Mikardis Plus tablets: reviews, instructions for use, price, analogues

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Micardis Plus is a combination of telmisartan angiotensin type II receptor blocker hydrochlorothiazide ( diuretic ). The combined use of these components causes a stronger antihypertensive effect than using them separately. Taking the drug once a day leads to a pronounced gradual decrease in blood pressure.

Telmisartan is a selective angiotensin type 2 receptor blocker. Has high affinity for angiotensin II receptors of the AT1 subtype . It displaces angiotensin II from the receptor. The binding is long-term. Telmisartan does not block other receptors (including AT2 type receptors) of angiotensin . Telmisartan also reduces aldosterone .

In persons with arterial hypertension 80 mg of telmisartan per day completely suppresses the effects of angiotensin II . The onset of action occurs three hours after ingestion of the drug. The effect lasts for 24 hours. A permanent antihypertensive effect is observed a month after regular use of telmisartan .

Hydrochlorothiazide is diuretic . Affects the reabsorption of electrolytes in the renal tubules, directly increasing the excretion of sodium and chlorides. This causes a decrease in circulating blood volume, an increase in renin aldosterone synthesis .

After administration of hydrochlorothiazide, diuresis increases after two hours, and the maximum effect is achieved after four hours and persists for 6-12 hours.

Pharmacokinetics

Telmisartan. Quickly absorbed from the digestive tract. The maximum concentration of telmisartan occurs within an hour. Bioavailability is 50%.

Reaction with blood proteins is more than 99.5%. Metabolized by interaction with glucuronic acid . Telmisartan derivatives are pharmacologically inactive.

The half-life is approximately 20 hours. Excreted with feces in its original form and with the kidneys - up to 2%.

The pharmacokinetics of telmisartan in elderly patients does not differ from those in younger patients. No dose selection is required.

Hydrochlorothiazide. After oral administration of hydrochlorothiazide, maximum concentrations are achieved within 1-2 hours. Bioavailability reaches 60%.

Reaction with plasma proteins – 64%. It is not metabolized and is excreted unchanged through the kidneys.

MicardisPlus®

HYDROCHLOROTHIAZIDE

Renal dysfunction

In patients with impaired renal function, hydrochlorothiazide may cause azotemia. In case of renal failure, accumulation of hydrochlorothiazide is possible.

In patients with reduced renal function, periodic monitoring of creatinine clearance is necessary. If renal dysfunction progresses and/or oliguria (anuria) occurs, hydrochlorothiazide should be discontinued.

Liver dysfunction

When using thiazide diuretics in patients with impaired liver function, hepatic encephalopathy may develop. In patients with severe liver failure or hepatic encephalopathy, the use of thiazides is contraindicated. In patients with mild to moderate hepatic impairment and/or progressive liver disease, hydrochlorothiazide should be used with caution, since even slight changes in fluid and electrolyte balance and serum ammonium accumulation can cause hepatic coma. If symptoms of encephalopathy occur, diuretics should be discontinued immediately.

Water-electrolyte balance and metabolic disorders

Thiazide diuretics (including hydrochlorothiazide) can cause a decrease in the volume of circulating fluid (hypovolemia) and disturbances in water and electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis). Clinical symptoms of fluid and electrolyte imbalance are dry mouth, thirst, weakness, lethargy, fatigue, drowsiness, restlessness, muscle pain or cramps, muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, arrhythmia and gastrointestinal disorders (such as nausea and vomiting). In patients receiving hydrochlorothiazide therapy (especially with long-term course treatment), clinical symptoms of fluid and electrolyte imbalance should be identified and blood electrolyte levels should be regularly monitored.

Sodium

All diuretics can cause hyponatremia, sometimes leading to severe complications. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. A concomitant decrease in chlorine ions can lead to secondary compensatory metabolic alkalosis, but the frequency and severity of this effect are insignificant. It is recommended to determine the content of sodium ions in the blood plasma before starting treatment and regularly monitor this indicator while taking hydrochlorothiazide.

Potassium

When using thiazide and thiazide-like diuretics, there is a risk of a sharp decrease in the potassium content in the blood plasma and the development of hypokalemia (potassium concentration less than 3.4 mmol/l). Hypokalemia increases the risk of developing heart rhythm disturbances (including severe arrhythmias) and enhances the toxic effect of cardiac glycosides. In addition, hypokalemia (as well as bradycardia) is a condition that contributes to the development of polymorphic ventricular tachycardia of the “pirouette” type, which can be fatal.

Hypokalemia poses the greatest danger to the following groups of patients: elderly people, patients simultaneously receiving therapy with antiarrhythmic and non-antiarrhythmic drugs that can cause polymorphic ventricular tachycardia of the "pirouette" type or increase the duration of the QT interval on the ECG, patients with impaired liver function, coronary heart disease , chronic heart failure. In addition, patients with an increased QT interval are at increased risk. It does not matter whether this increase is caused by congenital causes or the effect of drugs. In all the cases described above, it is necessary to avoid the risk of developing hypokalemia and regularly monitor the potassium content in the blood plasma. The first measurement of the content of potassium ions in the blood must be carried out within the first week from the start of treatment. If hypokalemia occurs, appropriate treatment should be prescribed. Hypokalemia can be corrected by using potassium-containing medications or eating foods rich in potassium (dried fruits, fruits, vegetables).

Calcium

Thiazide diuretics may reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in plasma calcium levels. In some patients, with long-term use of thiazide diuretics, pathological changes in the parathyroid glands were observed with hypercalcemia and hyperphosphatemia, but without the typical complications of hyperparathyroidism (nephrolithiasis, decreased bone mineral density, peptic ulcer). Severe hypercalcemia may be a manifestation of previously undiagnosed hyperparathyroidism. Because of their effect on calcium metabolism, thiazides may interfere with laboratory parameters of parathyroid function. Thiazide diuretics (including hydrochlorothiazide) should be discontinued before testing parathyroid function.

Magnesium

Thiazides have been found to increase renal excretion of magnesium, which can lead to hypomagnesemia. The clinical significance of hypomagnesemia remains unclear.

Glucose

Treatment with thiazide diuretics may impair glucose tolerance. When using hydrochlorothiazide in patients with manifest or latent diabetes mellitus, it is necessary to regularly monitor the concentration of glucose in the blood. Dosage adjustment of hypoglycemic medications may be required.

Uric acid

In patients with gout, the frequency of attacks may increase or the course of gout may worsen. Careful monitoring of patients with gout and impaired uric acid metabolism (hyperuricemia) is necessary.

Lipids

When using hydrochlorothiazide, the concentration of cholesterol and triglycerides in the blood plasma may increase.

Choroidal effusion, acute myopia and secondary angle-closure glaucoma

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction resulting in choroidal effusion with visual field defects, acute transient myopia, and acute angle-closure glaucoma. Symptoms include: sudden loss of visual acuity or eye pain, usually occurring within hours to weeks of starting hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to irreversible vision loss. If symptoms appear, you should stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, emergency medical treatment or surgery may be required. Risk factors for the development of acute angle-closure glaucoma are a history of allergic reactions to sulfonamides or penicillin.

Immune system disorders

There are reports that thiazide diuretics (including hydrochlorothiazide) may cause exacerbation or progression of systemic lupus erythematosus, as well as lupus-like reactions. In patients receiving thiazide diuretics, hypersensitivity reactions may occur even in the absence of a history of allergic reactions or bronchial asthma.

Photosensitivity

There is information about cases of the development of photosensitivity reactions when taking thiazide diuretics. If photosensitivity occurs while taking hydrochlorothiazide, treatment should be discontinued. If continued use of the diuretic is necessary, the skin should be protected from exposure to sunlight or artificial ultraviolet rays.

Non-melanoma skin cancer

Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide use and an increased risk of non-melanoma skin cancer (NMSC) basal cell carcinoma and squamous cell carcinoma. The risk of developing NMSC increased with increasing total (cumulative) dose of hydrochlorothiazide. A possible mechanism for the development of NMSC is the photosensitizing effect of hydrochlorothiazide.

Patients taking hydrochlorothiazide as monotherapy or in combination with other drugs should be aware of the risk of developing NMSC.

It is recommended that such patients undergo regular skin examination to identify any new suspicious lesions as well as changes in existing skin lesions.

Any suspicious skin changes should be reported to your doctor immediately. Suspicious areas of skin should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.

To minimize the risk of developing NMSC, patients should be advised to follow preventive measures, such as limiting exposure to sunlight and UV rays, and using appropriate protective equipment. In patients with a history of non-melanoma skin cancer, it is recommended to reconsider the use of hydrochlorothiazide.

Alcohol

During the treatment period, it is not recommended to drink alcoholic beverages, because ethanol enhances the antihypertensive effect of thiazide diuretics.

Doping control

Hydrochlorothiazide may give a positive result during doping control in athletes.

Other

In patients with severe atherosclerosis of the cerebral and coronary arteries, hydrochlorothiazide should be used with extreme caution.

Thiazide diuretics can reduce the amount of iodine bound to plasma proteins without causing signs of thyroid dysfunction

TELMISARTAN

Conditions that increase the activity of the RAAS

In some patients, due to suppression of the activity of the RAAS, especially with the simultaneous administration of drugs acting on this system, renal function is impaired (including acute renal failure). Therefore, therapy accompanied by such a double blockade of the RAAS (for example, by adding an angiotensin-converting enzyme inhibitor (ACEI) or a direct renin inhibitor - aliskiren to angiotensin II receptor antagonists) should be carried out strictly individually and with regular monitoring of renal function, including periodic monitoring of blood levels potassium and creatinine in the blood serum (see section “Contraindications”).

The simultaneous use of angiotensin II receptor antagonists with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients. Concomitant use of angiotensin II receptor antagonists with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see section "Contraindications").

Renovascular hypertension

In patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney, the use of drugs that affect the RAAS increases the risk of developing severe arterial hypotension and renal failure.

Liver dysfunction

In patients with impaired liver function or progressive liver diseases, MicardisPlus® should be used with caution, since even slight changes in the water and electrolyte balance can contribute to the development of hepatic coma.

Diabetes

In patients with diabetes mellitus and an additional cardiovascular risk, for example, in patients with diabetes mellitus and coronary artery disease (CAD), when using drugs that lower blood pressure, such as angiotensin II receptor antagonists (ARA II) or ACE inhibitors, The risk of fatal myocardial infarction and sudden cardiovascular death may be increased. In patients with diabetes mellitus, CAD may be asymptomatic and therefore may be undiagnosed. In patients with diabetes mellitus, before starting the use of MicardisPlus®, appropriate diagnostic studies, including an exercise test, should be carried out to identify and treat coronary artery disease.

Acute myopia and secondary angle-closure glaucoma

Hydrochlorothiazide, being a sulfonamide derivative, can cause an idiosyncratic reaction in the form of acute transient myopia and acute angle-closure glaucoma. Symptoms of these disorders include a sudden decrease in visual acuity or eye pain, which typically occurs within a few hours to several weeks after starting to use the drug. If left untreated, acute angle-closure glaucoma can lead to vision loss. The main treatment is to discontinue hydrochlorothiazide as quickly as possible. It is important to keep in mind that if intraocular pressure remains uncontrolled, emergency medical or surgical treatment may be required. Risk factors for the development of acute angle-closure glaucoma include a history of allergies to sulfonamides or penicillin.

In patients with coronary heart disease, the use of any antihypertensive drug, in case of excessive reduction in blood pressure, can lead to myocardial infarction or stroke.

Liver dysfunction when prescribed telmisartan was observed in most cases in Japanese residents.

MicardisPlus® is less effective in patients of the Black race.

Contraindications

The drug has the following contraindications:

obstruction of the biliary tract;
severe liver or kidney dysfunction;
refractory hypercalcemia, hypokalemia ;
fructose intolerance ;
lactase deficiency galactose or lactose intolerance ;
age less than 18 years;
lactation;
pregnancy;
allergy to the components of the drug.

Carefully:

stenosis of both renal arteries, severe kidney damage;
liver dysfunction or progressive liver damage;
hyperkalemia;
hypovolemia after treatment with diuretics , as well as after limiting salt intake, vomiting or diarrhea ;
chronic heart failure , functional class III-IV;
mitral and aortic valve ;
condition after kidney transplant;
obstructive cardiomyopathy;
primary aldosteronism ;
diabetes;
gout.

Micardis plus overdose, symptoms and treatment

There are no definitive data regarding overdose associated with the use of Micardisplus. Monitoring of vital functions, supportive and symptomatic therapy should be carried out. The therapy performed depends on the time of taking the pill and the severity of the symptoms: it is recommended to induce vomiting and rinse the stomach. It is necessary to prescribe activated carbon. Monitor the level of electrolytes and creatinine in the blood serum. If hypotension occurs, the patient should be placed in a horizontal position and given an infusion of saline and plasma-substituting solutions. The most likely manifestations of a telmisartan overdose are hypotension and tachy- or bradycardia. An overdose of hydrochlorothiazide is accompanied by dehydration, a decrease in electrolytes (hypokalemia, hypochloremia) and symptoms of dehydration due to excessive diuresis. The other most common symptoms of overdose are nausea and drowsiness. Hypokalemia can lead to muscle spasms or arrhythmias when taking digitalis glycosides or certain antiarrhythmic drugs. Telmisartan is not excreted during hemodialysis. The extent of hydrochlorothiazide elimination during hemodialysis has not been established.

Side effects

From the respiratory system: shortness of breath, respiratory distress syndrome .
From the circulatory system: tachycardia , arrhythmias , bradycardia , severe decrease in blood pressure.
From the nervous system: fainting, paresthesia , dizziness, insomnia , anxiety, depression , excitability, headache.
From the digestive system: flatulence, diarrhea, dry mouth, abdominal pain, constipation, gastritis, hypercholesterolemia, hyperglycemia, pancreatitis, jaundice, dyspepsia.
Skin: sweating.
From the musculoskeletal system: muscle spasms, arthralgia , myalgia , arthrosis , chest pain.
From the hematopoietic system: leukopenia, eosinophilia, anemia, neutropenia, thrombocytopenia, thrombocytopenia.
From the genitourinary system: renal failure, nephritis, glucosuria.
From the eyes: visual impairment, glaucoma, xanthopsia, acute myopia .
Infections: sepsis , respiratory tract infections ( pharyngitis, bronchitis, sinusitis ), inflammation of the salivary glands.
Metabolic disorders: increased creatinine, liver enzymes, creatine phosphokinase, uric acid in the blood, hypertriglyceridemia, hyperkalemia, hypokalemia, hypoglycemia, hyponatremia, decreased hemoglobin .
Allergic reactions : skin itching, angioedema , rash, erythema , anaphylactic reactions , eczema, systemic vasculitis, necrotizing vasculitis .

Side effects of Micardis plus

Most side effects are not dose-related and are not related to the gender, age, or race of patients. The following adverse reactions were identified in clinical trials of the combination of telmisartan and hydrochlorothiazide. Adverse reactions not observed in clinical trials, but expected during treatment with Micardisplus, are based on experience with the use of telmisartan or hydrochlorothiazide as monotherapy. They are designated as follows: 1) side effects can be expected taking into account the experience of using telmisartan as monotherapy; 2) a side effect can be expected taking into account the experience of using hydrochlorothiazide as monotherapy. Infections and infestations: bronchitis, pharyngitis, sinusitis, upper respiratory tract infections, genitourinary tract infections, sialadenitis2). From the hematopoietic and lymphatic systems: eosinophilia1), anemia (including aplastic2), hemolytic)2), myelosuppression2), leukopenia2), neutropenia/agranulocytosis2), thrombocytopenia1), 2). From the immune system: allergies, anaphylactic reactions2). Endocrine disorders: decompensation of diabetes mellitus. Metabolic disorders: hypercholesterolemia, hyperuricemia, hypokalemia1), body dehydration2), electrolyte imbalance2), hyponatremia2), anorexia2) loss of appetite 2), hyperglycemia2). Mental disorders: anxiety, depression1), 2), anxiety. Neurological disorders: dizziness, syncope/impaired consciousness1), insomnia1), paresthesia2), sleep disorders 2). Visual impairment: visual impairment1), transient blurred vision2), xanthopsia2). Vestibular disorders: dizziness. From the cardiovascular system: bradycardia1), tachycardia1), arrhythmia 2), hypotension1), postural hypotension2), necrotizing vasculitis2). Respiratory disorders: dyspnea1), respiratory distress syndrome (includes pneumonitis or pulmonary edema)2). Gastrointestinal disorders: abdominal pain, diarrhea, dyspepsia, gastritis, dry mouth1), flatulence1), vomiting1), constipation2), pancreatitis2). Hepatobiliary disorders: impaired liver function1), jaundice (hepatocellular or cholestatic)2). On the part of the skin: eczema, increased sweating1), erythema1), itching1), skin reactions resembling systemic lupus erythematosus2), vasculitis2), photosensitivity2), skin rash 2), exacerbation of systemic lupus erythematosus2), toxic epidermal necrolysis2). From the musculoskeletal system: arthralgia, arthrosis, back pain, leg pain, myalgia, calf muscle cramps1), tendinitis-like symptoms1), weakness1),2), muscle cramps2). From the urinary system: interstitial nephritis2), impaired renal function2), glycosuria2), renal failure, including acute renal failure 1), see PECULIARITIES OF APPLICATION). Sexual disorders: impotence. General disorders: flu-like symptoms, chest pain1), fever2). Changes in laboratory parameters: decreased hemoglobin level1), increased level of uric acid1), creatinine1), activity of liver enzymes1), TG2), level of CPK in blood serum1). As with the use of other angiotensin II antagonists, isolated cases of angioedema, urticaria and other similar reactions have been reported.

Interaction

When using telmisartan with:

other antihypertensive drugs – it is possible to increase the strength of the antihypertensive effect ;
lithium preparations – a temporary increase in lithium in the blood is possible;
non-steroidal anti-inflammatory drugs acute renal failure may occur in patients with a reduced volume of circulating blood;
digoxin – it is possible to increase the concentration of digoxin in the blood by 20%.

When using hydrochlorothiazide with:

barbiturates, ethanol or opioid orthostatic hypotension may develop ;
Metformin – possible development of lactic acidosis ;
hypoglycemic agents and insulin - dose adjustment of hypoglycemic drugs ;
cholestyramine and colestipol - possible inhibition of hydrochlorothiazide ;
non-depolarizing muscle relaxants – their effect may be enhanced;
cardiac glycosides – possible development of hypokalemia or hypomagnesemia ;
anti-gout medications – it is possible to increase the level of uric acid in the blood.
calcium preparations – it is possible to increase the concentration of calcium in the blood due to inhibition of its excretion by the kidneys.
amantadine – there may be an increased risk of developing undesirable effects of amantadine ;
m-anticholinergic blockers ( atropine , biperiden ) – possible weakening of intestinal motility, increasing the bioavailability of thiazide diuretics ;
non-steroidal anti-inflammatory drugs - may weaken the diuretic and antihypertensive effects .

Pharmacological properties of the drug Mikardis plus

Pharmacodynamics. Micardisplus is a combination of the angiotensin II receptor antagonist (type AT1) telmisartan and the thiazide diuretic hydrochlorothiazide. The combination of these ingredients provides additional antihypertensive effect. Micardisplus, prescribed once daily, effectively and slowly reduces blood pressure when used in therapeutic doses. Telmisartan is a specific angiotensin II receptor antagonist that selectively and with a high degree of affinity replaces angiotensin II at its binding sites on the AT1 receptors, which are responsible for the physiological effects of angiotensin II. Telmisartan does not have partial agonist activity at these receptors. The binding to receptors is long lasting. Telmisartan does not show affinity for other receptors, including AT2 and other less common AT receptors. The functional role of these receptors is unknown, as is the effect of possible overstimulation by angiotensin II, the level of which increases under the influence of telmisartan. Telmisartan and renin in the blood serum do not block ion channels, nor do they inhibit ACE (kinase II), an enzyme that destroys bradykinin. Therefore, there is no potentiation of bradykinin-associated side effects. When telmisartan is prescribed at a dose of 80 mg, the hypotensive effect persists for 24 hours and remains significant up to 48 hours. After taking the first dose of telmisartan, the antihypertensive effect develops gradually over 3 hours. The maximum reduction in blood pressure is observed 4–8 weeks after the start of treatment, and persists with long-term treatment. Measuring blood pressure over time showed that the antihypertensive effect is constant for 24 hours after dosing, including the last 4 hours before the next dose. In patients with hypertension (arterial hypertension), telmisartan reduces both systolic and diastolic blood pressure without affecting heart rate. If treatment with telmisartan is suddenly discontinued, blood pressure gradually returns to its original level over several days without the development of withdrawal symptoms. Telmisartan is less likely to cause a dry cough than ACE inhibitors. Hydrochlorothiazide is a thiazide diuretic. The mechanism of action of thiazide diuretics is still unknown. Thiazides affect the renal tubular process of tubular reabsorption of electrolytes, thereby increasing the excretion of sodium and chloride ions in approximately equivalent volumes. The diuretic effect leads to a decrease in blood volume, an increase in renin activity in the blood plasma, an increase in the secretion of aldosterone, an increase in the release of potassium and bicarbonate, and a decrease in the level of potassium in the blood serum. It is likely that by blocking the renin-angiotensin-aldosterone system, coadministration of telmisartan contributes to the potassium loss associated with these diuretics. When using hydrochlorothiazide, an increase in diuresis is noted after 2 hours, the maximum effect is achieved after approximately 4 hours, the effect lasts about 6-12 hours. Epidemiological studies have found that long-term therapy with hydrochlorothiazide reduces the risk of cardiovascular morbidity and mortality. Pharmacokinetics. The simultaneous use of hydrochlorothiazide and telmisartan affects their pharmacokinetics. Suction. Telmisartan. After oral administration, the maximum concentration of telmisartan is reached after 0.5–1.5 hours. The absolute bioavailability when taken at a dose of 40 and 160 mg is 42 and 58%, respectively. Food slightly reduces the bioavailability of telmisartan, the decrease in AUC value ranges from 6% (taken at a dose of 40 mg) to 19% (taken at a dose of 160 mg). 3 hours after application, the concentration in the blood plasma is the same and does not depend on simultaneous food intake. A slight decrease in AUC does not cause a decrease in therapeutic efficacy. The pharmacokinetics of oral telmisartan are nonlinear as the dose is increased from 20 to 160 mg, with greater than proportional increases in maximum concentration and plasma AUC. Telmisartan does not accumulate in the blood plasma to a significant extent with repeated use. Hydrochlorothiazide. After oral administration of the drug, the maximum concentration of hydrochlorothiazide in the blood serum is achieved after 1–3 hours. Taking into account the total renal excretion of hydrochlorothiazide, the absolute bioavailability is about 60%. Distribution. Telmisartan. Telmisartan is highly bound to plasma proteins (99.5%), mainly to albumin and acidic α1-glycoprotein. The distribution volume is approximately 500 l. Hydrochlorothiazide. About 64% of hydrochlorothiazide is bound to plasma proteins, the volume of distribution is 0.8±0.3 l/kg. Biotransformation and excretion. Telmisartan. Following oral administration of 14C-labeled telmisartan, the majority of the dose (97%) is excreted in the feces by biliary excretion; excreted in urine in small quantities. Telmisartan is metabolized in the liver by conjugation to form a pharmacologically inactive acyl glucuronide. The glucuronide of the parent compound is the only metabolite identified in humans. Following a single dose of 14C-labeled telmisartan, glucuronide accounts for approximately 11% of the measured radioactivity in plasma. Cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan. The total clearance of telmisartan after oral administration is 1500 ml/min. The half-life is 20 hours. Hydrochlorothiazide. It is not metabolized and is excreted almost completely unchanged in the urine; about 60% of an orally administered dose is eliminated unchanged within 48 hours. Renal clearance is 250–300 ml/min. The terminal half-life is 10–15 hours. Special categories of patients Thiazides should be prescribed with caution to patients with impaired liver function. The pharmacokinetics of telmisartan do not differ between elderly patients (over 65 years of age) and younger patients. Floor. The concentration of telmisartan in the blood plasma in women is 2-3 times higher than in men, but there was no significant increase in the incidence of orthostatic hypotension in women. There is no need for dose adjustment in women; they tend to have higher concentrations of hydrochlorothiazide than men, which has no clinical significance. Patients with impaired renal function. There is no need for dose adjustment in patients with moderately severe renal impairment (creatinine clearance 30–60 ml/min, average about 50 ml/min). Telmisartan is not eliminated during hemodialysis. In patients with renal failure, the rate of elimination of hydrochlorothiazide is reduced. In patients with an average creatinine clearance of 90 ml/min, the half-life of hydrochlorothiazide is increased. In patients with a removed or absent kidney, the half-life is about 34 hours. Patients with impaired liver function. Pharmacokinetic studies in patients with impaired liver function revealed an increase in absolute bioavailability to approximately 100%, while the half-life did not change.

special instructions

In patients with coronary heart disease, the use of any blood pressure-lowering drug, in case of a strong decrease in pressure, can lead to the development of myocardial or cerebral infarction.

Micardis Plus has a weaker therapeutic effect in people of the Negroid race.

When driving vehicles, you should be aware of the possibility of dizziness and drowsiness after taking the drug.

Special instructions for the use of Micardis plus

During pregnancy and breastfeeding. Preclinical studies of telmisartan did not reveal a teratogenic effect, but demonstrated the presence of fetotoxic effects. The drug should not be used during pregnancy. Before planning a pregnancy, it is necessary to switch to appropriate alternative treatment. In the second and third trimester of pregnancy, drugs that affect the renin-angiotensin-aldosterone system can cause damage and even death of the fetus. If pregnancy is diagnosed, the drug should be stopped immediately. Thiazides penetrate the placental barrier and enter the umbilical cord blood. They can cause electrolyte disturbances in the fetus and other side effects that occur in adults. When using thiazides, cases of neonatal thrombocytopenia, fetal or neonatal jaundice have been described. Micardisplus is contraindicated during breastfeeding as it is not known whether it is excreted in breast milk. Thiazides are excreted in breast milk and can inhibit lactation. Micardisplus should not be administered to patients with cholestasis, biliary obstructive disorders or severe liver failure, as telmisartan is excreted primarily in the bile. In these patients, a decrease in the hepatic clearance of telmisartan can be expected. Micardisplus should be used with caution when treating patients with impaired liver function or progressive liver disease, since minor changes in fluid and electrolyte balance may lead to the development of hepatic coma. There is no clinical experience with the use of Micardisplus for the treatment of patients with liver failure. AH (arterial hypertension). There is an increased risk of severe hypotension and renal failure in patients with bilateral renal artery stenosis or solitary renal artery stenosis. Kidney failure and kidney transplantation. The drug should not be prescribed to patients with severe renal failure (creatinine clearance ≤30 ml/min) (see CONTRAINDICATIONS). There is no experience with the drug in patients with severe renal failure or a recently transplanted kidney. There is limited experience with the use of the drug for the treatment of patients with mild and moderate renal failure, therefore it is recommended to periodically monitor the levels of potassium, creatinine and uric acid in the blood serum. In patients with impaired renal function, azotemia may occur due to thiazide diuretics. Decreased intravascular fluid volume. Symptomatic hypotension, especially after the first dose, may occur in patients with dehydration and/or hyponatremia caused by prolonged diuretic therapy, salt restriction in the diet, diarrhea or vomiting. Before prescribing the drug, correction of these conditions should be carried out. Other conditions requiring stimulation of the renin-angiotensin-aldosterone system. In patients with vascular tone and renal function that depend primarily on the activity of the renin-angiotensin-aldosterone system (for example, in patients with congestive heart failure or severe renal pathology, including renal artery stenosis), taking drugs that affect the renin-angiotensin-aldosterone system the system can cause severe hypotension, hyperazotemia, oliguria, and rarely, acute renal failure. Primary hyperaldosteronism. The effectiveness of antihypertensive drugs that block the renin-angiotensin-aldosterone system in patients with primary hyperaldosteronism is low, so the use of Micardisplus in this situation is not recommended. Stenosis of the aorta and mitral valve, obstructive hypertrophic cardiomyopathy. Particular care should be taken when treating patients with aortic and mitral valve stenosis, as well as hypertrophic obstructive cardiomyopathy. Metabolic and endocrine effects. Thiazide therapy may decrease glucose tolerance. In patients with diabetes mellitus, it may be necessary to adjust the dose of insulin or oral hypoglycemic agents. When using thiazides, latent diabetes mellitus may occur. The use of thiazides may be accompanied by an increase in the level of cholesterol and TG in the blood serum, however, when using Micardisplus, containing 12.5 mg of hydrochlorothiazide, this effect is minimal or absent. Hyperuricemia or gout may occur in some patients receiving thiazide therapy. Electrolyte imbalance. All patients receiving diuretic therapy should have serum electrolyte levels periodically determined. Thiazides, including hydrochlorothiazide, can cause disturbances in water-salt balance (hypokalemia, hyponatremia and hypochloraemic alkalosis). Signs of water-salt imbalance are dry mouth, thirst, weakness, lethargy, drowsiness, anxiety, myalgia or cramps, muscle weakness, hypotension, oliguria, tachycardia, nausea and vomiting. Although hypokalemia may occur with the use of thiazide diuretics, concomitant therapy with telmisartan may reduce diuretic-induced hypokalemia. The risk of hypokalemia is higher in patients with liver cirrhosis, in patients with significant diuresis, with inadequate oral intake of electrolytes, and in patients receiving corticosteroids or ACTH therapy. In turn, due to the angiotensin II (AT1) receptor antagonism caused by telmisartan, hyperkalemia may occur. When using the drug, the development of hyperkalemia is possible, the risk factors for which are renal and heart failure, diabetes mellitus, but clinically significant hyperkalemia due to taking Micardisplus has not been documented. Potassium-sparing diuretics, potassium supplements, or potassium-based salt substitutes should be used with caution concomitantly with Micardisplus. There is no evidence that Micardisplus will reduce or prevent diuretic-induced hyponatremia. Chlorine deficiency when using the drug is usually mild and does not require correction. Thiazides can reduce calcium excretion and cause the development of mild hypercalcemia in the absence of a previous disorder of calcium metabolism. Significant hypercalcemia may be a sign of latent hyperparathyroidism. You should stop taking the drug before testing the function of the parathyroid glands. Thiazides can cause an increase in the excretion of magnesium in the urine, which can lead to the development of hypomagnesemia. Sorbitol. The recommended daily dose of Micardisplus 40/12.5 mg and Micardisplus 80/12.5 mg tablets contains 169 and 338 mg of sorbitol, respectively, so the drug should not be prescribed to patients with hereditary fructose intolerance. Other. Just as with the use of any other antihypertensive drug, a significant decrease in blood pressure in patients with coronary artery disease can lead to the development of myocardial infarction or stroke. General violations. The likelihood of hypersensitivity reactions to hydrochlorothiazide is higher in patients with allergic reactions and a history of asthma. When using thiazide diuretics, exacerbation of systemic lupus erythematosus is noted. Studies of the effect of telmisartan on the ability to drive vehicles and operate machinery have not been conducted. However, when driving vehicles and working with potentially dangerous mechanisms, the possibility of dizziness or drowsiness should be taken into account.

Analogues of Mikardis Plus

Level 4 ATX code matches:
Diokor

Gizaar

Teveten Plus

Atacand Plus

Co Diovan

Vazar N

Valz N

The following analogues of the drug are known: Atakand Plus , Valzap Plus , Valsacor , Gizaar Forte , Co-Diovan , Teveten Plus and others.

Price Mikardis Plus

In Ukraine, the price of the drug in a dosage of 80 mg/12.5 mg No. 28 averages 450 hryvnia; in Russia, such a package will cost 855-1000 rubles.

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ZdravCity

Mikardis Plus tablets 80 mg + 12.5 mg 28 pcs. Boehringer Ingelheim
RUB 1,147 order

Pharmacy Dialogue

Mikardis plus (tab. 80 mg/12.5 mg No. 28)Boehringer Ingelheim
1104 rub. order
Mikardis plus (tab. 80 mg/12.5 mg No. 28)Boehringer Ingelheim
1115 rub. order