Co-diovan, pills 160/12.5mg, 28pcs

Composition

1 coated tablet contains: Valsartan 160 mg, Hydrochlorothiazide 125 mg

Auxiliary substances:

Colloidal anhydrous silicon dioxide,

crospovidone,

magnesium stearate,

microcrystalline cellulose

Shell composition:

Hypromellose,

macrogol 8000,

talc,

titanium dioxide (E 171),

iron oxide red (E 172)

Pharmacological action

Co-diovan is an antihypertensive drug that includes an angiotensin II receptor antagonist and a thiazide diuretic.

The active hormone of the renin-angiotensin-aldosterone system (RAAS) is angiotensin II, which is formed from angiotensin I with the participation of 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 involvement in the regulation of blood pressure. Being a powerful vasoconstrictor, angiotensin II induces a direct pressor response. In addition, it stimulates the secretion of aldosterone and promotes sodium retention.

Valsartan is an active and specific angiotensin II receptor antagonist intended for oral use. It acts selectively on AT1 subtype receptors, which are responsible for the known effects of angiotensin II. Increased serum angiotensin II levels due to AT1-receptor blockade by valsartan may stimulate free AT2-receptors, which counterbalances the effect of AT1-receptors. Valsartan does not show any pronounced agonistic activity against AT1 receptors. The affinity of valsartan for AT1 receptors is approximately 20,000 times higher than for AT2 receptors.

Valsartan does not inhibit ACE, also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. No bradykinin-related side effects have been observed. In clinical trials comparing valsartan with an ACE inhibitor, the incidence of dry cough was significantly higher (p In a clinical study that included patients who had previously developed a dry cough during treatment with an ACE inhibitor, this complication was observed in 19.5% of cases when treated with valsartan, and in 19% of cases when treated with a thiazide diuretic; while in the group of patients treated with an ACE inhibitor, cough was observed in 68.5% of cases (p

When treating patients with arterial hypertension with valsartan, a decrease in blood pressure is noted, which is not accompanied by a change in heart rate.

After oral use of a single dose of the drug in most patients, the onset of antihypertensive action is noted within 2 hours, and the maximum decrease in blood pressure is achieved within 4-6 hours. After taking the drug, the antihypertensive effect persists for more than 24 hours. With repeated use of the drug, the maximum reduction in blood pressure, regardless of the dose taken, is usually achieved within 2-4 weeks and maintained at the achieved level during long-term therapy. When combined with hydrochlorothiazide, a significant additional reduction in blood pressure is achieved.

The point of application of the action of thiazide diuretics is the cortical part of the distal convoluted renal tubules, where the receptors that are highly sensitive to the action of diuretics are located and where the transport of sodium and chlorine ions is suppressed. The mechanism of action of thiazides is associated with the suppression of the Na + Cl-pump, which, apparently, occurs due to competition for Cl-transport sites. As a result, the excretion of sodium and chlorine ions increases approximately equally. As a result of diuretic action, there is a decrease in the volume of circulating plasma, which increases the activity of renin, aldosterone secretion, excretion of potassium in the urine and, consequently, a decrease in the concentration of potassium in the serum. The relationship between renin and aldosterone is mediated by angiotensin II, so the appointment of an angiotensin II receptor antagonist will reduce the potassium loss associated with the use of a thiazide diuretic.

Indications

Arterial hypertension.

Use during pregnancy and lactation

Given the mechanism of action of angiotensin II antagonists, the risk of negative effects on the fetus cannot be excluded when using drugs of this group. It is known that the action of ACE inhibitors on the uterus, if they are prescribed to pregnant women in the second and third trimesters, leads to damage or death of the developing fetus.

The introduction of a thiazide diuretic into the uterine cavity led to the development of thrombocytopenia in the fetus or in the neonatal period, as well as to the development of other adverse events that occur later in adults. Therefore, Co-Diovan, like any other drug that has a direct effect on the RAAS, should not be used during pregnancy and lactation. If pregnancy is detected during Co-Diovan treatment, the drug should be discontinued as soon as possible.

It is not known whether valsartan passes into human breast milk.

Hydrochlorothiazide penetrates the placental barrier and is also excreted in breast milk. Therefore, it is not recommended to use Co-Diovan in nursing mothers.

Experimental studies have shown that valsartan is excreted in breast milk in rats.

Contraindications

-Severe liver function disorders, biliary cirrhosis and cholestasis. – Anuria, severe renal impairment ( creatinine clearance- Hypokalemia, hyponatremia, hypercalcemia, hyperuricemia with clinical manifestations that are refractory to adequate therapy. – Pregnancy. – Hypersensitivity to the components of Co-Diovan.

Side effects

Adverse events such as abdominal pain, visual disturbances, restlessness, arthralgia, arthritis, bronchitis, dyspepsia, shortness of breath, impotence, insomnia, lower limb muscle cramps, rapid urination, palpitation, rash, sprains, urinary tract infections, viral infections, edema, asthenia, vertigo were observed with a frequency of less than 1%. The causal relationship of these phenomena with the use of the Code has not been established.

Post-marketing studies indicate very rare cases of angioedema, rash, pruritus, and other hypersensitivity/allergic reactions, including serum sickness and vasculitis. In some cases, renal dysfunction was observed.

On the part of laboratory parameters: in 2.2% of patients treated with Co-Diovan, serum potassium concentrations decreased by more than 20% (the decrease in this indicator in the group of patients treated with placebo was 3.3%). In controlled clinical trials,1.4% of patients treated with Co-Diovan experienced an increase in serum creatinine (compared to 1.1% for the placebo group).

In those clinical trials where valsartan was used as monotherapy, other adverse events were also noted (the causal relationship of these events with the use of valsartan has not been established). : with a frequency of more than 1% – arthralgia; with a frequency of less than 1% – edema, asthenia, insomnia, rash, decreased libido, vertigo.

Hydrochlorothiazide has been widely used for many years, and more often in doses higher than that included in the Co-Diovan. The following adverse reactions have been reported during monotherapy with thiazide diuretics, including hydrochlorothiazide. Often – urticaria and other types of rashes, loss of appetite, nausea and vomiting, postural hypotension (the severity of which increases with alcohol intake, the use of anesthesia or sedatives), impotence. Rarely-photosensitivity, abdominal pain, constipation, diarrhea, gastrointestinal discomfort, intrahepatic cholestasis, jaundice, arrhythmias, headache, dizziness, sleep disorders, depression, paresthesia, visual disturbances, thrombocytopenia, sometimes with purpura. Very rarely-necrotizing vasculitis, toxic epidermal necrolysis, lupus-like reactions, exacerbation of skin manifestations of systemic lupus erythematosus, pancreatitis, leukopenia, agranulocytosis, suppression of bone marrow hematopoiesis, hemolytic anemia, hypersensitivity reactions, respiratory disorders (including pneumonitis and pulmonary edema). Possible water-electrolyte and metabolic disorders.

Interaction

It is possible to increase the antihypertensive effect when combined with other antihypertensive drugs.

When using potassium salts, potassium-sparing diuretics, potassium-containing food salt substitutes, or any other medications that may cause an increase in the concentration of potassium in the blood (for example, heparin ), caution is required and frequent determination of the concentration of potassium in the blood is required.

When lithium preparations were co-administered with ACE inhibitors or thiazide diuretics, a reversible increase in serum lithium concentrations and an increase in toxic manifestations were observed. Experience with the combined use of valsartan and lithium preparations is not yet available, so in this case, monitoring the concentration of lithium in the serum is recommended.

There was no clinically significant interaction during valsartan monotherapy with the following medications: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide.

Since Co-Diovan contains a thiazide diuretic, the following drug interactions are potentially possible.

Thiazides potentiate the action of curare-like muscle relaxants.

It is possible to reduce the diuretic and antihypertensive effects of hydrochlorothiazide, which is part of Co-Diovan, when used simultaneously with NSAIDs (for example, with salicylic acid derivatives, Indometacin). Concomitant hypovolemia can lead to the development of acute renal failure.

The risk of hypokalemia increases with concomitant use of saluretics, corticosteroids, ACTH, amphotericin, carbenoxolone, penicillin G and salicylic acid derivatives.

Thiazide diuretics may cause undesirable effects such as hypokalemia or hypomagnesemia, which in turn increase the risk of arrhythmia when cardiac glycosides are co-administered.

It may be necessary to adjust the dose of insulin or an oral hypoglycemic drug.

Concomitant use of thiazide diuretics may increase the frequency of hypersensitivity reactions to allopurinol; increase the risk of side effects of amantadine ; increase the hyperglycemic effect of diazoxide; reduce renal excretion of cytotoxic drugs (for example, cyclophosphamide, methotrexate) and lead to potentiation of their myelosuppressive effect.

An increase in the bioavailability of a thiazide diuretic is observed with simultaneous use of holinoblockers (for example, atropine, biperiden), which, apparently, is associated with a decrease in the motor activity of the gastrointestinal tract and a slowdown in gastric emptying.

Cases of hemolytic anemia have been reported with concomitant use of a thiazide diuretic and methyldopa.

Colestyramine reduces the absorption of thiazide diuretics.

When combined with the use of thiazide diuretics with vitamin D or calcium salts, it is possible to potentiate the increase in serum calcium concentration.

Concomitant use of cyclosporine may increase the risk of hyperuricemia and gout-like symptoms.

How to take, course of use and dosage

Co-Diovan is prescribed for 1 tab. 1 time / day daily.

Use in patients with impaired liver function: Patients with mild or moderate hepatic insufficiency of non-biliary origin without concomitant phenomena of cholestasis do not need to change the dose of the drug.

Use in patients with impaired renal function: Patients with mild or moderate renal impairment ( creatinine clearance > 30 ml / min) do not need to change the dose of the drug.

Overdose

-Symptoms: although there is currently no information about Co-Diovan overdose, the main manifestation that could be expected is severe hypotension.

– Treatment: if the drug has been taken recently, induce vomiting. In case of hypotension, the usual method of therapy is intravenous use of saline solution. Valsartan cannot be eliminated from the body by hemodialysis due to its significant binding to plasma proteins. At the same time, hemodialysis is effective for removing hydrochlorothiazide from the body.

Special instructions

Changes in serum electrolyte balance: Caution should be exercised when using Co-Diovan concomitantly with potassium salts, potassium-sparing diuretics, potassium-containing food salt substitutes, as well as with medications that may cause an increase in the concentration of potassium in the blood (for example, heparin ). Hypokalemia has been reported in patients treated with thiazide diuretics. Frequent monitoring of blood potassium concentrations is recommended. Hyponatremia and hypochloremic alkalosis may occur when thiazide diuretics are used. Thiazides cause increased urinary excretion of magnesium, which can lead to hypomagnesemia.

Lack of sodium and/or circulating blood volume (BCC)in the body: In patients with severe sodium and/or BCC deficiency, such as those receiving high-dose diuretics, hypotension with clinical manifestations may occur in rare cases at the beginning of Co-Diovan treatment. Before starting treatment with Co-Diovan, the body’s sodium content and/or BCC should be corrected. If hypotension develops, the patient should be laid down and, if necessary, given an intravenous infusion of saline solution. After blood pressure stabilizes, treatment with Co-Diovan can be continued.

Renal artery stenosis: The drug should be used with caution in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery of a single kidney. The safety of Co-Diovan in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery of a single kidney has not been established.

Use in patients with impaired liver function: No dose adjustment is required in patients with mild or moderate hepatic impairment in the absence of cholestasis, although the drug should be used with caution in this category of patients. Liver diseases do not significantly affect the pharmacokinetics of hydrochlorothiazide, so no dose reduction is required. Currently, there are no data on the use of valsartan in patients with severe hepatic impairment.

Use in patients with impaired renal function: Patients with impaired renal function with creatinine clearance greater than 30 ml / min do not need to adjust the dose of the drug. Currently, there are no data on the use of Co-Diovan in patients with severe renal impairment (creatinine clearance less than 30 ml / min) and in patients undergoing hemodialysis.

Other metabolic disorders: Thiazide diuretics may cause changes in glucose tolerance, as well as increased serum cholesterol, triglycerides, and uric acid concentrations.

Use in pediatrics: The safety and efficacy of Co-Diovan in children have not yet been established.

Influence on the ability to drive motor vehicles and manage mechanisms: When prescribing Co-Diovan, it is recommended to use caution when driving a car and operating mechanisms.

Form of production

Coated tablets.

Storage conditions

In a dry place, at a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Valsartan, Hydrochlorothiazide

Conditions of release from pharmacies

By prescription

Dosage form

Tablets