, depression, insomnia, paresthesia, alopecia, increased sweating, pemphigus, pruritus, exfoliative dermatitis, photosensitivity, dermatopolymyositis, impotence, acute renal failure, eosinophilic pneumonitis, amblyopia, pharyngitis, agranulocytosis, hepatitis, thrombocytopenia.

A syndrome which may include fever, myalgia, arthralgia, interstitial nephritis, vasculitis, rash, eosinophilia and positive ANA, and elevated ESR has been reported with ACE inhibitors. In addition, pancreatitis and agranulocytosis (particularly in patients with collagen-vascular disease or renal impairment) have been associated with many ACE inhibitors.

Mild hypotension has been the only toxic effect seen with acute overdose. Bradycardia may also occur; hyperkalemia occurs even with therapeutic doses, especially in patients with renal insufficiency and those taking NSAIDs.

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning.

Alpha₁ blockers: Hypotensive effect increased.

Aspirin and NSAIDs may decrease ACE inhibitor efficacy and/or increase risk of adverse renal effects.

Diuretics: Hypovolemia due to diuretics may precipitate acute hypotensive events or acute renal failure.

Insulin: Risk of hypoglycemia may be increased.

Lithium: Risk of lithium toxicity may be increased; monitor lithium levels, especially the first 4 weeks of therapy.

Mercaptopurine: Risk of neutropenia may be increased.

Potassium-sparing diuretics (amiloride, spironolactone, triamterene): Increased risk of hyperkalemia.

Potassium supplements may increase the risk of hyperkalemia.

Quinolones: Absorption may be decreased by quinapril; separate administration by at least 2-4 hours.

Tetracyclines: Absorption may be reduced by quinapril; separate administration by at least 2-4 hours.

Trimethoprim (high dose) may increase the risk of hyperkalemia.

Store at room temperature; unstable in aqueous solutions; to prepare solution for oral administration, mix prior to administration and use within 10 minutes

Competitive inhibitor of angiotensin-converting enzyme (ACE); prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion; a CNS mechanism may also be involved in hypotensive effect as angiotensin II increases adrenergic outflow from CNS; vasoactive kallikreins may be decreased in conversion to active hormones by ACE inhibitors, thus reducing blood pressure

Onset of action: 1 hour

Duration: 24 hours

Metabolism: Rapidly hydrolyzed to quinaprilat, the active metabolite

Half-life, elimination: Quinapril: 0.8 hours; Quinaprilat: 2 hours

Time to peak serum concentration: Quinapril: 1 hour; Quinaprilat: ~2 hours

Elimination: 50% to 60% of quinapril excreted in urine primarily as quinaprilat

Adults: Oral: Initial: 10 mg once daily, adjust according to blood pressure response at peak and trough blood levels; in general, the normal dosage range is 20-80 mg/day for hypertension and 20-40 mg/day for edema in single or divided doses.

Elderly: Initial: 2.5-5 mg/day; increase dosage at increments of 2.5-5 mg at 1- to 2-week intervals.

Dosing adjustment in renal impairment:

Cl_cr >60 mL/minute: Administer 10 mg/day.

Cl_cr 30-60 mL/minute: Administer 5 mg/day.

Cl_cr 10-30 mL/minute: Administer 2.5 mg/day.

Dosing comments in hepatic impairment: In patients with alcoholic cirrhosis, hydrolysis of quinapril to quinaprilat is impaired; however, the subsequent elimination of quinaprilat is unaltered.

There is some evidence that quinapril may have effects on improving endothelial function in patients with hypertension. The implications of this effect in terms of cardiovascular outcomes, however, has not been established.

ACE-inhibitor therapy may elicit rapid increases in potassium and creatinine, especially when used in patients with bilateral renal artery stenosis. When ACE inhibition is introduced in patients with pre-existing diuretic therapy who are hypovolemic, the ACE inhibitor may induce acute hypotension. In those patients experiencing cough on an ACE inhibitor, the ACE inhibitor may be discontinued and, if necessary, angiotensin-receptor blocker therapy instituted. Because of the potent teratogenic effects of ACE inhibitors, these drugs should be avoided, if possible, when treating women of childbearing potential not on effective birth control measures.

May cause dizziness or drowsiness; may rarely cause insomnia or depression

May cause neutropenia; use caution with clozapine and carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels

No information available to require special precautions

No effects or complications reported

Take exactly as directed; do not discontinue without consulting prescriber. Take first dose at bedtime. Take all doses on an empty stomach (30 minutes before or 2 hours after meals). This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. May cause dizziness, fainting, lightheadedness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); postural hypotension (use caution when rising from lying or sitting position or climbing stairs); nausea, vomiting, altered taste, abdominal pain, dry mouth, or transient loss of appetite (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help) - report if these persist. Report chest pain or palpitations; mouth sores; fever or chills; swelling of extremities; skin rash; numbness, tingling, or pain in muscles; difficulty in breathing or unusual cough; or other persistent adverse reactions. Pregnancy/breast-feeding precautions: Do not get pregnant; use appropriate contraceptive measures. Consult prescriber if breast-feeding.

May cause depression in some patients; discontinue if angioedema of the face, extremities, lips, tongue, or glottis occurs; watch for hypotensive effects within 1-3 hours of first dose or new higher dose

Tablet, as hydrochloride: 5 mg, 10 mg, 20 mg, 40 mg

Alcocer L, Novoa G, and Sotres D, "Quinapril in the Treatment of Hypertension in Primary Care Centers," Clin Ther, 1993, 15(6):1021-30.

Herings RM, deBoer A, Stricker BH, et al, "Hypoglycaemia Associated With Use of Inhibitors of Angiotensin Converting Enzyme," Lancet, 1995, 345(8959):1195-8.

Konstam MA, Drakup K, Baker DW, et al, "Heart Failure: Evaluation and Care of Patients With Left Ventricular Systolic Dysfunction," Clinical Practice Guideline No 11, Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services, 1994.

Lewis EJ, Hunsicker LG, Bain RP, et al, "The Effect of Angiotensin-Converting Enzyme Inhibition on Diabetic Nephropathy," N Engl J Med, 1993, 329(20):1456-62.

McAreavey D and Robertson JIS, "Angiotensin Converting Enzyme Inhibitors and Moderate Hypertension," Drugs, 1990, 40(3):326-45.

Wadworth AN and Brogden RN, "Quinapril: A Review of Its Pharmacological Properties and Therapeutic Efficacy in Cardiovascular Disorders," Drugs, 1991, 41(3):378-99.

Williams JF, Bristow MR, Fowler MB, et al, "Guidelines for the Evaluation and Management of Heart Failure: Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure)," J Am Coll Cardiol, 1995, 26:1376-8.

Woo OF, "Captopril and Related Drugs," Poisoning and Drug Overdose, 2nd ed, Olson KR, ed, East Norwalk, CT: Appleton and Lange, 1994, 117-8.