Micafor, tablets 12.5mg+80 mg 28 pcs

Pharmacotherapeutic group: Hypotensive drug combined (diuretic + angiotensin II receptor antagonist).

ATX code:C09DA07

Pharmacological properties

Pharmacodynamics

The efficacy of the combined drug is greater than that of its individual components.

Mechanism of action

The drug MIKAFOR is a combination of hydrochlorothiazide (thiazide diuretic) and telmisartan (angiotensin II receptor antagonist). Simultaneous use of these components leads to a more pronounced antihypertensive effect than the use of each of them separately.

The administration of MIKAFOR once daily leads to a significant gradual decrease in blood pressure (BP).

The maximum antihypertensive effect of MIKAFOR is usually achieved 4 weeks after the start of treatment.

Hydrochlorothiazide

The mechanism of action of thiazide diuretics (thiazides) is not fully understood. Thiazides block reabsorption of sodium and chlorine ions at the beginning of the renal tubules. Thus, they increase the excretion of sodium and chlorine ions and therefore the excretion of water from the body.

The diuretic effect of hydrochlorothiazide decreases the volume of circulating fluid, resulting in increased renin activity and plasma aldosterone content. This leads to increased urinary excretion of potassium ions and decreased content of potassium ions in blood (hypokalemia). Hydrochlorothiazide also increases the excretion of magnesium ions and decreases the excretion of calcium ions in the urine. Thiazide diuretics decrease renal excretion of uric acid and increase its content in blood.

Thiazide diuretics also reduce carboangiradase activity by increasing the excretion of bicarbonate ions. But this effect is usually weak and has no effect on urine pH.

In the maximum therapeutic doses, the diuretic/natriuretic effect of all thiazide diuretics is approximately the same. Sodiumureas and diuresis occur within 2 hours and reach their maximum after about 4 hours. Duration of diuretic action of hydrochlorothiazide is 6 to 12 hours.

Hydrochlorothiazide has an antihypertensive effect. Normal blood pressure is not affected by thiazide diuretics.

Telmisartan

Telmisartan is a specific angiotensin II receptor antagonist (subtype AT1) effective when taken orally. It has high affinity for subtype AT1 of angiotensin II receptors, through which the action of angiotensin II is realized. It displaces angiotensin II P from binding to the receptor without exhibiting agonist properties against this receptor. Telmisartan binds only to the AT1 subtype of the angiotensin II receptor. The binding is long-lasting. It has no affinity for other receptors, including AT2 receptor and other less studied angiotensin receptors. The functional significance of these receptors, as well as the effect of their possible overstimulation by angiotensin II, the concentration of which increases when telmisartan is administered, has not been studied. Telmisartan reduces blood aldosterone concentration, does not inhibit plasma renin and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kinininase II) (an enzyme that also degrades bradykinin). Therefore, an increase in bradykinin-induced side effects is not expected.

In patients with arterial hypertension, telmisartan at a dose of 80 mg completely blocks the hypertensive effects of angiotensin P. The onset of antihypertensive action is noted within 3 hours after the first oral dose of telmisartan. The action of the drug persists for 24 hours and remains significant up to 48 hours. A pronounced antihypertensive effect usually develops 4 weeks after regular use.

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

In case of abrupt telmisartan withdrawal, BP gradually returns to baseline without development of “withdrawal” syndrome.

The study with telmisartan evaluated cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for chronic heart failure. Cardiovascular morbidity and mortality have been shown to decrease in patients at high cardiovascular risk (with coronary artery disease, stroke, peripheral artery disease, or diabetes with concomitant target organ damage such as retinopathy, left ventricular hypertrophy, and a history of macro- or microalbuminuria) over the age of 55.

Pharmacokinetics

The co-administration of telmisartan and hydrochlorothiazide has no effect on the pharmacokinetics of either drug component.

Hydrochlorothiazide

absorption and distribution

Hydrochlorothiazide is incompletely but fairly rapidly absorbed from the gastrointestinal tract. After oral administration at a dose of 100 mg, the maximum concentration of hydrochlorothiazide in blood plasma is reached after 1.5 – 2.5 hours. At the maximum of diuretic activity (about 4 hours after intake), the plasma concentration of hydrochlorothiazide is 2 µg/ml. The binding to plasma proteins is 40%.

Hydrochlorothiazide penetrates the placental barrier and is excreted into the breast milk, it does not penetrate the blood-brain barrier.

Metabolism

Hydrochlorothiazide is not metabolized in humans.

Evolution

The primary route of excretion is through the kidneys (filtration and secretion) in unchanged form. Approximately 61% of the ingested dose is excreted within 24 hours. In patients with normal renal function, the elimination half-life ranges from 5.6 to 14.8 hours (6.4 hours on average).

Pharmacokinetics in special patient groups

Disordered renal function

In patients with moderate renal impairment, the half-life of hydrochlorothiazide averages 11.5 hours, and 20.7 hours in patients with creatinine clearance less than 30 mL/min.

Telmisartan
absorption

. Telmisartan reaches maximum concentrations in 0.5 to 1.5 hours when taken orally. Absolute bioavailability at doses of 40 mg and 160 mg was 42% and 58%, respectively. Decrease of area under curve “concentration-time” (AUC) while taking simultaneously with food varies from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). Three hours after oral administration, plasma concentrations become similar to those of fasting telmisartan.

A slight decrease in AUC is expected to decrease therapeutic efficacy. The pharmacokinetics of telmisartan when administered orally are not linear over a dose range of 20 to 160 mg with a more than proportional increase in plasma concentrations (Cmax and AUC) as the dose increases. Telmisartan does not significantly accumulate in plasma on repeated use.

Distribution

Telmisartan is largely bound to plasma proteins (> 99.5%), primarily to albumin and alpha1-acid glycoprotein. The apparent volume of distribution of telmisartan is approximately 500 liters, indicating additional binding of the drug in tissues.

Metabolism and excretion

After intravenous or oral administration of ”C-labeled telmisartan, most of the administered dose (> 97%) was excreted with feces via excretion with bile. Only a small amount of the substance was detected in the urine.

Telmisartan is metabolized by conjugation to form the pharmacologically inactive acyl glucuronide. The glucuronide of the parent compound is the only metabolite that has been identified in humans.

On a single administration of ¹⁴C-labeled telmisartan, glucuronide accounts for approximately 11% of the measured plasma radioactivity. Cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan. Total plasma clearance of telmisartan after oral administration is > 1500 ml/min. The terminal elimination half-life was > 20 hours.

Pharmacokinetics in special patient groups

Elderly age

The pharmacokinetics of telmisartan in elderly patients does not differ from the pharmacokinetics in patients younger than 65 years of age.

Gender

The plasma concentrations of telmisartan are generally 2-3 times higher in women than in men. However, no statistically significant increase in blood pressure response or incidence of orthostatic hypotension has been observed in women in clinical studies. No dose adjustment is required. Higher plasma concentrations of hydrochlorothiazide have been observed in women than in men. These differences are not considered clinically significant.

Renal function impairment

Renal excretion does not affect telmisartan clearance. Based on experience with the drug in patients with mild to moderate renal impairment (creatinine clearance 30-60 ml/min, mean approximately 50 ml/min), no dose adjustment is required in patients with impaired renal function. Telmisartan is not excreted with hemodialysis.

Hepatic impairment

Pharmacokinetic studies conducted in patients with hepatic impairment have shown that the absolute bioavailability of telmisartan is increased to almost 100%. In patients with hepatic impairment the T _1/2 (elimination half-life) is not altered.

Indications

Active ingredient

Composition

How to take, the dosage

Ingestion, regardless of meals

MIKAFOR should be taken once daily.

In patients with severe arterial hypertension, the maximum daily dose of telmisartan 160 mg in combination with hydrochlorothiazide at a daily dose of 12.5-25 mg is effective and well tolerated.

The maximum daily dose of MIKAFOR is 2 tablets 12.5 mg + 80 mg once daily.

Renal dysfunction

In mild to moderate renal dysfunction (CKR over 30 ml/min) no change in the drug dose is required. Renal function should be monitored in these patients.

Hepatic impairment

In patients with mild to moderate hepatic impairment (Child-Pugh class A and B), the daily dose of the drug should not exceed 12.5 mg + 40 mg daily (see section on Pharmacokinetics).

Elderly patients

There is no need for dosing adjustment in elderly patients.

Interaction

Hydrochlorothiazide

.Unrecommended drug combinations

Lithium preparations

Concomitant use of hydrochlorothiazide and lithium preparations decreases renal clearance of lithium, which may increase plasma lithium concentrations and increase its toxicity. If simultaneous use of hydrochlorothiazide is necessary, the dose of lithium preparations should be carefully selected, plasma concentration of lithium should be monitored regularly, and the dose of the drug should be adjusted accordingly.

Drug combinationswhich require special attention

Drugs that

Special Instructions

The use of MIKAFOR in patients with acute myocardial infarction is not recommended due to insufficient experience in clinical use.

The drug MIKAFOR should not be used to control hypertensive crisis.

Hydrochlorotazide

Kidney function disorders.

In patients with impaired renal function, hydrochlorothiazide may cause azotemia. Cumulation of hydrochlorothiazide is possible in renal impairment.

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

Hepatic disorders

When using thiazide diuretics in patients with hepatic dysfunction, hepatic encephalopathy may develop. In patients with severe hepatic insufficiency or hepatic encephalopathy the use of thiazide diuretics is contraindicated. In patients with mild to moderate hepatic insufficiency and/or progressive liver disease, hydrochlorothiazide should be used with caution, since even a slight change of electrolyte-water balance and accumulation of ammonium in blood serum may cause hepatic coma. In case of symptoms of encephalopathy the use of diuretics should be stopped immediately.

Water-electrolyte balance and metabolic disorders

The thiazide diuretics (including hydrochlorothiazide) may cause decreased circulating fluid volume (hypovolemia) and water-electrolyte balance disorders (including hypoxia).hypokalemia, hyponatremia, hypochloremic alkalosis). Clinical symptoms of water-electrolyte balance disorders 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 prolonged course of treatment), clinical symptoms of water-electrolyte imbalance should be identified and blood electrolytes should be monitored regularly.

Natrium

All diuretics can cause hyponatremia, sometimes leading to severe complications. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. Concomitant decrease in chlorine ions may 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 plasma before the start of treatment and monitor this parameter regularly during hydrochlorothiazide therapy.

Kalium

When using thiazide and thiazide-like diuretics there is a risk of plasma potassium reduction and hypokalemia (potassium concentration less than 3.4 mmol/l). Hypokalemia increases the risk of cardiac rhythm disorders (including severe arrhythmias) and enhances the toxic effects of cardiac glycosides. In addition, hypokalemia (as well as bradycardia) is a condition contributing to the development of polymorphic ventricular tachycardia of the “pirouette” type, which can be fatal.

Hypokalemia is most dangerous for the following patient groups: elderly patients, patients receiving concurrent antiarrhythmic and non-antiarrhythmic drugs that may cause pirouette ventricular tachycardia or prolong QT interval on ECG, patients with liver dysfunction, ischemic heart disease, chronic heart failure. In addition, patients with prolonged QT interval are at high risk. It does not matter if the QT interval is prolonged due to congenital causes or due to medication.

In all of the above cases the risk of hypokalemia should be avoided and plasma potassium should be monitored regularly. The first measurement of blood potassium ions should be made within the first week of the start of treatment. If hypokalemia occurs, appropriate treatment should be prescribed. Hypokalemia may be corrected by use of potassium-containing preparations or intake of food products rich in potassium (dried fruits, vegetables).

Calcium

Thiazide diuretics may decrease renal excretion of calcium ions, leading to a slight and temporary increase in plasma calcium. In some patients with long-term use of thiazide diuretics pathological changes of parathyroid glands with hypercalcemia and hyperphosphatemia have been observed, but without the typical complications of hyperparathyroidism (nephrolithiasis, reduced bone mineral density, ulcer disease). Severe hypercalcemia may be a manifestation of previously undiagnosed hyperparathyroidism.

Because of their effect on calcium metabolism, thiazides may affect laboratory indicators of parathyroid gland function. Thiazide diuretics (including hydrochlorothiazide) should be discontinued before parathyroid function tests.

Magnesium

Thiazides have been found to increase magnesium excretion by the kidneys, which may lead to hypomagnesemia. The clinical significance of hypomagnesemia remains unclear.

Glucose

The treatment with thiazide diuretics may impair glucose tolerance. When using hydrochlorothiazide in patients with manifest or latent diabetes mellitus, blood glucose concentrations should be monitored regularly. Dose adjustment of hypoglycemic drugs may be required.

Ric acid

Patients with gout may have an increased frequency of attacks or worsen the course of gout. Close monitoring of patients with gout and impaired uric acid metabolism (hyperuricemia) is necessary.

Lipids

The use of hydrochlorothiazide may increase plasma cholesterol and triglyceride concentrations.

Acute myopia/secondary closed-angle glaucoma

Hydrochlorothiazide may cause an idiosyncratic reaction leading to the development of acute myopia and an acute onset of secondary closed-angle glaucoma. Symptoms include a sudden decrease in visual acuity or eye pain that usually occurs within hours to weeks of starting hydrochlorothiazide therapy.

If left untreated, acute angle-closure glaucoma can lead to permanent vision loss. If symptoms occur, hydrochlorothiazide should be stopped as soon as possible. If the intraocular pressure remains uncontrolled, emergency medication or surgery may be necessary. Risk factors for acute angle-closure glaucoma include a history of allergic reaction 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 if there is no history of allergic reactions or bronchial asthma.

Photosensitivity

There have been reports of photosensitivity reactions when taking thiazide diuretics. If photosensitivity occurs while taking hydrochlorothiazide, treatment should be discontinued. If continuation of the diuretic is necessary, the skin should be protected from sunlight or artificial ultraviolet rays.

Nemelanoma skin cancer (NSCLC)

. Two pharmacoepidemiologic studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide intake and an increased risk of nonmelanoma skin cancer (NSCLC) – basal cell carcinoma and squamous cell carcinoma. The risk of developing NSCLC increased with increasing total (cumulative) dose of hydrochlorothiazide. A possible mechanism for the development of NSCLC is the photosensitizing effect of hydrochlorothiazide.

Patients taking hydrochlorothiazide as monotherapy or in combination with other medications should be aware of the risk of NMRK. These patients are advised to have regular skin examinations to look for any new suspicious lesions, as well as changes to existing skin lesions.

All suspicious skin changes should be promptly reported to the physician. Suspicious skin areas should be examined by a specialist. Histological examination of skin biopsy specimens may be necessary to confirm the diagnosis.

Patients should be advised to use preventive measures such as limiting exposure to sunlight and UV rays and appropriate protective equipment to minimize the risk of developing SLE.

In patients with a history of NMRK, it is recommended that the appropriateness of hydrochlorothiazide be reconsidered.

Athletes

Hydrochlorothiazide may test positive in doping controls in athletes.

Other

Patients with significant atherosclerosis of the cerebral and coronary arteries should use preparations containing hydrochlorothiazide with extreme caution.

The thiazide diuretics may decrease the amount of iodine bound to plasma proteins without evidence of thyroid dysfunction.

Telmisartan

Liver function disorders

. The use of telmisartan is contraindicated in patients with cholestasis, biliary obstruction, or severe hepatic impairment (Child-Pugh class C) because telmisartan is mostly excreted with bile. It is assumed that hepatic clearance of telmisartan is reduced in such patients. Telmisartan should be used with caution in patients with mild to moderate hepatic impairment (Child-Pugh grades A and B).

Liver dysfunction with telmisartan has been observed in the majority of patients in Japan.

Kidney function impairment

In telmisartan use in patients with impaired renal function, periodic monitoring of plasma potassium and creatinine is recommended.

Kidney transplantation

There is no clinical experience with telmisartan in patients who have recently had a kidney transplant.

Renovascular Hypertension

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

Circulating blood volume (CBC)

Symptomatic arterial hypotension, especially after the first administration of telmisartan may occur in patients with decreased CBC and/or plasma sodium content on the background of previous diuretic treatment. Restricted intake of table salt, diarrhea or vomiting. Such conditions (fluid and/or sodium deficiency) should be eliminated before starting telmisartan.

Double blockade of the renin-angiotheisin-aldosterone system (RAAS)

As a result of RAAS suppression, there have been noted: Arterial hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal failure) in predisposed patients, especially when several drugs that also act on this system are used together. Therefore, dual RAAS blockade (e.g. against the background of telmisartan with other RAAS antagonists) is not recommended. If dual RAAS blockade is necessary, each case should be considered individually and renal function, electrolyte-water balance and blood pressure parameters should be monitored carefully.

The concomitant use of telmisartan with aliskiren or drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to severe renal impairment (FFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients.

The concomitant use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Other conditions associated with increased RAAS activity

In patients whose vascular tone and renal function are predominantly dependent on RAAS activity (e.g., patients with chronic heart failure or renal disease, including renal artery stenosis, or artery stenosis of the sole kidney), use of drugs affecting this system may be accompanied by the development of acute arterial hypotension, hyperazotemia, oliguria, and, in rare cases, acute renal failure.

Primary hyperaldosteronism

In patients with primary hyperaldosteronism, treatment with hypotensive drugs that work by inhibiting the RAAS is generally ineffective. Therefore, the use of drugs containing telmisartan is not recommended.

Aortic or mitral valve stenosis, hypertrophic obstructive cardiomyopathy

. As with other vasodilators, patients with aortic or mitral stenosis and hypertrophic obstructive cardiomyopathy should use telmisartan with extreme caution.

Patients with diabetes mellitus who have received oral insulin or hypoglycemic agents

Patients with diabetes mellitus. Patients with diabetes mellitus treated with insulin or oral hypoglycemic agents may develop hypoglycemia with telmisartan. Glycemic control should be strengthened, since it may be necessary to adjust the dose of insulin or hypoglycemic agent.

Diabetes mellitus

. Patients with diabetes and additional cardiovascular risk, such as those with diabetes and coronary heart disease (CHD), may have an increased risk of myocardial infarction and sudden cardiovascular death when using blood pressure-lowering drugs such as angiotensin II receptor antagonists (ARA II) or ACE inhibitors. In patients with diabetes mellitus, CHD may be asymptomatic and therefore undiagnosed. Therefore, in patients with diabetes mellitus, appropriate diagnostic tests, including exercise testing, should be performed before initiating use of the drug to detect and treat CHD.

Hyperkalemia

The administration of drugs acting on the RAAS may cause hyperkalemia. Hyperkalemia can be fatal in elderly patients, patients with renal insufficiency or diabetes, patients also taking drugs which increase plasma potassium and/or patients with comorbidities.

The risk-benefit ratio should be evaluated when deciding on concomitant use of drugs acting on the RAAS.

The main risk factors for hyperkalemia that should be considered are:

Patients at risk are advised to monitor plasma potassium carefully.

Ethnic differences

. As noted for ACE inhibitors, telmisartan and other ARAIIs appear to be less effective in reducing BP in non-Hispanic patients than in other races, possibly due to a greater predisposition to decrease renin activity in this patient population.

Other

As with other hypotensive medications, excessive BP reduction in patients with coronary heart disease can lead to myocardial infarction or stroke.

Do not drink alcoholic beverages while taking this medication because ethanol potentiates the antihypertensive effects of thiazide diuretics and ARA II.

The content of minimal carbohydrates allows MIKAFOR to be indicated in patients with diabetes.

Influence on driving, operating machinery

The possibility of dizziness and drowsiness must be taken into consideration when driving motor vehicles and engaging in potentially dangerous activities, which requires caution.

Synopsis

Contraindications

Side effects

Infectious and parasitic diseases:
Infrequent: upper respiratory tract infection1), urinary tract infection (including cystitis)1)
Rarely: Bronchitis, pharyngitis, sinusitis, sepsis, including cases with fatal outcome1)
Unknown: salivary gland inflammation2)
Blood and lymphatic system disorders:
Infrequent: anemia1)
Rare: thrombocytopenia (sometimes with purpura)1), eosinophilia1)
Unknown: Thrombocytopenia (sometimes with purpura)2), aplastic anemia2), hemolytic anemia2), suppression of bone marrow function2), leukopenia2), neutropenia/agranulocytosis2)
Immune system disorders:
Rarely: exacerbation or worsening of symptoms of systemic lupus erythematosus, anaphylactic reactions1), hypersensitivity1), allergy1)
Unknown: anaphylactic reactions2), hypersensitivity2), allergy2)
Endocrine system disorders:
Unknown: insufficient control of diabetes mellitus (impaired glucose tolerance)2)
Metabolic and nutritional disorders:
Infrequent: hypokalemia, hyperkalemia1)
Rarely: hyponatremia, hyperuricemia, hypoglycemia (in patients with diabetes)1)
Unknown: decreased OCC2), impaired electrolyte balance2), decreased appetite2), anorexia2), hyperglycemia2), hypercholesterolemia2), hypomagnesemia2), hypercalcemia2), hypochloremic alkalosis2)
Psychiatric disorders:
Infrequently: anxiety
Rarely: depression
Unknown: agitation2)
Nervous system disorders:
Infrequently: Dizziness, syncope/fainting spells, paresthesia
Rarely: sleep disturbances, insomnia
Unknown: dizziness2) headache2)
Visual disturbances:
Rare: visual disturbances, transient blurred vision
Unknown: xantopsia2), acute myopia2) acute closed-angle glaucoma2)
Hearing organ and labyrinth disturbances:
Infrequent: vertigo
Vascular disturbances:
Infrequent: Arrhythmias, tachycardia, bradycardia1)
Vascular disorders:
Infrequent: marked decrease in BP (including orthostatic hypotension)
Unknown: necrotizing vasculitis2)
Respiratory, thoracic and mediastinal disorders:
Infrequent: dyspnea
Rarely: respiratory distress syndrome (including pneumonia and noncardiogenic pulmonary edema)
Gastrointestinal tract disorders:
Infrequent: diarrhea, dry mouth, flatulence,
Rare: abdominal pain, constipation, dyspepsia, vomiting, gastritis, upset stomach1)
Unknown: upset stomach2), pancreatitis2), nausea2)
Liver and biliary tract disorders:
Rare: impaired liver function
Unknown: jaundice (hepatocellular or cholestatic)2)
Skin and subcutaneous tissue disorders:
Rarely: angioedema (including fatal cases), erythema, pruritus, rash, increased sweating, urticaria, eczema1), drug rash1), toxic skin rash1)
Unknown: toxic epidermal necrolysis2), lupus-like reactions2), relapse of systemic lupus erythematosus2), cutaneous vasculitis2), photosensitization reaction2), erythema multiforme2)
Musculoskeletal and connective tissue disorders:
Infrequent: back pain, muscle spasms myalgia
Rare: arthralgia, limb pain, calf muscle cramps, osteoarthritis1), tendinitis-like symptoms1)
Unknown: muscle weakness2)
Renal and urinary tract disorders:
Infrequent: renal failure, including acute renal failure1)
Unknown: Interstitial nephritis2), renal dysfunction2), glucosuria2)
Genital and mammary disorders:
Infrequent: erectile dysfunction
General disorders and disorders at the site of administration:
Infrequent: chest pain, asthenia (weakness)1)
Rarely: Flu-like symptoms, pain
Unknown: fever2)
Effect on laboratory and instrumental findings:
Infrequent: increased blood uric acid concentration
Rarely: increased plasma creatinine concentration, increased “hepatic” enzyme activity, increased creatine phosphokinase activity, decreased blood hemoglobin1)
Unknown: hypertriglyceridemia1)

1) expected based on experience with telmisartan
2) expected based on experience with hydrochlorothiazide”

Overdose

The information about overdose is limited. Possible symptoms of overdose are composed of symptoms from the individual components of the drug.

Hydrochlorothiazide

Symptoms

. The most common manifestations of hydrochlorothiazide overdose are increased – diuresis, accompanied by acute fluid loss (dehydration) and electrolyte disturbances (hypokalemia, hyponatremia, hypochloremia). Overdose with hydrochlorothiazide may manifest as the following symptoms:

Treatment

In case of overdose, symptomatic and supportive therapy is given. If the drug has been taken recently, induction of vomiting or gastric lavage are indicated for excretion of hydrochlorothiazide. Absorption of hydrochlorothiazide may be reduced by ingestion of activated charcoal. In case of BP decrease or shock the circulating blood volume should be replenished by administration of plasma exchange fluids and electrolyte deficit (potassium, sodium). In case of respiratory disorders, oxygen inhalation or artificial lung ventilation is indicated. Water-electrolyte balance (especially serum potassium) and renal function should be monitored until their normalization.

There is no specific antidote. Hydrochlorothiazide is excreted by hemodialysis, but the extent of its excretion has not been established.

Telmisartan

Symptoms

Performance of marked BP decrease, tachycardia, bradycardia.

Treatment

There is no specific treatment. Close monitoring of the patient’s condition is necessary. Symptomatic and supportive therapy is indicated, depending on the time since the use of the drug and the severity of symptoms. Regular monitoring of serum electrolytes and creatinine is necessary.

If arterial hypotension develops, the patient should be placed on his back and electrolytes and RBC should be rapidly replaced.Telmisartan is not excreted by hemodialysis.

Pregnancy use

The use of the drug MIKAFOR is contraindicated during pregnancy and during breast-feeding.

In case of a planned pregnancy the drug MIKAFOR should be replaced by other drugs approved for use during pregnancy. If pregnancy is established, MIKAFOR should be discontinued immediately.

Hydrochlorothiazide

Pregnancy

. There is limited experience with hydrochlorothiazide during pregnancy (especially in the first trimester) Preclinical data regarding safety are insufficient.

Hydrochlorothiazide penetrates the placental barrier and is detected in umbilical cord blood. Given the mechanism of pharmacological action of hydrochlorothiazide, its use in the second and third trimesters of pregnancy may disrupt the feto-placental perfusion and lead to the development in the fetus and the newborn of such complications as jaundice, disorders of water-electrolyte balance and thrombocytopenia. Cases of thrombocytopenia have been described in newborns whose mothers received thiazide diuretics.

The use of hydrochlorothiazide during pregnancy is contraindicated. Hydrochlorothiazide should not be used for the treatment of gestosis in the second half of pregnancy (edema, arterial hypertension or preeclampsia), since it increases the risk of decreased circulating blood volume and placental hypoperfusion, but has no beneficial effect on the course of the mentioned complications of pregnancy. Diuretics do not prevent the development of gestosis.

Breastfeeding period

Hydrochlorothiazide penetrates the mother’s milk, therefore, its use during breastfeeding is contraindicated. If use of hydrochlorothiazide during lactation is absolutely necessary, breastfeeding should be stopped.

Telmisartan

Pregnancy

The use of angiotensin II receptor antagonists is not recommended during the first trimester of pregnancy; these drugs should not be prescribed during pregnancy. If pregnancy is diagnosed, the drug should be stopped immediately. If necessary, alternative therapy (other classes of hypotensive drugs approved for use during pregnancy) should be prescribed.

The use of angiotensin II receptor antagonists during the second and third trimesters of pregnancy is contraindicated.

In preclinical studies of telmisartan no teratogenic effect has been noted, but fetotoxicity has been established. It is known that exposure to angiotensin II receptor antagonists during the second and third trimesters of pregnancy causes fetotoxicity in humans (decreased renal function, oligohydramnios, delayed ossification of the skull bones) as well as neonatal toxicity (renal failure, arterial hypotension, hyperkalemia). Patients planning to become pregnant should be prescribed an alternative therapy with a proven safety profile in pregnant women. If treatment with angiotensin II receptor antagonists occurred during the second trimester of pregnancy, ultrasound examination of renal function and fetal cranial bone health is recommended. Newborns whose mothers received angiotensin II receptor antagonists should be closely monitored for arterial hypotension.

Period of breastfeeding

The use of telmisartan is contraindicated during breastfeeding.

Fertility

In animal studies, no effect of telmisartan on fertility has been observed. There have been no studies of the effects of telmisartanan on human fertility.

Similarities