ACCUPRIL 20MG TABLET
Quinapril hydrochloride (Accupril) 5 mg Tablet: Each tablet contains quinapril hydrochloride equivalent to 5 mg quinapril.
Quinapril hydrochloride (Accupril) 10 mg Tablet: Each tablet contains quinapril hydrochloride equivalent to 10 mg quinapril.
Quinapril hydrochloride (Accupril) 20 mg Tablet: Each tablet contains quinapril hydrochloride equivalent to 20 mg quinapril.
Quinapril hydrochloride is the salt of quinapril, the ethyl ester of a non-sulfhydryl, angiotensin-converting enzyme (ACE) inhibitor, quinaprilat.
Quinapril hydrochloride is chemically described as [3S-[2[R*(R*)], 3R*]]-2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid, monohydrochloride. Its empirical formula is C25H30N2O5?HCl and its molecular weight is 474.98.
Quinapril hydrochloride is a white to off-white amorphous powder, freely soluble in aqueous solvents with a melting point of 108 to 115?C.
Indications / Uses :
Hypertension: Quinapril is indicated for the treatment of hypertension. Quinapril is effective as monotherapy or concomitantly with thiazide diuretics and beta-blockers in patients with hypertension.
Congestive Heart Failure: Quinapril is effective in the treatment of congestive heart failure when given concomitantly with a diuretic and/or cardiac glycoside.
Should be taken on an empty stomach.
Quinapril is contraindicated in patients who are hypersensitive to any component of this product (i.e. quinapril hydrochloride, magnesium carbonate, gelatin, lactose, crospovidone, magnesium stearate, hypromellose, hydroxypropyl cellulose, titanium dioxide, macrogol 400, iron oxide red and candelilla wax) and in patients with a history of angioedema related to previous treatment with an angiotensin-converting enzyme (ACE) inhibitor.
Quinapril is also contraindicated in women who are pregnant, intend to become pregnant, or of childbearing potential who are not using adequate contraceptive measures. Quinapril should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazards to the fetus (see Use in Pregnancy & Lactation).
Do not administer quinapril in combination with aliskiren: In patients with diabetes, moderate to severe kidney insufficiency [glomerular filtration rate (GFR) <60 mL/min/1.73 m2], hyperkalemia (>5 mmol/L), in congestive heart failure patients who are hypotensive.
Do not administer quinapril in combination with angiotensin receptor blockers or other ACE inhibitors: In diabetic patients with end organ damage, in patients with moderate to severe kidney insufficiency (GFR <60 mL/min/1.73 m2), in patients with hyperkalemia (>5 mmol/L) and in congestive heart failure patients who are hypote
Special Precautions :
Head and Neck Angioedema: Angioedema has been reported in 0.1% of patients receiving quinapril. If laryngeal stridor or angioedema of the face, tongue, or glottis occur, treatment with quinapril should be discontinued immediately; the patient should be 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; antihistamines may be useful in relieving symptoms. Angioedema associated with laryngeal involvement may be fatal. Where there is involvement of the tongue, glottis, or larynx likely to cause airway obstruction, appropriate emergency therapy, including, but not limited to, subcutaneous adrenalin (epinephrine) solution 1:1000 (0.3 to 0.5 mL), should be promptly administered.
Black patients receiving ACE inhibitor therapy have been reported to have a higher incidence of angioedema compared to non-black patients. It should also be noted that in controlled clinical trials, ACE inhibitors have an effect on blood pressure that is less in black patients than in non-black patients. The incidence of angioedema in black and non-black patients during quinapril therapy has been calculated in two large open-label clinical trials evaluating the effectiveness of quinapril in the management of hypertension. In one study wherein 1656 black and 10,583 non-black patients were evaluated, the incidence of angioedema, regardless of association to quinapril treatment, was 0.3% in black patients and 0.39% in non-black patients. In the other study (1443 black and 9300 non-black patients), the incidence of angioedema was 0.55% in black patients and 0.17% in non-black patients.
Patients taking a concomitant mammalian target of rapamycin (mTOR) inhibitor (e.g. temsirolimus) or a concomitant dipeptidyl peptidase-IV (DPP-IV) inhibitor (e.g. vildagliptin) therapy may be at increased risk for angioedema. Caution should be used when starting on mTOR inhibitor or a DPP-IV inhibitor in a patient already taking an ACE inhibitor.
Intestinal Angioedema: Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases, there was no prior history of facial angioedema, and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk for angioedema while receiving an ACE inhibitor.
Anaphylactoid Reactions: Desensitization: Patients receiving ACE inhibitors during desensitizing treatment with hymenoptera venom have sustained life-threatening anaphylactoid reactions. In the same patients, these reactions have been avoided when ACE inhibitors were temporarily withheld, but they have reappeared upon inadvertent rechallenge.
Low-Density Lipoprotein Apheresis: Patients undergoing low-density lipoprotein (LDL) apheresis with dextran-sulfate absorption when treated concomitantly with an ACE inhibitor, have reported anaphylactoid reactions.
Hemodialysis: Clinical evidence has shown that patients hemodialyzed using certain high-flux membranes (such as polyacrylonitrile membranes) are likely to experience anaphylactoid reactions with concomitant ACE inhibitor treatment. This combination should be avoided, either by use of alternative antihypertensive drugs, or alternative membranes for hemodialysis.
Dual Blockage of the Renin-Angiotensin System: Dual blockage of the renin-angiotensin system (RAS) with angiotensin receptors blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Routine combination therapy with RAS-acting agents is not recommended and should be limited to individually defined cases with close monitoring of renal function and blood potassium levels (see Contraindications).
Hypotension: Symptomatic hypotension was rarely seen in uncomplicated hypertensive patients treated with quinapril but is a possible consequence of ACE inhibitor therapy in salt/volume depleted patients such as those previously treated with diuretics, who have a dietary salt restriction, or who are on dialysis.
Patients already receiving a diuretic when quinapril is initiated can develop symptomatic hypotension. In patients receiving a diuretic, it is important, if possible, to stop the diuretic for 2 to 3 days before starting quinapril. If blood pressure is not controlled with quinapril alone, diuretic therapy should be resumed. If it is not possible to withdraw diuretic therapy, begin quinapril at a low initial dose (see Interactions).
In patients with congestive heart failure, who are at risk of excessive hypotension, quinapril therapy should be started at the recommended dose under close medical supervision; these patients should be followed closely for the first 2 weeks of treatment and whenever the dosage of quinapril is increased.
If symptomatic hypotension occurs, the patient should be placed in the supine position and, if necessary, receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses; however, lower doses of quinapril or any concomitant diuretic therapy should be considered if this event occurs.
Neutropenia/Agranulocytosis: ACE inhibitors have been rarely associated with agranulocytosis and bone marrow depression in patients with uncomplicated hypertension but more frequently in patients with renal impairment, especially if they also have collagen vascular disease.
Agranulocytosis has been rarely reported during treatment with quinapril. Monitoring of white blood cell counts in patients with collagen vascular disease and/or renal disease should be considered.
Fetal/Neonatal Morbidity and Mortality: See Use in Pregnancy & Lactation.
Renal Impairment: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with quinapril may be associated with oliguria and/or progressive azotemia and rarely acute renal failure and/or death (see Adverse Reactions).
The half-life of quinaprilat is prolonged as creatinine clearance falls. Patients with a creatinine clearance of <60 mL/min require a lower initial dosage of quinapril (see Dosage & Administration). These patients’ dosage should be titrated upwards based upon therapeutic response, and renal function should be closely monitored, although initial studies do not indicate that quinapril produces further deterioration in renal function.
Some patients with hypertension or heart failure with no apparent pre-existing renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when quinapril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of a diuretic and/or quinapril may be required.
In clinical studies in hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine have been observed in some patients following ACE inhibitor therapy. These increases were almost always reversible upon discontinuation of the ACE inhibitor and/or diuretic therapy. In such patients, renal function should be monitored during the first few weeks of therapy (see Adverse Reactions).
Hepatic Impairment: Quinapril when combined with a diuretic should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. The metabolism of quinapril to quinaprilat is normally dependent upon hepatic esterase. Quinaprilat concentrations are reduced in patients with alcoholic cirrhosis due to impaired deesterification of quinapril.
Hyperkalemia: Patients on quinapril alone may have increased serum potassium levels. Because of the risk of further potentiating increases in serum potassium, it is advised that combination therapy with potassium-sparing diuretics or other drugs known to raise serum potassium levels, be initiated with caution and the patient’s serum potassium levels be closely monitored (see Interactions). When administered concomitantly, quinapril may reduce the hypokalemia induced by thiazide diuretics.
Hypoglycemia and Diabetes: ACE inhibitors have been associated with hypoglycemia in diabetic patients on insulin or oral hypoglycemic agents; closer monitoring of diabetic patients may be required.
Cough: Cough has been reported with the use of quinapril. Characteristically, the cough is non-productive, persistent, and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.
Surgery/Anesthesia: Caution should be exercised when patients undergo major surgery or anesthesia since ACE inhibitors have been shown to block angiotensin II formation secondary to compensatory renin release. This may lead to hypotension, which can be corrected by volume expansion.
Effects on Ability to Drive and Use Machines: The ability to engage in activities, such as operating machinery or operating a motor vehicle may be impaired, especially when initiating quinapril therapy.