Quinapril-SZ (Tablets) Instructions for Use

Marketing Authorization Holder

Severnaya Zvezda, CJSC (Russia)

ATC Code

C09AA06 (Quinapril)

Active Substance

Quinapril (Rec.INN)

Dosage Forms

	Quinapril-SZ	Film-coated tablets, 5 mg: 30 or 60 pcs.
		Film-coated tablets, 10 mg: 30 or 60 pcs.
		Film-coated tablets, 20 mg: 30 or 60 pcs.
		Film-coated tablets, 40 mg: 30 or 60 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets yellow, round, biconvex, with a score; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate – 28.784 mg, magnesium carbonate hydroxide pentahydrate (basic magnesium carbonate) – 75 mg, croscarmellose sodium – 3 mg, povidone – 6 mg, colloidal silicon dioxide – 0.6 mg, magnesium stearate – 1.2 mg.

Coating composition Opadry II (polyvinyl alcohol, partially hydrolyzed – 1.6 mg, talc – 0.592 mg, titanium dioxide (E171) – 0.8748 mg, macrogol (polyethylene glycol 3350) – 0.808 mg, aluminum lake based on quinoline yellow dye – 0.1204 mg, aluminum lake based on sunset yellow FCF dye – 0.0028 mg, iron oxide (II) yellow – 0.0012 mg, aluminum lake based on indigo carmine dye – 0.0008 mg).

10 pcs. – blister packs (3) – cardboard cartons.
10 pcs. – blister packs (6) – cardboard cartons.
30 pcs. – blister packs (1) – cardboard cartons.
30 pcs. – blister packs (2) – cardboard cartons.
30 pcs. – polymer jars (1) – cardboard cartons.
30 pcs. – polymer bottles (1) – cardboard cartons.

Film-coated tablets yellow, round, biconvex; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate – 46.168 mg, magnesium carbonate hydroxide pentahydrate (basic magnesium carbonate) – 125 mg, croscarmellose sodium – 5 mg, povidone – 10 mg, colloidal silicon dioxide – 1 mg, magnesium stearate – 2 mg.

Coating composition Opadry II (polyvinyl alcohol, partially hydrolyzed – 2.4 mg, talc – 0.888 mg, titanium dioxide (E171) – 1.3122 mg, macrogol (polyethylene glycol 3350) – 1.212 mg, aluminum lake based on quinoline yellow dye – 0.1806 mg, aluminum lake based on sunset yellow FCF dye – 0.0042 mg, iron oxide yellow – 0.0018 mg, aluminum lake based on indigo carmine dye – 0.0012 mg).

10 pcs. – blister packs (3) – cardboard cartons.
10 pcs. – blister packs (6) – cardboard cartons.
30 pcs. – blister packs (1) – cardboard cartons.
30 pcs. – blister packs (2) – cardboard cartons.
30 pcs. – polymer jars (1) – cardboard cartons.
30 pcs. – polymer bottles (1) – cardboard cartons.

Film-coated tablets yellow, round, biconvex; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate – 48.736 mg, magnesium carbonate hydroxide pentahydrate (basic magnesium carbonate) – 157 mg, croscarmellose sodium – 6.3 mg, povidone – 12.5 mg, colloidal silicon dioxide – 1.3 mg, magnesium stearate – 2.5 mg.

Coating composition Opadry II (polyvinyl alcohol, partially hydrolyzed – 3.2 mg, talc – 1.184 mg, titanium dioxide (E171) – 1.7496 mg, macrogol (polyethylene glycol 3350) – 1.616 mg, aluminum lake based on quinoline yellow dye – 0.2408 mg, aluminum lake based on sunset yellow FCF dye – 0.0056 mg, iron oxide (II) yellow – 0.0024 mg, aluminum lake based on indigo carmine dye – 0.0016 mg).

10 pcs. – blister packs (3) – cardboard cartons.
10 pcs. – blister packs (6) – cardboard cartons.
30 pcs. – blister packs (1) – cardboard cartons.
30 pcs. – blister packs (2) – cardboard cartons.
30 pcs. – polymer jars (1) – cardboard cartons.
30 pcs. – polymer bottles (1) – cardboard cartons.

Film-coated tablets yellow, round, biconvex; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate – 70.672 mg, magnesium carbonate hydroxide pentahydrate (basic magnesium carbonate) – 250 mg, croscarmellose sodium – 10 mg, povidone – 20 mg, colloidal silicon dioxide – 2 mg, magnesium stearate – 4 mg.

Coating composition Opadry II (polyvinyl alcohol, partially hydrolyzed – 4.8 mg, talc – 1.776 mg, titanium dioxide (E171) – 2.6244 mg, macrogol (polyethylene glycol 3350) – 2.424 mg, aluminum lake based on quinoline yellow dye – 0.3612 mg, aluminum lake based on sunset yellow FCF dye – 0.0084 mg, iron oxide (II) yellow – 0.0036 mg, aluminum lake based on indigo carmine dye – 0.0024 mg).

10 pcs. – blister packs (3) – cardboard cartons.
10 pcs. – blister packs (6) – cardboard cartons.
30 pcs. – blister packs (1) – cardboard cartons.
30 pcs. – blister packs (2) – cardboard cartons.
30 pcs. – polymer jars (1) – cardboard cartons.
30 pcs. – polymer bottles (1) – cardboard cartons.

Clinical-Pharmacological Group

ACE inhibitor

Pharmacotherapeutic Group

Antihypertensive combination agent (ACE inhibitor + diuretic)

Pharmacological Action

ACE is an enzyme that catalyzes the conversion of angiotensin I to angiotensin II, which has a vasoconstrictive effect and increases vascular tone, including by stimulating aldosterone secretion by the adrenal cortex. Quinapril competitively inhibits ACE and causes a decrease in vasopressor activity and aldosterone secretion.

Elimination of the negative effect of angiotensin II on renin secretion via the feedback mechanism leads to an increase in plasma renin activity. At the same time, the decrease in blood pressure is accompanied by a decrease in total peripheral vascular resistance and renal vascular resistance, while changes in heart rate, cardiac output, renal blood flow, glomerular filtration rate and filtration fraction are insignificant or absent.

Quinapril increases exercise tolerance. With long-term use, it promotes the regression of myocardial hypertrophy in patients with arterial hypertension; improves blood supply to the ischemic myocardium. Enhances coronary and renal blood flow. Reduces platelet aggregation.

The onset of action after a single dose is within 1 hour, the maximum is within 2-4 hours, the duration of action depends on the dose taken (up to 24 hours).

A clinically pronounced effect develops several weeks after the start of therapy.

Pharmacokinetics

Absorption

The concentration of quinapril in blood plasma after oral administration reaches a maximum within 1 hour, quinaprilat – within 2 hours. Food intake does not affect the degree of absorption but may increase the time to reach maximum concentration (T_max) (fatty foods may reduce the rate and extent of quinapril absorption). Taking into account the excretion of quinapril and its metabolites by the kidneys, the degree of absorption is approximately 60%.

Distribution

Approximately 97% of quinapril and quinaprilat circulate in blood plasma in a protein-bound form. Quinapril and its metabolites do not penetrate the blood-brain barrier.

Metabolism

Under the action of liver enzymes, Quinapril is rapidly metabolized to quinaprilat by cleavage of the ester group (the main metabolite is the diacid quinaprilat), which is an ACE inhibitor. About 38% of the orally administered dose of quinapril circulates in the blood plasma as quinaprilat.

Excretion

T_1/2 of quinapril from blood plasma is about 1-2 hours, quinaprilat – 3 hours. Excreted by the kidneys – 61% (56% as quinapril and quinaprilat) and through the intestine – 37%.

Pharmacokinetics in special patient groups

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

The excretion of quinaprilat is also reduced in elderly patients (over 65 years) and closely correlates with impaired renal function; however, overall, no differences in the efficacy and safety of treatment between elderly and younger patients have been identified.

In patients with alcoholic liver cirrhosis, the concentration of quinaprilat decreases due to impaired de-esterification of quinapril.

Indications

• Arterial hypertension (as monotherapy or in combination with thiazide diuretics and beta-blockers);
• Chronic heart failure (as part of combination therapy).

ICD codes

Dosage Regimen

Take orally, without chewing, regardless of meal time, with water.

Arterial hypertension

For monotherapy, the recommended initial dose of Quinapril-SZ in patients not receiving diuretics is 10 mg once a day. Depending on the clinical effect, the dose can be increased (doubled) to a maintenance dose of 20 or 40 mg/day, which is usually prescribed in 1 or 2 doses. As a rule, the dose should be changed at intervals of 4 weeks. In most patients, the use of Quinapril-SZ once a day allows achieving a stable therapeutic response. The maximum daily dose is 80 mg/day.

For concomitant use with diuretics, the recommended initial dose of Quinapril-SZ in patients continuing to take diuretics is 5 mg once a day; subsequently, it is increased (as indicated above) until the optimal therapeutic effect is achieved.

Chronic heart failure

The recommended initial dose of Quinapril-SZ is 5 mg 1-2 times a day.

After taking the drug, the patient should be under medical supervision to detect symptomatic arterial hypotension. If the initial dose of Quinapril-SZ is well tolerated, it can be increased to 10-40 mg/day divided into 2 doses.

Based on clinical and pharmacokinetic data, in patients with impaired renal function, the initial dose is recommended to be selected as follows:

If the initial dose is well tolerated, then Quinapril-SZ can be used 2 times a day. The dose of Quinapril-SZ can be gradually, no more than once a week, increased taking into account the clinical, hemodynamic effects, as well as renal function.

The recommended initial dose of Quinapril-SZ in elderly patients is 10 mg once a day; subsequently, it is increased until the optimal therapeutic effect is achieved.

Adverse Reactions

Adverse events with the use of quinapril are usually mild and transient. The most common are headache (7.2%), dizziness (5.5%), cough (3.9%), increased fatigue (3.5%), rhinitis (3.2%), nausea and/or vomiting (2.8%) and myalgia (2.2%). It should be noted that the cough is typically non-productive, persistent, and resolves after discontinuation of treatment.

The frequency of quinapril discontinuation due to side effects was observed in 5.3% of cases.

The following is a list of adverse reactions distributed by organ system and frequency of occurrence (World Health Organization classification): very common (more than 1/10); common (from more than 1/100 to less than 1/10); uncommon (from more than 1/1000 to less than 1/100); rare (from more than 1/10,000 to less than 1/1000); very rare (less than 1/10,000, including isolated reports).

Nervous system disorders: common – headache, dizziness, insomnia, paresthesia, increased fatigue; uncommon – depression, increased excitability, drowsiness, vertigo.

Eye disorders: uncommon – visual impairment.

Gastrointestinal disorders: common – nausea and/or vomiting, diarrhea, dyspepsia, abdominal pain; uncommon – dryness of the mouth or throat mucosa, flatulence, pancreatitis*, angioedema of the intestine, gastrointestinal bleeding; rare – hepatitis.

Blood and lymphatic system disorders: uncommon – hemolytic anemia*, thrombocytopenia*.

Cardiac and vascular disorders common – pronounced decrease in blood pressure; uncommon – angina pectoris, palpitations, tachycardia, heart failure, myocardial infarction, stroke, increased blood pressure, cardiogenic shock, postural hypotension*, syncope*, vasodilation symptoms.

Respiratory, thoracic and mediastinal disorders: common – cough, dyspnea, pharyngitis, chest pain.

Skin and subcutaneous tissue disorders: uncommon – alopecia*, exfoliative dermatitis*, increased sweating, pemphigus*, photosensitivity reactions*, pruritus, rash.

Musculoskeletal and connective tissue disorders: common – back pain; uncommon – arthralgia.

Renal and urinary disorders: uncommon – urinary tract infections, acute renal failure.

Reproductive system and breast disorders uncommon – decreased potency.

Immune system disorders: uncommon – anaphylactic reactions*, rare – angioedema.

General disorders and administration site conditions: uncommon – edema (peripheral or generalized), malaise, viral infections.

Other: rare – eosinophilic pneumonitis.

Laboratory parameters: agranulocytosis and neutropenia have been very rarely reported, although a causal relationship with the use of quinapril has not yet been established.

Hyperkalemia (see “Special Instructions”).

Creatinine and blood urea nitrogen an increase (more than 1.25 times compared to the upper limit of normal) in serum creatinine and blood urea nitrogen was observed in 2% and 2% of patients, respectively, receiving quinapril monotherapy. The likelihood of an increase in these indicators in patients simultaneously receiving diuretics is higher than with the use of quinapril alone. With further therapy, the indicators often return to normal.

* – less common adverse events or noted during post-marketing studies.

When ACE inhibitors and gold preparations (sodium aurothiomalate, intravenous) are used concomitantly, a symptom complex including facial flushing, nausea, vomiting, and decreased blood pressure has been described.

Contraindications

• History of angioedema as a result of previous therapy with ACE inhibitors;
• Hereditary and/or idiopathic angioedema;
• Pregnancy;
• Breastfeeding period;
• Age under 18 years;
• Lactase deficiency, lactose intolerance and glucose-galactose malabsorption syndrome;
• Concomitant use with aliskiren and aliskiren-containing agents or with angiotensin II receptor antagonists (ARAs) or with other drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) (dual blockade of RAAS):
  • In patients with diabetes mellitus or in patients with diabetes mellitus with target organ damage (diabetic nephropathy);
  • In patients with impaired renal function (GFR less than 60 ml/min/1.73 m²);
  • In patients with hyperkalemia (more than 5 mmol/l);
  • In patients with chronic heart failure and arterial hypotension;
• Hypersensitivity to any component of the drug.

With caution

• Symptomatic arterial hypotension in patients previously taking diuretics and on a salt-restricted diet;
• Severe heart failure in patients at high risk of arterial hypotension;
• Severe chronic heart failure;
• Conditions accompanied by a decrease in circulating blood volume (including vomiting and diarrhea);
• Hyperkalemia;
• Bone marrow depression;
• Aortic stenosis, hypertrophic obstructive cardiomyopathy, mitral stenosis;
• Cerebrovascular insufficiency, coronary artery disease, coronary insufficiency – a sharp decrease in blood pressure during therapy with ACE inhibitors may worsen the course of these diseases;
• Bilateral renal artery stenosis or stenosis of the artery of a single kidney, condition after kidney transplantation;
• Impaired renal function;
• In patients on hemodialysis (creatinine clearance less than 10 ml/min) (data on the use of quinapril in such patients are insufficient);
• Autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma);
• Impaired liver function (especially with simultaneous use with diuretics);
• With simultaneous use with potassium-sparing diuretics;
• Diabetes mellitus;
• Major surgical interventions and general anesthesia;
• Concomitant use of other antihypertensive agents, as well as mTOR enzyme inhibitors and DPP-4 inhibitors.

Use in Pregnancy and Lactation

Use of the drug Quinapril-SZ is contraindicated during pregnancy, in women planning a pregnancy, and in women of reproductive age not using reliable methods of contraception.

Women of reproductive age taking the drug Quinapril-SZ should use reliable methods of contraception.

If pregnancy is diagnosed, the drug Quinapril-SZ should be discontinued as soon as possible.

Use of ACE inhibitors during pregnancy is associated with an increased risk of abnormalities of the fetal cardiovascular and nervous systems. Furthermore, cases of oligohydramnios, premature birth, birth of children with arterial hypotension, kidney pathology (including acute renal failure), skull bone hypoplasia, limb contractures, craniofacial deformities, lung hypoplasia, intrauterine growth retardation, patent ductus arteriosus, as well as cases of intrauterine fetal death and neonatal death have been described with the use of ACE inhibitors during pregnancy. Often, oligohydramnios is diagnosed after the fetus has been irreversibly damaged.

Newborns who were exposed to ACE inhibitors in utero should be observed for the detection of arterial hypotension, oliguria, and hyperkalemia. If oliguria occurs, blood pressure and renal perfusion should be maintained.

The drug Quinapril-SZ should not be prescribed during breastfeeding because ACE inhibitors, including Quinapril, penetrate into breast milk to a limited extent. Considering the possibility of developing serious adverse events in the newborn, the drug Quinapril-SZ must be discontinued during lactation or breastfeeding should be stopped.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Based on clinical and pharmacokinetic data in patients with impaired renal function, the initial dose should be selected according to the formula (see the “Dosage Regimen” section).

The drug should be prescribed with caution in patients with impaired renal function and in patients on hemodialysis (creatinine clearance less than 10 ml/min) (data on the use of quinapril in such patients are insufficient).

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

The recommended initial dose of the drug Quinapril-SZ in elderly patients is 10 mg once daily; subsequently, it is increased until the optimal therapeutic effect is achieved.

Special Precautions

Cases of angioedema involving the head and neck have been reported in patients treated with ACE inhibitors, including in 0.1% of patients receiving Quinapril. If laryngeal stridor or angioedema of the face, tongue, or vocal folds appears, Quinapril should be discontinued immediately. The patient should be given adequate treatment and observed until the symptoms of edema regress. Antihistamines may be used to reduce symptoms. Angioedema involving the larynx can be fatal. If edema of the tongue, vocal folds, or larynx threatens the development of airway obstruction, adequate emergency therapy is necessary, including subcutaneous administration of a 1:1000 epinephrine (adrenaline) solution (0.3-0.5 ml).

Cases of intestinal angioedema have also been reported in patients treated with ACE inhibitors. Patients experienced abdominal pain (with or without nausea or vomiting); in some cases without preceding facial angioedema and with normal C1-esterase activity. The diagnosis was established using abdominal CT, ultrasound, or at the time of surgery. Symptoms resolved after discontinuation of the ACE inhibitor. Therefore, in patients with abdominal pain taking ACE inhibitors, the possibility of intestinal angioedema should be considered in the differential diagnosis.

Patients with a history of angioedema not associated with ACE inhibitor use may be at increased risk of its development when treated with drugs of this class.

Patients receiving ACE inhibitors during desensitization therapy with hymenoptera venom may develop life-threatening anaphylactoid reactions. By temporarily discontinuing the ACE inhibitor, these reactions were avoided, but they recurred upon accidental re-administration of these drugs.

Anaphylactoid reactions may also develop with the use of ACE inhibitors in patients undergoing LDL apheresis with dextran sulfate absorption or in patients on hemodialysis using high-flux membranes such as polyacrylonitrile (e.g., AN69). Therefore, such combinations should be avoided by using either other antihypertensive drugs or alternative membranes for hemodialysis.

Symptomatic arterial hypotension is rarely encountered during treatment with quinapril in patients with uncomplicated arterial hypertension; however, it may develop as a result of therapy with ACE inhibitors in patients with reduced blood volume, for example, when following a diet with limited salt intake, or during hemodialysis. In case of symptomatic arterial hypotension, symptomatic therapy should be administered (the patient should assume a horizontal position and, if necessary, receive an intravenous infusion using a 0.9% sodium chloride solution). Transient arterial hypotension is not a contraindication to further use of the drug, but in such cases, its dose should be reduced or the advisability of concomitant therapy with diuretics should be assessed.

Other causes of decreased blood volume, such as vomiting or diarrhea, can also lead to a pronounced decrease in blood pressure. In such cases, patients should consult a doctor.

In patients receiving diuretics, the use of quinapril can also lead to the development of symptomatic arterial hypotension. In such patients, it is advisable to temporarily discontinue the diuretic 2-3 days before starting treatment with quinapril, except for patients with malignant or treatment-resistant arterial hypertension. If monotherapy with quinapril does not provide the necessary therapeutic effect, then treatment with diuretics should be resumed. If it is impossible to discontinue the diuretic, Quinapril should be used at a low initial dose.

In patients with chronic heart failure, who are at increased risk of pronounced arterial hypotension, treatment with quinapril should be started at the recommended dose under close medical supervision; patients should be monitored during the first two weeks of treatment, as well as in all cases where the dose of quinapril is increased.

During therapy with ACE inhibitors in patients with uncomplicated arterial hypertension, agranulocytosis has rarely developed; it was more common in patients with impaired renal function and connective tissue diseases. During treatment with quinapril, agranulocytosis developed rarely. When using quinapril (like other ACE inhibitors) in patients with connective tissue diseases and/or renal disease, the number of leukocytes in the blood should be monitored.

In susceptible patients, suppression of the RAAS activity may lead to impaired renal function. In patients with severe chronic heart failure, whose renal function may depend on RAAS activity, treatment with ACE inhibitors, including Quinapril, may be accompanied by oliguria and/or progressive azotemia, and in rare cases, acute renal failure and/or death. Use of ARB II, ACE inhibitors, or aliskiren may lead to dual blockade of RAAS activity. This effect may manifest as decreased blood pressure, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Blood pressure, renal function, and plasma electrolyte levels should be carefully monitored in patients taking Quinapril and other drugs affecting the RAAS. Concurrent use of RAAS-active agents and quinapril should be avoided. If use of this combination is necessary, the benefit-risk ratio of the combination should be assessed in each individual case, and renal function and potassium levels should be regularly monitored.

In patients with chronic heart failure or arterial hypertension with unilateral or bilateral renal artery stenosis, an increase in blood urea nitrogen and serum creatinine was observed in some cases during treatment with ACE inhibitors. These changes were almost always reversible and disappeared after discontinuation of the ACE inhibitor and/or diuretic. In such cases, renal function should be monitored during the first few weeks of treatment.

The T_1/2 of quinaprilat increases with decreasing creatinine clearance. In patients with creatinine clearance less than 60 ml/min, Quinapril should be used at a lower initial dose. In such patients, the dose of the drug should be increased based on the therapeutic effect, with regular monitoring of renal function, although further deterioration of renal function was not noted in clinical studies during treatment with the drug.

Quinapril in combination with diuretics should be used with caution in patients with impaired liver function or progressive liver disease, as minor changes in water-electrolyte balance can cause the development of hepatic coma.

ACE inhibitors, including Quinapril, may increase serum potassium levels.

Quinapril may reduce hypokalemia caused by thiazide diuretics when used concomitantly. The use of quinapril as part of combination therapy with potassium-sparing diuretics has not been studied. Given the risk of a further increase in serum potassium levels, combination therapy with potassium-sparing diuretics should be conducted with caution, under the control of serum potassium levels.

Patients with diabetes mellitus may require more careful observation and adjustment of the dose of oral hypoglycemic agents and insulin, and glycemic control, especially during the first month of therapy with an ACE inhibitor, including Quinapril.

The development of cough has been noted during treatment with ACE inhibitors, including Quinapril. Typically, it is non-productive, persistent, and resolves after discontinuation of therapy. When conducting a differential diagnosis of cough, its possible connection with ACE inhibitors should be considered.

Before surgery (including dentistry), it is necessary to inform the surgeon/anesthesiologist about the use of ACE inhibitors.

If any symptoms of infection appear (e.g., acute tonsillitis, fever), the patient should immediately consult a doctor, as they may be a manifestation of neutropenia.

Effect on the ability to drive vehicles and operate machinery

Caution should be exercised when driving vehicles or performing other work requiring increased attention while using the drug Quinapril-SZ, especially at the beginning of treatment, due to the risk of developing arterial hypotension and dizziness.

Overdose

Symptoms pronounced decrease in blood pressure, dizziness, weakness, visual disturbances.

Treatment symptomatic. The patient should assume a horizontal position; intravenous infusion using a 0.9% sodium chloride solution is advisable (to increase blood volume). Hemodialysis and peritoneal dialysis are ineffective.

Drug Interactions

Tetracycline and other drugs interacting with magnesium

Concomitant use of tetracycline with quinapril reduces the absorption of tetracycline by approximately 28-37% due to the presence of magnesium carbonate as an excipient in the drug. The possibility of such interaction should be considered during concomitant use.

Lithium

In patients simultaneously receiving lithium preparations and ACE inhibitors, an increase in serum lithium levels and signs of lithium intoxication have been observed due to increased sodium excretion. These drugs should be used concomitantly with caution; during treatment, regular determination of serum lithium levels is indicated. Concurrent intake of diuretics may increase the risk of lithium intoxication.

Diuretics

When quinapril is used concomitantly with diuretics, an enhancement of the antihypertensive effect is noted.

Drugs that increase serum potassium levels

If a patient receiving Quinapril requires potassium-sparing diuretics (e.g., spironolactone, triamterene, or amiloride), potassium preparations, and salt substitutes containing potassium, they should be used cautiously under the control of serum potassium concentration.

Ethanol (beverages containing alcohol)

Ethanol enhances the antihypertensive effect of quinapril.

Oral hypoglycemic agents and insulin

Therapy with ACE inhibitors is sometimes accompanied by the development of hypoglycemia in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents. Quinapril enhances the effect of oral hypoglycemic agents and insulin.

Other drugs

No signs of clinically significant pharmacokinetic interaction of quinapril with propranolol, hydrochlorothiazide, digoxin, or cimetidine have been identified. The use of quinapril twice daily did not significantly affect the anticoagulant effect of warfarin upon its single administration (assessed based on prothrombin time).

Concomitant multiple administration of atorvastatin at a dose of 10 mg with quinapril at a dose of 80 mg did not lead to significant changes in the steady-state pharmacokinetic parameters of atorvastatin.

Quinapril increases the risk of leukopenia when used concomitantly with allopurinol, cytotoxic agents, immunosuppressants, procainamide.

Antihypertensive drugs, narcotic analgesics, and medicinal products for general anesthesia enhance the antihypertensive effect of quinapril.

Estrogens, NSAIDs (including selective COX-2 inhibitors) weaken the antihypertensive effect of quinapril due to fluid retention. Furthermore, in elderly patients, in patients with decreased blood volume (including patients receiving diuretic therapy) or in patients with impaired renal function, the concomitant use of NSAIDs (including selective COX-2 inhibitors) with ACE inhibitors, including quinapril, may lead to deterioration of renal function, including possible acute renal failure. Renal function should be regularly monitored in patients receiving NSAIDs and Quinapril concomitantly.

Use of ARB II, ACE inhibitors, or aliskiren may lead to dual blockade of RAAS activity. This effect may manifest as decreased blood pressure, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.

Quinapril should not be used concomitantly with aliskiren and aliskiren-containing products or with ARB II or with other drugs inhibiting the RAAS (dual blockade of the RAAS)

• In patients with diabetes mellitus or in patients with diabetes mellitus with target organ damage (diabetic nephropathy);
• In patients with impaired renal function (GFR less than 60 ml/min/1.73 m²);
• In patients with hyperkalemia (more than 5 mmol/L);
• In patients with chronic heart failure and arterial hypertension.

Medicinal products that cause bone marrow function depression increase the risk of developing neutropenia and/or agranulocytosis.

When ACE inhibitors and gold preparations (sodium aurothiomalate, intravenous) are used concomitantly, a symptom complex including facial flushing, nausea, vomiting, and decreased blood pressure has been described.

Patients simultaneously receiving therapy with mTOR enzyme inhibitors (e.g., temsirolimus) or DPP-4 inhibitors (sitagliptin, vildagliptin, alogliptin, saxagliptin, linagliptin) or estramustine may be at greater risk of developing angioedema. Caution should be exercised when using these drugs concomitantly with the drug Quinapril-SZ.

Storage Conditions

The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 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.