Quinaphar (Tablets) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Manufactured By

Teva Pharmaceutical Works, Private Limited Company (Hungary)

ATC Code

C09AA06 (Quinapril)

Active Substance

Quinapril (Rec.INN registered by WHO)

Dosage Forms

	Quinaphar	Film-coated tablets, 10 mg: 20, 28 or 30 pcs.
		Film-coated tablets, 20 mg: 20, 28 or 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, oval, engraved with “10” on one side and a score on the other.

Excipients: magnesium carbonate, anhydrous dibasic calcium phosphate, gelatin, crospovidone (polyplasdone XL), magnesium stearate.

Tablet coating composition hypromellose 6cP, titanium dioxide (E171), macrogol 6000, macrogol 400.

7 pcs. – blisters (4) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.

Film-coated tablets white, oval, engraved with “20” on one side and a score on the other.

Excipients: magnesium carbonate, anhydrous dibasic calcium phosphate, gelatin, crospovidone (polyplasdone XL), magnesium stearate.

Tablet coating composition hypromellose 6cP, titanium dioxide (E171), macrogol 6000, macrogol 400.

7 pcs. – blisters (4) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

ACE inhibitor

Pharmacotherapeutic Group

ACE blocker

Pharmacological Action

Antihypertensive drug, ACE inhibitor. Quinapril is rapidly metabolized to form quinaprilat (quinapril diacid – the main metabolite), which is an ACE inhibitor.

The mechanism of action of quinapril is to inhibit the activity of circulating and tissue ACE, resulting in reduced formation of the vasoconstrictor peptide angiotensin II and aldosterone, which is accompanied by a decrease in blood pressure (antihypertensive effect).

The duration of the antihypertensive action of quinapril exceeds the duration of the inhibitory effect on circulating ACE, while inhibition of tissue ACE is more closely correlated with the duration of the drug’s antihypertensive action.

The use of quinapril at a dose of 10-40 mg in patients with arterial hypertension leads to a decrease in blood pressure both in sitting and standing positions, with minimal effect on heart rate.

The antihypertensive effect of the drug appears within 1 hour after oral administration, reaching a maximum within 2-4 hours. In some patients, the maximum antihypertensive effect is achieved only after 2 weeks of treatment.

In recommended doses, the antihypertensive effect of the drug lasts for 24 hours and is maintained during long-term therapy.

The use of quinapril in patients with chronic heart failure leads to a decrease in systemic vascular resistance, mean blood pressure, systolic and diastolic blood pressure, pulmonary capillary wedge pressure and an increase in cardiac output.

Quinapril, like other ACE inhibitors, may increase insulin sensitivity.

Pharmacokinetics

Absorption

C_max of quinapril in blood plasma is reached 1 hour after administration. The degree of absorption is about 60% and is not affected by food intake. After absorption, Quinapril is metabolized to form the main active metabolite – quinaprilat and a number of inactive metabolites.

C_max in blood plasma is reached approximately 2 hours after oral administration of quinapril.

Quinapril and its metabolites do not cross the blood-brain barrier.

Elimination

T_1/2 of quinapril is approximately 1 hour.

Quinaprilat is mainly excreted by the kidneys; the effective T_1/2 is 3 hours. Approximately 97% of quinapril or quinaprilat circulates in blood plasma bound to proteins.

Pharmacokinetics in special clinical cases

In patients with renal failure, T_1/2 of quinaprilat increases as creatinine clearance decreases.

Reduced excretion of quinaprilat is observed in elderly patients (over 65 years of age). The concentration of quinaprilat decreases in patients with alcoholic liver cirrhosis due to impaired metabolism of quinapril.

Indications

• Arterial hypertension (in monotherapy or in combination with thiazide diuretics and beta-blockers);
• Chronic heart failure (in combination with diuretics and/or cardiac glycosides).

ICD codes

Dosage Regimen

The drug is taken orally.

For monotherapy of arterial hypertension, the initial dose of Quinaphar in patients not taking diuretics is 10-20 mg once a day.

The dose of the drug should be titrated depending on the clinical effect, doubling it to a maintenance dose of 20 mg/day or 40 mg/day, which is taken in one dose or divided into two parts.

The dose should be changed, as a rule, at intervals of 4 weeks.

In most patients, adequate blood pressure control during long-term treatment is provided by a single dose of the drug.

The maximum daily dose is 80 mg.

For arterial hypertension in patients receiving diuretics, the initial dose of Quinaphar is 5 mg/day.

The dose of the drug should be titrated until the optimal antihypertensive effect is achieved.

In elderly patients with arterial hypertension, the initial dose of Quinaphar is 10 mg/day.

Further dose titration is carried out to achieve the optimal effect.

For chronic heart failure, the initial dose of Quinaphar is 5 mg 1-2 times/day.

After taking the first dose of the drug, patients should be monitored to exclude arterial hypotension.

If the initial dose of Quinaphar is well tolerated, it should be titrated to an effective dose, which is usually 10-40 mg/day in 2 equal doses in combination with concomitant therapy with diuretics and/or cardiac glycosides.

In patients with impaired renal function, the recommended initial dose of Quinaphar is 5 mg for creatinine clearance greater than 30 ml/min, 2.5 mg for creatinine clearance less than 30 ml/min.

If the initial dose is well tolerated, the drug may be prescribed 2 times/day.

In the absence of severe arterial hypotension or significant deterioration of renal function, the dose can be increased at weekly intervals, taking into account clinical and hemodynamic effects.

The maximum recommended dose is determined depending on creatinine clearance.

Adverse Reactions

From the nervous system: headache, dizziness, increased excitability, increased fatigue, depression, drowsiness, asthenia, vertigo, tinnitus.

From the cardiovascular system: vasodilation, postural hypotension, tachycardia, angina pectoris, palpitations, chest pain, transient ischemic attacks, syncope.

From the digestive system: dry mouth, dyspepsia, abdominal pain, nausea, vomiting, diarrhea, flatulence, pancreatitis, cholestasis, hepatitis.

From the respiratory system: dyspnea, bronchitis, bronchospasm, cough, rhinitis.

From the skin: itching, increased sweating, rash, alopecia.

Allergic reactions: urticaria, dermatitis, Stevens-Johnson syndrome, photosensitivity; rarely – angioedema.

From the urinary system: urinary tract infections, increased blood urea nitrogen and creatinine.

From the hematopoietic system: rarely – agranulocytosis, neutropenia, hemolytic anemia,

From metabolism: rarely – hyperkalemia, edema.

From the musculoskeletal system: arthralgia, back pain, myalgia, arthralgia.

Other: blurred vision, decreased potency.

Contraindications

• History of angioedema associated with ACE inhibitor treatment;
• Hemodynamically significant stenosis of the aortic or mitral valve;
• Hypertrophic cardiomyopathy;
• Primary hyperaldosteronism;
• Bilateral renal artery stenosis or stenosis of the artery of a single kidney;
• Severe renal impairment (creatinine clearance less than 10 ml/min);
• Hemodialysis;
• Condition after kidney transplantation;
• Pregnancy;
• Lactation period;
• Age under 18 years (efficacy and safety not established);
• Hypersensitivity to quinapril or any component of the drug.

With caution should be prescribed with a history of angioedema not associated with the use of ACE inhibitors, with symptomatic arterial hypotension in patients previously taking diuretics and on a salt-restricted diet, with severe heart failure in patients at high risk of severe arterial hypotension; conditions accompanied by a decrease in circulating blood volume (including vomiting, diarrhea); with hyperkalemia; bone marrow depression; aortic stenosis; cerebrovascular diseases (a sharp decrease in blood pressure during ACE inhibitor therapy may worsen the course of these diseases); severe autoimmune connective tissue diseases; impaired liver function (especially with simultaneous use with a diuretic); with combined therapy with potassium-sparing diuretics; diabetes mellitus; extensive surgical interventions and with general anesthesia.

Use in Pregnancy and Lactation

The use of Quinaphar is contraindicated during pregnancy. ACE inhibitors, including Quinapril, are excreted in breast milk.

Use in Hepatic Impairment

The drug should be used with caution in case of impaired liver function (especially with simultaneous use with a diuretic).

Use in Renal Impairment

In patients with impaired renal function, the maximum recommended dose is determined depending on creatinine clearance.

The drug is contraindicated in bilateral renal artery stenosis or stenosis of the artery of a single kidney, in severe renal impairment (creatinine clearance less than 10 ml/min), hemodialysis, condition after kidney transplantation.

Special Precautions

Quinapril should not be used in patients with hemodynamically significant aortic stenosis.

In patients on hemodialysis using high-flow polyacrylonitrile membranes, there is a high probability of anaphylactoid reactions with simultaneous use of ACE inhibitors.

Therefore, such combinations should be avoided and alternative antihypertensive agents or other membranes for hemodialysis should be used.

Similar reactions have been observed during LDL apheresis using dextran sulfate.

It is not recommended to use these methods in patients receiving Quinapril.

In patients receiving ACE inhibitors, anaphylactoid reactions, life-threatening to the patient, have sometimes been observed during desensitizing therapy using hymenoptera venom.

These reactions can be avoided by temporarily discontinuing the use of ACE inhibitors before desensitizing therapy.

In patients with renal failure, renal function should be monitored during treatment, although in most cases Quinapril does not affect renal function or may even improve it.

In some predisposed patients, a change in renal function can be expected as a result of inhibition of the renin-angiotensin-aldosterone system (RAAS).

In patients with severe chronic heart failure, in whom renal function may depend on the RAAS, therapy with ACE inhibitors, including Quinapril, may be associated with oliguria and/or progressive azotemia, and in rare cases may cause acute renal failure and/or death.

T_1/2 of quinapril increases with decreasing creatinine clearance.

In patients with creatinine clearance less than 60 ml/min, a lower initial dose of Quinaphar is used.

Then this dose is titrated, increasing it, based on the clinical effect, while renal function should be carefully monitored.

In patients with arterial hypertension and unilateral or bilateral renal artery stenosis, after treatment with ACE inhibitors, an increase in blood urea nitrogen and creatinine in plasma is observed.

These increases are reversible after discontinuation of ACE inhibitor and/or diuretic therapy.

In these patients, renal function should be monitored during the first weeks of treatment with quinapril.

In some patients with arterial hypertension or chronic heart failure who had no obvious signs of renal vascular disease, an increase in blood urea nitrogen and creatinine levels may be observed, which are usually minor and transient, especially if Quinapril is taken together with diuretics, which is observed in 4% and 3% of patients, respectively.

This is more often noted in patients with impaired renal function.

In these cases, it may be necessary to reduce the dose or discontinue the diuretic and/or quinapril.

In patients receiving ACE inhibitors, angioedema may develop.

In case of development of laryngospasm, angioedema of the face, tongue or epiglottis, treatment with Quinaphar should be immediately discontinued, appropriate treatment should be prescribed and the patient should be carefully monitored until the edema disappears.

Swelling of the face and lips usually resolves without treatment; antihistamines can be successfully used to relieve symptoms.

Laryngeal angioedema can be fatal.

If there is a risk of airway obstruction due to swelling of the tongue, epiglottis or larynx, appropriate emergency therapy is required in these cases, for example, s.c. administration of epinephrine (adrenaline) 1:1000 (0.3-0.5 ml).

Arterial hypotension, accompanied by clinical symptoms, is rarely observed in patients with arterial hypertension receiving treatment with quinapril.

However, arterial hypotension is a possible complication when using ACE inhibitors, especially in patients with hyponatremia or on dialysis.

If symptoms of arterial hypotension occur, the patient should be placed on his back and, if necessary, 0.9% sodium chloride solution should be administered intravenously.

Transient arterial hypotension is not a contraindication to continuing therapy, but the possibility of reducing the dose of quinapril or discontinuing concomitant diuretic therapy should be considered.

In rare cases, treatment of patients with uncomplicated arterial hypertension with ACE inhibitors may be accompanied by agranulocytosis and bone marrow depression, which is more common in patients with impaired renal function.

It is necessary to monitor the level of blood leukocytes.

In patients undergoing surgical interventions or general anesthesia, ACE inhibitors should be used with caution, because they block the formation of angiotensin II, as a result of which renin is released compensatorily.

This can cause arterial hypotension, which is corrected by fluid administration.

Effect on ability to drive vehicles and mechanisms

Caution should be exercised when driving vehicles or performing other work that requires increased attention, especially at the beginning of treatment.

Overdose

Symptoms: marked decrease in blood pressure.

Treatment: intravenous fluid administration, symptomatic therapy; hemodialysis and peritoneal dialysis have little effect on the excretion of quinapril and quinaprilat.

Drug Interactions

The use of tetracycline with quinapril was accompanied by a 28-37% decrease in the absorption of tetracycline due to the presence of magnesium carbonate as an inactive component of the drug.

Simultaneous administration of tetracycline and quinapril should be avoided.

In patients receiving diuretics, excessive lowering of blood pressure may be observed after starting therapy with quinapril.

This hypotensive effect can be minimized by discontinuing the diuretic and increasing salt intake before taking the first dose of quinapril.

If it is not possible to discontinue the diuretic, it is necessary to monitor the patient for 2 hours after taking the first dose of the drug.

An increase in serum potassium levels is possible with the simultaneous use of quinapril and potassium-sparing diuretics, potassium preparations or its salts (combinations should be used with caution under the control of plasma potassium levels).

As with the use of other ACE inhibitors, hyperkalemia may be observed in patients taking Quinapril as monotherapy.

When used in combination, Quinapril may reduce hypokalemia caused by thiazide diuretics.

There are data on increased lithium levels in blood plasma and symptoms of lithium intoxication in patients simultaneously receiving lithium preparations and ACE inhibitors, due to increased sodium excretion under the influence of these drugs (combined therapy should be carried out with caution, under the control of lithium concentration in blood plasma).

If diuretics are also used, this may increase the risk of lithium intoxication.

In some patients, simultaneous use of NSAIDs may cause a decrease in the antihypertensive effect of ACE inhibitors.

Moreover, it has been shown that with the simultaneous use of NSAIDs and ACE inhibitors, an additional increase in plasma potassium levels is observed; while renal function may decrease.

These changes are reversible and are usually observed in patients with impaired renal function.

Simultaneous use of allopurinol, cytotoxic and immunosuppressive agents, systemic corticosteroids and procainamide with ACE inhibitors may increase the risk of leukopenia.

When used concomitantly with quinapril, an enhancement of the effect of other antihypertensive agents may be observed.

Antacids may reduce the bioavailability of quinapril.

With simultaneous use with barbiturates, anesthetics, as well as with alcohol, potentiation of orthostatic arterial hypotension is possible.

When used concomitantly with hypoglycemic agents ( oral and insulin), a dose adjustment of the latter may be required.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life is 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.