Active substanceHydrochlorothiazide + HinaprilHydrochlorothiazide + Hinapril
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Dosage form: & nbspfilm-coated tablets
Composition:

Each tablet, film-coated, with a dosage of 12.5 mg + 10 mg contains:

Active substances: quinapril hydrochloride - 10.832 mg (equivalent to 10.00 mg of quinapril), hydrochlorothiazide - 12.50 mg;

Excipients: lactose monohydrate - 32,348 mg, magnesium carbonate - 35,320 mg, povidone - K25 - 4,000 mg, crospovidone - 4,000 mg, magnesium stearate - 1,000 mg,

Film sheath: Opadrai Pink OY-S-6937* - 3,000 mg, herb wax - 0,050 mg.

Each tablet, film-coated, with a dosage of 12.5 mg + 20 mg contains:

Active substances: quinapril hydrochloride - 21.664 mg (equivalent to 20.00 mg of quinapril), hydrochlorothiazide - 12.50 mg;

Excipients: lactose monohydrate - 77.196 mg, magnesium carbonate - 70.640 mg, povidone - K25 - 8,000 mg, crospovidone - 8,000 mg, magnesium stearate - 2,000 mg,

Film sheath: Opadrai Pink OY-S-6937* - 6,000 mg, herbal wax - 0,100 mg.

Each tablet, film-coated, with a dosage of 25 mg + 20 mg contains:

Active substances: quinapril hydrochloride - 21.664 mg (equivalent to 20.00 mg of quinapril), hydrochlorothiazide - 25.00 mg;

Excipients: lactose monohydrate - 64.696 mg, magnesium carbonate - 70.640 mg, povidone - K25 - 8,000 mg, crospovidone - 8,000 mg, magnesium stearate - 2,000 mg;

Film sheath: Opadrai Pink OY-S-6937* - 6,000 mg, herbal wax - 0,100 mg.

* Pick up pink OY-S-6937 contains: hypromellose, giprolose, titanium dioxide, macrogol-400, iron dye oxide yellow, iron oxide dye red.

Description:

Dosage of 12.5 mg + 10 mg: oval, biconvex tablets, covered with a film coating of pink color with a risk on both sides and labeling "PD 222 "on one side.

Dosage of 12.5 mg + 20 mg: triangular, biconvex tablets, covered with a film coating of pink color with a risk and labeling "PD 220 "on one side.

Dosage of 25 mg + 20 mg: round, biconvex tablets, covered with a film coating of pink color with marking "PD 223 "on one side.

Pharmacotherapeutic group:Hypotensive combined agent (diuretic + angiotensin-converting enzyme inhibitor)
ATX: & nbsp

C.09.B.A.06   Hinapril in combination with diuretics

Pharmacodynamics:
Akkudid® is a combined preparation that contains an angiotensin-converting enzyme (ACE) inhibitor - quinapril and thiazide diuretic hydrochlorothiazide.
ACE is an enzyme that catalyzes the conversion of angiotensin I into angiotensin II, which has a vasoconstrictive effect and controls the tone of the vessels,including by stimulating the secretion of aldosterone with the adrenal cortex. Hinapril competitively inhibits circulating in blood 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 renin plasma activity. At the same time, lowering blood pressure (BP) is accompanied by a decrease in the total peripheral vascular resistance (OPSS) and resistance of renal vessels, while changes in the heart rate (HR), cardiac output, renal blood flow, glomerular filtration rate and filtration fraction are minor or absent .
Hinapril increases exercise tolerance. With prolonged use contributes to the reverse development of myocardial hypertrophy in patients with arterial hypertension; improves the blood supply of the ischemic myocardium. Strengthens coronary and renal blood flow. Reduces the aggregation of platelets. Besides, quinapril slightly reduces the excretion of potassium caused by hydrochlorothiazide,which due to its diuretic action also increases the activity of renin of blood plasma, the secretion of aldosterone, reduces the potassium content in the serum and increases its excretion by the kidneys.
Hydrochlorothiazide is a diuretic with a direct effect on the kidneys, increasing the excretion of sodium, chloride, liquid, and also potassium and hydrocarbonates, and reducing the excretion of calcium. With prolonged use there is a decrease in OPSS. 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. Antihypertensive effect of quinapril develops within 1 hour after ingestion, reaches a maximum after 2-4 hours and persists for 24 hours with prolonged treatment. In some cases, at least 2 weeks of therapy are required to achieve the maximum antihypertensive effect.
The diuretic effect of hydrochlorothiazide develops within 2 hours, reaches a maximum in about 4 hours and lasts about 6-12 hours.
Pharmacokinetics:
Hinapril and hydrochlorothiazide do not affect the pharmacokinetics of each other.The concentration of quinapril in blood plasma upon ingestion reaches a maximum within 1 hour. Hinapril is rapidly metabolized to quinaprilate by cleavage of the ester group (the main metabolite is dibasic acid of quinapril), which is a potent inhibitor of ACE.
Taking into account the excretion of quinapril and its metabolites by the kidneys, the degree of absorption is approximately 60%. About 38% of the ingested dose of quinapril circulates in the blood plasma in the form of quinaprilate. Half-life (T1/2) of quinapril from the blood plasma is about 1 hour. The concentration of quinaprilat in the blood plasma reaches a maximum about 2 hours after ingestion of quinapril. Hinaprilat is excreted mainly by the kidneys, T1/2 - about 3 hours. Approximately 97% of quinapril and quinaprilat circulate in blood plasma in protein-related form. Hinapril and its metabolites do not penetrate the blood-brain barrier.
In patients with renal insufficiency T1/2 Hinaprilat increases with decreasing creatinine clearance (CK). The excretion of quinaprilat is also reduced in elderly patients (over 65 years of age) and closely correlates with the degree of impaired renal function, however, in general, there is no difference in the efficacy and safety of treatment in elderly and younger patients.
The absorption of hydrochlorothiazide is somewhat slower (1-2.5 hours) and fuller (50-80%). Hydrochlorothiazide It is not metabolized in the liver and is excreted unchanged by the kidneys. T1/2 is between 4 and 15 hours. About 61% of the ingested dose is excreted unchanged for 24 hours. Hydrochlorothiazide penetrates the placenta and into breast milk, but does not pass through the blood-brain barrier.
Indications:Arterial hypertension in patients who are shown combined therapy with quinapril and hydrochlorothiazide.
Contraindications:

Hypersensitivity to the active substances, other auxiliary components of the preparation, to derivatives of sulfonamide.

Angioedema in the history as a result of previous therapy with ACE inhibitors.

Idiopathic and hereditary angioedema. Severe renal failure (CC less than 30 ml / min).

Anuria.

Severe hepatic insufficiency. Addison's disease.

Refractory hypokalemia, hypercalcemia and hyponatremia. Obstruction of the outflow tract of the left ventricle of the heart.

Diabetes mellitus with the presence of chronic kidney disease with renal insufficiency of moderate severity (glomerular filtration rate (GFR) <60 ml / min).

Age to 18 years (effectiveness and safety not established).

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Do not take at the same time aliskiren and the drug Akkudid® in patients with diabetes mellitus, in patients with impaired renal function (GFR <60 mL / min / 1.73 m2), in patients with hyperkalemia (> 5 mmol / l), in patients with chronic heart failure with low blood pressure. Do not use quinapril and hydrochlorothiazide concomitantly with antagonists of angiothezipin receptors II or other ACE inhibitors in patients with sugar diabetes and target organ damage in the terminal stage, in patients with impaired renal function from medium to severe severity (GFR <60 mL / min / 1.73 m), in patients with hyperkalemia (> 5 mmol / L), in patients with chronic heart failure with low blood pressure.

Carefully:In patients who had previously taken diuretics and followed a diet with restriction of table salt or on hemodialysis; severe chronic heart failure in patients with concomitant renal failure or without it; Condition, accompanied by a decrease in the volume of circulating blood (bcc) (incl.vomiting and diarrhea); oppression of bone marrow hematopoiesis; aortic stenosis; cerebrovascular diseases (a sharp decrease in blood pressure on the background of therapy with ACE inhibitors may 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 diseases of connective tissue (including systemic lupus erythematosus, scleroderma); impaired liver function or progressive liver disease; diabetes; extensive surgical interventions and general anesthesia, simultaneous administration of other antihypertensive agents, as well as inhibitors of mTOR and DPP-4 enzymes; disturbances of water-electrolyte balance (hyperkalemia, hypokalemia, hyponatremia, hypercalcemia); gout, symptomatic hyperuricemia, advanced age, with the simultaneous use of cardiac glycosides and other drugs that can lead to the development of ventricular tachycardia as pirouette; systemic lupus erythematosus, angle-closure glaucoma.
Pregnancy and lactation:
The use of the drug Akkudid® is contraindicated during pregnancy,women planning pregnancy, as well as women of reproductive age who do not use reliable methods of contraception.
Women of reproductive age who take Acquidоо should use reliable methods of contraception.
When diagnosing pregnancy, the drug should be discarded as soon as possible.
The appointment of ACE inhibitors during pregnancy is accompanied by an increased risk of anomalies in the cardiovascular and nervous system of the fetus. In addition, against the background of the use of ACE inhibitors during pregnancy, cases of low blood pressure, premature birth, birth of children with arterial hypotension, impaired renal function, including acute renal failure, hypoplasia of the skull bones, limb contractures, craniofacial anomalies, lung hypoplasia, delay intrauterine development, an open arterial duct, as well as cases of intrauterine fetal death and death of newborns. Often, anhydration is diagnosed after the fetus has been irreversibly damaged.
The newborns, who underwent intrauterine exposure to ACE inhibitors,should be observed in order to identify arterial hypotension, oliguria and hyperkalemia. When oliguria occurs, blood pressure and renal perfusion should be maintained. Thiazides penetrate 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 other undesirable effects observed in the mother are also possible.
ACE inhibitors, including quinapril, to a limited extent penetrate into breast milk. Thiazides penetrate into breast milk. Given the possibility of developing serious adverse events in the newborn, the drug Akkudid® should be abolished during lactation or stop breastfeeding.
Dosing and Administration:

Inside 1 time per day, regardless of food intake.

For patients who do not receive diuretics (regardless of whether previous monotherapy with quinapril or not), the recommended initial dose of the drug Akkudid® is 10 mg + 12.5 mg once a day. In the subsequent if necessary, the dose can be increased to a maximum of 20 mg + 25 mg once a day.

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

Patients with impaired renal function

Patients with impaired mild renal function (creatinine clearance of> 60 ml / min) Akkuzid® initial dose of the drug is 10 mg + 12.5 mg.

Akkuzid® The drug should not be administered as an initial treatment for patients with impaired renal function with creatinine clearance <60 mL / min. Patients with impaired renal function moderate severity (QC 60 - 30 ml / min) to be applied quinapril in an initial dose of 5 mg with further titration.

Elderly patients

Correction of the dose of the drug Akkuziyd® in elderly patients is not required. The initial dose of the drug Akkudid® is 10 mg + 12.5 mg.

Side effects:

Adverse events occurring in more than 1.0% of patients who received quinapril in combination with hydrochlorothiazide, included the following: headache, dizziness, cough, persistent cough nonproductive (passed after the cessation of therapy); fatigue, myalgia, viral infections, rhinitis, nausea, vomiting, upper respiratory tract infection, insomnia, bronchitis, dyspepsia, fatigue, sore throat, symptoms of vasodilation, vertigo, chest pain, abdominal pain, back pain.

In general, the adverse events were mild and transient, independent of age, sex, race, and duration of therapy.

Laboratory indicators: the increase (more than 1.25 times as compared with the upper limit of the norm) of the concentration of creatinine and urea nitrogen in the blood, respectively, in 3% and 4% of patients who received quinapril and hydrochlorothiazide.

Adverse events occurring in 0.5-1.0% of patients receiving chiapril in combination with hydrochlorothiazide included the following:

On the part of the hematopoiesis system: hemolytic anemia, thrombocytopenia, leukopenia, agranulocytosis.

From the nervous system: increased excitability, paresthesia, depression, drowsiness.

From the cardiovascular system: heart palpitations, tachycardia, marked decrease in blood pressure, orthostatic hypotension, fainting, heart rhythm disturbances, myocardial infarction, ischemic stroke, peripheral edema (including generalized), hypertensive crisis, angina, heart failure.

From the respiratory system: shortness of breath, sinusitis.

From the digestive system: dryness of the mucous membrane of the mouth and throat, constipation or diarrhea, flatulence, pancreatitis, hepatitis, angioedema, intestinal edema, gastrointestinal bleeding, impaired functional "hepatic" tests.

Allergic reactions: skin rash, itching, urticaria, angioedema, photosensitization, multiforme exudative erythema, exfoliative dermatitis, pemphigus, Stevens-Johnson syndrome, anaphylactic reactions, increased sweating.

From the side of the musculoskeletal and connective tissue: joint pain.

From the genitourinary system: urinary tract infections, renal dysfunction, acute renal failure, decreased potency.

From the side of the organ of vision: impaired vision.

Other: alopecia, hyperkalemia.

With simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate, intravenously) describes a symptom complex, including facial flushing, nausea, vomiting, lowering blood pressure and flu-like syndrome.

Adverse reactions noted with the use of hydrochlorothiazide:

From the side of metabolism: hypokalemia, hypomagnesemia,hypercalcaemia and hypochloraemic alkalosis (dryness of the oral mucosa, thirst, heart rhythm disturbance, changes in mood or psyche, convulsions and muscle pain, nausea, vomiting, fatigue or weakness). Hypochloremic alkalosis can cause hepatic encephalopathy or hepatic coma.

Hyponatremia (confusion, convulsions, lethargy, slowing down the thinking process, increased fatigue, excitability, muscle cramps).

Metabolic disorders: hyperglycemia, glucosuria, hyperuricemia with the development of an attack of gout.

Treatment with thiazides can reduce glucose tolerance, and latent diabetes mellitus can manifest. When using high doses, lipid concentrations in the blood plasma can increase.

From the digestive system: cholecystitis, sialadenitis, anorexia.

From the cardiovascular system: arrhythmias, orthostatic hypotension, vasculitis.

From the nervous system: temporarily blurred vision.

From the hematopoiesis: aplastic anemia.

Allergic reactions: purpura, necrotizing vasculitis, respiratory distress syndrome (including pneumonitis and noncardiogenic pulmonary edema), photosensitivity, anaphylactic reactions up to shock.

From the side of the organ of vision: transient acute myopia and acute open-angle glaucoma.

Other: decreased potency, impaired renal function, interstitial nephritis.

Postmarketing research

From the cardiovascular system: bradycardia, pulmonary heart, vasculitis, deep vein thrombosis.

From the digestive system: tumors of the gastrointestinal tract, cholestatic jaundice, hepatitis, esophagitis, vomiting, diarrhea.

On the part of the hematopoiesis system: anemia.

From the side of metabolism: decrease in body weight.

From the musculoskeletal system: Myopathy, myositis, arthritis.

From the nervous system: paralysis, hemiplegia, speech disorders, gait disturbance, phenomena of meningism, amnesia.

From the respiratory system: pneumonia, bronchial asthma.

From the skin: urticaria, maculopapular rash, petechiae.

From the urinary system: albuminuria, pyuria, hematuria, nephrosis.

Other: shock, accidental injuries, inflammation of subcutaneous fat, generalized edema, hernia.

Overdose:
There is no information about an overdose of the drug Akkudyod ® and special measures for its therapy.
Symptoms: marked decrease in blood pressure, disturbance of water-electrolyte balance: hyponatremia, hypochloraemia, hypokalemia (with simultaneous use with cardiac glycosides, the risk of arrhythmia increases), a decrease in bcc against the background of forced diuresis.
Treatment: stop taking the drug, rinse the stomach, take Activated carbon, intravenous administration of 0.9% sodium chloride solution, restoration of water-electrolyte balance of blood, symptomatic and maintenance therapy. Hemodialysis and peritoneal dialysis have little effect on the excretion of quinapril and quinaprilate.
Interaction:

Tetracycline and other drugs that interact with magnesium

With the simultaneous use of the drug Akkudyod® and tetracycline, the absorption of the latter decreases by approximately 28-37% because of the presence of the drug Akkidod® magnesium carbonate as a filler. This interaction should be taken into account when using the drug Akkudid® and tetracycline or other drugs capable of interacting with magnesium.

Lithium

Lithium usually should not be used in combination with diuretics, since the latter reduce the renal clearance of lithium and increase the risk of unwanted effects. In patients taking lithium drugs and ACE inhibitors. there is an increase in serum lithium concentrations and symptoms of lithium intoxication. These changes are associated with the loss of sodium under the influence of ACE inhibitors. When using the drug Akkudid ®, the risk of lithium intoxication can be increased. At the same time, use these drugs with caution.

Diuretics

With the simultaneous use of hiparyl with diuretics, there is an increase in antihypertensive action (see section "Special instructions").

Ethanol, barbiturates or narcotic analgesics

When used simultaneously with the drug, Accoucad® can increase the risk of orthostatic hypotension (the drug includes a thiazide diuretic - hydrochlorothiazide).

Hypoglycemic agents (hypoglycemic agents for admission inside and insulin)

It may be necessary to correct the dose of hypoglycemic agents.

Hyperglycemia induced by thiazide diuretics can disrupt the control of glucose concentration in the blood plasma. Reducing the potassium content in blood plasma leads to increased tolerance to glucose.It is necessary to monitor the concentration of glucose in the blood plasma, but the need to prescribe potassium preparations, in order to maintain the potassium content in blood plasma and correct hypoglycemic therapy.

Other antihypertensives

The thiazide diuretic, which is part of the drug Akkudid®, can enhance the action of other antihypertensive drugs, especially ganglion blockers or beta-blockers. Due to the content of hydrochlorothiazide, the antihypertensive effect of the drug Akkudiad® can intensify after sympathectomy.

Glucocorticosteroids, adrenocorticotropic hormone (ACTH)

Increased loss of electrolytes, especially potassium.

Pressor amines (e.g., norepinephrine)

It is possible to reduce the therapeutic effect of PRSs (clinical significance is negligible).

Nondepolarizing miorslaxants (for example, tubocurarine chloride)

Possible strengthening of the action of miorslaksantov.

Non-steroidal anti-inflammatory drugs (NSAIDs)

In some patients, NSAIDs may cause a decrease in diuretic, natriuretic and antihypertensive effect of "loop", potassium-sparing and thiazide diuretics.In this regard, while the use of these drugs with the drug Akkuzid® patients should be monitored to assess the effectiveness of therapy. Furthermore, elderly patients, patients with reduced BCC (including patients receiving diuretics) or patients with impaired renal function, the simultaneous use of NSAIDs (including selective inhibitors of cyclooxygenase 2), with ACE inhibitors including quinapril, can lead to deterioration of renal function, including possible acute renal failure. It is necessary to regularly monitor the status of kidney function in patients receiving both NSAIDs and quinapril.

There may also be a weakening of the antihypertensive effect ACE inhibitors, including quinaril, when used simultaneously with NSAIDs.

Drugs that can cause hyperkalemia

Quinapril - ACE inhibitor, reduces the concentration of aldosterone, which in turn can lead to hyperkalemia. In this connection, in the treatment of drug Akkuzid "potassium supplements, salt substitutes containing potassium and other drugs affecting pas increased potassium content in blood serum, it should be used with caution, controlling the content of potassium in serum.Since the composition of the drug Acquidade® includes a diuretic, the addition of a potassium-sparing diuretic is not recommended. In elderly patients and patients with impaired AFP simultaneous reception of inhibitors of renal function with sulfamethoxazole / trimethoprim was accompanied by severe hyperkalemia, which is believed to have been caused by trimethoprim. Therefore, the drug Akkudid® should be used with caution at the same time as preparations containing trimethoprim, regularly monitoring the potassium content in the blood plasma.

Digoxin

Water-electrolyte disturbances, caused by thiazide diuretics (eg hypokalemia, hypomagnesemia), increase the risk of developing digoxin toxicity symptoms, which can lead to fatal rhythm disturbances (see section "Special instructions").

Ion exchange resins

Absorption of hydrochlorothiazide decreases in the presence of colestyramine and colestipol. With a single application, these drugs bind hydrochlorothiazide and reduce its absorption in the gastrointestinal tract by 85 and 43%, respectively.

Drugs for the treatment of gout (allopurinol, uricosuric drugs, inhibitors of xanthine oxidase) Hyperuricemia induced by thiazide diuretics can disrupt the control of gout patients with allopurinol and probenecid. The simultaneous use of hydrochlorothiazide and allopurinol may increase the frequency of hypersensitivity reactions to allopurinol.

Other drugs

The signs of clinically significant pharmacokinetic interaction of quinapril with propranolol, hydrochlorothiazide or cimetidine was not detected. The use of quinapril 2 times a day did not significantly affect the anticoagulant effect of warfarin when it was applied once (evaluated on the basis of prothrombin time). Simultaneous multiple use of atorvastatin at a dose of 10 mg with quinapril at a dose of 80 mg did not lead to significant changes in equilibrium pharmacokinetic parameters atorvastatin. Hypotensive drugs, narcotic analgesics, drugs for general anesthesia enhance antihypertensive effect of quinapril. Hinapril increases the risk of developing leukopenia with simultaneous application with allopurinol, cytostatic agents, immunosuppressants, procainamide.With simultaneous use of ACE inhibitors and preparations of gold (sodium aurotomy malate, intravenously) describes a symptom complex, including facial flushing, nausea, vomiting, lowering blood pressure and flu-like syndrome. With the simultaneous use of cardiac glycosides and other drugs that can lead to the development of ventricular tachycardia as pirouette, care should be taken in connection with the possibility of developing hypokalemia and, consequently, enhancing the toxic effect of these drugs.

The use of angiotensin II receptor antagonists, ACE inhibitors or aliskireia may result in a double blockade of RAAS activity. This effect can be manifested by a decrease in blood pressure, hyperkalemia and changes in kidney function (including acute renal failure) compared with monotherapy.

Do not use quinapril and hydrochlorothiazide simultaneously with aliskiren in patients with diabetes mellitus, in patients with impaired renal function from moderate to severe severity (GFR <60 mL / min / 1.73 m2), in patients with hyperkalemia (> 5 mmol / l), in patients with chronic heart failure with low blood pressure (see section "Contraindications").

Do not use quinapril and hydrochlorothiazide concomitantly with angiotensin II receptor antagonists or other ACE inhibitors in patients with diabetes mellitus and end-stage target organ damage in patients with moderate to severe renal dysfunction (GFR <60 mL / min / 1.73 m2), in patients with hyperkalemia (> 5 mmol / l), in patients with chronic heart failure with low blood pressure (see section "Contraindications").

Patients simultaneously receiving therapy with enzyme inhibitors mTOR (eg, tessirolimus) and DPP-4 (for example, vildagliptin) may be at greater risk of developing angioedema. Care should be taken when simultaneous application of these drugs with the drug Akkudid®.

Special instructions:

Angioedema

In the treatment with ACE inhibitors, cases of angioedema of the face and neck have been described, including 0.1% of patients who received quinapril. When a laryngeal whistle or angioedema occurs, face, eyes, tongue, or vocal cords, difficulties in swallowing food or breathing, the drug should be immediately discarded.The patient should be given adequate treatment and observed until the symptoms of edema disappear. Anti-histamines can be used to reduce symptoms. Angioedema with involvement of the larynx can lead to death. If edema of the tongue, vocal cords or larynx threatens with the development of airway obstruction, adequate emergency therapy, including subcutaneous injection of an adrenaline solution 1: 1000 (0.3-0.5 ml), is necessary.

In the treatment of ACE inhibitors, cases of angioedema of the intestine are also described. Patients noted abdominal pain (with / without nausea and vomiting); in some cases without a previous angioedema and a normal activity of C1-esterase. The diagnosis was established using computed tomography of the abdominal region, ultrasound examination, or at the time of surgery. Symptoms disappeared after discontinuation of ACE inhibitors. Patients who suffered angioedema, not associated with the administration of ACE inhibitors. may have a risk of developing it when treated with drugs of this group.Patients simultaneously receiving therapy with enzyme inhibitors mTOR (eg, tessirolimus) and DPP-4 (eg, vildaglipt) may be at greater risk of developing angioedema.

Ethnic differences

ACE inhibitors more often cause angioedema in patients of the Negroid race than in Caucasoid. Just as with the use of other ACE inhibitors, quinapril may be less effective for reducing blood pressure in patients of the Negroid race.

Carrying out desensitizing therapy

Patients receiving ACE inhibitors during the desensitizing therapy with Hepaticoptera venom (wasps, bees) can develop persistent anaphylactoid reactions that threaten life. The temporary cessation of the ACE inhibitor regresses the symptoms, but they can appear again when the therapy with ACE inhibitors is resumed.

Hemodialysis

Anaphylactoid reactions can also develop with the use of ACE inhibitors in patients undergoing low-density lipoprotein apheresis using dextran sulfate or patients on hemodialysis using high-flow membranes, such as polyacrylonitrile.You must use an alternative lipid-lowering therapy or use other membranes for hemodialysis.

Arterial hypotension

Akkuzid® drug can cause transient hypotension, but no more frequently than in the monotherapy components that make up the drug. Symptomatic hypotension is rarely found in the treatment of quinapril in patients with uncomplicated hypertension, but may develop as a result of ACE inhibitor therapy in patients with reduced BCC, for example, after previous treatment with diuretics, with a diet restricted salt or during hemodialysis. In case of symptomatic arterial hypotension, the patient should take a position of "lying" to hold his legs raised intravenous infusion of 0.9% sodium chloride solution. Transient arterial hypotension is not contraindication to further use of the drug Akkudid®, however in such cases it is advisable to reduce its dose.

Chronic heart failure

In patients with chronic heart failure with the presence of renal failure.and / or chronic heart failure without the presence of renal failure therapy with an inhibitor APF about arterial hypertension can lead to excessive reduction in blood pressure, which can be accompanied by oliguria, azotemia and, in rare cases, acute renal failure and even death. The treatment of such patients with Acquidol® should be started under close medical supervision and supervision during the first 2 weeks of therapy and with an increase in the dose of the drug.

Agranulocytosis

In rare cases, therapy with ACE inhibitors may be accompanied by the development of agranulocytosis and suppression of bone marrow function in patients with uncomplicated arterial hypertension, but more often in patients with impaired renal function, especially with connective tissue diseases. In these cases, the number of leukocytes in the blood should be monitored. If any symptoms appear (eg, sore throat, fever), patients should immediately consult a doctor, as they may be a manifestation of neutropenia.

Systemic lupus erythematosus

Thiazide diuretics can sometimes cause an exacerbation of the systemic lupus erythematosus.

Kidney function

The drug Akkudid® is not recommended for patients with severe renal dysfunction (CC less than 30 ml / min. Thiazide diuretics contribute to the progression of azotemia and have a cumulative effect with prolonged use in such patients. Drugs of choice in this group of patients receiving hipapril therapy are looped diuretics. For this reason, a fixed combination of hydrochlorothiazide / quinapril should not be used in patients with severe renal failure (see "Contraindications").

T1/2 Hinaprilata increases with a decrease in CK. Patients with SC less than 60 ml / min, but more than 30 ml / min quinapril should be administered at a lower initial dose. In such patients, the dose of Acquidol® should be increased taking into account the clinical state of the patient, with regular monitoring of kidney function, although in clinical studies there was no further impairment of kidney function when treated with the drug Acquidade®.

In patients with hypertension without obvious signs of an initial impairment of kidney function with the use of quinapril, especially in combination with a diuretic,An increase in the concentration of urea nitrogen in the blood and creatinine in the serum, which is usually weakly expressed, is usually transient. Similar changes are most likely in patients with initial renal dysfunction. In such cases, you may need to reduce the dose of Acquidol®. In all patients with hypertension, renal function should be monitored. Do not use the drug Akkudyod ® as an initial therapy in patients with SC less than 60 ml / min.

The effect of the renin-angiotensin-aldosterone system (RAAS)

In some patients, suppression of RAAS activity can lead to impaired renal function. In patients with severe chronic heart failure, kidney function depends on the activity of RAAS, so treatment with ACE inhibitors, including quinapril, can lead to oliguria and / or progressive azotemia, and in rare cases, to acute renal failure and / or death.

Double blockade of RAAS activity The use of antagonists of angiothezin II receptors, ACE inhibitors or aliskiren can lead to a double blockade of the activity of RAAS.This effect may be manifested by a decrease in blood pressure. hyperkalemia and changes in renal function (including acute renal failure) compared with monotherapy. Blood pressure, renal function and electrolyte content in blood plasma should be closely monitored in patients taking Acquidol® and other drugs that affect RAAS. It should avoid simultaneous use of RAAS-active agents and quinapril. The use of this combination should be narrowed down to individual cases with careful monitoring of kidney function and potassium levels in the blood plasma.

Stenosis of the renal arteries

In clinical studies in patients with hypertension with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, in the treatment of ACE inhibitors, in some cases an increase in the concentration of urea nitrogen and creatinine in the serum was observed. These changes are almost always reversible and passed after the withdrawal of the ACE inhibitor and / or diuretic. In such cases, during the first few weeks of treatment with the drug Akkudid®, monitoring of kidney function is necessary.

Impaired liver function

The drug Akkudid® should be used with caution in patients with impaired liver function or progressive liver disease, since even small disturbances of the water-electrolyte balance can cause the development of a "hepatic" coma.

Water-electrolyte balance

FROM To identify possible violations of the water-electrolyte balance, it is necessary to regularly monitor the content of electrolytes in the blood serum. In patients receiving monotherapy with hipapril, as with other ACE inhibitors, the potassium content may increase.

Potassium of blood serum

Hyperkalemia (5.8 mmol / l) was observed in about 2% of patients taking quinapril, but in most cases this deviation was a single one and occurred during further therapy. The risk factors for the development of hyperscalcemia are: renal dysfunction, diabetes mellitus and simultaneous administration of potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, or other drugs that affect the increase in potassium in the blood serum. Simultaneous intake of potassium-sparing diuretics with the drug Acquidade®, which includes a thiazide diuretic, is not recommended.Treatment with thiazide diuretics is accompanied by hypokalemia, hyponatremia and hypochloraemic alkalosis. These disorders are sometimes manifested by the following symptoms: dryness of the oral mucosa. thirst, weakness, lethargy, drowsiness, restlessness, muscle weakness, muscle pain or spasm, lowering blood pressure. oliguria, tachycardia, nausea, confusion, convulsions and vomiting.

Hypokalemia can also enhance the toxic effect of cardiac glycosides. The risk of hypokalemia increased with cirrhosis of the liver, forced diuresis, inadequate use of drugs that improve myocardial metabolism, concomitant therapy glucocorticosteroid or adrenocorticotropic hormone (ACTH), concomitant use with drugs that increase the risk of hypokalemia with thiazide diuretics. The majority of patients can be expected balancing of opposite effects of quinapril and hydrochlorothiazide with respect to the content of potassium in the blood serum. In some cases the effect of one component Akkuzid® preparation may predominate over the other.Prior to and during treatment with the drug Akkudid®, the electrolyte content should be periodically monitored in order to detect possible disturbances in the water-electrolyte balance. Chloride deficiency associated with thiazide diuretic therapy is usually mild and only in exceptional cases requires appropriate treatment (eg, in diseases liver and / or kidney).

Hyponatremia

In hot weather, patients with peripheral edema can develop hyponatremia. When hyponatremia, adequate substitution therapy.

Hypocalcemia

Thiazide diuretics reduce excretion calcium by the kidneys.

Parathyroid glands

In rare cases, who received long-term therapy with thiazide diuretics. changes in the parathyroid glands accompanied by hypercalcemia and hypophosphatemia. More serious complications Hyperparathyrosis (nephrolithiasis, resorption bone tissue and peptic ulcer) is not are described. Before research functions parathyroid glands of thiazide diuretics needed cancel.

Magnesium

Thiazide diuretics increase the excretion of magnesium by the kidneys and can cause hypomagnesemia.

Glucose

Thiazide diuretics increase serum cholesterol concentrations, triglycerides and uric acid. These the effects are usually minor, but the development of overt gout or diabetes can be provoked in patients with a predisposition to these diseases.

Diabetes

Hyperglycaemia induced high doses of thiazide diuretics (including hydrochlorothiazide in a dose 100 mg / day), may interfere with the control of the glucose concentration in the blood plasma. Reducing the potassium content in blood plasma leads to increased tolerance to glucose. It is necessary to monitor the concentration of glucose in the blood plasma, if necessary, prescribe potassium preparations, in order to maintain the potassium content in the blood plasma and adjust hypoglycemic therapy. Therapy with ACE inhibitors may be accompanied by the development of hypoglycemia in patients with diabetes mellitus receiving insulinic hypoglycemic agents for oral ingestion. In the treatment of patients with diabetes, more careful monitoring and correction of the dose of hypoglycemic agents may be required.

Cough

When treated with ACE inhibitors. including quinapril, noted the development of cough. In a typical case, it is unproductive, persistent and passes after discontinuation of therapy. When differential diagnosis of cough should take into account its possible relationship with the use of inhibitors APF.

Surgical intervention

In patients undergoing surgery or general anesthesia, ACE inhibitors should be used with caution, as they block the formation of angiotensin II caused by compensatory renin secretion. This can lead to arterial hypotension, which is eliminated by increasing the BCC. In the case of surgical intervention, the patient should notify the anesthetist, that he is taking an inhibitor APF.

BCC

Patients should be warned that insufficient fluid intake, increased sweating can lead to excessive blood pressure lowering due to a decrease in BCC. Other reasons for the reduction of BCC. such as vomiting or diarrhea, can also lead to a sharp drop in blood pressure.

Acute myopia and occlusive glaucoma

Hydrochlorothiazide (derivative sulfonamide) can lead to the development of acute transient myopia and acute closed-angle glaucoma.Symptoms include an acute attack of reduced visual function or eye pain and usually occurs within the first hours or weeks after initiation of therapy. Without appropriate treatment, an angle-closure glaucoma can lead to irreversible loss of vision. The main way to treat this condition is to cancel hydrochlorothiazide therapy as soon as possible. You may need prompt medical or surgical intervention if the intraocular pressure remains uncontrolled. Risk factors for the development of acute angle-closure glaucoma may include allergic reactions to sulfopamides and penicillin in the anamnesis.

Doping control results

Hydrochlorothiazide can give a positive result in doping control.

Effect on the ability to drive transp. cf. and fur:Care should be taken when driving vehicles or doing other work that requires special attention, especially at the beginning of treatment with the drug Acquidade®.
Form release / dosage:
Tablets, film-coated, 12.5 mg + 10 mg; 12.5 mg + 20 mg; 25 mg + 20 mg.
Packaging:
10 tablets in a blister of PA / A1 / PVC foil; 3 blisters with instructions for use in a cardboard pack.
Storage conditions:At a temperature of no higher than 25 ° C. Keep out of the reach of children.
Shelf life:
3 years. Do not use after the expiration date printed on the package.
Terms of leave from pharmacies:On prescription
Registration number:LS-000752
Date of registration:07.06.2010 / 22.10.2012
Expiration Date:Unlimited
The owner of the registration certificate:Pfizer Manufakchuring Deutschland GmbH Pfizer Manufakchuring Deutschland GmbH Germany
Manufacturer: & nbsp
Representation: & nbspPfizer LtdPfizer LtdUSA
Information update date: & nbsp24.06.2017
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