Quinapril is a nonpeptide, nonsulphydryl inhibitor of angiotensin converting enzyme (ACE), which is used in the treatment of hypertension.

Angiotensin converting enzyme (ACE) is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor angiotensin II. After absorption, quinapril is rapidly de-esterified to quinaprilat (quinapril diacid), its principal active metabolite. Its primary mode of action is to inhibit circulating and tissue ACE, thereby decreasing vasopressor activity and aldosterone secretion. Although the decrease in aldosterone is small, it results in a small increase in serum K(see Precautions). Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity. Although quinapril had antihypertensive activity in all races studied, black hypertensive patients (usually a low-renin hypertensive population) had a smaller average response to ACE inhibitor monotherapy than nonblack patients.

ACE is identical to kininase II. Thus, quinapril may interfere with the degradation of bradykinin, a potent peptide vasodilator. However, it is not known whether this system contributes to the therapeutic effects of quinapril.

The antihypertensive effect of quinapril outlasts its inhibitory effect on circulating ACE in animal studies. Tissue ACE inhibition more closely correlates with the duration of antihypertensive effects and this may be related to enzyme binding characteristics as shown for quinapril on purified ACE from human kidney and heart.

Pharmacokinetics: Following oral administration of quinapril, peak plasma concentrations of quinapril occur within 1 hour. Based on the recovery of quinapril and its metabolites in urine, the extent of absorption is at least 60%. Following absorption, quinapril is de-esterified to its major active metabolite, quinaprilat (quinapril diacid) a potent ACE inhibitor, and to minor inactive metabolites. Quinapril has an apparent half-life in plasma of approximately 1 hour. Peak plasma quinaprilat concentrations occur approximately 2 hours after an oral dose of quinapril. Quinaprilat is eliminated primarily by renal excretion and has an effective accumulation half-life of approximately 3 hours. Quinaprilat has an elimination half-life in plasma of approximately 2 hours with a prolonged terminal phase of 25 hours. Approximately 97% of either quinapril or quinaprilat circulating in plasma is bound to proteins.

Pharmacokinetic studies in patients with end-stage renal disease on chronic hemodialysis or continuous ambulatory peritoneal dialysis indicate that dialysis has little effect on the elimination of quinapril and quinaprilat.

The disposition of quinapril and quinaprilat in patients with renal insufficiency is similar to that in patients with normal renal function until creatinine clearance is 60 mL/minute or less. With creatinine clearance less than 60 mL/minute, peak and trough quinaprilat concentrations increase, apparent half-life increases, and time to steady state may be delayed. The elimination of quinaprilat may be reduced in elderly patients (>65 years) and in those with heart failure; this reduction is attributable to decrease in renal function (see Dosage). Quinaprilat concentrations are reduced in patients with alcoholic cirrhosis due to impaired de-esterification of quinapril.

The rate and extent of quinapril absorption are diminished moderately (approximately 25 to 30%) when quinapril tablets are administered during a high-fat meal. However, no effect on quinapril absorption occurs when taken during a regular meal.

Studies in rats indicate that quinapril and its metabolites do not cross the blood-brain barrier.

Pharmacodynamics: Administration of 10 to 40 mg of quinapril to patients with essential hypertension results in a reduction of both sitting and standing blood pressure with minimal effect on heart rate. Antihypertensive activity commences within 1 hour with peak effects usually achieved by 2 to 4 hours after dosing. Achievement of maximum blood pressure lowering effects may require 2 weeks of therapy in some patients. At the recommended doses, antihypertensive effects are maintained throughout the 24-hour dosing interval in most patients. While the dose response relationship is relatively flat, a dose of 40 mg was somewhat more effective at trough than 10 to 20 mg, and twice daily dosing tended to give a somewhat lower blood pressure than once daily dosing with the same total daily dose. The antihypertensive effect of quinapril was maintained during long-term therapy with no evidence of loss of effectiveness.

Hemodynamic assessments in patients with essential hypertension indicate that blood pressure reduction produced by quinapril is accompanied by a reduction in total peripheral resistance and renal vascular resistance with little or no change in heart rate and cardiac index. There was an increase in renal blood flow which was not significant. Little or no change in glomerular filtration rate or filtration fraction was observed.

When quinapril is given together with thiazide-type diuretics, the antihypertensive effects are approximately additive.

Administration of quinapril to patients with congestive heart failure (CHF) reduces peripheral vascular resistance, systolic and diastolic blood pressure, pulmonary capillary wedge pressure, and increases cardiac output. The onset of effects was observed within 1 hour and maximal effects occurred at 1.25 to 4 hours after administration of quinapril. Peak hemodynamic effects correlated well with peak plasma levels of quinaprilat (1 to 4 hours after administration).

Exercise tolerance was improved with quinapril therapy.

The effect of quinapril on survival in patients with heart failure has not been evaluated.

Therapeutic effects appear to be the same for elderly (>65 years of age) and younger adult patients given the same daily dosages, with no increase in adverse events in elderly patients.

The antihypertensive effect of ACE inhibitors is generally lower in black patients than in non-blacks.

Hypertension: In the treatment of essential hypertension. It is usually administered in association with other drugs, particularly thiazide diuretics.

In using quinapril consideration should be given to the risk of angioedema (see Warnings).

Quinapril should normally be used in those patients in whom treatment with a diuretic or a beta-blocker was found ineffective or has been associated with unacceptable adverse effects. Quinapril can also be tried as an initial agent in those patients in whom use of diuretics and/or beta-blockers is contraindicated or in patients with medical conditions in which these drugs frequently cause serious adverse effects.

The safety and efficacy of quinapril in renovascular hypertension have not been established; therefore, use in this condition is not recommended.

Congestive Heart Failure: In the treatment of congestive heart failure as adjunctive therapy when added to diuretics and/or digitalis glycosides.

Treatment with quinapril should be initiated under close medical supervision.

When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury or even death of the developing fetus. When pregnancy is detected quinapril should be discontinued as soon as possible (see Warnings, Pregnancy and Information for the Patient).

Patients who are hypersensitive to this product, and patients with a history of angioedema related to previous treatment with an ACE inhibitor.

Angioedema: Angioedema has been reported in patients treated with quinapril. Angioedema associated with laryngeal involvement may be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, quinapril should be discontinued immediately, the patient treated appropriately in accordance with accepted medical care, and carefully observed until the swelling disappears. In instances where swelling is confined to the face and lips, the condition generally resolves without treatment, although antihistamines may be useful in relieving symptoms. Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, appropriate therapy (including but not limited to 0.3 to 0.5 mL of s.c. epinephrine solution 1:1 000) should be administered promptly (see Adverse Effects).

The incidence of angioedema during ACE inhibitor therapy has been reported to be higher in black than in non-black patients.

Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor (see Contraindications).

Hypotension: Symptomatic hypotension has occurred after administration of quinapril, usually after the first or second dose or when the dose was increased. It is more likely to occur in patients who are volume depleted by diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting. In patients with ischemic heart or cerebrovascular disease, an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident (see Adverse Effects). Because of the potential fall in blood pressure in these patients, therapy with quinapril should be started under close medical supervision. Such patients should be followed closely for the first weeks of treatment and whenever the dose is increased. In patients with severe congestive heart failure, with or without associated renal insufficiency, excessive hypotension has been observed and may be associated with oliguria and/or progressive azotemia, and rarely with acute renal failure and/or death.

If hypotension occurs, the patient should be placed in supine position and, if necessary, receive an i.v. infusion of 0.9% sodium chloride. A transient hypotensive response is not a contraindication to further doses which usually can be given without difficulty once the blood pressure has increased after volume expansion. However, lower doses of quinapril and/or reduced concomitant diuretic therapy should be considered.

Neutropenia/Agranulocytosis: Agranulocytosis and bone marrow depression have been caused by ACE inhibitors. Agranulocytosis did occur during quinapril treatment in 1 patient with a history of neutropenia during previous captopril therapy. Periodic monitoring of white blood cell counts should be considered, especially in patients with collagen vascular disease and/or renal disease.

Pregnancy: ACE inhibitors can cause fetal and neonatal morbidity and mortality when administered to pregnant women. Several dozen cases have been reported in the world literature. When pregnancy is detected, quinapril should be discontinued as soon as possible.

In rare cases (probably <0.1% of pregnancies) in which no alternative to ACE inhibitor therapy will be found, the mothers should be apprised of the potential hazards to their fetuses. Serial ultrasound examinations should be performed to assess fetal development and well-being and the volume of amniotic fluid.

If oligohydramnios is observed, quinapril should be discontinued unless it is considered life-saving for the mother. A nonstress test (NST), and/or a biophysical profiling (BPP) may be appropriate, depending upon the week of pregnancy. If concerns regarding fetal well-being still persist, a contraction stress testing (CST) should be considered. Patients and physicians should be aware, however, the oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Infants with a history of in utero exposure to ACE inhibitors should be closely observed for hypotension, oliguria and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as a means of reversing hypotension and/or substituting for impaired renal function; however, limited experience with those procedures has not been associated with significant clinical benefit. Hemodialysis and peritoneal dialysis have little effect on the elimination of quinapril and quinaprilat.

Human Data: It is not known whether exposure limited to the first trimester of pregnancy can adversely affect fetal outcome. The use of ACE inhibitors during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation and hypoplastic lung development. Prematurity, intrauterine growth retardation and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to the ACE inhibitor exposure.

Animal Data: No fetotoxic or teratogenic effects were observed in rats at doses as high as 300 mg/kg/day (180 times the maximum daily human dose), despite maternal toxicity at 150 mg/kg/day. Offspring body weights were reduced in rats treated late in gestation and during lactation with doses of 25 mg/kg/day or more. Quinapril was not teratogenic in rabbits; however, maternal and embryo toxicity were seen in some rabbits at 1 mg/kg/day.

No adverse effects on fertility or reproduction were observed in rats at dose levels up to 100 mg/kg/day (60 times the maximum daily human dose).

Renal Impairment: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function have been seen in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, such as patients with bilateral renal artery stenosis, unilateral renal artery stenosis to a solitary kidney, or severe congestive heart failure, treatment with agents that inhibit this system has been associated with oliguria, progressive azotemia, and rarely, acute renal failure and/or death. In susceptible patients, concomitant diuretic use may further increase risk.

Use of quinapril should include appropriate assessment of renal function.

Anaphylactoid Reactions during Membrane Exposure: Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes (e.g.: polyacrylonitrile [PAN]) and treated concomitantly with an ACE inhibitor. Dialysis should be stopped immediately if symptoms such as nausea, abdominal cramps, burning, angioedema, shortness of breath and severe hypotension occur. Symptoms are not relieved by antihistamines. In these patients consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agents.

Anaphylactoid Reactions during LDL Apheresis: Rarely, patients receiving ACE inhibitors during low density lipoprotein apheresis with dextran sulfate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding the ACE inhibitor therapy prior to each apheresis.

Anaphylactoid Reactions during Desensitization: There have been isolated reports of patients experiencing sustained life-threatening anaphylactoid reactions while receiving ACE inhibitors during desensitizing treatment with hymenoptera (bees, wasps) venom. In the same patients, these reactions have been avoided when ACE inhibitors were temporarily withheld for at least 24 hours, but they have reappeared upon inadvertent rechallenge to an ACE inhibitor.

Hyperkalemia and Potassium-Sparing Diuretics: Elevated serum potassium (>5.7 mEq/L) was observed in approximately 2% of patients receiving quinapril. In most cases these were isolated values which resolved despite continued therapy. Hyperkalemia was a cause of discontinuation of therapy in less than 0.1% of hypertensive patients. Risk factors for the development of hyperkalemia may include renal insufficiency, diabetes mellitus, and the concomitant use of agents to treat hypokalemia (see Drug Interactions and Adverse Effects).

Valvular Stenosis: There is concern on theoretical grounds that patients with aortic stenosis might be at particular risk of decreased coronary perfusion when treated with vasodilators because they do not develop as much afterload reduction.

Surgery/Anesthesia: In patients undergoing major surgery or during anesthesia with agents that produce hypotension, quinapril will block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

Patients with Impaired Liver Function: Hepatitis (hepatocellular and/or cholestatic), elevations of liver enzymes and/or serum bilirubin have occurred during therapy with other ACE inhibitors in patients with or without pre-existing liver abnormalities. In most cases the changes were reversed on discontinuation of the drug.

Elevations of liver enzymes and/or serum bilirubin have been reported for quinapril (see Adverse Effects). Should the patient receiving quinapril experience any unexplained symptoms particularly during the first weeks or months of treatment, it is recommended that a full set of liver function tests and any other necessary investigation be carried out. Discontinuation of quinapril should be considered when appropriate.

There are no adequate studies in patients with cirrhosis and/or liver dysfunction. Quinapril should be used with particular caution in patients with pre-existing liver abnormalities. In such patients baseline liver function tests should be obtained before administration of the drug and close monitoring of response and metabolic effects should apply.

Cough: A dry, persistent cough, which usually disappears only after withdrawal or lowering of the dose of quinapril has been reported. Such possibility should be considered as part of the differential diagnosis of the cough.

Lactation: Quinapril is secreted to a limited extent in milk of lactating rats (5% or less of the plasma drug concentration was found in rat milk). It is not known whether quinapril or its metabolites are secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised when quinapril is given to a nursing mother, and in general, nursing should be interrupted.

Children: The safety and effectiveness of quinapril in children have not been established; therefore, use in this age group is not recommended.

Drug Interactions : Concomitant Diuretic Therapy: Patients concomitantly taking ACE inhibitors and diuretics, and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy. The possibility of hypotensive effects after the first dose of quinapril can be minimized by either discontinuing the diuretic or increasing the salt intake (except in patients with heart failure), prior to initiation of treatment with quinapril. If it is not possible to discontinue the diuretic, the starting dose of quinapril should be reduced and the patient should be closely observed for several hours following initial dose and until blood pressure has stabilized (see Warnings and Dosage).

Agents Increasing Serum Potassium: Since quinapril decreases aldosterone production, elevation of serum potassium may occur. Potassium sparing diuretics such as spironolactone, triamterene or amiloride, or potassium supplements should be given only for documented hypokalemia and with caution and frequent monitoring of serum potassium, since they may lead to a significant increase in serum potassium. Salt substitutes which contain potassium should also be used with caution.

Agents Causing Renin Release: The antihypertensive effect of quinapril is augmented by antihypertensive agents that cause renin release (e.g., diuretics).

Agents Affecting Sympathetic Activity: Agents affecting sympathetic activity (e.g., ganglionic blocking agents or adrenergic neuron blocking agents) may be used with caution. Beta-adrenergic blocking drugs add some further antihypertensive effect to quinapril.

Tetracycline: Concomitant administration of tetracycline with quinapril reduced the absorption of tetracycline in healthy volunteers (by 28 to 37%) due to the presence of magnesium carbonate as an excipient in the formulation. This interaction should be considered with concomitant use of quinapril and tetracycline or other drugs which interact with magnesium.

Lithium: As with other drugs which eliminate sodium, the lithium elimination may be reduced. Therefore, the serum lithium levels should be monitored carefully if lithium salts are to be administered.

Other Agents: In single dose pharmacokinetic studies, no important changes in pharmacokinetic parameters were observed when quinapril was used concomitantly with propranolol, hydrochlorothiazide, digoxin or cimetidine. No change in prothrombin time occurred when quinapril and warfarin were given together.

Information for the Patient: Note: As with many other drugs, certain advice to patients being treated with quinapril is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.

Angioedema: Angioedema, including laryngeal edema, may occur especially following the first dose of quinapril. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema, such as swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing. They should immediately stop taking quinapril and consult with their physician.

Hypotension: Patients should be cautioned to report light-headedness, especially during the first few days of quinapril therapy. If actual syncope occurs, the patients should be told to discontinue the drug and consult with their physician.

All patients should be cautioned that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients should be advised to consult with their physician.

Agranulocytosis/Neutropenia: Patients should be told to report promptly to their physician any indication of infection (e.g., sore throat, fever), as this may be a sign of neutropenia.

Impaired Liver Function: Patients should be advised to return to the physician if he/she experiences any symptoms possibly related to liver dysfunction. This would include “viral-like symptoms” in the first weeks to months of therapy (such as fever, malaise, muscle pain, rash or adenopathy which are possible indicators of hypersensitivity reactions), or if abdominal pain, nausea or vomiting, loss of appetite, jaundice, itching or any other unexplained symptoms occur during therapy.

Hyperkalemia: Patients should be told not to use salt substitutes containing potassium without consulting their physician.

Surgery: Patients planning to undergo surgery and/or anesthesia should be told to inform their physician that they are taking an ACE inhibitor.

Pregnancy: Since the use of ACE inhibitors during pregnancy can cause injury and even death of the developing fetus, patients should be advised to report promptly to their physician if they become pregnant.

Hypertension: Quinapril monotherapy has been evaluated for safety in 2 005 hypertensive patients enrolled in placebo-controlled clinical trials. These trials included 313 elderly patients. There was no increase in the incidence of adverse events in elderly patients given the same daily dosages. Quinapril has been evaluated for long-term safety in over 1 100 patients treated for 1 year or more. Adverse events were usually mild and transient in nature.

The most serious adverse event was angioedema (0.1%). Renal insufficiency (1 case), agranulocytosis (1 case) and mild azotemia (2 cases in CHF patients) have been reported. Myocardial infarction and cerebrovascular accident occurred, possibly secondary to excessive hypotension in high risk patients (see Warnings).

The most frequent adverse events in controlled clinical trials were headache (8.1%), dizziness (4.1%), cough (3.2%), fatigue (3.2%), rhinitis (3.2%), nausea and/or vomiting (2.3%), and abdominal pain (2.0%).

Discontinuation of therapy because of adverse events was required in 4.7% of patients treated with quinapril in placebo controlled trials.

Congestive Heart Failure: At least 1 adverse event was experienced by 605 (55%) of the 1 108 patients with congestive heart failure. Five hundred twenty five of these patients were evaluated for safety in controlled clinical trials. The frequencies of adverse events were similar for both sexes as for younger (³65 years) and older (>=65 years) patients.

The most serious nonfatal adverse events/reactions were angioedema (0.1%), chest pain of unknown origin (0.8%), angina pectoris (0.4%), hypotension (0.1%), and impaired renal function. Myocardial infarct and cerebrovascular accident occurred (see Warnings).

The most frequent adverse events in controlled clinical trials were dizziness (11.2%), cough (7.6%), chest pain (6.5%), dyspnea (5.5%), fatigue (5.1%), and nausea/vomiting (5.0%).

Discontinuation due to adverse events in controlled clinical trials was required for 41 (8.0%) of patients. Hypotension (0.8%) and cough (0.8%) were the most common reasons for withdrawal.

Adverse events occurring in ³0.5% of 2 005 hypertensive patients treated with quinapril monotherapy and in 525 patients with congestive heart failure treated with quinapril as adjunctive therapy, in controlled clinical trials, are presented in Table I.

Adverse events occurring in <0.5% of patients with hypertension or congestive heart failure include: Body as a whole: allergy, face edema, chill, weight increase, dehydration.

Cardiovascular: vasodilatation, cerebrovascular accident, heart failure, ventricular tachycardia, atrial flutter.

Digestive: constipation, tongue edema, gastrointestinal hemorrhage, flatulence, anorexia, bloody stools.

Hemic and Lymphatic: anemia, including hemolytic anemia, thrombocytopenia, agranulocytosis.

Nervous: confusion, amnesia, anxiety.

Musculoskeletal: arthritis.

Respiratory: asthma, hoarseness.

Skin and Appendages: dermatitis, photosensitivity reaction, urticaria, eczema, pemphigus, exfoliative dermatitis, Stevens-Johnson syndrome.

Urogenital: dysuria, polyuria, impaired renal function.

Special Senses: tinnitus.

Laboratory Deviations: hematuria, WBC decreased, elevated BUN, hyperglycemia, azotemia.

Clinical Laboratory Test Findings:

Hematology: See Warnings. Hyperkalemia: See Precautions

Creatinine and Blood Urea Nitrogen: Increases (>1.25 times the upper limit of normal) in serum creatinine and blood urea nitrogen were observed in 2% and 2%, respectively, of patients treated with quinapril alone. Increases are more likely to occur in patients receiving concomitant diuretic therapy than in those on quinapril alone. These increases often reversed on continued therapy. In controlled studies of heart failure, increases in blood urea nitrogen and serum creatinine were observed in 11% and 8%, respectively, of patients treated with quinapril. Most often these patients were receiving diuretics with or without digitalis.

Hepatic: Elevations of liver enzymes and/or serum bilirubin have occurred (see Precautions).

Symptoms and Treatment: No data are available regarding overdosage of quinapril in humans. The most likely clinical manifestation would be symptoms attributable to severe hypotension, which should be normally treated by i.v. volume expansion with 0.9% sodium chloride. Hemodialysis and peritoneal dialysis have little effect on the elimination of quinapril and quinaprilat.

Dosage must be individualized.

Hypertension: Initiation of therapy requires consideration of recent antihypertensive drug treatment, the extent of blood pressure elevation and salt restriction. The dosage of other antihypertensive agents being used with quinapril may need to be adjusted.

Monotherapy: The recommended initial dose of quinapril in patients not on diuretics is 10 mg once daily. An initial dose of 20 mg once daily can be considered for patients without advanced age, renal impairment, or concomitant heart failure and who are not volume depleted (see Precautions, Hypotension). Dosage should be adjusted according to blood pressure response, generally at intervals of 2 to 4 weeks. A dose of 40 mg daily should not be exceeded.

In some patients treated once daily, the antihypertensive effect may diminish towards the end of the dosing interval. This can be evaluated by measuring blood pressure just prior to dosing to determine whether satisfactory control is being maintained for 24 hours. If it is not, either twice daily administration with the same total daily dose, or an increase in dose should be considered. If blood pressure is not controlled with quinapril alone, a diuretic may be added. After the addition of a diuretic, it may be possible to reduce the dose of quinapril.

Concomitant Diuretic Therapy: Symptomatic hypotension occasionally may occur following the initial dose of quinapril and is more likely in patients who are currently being treated with a diuretic. The diuretic should, if possible, be discontinued for 2 to 3 days before beginning therapy with quinapril to reduce the likelihood of hypotension (see Warnings). 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.

Dosing Adjustment in Renal Impairment: See Precautions for use in hemodialysis patients.

Patients should subsequently have dosage titrated (as described above) to the optimal response.

Dosage in the Elderly (over 65 years): The recommended initial dosage is 10 mg once daily (depending on renal function), followed by titration (as described above) to the optimal response.

Congestive Heart Failure: Indicated as adjunctive therapy to diuretics, and/or cardiac glycosides. Therapy should be initiated under close medical supervision. Blood pressure and renal function should be monitored, both before and during treatment with quinapril because severe hypotension and, more rarely, consequent renal failure have been reported (see Warnings and Precautions).

Initiation of therapy requires consideration of recent diuretic therapy and the possibility of severe salt/volume depletion. If possible, the dose of diuretic should be reduced before beginning treatment, to reduce the likelihood of hypotension. Serum potassium should also be monitored (see Precautions, Drug Interactions).

The recommended starting dose is 5 mg once daily to be administered under close medical supervision to determine the initial effect on blood pressure. After the initial dose, the patient should be observed for at least 2 hours, or until the pressure has stabilized for at least an additional hour (see Warnings, Hypotension). 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 or after effective management of symptomatic hypotension following initiation of therapy, the dose should be increased gradually to 10 mg once daily, then 20 mg once daily, and to 40 mg per day given in 2 equally divided doses, depending on the patient's response. The maximum daily dose is 40 mg.

The dose titration may be done at weekly intervals, as indicated by the presence of residual signs or symptoms of heart failure.

Renal Impairment or Hyponatremia: Kinetic data indicate that quinapril elimination is dependent on the level of renal function. The recommended initial dose is 5 mg in patients with a creatinine clearance of 30 to 60 mL/minute and 2.5 mg in patients with a creatinine clearance of 10 to 30 mL/minute. There is insufficient data for dosage recommendation in patients with a creatinine clearance less than 10 mL/minute. 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.

5 mg: Each brown, film-coated, elliptical tablet, embossed “ã” on one side and “5” on the other, contains: quinapril 5 mg. Nonmedicinal ingredients: candelilla wax, crospovidone, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, lactose, magnesium carbonate, magnesium stearate, polyethylene glycol, synthetic red iron oxide and titanium dioxide. Bottles of 90.

10 mg: Each brown, film-coated, triangular tablet, embossed “à” on one side and “10” on the other, contains: quinapril 10 mg. Nonmedicinal ingredients: candelilla wax, crospovidone, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, lactose, magnesium carbonate, magnesium stearate, polyethylene glycol, synthetic red iron oxide and titanium dioxide. Bottles of 90.

20 mg: Each brown, film-coated, round tablet, embossed “â” on one side and “20” on the other, contains: quinapril 20 mg. Nonmedicinal ingredients: candelilla wax, crospovidone, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, lactose, magnesium carbonate, magnesium stearate, polyethylene glycol, synthetic red iron oxide and titanium dioxide. Bottles of 90.

40 mg: Each brown, film-coated, elliptical tablet, embossed “á” on one side and “40” on the other, contains: quinapril 40 mg. Nonmedicinal ingredients: candelilla wax, crospovidone, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose, lactose, magnesium carbonate, magnesium stearate, polyethylene glycol, synthetic red iron oxide and titanium dioxide. Bottles of 90.

All strengths are gluten-, paraben-, sodium-, sulfite- and tartrazine-free. Store at controlled room temperature, 15 to 30°C. Protect from moisture. Dispense in well-closed containers.