Co-Diovan - instructions for use, dose, side effects, contraindications

film sheath Premix: black 0,096 mg (iron dye oxide black (E 172) 14.30%, macrogol 4000 7.15%, talc 7.15%, hypromellose 71.40%); red 0.762 mg (iron dye oxide red (E 172) 14.30%, macrobodies 4000 7.15%, talc 7.15%,hypromellose 71.40%); yellow 3.808 mg (iron oxide oxide yellow (E 172) 14.30%, macrobodies 4000 7.15%, talc 7.15%, hypromellose 71.40%); white 5,334 mg (gitanium dioxide 14,30%, macrogol 4000 7,15%, talc 7.15%, hypromellose 71.40%).

Description:

Film-coated tablets, 160 mg + 25 mg: brown-orange, biconvex, oval. On one side of the tablet is engraved "NHN", on the other side - "NVR". On the cross section, the core of the white color is visible.

Pharmacotherapeutic group:antihypertensive agent combined (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:

Co-Diovan ® is a combined antihypertensive drug that contains an angiotensin II receptor antagonist 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 - active and specific antagonist of angiotensin II receptors. It selectively blocks AT receptor subtype₁ responsible for the vasopressor effect of angiotensin II. Increase in serum angiotensin II concentration due to blockade with valsartan AT₁-receptors can lead to stimulation of unblocked AT₂receptors, which balances the vasopressor effects associated with the excitation of AT₁receptors.

Valsartan does not have any pronounced agonistic activity against AT₁receptors. The affinity of valsartan for the receptors of the subtype AT₁ approximately 20 000 times higher than to the receptors of the subtype AT₂.

As valsartan does not inhibit ACE that converts angiotensin I to angiotensin II and causes bradykinin destruction, the development of side effects associated with the accumulation of bradykinin is unlikely.

When valsartan was compared with an ACE inhibitor, the incidence of dry cough was significantly (p <0.05) lower in patients who received valsartan, than in patients receiving an ACE inhibitor (2.6% vs. 7.9%, respectively). In a clinical study involving patients who previously developed a dry cough with ACE inhibitor treatment, in valsartan treatment, this complication was noted in 19.5% of cases, with thiazide diuretic treatment in 19.0% of cases, while in the group of patients treated with an ACE inhibitor, cough was observed in 68.5% of cases (p <0.05). Valsartan does not interact and does not block the receptors of other hormones or ion channels that are important for the regulation of cardiovascular functions.

The action application point thiazide diuretics are 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 ions (Na⁺) and chlorine (C1^-). Suppression of the co-transport system Na⁺ and C1^-, apparently, occurs due to competition for the sites of C1 ion binding^- in this system. As a result, 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 plasma is observed, as a result of which the activity of renin, the secretion of aldosterone, the excretion of potassium by the kidneys and, consequently, the decrease in the potassium content in serum are increased.

Pharmacokinetics:

Valsartan

Suction

After ingestion of valsartan, its maximum concentrations in the blood plasma are reached in 2-4 hours. The average bioavailability is 23%.

When taking valsartan with food, the area under the concentration-time curve (AUC) decreases by 48%, although starting from about the 8th hour 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 the same. Decrease AUC, nevertheless, is not accompanied by a clinically significant decrease in the therapeutic effect.

Distribution

Valsartan is bound to a significant extent (by 94-97%) with serum proteins, mainly albumin. After intravenous administration of valsartan volume of distribution in the period of the equilibrium state of about 17 liters, which indicates that valsartan to a large extent.

Biotransformation / metabolism

Valsartan does not undergo significant biotransformation, only about 20% of the dose is excreted as metabolites. Hydroxymetabolite is found in blood plasma in low concentrations (less than 10% of AUC). This metabolite is pharmacologically inactive.

Excretion

The pharmacokinetic curve of valsartan is of a downward multiexponential character: (half-life - T_1/2α<1 h and T_1/2β about 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 the blood plasma in women and men were the same.

Hydrochlorothiazide

Suction

After oral intake of hydrochlorothiazide occurs quickly, the time to reach the maximum concentration (T_m_Oh) - 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 availability in comparison with fasting, but the magnitude of these effects is small and does not have much clinical significance. Ingestion absolute bioavailability hydrochlorothiazide is 70%.

Distribution

The pharmacokinetics of hydrochlorothiazide in the phases of distribution and excretion is described as a whole by a 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 approximately three times that of plasma.

Biotransformation

Hydrochlorothiazide eliminated almost unchanged.

Excretion

The half-life 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 unchanged by the kidneys.

Valsartan / hydrochlorothiazide

When combined with valsartan, the systemic bioavailability of hydrochlorothiazide decreases by approximately 30%. The simultaneous administration of hydrochlorothiazide, for its part, does not have a significant effect on the kinetics of valsartan. This interaction does not affect the effectiveness of combined use of valsartan and hydrochlorothiazide. In controlled clinical trials, the distinct antihypertensive effect of this combination was found, which exceeded the effect of each of the components separately, as well as the placebo effect.

Pharmacokinetics in selected groups patients

Patients aged ≥65 years

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

A few data suggest that in elderly patients (both healthy and patients with hypertension) systemic clearance of hydrochlorothiazide lower than in healthy young volunteers.

Patients with impaired renal function

It is not necessary to correct the dose of the drug in patients with a glomerular filtration rate of 30-70 ml / min.

Currently, there is no data on the use of Co-Diovan ® in patients with severe renal dysfunction (glomerular filtration rate <30 ml / min) and in patients receiving hemodialysis. Valsartan is not excreted by hemodialysis because of significant binding to plasma 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 kidney function from mild to moderate severity half-life increases almost doubled.

Patients with impaired hepatic function

AUC valsartan in patients with lungs (5-6 points on the scale Child-Pugh) and moderate (7-9 points on the scale Child-Pugh) violations of liver function was 2 times more than in healthy volunteers. Currently, there is no data on the use of Co-Diovan ® in patients with severe (more than 9 points on the Child-Pugh scale) impaired liver function.

Since the dysfunction of the liver does not have a clinically significant effect on the pharmacokinetics of hydrochlorothiazide, correction of its dose in patients with impaired liver function is not required.

Contraindicated use of the drug Co-Diovan® patients with severe (more than 9 points on the scale Child-Pugh) violations of liver function. In patients with obstruction biliary tract preparation Co-Diovan ® should be used with caution.

Indications:

Arterial hypertension (patients who are shown combined therapy).

Co-Diovan® can be used as an initial therapy in patients who, most probably, may need several drugs to achieve the target values of the arterial pressure. The choice of Ko-Diovan® should be based on an assessment of the relationship between potential benefits and risks.

Contraindications:

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

- Pregnancy and pregnancy planning, the period of breastfeeding;

- tsevere (more than 9 on the Child-Pugh scale) liver function disorder;

- anuria, severe renal dysfunction (glomerular filtration rate <30 ml / min);

- dEthnic age to 18 years (safety and effectiveness of the drug in this category of patients have not been established to date);

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

Carefully:

If you have one of these diseases, always consult a doctor before using the drug.

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

Caution must be exercised while the use of the drug Ko Diovan® potassium salts, potassium-sparing diuretics, potassium-salt food substitutes as well as pharmaceuticals that may cause an increase in the potassium content of the blood (e.g., heparin).

Co-Diovan ® 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, hypercalcemia.

Caution should be exercised when using Ko-Diovan® in patients with severe sodium deficiency and / or reduced circulating blood volume (BCC) (eg, those receiving high doses of diuretics), with moderate impairment of liver function, chronic heart failure (CHF ) III-IV functional class by classification NYHA, mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, systemic lupus erythematosus, primary hyperaldosteronism, diabetes mellitus, hyperuricemia, elevated cholesterol and triglyceride levels, in patients with closed-angle glaucoma, as well as in patients after kidney transplantation.

Pregnancy and lactation:

Like any other drug that affects RAAS, Co-Diovan® 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 preparation of Co-Diovan ® in pregnancy is contraindicated, since, given the mechanism of action of receptor antagonists for angiotensin II, 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 second and third trimesters of pregnancy, leads to damage and death of the fetus. According to the retrospective data, when using ACE inhibitors in the first trimester of pregnancy, the risk of having children with congenital defects increases.

There are reports of spontaneous abortions, malnutrition and renal dysfunction in newborns whose mothers, during pregnancy, valsartan. Introduction of thiazide diuretics, including hydrochlorothiazide, in the uterus cavity led to the development of jaundice or thrombocytopenia in the fetus or in the neonatal period, as well as to the development of other undesirable phenomena, which are subsequently observed in adults. If pregnancy is detected during treatment with Co-Diovan®, 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, excreted in breast milk, so it is not recommended to use Co-Diovan® during breastfeeding.

Dosing and Administration:

Before starting therapy with Co-Diovan®, water-electrolyte disturbances need to be corrected (see the sections "With caution" and "Special instructions").

Co-Diovan® is prescribed 1 tablet orally once a day; The tablet should be swallowed whole, taken with food, or on an empty stomach with a liquid.

Depending on the clinical situation, the recommended daily dose is 1 tablet of the preparation Ko-Diovan® containing valsartan / hydrochlorothiazide in a dose of 80 + 12.5 mg, 160 + 12.5 mg, 160 + 25 mg, 320 + 12.5 mg or, at most, 320 + 25 mg. If necessary, 1 tablet 160 mg + 25 mg per day is prescribed (the maximum daily dose for hydrochlorothiazide). The maximum decrease in blood pressure is usually achieved in 2-4 weeks of therapy.

Patients with mild to moderate renal impairment (glomerular filtration rate> 30 ml / min) no changes in the dose of the drug are required.

In patients with lungs (5-6 points on the Child-Pugh scale) and moderate hepatic impairment Without concomitant phenomena of cholestasis, the dose of valsartan should not exceed 80 mg.

Use in children

The safety and effectiveness of the use of Co-Diovan® in children (under 18 years of age) have not been established to date.

Side effects:

The adverse events (AEs), according to clinical and post-marketing studies, were more common with valsartan and hydrochlorothiazide compared with placebo. Against the background of therapy with the drug Ko-Diovan^®possibly the emergence of AEs, noted both with the use of valsartan and hydrochlorothiazide alone, and not identified in the clinical trials of the drug Ko-Diovan^®.

To estimate the frequency, the following criteria were used (according to the classification of the World Health Organization (WHO)):

very often - (≥1 / 10);

often - (≥1 / 100, <1/10);

infrequently - (≥1 / 1000, <1/100);

rarely - (≥1 / 10000, <1/1000);

very rarely - (<1/10000),

frequency unknown - (insufficient data to estimate frequency of development).

Disorders from the metabolism and nutrition:

infrequently - dehydration.

Violations from the nervous system.

often - headache;

infrequently paresthesia;

very rarely - dizziness;

the frequency is unknown - syncope.

Impaired vision:

infrequent - reduced visual acuity.

Hearing disorders and labyrinthine disturbances:

infrequently, 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:

the frequency is unknown - increased serum uric acid concentration, increased serum bilirubin, increased serum creatinine, hypokalemia, hyponatremia, neutropenia, increased urea nitrogen concentration in the blood serum.

The following AEs were observed in patients with arterial hypertension during clinical trials of the Co-Diovan® preparation without an obvious association with the drug: abdominal pain,pain in the upper abdomen, anxiety, arthritis, asthenia, back pain, bronchitis (including acute), chest pain, postural dizziness, dyspepsia, dyspnea, dryness of the oral mucosa, nosebleeds, erectile dysfunction, gastroenteritis, headache pain, increased sweating, hypoesthesia, flu-like condition, insomnia, sprain, muscle spasms, muscle hypertonia, nasal congestion, nasopharyngitis, nausea, neck pain, peripheral edema, otitis media, pain in the extremities, palpitation, pain in the larynx and pharynx, pyrexia, pollakiuria, hyperthermia, sinusitis, drowsiness, upper respiratory tract infections, urinary tract infections, vertigo, viral infections, visual impairment.

Below are the AEs associated with the use of each component separately.

Valsartan

Violations from the blood and lymphatic system:

the frequency is unknown - a decrease in hemoglobin, a decrease in hematocrit, thrombocytopenia.

Immune system disorders:

frequency unknown - hypersensitivity phenomena / allergic reactions, including serum sickness.

Disorders from the metabolism and nutrition:

the frequency is unknown - an increase in the potassium content in the serum.

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, bullous dermatitis, itching.

Disorders from the kidneys and urinary tract:

frequency unknown - renal failure.

The following AEs were observed during clinical trials of valsartan in patients with arterial hypertension, regardless of their causal relationship with the study drug: arthralgia, asthenia, back pain, diarrhea, dizziness, headache, insomnia, decreased libido, nausea, edema, pharyngitis, rhinitis, sinusitis, upper respiratory tract infections, viral infections.

Hydrochlorothiazide

Disorders from the metabolism and nutrition:

very often - increase 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.

Violations of the blood and lymphatic system:

rarely - thrombocytopenia, sometimes in combination with purpura;

very rarely - agranulocytosis, oppression of the medullar hemopoiesis, hemolytic anemia, leukopenia;

frequency unknown - aplastic anemia.

Immune system disorders:

very rarely - reactions hypersensitivity.

Disorders of the psyche:

rarely - sleep disorders, depression.

Impaired nervous system:

rarely - headache, paresthesia, dizziness.

Vascular disorders:

often - orthostatic hypotension (may increase with the use of ethanol, sedatives or anesthetics).

Heart Disease:

rarely - arrhythmia.

Disturbances from the respiratory system, chest and mediastinal organs:

very rarely respiratory distress, 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.

Disturbances from the liver and bile ducts:

rarely - intrahepatic cholestasis or jaundice.

Disturbances from the skin and subcutaneous tissues:

often - hives and other skin rashes;

rarely - photosensitivity;

very rarely - necrotizing vasculitis and toxic epidermal necrolysis, lupus-like reactions, exacerbation of cutaneous manifestations of systemic lupus erythematosus;

frequency is unknown - erythema multiforme.

Violations of the genitals and mammary gland:

often - impotence.

Disturbances on the part of the organ of sight:

rarely - visual impairment (especially in the first few weeks of treatment);

frequency unknown - acute attack of angle-closure glaucoma.

Disorders from the kidneys and urinary tract:

frequency unknown - acute renal failure, impaired renal function.

Disturbances from the muscles, skeleton and connective tissue:

frequency unknown - muscle spasms.

General disorders and disorders at the site of administration:

frequency is unknown - hyperthermia, asthenia.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Symptoms: with an overdose of valsartan, one can expect the development of a pronounced decrease in blood pressure down to depression of consciousness, vascular collapse and / or shock with a lethal outcome.

In case of an overdose with hydrochlorothiazide, the following symptoms may appear: nausea, drowsiness, hypovolemia, as well as heart rhythm disturbances and muscle spasms caused by 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 the event of a marked decrease in blood pressure, the patient should be laid, lifting his legs, for a period of time necessary for therapy, to take active measures to support the activity of the cardiovascular system, including regular monitoring of the heart and respiratory system, circulating blood volume (BCC) urine.

Valsartan is not excreted by hemodialysis because of its significant binding to plasma proteins. At the same time for removal from the body of hydrochlorothiazide, hemodialysis is effective.

Interaction:

General drug interactions for valsartan and hydrochlorothiazide

Medicines that should be avoided together:

Lithium preparations

With simultaneous use of lithium preparations with ACE inhibitors, angiotensin II receptor antagonists or thiazide diuretics, a reversible increase in serum lithium blood and associated increased toxic effects. The risk of toxic manifestations associated with the use of lithium drugs may be further increased with simultaneous use with the preparation of Co-Diovan®, 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 intensify the hypotensive effect when combined with other means that reduce blood pressure (ACE inhibitors, beta-adrenoblockers, slow calcium channel blockers, guanethidine, methyldopa, vasodilators, direct renin inhibitors, antagonists of AT-II).

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 hypotensive effect of the drug Co-Diovan® 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 increased incidence of arterial hypotension, hyperkalemia, impaired renal function. It is necessary to monitor blood pressure, kidney function, as well as the content of plasma electrolytes in the prescription of Ko-Diovan® 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 precautions, including the frequent determination of potassium in the blood.

Non-steroidal anti-inflammatory drugs (NSAIDs)

When valsartan is used concomitantly with NSAIDs (including selective inhibitors cyclooxygenase-2) may reduce its hypotensive effect. Simultaneous use of angiotensin II receptor antagonists and NSAIDs, especially in patients with impaired renal function and / or hypovolemia (including with 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 OATP 1B1 (rifampicin, ciclosporin) and with an inhibitor of carrier protein MRP2 (ritonavir) can increase the systemic exposure of valsartan (maximum concentration in blood plasma C_m_Oh and the area under the pharmacokinetic curve AUC).

Lack of medicinal interactions:

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

Other antihypertensive drugs

Thiazide diuretics increase the antihypertensive effect of other antihypertensive drugs (including guanethidine, methyldopy, beta-adrenoblockers, vasodilators, "slow" calcium channel blockers, ACE inhibitors, angiotensin receptor antagonists, renin inhibitors).

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 enhanced, while the application of glucocorticosteroids (GCS), adrenocorticotropic hormone (ACTH), amphotericin B, carbenoxolone, penicillins, 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. Caution should be exercised in the long-term combined use of hydrochlorothiazide together with the above preparations.

Hypoglycemic agents

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

Cardiac glycosides

Hypokalemia and hypomagnesemia (undesirable effects of thiazide diuretics) can to promote 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 hypotensive 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 gastrointestinal peristalsis and gastric emptying rate. 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 concomitant administration 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

Simultaneous application thiazide diuretics, including hydrochlorothiazide, may lead to an increase in the frequency of hypersensitivity reactions to allopurinol; increased risk of side effects of amantadine; increase the hyperglycemic effect of diazoxide, reduce the excretion of drugs that have a cytotoxic effect (eg, cyclophosphamide, methotrexate), and potentiate their mielosuppressive effects.

Ethanol, barbiturates and narcotic drugs

Their combined use with hydrochlorothiazide can potentiate the development of orthostatic hypotension.

Special instructions:

Co-Diovan^® can be used as an initial therapy in patients who are most likely to require several drugs to achieve target blood pressure values. Choosing Co-Diovan® for initial therapy Arterial hypertension should be based on an assessment of the ratio of potential benefits and risks.

Impaired liver function

Co-Diovan® 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.

Content changes electrolytes in blood serum

Thiazide diuretics, because of the ability to reduce the potassium and magnesium levels in serum, should be used with caution in patients with conditions accompanied by violations of the water-electrolyte balance: Nephropathy accompanied by loss of salts, and prerenal (cardiogenic) renal dysfunction. If there are clinical manifestations of hypokalemia (muscle weakness, paresis, changes in ECG parameters) treatment with Co-Diovan® should be stopped.

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 content of plasma electrolytes, especially potassium.

When using the drug Ko-Diovan^®should take into account the ability of thiazide diuretics to cause hyponatremia and hypochloremic alkalosis, and also 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 plasma.

Deficiency in the body of sodium and / or volume of circulating blood (BCC)

Patients with a marked deficit in the body of sodium and / or BCC (for example, in patients receiving high doses of diuretics), in rare cases at the beginning of treatment with the drug Ko-Diovan^® there may be a marked decrease in blood pressure with clinical manifestations. Before starting treatment, the body should be corrected and / or replenished with BCC, otherwise treatment should be started under strict medical supervision.

In case of a pronounced decrease in blood pressure, the patient should be placed with an elevated position of the lower extremities and, if necessary, an intravenous infusion of 0.9% sodium chloride solution. After stabilization of blood pressure, treatment with Co-Diovan® 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, taking Co-Diovan® may be accompanied by an increase in the concentration of urea and creatinine in the blood serum, so in such patients, the preparation of Co-Diovan® should be used with caution.

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

In patients whose renal function depends on the state of RAAS (eg, patients with CHF III-IV functional class for NYHA), therapy with ACE inhibitors and antagonists of angiotensin II receptors may be accompanied by oliguria and / or progressive azotemia, in rare cases acute renal failure. The examination of patients with circulatory failure and patients who underwent myocardial infarction should include a study of kidney function.

Systemic lupus erythematosus

There are reports of an exacerbation and worsening of the course of diseases connective tissue (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 occurrence of reactions hypersensitivity against the background of hydrochlorothiazide was most often noted in patients with allergic reactions and a bronchial asthma in the anamnesis.

Angioedema, including Quincke's edema

Angioedema, including edema of the larynx and vocal cords, leading to airway obstruction, and / or edema of the face, lips, pharynx and / or tongue edema, occurred in patients who received valsartan, some of these patients had angioedema earlier with other drugs, including ACE inhibitors. Taking Co-Diovan® in case of angioedema development should be immediately canceled, resumption of Co-Diovan® 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 sulfanylamide derivatives and penicillins.

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:

Patients taking Co-Diovan® should be careful in driving and handling machinery.

Form release / dosage:Tablets, film-coated, 160 mg + 25 mg.

Packaging:

For 14 tablets in a blister of PVC / PE / PVDC.

For 1, 2 or 7 blisters together with instructions for use in a cardboard box.

Storage conditions:

In a dry place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

The drug should not be used after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-001973

Date of registration:13.02.2012

The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland

Manufacturer: & nbsp

NOVARTIS FARMA, S.p.A. Italy

NOVARTIS PHARMA STEIN, AG Switzerland

Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC

Information update date: & nbsp08.12.2015

Illustrated instructions

Instructions

Co-Diovan® (Co-Diovan®)