Micardis Plus, pills 80mg+12.5mg, 28pcs

Composition

Active ingredients:  

telmisartan 40 and 80 mg,

hydrochlorothiazide 12.5 mg;

excipients:

povidone,

meglumin,

sodium hydroxide,

sorbitol,

magnesium stearate,

microcrystalline cellulose,

red iron oxide,

sodium starch glycolate,

lactose monohydrate,

corn starch

Pharmacological action

Micardis Plus is an antihypertensive drug. It is a combination of telmisartan (an angiotensin II receptor antagonist) and hydrochlorothiazide (a thiazide diuretic). The simultaneous use of these components leads to a greater antihypertensive effect than the use of each of them separately. Taking Micardis Plus 1 time / day leads to a significant gradual decrease in blood pressure.

Telmisartan is a specific angiotensin II receptor antagonist. It has a high affinity for the AT1 subtype of angiotensin II receptors, through which the action of angiotensin II is realized. Telmisartan displaces angiotensin II from binding to the receptor, without having an agonist effect on this receptor. Telmisartan binds only to the AT1 receptor subtype of angiotensin II. Binding is long-term. Telmisartan has no affinity for other angiotensin receptors (including AT2 receptors). The functional significance of these receptors, as well as the effect of their possible overstimulation with angiotensin II, the concentration of which increases with the appointment of telmisartan, have not been studied. Telmisartan reduces the level of aldosterone in the blood. Telmisartan does not block blood renin and ion channels, does not block ACE, and does not inactivate bradykinin.

In patients with arterial hypertension, telmisartan reduces systolic and diastolic blood pressure without affecting heart rate.

Telmisartan at a dose of 80 mg completely blocks the hypertensive effect of angiotensin II. Its effect lasts for more than 24 hours, including the last 4 hours before taking the next dose. The onset of antihypertensive action is noted within 3 hours after the first use of telmisartan. In the case of abrupt withdrawal of telmisartan, blood pressure gradually returns to its original level without the development of “withdrawal”syndrome.

Hydrochlorothiazide is a thiazide diuretic. Thiazide diuretics affect the reabsorption of electrolytes in the renal tubules, directly increasing the excretion of sodium and chloride (in approximately equivalent amounts). The diuretic effect of hydrochlorothiazide leads to a decrease in BCC, an increase in plasma renin activity, an increase in aldosterone secretion and is accompanied by an increase in the content of potassium and bicarbonates in the urine, as well as hypokalemia. When telmisartan is co-administered, there is a tendency to stop the potassium loss caused by these diuretics, presumably due to RAAS blockade.

Long-term use of hydrochlorothiazide reduces the risk of developing complications of cardiovascular diseases and mortality from them.

After taking hydrochlorothiazide, diuresis increases after 2 hours, and the maximum effect is observed after about 4 hours. The diuretic effect of the drug persists for about 6-12 hours.

The maximum antihypertensive effect of Micardis Plus® is usually achieved 4 weeks after the start of treatment.

Pharmacokinetics

The combined use of hydrochlorothiazide and telmisartan does not affect the pharmacokinetics of each of the components of the drug.

Telmisartan

Suction

When taken orally, the Cmax of telmisartan is reached within 0.5-1.5 hours after use. The absolute bioavailability of telmisartan at doses from 40 to 160 mg was 42% and 58%, respectively. When taken simultaneously with food, the bioavailability of telmisartan decreases slightly, with a decrease in the AUC value by 6% at a dose of 40 mg and about 19% at a dose of 160 mg. After 3 hours after ingestion, the concentration in the blood plasma is leveled, regardless of whether the drug was taken with food or on an empty stomach. The pharmacokinetics of telmisartan when administered orally are non-linear at doses of 20-160 mg with a more than proportional increase in plasma concentrations (Cmax and AUC) with increasing doses.

Distribution

Binding to plasma proteins is significant (more than 99.5%), mainly with albumin and α1-glycoprotein. Vd for telmisartan approximately 500 l.

Penetrates the placental barrier and is detected in the blood of the umbilical cord.

Metabolism

Telmisartan is metabolized by conjugation with glucuronic acid. The metabolite (acylglucuronide) is pharmacologically inactive. Glucuronide is the main metabolite that is determined only in humans.

Deduction

Most of the administered dose (more than 97%) is excreted in the bile, and then in the feces. In small amounts, telmisartan is excreted in the urine. The total plasma clearance is more than 1500 ml / min. T 1/2 is more than 20 hours.

Pharmacokinetics in special clinical cases

In women, the plasma concentration of telmisartan is 2-3 times higher than in men. However, an increase in the hypotensive effect is not observed in women.

The pharmacokinetic parameters of telmisartan do not differ significantly in young and elderly patients.

Renal excretion does not affect the clearance of telmisartan. Based on the level of excretion in patients with mild to moderate renal impairment (creatinine clearance from 30 to 60 ml/min), no dosage adjustment is required. Telmisartan is not removed during dialysis.

Pharmacokinetic studies in patients with hepatic insufficiency have shown an increase in absolute bioavailability to almost 100%. With hepatic insufficiency, T 1/2 does not change.

Hydrochlorothiazide

Suction

After oral use of Micardis Plus®, Cmax of hydrochlorothiazide is reached within 1-3 hours. Absolute bioavailability is estimated by cumulative renal excretion of hydrochlorothiazide and is about 60%.

Distribution

Binds to plasma proteins by 64%. Vd – 0.8±0.3 l / kg.

Metabolism and elimination

It is not metabolized in the human body and is excreted in the urine almost unchanged. About 60% of the oral dose is eliminated within 48 hours. Renal clearance is about 250-300 ml / min. T 1/2 – 10-15 h.

Pharmacokinetics in special clinical cases

In women, there is a tendency to increase plasma concentrations of hydrochlorothiazide. However, an increase in the hypotensive effect is not observed in women.

In patients with impaired renal function, the rate of elimination of hydrochlorothiazide is reduced. T 1/2 of hydrochlorothiazide at creatinine clearance of 90 ml/min increases and is about 34 hours.

Indications

Arterial hypertension (in case of ineffectiveness of telmisartan or hydrochlorothiazide as monotherapy).

Use during pregnancy and lactation

While it is not yet known whether telmisartan passes into breast milk, hydrochlorothiazide passes into breast milk and may inhibit lactation. Therefore, Micardis Plus is contraindicated for use during lactation. Telmisartan does not have a teratogenic effect, but it has a fetotoxic effect. Therefore, Micardis Plus should not be used in the first trimester of pregnancy. In the case of a planned pregnancy, Micardis Plus should be replaced with drugs approved for use during pregnancy. If pregnancy is established, you should immediately stop taking the drug. In the second and third trimesters, the use of the drug may cause electrolyte disturbances in the fetus, as well as, possibly, other disorders that are known in adults. Neonatal thrombocytopenia, jaundice (in the fetus or in the newborn) have been reported when the mother takes thiazide diuretics (including hydrochlorothiazide). Therefore, the drug is contraindicated in the second and third trimester of pregnancy.

Contraindications

• obstructive cholestasis and bile duct diseases;
• severe liver dysfunction;
• severe renal dysfunction (CC < 30 ml/min);
• hypokalemia, hyponatremia, hypercalcemia;
• hereditary fructose intolerance (contains sorbitol);
• the age of 18 years (safety and efficacy have not been established);
• II and III trimester of pregnancy;
• lactation;
• hypersensitivity to Mikardisplûs or other derivatives of sulfonamides.

With caution:  Micardis Plus should be prescribed in patients with impaired liver function or progressive liver diseases; bilateral renal artery stenosis or stenosis of the artery of a single kidney; impaired renal function; condition after kidney transplantation; BCC decrease due to previous diuretic therapy, restriction of salt intake, diarrhea or vomiting; chronic heart failure; aortic and mitral valve stenosis; obstructive hypertrophic cardiomyopathy; diabetes mellitus; CHD; systemic lupus erythematosus; gout.

Side effects

1) – side effects expected based on experience with telmisartan.

2) – side effects expected based on the experience of using hydrochlorothiazide.

Respiratory system disorders:  upper respiratory tract infections (including bronchitis, pharyngitis, sinusitis), dyspnea 1), dyspnea, respiratory distress syndrome (including pneumonia and pulmonary edema)2).

From the cardiovascular system:  bradycardia 1), tachycardia 1), arrhythmias 2), marked decrease in blood pressure 1), orthostatic hypotension 2), necrotic angiitis (vasculitis)2), chest pain 1).

From the central nervous system:  excitability, fear, depression 1)2), feeling restless 2), dizziness, fainting 1), insomnia 1), staggering when walking 2), paresthesia 2).

From the digestive system: abdominal pain, diarrhea, dyspepsia, gastritis, anorexia 2), decreased appetite 2), sialoadenitis 2), dry mouth 1), flatulence 1), vomiting 1), constipation 2), pancreatitis 2), liver dysfunction 1), jaundice (hepatocellular or cholestatic)2).

From the endocrine system: loss of control of hypoglycemia in diabetes mellitus.

Metabolic disorders: hypercholesterolemia, hyperuricemia, hypokalemia, hyperkalemia, hyponatremia 2), BCC decrease 2), electrolyte metabolism disorder 2), hyperglycemia 2), hypercalcemia 1).

From the hematopoietic system: eosinophilia 1), anemia (including aplastic anemia 2), hemolytic anemia 2), inhibition of bone marrow hematopoiesis 2), leukopenia 2), neutropenia/agranulocytosis 2), thrombocytopenia 1) 2).

From the urinary system: urinary tract infections, interstitial nephritis 2), impaired renal function 2), acute renal failure 1), glucosuria 2).

Musculoskeletal disorders: arthralgia, osteoarthritis, back pain, shin pain, myalgia, convulsive twitching of the calf muscles (crampi)1), tendinitis-like symptoms 1), weakness 1)2), muscle spasm 2).

Allergic reactions: anaphylactic reactions 2), eczema, erythema 1), pruritus 1), lupus-like skin reactions 2), cutaneous vasculitis 2), photosensitivity reactions 2), rash 2), reactivation of cutaneous lupus erythematosus 2), toxic epidermal necrolysis 2), angioedema, urticaria and other similar reactions (as with other angiotensin II antagonists).

From the side of the senses: visual acuity disorders 1), transient blurred vision 2), xanthopsia 2), vertigo.

From the side of the reproductive system: reduced potency.

Laboratory parameters: decreased hemoglobin 1), increased uric acid 1), creatinine 1), liver enzymes 1), blood creatine phosphokinase 1), triglycerides 2).

Other services: flu-like symptoms, fever 2), increased sweating 1).

The use of thiazide diuretics may impair glucose tolerance.

Interaction

With simultaneous use, it is possible to increase the concentration of digoxin in blood plasma. When used concomitantly with antihypertensive drugs, it is possible to increase the antihypertensive effect. When used concomitantly with lithium preparations, it is possible to increase the concentration of lithium in blood plasma. When used concomitantly with potassium-sparing diuretics, heparin, dietary supplements, salt substitutes containing potassium, hyperkalemia may develop.

How to take, course of use and dosage

Mikardis Plus is taken regardless of food intake,1 time a day

Overdose

Symptoms of telmisartan: tachycardia and / or bradycardia, marked decrease in blood pressure. Overdose of hydrochlorothiazide is accompanied by loss of electrolytes (hypokalemia, hypochloremia) and dehydration resulting from massive diuresis. The most common signs and symptoms of a hydrochlorothiazide overdose are nausea and drowsiness. Hypokalemia can lead to muscle spasms and / or increase cardiac arrhythmias caused by the simultaneous use of cardiac glycosides or certain antiarrhythmic drugs. Treatment: symptomatic and supportive therapy, the nature of which depends on the time elapsed since taking the drug, and on the severity of symptoms. It is recommended to induce vomiting and / or gastric lavage, prescribe activated charcoal. Frequent monitoring of electrolytes and serum creatinine is necessary. If arterial hypotension develops, the patient should be placed on his back and quickly undergo therapy aimed at replacing electrolytes and BCC. Telmisartan is not removed by hemodialysis. The degree of removal of hydrochlorothiazide during hemodialysis has not been established.

Special instructions

A special study of the effect of the drug on the ability to drive a car and work with mechanisms was not conducted. However, when driving a car and working with mechanisms, you should be aware of the possibility of developing dizziness and drowsiness when using the drug Micardis Plus. Influence on the ability to drive motor vehicles and manage mechanisms:

Composition

Tablet Form of production

Storage conditions

The drug should be stored in a place protected from moisture at a temperature not exceeding 25°C.

Shelf life

3 years

Active ingredient

Telmisartan, Hydrochlorothiazide

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension