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

Excipients: microcrystalline cellulose 31.5 mg, 75.5 mg, 63.0 mg, 151.5 mg, 151.0 mg (corresponding to the aforementioned dosages of the active substances); crospovidone 20.0 mg, 40.0 mg, 40.0 mg, 80.0 mg, 80.0 mg; magnesium stearate 4.5 mg, 9.0 mg, 9.0 mg, 18.0 mg, 18.0 mg; silicon dioxide colloidal anhydrous 1.5 mg, 3.0 mg, 3.0 mg, 6.0 mg, 6.0 mg;

composition of the sheath of film-coated tablets, 160/25 mg: shell Premix black (iron oxide black (E 172), macrogol-4000, talcum, hypromellose) 0.096 mg; shell Premix red (iron oxide red (E 172), macrogol-4000, talc, hypromellose) 0.762 mg; shell Premix yellow (iron oxide yellow (E 172), macrogol-4000, talc, hypromellose) 3.808 mg; shell Premix white (titanium dioxide, macrogol-4000, talc, hypromellose) 5,334 mg;

composition of the coating of tablets coated with a film coating, 320 / 12.5 mg: shell Premix black (iron oxide black (E 172), macrogol-4000, talc; hypromellose) 0.06 mg; shell Premix red (iron oxide, red (E 172), macrogol-4000, talc, hypromellose) 0.28 mg; shell Premix white (titanium dioxide, macrogol-4000, talc / hypromellose) 19.66 mg;

composition of the coating of tablets coated with a film coating, 320/25 mg: shell Premix white (titanium dioxide, macrogol-4000, talc, hypromellose) 15.60 mg; Casing Premix yellow (iron oxide yellow (E 172), macrogol-4000, talc, hypromellose) 4.4 mg.

Description:

Film-coated tablets, 80 / 12.5 mg: light orange color, oval, biconvex. On one side of the tablet is labeled "HGH", on the other "CG".

Tablets, film-coated, 160 / 12.5 mg: from dark red to brownish-red color, oval, biconvex. On one side of the tablet is labeled "IUU", on the other "CG".

Tablets, film-coated, 160/25 mg: brown-orange, oval, biconvex. On one side of the tablet is labeled "NHN", on the other "NVR".

Film-coated tablets, 320 / 12.5: oval, with a bevelled edge, covered with a film shell of pink color. On one side is labeled: "NVR", on the other - "HIL".

Tablets coated with a film coating, 320/25 mg: oval, with a bevelled edge, covered with a film coating of yellow color. On one side it is marked: "NVR", on the other - "СТI".

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 concentrations of angiotensin II 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 marked agonistic activity in relation to AT₁receptors. The affinity of valsartan for AT subtype receptors₁ approximately 20,000 times higher than to the AT subtype receptors₂.

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 oral administration of valsartan, its peak plasma concentrations are achieved after 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, the volume of distribution during the equilibrium period is about 17 liters, indicating that valsartan to a large extent.

Biotransformation / metabolism

Valsartan does not undergo significant biotransformation, only about 20% of the dose is excreted as metabolites. Valeryl-4-hydroxy valsartan is found in blood plasma in low concentrations (less than 10% of AUC). This metabolite is pharmacologically inactive.

Excretion

Pharmacokinetic curve valsartan has a downward multi-exponential (T_1/2α<1 h and T_1/2β about 9 hours). Valsartan is excreted with feces (about 83% of the dose) and urine (about 13% of the dose), mostly in unchanged form. 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 (HCTZ)

Suction

After oral intake of hydrochlorothiazide occurs rapidly (T_ma_x - 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 HCTZ 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. When administered, the absolute bioavailability of hydrochlorothiazide is 70%.

Distribution

The pharmacokinetics of hydrochlorothiazide in the phases of distribution and excretion is described as a whole band an exponential downward curve. The apparent volume of distribution is 4-8 l / kg. Binding to plasma proteins (mainly with albumins) is 40-70%. Hydrochlorothiazide also accumulates in erythrocytes in a concentration approximately three times that of plasma.

Biotransformation

HCTZ is 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 in the urine.

Valsartan / hydrochlorothiazide

When combined with valsartan, the system bioavailability of HCTZ is reduced by about 30%. Simultaneous reception of GTCT, for its part, does not have a significant effect on the kinetics of valsartan. The noted interaction has no effect on the effectiveness of the combined use of valsartan and GTC. 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 of patients

Patients aged ≥65 years

In some elderly patients, Valsartan AUC 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 HCTZ is 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 effectively remove HCTZ from the body.

In the presence of renal insufficiency, the average plasma concentration peaks and AUC values of hydrochlorothiazide increase, 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

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 greater 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 HCTZ, correction of its dose in patients with impaired liver function is not required.

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

Indications:

Arterial hypertension (patients who are shown combined therapy).

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 should be exercised when using Co-Diovan® with potassium salts, potassium-sparing diuretics, potassium-containing substitutes for edible salt, as well as with drugs that can cause an increase in potassium levels in the blood plasma (eg, 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 (according to NYHA classification), mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, systemic lupus erythematosus, primary hyperaldosteronism, diabetes mellitus, hypera rickemia, 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, the Co-Diovan® drug should not be used in women planning a pregnancy. When prescribing any drug that affects RAAS, the doctor should inform women of childbearing age of the potential dangers of these drugs during pregnancy.

The use of the drug Ko-Diovan ® during pregnancy is contraindicated, since, considering the mechanism of action of receptor antagonists to 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, water scarcity and renal dysfunction in newborns whose mothers were unintentionally exposed to valsartan during pregnancy. The introduction of thiazide diuretics, including HCTT, into the uterus cavity caused jaundice or thrombocytopenia in the fetus or in the neonatal period, as well as the development of other undesirable phenomena that 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 into human milk in human milk. In experimental studies it was shown that valsartan excreted in breast milk.

HCTZ penetrates the placenta, excreted in human breast milk, therefore it is not recommended to use Co-Diovan® during breastfeeding.

Dosing and Administration:

Before the start of therapy, it is necessary to correct water-electrolyte disturbances (the drug is not indicated for patients with reduced BCC).

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

Depending on the clinical situation, the recommended daily dose is 1 a tablet of the preparation Ko-Diovan®, containing valsartan / hydrochlorothiazide at a dose of 80 / 12.5 mg, 160 / 12.5 mg, 160/25 mg, 320 / 12.5 mg, or a maximum of 320/25 mg.

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 impairment of liver function 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 research, were more common with Valsartan and hydrochlorothiazide in comparison with placebo. Against the background of therapy with the drug Ko-Diovan^®possibly the emergence of AEs, observed both with the use of valsartan and hydrochlorothiazide alone, and not detected in the clinical trials of the drug Ko-Diovan®.

The following criteria were used to estimate the frequency (according to the classification of the World Health Organization (WHO)): very often (≥1 / 10 appointments); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000); frequency is unknown (insufficient data to estimate the frequency of development).

Disorders from the metabolism and nutrition: infrequently - dehydration.

Disturbances from the nervous system: infrequently paresthesia; very rarely - dizziness; the frequency is unknown - syncope.

Disturbance of 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: rarely - diarrhea.

Disturbances from 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 - increased serum uric acid concentration, increased serum bilirubin, increased serum creatinine, hypokalemia, hyponatremia, neutropenia, increased urea nitrogen in the blood serum.

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

Below are the AEs that were noted against the background of each of the components taken separately.

Valsartan

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

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

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

Hearing disorders and labyrinthine disorders: infrequently - Vertigo.

Vascular disorders: the frequency is unknown - vasculitis.

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

Disorders 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 itching, bullous dermatitis.

Infringements from 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.

HCTZ

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

Violations from skin and subcutaneous tissue: 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 from the sides of the digestive system: often - decreased appetite, mild nausea, vomiting; rarely - discomfort in the abdomen, constipation, diarrhea; very rarely - pancreatitis.

Violations from sides of the liver and bile ducts: rarely intrahepatic cholestasis or jaundice.

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

Heart Disease: rarely - arrhythmia.

Violations from the sides of the nervous system: rarely - headache, paresthesia, dizziness.

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

Violations from 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.

Violations from side 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.

Violations from side of the immune system: very rarely - reactions hypersensitivity.

Violations from side of the respiratory system, chest and mediastinal organs: rarely - Respiratory disorders (distress syndrome), including pulmonary edema and pneumonitis.

Violations from the sides of the genitals and the breast: often - erectile dysfunction.

Violations from hand kidney and urinary tract: frequency unknown - acute renal failure, impaired renal function.

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

Disturbances from the musculoskeletal and connective tissue: frequency unknown - muscle spasms.

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, 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 the case of early detection of an overdose of the drug, it is recommended to induce vomiting in the patient. In the event of a marked decrease in blood pressure, an intravenous infusion of 0.9% sodium chloride solution is recommended, accompanied by regular monitoring of the heart and respiratory system, bcc and the amount of urine released. For the period of time necessary for therapy, the patient should be laid, lifting his legs.

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

Interaction:

General drug interactions for valsartan and HCTZ

Medicines, simultaneous use with which to avoid:

Lithium preparations

With the simultaneous use of lithium preparations with ACE inhibitors, angiotensin II receptor antagonists 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 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, simultaneous use with which requires caution:

Hypotensive drugs

It is possible to intensify the hypotensive effect when used simultaneously with other means that reduce blood pressure (ACE inhibitors, beta-adrenoblockers, blockers of "slow" calcium channels, guanethidine, methyldopa, vasodilators, direct renin inhibitors, antagonists of AT-II).

Pressor amines

Possible weakening of pressor amines (norepinephrine, epinephrine), which does not require the termination of simultaneous use.

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

Possible reduction of diuretic and hypotensive action of the drug Co-Diovan® with simultaneous use 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, simultaneous use with which to avoid:

Simultaneous use of angiotensin II receptor antagonists with other drugs that affect RAAS leads to an increased incidence of cases 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 simultaneously 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 (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 HCTZ

Other antihypertensive drugs

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

Curare like muscle relaxants

Thiazide diuretics, including hydrochlorothiazide, potentiate the action of nondepolarizing muscle relaxants.Drugs affecting the potassium content 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.

Medications, 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 prolonged simultaneous application of HCTZ 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

Simultaneous use of NSAIDs and HCTT 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

Hemolytic anemia cases have been reported with concomitant use hydrochlorothiazide and methyldopa.

Pressor amines

HCTZ 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 simultaneous 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; 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 simultaneous application with hydrochlorothiazide can to potentiate the development of orthostatic hypotension.

Special instructions:

Changes in the content of electrolytes in blood serum

Thiazide diuretics because of the ability to reduce the potassium and magnesium levels in blood serum should be used with caution in patients with conditions accompanied by water-electrolyte disorders: nephropathy,accompanied by loss of salts, and prerenal (cardiogenic) impairment of kidney function. 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 electrolyte content in the blood plasma, in particular potassium.

When using the drug Co-Diovan ® should take into account the ability of thiazide diuretics to cause hyponatremia and hypochloraemic alkalosis, as well as aggravate the existing hyponatremia. Hyponatremia in these cases is rarely accompanied by a neurological symptomatology. 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)

In patients with severe sodium deficiency and / or reduced bcc (for example, in patients receiving high doses of diuretics), in rare cases, a marked reduction in blood pressure with clinical manifestations may occur at the onset of treatment with Co-Diovan.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 placed and, if necessary, an intravenous infusion of 0.9% sodium chloride solution. After stabilization of blood pressure treatment with the drug Ko-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, the use of Ko-Diovan® can be accompanied by an increase the concentration of urea and creatinine in the serum, so in such patients, the preparation of Co-Diovan® should be used with caution. Chronic heart failure of III-IV functional class (according to NYHA classification), including after a previous myocardial infarction.

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

Systemic lupus erythematosus

There are reports of the development of exacerbations 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 HCTT, can cause a change in glucose tolerance, as well as an increase in the concentration of cholesterol and triglycerides in the 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 in the urine 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. Several patients with hypercalcemia andhypophosphatemia against the background of long-term use of thiazide diuretics determined pathological changes in the parathyroid glands.

Hypersensitivity reactions

The occurrence of reactions Hypersensitivity to the background of the use of hydrochlorothiazide was most often noted in patients with allergic reactions and 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 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 sulfonamide derivatives 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.

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

Patients taking Co-Diovan® should be observed caution in managing vehicles and work with mechanisms.

Form release / dosage:

Tablets, film-coated, 80 mg + 12.5 mg, 160 mg + 12.5 mg, 160 mg + 25 mg, 320 mg + 12.5 mg and 320 mg + 25 mg.

Packaging:

Tablets, film-coated 80 mg + 12.5 mg, 160 mg + 12.5 mg or 160 mg + 25 mg: 14 tablets in a blister pack. 1, 2 or 7 blisters together with instructions for use in a cardboard pack.

Tablets, film-coated 320 mg + 12.5 mg and 320 mg + 25 mg: 7 or 14 tablets in a blister of PVC / PVDC or Al-Al. 1 blister (7 tablets) or 1, 2, 4, 7 or 20 blisters (14 tablets) 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:

Tablets 80 mg + 12.5 mg, 160 mg + 12.5 mg, 320 mg + 12.5 mg and 320 mg + 25 mg: 3 years.

Tablets 160 mg + 25 mg: 2 years

The drug should not be used after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000689

Date of registration:28.09.2011

Date of cancellation:2016-09-28

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: & nbsp09.12.2015

Illustrated instructions

Instructions

Co-Diovan® (Co-Diovan®)