Coaprovel tabs 150mg/12.5mg #28

Coaprovel instruction

You can buy Coaprovel here

DESCRIPTION

Biconvex oval tablets engraved in the shape of a heart on one side and "2775" on the other for tablets 150 mg / 12.5 mg, "2776" for tablets 300 mg / 12.5 mg of "peach" (orange-pink) color with white patches.
PHARMACOTHERAPY GROUP
Antihypertensive agent, combination drug:
ATX Code: C09DA04

Pharmacodynamics

COAPROVEL is a combination of an angiotensin-P receptor antagonist - irbesartan and thiazide diuretic - hydrochlorothiazide. The combination of these ingredients has an additive antihypertensive effect, reducing blood pressure to a higher degree than each of them separately.
Irbesartan is the active dosage form of the selective ATI receptor antagonist (AT subtype |) of angiotensin-II. Selective antagonism of irbesartan in relation to AT receptors | leads to increased levels of renin and angiotensin-P and to a decrease in the level of aldosterone in serum. The level of potassium in the blood serum varies slightly during treatment with irbesartan in monotherapy at the recommended doses (see the sections "Special Warnings and Precautions for Use" and "Interactions with Other Medicines and Other Forms of Interaction"). Irbesartan does not suppress ACE (kininazu-P), which promotes the formation of angiotensin-P, and also turns bradykinin into inactive metabolites. Irbesartan does not need 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, inhibiting sodium reabsorption. Hydrochlorothiazide reduces plasma volume by increasing plasma renin activity and aldosterone secretion, followed by an increase in potassium in the urine and a decrease in its content in blood serum. Presumably, through the blockade of the renin-angiotensin-aldosterone system, the combined use of irbesartan leads to the prevention of the loss of potassium in the blood serum caused by this diuretic. In the case of hydrochlorothiazide, the onset of diuresis occurs in the first 2 hours after ingestion, reaches a peak in about 4 hours, the effect persists for about 6-12 hours.
A decrease in blood pressure appears after taking the first dose of Coaprovel, the maximum effect is observed after 6-8 weeks of treatment. The effect persists during long-term treatment (one year). An increase in blood pressure, although not studied in the case of COAPROVEL, was not detected with discontinuation of irbesartan or hydrochlorothiazide used separately.
There is no difference in response to CAPROVEL depending on age or gender.

Pharmacokinetics

After ingestion of COAPROVEL, the absolute bioavailability of irbesartan is 60-80%, and that of hydrochlorothiazide, 50-80%. After oral administration, maximum serum concentrations are reached after 1.5-2 hours for irbesartan and after 1-2.5 hours for hydrochlorothiazide.
The binding of irbesartan to plasma proteins is approximately 96%. The volume of distribution of irbesartan is 53-93 liters. 68% of hydrochlorothiazide binds to plasma proteins, the volume of its distribution is 0.83-1.14 l / kg.
The pharmacokinetic parameters of irbesartan are characterized by a linear dose dependence in the dose range from 10 to 600 mg. A weaker than proportional increase in absorption was observed when oral doses were taken above 600 mg. Total and renal clearance is 157-176 and 3.0-3.5 ml / min, respectively. The half-life of irbesartan is 11-15 hours. Serum concentrations reach a stable value within 3 days after the start of therapy. With repeated administrations once a day, there is a limited accumulation of irbesartan in the blood plasma (<20%). Somewhat higher serum concentrations of irbesartan were found in women with high blood pressure than in men. However, there was no difference in the half-life and accumulation of irbesartan. Therefore, there is no need to adjust the dosage of irbesartan in female patients. AUC and Stach values ​​were higher in the elderly (> 65 years) than in young people (18-40 years). However, the half-life was not significantly changed. Therefore, dosage adjustment in the elderly is not required. The average half-life of hydrochlorothiazide ranges from 5 to 15 hours.
After oral administration of C-irbesartan, 80-85% of the circulating radioactive carriers in plasma are unchanged irbesartan. Irbesartan is metabolized in the liver by conjugation with glucuronic acid and oxidation. The main circulating metabolite is irbesartan glucuronide (approximately 6%). In vitro studies indicate that irbesartan is oxidized mainly by the cytochrome p450 CYP2C9 isoenzyme. Irbesartan and its metabolites are excreted in bile and urine. After ingestion or intravenous administration of 14C-irbesartan, 20% of the radioactivity is detected in the urine and traces in the feces. Less than 2% of unchanged irbesartan is excreted in the urine. Hydrochlorothiazide is not metabolized, but is rapidly excreted through the kidneys. At least 61% of the ingested dose is excreted unchanged within 24 hours. Hydrochlorothiazide penetrates the placental barrier and is secreted into breast milk, but does not pass through the blood-brain barrier.
Renal failure: in patients with renal insufficiency or on hemodialysis, the pharmacokinetic parameters of irbesartan change slightly. Irbesartan is not removed by hemodialysis. It was reported that in patients with creatinine clearance <20 ml / min an increase in the half-life to 21 hours was observed.
Hepatic insufficiency: in patients with mild and moderate disruption of liver functions, the pharmacokinetic parameters of irbesartan change slightly. In patients with severe hepatic insufficiency studies have not been conducted.
INDICATIONS FOR USE
Arterial hypertension.

CONTRAINDICATIONS for Coaprovel

The second and third trimester of pregnancy (see section "Pregnancy and lactation"). Lactation period (see section "Pregnancy and lactation").
Hypersensitivity to active substances, to any of the excipients (see “Composition”) or to other drugs derived from sulfonamides (Hydrochlorothiazide is a sulfonamide derivative). The following contraindications are associated with the use of hydrochlorothiazide:
• severe renal insufficiency (creatinine clearance <30 ml / min),
• refractory hypokalemia, hypercalcemia,
• severe liver failure, biliary cirrhosis, cholestasis.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

Patients with arterial hypotension - low (blood circulation volume) BCC: COAPROVEL rarely causes symptomatic hypotension in patients with high blood pressure. Symptomatic hypotension may presumably be observed in patients with a reduced circulating blood volume or low sodium content due to diuretic therapy, with a diet limited in salt, with diarrhea or vomiting. Such conditions must be corrected before the start of KOPROVEL therapy. Renal artery stenosis - vasorenal hypertension: an increased risk of severe arterial hypotension and renal failure in patients with bilateral renal artery stenosis or arterial stenosis of the only functioning kidney with ACE inhibitors or angiotensin II receptor blockers. Although there are no reports on this in the case of a CO-MANAGEMENT, this effect should be taken into account.
Renal failure and kidney transplantation: when Coaprovel is used in patients with impaired renal function, periodic monitoring of serum levels of potassium, cretinin and uric acid is recommended. There is no experience regarding the use of Coaprovel in patients with recent kidney transplantation. Coaprovel should not be used in patients with severe renal failure (creatinine clearance <30 ml / min). In patients with impaired renal function, azotemia may occur during thiazide diuretic therapy.
Stenosis of the aortic orifice and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: special care is required when administering a CAPROVEL to such patients.
Primary aldosteronism: use of Coaprovel is not recommended.
Metabolic and endocrine effects: Thiazide therapy may decrease glucose tolerance. In patients with diabetes mellitus, dosage adjustment of insulin or oral antidiabetic drugs may be required. Thiazide therapy can cause minifestation of latent diabetes. Therapy with hydrochlorothiazide in a dose of 12.5 mg contained in Coaprovel practically does not affect the level of cholesterol and triglycerides.
With thiazide therapy, hyperuricemia or exacerbation of gout may occur in some patients.
Electrolyte imbalance: Thiazides, including hydrochlorothiazide, can cause disruption of water and electrolyte balance (hypokalemia, hyponatremia, and hypochloraemic alkalosis). Although the use of thiazide diuretics may develop hypokalemia, concurrent therapy with irbesartan may reduce the hypokalemia caused by diuretics. The risk of hypokalemia increases in patients who are under concomitant treatment with glucocorticosteroids or ACTH. Conversely, due to irbesartan, a component of Coaprovel, hyperkalemia can occur, especially in the presence of renal failure and / or heart failure or diabetes. Adequate monitoring of serum potassium is recommended for patients at risk.
Potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes should be carefully prescribed together with Coaprovel (see the section "Interactions with other drugs and other forms of interaction").
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 the level of calcium 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 has to be stopped before carrying out research of function of a parathyroid gland. It has been demonstrated that thiazides increase the excretion of magnesium in the urine, which can lead to hypomagnesemia.
Lithium: The combination of lithium with Coaprovel is not recommended.
Anti-dosing test: hydrochlorothiazide may cause positive analytical result in the test for doping.
General precautions: in patients in whom vascular tone and renal function depends mainly on the activity of the renin-angiotensin-aldosterone system (for example, in patients with chronic heart failure or kidney disease, including renal artery stenosis), therapy Angiotensin-P receptor antagonists can cause acute arterial hypotension, azotemia, oliguria, or, in rare cases, acute renal failure. Excessive reduction in blood pressure in patients with coronary heart disease or other cardiovascular diseases can lead to myocardial infarction or cerebral stroke.
The development of allergic reactions to hydrochlorothiazide is more likely in patients in whom similar reactions have been noted in the anamnesis. When using thiazide diuretics, exacerbation of systemic lupus erythematosus was noted. In the first trimester of pregnancy, the use of co-op is not recommended (see the section "Pregnancy and lactation").

PREGNANCY AND LACTATION

Pregnancy:
Coaprovel is contraindicated during the second and third trimesters of pregnancy. If pregnancy is diagnosed, the CAPROVEL should be canceled as soon as possible, the skull and kidney function should be checked with the help of echography if, due to inattention, the therapy lasted for a long time.
Lactation: COAPULAT is contraindicated during the entire lactation period

INFLUENCE ON THE ABILITY OF MANAGEMENT OF VEHICLES AND MECHANISMS

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

METHOD OF ADMINISTRATION AND DOSES

COAPROVEL can be applied once a day with meals or until patients whose blood pressure is not sufficiently controlled by irbesartan or hydrochlorothiazide alone.
Coaprovel 150 / 12.5 mg may be prescribed to patients in whom blood pressure is not sufficiently controlled by hydrochlorothiazide or irbesartan (150 mg / day) in monotherapy.
COAPROVEL 300 / 12.5 mg may be prescribed to patients in whom blood pressure is not sufficiently controlled by irbesartan (300 mg) or Coaprovel (150 / 12.5 mg).
Doses higher than 300 mg of irbesartan / 25 mg of hydrochlorothiazide once a day are not recommended.
Renal failure: since Coaprovel contains hydrochlorothiazide Coaprovel is not recommended for patients with severe impaired renal function (creatinine clearance <30 ml / min). In these patients, the use of loop diuretics is more preferable than the use of thiazides. Dosage adjustment is not required in patients with renal insufficiency, in whom creatinine clearance is> 30 ml / min (see sections "Contraindications" and "Special warnings and precautions for use").
Reduction in circulating blood volume: Prior to the use of Coaprovel, it is necessary to correct reduced BCC and / or sodium content. If this fails, consider taking a lower initial dose. Hepatic impairment: COAPULATION is not recommended for patients with severe hepatic impairment. In patients with impaired liver function, thiazides should be used with caution, but in patients with mild and moderate hepatic insufficiency, dosage adjustment of COAROVEL is not required (see "Contraindications").
Elderly patients: there is no need to adjust the dosage of Coaprovel in elderly patients.
Children: safety and efficacy of Coaprovel in children (<18 years) have not been established.

SIDE EFFECTs of Coaprovel

The frequency of the side reactions listed below was determined according to the following: very often (> 1/10), often (> 1/100, <1/10); sometimes (> 1/1000, <1/100); rarely: (> 1/10000, <1/1000); very rarely (<1/10000), including individual messages.
Irbesartan / Hydrochlorothiazide Combination
In placebo-controlled studies in patients with arterial hypertension, the overall frequency 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 those who took placebo. The frequency of adverse events did not depend on gender, age, race or dose. In placebo-controlled studies in which various doses (from 37.5 mg / 6.25 mg to 300 mg / 25 mg of irbesartan / hydrochlorothiazide) received 898 patients with arterial hypertension, the following side effects were noted:
Nervous system disorders: Often: dizziness Sometimes: orthostatic dizziness
Cardiac:
Sometimes: arterial hypotension, edema, syncope, tachycardia
Vascular:
Sometimes: tides
Gastrointestinal: Common: nausea / vomiting Sometimes: diarrhea
Musculoskeletal system, connective tissues and bones: Sometimes: swelling of the upper and lower extremities
Kidneys and urinary system: Often: impaired urination
Reproductive system and mammary glands:
Sometimes: changes in sexual desire, sexual dysfunction
General condition and condition of the injection site: Often: fatigue
Laboratory studies: in patients treated with irbesartan / hydrochlorothiazide, changes in laboratory parameters were noted, which rarely reached the threshold of clinical significance. Often: an increase in urea nitrogen, creatinine and plasma creatine kinase
Sometimes: a decrease in serum potassium and sodium levels
In addition, since the appearance of the combination of irbesartan and hydrochlorothiazide on the market, the following adverse reactions have also been noted:
Immune system disorders:
Rarely: as with all angiotensin-II receptor antagonists, there have been rare cases of allergic reactions, such as rashes, urticaria, angioedema.
Metabolism and nutrition disorders: Very rare: hyperkalemia
Nervous system disorders: Very rare: headache
Hearing and vestibular disorders: Very rare: tinnitus
Respiratory: Sometimes: cough
Gastrointestinal disorders:
Very rare: change in taste, dyspepsia
Hepatitis disorders:
Very rare: liver function abnormalities, hepatitis
Disturbances of skeletal-muscular system, connective tissues and bones: Very rare: myalgia, arthralgia
Disturbances of the kidneys and urinary system:
Very rarely: impaired renal function, including isolated cases of renal failure in high-risk patients
Additional information on individual components: In addition to the side effects listed above, other side effects previously reported in the case of each of the components may be possible side effects in the case of a COAP.
Irbesartan:
Common violations:
Sometimes: chest pain
Hydrochlorothiazide,
Side effects (regardless of the connection with Coaprovel), noted when using hydrochlorothiazide in monotherapy, include the following:
Blood and lymphatic system:
Aplastic anemia, bone marrow depression, hemolytic anemia, leukopenia,
neutropenia / agranulocytosis. tromopenia.
Mental Disorders: Depression, Sleep Disorders
Nervous System Disorders: Dizziness, paresthesias, anxiety,
Visual impairment:
Transient blurred vision, xantopsia
Heart disorders: Arrhythmias
Vascular disorders: Postural hypotension
Respiratory disorders
Respiratory Distress Syndrome (including pneumonitis and pulmonary edema)
Hepatobiliary disorders:
Jaundice (intrahepatic cholestatic jaundice)
Leather and subcutaneous tissue
Anaphylactic reactions, toxic necrosis of the epidermis, skin reactions such as lupus erythematosus, necrotized angiitis (vasculitis, skin vasculitis), photosensitivity reactions, rash, exacerbation of skin manifestations of lupus erythematosus, urticaria.
Disorders of the musculoskeletal system, connective tissues and bones: Muscle spasms, weakness
Renal and urinary system disorders: Interstitial nephritis, renal dysfunction
General Disorders: Fever
Laboratory research:
Electrolyte imbalance (including hypokalemia and hyponatremia, see section 4.4), glucosuria, hyperglycemia, hyperuricemia, increased cholesterol and triglycerides.

INTERACTIONS WITH OTHER MEDICATIONS AND OTHER FORMS OF INTERACTIONS

Other antihypertensive drugs: the antihypertensive effect of Coaprovel can be enhanced by using other antihypertensive drugs. Irbesartan and hydrochlorothiazide (at doses: 300 mg of irbesartan / 25 hydrochlorothiazide) should be used with caution along with other antihypertensive drugs, including calcium channel blockers and beta-blockers. High-dose pre-treatment with diuretics can lead to hypovolemia and risk of arterial hypotension (see section "Special Warnings and Precautions for Use").
Lithium: reversible increases in serum lithium concentrations and toxic effects were observed with the concomitant use of lithium with angiotensin-converting enzyme inhibitors (ARP). With regard to irbesartan, similar effects have been extremely rare to date. In addition, renal clearance of lithium is reduced by thiazides, therefore, in the case of COAPROVEL, the risk of the toxic effect of lithium may be increased. Therefore, the combination of lithium and co-suspension is not recommended. If a combination is necessary, careful monitoring of serum lithium levels is recommended.
Drugs affecting blood potassium: the hypokalemic effect of hydrochlorothiazide is weakened by the potassium-saving 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 the experience of using other drugs that reduce the activity of the renin-angiotensin system, the concomitant use of potassium-saving diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs that can increase serum potassium levels (for example, heparin sodium salt), may lead to an increase in the amount of potassium in the serum. Patients at risk are recommended to adequately control serum potassium levels.
Drugs that are affected by serum imbalance: Periodic monitoring of serum potassium levels is recommended in the case of co-administration of Coaprovel and drugs that are affected by potassium imbalance in blood serum (for example, digitalis glycosides, antiarrhythmic drugs).
Non-steroidal anti-inflammatory drugs: with the 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 hypotensive effect may occur.
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, especially in patients with impaired renal function. At introduction of this combination it is necessary to observe precautionary measures, especially for elderly patients. Patients should not be dehydrated. Monitoring of the kidney function should be carried out after the initiation of combination therapy and periodically thereafter.
Additional information on the interactions of irbesartan: The pharmacokinetics of irbesartan are not affected when given in combination with hydrochlorothiazide. Irbesartan is mainly metabolized by CYP2C9 and, to a lesser extent, by glucuronidation. No significant pharmacokinetic and pharmacodynamic interactions were observed when irbesartan was used in conjunction with warfarin, a drug metabolized using CYP2C9. The 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: from
The following drugs may interact with thiazide diuretics:
Alcohol, barbiturates or narcotic drugs: there may be increased orthostatic hypotension;
Hypoglycemic drugs (oral agents and insulin): a dose adjustment of the hypoglycemic agent may be necessary (see section "Special warnings and precautions for use");
Colestyramine and colestyrene resins: the absorption of hydrochlorothiazide is reduced in the presence of anion exchange resins;
Glucocorticosteroids, ACTH: a more pronounced violation of the electrolyte composition is possible, in particular, increased hypokalemia;
Digitalis glycosides: hypokalemia and hypomagnesemia caused by thiazide diuretics contribute to the development of arrhythmias caused by digitalis (see section "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 noradrenapine) '. the effect of these agents may be weakened;
Non-depolarizing muscle relaxant: The effect of non-depolarizing muscle relaxants can be enhanced by hydrochlorothiazide;
Anti-gouty agents: Correction of anti-gouting dosages may be necessary, since hydrochlorothiazide may increase serum uric acid levels. It may be necessary to increase the dosage of probenecid or sulfinpyrazone. Combined use with thiazide diuretics may increase the frequency of allergic reactions to allopurinol;
Calcium salts: Thiazide diuretics can increase serum calcium levels due to decreased clearance. If calcium supplements or drugs affecting calcium levels are to be prescribed (for example, with vitamin D therapy), then serum calcium levels should be monitored and the dosage of calcium should be adjusted accordingly.
Other interactions: the hyperglycemic effect of beta-blockers and diazoxide can be enhanced by thiazides. Anticholinergics (for example, atropine) can increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility. Thiazides may increase the risk of side effects caused by amantadine. Thiazides can decrease the excretion of cytotoxic drugs with urine (for example, cyclophosphamide, methotrexate) and enhance their myelosuppressive effects.

OVERDOSE

There is no specific information about overdose with co-conduction therapy. In the case of overdose, careful monitoring of the patient’s condition is required, and therapy should be symptomatic and supportive. The type of assistance depends on the time elapsed since taking the medicine and on the severity of the symptoms. Recommended measures include provoking vomiting and / or gastric lavage. In overdose, the use of activated carbon may be beneficial. Frequent monitoring of electrolyte and serum creatinine levels should be carried out. In case of arterial hypotension, the patient must be laid on his back with the lower limbs elevated and the salts and fluids should be replaced as soon as possible.
As the most likely manifestations of irbesartan overdose, arterial hypotension and tachycardia can be expected; bradycardia may also occur.
An overdose of hydrochlorothiazide is accompanied by a decrease in the content of electrolytes in the body (hypokalemia, hyponatremia) and 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 digitalis glycosides and antiarrhythmic agents.
Irbesartan is not eliminated by hemodialysis. The degree of elimination of hydrochlorothiazide with hemodialysis has not been established.

FORM OF ISSUE

14 tablets in PVC / Al blister. On 1, 2, 4, 7 blisters with the application instruction in a cardboard box.

STORAGE CONDITIONS

Store at a temperature not higher than 30 ° C.
Keep the medicine out of the reach of children.
SHELF LIFE - 3 years
Do not take beyond the expiration date stated on the package.

Terms of sell

You can buy Coaprovel without a prescription.