Hydrochlorothiazide, Telmisartan

MicardisPLUS^® (MICARDISPLUS^®)

Boehringer Ingelheim C09D A07

COMPOSITION AND FORM OF ISSUE:

tab. 40 mg + 12.5 mg, No. 14, No. 28

Other ingredients: povidone (E 1201), meglumine, sodium hydroxide, sorbitol (E 420), magnesium stearate (E470b), microcrystalline cellulose, red iron oxide (E 172), sodium starch glycolate, lactose monohydrate, corn starch.

No. UA / 0465/01/01 from 02/02/2009 to 02/02/2014

tab. 80 mg + 12.5 mg, No. 14, No. 28

Other ingredients: povidone (E 1201), meglumine, sodium hydroxide, sorbitol (E 420), magnesium stearate (E470b), microcrystalline cellulose, red iron oxide (E 172), sodium starch glycolate, lactose monohydrate, corn starch.

No. UA / 0465/01/02 from 02.02.2009 to 02.02.2014

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamics MicardisPlus is a combination of the angiotensin II receptor antagonist telmisartan and the thiazide hydrochlorothiazide diuretic. The combination of these ingredients provides an additional antihypertensive effect, lowering blood pressure more than each component separately.
Micardis Plus, used once a day in therapeutic doses, effectively and slowly reduces blood pressure.
Telmisartan is a specific antagonist of angiotensin II receptors (type AT₁), with a high degree of affinity, replaces angiotensin II at its binding sites on AT subtype receptors₁responsible for the physiological effects of angiotensin II. Telmisartan does not have partial agonistic activity against these receptors. Binding to receptors is long. Telmisartan does not show affinity for other receptors, including AT₂ and other less described AT receptors. The functional role of these receptors is unknown, as is the effect of the likely excessive stimulation with angiotensin II, the level of which increases under the influence of telmisartan. Telmisartan reduces plasma aldosterone levels.
Telmisartan does not inhibit serum renin, does not block ion channels, and does not inhibit ACE (kinase II), an enzyme that destroys bradykinin. Therefore, potentiation of bradykinin-accompanying side effects is not observed.
When using Telmisartan 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 decrease in blood pressure observed after 4-8 weeks from the start of treatment, persists with prolonged treatment.
An outpatient measurement of blood pressure showed that the antihypertensive effect is constant for 24 hours after a dose, including the last 4 hours before the next dose.
In patients with hypertension, telmisartan reduces both systolic and diastolic blood pressure without affecting the pulse rate. With the sudden cessation of treatment with telmisartan, blood pressure gradually returns to its original level over several days without the development of withdrawal syndrome.
In clinical trials, cases of dry cough were noted much less frequently in patients using telmisartan than in those taking ACE inhibitors.
The effect of telmisartan on mortality and cardiovascular disease is unknown.
Hydrochlorothiazide is a thiazide diuretic. The mechanism of the antihypertensive effect of thiazide diuretics is not fully known.Thiazides affect the renal tubular process of tubular reabsorption of electrolytes, thereby increasing the excretion of sodium and chlorine ions in approximately equivalent volumes. The diuretic effect leads to a decrease in BCC, an increase in plasma renin activity, an increase in aldosterone secretion, followed by an increase in the excretion of potassium and bicarbonate and a decrease in the level of potassium in the blood plasma. Probably, by blocking the renin-angiotensin-aldosterone system, the simultaneous use of telmisartan contributes to the reversible loss of potassium associated with these diuretics.
When using hydrochlorothiazide, an increase in diuresis is noted after 2 hours, the maximum effect is achieved after about 4 hours, the effect lasts about 6-12 hours.
Epidemiological studies have found that prolonged hydrochlorothiazide therapy reduces the risk of cardiovascular morbidity and mortality.
The effect of the fixed combination telmisartan / hydrochlorothiazide on mortality and cardiovascular disease is unknown.
Pharmacokinetics The simultaneous use of hydrochlorothiazide and telmisartan does not affect the pharmacokinetics of each drug separately in healthy people.
Suction. Telmisartan. After oral administration C_max Telmisartan is achieved in 0.5-1.5 hours. Absolute bioavailability when taken at a dose of 40 and 160 mg is 42 and 58%, respectively. Food slightly reduces the bioavailability of telmisartan, a decrease in AUC ranges from 6% (use at a dose of 40 mg) to 19% (intake at a dose of 160 mg). 3 hours after application, the concentration in blood plasma is the same when applied on an empty stomach or with food and does not depend on food intake. A slight decrease in AUC does not cause a decrease in therapeutic efficacy.
The pharmacokinetics of telmisartan when taken orally is non-linear with increasing doses from 20 to 160 mg, which is manifested in an increase in C_max and plasma AUC in excess of proportional. Telmisartan does not accumulate in blood plasma to a large extent with repeated applications.
Hydrochlorothiazide. After oral administration of the drug MicardisPlus C_max serum hydrochlorothiazide is reached after 1-3 hours. Given the total renal excretion of hydrochlorothiazide, the absolute bioavailability is about 60%.
Distribution. Telmisartan. Telmisartan is significantly bound to plasma proteins (> 99.5%), mainly albumin and acidic α₁-glycoprotein. The distribution volume is about 500 L, which indicates a high binding to tissues.
Hydrochlorothiazide. About 68% of hydrochlorothiazide binds to blood plasma proteins; the distribution volume is 0.83–1.14 l / kg body weight.
Biotransformation and breeding. Telmisartan. After oral administration ¹⁴C-labeled telmisartan most of the dose (> 97%) is excreted in the feces by biliary excretion; in small quantities excreted in the urine. Telmisartan is metabolized in the liver by conjugation to form a pharmacologically inactive acylglucuronide.The glucuronide of the parent compound is the only metabolite identified in humans.
After applying a single dose ¹⁴C-labeled telmisartan glucuronide accounts for about 11% of the measured plasma radioactivity. Cytochrome P450 isoenzymes do not participate in the metabolism of telmisartan. The total clearance of telmisartan after oral administration is> 1500 ml / min. Total T_½ > 20 hours
Hydrochlorothiazide. It is not metabolized and excreted almost completely unchanged in the urine, about 60% of the orally taken dose is eliminated unchanged over 48 hours. Renal clearance is 250–300 ml / min. Terminal T_½ - 10-15 hours
Special categories of patients
Elderly patients. The pharmacokinetics of telmisartan are not different in the elderly and in patients younger than 65 years of age.
Floor. The concentration of telmisartan in blood plasma in women is 2-3 times higher than in men, but there was no significant increase in the effect on blood pressure or the incidence of orthostatic hypotension in women. There is no need for dose adjustment in women, they have a tendency to a higher concentration of hydrochlorothiazide than men, which does not have clinical significance.
Patients with impaired renal function. Given the small experience of using the drug for the treatment of persons with impaired renal function (creatinine clearance is 30-60 ml / min, on average about 50 ml / min), there is no need for dose adjustment in patients with impaired renal function. Telmisartan is not excreted during hemodialysis. In individuals with renal failure, the rate of elimination of hydrochlorothiazide is reduced. In typical studies in patients with creatinine clearance, an average of 90 ml / min T_½ hydrochlorothiazide increases. In persons with a removed or absent kidney T_½ is about 34 hours
Patients with impaired liver function. In pharmacokinetic studies in individuals with impaired liver function, an increase in absolute bioavailability to ≈100% was detected, while T_½ does not change.

INDICATIONS:

AH. As a combination with a fixed dose, MicardisPlus is prescribed to patients in whom blood pressure is not adequately controlled with telmisartan alone.

APPLICATION:

adults
Patients in whom blood pressure is not sufficiently regulated by telmisartan alone should take MicardisPlus. Before switching to a fixed-dose combination, individual dose titration of each component is recommended. With clinical feasibility, you can consider a direct transition from monotherapy to treatment with a combination of fixed doses.
Micardis Plus 40 mg / 12.5 mg can be prescribed to patients in case of insufficient control of blood pressure with the use of Micardis 40 mg tablets.
Micardis Plus 80 mg / 12.5 mg can be prescribed to patients in case of insufficient blood pressure control with the use of Micardis 80 mg tablets.
Special categories of patients
Renal failure. Periodic monitoring of renal function is desirable.
Liver failure. In patients with mild to moderate hepatic insufficiency, the dosage should not exceed Micardis Plus 40 mg / 12.5 mg once a day.MicardisPlus is not indicated for persons with severe liver failure. In patients with impaired liver function, thiazides should be used with caution (see SPECIAL INSTRUCTIONS).
Elderly patients. There is no need for dose adjustment.
Mode of application
MicardisPlus is taken 1 time per day orally with a sufficient amount of liquid, with or without food.
Tablets should be stored in a sealed blister to protect against moisture. Tablets must be removed from the blister just before use.

CONTRAINDICATIONS:

• hypersensitivity to any active substance or any of the excipients of the drug;
• hypersensitivity to other substances - sulfonamide derivatives (since hydrochlorothiazide is a drug derived from sulfonamide);
• II and III trimester of pregnancy;
• cholestatic and biliary obstructive disorders;
• severe liver failure;
• severe renal impairment (creatinine clearance <30 ml / min);
• refractory hypokalemia, hypercalcemia.

SIDE EFFECTS:

the most commonly reported side effect is dizziness. Serious angioedema can occur in isolated cases (<1 case per 1000 patients).
Fixed dose combination
The dependence of the side effects on the doses has not been established and they were not associated with gender, age or race.
Side effects that were reported during all clinical trials and that occurred more often with the combination of telmisartan with hydrochlorothiazide than with placebo are listed below according to the classes of organ systems. Side effects that are detected when each component is used separately, but which did not appear during clinical trials, may occur during the treatment with MicardisPlus are also given below in separate sections.
Adverse reactions are presented indicating the frequency using the following notation: very often (≥1 / 10); often (≥1 / 100 to <1/10); infrequently (≥1 / 1000 to <1/100); rarely (≥1 / 10,000 to <1/1000); very rarely (<1/10 000); frequency is unknown (cannot be determined from available data).
In each group, adverse reactions are presented in decreasing order of severity.
Infections and infestations: rarely - bronchitis, pharyngitis, sinusitis.
From the immune system: rarely - enhancement or activation of systemic lupus erythematosus.
Metabolic disease: infrequently - hypokalemia; rarely - hyperuricemia, hyponatremia.
From the side of the psyche: infrequently - anxiety; rarely depression.
From the nervous system: often dizziness; infrequently - syncope, paresthesia; rarely - insomnia, sleep disturbance.
From the side of the organ of vision: rarely - visual impairment, blurred vision.
On the part of the organ of hearing, vestibular disorders: infrequently - vertigo.
From the heart: infrequently - tachycardia, arrhythmia.
From the vessels: infrequently - arterial hypotension, orthostatic hypotension.
From the respiratory system: infrequently - dyspnea; rarely, respiratory distress syndrome (including pneumonitis and pulmonary edema).
From the digestive tract: infrequently - diarrhea, dry mouth, flatulence; rarely - abdominal pain, constipation, dyspepsia, vomiting, gastritis.
Hepatobiliary disorders: rarely - liver function disorders / liver disease¹.
On the part of the skin and subcutaneous tissue: rarely - angioedema (also fatal), erythema, pruritus, rash, hyperhidrosis, urticaria.
From the musculoskeletal system: infrequently - back pain, muscle cramps, myalgia; rarely - arthralgia, muscle cramps, leg pain.
From the reproductive system and mammary glands: infrequently - erectile dysfunction.
Common violations: infrequently - chest pain; rarely - flu-like symptoms, pain.
Laboratory data: infrequently - increased uric acid levels; rarely - increased creatinine, CPK blood, liver enzymes.
¹According to post-marketing data, most cases of impaired liver function / liver disease were observed in patients in the Japanese population. Patients in the Japanese population are more prone to these adverse reactions.
Additional information regarding individual components
Side effects that were previously reported in connection with one of the components may be potential side effects when using MicardisPlus, even if they were not observed during clinical trials of this drug.
Telmisartan
Side effects with the same frequency were observed both with telmisartan and with placebo.
The following adverse reactions were collected during all clinical trials involving patients treated with telmisartan in connection with hypertension, or among patients over the age of 50 years with a high risk of cardiovascular disorders.
Infections and infestations: infrequently - upper respiratory tract infections, urinary tract infections, including cystitis; rarely - sepsis, including fatal².
From the blood system and lymphatic system: infrequently - anemia; rarely - eosinophilia, thrombocytopenia.
From the immune system: rarely - hypersensitivity, anaphylactic reactions.
Metabolic disease: infrequently - hyperkalemia; rarely - hypoglycemia (in patients with diabetes).
From the heart: infrequently - bradycardia.
From the digestive tract: rarely - stomach discomfort.
On the part of the skin and subcutaneous tissue: rarely - eczema, medical dermatitis, toxic epidermal necrolysis.
From the musculoskeletal system: rarely - arthrosis, tendon pain.
From the kidneys and urinary tract: infrequently - renal failure (including acute renal failure).
Common violations: infrequently - asthenia.
Laboratory data: rarely - a decrease in hemoglobin.
²The PRoFESS study showed a higher incidence of sepsis among patients using telmisartan than among those receiving placebo. This can be either an accident or a sign of a process, the essence of which is now unknown.
Hydrochlorothiazide
Hydrochlorothiazide can cause or exacerbate hypovolemia, which can lead to electrolyte imbalance (see SPECIAL INSTRUCTIONS).
Side effects with an unknown frequency observed with a separate use of hydrochlorothiazide.
Infections and infestations: frequency unknown - sialadenitis.
From the circulatory and lymphatic systems: frequency unknown - aplastic anemia, hemolytic anemia, inhibition of bone marrow function, leukopenia, neutropenia, agranulocytosis, thrombocytopenia.
From the immune system: frequency unknown - anaphylactic reactions, hypersensitivity.
Endocrine Disorders: frequency unknown - loss of diabetes control.
Metabolic disease: the frequency is unknown - anorexia, loss of appetite, electrolyte imbalance, hypercholesterolemia, hyperglycemia, hypovolemia.
From the side of the psyche: frequency unknown - concern.
From the nervous system: frequency unknown - dizziness.
From the side of the organ of vision: frequency unknown - xanthopsia.
Vascular Disorders: frequency unknown - necrotizing vasculitis.
From the digestive tract: frequency unknown - pancreatitis, stomach discomfort.
Hepatobiliary disorders: frequency unknown - jaundice (hepatocellular or cholestatic).
On the part of the skin and subcutaneous tissue: frequency unknown - lupus erythematosus syndrome, photosensitivity reactions, skin vasculitis, toxic epidermal necrolysis.
From the musculoskeletal system: frequency unknown - weakness.
From the kidneys and urinary tract: frequency unknown - interstitial nephritis, impaired renal function, glucosuria.
Common violations: frequency unknown - chills.
Laboratory data: frequency unknown - elevated TG.

SPECIAL INSTRUCTIONS:

liver failure. MicardisPlus should not be prescribed to patients with cholestasis, obstructive diseases of the bile ducts and severe liver failure, since telmisartan is excreted mainly with bile. In such patients, a decrease in hepatic clearance of telmisartan can be expected. In addition, MicardisPlus should be used with caution in patients with impaired liver function or progressive liver disease, since even slight changes in water-electrolyte balance can cause hepatic coma. There is no clinical experience with the use of MicardisPlus in patients with liver failure.
Renovascular hypertension. There is an increased risk of severe hypotension and renal failure if patients with bilateral renal artery stenosis or renal artery stenosis of a single functioning kidney take medications that affect the renin-angiotensin-aldosterone system.
Impaired renal function and kidney transplantation. MicardisPlus should not be used in patients with severe renal impairment (creatinine clearance <30 ml / min) (see CONTRAINDICATIONS).There is no experience with MicardisPlus in patients who, shortly before use, underwent kidney transplantation. Since the experience of using MicardisPlus in patients with impaired renal function of mild to moderate severity is limited, it is recommended that periodic monitoring of the levels of potassium, creatinine and uric acid in blood plasma is recommended. In individuals with impaired renal function, azotemia associated with thiazide diuretics may occur.
Decreased intravascular fluid volume. In patients with sodium deficiency and / or bcc in the body, symptomatic hypotension may occur due to powerful diuretic therapy, limited salt in the diet, diarrhea, or vomiting, especially after the first dose. Therefore, before the appointment of Micardis Plus, the above conditions should be corrected.
Double blockade of the renin-angiotensin-aldosterone system. As a result of inhibition of the renin-angiotensin-aldosterone system in more sensitive patients, changes in renal function (including acute renal failure) were noted, especially if the combination of drugs included drugs that affect this system. Therefore, the double blockade of the renin-angiotensin-aldosterone system (for example, the addition of an ACE inhibitor to the angiotensin II receptor antagonist) is not recommended for people who already have already blocked AD, and should be limited in some cases with careful monitoring of renal function.
Other conditions accompanied by stimulation of the renin-angiotensin-aldosterone system. In patients whose vascular tone and renal function mainly depend on the activity of the renin-angiotensin-aldosterone system (for example, patients with severe congestive heart failure, including renal artery stenosis), treatment with drugs that affect this system can cause acute hypotension, hyperazotemia, oliguria, occasionally - acute renal failure (see ADVERSE EFFECTS).
Primary aldosteronism. Patients with primary aldosteronism usually do not respond to antihypertensive drugs, the action of which involves the inhibition of the renin-angiotensin system, so the use of MicardisPlus in such patients is not recommended.
Stenosis of the aorta and mitral valve, obstructive hypertrophic cardiomyopathy. As with other vasodilators, special care is required in the treatment of patients with aortic stenosis and mitral valve or obstructive hypertrophic cardiomyopathy.
Metabolic and endocrine action. Thiazide treatment may impair glucose tolerance. For patients with diabetes, there may be a need for dose adjustment of insulin or oral hypoglycemic drugs. Latent diabetes mellitus may occur during thiazide therapy. With treatment with thiazide diuretics, an increase in the level of cholesterol and triglycerides is associated. However, when using a drug containing 12.5 mg of hydrochlorothiazide, a minimal effect or its absence was noted.Some patients using thiazide drugs may develop hyperuricemia or the sudden onset of exacerbation of gout.
Electrolyte imbalance. As for any patient treated with diuretics, periodic determination of the level of plasma electrolytes should be carried out at certain intervals.
Thiazides, including hydrochlorothiazide, can cause fluid or electrolyte imbalances (including hypokalemia, hyponatremia, and hypochloremic alkalosis). Warning signs of fluid or electrolyte imbalance are dry mouth, thirst, weakness, lethargy, drowsiness, anxiety, muscle pain or cramps, muscle fatigue, arterial hypotension, oliguria, tachycardia, and such gastrointestinal disorders as nausea and vomiting (see. )
Hypokalemia. Although hypokalemia may develop as a result of thiazide diuretics, concomitant telmisartan therapy can reduce the hypokalemia caused by diuretics. The risk of hypokalemia is highest in patients with cirrhosis of the liver, in patients with significant diuresis, in patients who inadequately apply electrolytes orally, and in patients receiving concomitant therapy with corticosteroids or ACTH (see INTERACTIONS).
Hyperkalemia In connection with the antagonism of angiotensin II receptors (AT₁) caused by telmisartan - a component of MicardisPlus, hyperkalemia may occur. However, clinically significant hyperkalemia due to the use of the drug MicardisPlus is not documented, risk factors for hyperkalemia include renal failure and / or heart failure and diabetes mellitus. Potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium should be used with caution in conjunction with MicardisPlus (see INTERACTIONS).
Hyponatremia and hypochloremic alkalosis. There is no evidence that MicardisPlus will reduce or prevent hyponatremia caused by diuretics. Chlorine deficiency is mostly mild and usually does not require treatment.
Hypercalcemia. Thiazides can reduce the excretion of calcium in the urine and cause a spasmodic and insignificant increase in the level of calcium in the blood plasma in the absence of known disorders of calcium metabolism. Significant hypercalcemia may be a sign of latent hyperparathyroidism. Thiazides should be discontinued before parathyroid function analysis.
Hypomagnesemia. Thiazides have shown an increase in urination of magnesium, which can lead to hypomagnesemia.
Sorbitol and lactose monohydrate. The drug contains lactose monohydrate and sorbitol. Patients with rare hereditary fructose intolerance states and / or rare hereditary galactose intolerance states, Lapp lactase deficiency or glucose-galactose malabsorption should not use this drug.
Ethnic differences. Like all other angiotensin II receptor antagonists, telmisartan is less effective in lowering blood pressure in patients of the Negroid race than in representatives of other races. Perhaps this is due to the high prevalence of low renin states in patients of the Negroid race with hypertension.
Other conditions. As with any other antihypertensive drug, an excessive decrease in blood pressure in patients with ischemic cardiopathy or coronary heart disease can cause myocardial infarction or stroke.
General violations. Hypersensitivity reactions to hydrochlorothiazide may occur in individuals with an allergy or AD in the anamnesis, but in those who have such diseases, the occurrence of these manifestations is more reliable. It is known that the use of thiazide diuretics can lead to exacerbation or increased activity of systemic lupus erythematosus.
When thiazide diuretics were used, cases of photosensitivity reactions were observed (see ADVERSE EFFECTS). If photosensitivity reactions occur during treatment, it is recommended to discontinue use of the drug. If it is considered necessary to reuse diuretics, it is recommended to protect exposed areas from the action of the sun or artificial ultraviolet radiation.
During pregnancy and breastfeeding. The use of angiotensin II receptor antagonists is not recommended in the first trimester of pregnancy. The use of angiotensin II receptor antagonists is contraindicated in the second and third trimester of pregnancy.
There is insufficient data on the use of MicardisPlus in pregnant women.
The epidemiological rationale for teratogenic risk after ACE inhibitors in the first trimester of pregnancy is inconclusive, but a slight increase in risk cannot be ruled out. Although there is no controlled epidemiological data regarding the risk of teratogenicity with angiotensin II receptor antagonists, similar risks may exist for this class of drugs. If the continuation of therapy with angiotensin II receptor antagonists is not considered essential, patients planning a pregnancy should switch to antihypertensive drugs that have an established safety profile for use during pregnancy. When pregnancy is established, treatment with angiotensin II receptor antagonists must be urgently discontinued and alternative treatment initiated if necessary. In the II and III trimester of pregnancy, angiotensin II receptor antagonists are known to cause fetotoxicity (decreased renal function, oligohydramniosis, delayed formation of cranial bones) and neonatal toxicity (renal failure, hypotension, hyperkalemia). If the use of angiotensin II receptor antagonists began from the second trimester of pregnancy, it is recommended to conduct an ultrasound examination of the kidney and skull bones. Infants whose mothers have taken angiotensin II receptor antagonists should be carefully examined for arterial hypotension.
Thiazides cross the placental barrier and are detected in cord blood. They can cause disturbances in the electrolyte balance in the fetus and, possibly, other reactions observed in adults. Cases of neonatal thrombocytopenia and embryonic or neonatal jaundice are known if mothers were treated with thiazides.
Due to the lack of information regarding the use of MicardisPlus during breastfeeding, the drug is not recommended for use. Alternative treatment with a better-studied safety profile is preferred. Thiazides are excreted in breast milk and may inhibit lactation.
The ability to influence the reaction rate when driving vehicles or working with mechanisms. Studies of the effect of telmisartan on the ability to drive vehicles or work with mechanisms have not been conducted. However, when performing such work, it must be taken into account that dizziness or hypersomnia may occur during antihypertensive therapy.

INTERACTIONS:

interaction studies were conducted only in adults.
Lithium. With the simultaneous use of lithium with ACE inhibitors, a reversible increase in the concentration of lithium in blood plasma and an increase in its toxicity have been recorded. Such cases of interaction have been reported with angiotensin II receptor antagonists (including MicardisPlus). The simultaneous use of lithium and MicardisPlus is not recommended (see CONTRAINDICATIONS). If the effectiveness of this combination with simultaneous use is proven, careful monitoring of serum lithium levels is recommended.
Medicines Associated with Potassium Loss and Hypokalemia (for example, other diuretics that remove potassium, laxatives, corticosteroids, ACTH, amphotericini, carbenoxolones, penicillin G sodium, salicylic acid and derivatives). When using these drugs, along with the combination of hydrochlorothiazide-telmisartan, it is recommended to monitor the level of potassium in the blood plasma. These drugs may increase the effect of hydrochlorothiazide on potassium in the blood plasma (see SPECIAL INSTRUCTIONS).
Medicines that can increase potassium levels and cause hyperkalemia (for example, drugs that suppress the renin-angiotensin system, potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, cyclosporine, or other drugs such as sodium heparin). When using these drugs, along with the combination of hydrochlorothiazide-telmisartan, it is recommended to monitor the level of potassium in the blood plasma. Based on the experience of using other drugs that suppress the renin-angiotensin system, the simultaneous use of these drugs can lead to an increase in the level of potassium in the blood plasma and therefore is not recommended (see SPECIAL INSTRUCTIONS).
Medicines that cause a violation of the level of potassium in the blood plasma. Periodic monitoring of potassium levels is recommended.