Quinapril Hydrochloride (4 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- ACCUPRIL
- ACCURETIC
- QUINAPRIL HYDROCHLORIDE
- QUINAPRIL HYDROCHLORIDE AND HYDROCHLOROTHIAZIDE
Boxed Warning
When pregnancy is detected, discontinue quinapril hydrochloride as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. See WARNINGS: Fetal Toxicity
Indications and Usage
Hypertension Quinapril tablets, USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with quinapril tablets, USP. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varyin
Dosage and Administration
Hypertension Monotherapy The recommended initial dosage of quinapril tablets in patients not on diuretics is 10 or 20 mg once daily. Dosage should be adjusted according to blood pressure response measured at peak (2 to 6 hours after dosing) and trough (predosing). Generally, dosage adjustments should be made at intervals of at least 2 weeks. Most patients have required dosages of 20, 40, or 80 mg/day, given as a single dose or in two equally divided doses. In some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval. In such patients an increase in dosage or twice daily administration may be warranted. In general, doses of 40 to 80 mg and divided doses give a somewhat greater effect at the end of the dosing interval. Concomitant Diuretics If blood pressure is not adequately controlled with quinapril tablets monotherapy, a diuretic may be added. In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally can occur following the initial dose of quinapril tablets. To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued 2 to 3 days prior to beginning therapy with quinapril tablets (see WARNINGS ). Then, if blood pressure is not controlled with quinapril tablets alone, diuretic therapy should be resumed. If the diuretic cannot be discontinued, an initial dose of 5 mg quinapril tablets should be used with careful medical supervision for several hours and until blood pressure has stabilized. The dosage should subsequently be titrated (as described above) to the optimal response (see WARNINGS, PRECAUTIONS, and Drug Interactions ). Renal Impairment Kinetic data indicate that the apparent elimination half-life of quinaprilat increases as creatinine clearance decreases. Recommended starting doses, based on clinical and pharmacokinetic data from patients with renal impairment, are as follows: Creatinine Clearance Maximum RecommendedInitial Dose >60 mL/
Contraindications
Quinapril tablets are contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an ACE inhibitor. Quinapril tablets are contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer quinapril tablets are within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor (see WARNINGS and PRECAUTIONS ). Do not co-administer quinapril tablets with aliskiren in patients with diabetes.
Adverse Reactions
Hypertension Quinapril hydrochloride has been evaluated for safety in 4960 subjects and patients. Of these, 3203 patients, including 655 elderly patients, participated in controlled clinical trials. Quinapril hydrochloride has been evaluated for long-term safety in over 1400 patients treated for 1 year or more. Adverse experiences were usually mild and transient. In placebo-controlled trials, discontinuation of therapy because of adverse events was required in 4.7% of patients with hypertension. Adverse experiences probably or possibly related to therapy or of unknown relationship to therapy occurring in 1% or more of the 1563 patients in placebo-controlled hypertension trials who were treated with quinapril hydrochloride are shown below. Adverse Events in Placebo-Controlled Trials Quinapril Hydrochloride (N=1563) Incidence (Discontinuance) Placebo (N=579) Incidence (Discontinuance) Headache 5.6 (0.7) 10.9 (0.7) Dizziness 3.9 (0.8) 2.6 (0.2) Fatigue 2.6 (0.3) 1 Coughing 2 (0.5) 0 Nausea and/or Vomiting 1.4 (0.3) 1.9 (0.2) Abdominal Pain 1 (0.2) 0.7 Heart Failure Quinapril hydrochloride has been evaluated for safety in 1222 quinapril hydrochloride treated patients. Of these, 632 patients participated in controlled clinical trials. In placebo-controlled trials, discontinuation of therapy because of adverse events was required in 6.8% of patients with congestive heart failure. Adverse experiences probably or possibly related or of unknown relationship to therapy occurring in 1% or more of the 585 patients in placebo-controlled congestive heart failure trials who were treated with quinapril hydrochloride are shown below. Quinapril Hydrochloride (N=585) Incidence (Discontinuance) Placebo (N=295) Incidence (Discontinuance) Dizziness 7.7 (0.7) 5.1 (1) Coughing 4.3 (0.3) 1.4 Fatigue 2.6 (0.2) 1.4 Nausea and/or Vomiting 2.4 (0.2) 0.7 Chest Pain 2.4 1 Hypotension 2.9 (0.5) 1 Dyspnea 1.9 (0.2) 2 Diarrhea 1.7 1 Headache 1.7 1 (0.3) Myalgia 1.5 2 Rash 1.4 (0.2) 1 Back Pain 1.2 0
Drug Interactions
Concomitant diuretic therapy As with other ACE inhibitors, patients on diuretics, especially those on recently instituted diuretic therapy, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with quinapril hydrochloride. The possibility of hypotensive effects with quinapril hydrochloride may be minimized by either discontinuing the diuretic or cautiously increasing salt intake prior to initiation of treatment with quinapril hydrochloride. If it is not possible to discontinue the diuretic, the starting dose of quinapril should be reduced (see DOSAGE AND ADMINISTRATION ). Agents increasing serum potassium Coadministration of quinapril hydrochloride with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients. Tetracycline and other drugs that interact with magnesium Simultaneous administration of tetracycline with quinapril hydrochloride reduced the absorption of tetracycline by approximately 28% to 37%, possibly due to the high magnesium content in quinapril tablets. This interaction should be considered if coprescribing quinapril hydrochloride and tetracycline or other drugs that interact with magnesium. Lithium Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy. These drugs should be coadministered with caution and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, it may increase the risk of lithium toxicity. Gold Nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy. Non-steroidal anti-inflammatory agents including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) In patients who are elderly, volume-depleted (including those on diuretic therapy), or with
Overdosage
Doses of 1440 to 4280 mg/kg of quinapril cause significant lethality in mice and rats. No specific information is available on the treatment of overdosage with quinapril. The most likely clinical manifestation would be symptoms attributable to severe hypotension. Laboratory determinations of serum levels of quinapril and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of quinapril overdose. No data are available to suggest physiological maneuvers (e.g., maneuvers to change pH of the urine) that might accelerate elimination of quinapril and its metabolites. Hemodialysis and peritoneal dialysis have little effect on the elimination of quinapril and quinaprilat. Angiotensin II could presumably serve as a specific antagonist-antidote in the setting of quinapril overdose, but angiotensin II is essentially unavailable outside of scattered research facilities. Because the hypotensive effect of quinapril is achieved through vasodilation and effective hypovolemia, it is reasonable to treat quinapril overdose by infusion of normal saline solution.