ACUILIX

Quinapril is the ethyl ester prodrug of the non-sulfhydryl angiotensin converting enzyme inhibitor quinaprilat. 6, 7 It is used to treat hypertension and heart failure. 6, 7 ACE inhibitors are commonly used as a first line therapy in the treatment of hypertension, along with thiazide diuretics or beta blockers.

Quinapril was granted

FDA approval on 19 November 1991.

A combination tablet with hydrochlorothiazide was also approved on 28 December 1999.

Quinapril is indicated for the treatment of hypertension and as an adjunct therapy in the treatment of heart failure.

Quinapril in combination with hydrochlorothiazide is indicated for the treatment of hypertension.

Quinapril is a prodrug of an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension or adjunct in the treatment of heart failure. 1, 2, 6 Quinapril has a wide therapeutic window and a long duration of action as it is given in doses of 10-80 mg once daily.

Quinapril if 50-80% bioavailable.

Quinapril has a

T max of <1 hour, 6 while quinaprilat has a T max of 2.5h.

C max of quinaprilat is highly variable but reaches 1526ng/mL with an AUC of 2443ng*h/mL in healthy males given a 10 mg dose.

A high fat meal reduces the absorption of quinapril by 25-30%.

The mean volume of distribution of quinaprilat is 13.9 L.

Quinapril is de-esterified to the active quinaprilat or dehydrated to form the inactive PD109488. 1, 3 PD109488 can undergo O-deethylation to form another inactive metabolite, PD113413. 1, 3 Hover over products below to view reaction partners Quinapril Quinaprilat Quinapril Metabolite PD109488 Quinapril Metabolite PD113413.

Quinaprilat is up to 96% eliminated in the urine.

The eliminated metabolites

PD109488 and PD113413 account for approximately 6% of a dose of quinapril each. 1, 3 A small fraction of the dose recovered in the urine is accounted for by unmetabolized quinapril.

The active metabolite quinaprilat has an elimination half life of 2.3 hours. 1, 6.

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The oral

LD in rats is 3541 mg/kg and in mice is 1739 mg/kg.

Patients experiencing an overdose may present with symptoms of severe hypotension. 6, 7 Due to the extensive protein binding of quinapril and the active metabolite quinaprilat, hemodialysis is not expected to remove the drug from circulation. 6, 7 Treat patients with symptomatic and supportive measures, including normal saline infusions to restore normal blood pressure. 6, 7.

• 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.

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 within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor." Do not co-administer quinapril tablets with aliskiren in patients with diabetes.

The recommended initial dosage of quinapril in patients not on diuretics is 10 or 20 mg once daily.

Dosage should be adjusted according to blood pressure response measured at peak (2–6 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 40–80 mg and divided doses give a somewhat greater effect at the end of the dosing interval.

If blood pressure is not adequately controlled with quinapril 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.

To reduce the likelihood of hypotension, the diuretic should, if possible, be discontinued to 3 days prior to beginning therapy with quinapril See WARNINGS.

Then, if blood pressure is not controlled with quinapril alone, diuretic therapy should be resumed.

If the diuretic cannot be discontinued, an initial dose of 5 mg quinapril 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.

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/min 10 mg 30–60 mL/min 5 mg 10–30 mL/min 2.5 mg <10 mL/min Insufficient data for dosage recommendation Patients should subsequently have their dosage titrated (as described above) to the optimal response.

Elderly (≥65 years): The recommended initial dosage of quinapril in elderly patients is 10 mg given once daily followed by titration (as described above) to the optimal response.

Quinapril is indicated as adjunctive therapy when added to conventional therapy including diuretics and/or digitalis.

The recommended starting dose is 5 mg twice daily.

This dose may improve symptoms of heart failure, but increases in exercise duration have generally required higher doses.

Therefore, if the initial dosage of quinapril is well tolerated, patients should then be titrated at weekly intervals until an effective dose, usually to 40 mg daily given in two equally divided doses, is reached or undesirable hypotension, orthostatis, or azotemia See WARNINGS prohibit reaching this dose.

Following the initial dose of quinapril, the patient should be observed under medical supervision for at least two hours for the presence of hypotension or orthostatis and, if present, until blood pressure stabilizes.

The appearance of hypotension, orthostatis, or azotemia early in dose titration should not preclude further careful dose titration.

Consideration should be given to reducing the dose of concomitant diuretics.

DOSE ADJUSTMENTS IN PATIENTS WITH HEART FAILURE AND RENAL IMPAIRMENT OR HYPONATREMIA Pharmacokinetic data indicate that quinapril elimination is dependent on level of renal function.

In patients with heart failure and renal impairment, the recommended initial dose of quinapril is 5 mg in patients with a creatinine clearance above 30 mL/min and 2.5 mg in patients with a creatinine clearance of to 30 mL/min. There is insufficient data for dosage recommendation in patients with a creatinine clearance less than 10 mL/min See DOSAGE AND ADMINISTRATION, Heart Failure, WARNINGS, and PRECAUTIONS, Drug Interactions.

If the initial dose is well tolerated, quinapril may be administered 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.

Tablets, USP are supplied as follows: 10-mg tablets: Pink, round film-coated tablets, debossed “HH” on one side and “310” on the other side.

NDC 71205-484-30 Bottles of 30 tablets NDC 71205-484-60 Bottles of 60 tablets NDC 71205-484-90 Bottles of 90 tablets Dispense in well-closed containers as defined in the USP.

Store at 20°C to 25°C (68°F to 77°F); excursion permitted between 15°C and 30°C (59ºF and 86ºF) .

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