Micardis Plus tabs 80mg + 12.5mg #28

Instruction for Micardis Plus

You can buy Micardis Plus here

Micardis Plus is a combined antihypertensive agent; angiotensin II (A-II) receptor antagonist + thiazide diuretic.

Release form and composition

Micardis Plus is released in the form of tablets - biconvex, oval, two-layer:
    dosage 40 / 12.5 mg and 80 / 12.5 mg - one layer is pink-beige, the second is white with possible splashes of pink-beige, on the white surface there is an impression "H4" (40 / 12.5 mg) or "H8" (80 / 12.5 mg), and the company logo (7 pcs. in a blister, in a cardboard box 2, 4 or 8 blisters);
    dosage 80/25 mg - one layer is white, with possible splashes of yellow, the second is yellow; on the white surface there is an imprint "H9" and the company logo (7 pcs. in a blister, in a cardboard box 1, 2 or 4 blisters).
1 tablet contains:
    active ingredients: telmisartan - 40/80 mg + hydrochlorothiazide - 12.5 mg or telmisartan - 80 mg + hydrochlorothiazide - 25 mg;
    additional components: povidone, sodium hydroxide, meglumine, magnesium stearate, sorbitol, microcrystalline cellulose, lactose monohydrate, corn starch, sodium carboxymethyl starch, iron dye red oxide (40 / 12.5 and 80 / 12.5), iron dye yellow oxide ( 80/25).

Pharmacodynamics

Micardis Plus is an antihypertensive drug that is a combination of telmisartan (an A-II receptor blocker) and hydrochlorothiazide (a thiazide diuretic). The combined use of these components provides a stronger antihypertensive effect than the use of each of them separately. Taking this agent within therapeutic doses once a day leads to a gradual pronounced decrease in blood pressure (BP).

Telmisartan

Telmisartan is a specific antagonist (blocker) of A-II receptors (AT1 subtype), demonstrating an antihypertensive effect when used orally. It has a high affinity for the AT1 subtype of A-II receptors, through which the latter acts. Does not have any agonistic effect on the receptor, from which it displaces A-II. The active substance selectively long-term binds to the AT1 subtype of A-II receptors, while it does not have an affinity for the AT2 subtype, as well as for other angiotensin receptors. The functional significance of these receptors and the result of their possible excessive activation due to the influence of A-II, the level of which increases with telmisartan, have not been studied. The active ingredient causes a decrease in the concentration of aldosterone in the blood, does not block ion channels and does not suppress the level of renin in the blood plasma. Telmisartan also does not inhibit angiotensin-converting enzyme (ACE) - kininase II, which degrades bradykinin, therefore, an aggravation of the risk of adverse reactions caused by bradykinin is not expected.
In the presence of arterial hypertension, the use of telmisartan at a dose of 80 mg completely inhibits the hypertensive effect of A-II. The antihypertensive activity of the substance after its first oral administration is manifested within 3 hours. The action of the remedy lasts for 24 hours and remains significant up to 48 hours. It is usually possible to achieve a pronounced hypotensive effect 28 days after the start of the course, provided that Micardis Plus is taken regularly.
In patients with arterial hypertension, telmisartan reduces both systolic and diastolic blood pressure without changing the heart rate (HR). If it is necessary to abruptly cancel the substance, blood pressure gradually returns to its original values ​​without the risk of developing a withdrawal syndrome.
In the course of studies of telmisartan, an assessment was made of cases of cardiovascular death, non-fatal stroke, non-fatal myocardial infarction or hospitalization due to chronic heart failure (CHF). In patients over 55 years of age with stroke, coronary artery disease, peripheral arterial disease or diabetes mellitus with concomitant damage to target organs (left ventricular hypertrophy, retinopathy, macro- or microalbuminuria in history), a decrease in cardiovascular morbidity and mortality was found.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. The substance, like other representatives of this class of antihypertensive drugs, affects the mechanism of electrolyte reabsorption in the renal tubules, directly increasing the excretion of sodium and chloride (approximately in equal amounts). The result of the diuretic activity of the drug is a decrease in the volume of circulating blood (BCC), an increase in the plasma level of renin in the blood, an increase in the production of aldosterone and a subsequent increase in the content of potassium and hydrocarbonates in the urine, which leads to a decrease in the concentration of potassium in the blood plasma.
With the combined use of the substance with telmisartan, possibly due to blockade of the renin-angiotensin-aldosterone system (RAAS), the loss of potassium associated with this diuretic is reduced. After oral administration of hydrochlorothiazide, increased diuresis is noted after 2 hours, and the maximum effect is observed after about 4 hours. Diuretic activity of Micardis Plus is observed for about 6-12 hours.
Prolonged use of hydrochlorothiazide reduces the risk of complications and mortality from cardiovascular lesions.
The antihypertensive effect of Micardis Plus, as a rule, reaches its maximum 4–8 weeks after the start of the course of treatment.

Pharmacokinetics

The combined use of hydrochlorothiazide and telmisartan does not affect the pharmacokinetics of each of these active substances separately.

Telmisartan

When used orally, the agent is rapidly absorbed from the gastrointestinal tract (GIT), bioavailability is approximately 50%. The maximum concentration of the substance in the blood plasma (Cmax) is observed on average after 0.5-1.5 hours. When taken simultaneously with food, a decrease in the area under the concentration-time curve (AUC) can range from 6% (at a dosage of 40 mg) to 19% (at a dosage of 160 mg). After 3 hours after oral administration, the plasma level of the substance in the blood levels off, regardless of food intake.
Telmisartan is characterized by a high bond with blood plasma proteins (more than 99.5%), mainly with α1-glycoprotein and albumin. The volume of distribution (Vd) is approximately 500 liters.
The metabolic transformation of a substance occurs through conjugation with glucuronic acid. The metabolites of the drug are pharmacologically inactive, the half-life (T1 / 2) is over 20 hours. The substance is excreted unchanged through the intestines, less than 2% is excreted by the kidneys. The total plasma clearance is about 900 ml / min.
In women, the Cmax of telmisartan is approximately 2-3 times higher than in men, but this does not have a significant effect on the effectiveness of Micardis Plus. Also in women, there is a tendency to an increase in the plasma level of hydrochlorothiazide, which is clinically insignificant.

Hydrochlorothiazide

After oral administration of Micardis Plus in the blood plasma Cmax of hydrochlorothiazide is observed within 1-3 hours. Based on the total excretion by the kidneys, the absolute bioavailability of the substance reaches approximately 60%. It binds to plasma proteins by 64%, Vd is 0.8 ± 0.3 l / kg. The agent is not metabolized in the body and is excreted by the kidneys almost unchanged. Approximately 60% of an oral dose of hydrochlorothiazide is eliminated within 48 hours, renal clearance is approximately 250-300 ml / min., T1 / 2 - 10-15 hours.

Indications for use

According to the instructions, Micardis Plus is recommended for use for the complex treatment of arterial hypertension in case of ineffectiveness of taking telmisartan or hydrochlorothiazide as monotherapy drugs.

Contraindications

Absolute:
    severe renal dysfunction, with creatinine clearance (CC) below 30 ml / min;
    severe liver dysfunction (class C on the Child-Pugh scale);
    obstructive diseases of the biliary tract;
    refractory hypercalcemia, hypokalemia;
    hereditary fructose intolerance (sorbitol is included in the composition);
    syndrome of glucose-galactose malabsorption, lactase deficiency and galactose intolerance;
    age under 18;
    concomitant treatment with aliskiren in patients with diabetes mellitus and renal failure, with a glomerular filtration rate (GFR) <60 ml / min / 1.73 m²;
    pregnancy and lactation;
    hypersensitivity to any of the components of the drug or other sulfonamide derivatives.
Relative (Micardis Plus tablets must be used with extreme caution):
    a decrease in BCC due to previous diuretic therapy, restrictions on salt intake, diarrhea or vomiting;
    functional liver disorders or progressive liver disease (class A and B on the Child-Pugh scale);
    stenosis of an artery of a single kidney or bilateral stenosis of the renal arteries (the threat of severe arterial hypotension and the development of renal failure is aggravated);
    condition after kidney transplantation (due to lack of experience in use);
    idiopathic hypertrophic subaortic stenosis;
    stenosis of the aortic and mitral valve;
    hypertrophic obstructive cardiomyopathy;
    CHF III – IV functional class according to NYHA classification (New York Heart Association);
    hyperkalemia;
    diabetes;
    gout (thiazide diuretics can provoke hyperuricemia and exacerbation of gout);
    primary aldosteronism;
    angle-closure glaucoma.

Instructions for use Micardis Plus: method and dosage

The tablets are taken orally once a day. The effectiveness of the antihypertensive drug does not depend on food intake.
Micardis Plus at a dosage of 40 / 12.5 mg can be prescribed to patients in whom blood pressure is insufficiently controlled when using hydrochlorothiazide or taking Micardis at a dosage of 40 mg.
Micardis Plus at a dosage of 80 / 12.5 mg can be prescribed to patients in whom taking it at a dosage of 40 / 12.5 mg or taking Micardis at a dosage of 80 mg does not provide adequate blood pressure control.
Micardis Plus at a dosage of 80/25 mg can be prescribed to patients in whom taking it at a dosage of 80 / 12.5 mg or taking Micardis at a dosage of 80 mg does not lead to adequate blood pressure control, or in cases where the patient's condition was previously stabilized telmisartan or hydrochlorothiazide when used separately.
In severe arterial hypertension, the use of telmisartan at a dose of 160 mg or in combination with hydrochlorothiazide at a dose of 12.5-25 mg per day is effective and is usually well tolerated.

Side effects

    cardiovascular system: bradycardia1), tachycardia3), arrhythmias3), marked decrease in blood pressure (including orthostatic hypotension) 3);
    respiratory system: shortness of breath3), respiratory distress syndrome (including pneumonia and pulmonary edema) 3);
    central nervous system: insomnia3), sleep disturbances3), dizziness2) 3), increased excitability2), depression3), anxiety3), paresthesia3), fainting / light-headedness3);
    hematopoietic system and lymphatic system: anemia1), hemolytic anemia2), aplastic anemia2), eosinophilia1), thrombocytopenia1) 2), neutropenia / agranulocytosis2), leukopenia2), bone marrow suppression2);
    digestive system: dry mouth3), flatulence3), diarrhea3), constipation3), abdominal pain3), vomiting3), anorexia2), decreased appetite2), hypercholesterolemia2), hyperglycemia2), dyspepsia1) 2) 3), gastritis3), dysfunction liver3), liver disease3), pancreatitis2), jaundice (hepatocellular or cholestatic) 2);
    musculoskeletal system: pain in the lower extremities3), back pain3), calf muscle cramps3), muscle spasms3), chest pain3), tendinitis-like symptoms (pain in the tendons) 1), arthralgia3), myalgia3), arthrosis1);
    urinary system: glucosuria2), interstitial nephritis2), renal failure (including acute renal failure) 1);
    reproductive system: impotence3);
    sense organs: transient blurred vision3), visual impairment3), xanthopsia2), acute myopia2), acute angle-closure glaucoma2);
    skin: increased sweating3);
    allergic reactions: skin itching3), rash3), drug rash1) 2), urticaria3), erythema3), eczema1), toxic skin rash1), photosensitivity reaction2), toxic epidermal necrolysis1) 2), anaphylactic reactions1) 2), exacerbation or aggravation symptoms of systemic lupus erythematosus3), lupus-like reactions2), angioedema (including fatal cases) 3), systemic vasculitis2), necrotizing angiitis (vasculitis) 2), recurrence of systemic lupus erythematosus2), necrotizing vasculitis2);
    infections: inflammation of the salivary glands2), urinary tract infections (including cystitis) 1), upper respiratory tract infections (sinusitis, pharyngitis, bronchitis) 1) 3), sepsis (including fatal cases) 1 );
    metabolic disorders: an increase in the activity of creatine phosphokinase (CPK) 3), an increase in the activity of hepatic enzymes3), an increase in the level of creatinine in the blood plasma3), an increase in the concentration of uric acid in the blood3), hyperuricemia3), a violation of the water-electrolyte balance2), hyponatremia3), hyperkalemia1), hypokalemia3), hypertriglyceridemia2), deterioration of glycemic control2), hypoglycemia (in patients with diabetes mellitus) 1), a decrease in the level of hemoglobin in the blood1), a decrease in BCC2);
    others: weakness1) 2), pain syndrome of various localization3), fever2), flu-like syndrome3).
1) - adverse reactions observed during clinical trials of telmisartan.
2) - adverse reactions observed in clinical studies of hydrochlorothiazide.
3) - adverse reactions not observed in clinical studies with the combined use of telmisartan and hydrochlorothiazide, but expected while taking the drug.

Overdose

Cases of overdose of Micardis Plus tablets have not been recorded.
Symptoms of an overdose of the active components of the drug may be:
    telmisartan: bradycardia, tachycardia, marked decrease in blood pressure;
    hydrochlorothiazide: hypokalemia, hypochloremia and other disturbances in the water-electrolyte balance of the blood, a decrease in the BCC, causing muscle spasms and / or aggravating disorders of the cardiovascular system (arrhythmias caused by the simultaneous use of cardiac glycosides or some other antiarrhythmic drugs).
With the development of these reactions, symptomatic therapy is prescribed, telmisartan is not removed from the blood using hemodialysis. Hydrochlorothiazide is excreted from the body by hemodialysis, but the extent of its removal has not been established. It is necessary to carry out regular monitoring of the level of creatinine and electrolyte balance in the blood serum.

Special instructions

In some cases, as a result of inhibition of RAAS activity during drug therapy, mainly with concomitant treatment with drugs that affect this system, renal activity is impaired (including the development of acute renal failure). As a result, treatment, accompanied by a double blockade of the RAAS (for example, when combining Micardis Plus with ACE inhibitors or aliskiren), should be carried out strictly individually, with systematic careful monitoring of renal function (including monitoring the level of potassium and serum creatinine).
In patients with ischemic heart disease (IHD) and diabetes mellitus, while taking A-II receptor antagonists, the risk of fatal myocardial infarction and sudden cardiovascular death may increase. Since in the presence of diabetes mellitus, coronary artery disease can be undiagnosed due to asymptomatic course, in order to identify and treat it before starting treatment with Micardis Plus, an appropriate diagnosis (including exercise stress test) is required.
Hydrochlorothiazide belongs to sulfonamide derivatives and can cause the development of an idiosyncratic reaction, manifested in the form of acute angle-closure glaucoma and acute transient myopia. Symptoms of these complications include eye pain or a sharp decrease in visual acuity, which occurs in most cases for several hours to several weeks after you start taking Micardis Plus. In the absence of therapy, developed acute angle-closure glaucoma can cause vision loss. To treat this reaction, the first step is to immediately stop taking hydrochlorothiazide. If intraocular pressure remains uncontrolled, it may be necessary to conduct urgent conservative or surgical treatment. Risk factors for acute angle-closure glaucoma may include a history of allergy to penicillin or sulfonamides.
Hydrochlorothiazide, like other thiazide diuretics, can lead to disturbances in the water-electrolyte balance and acid-base state (hyponatremia, hypokalemia and hypochloremic alkalosis). Signs of this complication may be thirst, dry mouth, general weakness, anxiety, drowsiness, muscle weakness, myalgia or twitching of the calf muscles (cramps), a marked decrease in blood pressure, nausea, vomiting, tachycardia, oliguria.
The threat of hypokalemia increases mainly in patients with cirrhosis of the liver, against the background of increased diuresis, with a salt-free diet and in the case of a combination of the drug with gluco- and mineralocorticosteroids or corticotropin.
Despite the fact that during the treatment of the drug clinically significant hyperkalemia was not recorded, it should be borne in mind that the risk factors for its occurrence include diabetes mellitus, heart and / or renal failure.
There is no information confirming the ability of the drug to reduce or prevent the development of hyponatremia caused by taking diuretics. Hypochloremia is noted, as a rule, insignificant and does not require treatment.
Thiazide diuretics increase the likelihood of a decrease in renal calcium excretion and the appearance of a transient and small increase in serum calcium levels. The development of severe hypercalcemia may be a symptom of latent hyperparathyroidism. If an assessment of the function of the parathyroid glands is required, thiazide diuretics should be discontinued.
The action of Micardis Plus is less effective in patients of the Negroid race.

Influence on the ability to drive vehicles and complex mechanisms

Since dizziness and drowsiness may develop while taking Micardis Plus, special care must be taken when driving vehicles and performing work related to controlling mechanisms that require increased attention.

Application during pregnancy and lactation

The use of Micardis Plus is contraindicated for pregnant women. The use of A-II receptor antagonists in the first trimester of pregnancy is not recommended. If pregnancy is confirmed, the use of these drugs should be discontinued immediately. If necessary, patients are prescribed alternative antihypertensive drugs that have an established pregnancy safety profile.
In the II-III trimesters, therapy with A-II receptor blockers is contraindicated, since in the course of preclinical studies it was found that during these periods of pregnancy they can cause fetotoxicity in humans (slowing of cranial ossification, oligohydramnios, impairment of renal activity), as well as neonatal toxicity (hyperkalemia, hypotension, renal failure). If in the second trimester of pregnancy, treatment with A-II receptor antagonists was prescribed, the fetus should undergo an ultrasound examination of the skull bones and kidney function. Newborns whose mothers took drugs of this class should be carefully monitored for arterial hypotension.
The experience of using hydrochlorothiazide by pregnant women, especially in the first trimester, is limited. It is known that this substance passes through the placental barrier and, taking into account the pharmacological mechanism of its action, it can be expected that taking Micardis Plus in the II-III trimesters of pregnancy can provoke a violation of placental perfusion and cause such undesirable effects in the embryo / fetus as thrombocytopenia, jaundice, electrolyte imbalance. Hydrochlorothiazide should not be used for hypertension and edema associated with pregnancy, with preeclampsia (due to the aggravation of the threat of a decrease in plasma volume and a decrease in placental perfusion), and in the absence of a positive effect in these clinical situations.
For the treatment of essential hypertension in pregnant women, hydrochlorothiazide can be prescribed only in extremely rare cases, if it is impossible to use another treatment.
Taking the drug during breastfeeding is contraindicated.
Studies of the effect of the drug on human fertility have not been conducted.

Childhood use

Since the safety and efficacy of using the drug in children and adolescents has not been established, the drug is contraindicated in patients under 18 years of age.

With impaired renal function

In the presence of severe renal dysfunction (CC below 30 ml / min), the use of Micardis Plus is contraindicated.
It is recommended to use an antihypertensive agent with caution against the background of stenosis of the artery of a single kidney or bilateral stenosis of the renal arteries and in the condition after kidney transplantation. In patients with mild / moderate functional impairment of the kidneys (CC above 30 ml / min), dose adjustment of Micardis Plus is not required, but they should be periodically monitored for renal activity.

For violations of liver function

In the presence of severe liver dysfunctions (class C on the Child-Pugh scale), the use of Micardis Plus is contraindicated.
Patients with functional impairment of the liver or progressive liver disease (class A and B on the Child-Pugh scale) should use the drug with caution, since even with small changes in the water-electrolyte balance, the risk of developing hepatic coma is aggravated. In case of mild / moderate liver dysfunction, the maximum daily dose of Micardis Plus should not exceed 40 / 12.5 mg.

Use in the elderly

The pharmacokinetic parameters of Micardis Plus in elderly patients do not differ from those in young patients, as a result of which a dose change in the elderly is not required.

Drug interactions

Interaction reactions possible with the combined use of telmisartan with other medicinal substances / agents:
    hydrochlorothiazide, warfarin, digoxin, simvastatin, glibenclamide, amlodipine: no clinically significant interaction was found; revealed an increase in the average plasma concentration of digoxin in the blood by about 20%; with the combined use of telmisartan and digoxin, it is recommended to periodically determine the level of the latter in the blood;
    lithium preparations: in rare cases, a reversible increase in the lithium content in the blood is possible, proceeding with toxic phenomena, and therefore its concentration in serum should be monitored;
    other antihypertensive drugs: an increase in the antihypertensive effect is possible; with the combination of telmisartan and ramipril, there was an increase in AUC0-24 and Cmax of the latter and its metabolite (ramiprilat) by 2.5 times; the clinical significance of this interaction is unknown;
    non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid, used as an anti-inflammatory agent (in a daily dose of not more than 3 g): non-selective NSAIDs and cyclooxpgenase-2 (COX-2) inhibitors in patients with reduced BCC can lead to the development of acute renal failure ; agents that affect the RAAS can exhibit a synergistic effect; with a combination of telmisartan and NSAIDs at the beginning of therapy, it is necessary to compensate for the BCC and monitor renal function; with this combination, also as a result of the suppression of the vasodilating effect of prostaglandins, a decrease in the effect of telmisartan was noted; when combined with paracetamol and ibuprofen, a clinically significant effect was not revealed.
Interaction reactions possible with the combined use of hydrochlorothiazide with other drugs / agents:
    antidiabetic oral agents and insulin: dose adjustment of these drugs may be necessary;
    barbiturates, opioid analgesics, ethanol: the threat of orthostatic hypotension is aggravated;
    cholestyramine, colestipol: absorption of hydrochlorothiazide is impaired;
    metformin: the risk of lactic acidosis increases;
    pressor amines (including norepinephrine): the effect of these agents may be weakened;
    cardiac glycosides: the risk of developing hypomagnesemia / hypokalemia caused by thiazide diuretics, as well as the appearance of arrhythmias caused by the use of cardiac glycosides, is aggravated;
    non-depolarizing muscle relaxants (including tubocurarine chloride): it is possible to enhance the action of these funds;
    calcium preparations: the level of calcium in the blood serum may increase due to a decrease in its excretion by the kidneys; with this combination, it is required to regularly monitor the concentration of calcium in the blood and, if necessary, change its dose;
    anti-gout agents: an increase in the level of uric acid in the blood serum is possible, which may require correction of the dosage of uricosuric agents; there may be an increase in the incidence of hypersensitivity reactions to allopurinol;
    biperidine, atropine and other m-anticholinergics: gastrointestinal motility is weakened; increases the bioavailability of thiazide diuretics;
    diazoxide, beta-blockers: it is possible to increase the hyperglycemia caused by these drugs;
    laxatives, potassium-eliminating diuretics; gluco- and mineralocorticosteroids, amphotericin B, corticotropin, benzylpenicillin, carbenoxolone, acetylsalicylic acid derivatives and other agents leading to the excretion of potassium and the development of hypokalemia: the hypokalemic effect is enhanced; hypokalemia due to hydrochlorothiazide is compensated for by the potassium-sparing effect of telmisartan;
    NSAIDs: possible weakening of the antihypertensive and diuretic action;
    potassium preparations, potassium-sparing diuretics and other drugs that lead to an increase in serum potassium levels (heparin); replacement of sodium in table salt with potassium salts: hyperkalemia may appear; should periodically monitor the plasma concentration of potassium in the blood;
    cytotoxic agents (for example, cyclophosphamide, methotrexate): the renal excretion of these agents decreases and their myelosuppressive effect increases;
    glycyrrhizic acid (licorice root): a decrease in the level of potassium in the blood serum is possible (the development of hypokalemia);
    amantadine: the risk of undesirable effects caused by this substance is aggravated.

Terms and conditions of storage

Store in a dry place, out of reach of children, at a temperature not exceeding 25 ° C.
Shelf life is 3 years.

Reviews

Reviews of Micardis Plus from patients and cardiologists are mostly positive. The drug is considered effective, showing good results even in the treatment of chronic hypertension. There is a minimal effect of the drug on the heart rate and its more pronounced therapeutic effect in comparison with Micardis.
There are no complaints about the development of side effects. The disadvantage of Micardis Plus is considered by many to be its high cost.

Terms of sell

You can buy Micardis Plus without a prescription from a doctor.