Coaprovel pill 300mg/25mg №28

Release form, composition and packaging

Excipients: lactose monohydrate - 53.3 mg, microcrystalline cellulose - 90 mg, croscarmellose sodium - 30 mg, pregelatinized starch - 90 mg, Magnesium stearate - 6 mg, silicon dioxide - 4.5 mg, iron dye red oxide (E172) - 0.6 mg, iron dye yellow oxide (E172) - 0.6 mg, opadry^® pink (lactose monohydrate, hypromellose, macrogol 3350, titanium dioxide (E171), iron dye red oxide (E172), iron dye yellow oxide (E172) - 21 mg, carnauba wax - traces.

Indications

- moderate to severe arterial hypertension (treatment of patients for whom combination therapy is indicated).

Dosage and administration

Coaprovel^® take 1 time / day, regardless of the meal.

Coaprovel^® prescribed to patients whose blood pressure is not sufficiently controlled by irbesartan or hydrochlorothiazide in monotherapy.

Coaprovel^® 150 / 12.5 mg (tablets containing irbesartan / hydrochlorothiazide 150 / 12.5 mg, respectively) may be given to patients whose blood pressure is not sufficiently controlled by hydrochlorothiazide (12.5 mg / day) or irbesartan (150 mg / day) in monotherapy.

Coaprovel^® 300 / 12.5 mg (tablets containing irbesartan / hydrochlorothiazide 300 / 12.5 mg, respectively) may be given to patients whose blood pressure is not sufficiently controlled by irbesartan (300 mg) or Coaprovel (150 / 12.5 mg).

If necessary, use in patients whose blood pressure is not sufficiently controlled by the drug Coaprovel^® 300 mg / 12.5 mg, the doses of drugs in combination can be increased to 300 mg of irbesartan and 25 mg of hydrochlorothiazide per day: 2 pills of the drug Coaprovel^® 150 / 12.5 mg or 1 pill of the drug Coaprovel^® 300/25 mg.

Maximum daily dose: 2 pills of the drug Coaprovel^® 150 / 12.5 mg or 1 pill of the drug Coaprovel^® 300/25 mg. If it is impossible to achieve the target blood pressure with the use of Coaprovel 300/25 mg, other antihypertensive drugs may be added to it (beta-blockers, Calcium channel blockers of prolonged action).

Coaprovel^® 300/25 mg not recommended patients with severe impaired renal function (CC <30 ml / min). Loop diuretics are preferred.

Have patients with impaired renal function (CC ≥ 30 ml / min) dose adjustment of the drug is not required.

At hepatic failure mild to moderate gravity (5-6 and 7-9 points on the Child-Pugh scale) does not require reducing the dose of the drug.

Have elderly patients dose adjustment of the drug is not required.

Adverse effects

Determination of the frequency of adverse reactions: very often (≥1 / 10), often (≥1 / 100, <1/10), sometimes (≥1 / 1000, <1/100), rarely (≥1 / 10 000, <1 / 1000), very rarely (<1/10 000) (including individual cases), the frequency is unknown (cannot be determined from the available data).

In clinical studies, the safety of the combination of irbesartan and hydrochlorothiazide was studied in approximately 2,750 patients,including 1540 patients with arterial hypertension who received this treatment for 6 months and more than 960 patients who received it for one year or more. The side effects in patients receiving Coaprovel® were usually mild and transient, their frequency was not related to the size of the dose taken (within the recommended dose range). The incidence of side effects is also independent of age, gender, and race.

In placebo-controlled studies in patients with arterial hypertension, the overall incidence of adverse events in the irbesartan / hydrochlorothiazide and placebo groups did not differ. Discontinuation of therapy due to any clinical or laboratory adverse event was less frequent in patients taking combinations of irbesartan and hydrochlorothiazide than in patients taking placebo.

In spontaneous reports of adverse reactions and in placebo-controlled studies in which 898 patients with arterial hypertension received various doses (from 37.5 mg / 6.25 mg to 300 mg / 25 mg of irbesartan / hydrochlorothiazide), the side effects listed below were noted.

Nervous system: often - dizziness, headache; infrequently - orthostatic dizziness.

Cardiovascular: infrequently - syncope, tachycardia, excessive decrease in blood pressure, peripheral edema (including edema of the lower extremities), flushing of blood to the skin of the face.

Gastrointestinal: often – nausea, vomiting; infrequently - diarrhea, dryness of the oral mucosa.

From the urinary system: often - change in frequency of urination.

From the reproductive system: infrequently - violation of libido, erectile dysfunction.

Musculoskeletal system: infrequently - myalgia, bone pain, arthralgia.

Dermatological: infrequently - skin rash.

General reactions: often - increased fatigue; infrequently - weakness.

When taking the drug Coaprovel^®In addition to the side effects listed above, other side effects are possible that were previously reported for each active ingredient in this combination.

Irbesartan

From the nervous system: frequency unknown - vertigo.

General reactions: infrequently - chest pain, feeling of weakness in the limbs; frequency is unknown - asthenia.

Since the cardiovascular system: Infrequently - deviations on an ECG.

Allergic reactions: frequency is unknown - angioedema, urticaria.

From the digestive system: infrequently - abdominal pain; frequency is unknown - jaundice, abnormal liver function tests, hepatitis.

Skin and Subcutaneous Tissues: infrequently - pruritus.

From the urinary system: frequency unknown - impaired renal function, including isolated cases of development of renal failure in patients at risk.

Metabolism: frequency unknown hyperkalemia.

Hydrochlorothiazide (without indicating the frequency of occurrence)

From the hemopoietic system: aplastic anemia, hemolytic anemia, leukopenia, neutropenia / agranulocytosis, thrombocytopenia.

From the nervous system: vertigo, paresthesia, anxiety.

On the part of the organ of vision: transient blurred visual perception, xanthopsia.

On the part of the respiratory system: respiratory distress syndrome (including pneumonitis and pulmonary edema).

From the digestive system: anorexia, irritation of the gastric mucosa, diarrhea, constipation, pancreatitis, sialadenitis, jaundice associated with intrahepatic cholestasis).

Skin and Subcutaneous Tissues: toxic epidermal necrolysis, necrotizing angiitis (vasculitis, cutaneous vasculitis), skin lupus-like reactions, worsening or worsening of the course of cutaneous lupus erythematosus, photosensitivity reactions.

Allergic reactions: urticaria, Anaphylactic reactions.

From the musculoskeletal system: muscle spasms.

From the urinary system: interstitial nephritis, impaired renal function.

General violations: fever, weakness.

Laboratory and instrumental data: violations of water and electrolyte balance (including hypokalemia, hypomagnesemia and hyponatremia), glycosuria, hyperglycemia, hyperuricemia, increased concentrations of cholesterol and triglycerides in the blood.

Dose-dependent side effects of hydrochlorothiazide (especially disturbances in water and electrolyte balance) may increase with increasing doses of hydrochlorothiazide.

Contraindications

- hypersensitivity to the drug;

- hypersensitivity to other sulfonamide derivatives (hydrochlorothiazide is a sulfonamide derivative);

- severe renal failure (CK ≤ 30 ml / min), anuria (due to the presence of hydrochlorothiazide in the preparation);

- refractory hypokalemia, hypomagnesemia, hypercalcemia (due to the presence of hydrochlorothiazide in the preparation);

- severe liver failure (class С / more than 9 points / on the Child-Pugh scale), biliary cirrhosis, cholestasis (due to the presence of hydrochlorothiazide in the preparation, since minimal impairment of electrolyte balance in such patients can provoke hepatic to whom);

- simultaneous use with drugs containing aliskiren in patients with diabetes mellitus or with moderate to severe renal insufficiency (GFR <60 ml / min / 1.73 m²);

- hereditary intolerance to galactose, lactase deficiency or impaired absorption of glucose and galactose;

- pregnancy;

- lactation period;

- children's and teenage age up to 18 years (efficiency and safety are not established);

WITH caution should use the drug:

- in case of stenosis of the aortic or mitral valve; hypertrophic obstructive cardiomyopathy;

- with hypovolemia, hyponatremia, arising, for example, in the treatment with diuretics, hemodialysis, diet with restriction of salt intake, diarrhea, vomiting (the risk of severe arterial hypotension), especially when taking the first dose;

- in case of bilateral or unilateral stenosis of the renal arteries, chronic heart failure of the III-IV functional class according to the NYHA classification (as with the use of other agents affecting the RAAS, there is a risk of arterial hypotension, oliguria and / or azotemia and progressive acute renal failure and / or death, although when using the drug Coaprovel^® similar effects were not observed);

- in case of ischemic heart disease and / or atherosclerotic lesion of cerebral vessels (risk of increased myocardial ischemia or brain up to the development of myocardial infarction or stroke with an excessive decrease in blood pressure);

- in case of renal failure of mild and moderate severity (CC from 60 to 30 ml / min), hemodialysis (risk of increasing azotemia, increasing the concentration of uric acid in the blood due to the presence of hydrochlorothiazide in the composition, and the development of hyperkalemia due to the presence of drug irbesartan);

- after kidney transplantation (lack of experience in clinical use);

- in case of hepatic insufficiency (classes A and B / 5-6 points and 7-9 points / according to Child-Pugh classification) (lack of clinical experience, danger of developing hepatic coma, even with minor violations of water-electrolyte balance);

- in case of diabetes mellitus (due to the presence of hydrochlorothiazide in the composition of the preparation, a decrease in glucose tolerance, an increase in the need for insulin and oral hypoglycemic agents is possible);

- at elevated levels of cholesterol and triglycerides in the blood (due to the presence of hydrochlorothiazide in the preparation, because thiazide diuretics, especially in high doses, can increase cholesterol and triglycerides in the blood; however, at a dose of 12.5 mg hydrochlorothiazide, these effects were minimal or absent);

- with gout (due to the presence of hydrochlorothiazide in the preparation, it is possible to increase the concentration of uric acid salts in the blood);

- in case of hyperkalemia, concomitant use of potassium-sparing drugs and or potassium-containing salt substitutes (risk of hyperkalemia);

- in case of systemic lupus erythematosus (due to the presence of hydrochlorothiazide in the preparation, an exacerbation of this disease is possible);

- while taking other antihypertensive drugs (the possibility of potentiation of their hypotensive action);

- with latent hyperparathyroidism (due to the presence of hydrochlorothiazide in the composition of the drug, because thiazide diuretics, especially in high doses, increase the risk of developing or increasing hypercalcemia);

- after sympathectomy (risk of increasing the hypotensive effect of hydrochlorothiazide);

- simultaneously with drugs containing aliskiren (double blockade of the RAAS),since there is an increased risk of excessive reduction in blood pressure, the development of hyperkalemia and deterioration of renal function (in relation to patients with diabetes mellitus and moderate and severe renal failure);

- in case of allergic reactions to penicillins and sulfonamides in the anamnesis, which are risk factors for the development of the idiosyncrasy reaction that occurred when taking sulfonamides or sulfonamide derivatives, manifested in the form of acute angle-closure glaucoma.

Use during pregnancy and lactation

Taking the drug Coaprovel^® during pregnancy is contraindicated.

The use of ACE inhibitors in the II and III trimesters of pregnancy caused damage and death of the developing fetus. Therefore, during pregnancy, the use of irbesartan, as well as any other drug that acts directly on the RAAS is contraindicated.

Thiazide diuretics penetrate the placental barrier and are found in umbilical cord blood. Usually, the use of diuretics in pregnant women is not recommended due to the increased risk for the mother and fetus, including the development of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that are observed in adults. Especially not recommended to receive hydrochlorothiazide in the first trimester of pregnancy.

If the patient is planning a pregnancy or if during the treatment with the drug Coaprovel^® established pregnancy, then taking the drug Coaprovel^® should be terminated (in the event of pregnancy, as soon as possible). If it is necessary to continue antihypertensive therapy, the patient should be prescribed alternative antihypertensive therapy with drugs that have an established safety profile during pregnancy.

It is not known whether irbesartan is excreted in breast milk. Hydrochlorothiazide is excreted in breast milk.

Coaprovel^® contraindicated for use during the entire period of breastfeeding due to the potential risk to the child. In addition, thiazides in high doses, causing intense diuresis, can suppress lactation. If necessary, take the drug Coaprovel^® mother, breastfeeding should be discontinued.

Application for violations of the liver

Coaprovel^® not recommended for patients with severe liver failure. In patients with impaired liver function, thiazides should be used with caution, but in patients with mild to moderate hepatic insufficiency does not require dose adjustment.

Application for violations of kidney function

Since the preparation contains hydrochlorothiazide, Coaprovel^® not recommended for patients with severe impaired renal function (CC 30 ml / min).

No dose adjustment is required in patients with renal insufficiency with CC> 30 ml / min.

Use in children

Contraindication: age up to 18 years (efficacy and safety have not been established).

Use in elderly patients

Have elderly patients dose adjustment of the drug is not required.

special instructions

Coaprovel^® occasionally causes excessive arterial hypotension in patients with elevated blood pressure without concomitant additional risk factors for its excessive reduction. Excessive reduction in blood pressure occurring with clinical symptoms, possibly in patients with reduced BCC or hyponatremia due to intensive diuretic therapy, a diet with limited salt, diarrhea or vomiting. Such conditions should be adjusted prior to the initiation of therapy with Coaprovel^®. Thiazide diuretics can potentiate the action of other antihypertensive drugs.

Patients with stenosis of one or two renal arteries with the use of ACE inhibitors or angiotensin II receptor antagonists have an increased risk of marked reduction in blood pressure and the development of renal failure. Although when using the drug Coaprovel^® until now, such side effects have not been observed, it is impossible to completely exclude the possibility of their development.

When using the drug Coaprovel^® In patients with impaired renal function, periodic monitoring of the content of potassium, serum creatinine and uric acid is recommended. No experience with the drug in patients after kidney transplantation. Coaprovel^® should not be used in patients with severe renal failure (CC = 30 ml / min).In patients with impaired renal function, thiazide diuretics may cause increased azotemia.

Special care is required when using vasodilators, including Co-Rapwell^®, in patients with stenosis of the aortic orifice and mitral valve stenosis, with hypertrophic obstructive cardiomyopathy.

In patients with primary hyperaldosteronism, use of the drug Coaprovel^® impractical because in these patients antihypertensive drugs that affect the RAAS are usually ineffective.

Thiazide diuretic therapy may decrease glucose tolerance. In patients with diabetes mellitus, it may be necessary to increase the doses of insulin or hypoglycemic drugs for oral administration. Thiazide Therapy
diuretics can cause the manifestation of latent diabetes.

Therapy with hydrochlorothiazide at a dose of 12.5 mg contained in some dosage forms of the drug Coaprovel^®, practically does not affect the concentration of cholesterol and triglycerides.

In the treatment of thiazide diuretics in some patients, possible hyperuricemia or exacerbation of the course of gout.

Thiazides, including hydrochlorothiazide, can cause a disturbance of water and electrolyte balance (hypokalemia, hyponatremia, and hypochloraemic alkalosis). Thiazides have been shown to increase the excretion of magnesium ions by the kidneys, which can lead to hypomagnesemia. Although the use of thiazide diuretics may develop hypokalemia, simultaneous therapy with irbesartan may reduce the hypokalemia caused by the diuretic. The risk of hypokalemia increases in patients who simultaneously receive GCS or ACTH.

On the contrary, thanks to irbesartan, which is part of the drug Coaprovel^®, hyperkalemia is possible, especially in the presence of renal failure and / or heart failure or diabetes. Regular monitoring of serum potassium in patients at risk is recommended. Potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes should be used with caution along with 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 by the kidneys and cause a slight increase in the calcium content in the blood serum, provided that there are no disturbances in calcium metabolism. Marked hypercalcemia may be a sign of latent hyperparathyroidism. Reception of thiazides should be stopped before the study of the function of the parathyroid glands.

Patients at risk of impaired water and electrolyte balance and metabolic disorders may require monitoring of laboratory parameters.

Hydrochlorothiazide can give a positive result during doping control.

The development of allergic reactions to hydrochlorothiazide is more likely in patients with aggravated allergic history or in patients with bronchial asthma.

When using thiazide diuretics, exacerbation of systemic lupus erythematosus was noted.

Sulfonamides, or derivatives of sulfonamide, can cause idiosyncrasy reactions, leading to the development of transient myopia and acute angle-closure glaucoma. Despite the fact that hydrochlorothiazide is a derivative of sulfonamide, so far only a few cases of acute angle-closure glaucoma have been reported without establishing a causal relationship with its administration. Symptoms of acute angle-closure glaucoma are: acute decrease in visual acuity or eye pain, usually occurring from a few hours to several weeks after starting the drug. Left untreated acute angle-closure glaucoma can lead to permanent loss of vision. If you experience these symptoms, you should stop taking the drug as soon as possible. If it is not possible to normalize intraocular pressure, then urgent therapeutic or surgical treatment may be required. Risk factors for the development of acute angle-closure glaucoma are
indications in the history of allergic reactions to sulfonamides and penicillins.

Joint use of the drug Coaprovel is not recommended.^® with drugs containing aliskiren (double blockade of the RAAS), since there is an increased risk of an excessive decrease in blood pressure, the development of hyperkalemia and deterioration of renal function.

Use of the drug Coaprovel^® in combination with drugs containing aliskiren, in patients with diabetes mellitus and renal failure, moderate and severe contraindicated.

Influence on ability to drive motor transport and control mechanisms

The influence of the drug Coaprovel^® the ability to drive vehicles and mechanisms has not been studied, but on the basis of its pharmacodynamic properties it is unlikely that the drug affects this ability. While driving a vehicle or machinery, it is necessary to take into account that in rare cases dizziness and increased fatigue may occur during therapy of high blood pressure.

Overdose

Symptoms: There is an experience of taking irbesartan in doses up to 900 mg / day for 8 weeks without the development of toxic effects. With an overdose of irbesartan, a pronounced decrease in blood pressure, tachycardia, bradycardia is most likely; with hydrochlorothiazide overdose, hypokalemia, hyponatremia, dehydration due to excessive diuresis. The most common signs and symptoms of overdose are nausea and drowsiness. Hypokalemia can lead to convulsions and / or increased arrhythmias in the case of concomitant use of cardiac glycosides (eg, digoxin) and antiarrhythmic drugs (eg, sotalol).

Treatment: there is no specific information about drug overdose^®. In case of overdose, careful monitoring of the patient’s condition is required, therapy should be symptomatic and supportive. Treatment depends on the time elapsed from the moment of taking the drug, and on the severity of the symptoms.Recommended measures are provoking vomiting and / or gastric lavage, the use of Activated carbon , careful monitoring of the patient’s condition, and symptomatic and supportive therapy. Should regularly monitor the content of electrolytes and creatinine in the serum. In case of arterial hypotension, the patient should be laid on his back with raised lower limbs and as soon as possible to replace the salts and fluids.

Irbesartan is not displayed during hemodialysis.

Drug interaction

Antihypertensive effect of the drug Coaprovel^® can be potentiated with the simultaneous use of other antihypertensive drugs, especially ganglioblockers, beta-blockers, diazoxide. Irbesartan and hydrochlorothiazide (at doses up to 300 mg of irbesartan / 25 mg of hydrochlorothiazide) have been safely used in combination with other antihypertensive drugs, including blockers of slow calcium channels and beta-blockers. High-dose diuretic therapy can lead to hypovolemia and an increased risk of excessive arterial hypotension.

Diuretics reduce the renal clearance of lithium and increase the risk of developing the toxic effects of lithium. In addition, the combination of lithium preparations with ACE inhibitors also showed an increase in plasma concentrations of lithium. So far, similar effects when taking Irbesartan were observed extremely rarely. In the case of taking the drug Coaprovel^® The risk of a toxic effect of lithium may be increased. The use of a combination of the drug Coaprovel^® with lithium preparations is not recommended. If this combination is still necessary, then the concentration of lithium in the plasma should be controlled.

Excretion of potassium when taking hydrochlorothiazide is reduced due to 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). On the contrary, based on the experience of using other medicines that reduce the activity of the RAAS, the concomitant use of potassium-saving diuretics, dietary supplements, salt substitutes containing potassium, or other medicines that can increase the content of potassium in the blood serum (eg, heparin), may lead to an increase in serum potassium. Hydrochlorothiazide used simultaneously with irbesartan can reduce the incidence of this effect. Patients at risk are recommended to conduct adequate monitoring of serum potassium.

Use of the drug Coaprovel^® in combination with drugs containing aliskiren, is contraindicated in patients with diabetes mellitus or renal failure (moderate to severe form - GFR <60 ml / min / 1.73 m²) and is not recommended in other patients.

With the combined use of cardiac glycosides, antiarrhythmic drugs with the drug Coaprovel^®in case of occurrence of hypokalemia and hypomagnesaemia caused by thiazide diuretic in its composition, the risk of arrhythmias increases, including and life threatening. The use of such combinations requires regular monitoring of the level of potassium in the serum.

With simultaneous use of the drug Coaprovel^® and NSAIDs (including selective COX-2 inhibitors, acetylsalicylic acid> 3 g / day and non-selective NSAIDs) may weaken the antihypertensive effect of Co -provel^® by reducing the effectiveness of hydrochlorothiazide and irbesartan.

As in the case of ACE inhibitors, the combined use of angiotensin II antagonists and NSAIDs can increase the risk of renal dysfunction, including the likelihood of acute renal failure, and lead to an increase in serum potassium in elderly patients and patients with reduced BCC, including receiving diuretics , in patients with impaired renal function. These effects are usually reversible. When using this combination, patients should not be dehydrated, treatment should be carried out under regular monitoring of indicators of renal function.

Based on in vitro research, Irbesartan is not expected to interact with substances metabolized by the isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2E1 or CYP3A4. Irbesartan is mainly metabolized with the participation of the CYP2C9 isoenzyme and, to a lesser extent, by glucuronidation.

The pharmacokinetics of irbesartan when it is combined with hydrochlorothiazide and Nifedipine does not change.

No significant pharmacokinetic and pharmacodynamic interactions were observed with joint
the use of irbesartan with Warfarin , a drug that is metabolized by the isoenzyme CYP2C9.

The effects of CYP2C9 isoenzyme inducers, such as rifampicin, on the pharmacokinetics of irbesartan have not been evaluated.

When combined with irbesartan, the pharmacokinetics of Digoxin and Simvastatin did not change.

If ethanol, barbiturates or anesthetics are used with thiazide diuretics at the same time, orthostatic hypotension may be increased.

When using hydrochlorothiazide, you may need to increase the dose of hypoglycemic agents, because hydrochlorothiazide may increase blood glucose levels.

Hydrochlorothiazide absorption is reduced in the presence of anion exchange resins. It is necessary to divide by time the administration of these drugs (colestiramine or colestipol) for at least 4 hours.

With the simultaneous use of hydrochlorothiazide and GCS or ACTH perhaps a more pronounced electrolyte imbalance, in particular, increased hypokalemia.

May decrease the effectiveness of catecholamines (eg, norepinephrine) under the influence of hydrochlorothiazide.

The effects of non-depolarizing muscle relaxants, agents for local anesthesia, agents for general anesthesia and agents for sedation before general anesthesia can be potentiated by hydrochlorothiazide, and