Coaprovel, pills 300/12.5mg, 28pcs

Composition

1 tablet contains:

Irbesartan 300 mg,

Hydrochlorothiazide 125 mg

Auxiliary substances:

Microcrystalline cellulose,

sodium croscarmellose,

lactose monohydrate,

magnesium stearate,

colloidal hydrated silicon dioxide,

pregelatinized corn starch,

iron oxide red,

iron oxide yellow

Pharmacological action

Coaprovel is a combined antihypertensive drug containing the angiotensin II receptor antagonist irbesartan and the thiazide diuretic hydrochlorothiazide. The combination of these ingredients has an additive antihypertensive effect, lowering blood pressure to a higher degree than each of them individually.

Selective antagonism of irbesartan against AT1 receptors is manifested by an increase in the content of renin and angiotensin II and a decrease in the content of aldosterone in the blood serum. The level of potassium in the blood serum slightly changes during treatment with irbesartan in monotherapy at the recommended doses.

Irbesartan does not inhibit ACE (kininase II), which promotes the formation of angiotensin II, and also converts bradykinin to inactive metabolites. Irbesartan does not require metabolic activation to manifest its action.

Hydrochlorothiazide is a thiazide diuretic. Thiazide diuretics affect the renal mechanisms of electrolyte reabsorption, increasing the excretion of sodium and chlorides in approximately equivalent amounts, and inhibiting sodium reabsorption. Hydrochlorothiazide reduces plasma volume by increasing plasma renin activity and aldosterone secretion, followed by an increase in urinary potassium and a decrease in serum potassium. Presumably, by blocking the renin-angiotensin-aldosterone system, the combined use of irbesartan leads to the prevention of serum potassium loss caused by this diuretic.

When taking hydrochlorothiazide, the onset of diuresis occurs in the first 2 hours after ingestion, reaches a maximum peak within 4 hours, and the effect persists for about 6-12 hours.

A decrease in blood pressure occurs after taking the first dose of Coaprovel, the maximum effect is observed after 6-8 weeks of treatment. The effect persists during long-term use (1 year). An increase in blood pressure, although not studied during treatment with Coaprovel, was not detected when irbesartan or hydrochlorothiazide were discontinued separately.

There are no differences in the response to Coaprovel depending on age or gender.

Indications

Arterial hypertension.

Use during pregnancy and lactation

Coaprovel is contraindicated in the second and third trimesters of pregnancy.

If pregnancy is diagnosed, then Coaprovel should be discontinued as soon as possible. The skull and kidney function should be checked by ultrasound if, due to inattention, therapy was continued for a long time.

Coaprovel is contraindicated during the entire lactation period.

Contraindications

: Hereditary galactose intolerance, lactase deficiency, or glucose and galactose malabsorption. – Pregnancy. – Lactation period. – Age up to 18 years (efficacy and safety have not been established). – Hypersensitivity to the components of the drug.

For the use of hydrochlorothiazide:

– Severe renal failure ( CC-Refractory hypokalemia, hypercalcemia. – Severe form of liver failure. – Biliary cirrhosis of the liver. – Cholestasis. – Hypersensitivity to other drugs derived from sulfonamide.

Side effects

Hematopoietic disorders: aplastic anemia, bone marrow depression, hemolytic anemia, leukopenia, neutropenia/agranulocytosis, thrombocytopenia.

From the central nervous system and peripheral nervous system: depression, sleep disorders, dizziness, paresthesia, anxiety.

From the side of the visual organ: transient blurred vision, xanthopsy.

From the cardiovascular system: arrhythmias, postural hypotension.

Respiratory system disorders: respiratory distress syndrome (including pneumonitis and pulmonary edema).

From the digestive system: jaundice (intrahepatic cholestatic jaundice).

Allergic reactions: anaphylactic reactions, toxic necrosis of the epidermis, skin reactions such as lupus erythematosus, necrotic angiitis (vasculitis, cutaneous vasculitis), photosensitivity reactions, rash, exacerbation of skin manifestations of lupus erythematosus, urticaria.

Musculoskeletal system disorders: muscle spasms, weakness.

Urinary system disorders: interstitial nephritis, renal dysfunction.

Other: increased body temperature.

From laboratory parameters: electrolyte balance disorders (including hypokalemia and hyponatremia), glucosuria, hyperglycemia, hyperuricemia, increased cholesterol and TG.

Interaction

It is possible to increase the antihypertensive effect of Coaprovel with the simultaneous use of other antihypertensive drugs. The combination of irbesartan / hydrochlorothiazide at doses of 300 mg / 25 mg should be used with caution simultaneously with other antihypertensive agents, including calcium channel blockers and beta-blockers. Pretreatment with high-dose diuretics may lead to hypovolemia and the risk of hypotension.

Reversible increases in serum lithium concentrations and toxic effects were observed with concomitant use of lithium with ACE inhibitors. For irbesartan, similar effects have been extremely rare to date. In addition, the renal clearance of lithium is reduced by thiazides, so if Coaprovel is used, the risk of lithium toxicity may be increased. Therefore, the combination of lithium and Coaprovel is not recommended. If a combination is necessary, careful monitoring of serum lithium levels is recommended.

The hypokalemic effect of hydrochlorothiazide is weakened by the potassium-sparing effect of irbesartan. However, this effect of hydrochlorothiazide can be enhanced by other drugs that cause potassium loss and hypokalemia (for example, diuretics, laxatives, amphotericin, carbenoxolone, penicillin G sodium salt, salicylic acid derivatives). Conversely, based on experience with other drugs that reduce the activity of the renin-angiotensin system, concomitant use of potassium-sparing diuretics, dietary supplements, salt substitutes containing potassium, or other drugs that can increase serum potassium levels (for example, sodium salt of heparin) may lead to an increase in the amount of potassium in the blood serum. Patients at risk should be adequately monitored for serum potassium levels.

Periodic monitoring of serum potassium levels is recommended in the case of co-use of Coaprovel and drugs that are affected by a violation of the potassium balance in the blood serum (for example, digitalis glycosides, antiarrhythmic agents).

Concomitant use of angiotensin II antagonists and NSAIDs (for example, selective COX-2 inhibitors, acetylsalicylic acid >3 g/day, and non-selective NSAIDs) may weaken the antihypertensive effect.

As with ACE inhibitors, concomitant use of angiotensin II antagonists and NSAIDs may increase the risk of impaired renal function, including the likelihood of acute renal failure, and lead to increased serum potassium, especially in patients with pre-existing impaired renal function. This combination should be used with caution, especially in elderly patients. Patients should not be dehydrated. Monitoring of renal function should be performed after initiation of combination therapy and periodically thereafter.

The pharmacokinetics of irbesartan are not affected when co-administered with hydrochlorothiazide. Irbesartan is mainly metabolized by CYP2C9 and to a lesser extent by glucuronidation. No significant pharmacokinetic or pharmacodynamic interactions were observed when irbesartan was co-administered with warfarin, a drug metabolized with CYP2C9. The effect of CYP2C9 inducers, such as rifampicin, on the pharmacokinetics of irbesartan has not been evaluated.

The pharmacokinetics of digoxin did not change when co-administered with irbesartan.

When used concomitantly with thiazide diuretics, ethanol, barbiturates, or anesthetics may increase orthostatic hypotension.

When using hydrochlorothiazide, it may be necessary to adjust the dose of the hypoglycemic agent.

Absorption of hydrochlorothiazide decreases in the presence of anion exchange resins.

With simultaneous use of hydrochlorothiazide and corticosteroids or ACTH, a more pronounced violation of the electrolyte balance is possible, in particular, increased hypokalemia.

Hypokalemia and hypomagnesemia caused by a thiazide diuretic contribute to the manifestation of digitalis-induced arrhythmias.

NSAIDs may reduce the effects of thiazide diuretics in some patients.

It is possible to reduce the effectiveness of catecholamines (for example, norepinephrine ) under the influence of hydrochlorothiazide.

The effect of non-depolarizing muscle relaxants can be enhanced by hydrochlorothiazide.

Adjustments to the dosage of gout medications may be necessary, as hydrochlorothiazide may increase serum uric acid levels. It may be necessary to increase the dose of probenecid or sulfinpyrazone. Concomitant use with thiazide diuretics may increase the frequency of allergic reactions to allopurinol.

Thiazide diuretics may increase serum calcium levels due to reduced excretion.If calcium supplements or drugs that affect calcium levels are to be prescribed (for example, during vitamin D therapy), then serum calcium levels should be monitored and the dose of the calcium preparation adjusted accordingly.

The hyperglycemic effect of beta-blockers and diazoxide may be enhanced by thiazides.

Anticholinergic agents (e. g., atropine ) may increase the bioavailability of thiazide diuretics due to decreased gastrointestinal motility.

Thiazides may increase the risk of side effects caused by amantadine.

Thiazides can reduce the urinary excretion of cytotoxic drugs (for example, cyclophosphamide, methotrexate ) and increase their myelosuppressive effects.

How to take, course of use and dosage

Coaprovel can be applied 1 time/day. before or during meals in patients whose blood pressure is insufficiently controlled by irbesartan or hydrochlorothiazide alone.

Coaprovel 300/25 mg is prescribed to patients whose blood pressure is insufficiently controlled by irbesartan (300 mg) or Coaprovel (300/12.5 mg).

Use of the drug in doses of more than 300 mg of irbesartan/25 mg of hydrochlorothiazide 1 time / day. not recommended.

Before starting the use of Coaprovel, it is necessary to correct the reduced BCC and / or sodium content. If this fails, a lower initial dose should be considered.

– Use in patients with impaired liver function: Coaprovel is contraindicated in patients with severe hepatic insufficiency. In patients with impaired liver function, thiazides should be used with caution, but in patients with mild to moderate hepatic insufficiency, no dose adjustment is required.

– Use in patients with impaired renal function: Since the drug contains hydrochlorothiazide, Coaprovel is contraindicated in patients with severe renal impairment ( creatinine clearance 30 ml / min

. – Use in elderly patients: There is no need to adjust the dose of Coaprovel.

Overdose

There is no specific information about overdose of Coaprovel.

– Symptoms: with an overdose of irbesartan, hypotension, tachycardia, bradycardia are most likely; with an overdose of hydrochlorothiazide, hypokalemia, hyponatremia, dehydration as a result of excessive diuresis. The most common signs and symptoms of overdose are nausea and drowsiness. Hypokalemia can lead to seizures and / or increased arrhythmias if digitalis glycosides and antiarrhythmic agents are used concomitantly.

– Treatment: recommended measures depending on the time elapsed since taking the drug and the severity of the symptoms – provoking vomiting and / or gastric lavage, the use of activated charcoal, careful monitoring of the patient’s condition, conducting symptomatic and maintenance therapy. Frequent monitoring of serum electrolytes and creatinine should be performed. In case of arterial hypotension, the patient should be placed on his back with his lower limbs raised and as soon as possible to replace the salts and fluids. Irbesartan is not eliminated by hemodialysis. The degree of elimination of hydrochlorothiazide during hemodialysis has not been established.

Special instructions

Coaprovel rarely causes symptomatic hypotension in patients with elevated blood pressure. Symptomatic hypotension may be suspected in patients with reduced BCC or low sodium levels due to diuretic therapy, a salt-restricted diet, diarrhea, or vomiting. Such conditions should be corrected before starting therapy with Coaprovel.

Coaprovel should be used with extreme caution in patients with aortic stenosis and mitral valve stenosis, obstructive hypertrophic cardiomyopathy.

It is not recommended to use Coaprovel for primary aldosteronism.

During therapy with thiazide diuretics, glucose tolerance may decrease. In patients with diabetes mellitus, it may be necessary to adjust the dose of insulin or oral hypoglycemic drugs. Thiazide therapy can cause the manifestation of latent diabetes mellitus.

Treatment with hydrochlorothiazide at a dose of 12.5 mg contained in Coaprovel has virtually no effect on cholesterol and TG levels.

With thiazide therapy, some patients may experience hyperuricemia or exacerbation of gout.

Thiazides, including hydrochlorothiazide, may cause impaired water and electrolyte balance (hypokalemia, hyponatremia, and hypochloremic alkalosis). Although hypokalemia may occur with thiazide diuretics, concurrent irbesartan therapy may reduce diuretic-induced hypokalemia. The risk of hypokalemia increases in patients who receive corticosteroids or ACTH. On the contrary, due to irbesartan, a component of Coaprovel, hyperkalemia is possible, especially in the presence of renal failure and / or heart failure, or diabetes mellitus. Adequate monitoring of serum potassium levels is recommended for patients at risk.

Potassium-sparing diuretics, potassium supplements or substitutes containing potassium should be administered with caution at the same time as Coaprovel.

There is no evidence that irbesartan can reduce or prevent hyponatremia caused by diuretics. Chloride deficiency is usually minor and does not require treatment.

Thiazides can reduce the excretion of calcium through the kidneys and cause a slight increase in serum calcium levels, provided that there are no violations in calcium metabolism. The observed hypercalcemia may be a sign of latent hyperparathyroidism. Thiazide supplementation should be discontinued prior to parathyroid function testing.

Thiazides increase the excretion of magnesium in the urine, which can lead to hypomagnesemia.

It is not recommended to prescribe Coaprovel in combination with lithium preparations.

Hydrochlorothiazide can cause a positive result in a doping test.

In patients whose vascular tone and renal function depend mainly on the activity of the renin-angiotensin-aldosterone system (for example, in patients with chronic heart failure or kidney diseases, including renal artery stenosis), therapy with angiotensin II receptor antagonists may cause acute hypotension, azotemia, oliguria or, in rare cases, acute renal failure. Excessive lowering of blood pressure in patients with CHD or other cardiovascular diseases can lead to myocardial infarction or brain stroke.

The development of allergic reactions to hydrochlorothiazide is more likely in patients who have a history of such reactions.

With the use of thiazide diuretics, an exacerbation of systemic lupus erythematosus was noted.

In the first trimester of pregnancy, the use of Coaprovel is not recommended.

– Use in patients with impaired liver function: Coaprovel is not recommended for patients with severe hepatic insufficiency. In patients with impaired liver function, thiazides should be used with caution, but in patients with mild to moderate hepatic insufficiency, no dose adjustment is required.

– Use in patients with impaired renal function: Since the drug contains hydrochlorothiazide, Coaprovel is not recommended for patients with severe renal impairment (creatinine clearance 30 ml / min). No dose adjustment is required in patients with renal insufficiency with creatinine clearance >30 ml/min. The risk of developing severe arterial hypotension and renal failure is increased in patients with bilateral renal artery stenosis or with stenosis of the artery of the only functioning kidney when using ACE inhibitors or angiotensin II receptor blockers. Although there are no such messages when applying the Caeprovel, this effect should be taken into account. When using Coaprovel in patients with impaired renal function, periodic monitoring of serum potassium, creatinine and uric acid levels is recommended. In patients after a recent kidney transplant, there is no experience of using Coaprovel. Coaprovel should not be used in patients with severe renal insufficiency ( CC

-Use in pediatrics The safety and efficacy of Coaprovel in children and adolescents under 18 years of age have not been established.

– Effects on the ability to drive vehicles and manage mechanisms: The effect of Coaprovel on the ability to drive vehicles and mechanisms has not been studied, but based on its pharmacodynamic properties, it is unlikely that Coaprovel affects this ability. When driving vehicles or mechanisms, it should be taken into account that in rare cases, dizziness and increased fatigue may occur during the treatment of high blood pressure.

Form of production

Pills.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Active ingredient

Hydrochlorothiazide, Irbesartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets