Quinapril

Pronunciation

(KWIN a pril)

U.S. Brand Names

Accupril®

Synonyms

Quinapril Hydrochloride

Generic Available

Yes

Canadian Brand Names

Accupril®

Use

Management of hypertension; treatment of congestive heart failure

Use - Unlabeled/Investigational

Treatment of left ventricular dysfunction after myocardial infarction

Pregnancy Risk Factor

C/D (2nd and 3rd trimesters)

Pregnancy Implications

Cranial defects, hypocalvaria/acalvaria, oligohydramnios, persistent anuria following delivery, hypotension, renal defects, renal dysgenesis/dysplasia, renal failure, pulmonary hypoplasia, limb contractures secondary to oligohydramnios, and stillbirth reported. ACE inhibitors should be avoided during pregnancy, particularly in the 2nd and 3rd trimesters.

Lactation

Excretion in breast milk unknown

Contraindications

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

Warnings/Precautions

Anaphylactic reactions can occur. Angioedema can occur at any time during treatment (especially following first dose). Angioedema may involve head and neck (potentially affecting the airway) or the intestine (presenting with abdominal pain). 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. Rare toxicities associated with ACE inhibitors include cholestatic jaundice (which may progress to hepatic necrosis) and neutropenia/agranulocytosis with myeloid hyperplasia. 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). Patients receiving ACE inhibitors have experienced rare life-threatening anaphylactoid reactions during desensitization. Rare hepatic reactions, progressing from cholestatic jaundice to hepatic necrosis, have been reported with ACE inhibitors. Discontinue if marked elevation of hepatic transaminases or jaundice occurs.

Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency. Deterioration in renal function can occur with initiation.

Adverse Reactions

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

1% to 10%:

Cardiovascular: Hypotension (3%), chest pain (2%), first-dose hypotension (up to 3%)

Central nervous system: Dizziness (4% to 8%), headache (2% to 6%), fatigue (3%)

Dermatologic: Rash (1%)

Endocrine & metabolic: Hyperkalemia (2%)

Gastrointestinal: Vomiting/nausea (1% to 2%), diarrhea (2%)

Neuromuscular & skeletal: Myalgias (2% to 5%), back pain (1%)

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%; up to 13% in some studies), dyspnea (2%)

<1% (Limited to important or life-threatening): Anaphylactoid reaction, angioedema, arthralgia, edema, back pain, malaise, viral infection, palpitation, vasodilation, tachycardia, heart failure, hyperkalemia, MI, 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 diaphoresis, 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, hepatic necrosis, neutropenia, and/or agranulocytosis (particularly in patients with collagen-vascular disease or renal impairment) have been associated with many ACE inhibitors.

Overdosage/Toxicology

Mild hypotension has been the primary 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. Treatment is symptom-directed and supportive.

Drug Interactions

Alpha1 blockers: Hypotensive effect increased.

Aspirin: The effects of ACE inhibitors may be blunted by aspirin administration, particularly at higher dosages (see Cardiovascular Considerations) and/or increase 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.

NSAIDs: May attenuate hypertensive efficacy; effect has been seen with captopril and may occur with other ACE inhibitors; monitor blood pressure. May increase risk of adverse renal effects.

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.

Ethanol/Nutrition/Herb Interactions

Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).

Stability

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

Mechanism of Action

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

Pharmacodynamics/Kinetics

Onset of action: 1 hour

Duration: 24 hours

Absorption: Quinapril: 60%

Protein binding: Quinapril: 97%; Quinaprilat: 97%

Metabolism: Rapidly hydrolyzed to quinaprilat, the active metabolite

Half-life elimination: Quinapril: 0.8 hours; Quinaprilat: 3 hours; increases as Clcr decreases

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

Excretion: Urine (50% to 60% primarily as quinaprilat)

Dosage

Adults: Oral:

Hypertension: Initial: 10-20 mg once daily, adjust according to blood pressure response at peak and trough blood levels; initial dose may be reduced to 5 mg in patients receiving diuretic therapy if the diuretic is continued; usual dose range (JNC 7): 10-40 mg once daily

Congestive heart failure or post-MI: Initial: 5 mg once daily, titrated at weekly intervals to 20-40 mg daily in 2 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: Lower initial doses should be used; after initial dose (if tolerated), administer initial dose twice daily; may be increased at weekly intervals to optimal response:

Hypertension: Initial:

Clcr >60 mL/minute: Administer 10 mg/day

Clcr 30-60 mL/minute: Administer 5 mg/day

Clcr 10-30 mL/minute: Administer 2.5 mg/day

Congestive heart failure: Initial:

Clcr >30 mL/minute: Administer 5 mg/day

Clcr 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.

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take as directed; do not alter dose or discontinue without consulting prescriber. Take first dose at bedtime or when sitting down (hypotension may occur). This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. May cause increased cough (if persistent or bothersome, contact prescriber); postural hypotension (use caution when rising from lying or sitting position or climbing stairs); headache (consult prescriber for approved analgesic); dizziness (use caution when driving or engaging in tasks that require alertness until response to drug is known); nausea or vomiting (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); or muscle or back pain (consult prescriber for approved analgesic). Immediately report swelling of face, mouth, lips, tongue or throat; chest pain or respiratory difficulty. Report persistent cough; persistent pain in muscles, joints, or back; skin rash; or other persistent adverse reactions. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. This drug should not be used in the 2nd or 3rd trimester of pregnancy. Consult prescriber for appropriate contraceptive measures if necessary. Consult prescriber if breast-feeding.

Anesthesia and Critical Care Concerns/Other Considerations

ACE inhibitors decrease morbidity and mortality in patients with asymptomatic and symptomatic left ventricular dysfunction. ACE inhibitors are also indicated in patients postmyocardial infarction in whom left ventricular ejection fraction is <40%.

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. To prevent this, discontinue diuretics 2-3 days prior to initiating quinapril; may restart diuretics if blood pressure is not controlled by quinapril alone. 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.

Cardiovascular Considerations

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 inhibitors decrease morbidity and mortality in patients with asymptomatic and symptomatic left ventricular dysfunction. In this situation, they decrease hospitalizations for, and retard progression to, congestive heart failure. According to 2004 ACC/AHA STEMI guidelines, an ACE inhibitor should be administered orally within the first 24 hours of STEMI to patients with anterior infarction, pulmonary congestion or LVEF <0.4, in the absence of hypotension or known contraindications to that class of medicines. In the emergency management of complicated STEMI, a short-acting ACEI (eg, captopril 1-6.25 mg) may be added once the patient's systolic blood pressure is >100 mm Hg and not <30 mm Hg below baseline. When used in patients with heart failure, the target dose of 20 mg twice a day should be achieved, if possible. Lower daily doses of ACE inhibitors have not demonstrated the same cardioprotective effects. ACE inhibitors have renal protective effects in patients with proteinuria and possibly cardioprotective effects in high-risk patients.

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. Concomitant NSAID therapy may attenuate blood pressure control; use of NSAIDs should be avoided or limited, with monitoring of blood pressure control. In the setting of heart failure, NSAID use may be associated with an increased risk for fluid accumulation and edema. 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.

In the treatment of unstable angina/non-ST-segment elevation MI, ACE inhibitors are recommended when hypertension persists despite treatment with nitroglycerin and a beta-blocker in patients with LV systolic dysfunction or CHF and in ischemic patients with diabetes (Class I). ACE inhibitors are also recommended for all post-ACS individuals (Class IIa).

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

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

Mental Health: Effects on Psychiatric Treatment

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

Dosage Forms

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

References

Antman EM, Anbe SC, Alpert JS, et al, "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction)," Circulation, 2004, 110:588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed October 26, 2004.

Braunwald E, Antman EM, Beasley JW, et al, "ACC/AHA 2002 Guideline Update for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina)," J Am Coll Cardiol , 2002, 40(7):1366-74. Available at: http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm. Accessed May 20, 2003.

Chase MP, Fiarman GS, Scholz FJ, et al, "Angioedema of the Small Bowel Due to an Angiotensin-Converting Enzyme Inhibitor," J Clin Gastroenterol , 2000, 31(3):254-7.

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report," JAMA , 2003, 289(19):2560-71.

Conlin P, Moore T, Swartz S, et al, "Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients," Hypertension , 2000, 36(3):461-5.

"Consensus Recommendations for the Management of Chronic Heart Failure. On Behalf of the Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure," Am J Cardiol , 1999, 83(2A):1A-38A.

"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)," Circulation , 1995, 92(9):2764-84.

Hunt SA, Baker DW, Chin MH, et al, "ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure)," J Am Coll Cardiol , 2001, 38(7):2101-13.

"K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Kidney Disease Outcome Quality Initiative," Am J Kidney Dis , 2002, 39(2 Suppl 2):1-246. Available at: http://www.kidney.org/professionals/doqi/kdoqi/toc.htm. Accessed August 1, 2003.

Packer M, Poole-Wilson PA, Armstrong PW, et al, "Comparative Effects of Low and High Doses of the Angiotensin-Converting Enzyme Inhibitor, Lisinopril, on Morbidity and Mortality in Chronic Heart Failure," Circulation , 1999, 100(23):2312-8.

Pfeffer MA, Greaves SC, Arnold JM, et al, "Early Versus Delayed Angiotensin-Converting Enzyme Inhibition Therapy in Acute Myocardial Infarction. The Healing and Early Afterload Reducing Therapy Trial," Circulation , 1997, 95(12):2643-51.

Smoger SH and Sayed MA, "Simultaneous Mucosal and Small Bowel Angioedema Due to Captopril," South Med J , 1998, 91(11):1060-3.

International Brand Names

Accupril® (AR, AU, BE, BR); Accupril™ (CA); Accupril® (CL, CO, CR, GT, HK, HN, ID, LU, NZ, PA, SG, SV, TH, ZA); Accuprin® (IT); Accupro® (AT, CH, CZ, DE, DK, FI, GB, HU, IE, PL, RO, RU, SE); Accuzide® (HU); Acequin® (IT); Acuitel® (FR, TR); Acuprel® (ES); Acupril® (CL, MX, NL, PT); Asig® (AU); Ectren® (ES); Hemokvin® (YU); Korec® (FR); Lidaltrin® (ES); Quinapril Heumann® (DE); Quinapril MK® (CO); Quinapril STADA® (DE); Quinaten® (CO); Quinazide® (IT); Quinazil® (IT); Vasocor® (PT)

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