Accuzid-20 (quinaprilum) coated tablets 20 mg/12.5 mg. №30

Accuzid-20 Pharmachologic effect

Accuzid is a combination drug, which includes an ACE inhibitor – quinapril and a thiazide diuretic – hydrochlorothiazide.

ACE is an enzyme that catalyzes the conversion of angiotensin I to angiotensin II, which has a vasoconstrictive effect and controls vascular tone, incl. by stimulating the secretion of aldosterone by the adrenal cortex. Quinapril inhibits circulating plasma and tissue ACE and causes a decrease in vasopressor activity and aldosterone secretion. Elimination of the negative effect of angiotensin II on renin secretion by the feedback mechanism leads to an increase in plasma renin activity. At the same time, a decrease in blood pressure is accompanied by a decrease in peripheral vascular resistance and renal vascular resistance, while changes in heart rate, cardiac output, renal blood flow, glomerular filtration rate and filtration fraction are negligible or absent. Quinapril increases exercise tolerance. With prolonged use, it contributes to the reverse development of myocardial hypertrophy in patients with arterial hypertension; improves blood supply to ischemic myocardium. Enhances coronary and renal blood flow. Reduces platelet aggregation.

In addition, hinapril somewhat reduces the excretion of potassium caused by hydrochlorothiazide, which, due to its diuretic action, also increases the activity of blood plasma renin, the secretion of aldosterone, reduces the content of potassium in the blood serum and increases its excretion by the kidneys.

Hydrochlorothiazide is a diuretic that has a direct effect on the kidneys, increasing the excretion of sodium, chlorides, fluids, as well as potassium and bicarbonates, and reducing the excretion of calcium. With prolonged use, a decrease in OPSS is noted.

Thus, the use of a combination of quinapril and hydrochlorothiazide leads to a more pronounced decrease in blood pressure than therapy with each drug alone.

The antihypertensive effect of quinapril develops within 1 hour after ingestion, reaches a maximum after 2-4 hours and persists for 24 hours with long-term treatment. In some cases, at least 2 weeks of therapy is required to achieve the maximum antihypertensive effect.

The diuretic effect of hydrochlorothiazide develops within 2 hours, reaches a maximum after about 4 hours and lasts about 6-12 hours.

Arterial hypertension in patients who are indicated for combination therapy with quinapril and hydrochlorothiazide.

hypersensitivity to active substances, other auxiliary components of the drug, sulfonamide derivatives;

angioedema in history as a result of previous therapy with ACE inhibitors;

idiopathic and hereditary angioedema;

severe renal failure (Cl creatinine less than 30 ml / min);

anuria;

severe liver failure;

Addison’s disease;

refractory hypokalemia, hypercalcemia and hyponatremia;

obstruction of the outflow tract of the left ventricle of the heart;

diabetes mellitus with chronic kidney disease with moderate renal failure (glomerular filtration rate ( GFR ) <60 ml/min);

lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

simultaneous administration of aliskiren and Accuzid in patients with diabetes mellitus, impaired renal function (GFR <60 ml / min / 1.73 m ² ), hyperkalemia (≥5 mmol / l), chronic heart failure with low blood pressure;

concomitant administration with angiotensin II receptor antagonists or other ACE inhibitors in patients with diabetes mellitus and end-organ damage, moderate to severe nocturnal dysfunction (GFR <60 ml / min / 1.73 m ² ), hyperkalemia (≥5 mmol / l), chronic heart failure with low blood pressure;

children under 18 years of age (efficacy and safety have not been established).

With caution: patients who have previously taken diuretics and are on a diet with limited salt or who are on hemodialysis; severe chronic heart failure in patients with or without concomitant renal failure; conditions accompanied by a decrease in BCC (including vomiting and diarrhea); oppression of bone marrow hematopoiesis; aortic stenosis; cerebrovascular disease (a sharp decrease in blood pressure during therapy with ACE inhibitorsmay worsen the course of these diseases); condition after kidney transplantation; bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma); abnormal liver function or progressive liver disease; diabetes; major surgery and general anesthesia; concomitant use of other antihypertensive drugs, as well as inhibitors of mTOR enzymesand DPP-4; violation of water and electrolyte balance (hyperkalemia, hypokalemia, hyponatremia, hypercalcemia); gout; symptomatic hyperuricemia; elderly age; simultaneous use of cardiac glycosides and other drugs that can lead to the development of ventricular tachycardia of the “pirouette” type; systemic lupus erythematosus, angle-closure glaucoma).

Accuzid during pregnancy, women planning pregnancy, as well as women of reproductive age who do not use reliable methods of contraception.

Women of childbearing age who take Accuzid-20 should use reliable methods of contraception.

When pregnancy is diagnosed, Accuzid   should be discontinued as soon as possible.

The appointment of ACE inhibitors during pregnancy is accompanied by an increased risk of developing abnormalities of the cardiovascular system and the fetal nervous system. In addition, against the background of the use of ACE inhibitors during pregnancy, cases of oligohydramnios, premature birth, the birth of children with arterial hypotension, impaired renal function, including acute renal failure, hypoplasia of the bones of the skull, contractures of the limbs, craniofacial anomalies, pulmonary hypoplasia, intrauterine development, open ductus arteriosus, as well as cases of intrauterine fetal death and death of newborns. Often, oligohydramnios is diagnosed after the fetus has been irreversibly damaged.

Neonates exposed to ACE inhibitors in utero should be monitored for hypotension, oliguria, and hyperkalemia. When oliguria appears, blood pressure and renal perfusion should be maintained.

Thiazides cross the placenta and are found in the blood of the umbilical cord. Non-teratogenic effects of thiazides include jaundice and thrombocytopenia of the fetus and / or newborn, and the possibility of other adverse events observed in the mother is also possible.

ACE inhibitors , including quinapril, pass into breast milk to a limited extent. Thiazides pass into breast milk. Given the possibility of developing serious adverse events in a newborn, Accuzid ^® should be discontinued during lactation or breastfeeding should be discontinued.

Inside 1 time per day, regardless of the meal.

For patients not receiving diuretics (regardless of whether quinapril monotherapy was previously performed or not), the recommended initial dose is 1 table. drug Accuzid ^® (12.5 mg + 10 mg) 1 time per day. Subsequently, if necessary, the dose can be increased to a maximum of 25 mg + 20 mg 1 time per day.

Effective control of blood pressure is usually achieved with the use of the drug Accuzid ^® in the dose range from 12.5 mg + 10 mg to 12.5 mg + 20 mg.

Special patient groups

Impaired kidney function. In patients with mild renal impairment (Cl creatinine ≥60 ml / min), the initial dose of Accuzid ^® is 12.5 mg + 10 mg. The drug Accuzid ^® should not be prescribed as initial therapy in patients with impaired renal function with Cl creatinine <60 ml / min. In patients with moderate renal impairment (Cl creatinine 60-30 ml / min), quinapril should be used at an initial dose of 5 mg with further titration.

Elderly patients. Dose adjustment of Accuzid ^® in elderly patients is not required. The initial dose of the drug Accuzid ^®  – 1 tab. (12.5 mg + 10 mg).

Adverse events occurring in more than 1% of patients treated with quinapril in combination with hydrochlorothiazide

Headache, dizziness, cough, unproductive persistent cough (resolved after discontinuation of therapy), fatigue, myalgia, viral infections, rhinitis, nausea, vomiting, upper respiratory tract infections, insomnia, bronchitis, dyspepsia, asthenia, pharyngitis, symptoms of vasodilation, vertigo , chest pain, abdominal pain, back pain. In general, adverse events were mild and transient, independent of age, gender, race, and duration of therapy.

Laboratory indicators: an increase (more than 1.25 times compared with VGN) in the concentration of creatinine and urea nitrogen in the blood, respectively, in 3 and 4% of patients treated with quinapril and hydrochlorothiazide.