Quinapro

Quinapro 5 mg Tablet: Each tablet contains Quinapril equivalent to 5 mg Quinapro.

Quinapro 10 mg Tablet: Each tablet contains Quinapril equivalent to 10 mg Quinapro.

Quinapro 20 mg Tablet: Each tablet contains Quinapril equivalent to 20 mg Quinapro.

Quinapril is the salt of Quinapro, the ethyl ester of a non-sulfhydryl, angiotensin-converting enzyme (ACE) inhibitor, quinaprilat.

Quinapro 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.

Quinapro is a white to off-white amorphous powder, freely soluble in aqueous solvents with a melting point of 108 to 115°C.

Hypertension

Quinapro is 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 Quinapro.

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 varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Quinapro may be used alone or in combination with thiazide diuretics.

Heart Failure

Quinapro is indicated in the management of heart failure as adjunctive therapy when added to conventional therapy including diuretics and/or digitalis.

In using Quinapro, consideration should be given to the fact that another angiotensinconverting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease. Available data are insufficient to show that Quinapro does not have a similar risk.

Angioedema in black patients: Black patients receiving ACE inhibitor monotherapy have been reported to have a higher incidence of angioedema compared to non-blacks. 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-blacks.

Quinapro is used alone or together with other medicines to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. Lowering blood pressure can reduce the risk of stroke and heart attacks.

Quinapro is an angiotensin converting enzyme (ACE) inhibitor. It works by blocking a substance in the body that causes blood vessels to tighten. As a result, Quinapro relaxes the blood vessels. This lowers blood pressure and increases the supply of blood and oxygen to the heart.

Quinapro is also used to treat heart failure or may be used for other conditions as determined by your doctor.

Quinapro is available only with your doctor's prescription.

Hypertension: Monotherapy: The recommended initial dosage of Quinapro in patients not on diuretics is 10 mg or 20 mg once daily. Depending upon clinical response, the patient's dosage may be titrated (by doubling the dose) to a maintenance dosage of 20 mg/day or 40 mg/day, usually given as a single dose or may be divided in two doses. Generally, dosage adjustments should be made at intervals of 4 weeks. Long-term control is maintained in most patients with a single daily dosage regimen. Patients have been treated with dosages of Quinapro up to 80 mg/day.

Concomitant Diuretics: In patients who must continue treatment with a diuretic, the initial recommended dosage of Quinapro is 5 mg, which should subsequently be titrated (as described previously) to the optimal response.

Congestive Heart Failure: Quinapro is indicated as adjunctive therapy with diuretics and/or cardiac glycosides. The recommended initial dosage in patients with congestive heart failure is 5 mg once or twice daily, following which the patient should be monitored closely for symptomatic hypotension. If the initial dose of Quinapro is well tolerated, patients may be titrated up to an effective dose, usually 10 mg/day to 40 mg/day given in two equally divided doses with concomitant therapy.

Renal Impairment: See Precautions. Kinetic data indicate that Quinapro elimination is dependent on the level of renal function. The recommended initial dose of Quinapro is 5 mg in patients with a creatinine clearance above 30 mL/min and 2.5 mg in patients with a creatinine clearance less than 30 mL/min. If the initial dose is well tolerated, Quinapro 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. Recommended starting dosages based on clinical and pharmacokinetic data from patients with renal impairment are as follows: See Table 1.

Elderly: Age alone does not appear to affect the efficacy or safety profile of Quinapro. Therefore, the recommended initial dosage of Quinapro in elderly patients is 10 mg given once daily followed by titration to the optimal response.

Children: Safety and effectiveness of Quinapro in pediatric patients have not been established.

See also:
What is the most important information I should know about Quinapro?

Quinapro is contraindicated in patients who are hypersensitive to any component of this product (i.e. Quinapro, 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.

Quinapro is also contraindicated in women who are pregnant, intend to become pregnant, or of childbearing potential who are not using adequate contraceptive measures. Quinapro 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.

Do not administer Quinapro 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 Quinapro 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 hypotensive.

Use Quinapro as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• If you are taking a tetracycline antibiotic (eg, doxycycline) or a fluoroquinolone antibiotic (eg, ciprofloxacin), ask your doctor or pharmacist how to take it with Quinapro. This product contains magnesium, which can interfere with absorption of these antibiotics.
• Quinapro works best if it is taken at the same time each day. Taking Quinapro at the same time each day will help you remember to take it.
• Continue to use Quinapro even if you feel well. Do not miss any doses.
• If you miss a dose of Quinapro, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Quinapro.

Quinapro is used to treat high blood pressure (hypertension). Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems. It is also used to treat heart failure.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to help protect the kidneys from harm due to diabetes.

How to use Quinapro

Read the Patient Information Leaflet if available from your pharmacist before you start taking Quinapro and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth with or without food as directed by your doctor, usually once or twice a day. High-fat meals may decrease the absorption of this medication.

The dosage is based on your medical condition and response to treatment.

Use this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time(s) each day. It is important to continue taking this medication even if you feel well. Most people with high blood pressure do not feel sick.

For the treatment of high blood pressure, it may take 1 to 2 weeks before you get the full benefit of this medication. For the treatment of heart failure, it may take weeks to months before you get the full benefit of this medication. Tell your doctor if your condition does not improve or if it worsens (such as your blood pressure readings remain high or increase).

See also:
What other drugs will affect Quinapro?

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 Quinapro. The possibility of hypotensive effects with Quinapro may be minimized by either discontinuing the diuretic or cautiously increasing salt intake prior to initiation of treatment with Quinapro. If it is not possible to discontinue the diuretic, the starting dose of Quinapro should be reduced.

Agents Increasing Serum Potassium

Coadministration of Quinapro 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 Quinapro reduced the absorption of tetracycline by approximately 28% to 37%, possibly due to the high magnesium content in Quinapro tablets. This interaction should be considered if coprescribing Quinapro 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 compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including Quinapro, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving Quinapro and NSAID therapy.

The antihypertensive effect of ACE inhibitors, including Quinapro may be attenuated by NSAIDs.

Agents That Inhibit mTOR

Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema.

Other Agents

Drug interaction studies of Quinapro with other agents showed:

• Multiple dose therapy with propranolol or cimetidine has no effect on the pharmacokinetics of single doses of Quinapro.
• The anticoagulant effect of a single dose of warfarin (measured by prothrombin time) was not significantly changed by Quinapro coadministration twice-daily.
• Quinapro treatment did not affect the pharmacokinetics of digoxin.
• No pharmacokinetic interaction was observed when single doses of Quinapro and hydrochlorothiazide were administered concomitantly.
• Co-administration of multiple 10 mg doses of atorvastatin with 80 mg of Quinapro resulted in no significant change in the steady-state pharmacokinetic parameters of atorvastatin.

Dual Blockade Of The Renin-Angiotensin System (RAS)

Dual blockade of the RAS with angiotensin receptor 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. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Quinapro and other agents that affect the RAS.

Do not co-administer aliskiren with Quinapro in patients with diabetes. Avoid concomitant use of aliskiren with Quinapro in patients with renal impairment (GFR < 60 mL/min/1.73 m²).

See also:
What are the possible side effects of Quinapro?

Hypertension

Quinapro has been evaluated for safety in 4960 subjects and patients. Of these, 3203 patients, including 655 elderly patients, participated in controlled clinical trials. Quinapro 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 Quinapro are shown below.

Adverse Events in Placebo-Controlled Trials

Heart Failure

Quinapro has been evaluated for safety in 1222 Quinapro 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 Quinapro are shown below.

Hypertension And/Or Heart Failure

Clinical adverse experiences probably, possibly, or definitely related, or of uncertain relationship to therapy occurring in 0.5% to 1.0% (except as noted) of the patients with CHF or hypertension treated with Quinapro (with or without concomitant diuretic) in controlled or uncontrolled trials (N=4847) and less frequent, clinically significant events seen in clinical trials or post-marketing experience (the rarer events are in italics) include (listed by body system):

General: back pain, malaise, viral infections, anaphylactoid reaction

Cardiovascular: palpitation, vasodilation, tachycardia, heart failure, hyperkalemia, myocardial infarction, cerebrovascular accident, hypertensive crisis, angina pectoris, orthostatic hypotension, cardiac rhythm disturbances, cardiogenic shock

Hematology: hemolytic anemia

Gastrointestinal: flatulence, dry mouth or throat, constipation, gastrointestinal hemorrhage, pancreatitis, abnormal liver function tests, dyspepsia

Nervous/Psychiatric: somnolence, vertigo, syncope, nervousness, depression, insomnia, paresthesia

Integumentary: alopecia, increased sweating, pemphigus, pruritus, exfoliative dermatitis, photosensitivity reaction, dermatopolymyositis

Urogenital: urinary tract infection, impotence, acute renal failure, worsening renal failure

Respiratory: eosinophilic pneumonitis

Other: amblyopia, edema, arthralgia, pharyngitis, agranulocytosis, hepatitis, thrombocytopenia

Angioedema

Angioedema has been reported in patients receiving Quinapro (0.1%). Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis, and/or larynx occurs, treatment with Quinapro should be discontinued and appropriate therapy instituted immediately.

Clinical Laboratory Test Findings

Hematology:

Hyperkalemia:

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 all patients treated with Quinapro alone. Increases are more likely to occur in patients receiving concomitant diuretic therapy than in those on Quinapro alone. These increases often remit 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 Quinapro; most often these patients were receiving diuretics with or without digitalis.