Coaprovel, 12.5 mg+300 mg 28 pcs

Coaprovelle is a combination antihypertensive medication containing the angiotensin II receptor antagonist irbesartan and the thiazide diuretic hydrochlorothiazide. The combination of these ingredients has additive hypotensive effects, lowering BP to a higher degree than each ingredient alone.

The selective antagonism of irbesartan against AT 1 -receptors is manifested by an increase in renin and angiotensin II and a decrease in serum aldosterone . Serum potassium levels do not change significantly with irbesartan monotherapy at recommended doses.

Irbesartan does not inhibit ACE (kininase II), which promotes angiotensin II formation, and converts bradykinin to inactive metabolites. Irbesartan does not need metabolic activation to exhibit its action.

Hydrochlorothiazide is a thiazide diuretic. Thiazide diuretics affect renal mechanisms of electrolyte reabsorption, increasing sodium and chloride excretion in approximately equivalent amounts, inhibiting sodium reabsorption. Hydrochlorothiazide decreases plasma volume by increasing plasma renin activity and aldosterone secretion, with a subsequent increase in urinary potassium and decrease in serum potassium. Presumably, through blockade of the renin-angiotensin-aldosterone system, coadministration of irbesartan leads to prevention of serum potassium loss caused by this diuretic.

When hydrochlorothiazide is taken, the onset of diuresis occurs within the first 2 h after oral administration, peaks within 4 h, and the action lasts for about 6-12 h.

The decrease in BP is evident after the first dose of Coaprovel, the maximum effect is seen after 6-8 weeks of treatment. The effect lasts for long-term use (1 year). Increased BP, although not studied with Coaprovele, has not been seen when irbesartan or hydrochlorothiazide are withdrawn separately.

There were no differences in response to Coaprovelle based on age or gender.

Indications

Arterial hypertension .

Active ingredient

Composition

1 tablet contains:

Irbesartan 300 mg,

Hydrochlorothiazide 125 mg

Supplementary substances:

Cellulose microcrystalline,

Croscarmellose sodium,

Lactose monohydrate,

Magnesium stearate,

colloidal silicon dioxide hydrated,

corn starch pregelatinized,

iron oxide red,

iron oxide yellow

How to take, the dosage

Coaprovelle can be used once daily before or with meals in patients whose BP is not sufficiently controlled by irbesartan or hydrochlorothiazide alone.

Coaprovelle 300/25 mg is indicated for patients whose BP is not well controlled with irbesartan (300 mg) or Coaprovelle (300/12.5 mg).

The use of the drug in doses greater than 300 mg of irbesartan/25 mg of hydrochlorothiazide once daily is not recommended.

Before starting Coaprovelle, it is necessary to correct decreased CPR and/or sodium levels. If this is not possible, a lower starting dose should be considered.

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

– Use in patients with impaired renal function: Because the drug contains hydrochlorothiazide Coaprovel is contraindicated in patients with significant impaired renal function (CK30 ml/min).

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

Interaction

The antihypertensive effect of Coaprovelle may be enhanced with concomitant use of other antihypertensive drugs. The combination irbesartan/hydrochlorothiazide in doses of 300mg/25mg should be used with caution simultaneously with other antihypertensive agents, including calcium channel blockers and beta-adrenoblockers. Pretreatment with high-dose diuretics may lead to hypovolemia and risk of arterial hypotension.

Recoverable increases in serum lithium concentrations and toxic effects have been noted 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 the risk of lithium toxic effects may be increased with Coaprovel. Therefore, the combination of lithium and Coaprovel is not recommended. If the combination is necessary, close monitoring of serum lithium levels is recommended.

The hypokalemic effect of hydrochlorothiazide is attenuated by the potassium-saving effect of irbesartan. However, this effect of hydrochlorothiazide may be enhanced by other drugs that cause potassium loss and hypokalemia (e.g., diuretics, laxatives, amphotericin, carbenoxolone, sodium salt of penicillin G, salicylic acid derivatives). In contrast, based on experience with other drugs that reduce the activity of the renin-angiotensin system, concomitant use of potassium-saving diuretics, dietary supplements, salt substitutes containing potassium, or other drugs that can increase serum potassium levels (e.g., the sodium salt of heparin ) may result in an increase in serum potassium. Adequate monitoring of serum potassium levels is recommended in patients at risk.

Periodic monitoring of serum potassium levels is recommended in case of co-administration of Coaprovelle and drugs that are affected by impaired serum potassium balance (e.g., foxglove glycosides, antiarrhythmic drugs).

The simultaneous use of angiotensin II antagonists and NSAIDs (e.g., selective COX-2 inhibitors, acetylsalicylic acid >3 g/day and non-selective NSAIDs) may result in a decrease of the hypotensive effect.

As with ACE inhibitors, co-administration of angiotensin II antagonists and NSAIDs may increase the risk of renal dysfunction, including the possibility of acute renal failure, and lead to increased serum potassium, especially in patients with already impaired renal function. This combination should be used with caution, especially in elderly patients. Patients should not be dehydrated. Renal function monitoring should be performed after initiation of combination therapy and periodically thereafter.

The pharmacokinetics of irbesartan are not affected when combined with hydrochlorothiazide. Irbesartan is primarily metabolized by CYP2C9 and to a lesser extent by glucuronidation. No significant pharmacokinetic and pharmacodynamic interactions have been observed when irbesartan is coadministered with warfarin, a drug that is metabolized with CYP2C9. The effect of CYP2C9 inducers, such as rifampicin, on the pharmacokinetics of irbesartan has not been evaluated.

The pharmacokinetics of digoxin was not altered by co-administration with irbesartan.

When used concomitantly with ethanol thiazide diuretics, barbiturates, or anesthetics, increased orthostatic hypotension may be observed.

When using hydrochlorothiazide, a dose adjustment of the hypoglycemic agent may be required.

The absorption of hydrochlorothiazide is reduced in the presence of anion exchange resins.

In concomitant use of hydrochlorothiazide and GCS or ACTH a more pronounced electrolyte imbalance is possible, in particular an increase in hypokalemia.

Hypokalemia and hypomagnesemia caused by thiazide diuretic contribute to foxglove-induced arrhythmias.

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

The effectiveness of catecholamines (e.g., norepinephrine ) may be reduced by hydrochlorothiazide.

The effect of nondepolarizing myorelaxants may be enhanced by hydrochlorothiazide.

The doses of antipodagric agents may need to be adjusted because hydrochlorothiazide may increase serum uric acid levels. It may be necessary to increase the dose of probenecid or sulfinpyrazone. Co-administration with thiazide diuretics may increase the frequency of allopurinol allergic reactions.

Thiazide diuretics may increase serum calcium levels due to reduced excretion. If calcium supplements or medications that affect calcium levels must be prescribed (e.g., with vitamin D therapy), monitoring of serum calcium and making appropriate adjustments to the calcium medication dose is necessary.

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

The anticholinergic agents (e.g., atropine ) may increase bioavailability of thiazide diuretics due to decreased GI motility.

The thiazides may increase the risk of amantadine-induced side effects.

The thiazides may decrease urinary excretion of cytotoxic drugs (e.g., cyclophosphamide, methotrexate ) and increase their myelosuppressive effects.

Special Instructions

Coaprovel rarely causes symptomatic hypotension in patients with elevated BP. Symptomatic arterial hypotension may presumably occur in patients with decreased RBC or low sodium due to diuretic therapy, salt-restricted diet, diarrhea, or vomiting. These conditions should be corrected before initiating therapy with Coaprovele.

Particular caution should be used with Coaprovelle in patients with aortic orifice stenosis and mitral valve stenosis, obstructive hypertrophic cardiomyopathy.

The use of Coaprovel is not recommended in primary aldosteronism.

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

The therapy with hydrochlorothiazide at a dose of 12.5 mg contained in Coaprovelle has almost no effect on cholesterol and TG levels .

The thiazide therapy may cause hyperuricemia or worsening of gout in some patients.

The thiazides, including hydrochlorothiazide, may cause imbalances of water and electrolytes (hypokalemia, hyponatremia and hypochloremic alkalosis). Although the use of thiazide diuretics may cause hypokalemia, concomitant therapy with irbesartan may reduce hypokalemia caused by the diuretic. The risk of hypokalemia increases in patients who receive GCS or ACTH. On the contrary, due to irbesartan, a component of Coaprovelle, 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-saving diuretics, potassium supplements or substitutes containing potassium should be used with caution concomitantly with Coaprovelle.

There is no evidence that irbesartan can reduce or prevent diuretic-induced hyponatremia. Chloride deficiency is usually mild and does not require treatment.

The thiazides may decrease calcium excretion through the kidneys and cause a slight increase in serum calcium levels provided there is no impairment of calcium metabolism. The observed hypercalcemia may be a sign of latent hyperparathyroidism. Thiazide administration should be discontinued until parathyroid function tests are performed.

The thiazides increase urinary excretion of magnesium, which may lead to hypomagnesemia.

Coaprovelle is not recommended in combination with lithium preparations.

Hydrochlorothiazide may cause a positive result in a doping test.

. In patients in whom vascular tone and renal function depend primarily on renin-angiotensin-aldosterone system activity (e.g., in patients with chronic heart failure or with renal disease, including renal artery stenosis), therapy with angiotensin-II receptor antagonists may cause acute arterial hypotension, azotemia, oliguria or, in rare cases, acute renal failure. Excessive BP reduction in patients with CHD or other cardiovascular disease may lead to myocardial infarction or cerebral stroke.

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

A worsening of systemic lupus erythematosus has been reported with thiazide diuretics.

The use of Coaprovel is not recommended in the first trimester of pregnancy.

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

– Use in renal impairment: Since the drug contains hydrochlorothiazide, Coaprovel is not recommended for patients with significant renal impairment (CKD 30 ml/min). No dose adjustment is required in patients with renal impairment with a CK of >30 ml/min. The risk of severe arterial hypotension and renal failure is increased in patients with bilateral renal artery stenosis or artery stenosis of the only functioning kidney when using ACE inhibitors or angiotensin II receptor blockers. Although no such reports are available with Coaprovel, this effect should be considered. When using Coaprovel in patients with impaired renal function, periodic monitoring of serum potassium, creatinine and uric acid levels is recommended. There is no experience with Coaprovel in patients after recent kidney transplantation. Coaprovel should not be used in patients with severe renal impairment (CKD)

Pediatric use The safety and effectiveness of Coaprovel in children and adolescents less than 18 years of age has not been established.

– Effect on driving and operating ability: The effect of Coaprovel has not been studied on driving and operating ability, but based on its pharmacodynamic properties, it is unlikely that Coaprovel affects this ability. While driving vehicles or operating machinery, it should be taken into account that in rare cases, dizziness and increased fatigue may be observed during therapy of elevated BP.

Contraindications

– Hereditary intolerance of galactose, lactase deficiency or disorders of glucose and galactose absorption.
– Pregnancy.
– Lactation period.
– Age under 18 years (effectiveness and safety is not established).
– Hypersensitivity to the components of the drug.

To use hydrochlorothiazide:

– Severe renal failure ( CK – Refractory hypokalemia, hypercalcemia.
– Severe form of hepatic failure .
– Biliary cirrhosis of the liver .
– Cholestasis.
– Hypersensitivity to other drugs, sulfonamide derivatives.

Side effects

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

CNS and peripheral nervous system disorders: depression, sleep disturbances, dizziness, paresthesias, anxiety.

Visually: transient blurred vision, xanthopsia.

Cardiovascular system: arrhythmia, postural hypotension.

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

Digestive system disorders: jaundice (intrahepatic cholestatic jaundice).

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

Muscular system disorders: muscle cramps, weakness.

Urinary system: interstitial nephritis, renal dysfunction.

Others: increase in body temperature.

Laboratory disorders: electrolyte balance disorders (including hypokalemia and hyponatremia), glucosuria, hyperglycemia, hyperuricemia, elevated cholesterol and TG levels.

Overdose

There is no specific information about Coaprovelle overdose.

– Symptoms: in irbesartan overdose arterial hypotension, tachycardia, bradycardia are most likely; in hydrochlorothiazide overdose – hypokalemia, hyponatremia, dehydration due to excessive diuresis. The most common signs and symptoms of overdose are nausea and drowsiness. Hypokalemia may lead to seizures and/or increased arrhythmias in case of concomitant use of foxglove glycosides and antiarrhythmic drugs.

– Treatment: recommended measures depending on the time elapsed since drug administration and on the severity of symptoms – inducing vomiting and/or gastric lavage, use of activated charcoal, close monitoring of the patient’s condition, conducting symptomatic and supportive therapy. Frequent monitoring of serum electrolytes and creatinine should be performed. In case of arterial hypotension the patient should be laid on his back with elevated lower extremities and reimbursement of salts and fluids should be performed as soon as possible. Irbesartan is not excreted by hemodialysis. The degree of excretion of hydrochlorothiazide by hemodialysis has not been established.

Pregnancy use

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

If pregnancy is diagnosed, Coaprovel should be discontinued as soon as possible. The skull and renal function should be checked by echography if, inadvertently, therapy has been continued for a long time.

Coaprovel is contraindicated during the entire lactation period.