Valsartan-hydrochlorothiazide-Akrihin - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate 44,000 mg; croscarmellose sodium 10,500 mg; silicon dioxide colloidal anhydrous 1,125 mg; magnesium stearate 1,875 mg;

Shell composition (Advantia Prime): hypromellose-6 cp 2.344 mg; Macrogol-400 0.469 mg; titanium dioxide (E 171) 0.907 mg; iron oxide red (E 172) 0.030 mg.

1 tablet (160 mg + 12.5 mg) contains:

Active substances: valsartan 160.00 mg; hydrochlorothiazide 12,500 mg;

Excipients: lactose monohydrate 100,500 mg; croscarmellose sodium 21.0 mg; silicon dioxide colloidal anhydrous 2,250 mg; magnesium stearate 3,750 mg;

Shell composition (Advantia Prime): hypromellose-6 cP 4,6875 mg; Macrogol-400 0.9375 mg; titanium dioxide (E 171) 0.0750 mg; iron oxide red (E 172) 1.6800 mg; iron oxide yellow (E 172) 0.1125 mg; iron oxide black (E 172) 0.0075 mg.

1 A tablet (160 mg + 25 mg) contains:

Active substances: valsartan - 160,000 mg; hydrochlorothiazide - 25,000 mg;

Excipients: lactose monohydrate 88,000 mg; croscarmellose sodium 21.0 mg; silicon dioxide colloidal anhydrous 2,250 mg; magnesium stearate 3,750 mg;

Shell composition (Advantia Prime): hypromellose-6 cP 4,6875 mg; Macrogol-400 0.9375 mg; titanium dioxide (E 171) 1.4700 mg; iron oxide red (E 172) 0.1200 mg; iron oxide yellow (E 172) 0.2625 mg; iron oxide black (E 172) 0.0225 mg.

Description:

For tablets 80 mg + 12.5 mg: Prhodium-like, biconvex tablets, covered with a pink film shell, on a white rim with a pink edge.

For tablets 160 mg + 12.5 mg: Prhodium-like, biconvex tablets, covered with a film coating of orange-brown color, on a fracture of white color with an orange-brown edge.

For tablets 160 mg + 25 mg: oblong, biconvex tablets, covered with a film shell of light brown color, on a fracture of white color with a light brown edge.

Pharmacotherapeutic group:A combined hypotensive drug (angiotensin II receptor antagonist + diuretic)

ATX: & nbsp

C.09.D.A.03 Valsartan in combination with diuretics

C.09.D.A Angiotensin II antagonists in combination with diuretics

Pharmacodynamics:

Valsartan-Hydrochlorothiazide-Acrychin is a combined antihypertensive drug that contains an angiotensin II receptor antagonist (ARAII) and a thiazide diuretic.

Angiotensin II is an active hormone of the renin-angiotensin-aldosterone system (RAAS) and is formed from angiotensin I with the participation of an angiotensin-converting enzyme (ACE). Angiotensin II binds to specific receptors located on cell membranes in various tissues. It has a wide range of physiological effects, including primarily both direct and indirect participation in the regulation of blood pressure (BP). Being a potent vasoconstrictor, angiotensin II causes a direct pressor response.In addition, it stimulates the secretion of aldosterone and promotes the retention of sodium ions.

Valsartan - selective antagonist of angiotensin II receptors. Has a selective antagonistic effect on the AT subtype receptors₁, responsible for the vasopressor effect of angiotensin II. Increase in blood serum angiotensin II concentration due to blockade with valsartan AT₁-receptors can stimulate the free receptors of the subtype AT₂, which balances the effects associated with AT stimulation₁receptors. Has no agonistic activity against AT₁receptors. Does not inhibit ACE. Valsartan does not interact and does not block the receptors of other hormones or ion channels involved in the regulation of the functions of the cardiovascular system.

Hydrochlorothiazide is a thiazide diuretic. The point of application of the action of thiazide diuretics is distal convoluted renal tubules. When thiazide diuretics are applied to highly sensitive receptors in the distal tubules of the cortical layer of the kidneys, reabsorption of sodium and chlorine ions occurs.The suppression of the co-transport system of sodium and chlorine is apparently due to competition for the binding sites of chlorine ions, as a result of which the excretion of sodium and chlorine ions increases approximately to the same extent. As a result of diuretic action, a decrease in the volume of circulating blood (BCC) is observed, which increases the activity of renin, the secretion of aldosterone, the excretion of potassium by the kidneys and, consequently, the decrease in the potassium content in the serum.

Pharmacokinetics:

Valsartan

Suction

After oral administration, the maximum concentration (C_mOh) valsartan in the blood plasma is achieved in 2-4 hours. The average bioavailability is 23%. When taking valsartan at the same time as food, there is a decrease in the area under the concentration-time curve (AUC) by 48%, although approximately 8 hours after taking the drug, the concentrations of valsartan in the blood plasma, both in the case of taking it on an empty stomach, and in case of reception with food are equalized. Decrease AUC is not accompanied by a clinically significant decrease in the therapeutic effect, so valsartan can be administered regardless of the time of ingestion.

Distribution

Valsartan largely binds to blood serum proteins (94-97%), mainly with albumin. After intravenous administration of valsartan, the volume of distribution during the equilibrium period is about 17 liters, indicating that valsartan to a large extent.

Metabolism

Valsartan does not undergo a pronounced metabolism (about 20% of the dose is determined in the form of metabolites). Hydroxy-metabolite is determined in blood plasma at low concentrations (less than 10% of AUC valsartan). This metabolite is pharmacologically inactive.

Excretion

The pharmacological curve of valsartan has a downward multiexponential character (half-life T_1/2α<1 h and T_1/2βabout 9 hours). Valsartan is excreted through the intestine (about 83% of the dose) and kidneys (about 13% of the dose), mostly unchanged. After intravenous administration, the plasma clearance of valsartan is about 2 l / h, its renal clearance is 0.62 l / h (about 30% of the total clearance). The half-life of valsartan is 6 hours.

In the range of doses studied, the kinetics of valsartan is linear.With repeated use of valsartan, no changes in the kinetic parameters were noted. When taking valsartan once a day, cumulation is negligible. The concentrations of valsartan in blood plasma in women and men are the same.

Hydrochlorothiazide

Suction

After oral intake of hydrochlorothiazide occurs quickly, the time to reach the maximum concentration (TC_mOh) - about 2 hours. In the therapeutic range of doses, the average value AUC increases in direct proportion to the increase in dose. Simultaneous intake of hydrochlorothiazide with food can lead to both an increase and a decrease in systemic bioavailability compared with fasting, but the magnitude of these effects is small and clinically insignificant. When administered, the absolute bioavailability of hydrochlorothiazide is 70%.

Distribution

The pharmacokinetics of hydrochlorothiazide in the phases of distribution and elimination are generally described by the bi-exponential descending curve. The apparent volume of distribution is 4-8 l / kg. Binding to blood plasma proteins (mainly with albumins) is 40-70%. Hydrochlorothiazide also accumulates in erythrocytes in a concentration three times that of plasma.

Metabolism

Hydrochlorothiazide is eliminated in almost unchanged form.

Excretion

The half-life (T_1/2) of the final phase is 6-15 hours.

With repeated use of the drug kinetics of hydrochlorothiazide does not change, with the appointment of the drug once a day, the accumulation of the drug is minimal. More than 95% of the absorbed dose is excreted by the kidneys unchanged.

Valsartan / hydrochlorothiazide

When combined with valsartan, the systemic bioavailability of hydrochlorothiazide is reduced by about 30%. The concomitant administration of hydrochlorothiazide does not significantly affect the kinetics of valsartan. This interaction does not affect the effectiveness of combined use of valsartan and hydrochlorothiazide.

The distinct antihypertensive effect of this combination exceeds the effect of each of the components separately.

Pharmacokinetics in selected patient groups

Patients of advanced age (over 65 years)

In some elderly patients AUC Valsartan was slightly larger than in young patients, but this was not clinically significant.

Limited data suggest that in elderly patients (both healthy,and patients with arterial hypertension) the systemic clearance of hydrochlorothiazide is lower than in healthy young volunteers.

Patients with impaired renal function

In patients with creatinine clearance (CK) 30-70 ml / min, dose adjustment is not required.

Currently, there is no data on the use of the drug in patients with severe renal dysfunction (CK <30 ml / min) and in patients receiving hemodialysis. Valsartan is not excreted by hemodialysis due to significant binding to blood proteins. At the same time, hemodialysis can be effectively removed from the body hydrochlorothiazide.

In the presence of renal insufficiency, the average concentration peaks in plasma and the values AUC hydrochlorothiazide increases, and the rate of excretion decreases. In patients with impaired renal function from mild to moderate severity, the half-life increases almost twice.

Patients with impaired hepatic function

In patients with impaired liver function (5-6 on the Child-Pugh scale) and moderate (7-9 on the Child-Pugh scale), severity AUC Valsartan is on average 2 times more than healthy volunteers (of the corresponding age, sex and body weight).

Pharmacokinetic studies in patients with severe impairment of liver function (more than 9 points on the Child-Pugh scale) were not performed.

Since the violation of liver function does not have a clinically significant effect on the kinetics of hydrochlorothiazide, dose adjustment in patients with impaired liver function is not required.

Contraindicated the use of the drug Valsartan-Hydrochlorothiazide-Akrihin patients with severe (more than 9 points on the scale Child-Pugh) violations of liver function.

In patients with bile duct obstruction, the drug Valsartan-Hydrochlorothiazide-Acrichin should be used with caution.

Indications:

Arterial hypertension (in patients who are shown combined therapy).

Contraindications:

- Hypersensitivity to valsartan, hydrochlorothiazide and other sulfonamide derivatives, or any other component of the drug;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- severe violations of the liver (more than 9 points on the scale Child-Pugh);

- anuria, severe renal dysfunction (CK <30 mL / min);

- pregnancy, pregnancy planning and the period of breastfeeding;

- age under 18 years (safety and efficacy not established);

- simultaneous use with aliskiren in patients with type 2 diabetes mellitus.

Carefully:

Caution should be exercised when using the drug in patients with hereditary angioedema or angioedema due to previous therapy with angiotensin II receptor antagonists (APA II) or ACE inhibitors.

Caution should be exercised when using potassium preparations, potassium-sparing diuretics, potassium-containing substitutes for edible salt and other medicines that may cause an increase in potassium in the blood (for example, heparin).

The drug should be used with caution in patients with unilateral or bilateral stenosis of the renal artery or stenosis of the artery of a single kidney, with conditions accompanied by water-electrolyte disorders: nephropathy accompanied by loss of salts, and prerenal (cardiogenic) renal dysfunction, in patients with hypokalemia, hypomagnesemia, hyponatremia, hypocalcemia.

Care should be taken when using the drug in patients withpronounced deficiency in the body of sodium and / or with reduced bcc (for example, receiving high doses of diuretics), with moderately expressed violations of the liver function, chronic heart failure (III-IV functional class by classification NYHA), mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, systemic lupus erythematosus, primary hyperaldosteronism, diabetes mellitus, hyperuricemia, hypercholesterolemia and triglyceridemia, with obstructive bile duct disease and cholestasis, in patients with angle-closure glaucoma, as well as in patients after kidney transplantation.

Pregnancy and lactation:

Like any other drug that affects RAAS, the drug Valsartan-Hydrochlorothiazide-Akrihin should not be used in women planning a pregnancy. When appointing any drug that affects RAAS, the doctor should inform women of childbearing age of the potential danger of using these drugs during pregnancy.

The use of the drug Valsartan-Hydrochlorothiazide-Akrihin in pregnancy is contraindicated, since, given the mechanism of action of angiotensin II receptor antagonists, the risk to the fetus can not be ruled out.The effect of ACE inhibitors (drugs that affect RAAS) on the fetus, if prescribed in the II and III trimesters of pregnancy, leads to damage or death of the developing fetus. According to the retrospective data, the risk of the birth of children with congenital defects increases with the use of ACE inhibitors in the first trimester of pregnancy. There are reports of spontaneous abortions, malnutrition and renal dysfunction in newborns whose mothers were inadvertently receiving valsartan.

Introduction of thiazide diuretics, including hydrochlorothiazide, in the uterus cavity led to the development of jaundice and thrombocytopenia in the fetus or in the neonatal period, as well as to the development of other undesirable phenomena that are subsequently observed in adults. If the pregnancy is diagnosed during treatment with Valsartan-Hydrochlorothiazide-Akrihin, the drug should be discontinued as soon as possible.

It is not known whether the valsartan in breast milk. In experimental studies it was shown that valsartan is excreted with the milk of lactating animals. Hydrochlorothiazide penetrates the placenta and is excreted in breast milk.

If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Before starting therapy with Valsartan-Hydrochlorothiazide-Akrihin, water-electrolyte disturbances must be corrected (see the sections "With caution" and "Special instructions").

The drug Valsartan-Hydrochlorothiazide-Akrihin is taken orally, regardless of food intake, 1 tablet once a day, washed down with liquid.

Depending on the clinical situation, the recommended daily dose is 1 tablet of the drug Valsartan-Hydrochlorothiazide-Akrihin, containing valsartan / hydrochlorothiazide at a dose of 80 mg + 12.5 mg, 160 mg + 12.5 mg.

If necessary, 1 tablet of the drug Valsartan-Hydrochlorothiazide-Acrychin, containing valsartan / hydrochlorothiazide at a dose of 160 mg + 25 mg per day, the maximum daily dose for hydrochlorothiazide, is prescribed.

The maximum decrease in blood pressure is usually achieved in 2-4 weeks of therapy.

Use in selected patient groups

Patients of advanced age (over 65 years)

For elderly patients, dose adjustment is not required.

Patients with impaired renal function

In patients with impaired renal function of mild or moderate severity (CK ≥30 ml / min), dose adjustment is not required.

Patients with impaired hepatic function

In patients with lungs (5-6 points on the Child-Pugh scale) and moderate (7-9 points on the Child-Pugh scale) violations of liver function without concomitant phenomena of cholestasis, the dose of valsartan should not exceed 80 mg.

Side effects:

The following side effects are given in accordance with the following grades of their frequency in accordance with the classification of the World Health Organization: very often (≥ 1/10); often (≥ 1/100, <1/10); infrequently (≥ 1/1 000, <1/100); rarely (≥ 1/10 000, <1/1 000) and very rarely (<1/10 000), the frequency is unknown (insufficient data to estimate the frequency of development).

Adverse events were generally mild and transitory in nature.

The combination of valsartan / hydrochlorothiazide

Disorders from the metabolism and nutrition: infrequently - dehydration.

Impaired nervous system: often - headache; infrequently paresthesia; very rarely - dizziness; frequency unknown - faint.

Disorders from the side of the organ of vision: infrequent - reduced visual acuity.

Hearing disorders and labyrinthine disorders: rarely - noise in the ears.

Vascular disorders: infrequent - marked decrease in blood pressure, peripheral edema.

Disturbances from the respiratory system, chest and mediastinal organs: infrequently - cough; frequency unknown - noncardiogenic pulmonary edema.

Disorders from the gastrointestinal tract: infrequently - nausea; very rarely diarrhea.

Disturbances from the musculoskeletal and connective tissue: infrequently - myalgia; very rarely - arthralgia.

Disorders from the kidneys and urinary tract: frequency unknown - impaired renal function.

General disorders and disorders at the site of administration: infrequently - increased fatigue.

Laboratory and instrumental data: frequency unknown - increase concentration of uric acid in the blood serum, increased serum bilirubin concentration, increased serum creatinine, hypokalemia, hyponatremia, neutropenia, increased urea blood levels.

Allergic reactions: rarely - angioedema.

General disorders and disorders at the site of administration: infrequently - increased fatigue; very rarely - epistaxis, viral infection, fever.

In the clinical practice of the combination valsartan / hydrochlorothiazide, the following side effects were also observed (frequency unknown): abdominal pain, upper abdominal pain, anxiety, arthritis, asthenia, back pain, bronchitis (including acute), pain in the breast, postural dizziness, dyspepsia, dyspnea, dryness of the oral mucosa, nosebleeds, erectile dysfunction, gastroenteritis, headache, increased sweating, hypoesthesia, flu-like condition, insomnia, sprain, muscle spasms, muscle hypertension, nasal congestion, nasopharyngitis, nausea, neck pain, peripheral edema, otitis media, pain in the extremities, palpitations, pain in the larynx and pharynx, pyrexia, hyperthermia, sinusitis, drowsiness, upper respiratory tract infections, urinary tract infections, vertigo, viral infections, impaired vision.

The following are side reactions associated with the use of each component separately.

Valsartan

Violations from the blood and lymphatic system: the frequency is unknown - a decrease in hemoglobin and hematocrit, thrombocytopenia.

Immune system disorders: frequency unknown - hypersensitivity reactions / allergic reactions, including serum sickness.

Disorders from the metabolism and nutrition: frequency is unknown - an increase in serum potassium, hyponatremia.

Hearing disorders and labyrinthine disturbances: infrequently - vertigo.

Vascular disorders: frequency is unknown - vasculitis.

Disorders from the gastrointestinal tract: infrequently - pain in the abdomen.

Disturbances from the liver and bile ducts: frequency unknown - increased activity of "liver" enzymes.

Disturbances from the skin and subcutaneous tissues: frequency unknown - Quincke's edema, skin rash, skin itch.

Disorders from the kidneys and urinary tract: frequency unknown - renal failure.

In the clinical practice of valsartan, the following side effects were also observed (frequency unknown) in patients with arterial hypertension, regardless of their causal relationship with the drug: arthralgia, asthenia, back pain, diarrhea, dizziness, headache, insomnia, decreased libido, nausea, swelling , pharyngitis, rhinitis, sinusitis, upper respiratory tract infections, viral infections.

Hydrochlorothiazide

Violations from the blood and lymphatic system: rarely - thrombocytopenia (sometimes in combination with purpura); very rarely - agranulocytosis, oppression of bone marrow hematopoiesis, hemolytic anemia, leukopenia; frequency unknown - aplastic anemia.

Immune system disorders: very rarely - hypersensitivity reactions.

Disorders from the metabolism and nutrition: very often - an increase in the concentration of lipids in the blood plasma (especially against a background of high doses of hydrochlorothiazide); often hypomagnesemia and hyperuricemia; rarely - hypercalcemia, hyperglycemia, glucosuria and worsening of the course of diabetes mellitus; very rarely - hypochloraemic alkalosis.

Disorders of the psyche: rarely - depression, sleep disturbances.

Impaired nervous system: rarely - headache, dizziness, paresthesia.

Disorders from the side of the organ of vision: rarely - visual impairment (especially in the first few weeks of treatment); frequency unknown - acute attack of angle-closure glaucoma.

Heart Disease: rarely - arrhythmia.

Vascular disorders: often - orthostatic hypotension (may worsen with alcohol, sedatives or pain medications).

Disturbances from the respiratory system, chest and mediastinal organs: very rarely - respiratory distress syndrome, including pulmonary edema and pneumonitis.

Disorders from the digestive system: often - decreased appetite, mild nausea, vomiting; rarely - discomfort in the abdomen, constipation, diarrhea; very rarely - pancreatitis.

Disorders from the liver and bile ducts: rarely intrahepatic cholestasis or jaundice.

Disorders from the kidneys and urinary tract: frequency unknown - impaired renal function, acute renal failure.

Disturbances from the skin and subcutaneous tissues: often - hives or other forms of skin rash; rarely - photosensitivity; very rarely - necrotizing vasculitis, toxic epidermal necrolysis, lupus-like reactions, exacerbation of cutaneous manifestations of systemic lupus erythematosus; frequency is unknown - erythema multiforme.

Disturbances from the muscles, skeleton and connective tissueand: frequency unknown - muscle spasms.

Violations of the genitals and breast: often - impotence.

General disorders and disorders at the site of administration: frequency is unknown - hyperthermia, asthenia.

Overdose:

Symptoms: with an overdose of valsartan, there is a marked decrease in blood pressure down to depression, vascular collapse and / or shock with a fatal outcome. In case of an overdose with hydrochlorothiazide, the following symptoms may appear: nausea, drowsiness, hypovolemia, heart rhythm disturbances and muscle spasms caused by a disturbance of the water-electrolyte balance.

Treatment: Symptomatic, the nature of which depends on the time elapsed since the time of taking the drug, and on the severity of the symptoms. In case of early detection of an overdose of the drug, it is recommended to induce vomiting in the patient. In the case of a pronounced decrease in blood pressure, the patient should be placed on his back, lifting his legs, and as soon as possible to conduct intravenous administration of 0.9% solution of sodium chloride. At the same time, the heart and respiratory system, BCC and urine output should be monitored regularly.

Valsartan is not excreted by hemodialysis due to significant binding to blood plasma proteins. At the same time, hemodialysis can effectively be removed from the body hydrochlorothiazide.

Interaction:

General drug interactions for valsartan and hydrochlorothiazide

Medicines that should be avoided together

- Lithium preparations

With the simultaneous use of lithium drugs with ACE inhibitors, ARAII or thiazide diuretics, a reversible increase in lithium serum levels and associated increased toxic effects were noted. The risk of toxic manifestations associated with the use of lithium drugs may increase additionally with simultaneous use with the drug Valsartan-Hydrochlorothiazide-Akrihin, since the renal clearance of lithium preparations is reduced by thiazide diuretics. In this regard, careful monitoring of lithium content in blood serum is recommended.

Medicines that require joint use with caution

- Hypotensive drugs

It is possible to enhance the antihypertensive effect when combined with other means that reduce blood pressure (ACE inhibitors, beta-blockers, slow calcium channel blockers, guanethidine, methyldopa, vasodilators, direct renin inhibitors, ARAII).

- Pressor amines

Possible weakening of the action of pressor amines (norepinephrine, epinephrine), which does not require the termination of joint application.

- Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2)

It is possible to reduce the diuretic and antihypertensive action of the drug Valsartan-Hydrochlorothiazide-Akrihin when used simultaneously with NSAIDs, for example, with derivatives of salicylic acid, indomethacin. Concomitant hypovolemia can lead to the development of acute renal failure.

Drug Interactions for valsartan

Medicines that should be avoided together

Simultaneous use of angiotensin II receptor antagonists with other drugs that affect RAAS leads to an increase in the incidence of arterial hypotension, hyperkalemia, and renal dysfunction. It is necessary to monitor blood pressure, kidney function, and the content of plasma electrolytes in the appointment of Valsartan-Hydrochlorothiazide-Akrihins with other drugs that affect RAAS.

Simultaneous use of potassium-sparing diuretics, biologically active additives containing potassium; potassium-containing substitutes for edible salt; other drugs that increase the potassium content in the blood serum (for example, heparin) requires the observance of precautionary measures (including the frequent determination of potassium content in the blood serum).

Non-steroidal anti-inflammatory drugs (NSAIDs)

When valsartan is used simultaneously with NSAIDs (including selective inhibitors of COX-2), its antihypertensive effect may be reduced. The simultaneous use of ARA II and NSAIDs, especially in patients with impaired renal function and / or hypovolemia (including against a background of diuretic therapy), can lead to the development of acute renal failure. If it is necessary to jointly use valsartan and NSAIDs before starting treatment, it is necessary to evaluate the kidney function and correct the water-electrolyte disturbances.

Protein-carriers

By the results of the study in vitro on liver cultures valsartan is a substrate for the OATP1B1 carrier proteins and MRP2. Simultaneous administration of valsartan with inhibitors of the carrier protein OATP1B1 (rifampicin, ciclosporin) and with an inhibitor of carrier protein MRP2 (ritonavir) can increase the systemic exposure of valsartan (C_mOh and AUC).

Lack of drug interaction

There have been no clinically significant interactions with monotherapy with valsartan against the background of the following drugs: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.

Drug Interactions for Hydrochlorothiazide

Lithium

With simultaneous use with ACE inhibitors and diuretics, cases of a reversible increase in the plasma concentration of lithium and its toxic effect were reported. Studies of simultaneous use of hydrochlorothiazide with valsartan and lithium preparations have not been conducted. However, with the simultaneous use of hydrochlorothiazide and preparations containing lithium, it is recommended to monitor the concentration of lithium in the blood.

Other antihypertensive drugs

Thiazide diuretics increase the antihypertensive effect of other antihypertensive drugs (including guanethidine, methyldopy, beta adrenoblockers, vasodilators,blockers of "slow" calcium channels, ACE inhibitors, ARAII, inhibitors of renin).

Curare like muscle relaxants

Thiazide diuretics, including hydrochlorothiazide, potentiate the action of nondepolarizing muscle relaxants.

Drugs affecting the content of potassium in the blood

The risk of hypokalemia caused by diuretics can be exacerbated by the simultaneous use of glucocorticosteroids (GCS), adrenocorticotropic hormone (ACTH), amphotericin, carbenoxolone, penicillin, acetylsalicylic acid or its derivatives and antiarrhythmic drugs.

Drugs affecting the sodium content in the blood

Hyponatremic effect caused by diuretics can be intensified with simultaneous use with antidepressants, antipsychotic, anticonvulsants, etc. Care should be taken with long-term combined use of hydrochlorothiazide together with the above preparations.

Hypoglycemic agents

Thiazide diuretics can alter glucose tolerance, which may require correction of insulin doses and hypoglycemic agents for oral administration.

Cardiac glycosides

Hypokalemia and hypomagnesemia (undesirable effects of thiazide diuretics) can contribute to the development of cardiac arrhythmias in patients receiving cardiac glycosides.

NSAIDs

The simultaneous use of NSAIDs and hydrochlorothiazide can lead to a decrease in the diuretic and antihypertensive effects of the latter. Concomitant hypovolemia can provoke the development of acute renal failure.

H- and m-holinoblokatory

H- and m-holinoblokatory (incl. atropine, biperidene) can increase the bioavailability of hydrochlorothiazide, which is associated with a decrease in the peristalsis of the gastrointestinal tract (GIT) and the rate of gastric emptying. Accordingly, GI motility stimulants (cisapride) can reduce the bioavailability of hydrochlorothiazide.

Anion exchange resins

The absorption of hydrochlorothiazide is disturbed in the presence of colestyramine and colestipol. Hydrochlorothiazide should be taken either 4 hours or 4-6 hours after taking these compounds.

Vitamin D and calcium salts

Simultaneous intake of hydrochlorothiazide with vitamin D or calcium preparations can lead to hypercalcemia, due to increased reabsorption of calcium.

Cyclosporin

With the simultaneous use of hydrochlorothiazide and cyclosporine, the risk of hyperuricemia and exacerbation of the gout current increases.

Methyldopa

There have been reports of cases of hemolytic anemia with simultaneous administration of hydrochlorothiazide and methyldopa.

Pressor amines

Hydrochlorothiazide can reduce the body's response to the introduction of pressor amines (norepinephrine). The clinical significance of this interaction is insignificant and can not prevent their joint application.

Other types of interaction

The simultaneous use of thiazide diuretics, including hydrochlorothiazide, may lead to an increase in the frequency of hypersensitivity reactions to allopurinol; increased risk of side effects of amantadine; intensify the hyperglycemic effect of diazoxide, lead to a decrease in the excretion of drugs with cytotoxic effects (for example, cyclophosphamide, methotrexate) in the kidneys, to potentiate their mielosuppressive effect.

Ethanol, barbiturates and narcotic drugs

Co-administration with hydrochlorothiazide can potentiate the development of orthostatic hypotension.

Special instructions:

Valsartan-Hydrochlorothiazide-Acrychin may be used as an initial therapy in patients who are most likely to require several drugs to achieve target blood pressure values. The choice of the drug Valsartan-Hydrochlorothiazide-Akrihin for the initial treatment of arterial hypotension should be based on an assessment of the ratio of potential benefits and risks.

Impaired liver function

Valsartan-Hydrochlorothiazide-Acrychin is not used in patients with severe liver function disorders (more than 9 on the Child-Pugh scale), with bile duct obstruction and cholestasis should be used with caution.

Changes in the content of electrolytes in blood serum

Thiazide diuretics due to the ability to reduce the content of potassium and magnesium in serum should be used with caution in patients with states accompanied aqueous electrolyte disturbances: nephropathy accompanied by the loss of salt and prerenal (cardiogenic) renal dysfunction. If there are clinical manifestations of hypokalemia (muscle weakness, paresis, changes in ECG parameters), treatment with Valsartan-Hydrochlorothiazide-Acrychin should be discontinued.Before starting the use of the drug, it is necessary to correct hypokalemia and hypomagnesemia. All patients taking medications containing thiazide diuretics need regular monitoring of the electrolyte content in blood serum, in particular potassium.

When using the drug Valsartan-Hydrochlorothiazide-Acrychin, the ability of thiazide diuretics to cause hyponatremia and hypochloraemic alkalosis should be considered, as well as to aggravate the existing hyponatraemia. Hyponatremia in these cases is rarely accompanied by neurologic symptoms. It is necessary to regularly monitor the sodium content in the blood serum.

Deficiency in the body of sodium and / or BCC

In patients with severe deficiency in the body of sodium and / or with reduced bcc (for example, in patients receiving high doses of diuretics), in rare cases at the beginning of treatment with Valsartan-Hydrochlorothiazide-Akrihin, a marked decrease in blood pressure with clinical manifestations can occur. Before starting treatment, the body should be corrected and / or replenished with BCC, otherwise treatment should be started under strict medical supervision.

In the case of a pronounced decrease in blood pressure, the patient should be laid, legs elevated and, if necessary, an intravenous infusion of 0.9% sodium chloride solution. After stabilization of blood pressure, treatment with Valsartan-Hydrochlorothiazide-Akrihin can be continued.

Stenosis of the renal artery

In patients with unilateral or bilateral stenosis of the renal artery or stenosis of the artery of a single kidney, the use of Valsartan-Hydrochlorothiazide-Acrychin may be accompanied by an increase in the concentrations of urea and creatinine in the blood serum; therefore, in such patients, the drug Valsartan-Hydrochlorothiazide-Akrihin should be used with caution.

Chronic heart failure III-IV functional class (according to the classification NYHA), incl. after a recent myocardial infarction

For patients in whom renal function depends on the state of RAAS (eg, patients with chronic heart failure III-IV functional class), therapy with ACE inhibitors and ARAN can be accompanied by oliguria and / or progressive azotemia, in rare cases - with acute renal failure.The examination of patients with chronic heart failure and patients who underwent myocardial infarction should include a study of kidney function.

Systemic lupus erythematosus

There are reports of the development of exacerbation and worsening of the course of connective tissue diseases (eg, systemic lupus erythematosus) with the use of thiazide diuretics, including hydrochlorothiazide.

Other metabolic disorders

Thiazide diuretics, including hydrochlorothiazide, can cause a change in glucose tolerance, as well as an increase in the concentration of cholesterol and triglycerides in the blood serum. Reducing the clearance of uric acid can lead to hyperuricemia and the development of gout in predisposed patients.

Thiazide diuretics reduce the excretion of calcium by the kidneys and can cause a slight increase in calcium in the plasma in the absence of concomitant disorders of calcium metabolism. Expressed hypercalcemia with thiazide diuretic therapy (> 12 mg / dl) or not responding to withdrawal may indicate a concomitant metabolic disorder of calcium.In several patients with hypercalcemia and hypophosphatemia, long-term use of thiazide diuretics was determined by pathological changes in parathyroid glands.

Hypersensitivity reactions

The emergence of hypersensitivity reactions against the background of hydrochlorothiazide was most often observed in patients with allergic reactions and bronchial asthma in the anamnesis.

Angioedema, including Quincke's edema

Angioedema, including swelling of the larynx and vocal cords, leading to airway obstruction, and / or edema of the face, lips, pharynx and / or edema of the tongue, occurred in patients who received valsartan, some of these patients had angioedema earlier with other drugs, including ACE inhibitors. Taking Valsartan-Hydrochlorothiazide-Akrihin in case of angioedema development should be immediately canceled, resumption of Valsartan-Hydrochlorothiazide-Akrikhin preparation is prohibited.

Acute attack of angle-closure glaucoma

Against the background of the use of hydrochlorothiazide there have been cases of transient myopia and acute development of closed-angle glaucoma.The risk factor for acute development of an angle-closure glaucoma may be anamnestic data on allergic reactions to sulfanilamide and penicillin.

Symptoms: sudden onset, sudden drop in vision or pain in the eye, usually occurring between a few hours and a week after the start of therapy. An untreated, closed-angle glaucoma can lead to persistent loss of vision. The first step is to stop taking hydrochlorothiazide. Additional medication or surgical treatment may be required if intraocular pressure after drug withdrawal is not reduced.

Hydrochlorothiazide can give positive results in doping control.

Effect on the ability to drive transp. cf. and fur:

Care must be taken when driving vehicles and working with mechanisms that require special attention, as during the treatment it is possible to develop dizziness or weakness on the background of arterial hypotension.

Form release / dosage:

The film-coated tablets are 80 mg + 12.5 mg, 160 mg + 12.5 mg and 160 mg + 25 mg.

Packaging:

For 14 tablets in a foil foil Al / PVC / PVDC.

For 1 or 2 blisters together with the instruction for use are placed in a cardboard box.

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 the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002667

Date of registration:21.10.2014 / 16.06.2015

Expiration Date:21.10.2019

The owner of the registration certificate:Pharmaceutical factory "POLFARMA" JSCPharmaceutical factory "POLFARMA" JSC Poland

Manufacturer: & nbsp

Pharmaceutical Works POLPHARMA, S.A. Poland

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp20.01.2017

Illustrated instructions

Instructions

Valsartan-Hydrochlorothiazide-Akrihin (Valsartan-Hydrochlorothiazide-Akrihin)