Coaprovel, 25 mg+300 mg 28 pcs

Arterial hypertension.

Indications

Arterial hypertension.

Pharmacological effect

Coaprovel has a hypotensive effect.

Special instructions

The risk of developing a pronounced decrease in blood pressure increases against the background of a decrease in blood volume and hyponatremia caused by the use of diuretics, a diet low in Na +, diarrhea, and vomiting, so these conditions must be corrected before starting drug therapy. In patients with chronic renal failure, azotemia may occur during therapy with thiazide diuretics. Periodic monitoring of serum K+, creatinine and uric acid concentrations is recommended. There is no experience with the use of the drug in patients with recent kidney transplantation.

Therapy with thiazide diuretics can cause mini-formation of latent diabetes mellitus and also reduce glucose tolerance. In patients with diabetes mellitus, dose adjustment of insulin or oral hypoglycemic drugs may be required. Therapy with hydrochlorothiazide at a dose of 12.5 mg contained in the drug has virtually no effect on the concentration of cholesterol and triglycerides.

Hyperuricemia or exacerbation of gout may occur during therapy with thiazide diuretics. Treatment with hydrochlorothiazide can lead to disturbances in water and electrolyte balance (hypokalemia, hyponatremia and hypochloremic alkalosis). Concomitant use of irbesartan may reduce diuretic-induced hypokalemia. The risk of hypokalemia increases with concomitant treatment with corticosteroids or ACTH.

Irbesartan may lead to hyperkalemia, especially in the presence of renal failure and/or CHF or diabetes mellitus. During the treatment period, periodic monitoring of K+ concentration in the blood serum is recommended. There is no evidence that irbesartan can reduce or prevent diuretic-induced hyponatremia. Cl- deficiency is usually mild and does not require treatment. Thiazide diuretics can cause hypomagnesemia, as well as reduce renal calcium excretion and cause mild hypercalcemia, provided there are no disturbances in Ca2+ metabolism.

Hypercalcemia may be a sign of latent hyperparathyroidism; in this case, the drug should be discontinued until a study of the function of the parathyroid glands is carried out. Hydrochlorothiazide may cause a positive drug test result. In patients whose vascular tone and renal function depend mainly on the activity of the renin-angiotensin-aldosterone system (including CHF, kidney disease, including renal artery stenosis), therapy with angiotensin II receptor antagonists can cause a marked decrease in blood pressure, azotemia, oliguria or, in rare cases, acute renal failure.

An excessive decrease in blood pressure due to coronary artery disease or other cardiovascular diseases can lead to myocardial infarction or stroke. The development of allergic reactions to hydrochlorothiazide is more likely in patients with a history of such reactions. Exacerbation of SLE has been observed with the use of thiazide diuretics. It must be taken into account that in rare cases, dizziness and increased fatigue may occur during treatment, so caution should be exercised when engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reaction (including when driving a car).

Active ingredient

Hydrochlorothiazide, Irbesartan

Composition

1 tablet contains irbesartan 300 mg,

hydrochlorothiazide 12.5 mg,

excipients:

microcrystalline cellulose,

sodium croscarmellose,

lactose monohydrate,

magnesium stearate,

colloidal silicon dioxide hydrated,

pregelatinized corn starch,

iron oxide red,

iron oxide yellow.

Contraindications

— II and III trimesters of pregnancy;

– hypersensitivity to the components of Coaprovel;

– hypersensitivity to other sulfonamide derivatives.

To use hydrochlorothiazide:

— severe renal failure (creatinine clearance <30 ml/min);

– refractory hypokalemia, hypercalcemia;

– severe form of liver failure;

– biliary cirrhosis of the liver;

– cholestasis.

Side Effects

From the hematopoietic system: aplastic anemia, bone marrow depression, hemolytic anemia, leukopenia, neutropenia/agranulocytosis, thrombocytopenia.

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

From the organ of vision: transient blurred vision, xanthopsia.

From the cardiovascular system: arrhythmias, postural hypotension.

From the respiratory system: 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.

From the musculoskeletal system: muscle spasms, weakness.

From the urinary system: interstitial nephritis, renal dysfunction.

Other: increased body temperature.

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

Interaction

Other antihypertensive drugs: the antihypertensive effect of COAPROVEL can be enhanced by the use of other antihypertensive drugs. Irbesartan and hydrochlorothiazide (at doses of 300 mg irbesartan/25 mg hydrochlorothiazide) should be used with caution in combination with other antihypertensive agents, including calcium channel blockers and beta-blockers. Pre-treatment with high doses of diuretics may lead to hypovolemia and the risk of hypotension (see section “Special warnings and precautions for use”).

Lithium: Reversible increases in serum lithium concentrations and toxic effects have been observed with concomitant use of lithium with angiotensin-converting enzyme (ACE) inhibitors. With regard to irbesartan, similar effects have been extremely rare to date. In addition, the renal clearance of lithium is reduced by thiazides, so in the case of COAPROVEL, the risk of lithium toxicity may be increased. Therefore, the combination of lithium and COAPROVEL is not recommended. If the combination is necessary, careful monitoring of serum lithium levels is recommended.

Medicines that affect blood potassium levels: the hypokalemic effect of hydrochlorothiazide is weakened by the potassium-sparing effect of irbesartan. However, this effect of hydrochlorothiazide may be enhanced by other drugs that cause potassium loss and hypokalemia (for example, diuretics, laxatives, amphotericin, carbenoxolone, penicillin G sodium, 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, potassium supplements, potassium-containing salt substitutes, or other drugs that can increase serum potassium levels (eg, heparin sodium) may result in increased serum potassium levels. In patients at risk, adequate monitoring of serum potassium levels is recommended.

Medicines affected by serum potassium imbalance: Periodic monitoring of serum potassium levels is recommended when COAPROVEL is used concomitantly with medicinal products affected by serum potassium imbalance (eg, digitalis glycosides, antiarrhythmics).

Non-steroidal anti-inflammatory drugs: with simultaneous use of angiotensin II antagonists and non-steroidal anti-inflammatory drugs (for example, selective COX-2 inhibitors, acetylsalicylic acid (> 3 g / day) and non-selective NSAIDs), a weakening of the hypotensive effect may occur.

As with ACE inhibitors, concomitant use of angiotensin II antagonists and NSAIDs may increase the risk of impaired renal function, including the possibility of acute renal failure, and lead to an increase in serum potassium levels, especially in patients with already impaired renal function. Precautions should be taken when administering this combination, especially in elderly patients. Patients should not be dehydrated. Monitoring of renal function should be carried out after initiation of combination therapy and periodically thereafter.

Additional information on irbesartan interactions: The pharmacokinetics of irbesartan are not affected when coadministered with hydrochlorothiazide. Irbesartan is mainly metabolized by CYP2C9 and, to a lesser extent, by glucuronidation. No significant

pharmacokinetic and pharmacodynamic interactions when irbesartan was co-administered with warfarin, a drug metabolized by CYP2C9. Effects of CYP2C9 inducers such as rifampicin on
The pharmacokinetics of irbesartan have not been evaluated. The pharmacokinetics of digoxin did not change when combined with irbesartan.

Additional information on hydrochlorothiazide interactions: The following drugs may interact with thiazide diuretics:

Alcohol, barbiturates or narcotic drugs: increased orthostatic hypotension may occur;

Hypoglycemic drugs (oral drugs and insulin): dose adjustment of the hypoglycemic drug may be required (see section “Special warnings and precautions for use”);

Cholestyramine and colestyrene resins: absorption of hydrochlorothiazide is reduced in the presence of anion exchange resins;

Glucocorticosteroids, ACTH: a more pronounced disturbance of the electrolyte composition is possible, in particular, increased hypokalemia;

Digitalis glycosides: Hypokalemia and hypomagnesemia caused by thiazide diuretics contribute to digitalis-induced arrhythmias (see Special Warnings and Precautions for Use);

Non-steroidal anti-inflammatory drugs: The use of non-steroidal anti-inflammatory drugs may reduce the effects of thiazide diuretics in some patients;

Catecholamines (eg, norepinephrine): the effect of these drugs may be reduced;

Non-depolarizing muscle relaxants: The effect of non-depolarizing muscle relaxants may be enhanced by hydrochlorothiazide;

Antigout medications: Dosage adjustments of antigout medications may be necessary as hydrochlorothiazide may increase serum uric acid levels. It may be necessary to increase the dosage of probenecid or sulfinpyrazone.

Concomitant use with thiazide diuretics may increase the frequency of allergic reactions to allopurinol;

Calcium salts: Thiazide diuretics may increase serum calcium levels due to decreased excretion. If calcium supplements or drugs that affect calcium levels are to be prescribed (for example, during vitamin D therapy), serum calcium levels should be monitored and calcium dosage adjustments made accordingly.
Other interactions: The hyperglycemic effect of beta-blockers and diazoxide may be enhanced by thiazides.

Anticholinergics (eg, atropine) may increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility. Thiazides may increase the risk of side effects caused by amantadine. Thiazides may reduce the urinary excretion of cytotoxic drugs (eg, cyclophosphamide, methotrexate) and enhance their myelosuppressive effects.

Overdose

There is no specific information on overdose of Coaprovel.

– Symptoms: in case of an overdose of irbesartan, arterial hypotension, tachycardia, bradycardia are most likely; in case of 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 may lead to convulsions and/or increased arrhythmias in the case of concomitant use of digitalis glycosides and antiarrhythmic drugs.

– Treatment: recommended measures depending on the time elapsed since taking the drug and the severity of symptoms – provoking vomiting and/or gastric lavage, using activated charcoal, carefully monitoring the patient’s condition, conducting symptomatic and supportive therapy.

Serum electrolytes and creatinine should be monitored frequently. In case of arterial hypotension, the patient should be placed on his back with the lower limbs elevated and salts and fluids should be replaced as quickly as possible. Irbesartan is not eliminated by hemodialysis. The extent of hydrochlorothiazide elimination during hemodialysis has not been established.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

3 years

Manufacturer

Sanofi Winthrop Industries, France