Edarbi pills 20mg, 28pcs

Composition

Composition of 1 tablet: Active ingredient: medoxomil azilsartan-20 mg (medoxomil potassium azilsartan-21.34 mg); Excipients: mannitol – 47.815 mg, fumaric acid-1 mg, sodium hydroxide-0.345 mg, hyprolose-2.7 mg, croscarmellose sodium-6.9 mg, microcrystalline cellulose-9 mg, magnesium stearate-0.9 mg

Pharmacological action

Specific angiotensin II receptor antagonist type 1 (AT₁). Azilsartan medoxomil is a prodrug. It is rapidly converted to the active molecule azilsartan, which selectively inhibits the development of the effects of angiotensin II by blocking its binding to AT1 receptors in various tissues. Angiotensin II is the primary vasoactive hormone of RAAS with effects including vasoconstriction, cardiac stimulation, stimulation of aldosterone synthesis and release, and, as a consequence, renal sodium reabsorption.

Blockade of AT1 receptors inhibits_the negative regulatory response of angiotensin II to renin secretion, but the resulting increase in plasma renin activity and circulating angiotensin II levels does not suppress the antihypertensive effect of azilsartan.

The antihypertensive effect of azilsartan medoxomil develops during the first 2 weeks of use, with the maximum therapeutic effect achieved after 4 weeks. A reduction in blood pressure after a single oral dose is usually achieved within a few hours and persists for 24 hours.

Withdrawal syndrome after sudden discontinuation of Edarbi® during long-term therapy (for 6 months) was not observed.

The safety and efficacy of the drug do not depend on the age of patients, but a greater sensitivity to lowering blood pressure in some elderly patients cannot be excluded.

As with other angiotensin II receptor antagonists and ACE inhibitors, the antihypertensive effect is less pronounced in black patients (usually a population with low plasma renin activity). Concomitant use of Edarbi ® 40 mg and 80 mg with dihydropyridine slow calcium channel blockers (amlodipine) or thiazide diuretics (chlortalidone) leads to an additional decrease in blood pressure compared to therapy with antihypertensive agents used in monotherapy.

Influence on repolarization processes

The potential of Edarbi® to increase the QT/QT_c interval was evaluated in healthy volunteers during the QT/QT_{c study}. When using Edarbi® at a dose of 320 mg, there was no increase in the QT/QTC interval. QT_c – corrected (relative to heart rate) value of the QT interval, relative value. Since the duration of the QT interval depends on the heart rate (lengthening when it slows down), for evaluation it must be adjusted relative to the heart rate.

Prolongation of the QT interval reflects the heterogeneity of the processes of repolarization of the ventricular myocardium, and is regarded as an independent indicator indicating the possibility of fatal cardiac arrhythmias.

Indications

• essential hypertension.

Contraindications

• severe hepatic impairment (more than 9 points on the Child-Pugh scale) (no experience of use);
• pregnancy;
• simultaneous use of aliskiren in patients with diabetes mellitus;
• age up to 18 years (efficacy and safety have not been established);
• hypersensitivity to the Active ingredient and other components of the drug.

The drug should be used with caution in patients with severe chronic heart failure (NYHA functional class IV); severe renal insufficiency (CC

Side effects

the Frequency of adverse reactions was determined in accordance with who recommendations: very often (>1/10); often (>1/100, <1/10); infrequently (>1/1000, <1/100); rare (>1/10 000, <1/1000); very rare (<1/10 000), including individual messages; unspecified frequency (frequency cannot be estimated according to the available data).

Nervous system disorders:  often – dizziness.

From the cardiovascular system:  infrequently – a marked decrease in blood pressure.

From the digestive system:  often – diarrhea; infrequently-nausea.

Skin and subcutaneous tissue disorders:  infrequently-rash, pruritus; rarely-angioedema.

Musculoskeletal disorders:  infrequently-muscle spasms.

From the side of laboratory and instrumental studies:  often-increased CPK activity; infrequently-increased creatinine concentration, hyperuricemia.

Other services:  infrequently – increased fatigue, peripheral edema.

Description of individual adverse reactions

When Edarbi® is co – administered with chlortalidone, the frequency of adverse reactions – a marked decrease in blood pressure and an increase in creatinine concentration-increases in frequency from “infrequently” to “often”.

When Edarbi® is co-administered with amlodipine, the frequency of adverse reactions – peripheral edema-increases from infrequent to frequent, but occurs less frequently than with amlodipine monotherapy.

Rarely there is angioedema, including swelling of the face, lips and periorbital edema.

As with other angiotensin II receptor antagonists and ACE inhibitors, concomitant use of Edarbi® with diuretics (for example, chlortalidone) leads to an increase in creatinine concentrations. An increase in creatinine concentration when Edarbi® is co-administered with diuretics is associated with a more pronounced decrease in blood pressure compared to Edarbi®monotherapy. Most of these effects were short-lived or did not progress as long as patients continued therapy. After discontinuation of the drug, most cases of increased creatinine concentrations that did not go away during treatment were reversible. The creatinine concentration in most patients returned to values that are at the baseline, or values that are close to the baseline.

When treated with Edarbi®, there was a slight increase in serum uric acid concentration (10.8 mmol / l) compared to placebo (4.3 mmol/L).

As with other RAAS inhibitors, a slight decrease in hemoglobin and hematocrit was observed when Edarbi® was used as monotherapy (on average, they decreased by about 3 g/l and 1 vol.%, respectively).

If any of the side effects listed in the instructions get worse, or the patient notes other side effects that are not listed in the instructions, you should inform your doctor.

Interaction

A reversible increase in serum lithium concentrations and toxicity was observed with the simultaneous use of lithium preparations and ACE inhibitors and lithium preparations with angiotensin II receptor antagonists. Therefore, concomitant use of azilsartan medoxomil in combination with lithium preparations is not recommended. If necessary, the use of this combination is recommended for regular monitoring of the lithium content in the blood serum.

Concomitant use of angiotensin II antagonists and NSAIDs (for example, selective COX-2 inhibitors, acetylsalicylic acid (more than 3 g / day) and non-selective NSAIDs) may weaken the antihypertensive effect. Concomitant use of angiotensin II antagonists and NSAIDs may increase the risk of impaired renal function and increased serum potassium. Therefore, at the beginning of treatment, patients are recommended to regularly take sufficient fluids and monitor kidney function.

Concomitant use of potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium and other medications (for example, heparin) with azilsartan medoxomil may lead to an increase in serum potassium. Patients should monitor their serum potassium levels during combination therapy.

Dual blockade of the RAAS with angiotensin II receptor antagonists, ACE inhibitors, or aliskiren is associated with an increased risk of hypotension, hyperkalemia, and impaired renal function (including acute renal failure) compared to monotherapy.

No pharmacokinetic interactions were observed when azilsartan medoxomil or azilsartan was co-administered with amlodipine, antacids (magnesium and aluminum hydroxide), chlortalidone, digoxin, fluconazole, glibenclamide, ketoconazole, metformin and warfarin.

Azilsartan medoxomil is converted to the pharmacologically active metabolite azilsartan during absorption from the gastrointestinal tract by the enzyme carboxymethylenebutenolidase in the intestine and liver. In vitro studies have shown that interactions based on enzyme inhibition are unlikely.

The antihypertensive effect of azilsartan medoxomil therapy may be enhanced when combined with other antihypertensive agents, including diuretics (chlortalidone and hydrochlorothiazide) and dihydropyridine slow calcium channel blockers (amlodipine).

How to take, course of use and dosage

The drug is taken orally 1 time/day, regardless of food intake.

The recommended starting dose is 40 mg once a day. If it is necessary to further reduce blood pressure, the dose of the drug can be increased to a maximum of 80 mg 1 time/day. The maximum daily dose is 80 mg.

In case of inadequate blood pressure control when using Edarbi® as monotherapy, it may be used simultaneously with other antihypertensive drugs, including diuretics (chlortalidone and hydrochlorothiazide) and dihydropyridine slow calcium channel blockers (amlodipine).

Edarbi® should be taken daily, without interruption. If treatment is discontinued, the patient should inform the doctor.

If you miss the next dose, the patient should take the next dose at the usual time. Do not take a double dose of Edarbi®.

There is no need to adjust the initial dose of Edarbi® in elderly patients. However, in patients over 75 years of age, a dose of 20 mg may be considered as an initial dose (increased risk of hypotension).

No dosage adjustment is required in patients with mild to moderate renal impairment. There is no clinical experience of using Edarbi® in patients with severe renal impairment and end-stage renal failure, so the drug should be used with caution in this category of patients.

Due to limited experience with the use of Edarbi® in patients with mild to moderate hepatic impairment, it is recommended to start treatment with a dose of 20 mg 1 time / day and conduct it under close supervision. It is not recommended to use the drug in patients with severe hepatic impairment due to lack of clinical experience.

Edarbi® should only be prescribed to patients with reduced BCC and / or hyponatremia (for example, patients with prolonged vomiting, diarrhea, or taking high-dose diuretics) under strict medical supervision. It is recommended to start treatment with a dosage of 20 mg 1 time/day.

Due to the lack of clinical experience, Edarbi® should be used with caution in patients with severe chronic heart failure (NYHA functional Class IV).

No dose adjustment is required in black patients. As with other angiotensin II (AT₁) receptor antagonists and ACE inhibitors, patients of the black race show a smaller decrease in blood pressure compared to the rest of the population. In this regard, adequate blood pressure control in black patients may require an increase in the dose of Edarbi® and complex therapy more often than in other patients.

Overdose

Experience with the use of Edarbi® in adults in doses up to 320 mg / day for 7 days shows that the drug is well tolerated.

Symptoms: marked decrease in blood pressure, dizziness.

Treatment: with a marked decrease in blood pressure, the patient should be moved to a horizontal position with a low headboard; measures to increase BCC and symptomatic therapy are recommended. Hemodialysis is ineffective.

Special instructions

Patients whose vascular tone and renal function are highly dependent on RAAS activity (for example, in patients with severe chronic heart failure (NYHA functional Class IV), severe renal insufficiency, or renal artery stenosis), treatment with RAAS-acting drugs, such as ACE inhibitors and angiotensin II receptor antagonists, is associated with the possibility of developing acute arterial hypotension, azotemia, oliguria, or, rarely, acute renal failure. The possibility of developing these effects can not be excluded with the use of Edarbi®.

A sharp decrease in blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular diseases can lead to the development of myocardial infarction or stroke.

There are no data on the use of Edarbi® in patients who have recently undergone a kidney transplant.

There are no data on clinical experience with Edarbi® in patients with severe hepatic impairment, so the use of the drug in this category of patients is not recommended.

Patients with reduced BCC and / or hyponatremia (as a result of vomiting, diarrhoea, high-dose diuretics, or a salt-restricted diet) may develop clinically significant hypotension after starting Edarbi therapy. Hypovolemia should be corrected before starting treatment with Edarbi® or starting treatment with a dosage of 20 mg.

Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that affect the RAAS. Therefore, Edarbi® is not recommended for such patients.

Clinical experience with other drugs that affect the RAAS indicates that concomitant use of Edarbi® with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that may increase the potassium content in the blood (for example, heparin) may lead to hyperkalemia in patients with arterial hypertension. Elderly patients, patients with renal insufficiency, diabetes mellitus, and / or patients with other concomitant diseases increase the risk of developing hyperkalemia, which can be fatal. In such patients, it is recommended to monitor the content of potassium in the blood serum.

Caution should be exercised when using Edarbi in patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy.

As with other angiotensin II receptor antagonists, concomitant use of lithium and Edarbi is not recommended.

Influence on the ability to drive motor vehicles and manage mechanisms

Based on its pharmacodynamic properties, it is expected that azilsartan medoxomil will have a minor effect on the ability to drive vehicles and operate mechanisms. Caution should be exercised, as with any antihypertensive medication (risk of dizziness and fatigue).

Storage conditions

The drug should be stored in its original packaging to protect it from light and moisture, out of the reach of children at a temperature not exceeding 25°C.

Shelf

life is 3 years.

Active ingredient

Azilsartan medoxomil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension