MicardisPlus^® (Tablets) Instructions for Use

Marketing Authorization Holder

Boehringer Ingelheim International, GmbH (Germany)

Manufactured By

Boehringer Ingelheim Pharma, GmbH & Co. KG (Germany)

Boehringer Ingelheim Ellas, A.E. (Greece)

ATC Code

C09DA07 (Telmisartan and diuretics)

Active Substances

Hydrochlorothiazide (Rec.INN registered by WHO)

Telmisartan (Rec.INN registered by WHO)

Dosage Forms

	MicardisPlus^®	Tablets 12.5 mg+40 mg: 14, 28 or 56 pcs.
		Tablets 12.5 mg+80 mg: 14, 28 or 56 pcs.

Dosage Form, Packaging, and Composition

Tablets of oblong shape, biconvex, two-layer, one layer is pinkish-beige with possible small inclusions of white color, the other layer is white with possible inclusions of pinkish-beige color; on the white surface of the tablets there is an engraving “H4” and the symbol of the company Boehringer Ingelheim.

	1 tab.
Hydrochlorothiazide	12.5 mg
Telmisartan	40 mg

Excipients : telmisartan layer: sodium hydroxide, povidone K25 (polyvidone), meglumine, sorbitol, magnesium stearate; hydrochlorothiazide layer: lactose monohydrate, microcrystalline cellulose, corn starch, iron oxide red dye (E172), sodium carboxymethyl starch, magnesium stearate.

7 pcs. – blisters (2) – cardboard packs.
7 pcs. – blisters (4) – cardboard packs.
7 pcs. – blisters (8) – cardboard packs.

Tablets of oblong shape, biconvex, two-layer, one layer is pinkish-beige with possible small inclusions of white color, the other layer is white with possible inclusions of pinkish-beige color; on the white surface of the tablets there is an engraving “H8” and the symbol of the company Boehringer Ingelheim.

	1 tab.
Hydrochlorothiazide	12.5 mg
Telmisartan	80 mg

7 pcs. – blisters (2) – cardboard packs.
7 pcs. – blisters (4) – cardboard packs.
7 pcs. – blisters (8) – cardboard packs.

Clinical-Pharmacological Group

Antihypertensive drug

Pharmacotherapeutic Group

Agents acting on the renin-angiotensin system; angiotensin II receptor antagonists in combination with other agents; angiotensin II receptor antagonists in combination with diuretics

Pharmacological Action

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

Telmisartan is a specific angiotensin II receptor antagonist, effective when taken orally. It has a high affinity for the AT₁ receptor subtype of angiotensin II, through which the action of angiotensin II is realized. Telmisartan displaces angiotensin II from binding to the receptor, without having an agonist effect on this receptor. Telmisartan binds only to the AT₁ receptor subtype of angiotensin II. The binding is long-lasting. Telmisartan has no affinity for other angiotensin receptors (including AT₂ receptors). The functional significance of these receptors, as well as the effect of their possible excessive stimulation by angiotensin II, the concentration of which increases with the appointment of telmisartan, has not been studied. Telmisartan leads to a decrease in the concentration of aldosterone in the blood, does not inhibit plasma renin and does not block ion channels. Telmisartan does not inhibit ACE (kininase II), an enzyme that also breaks down bradykinin, so 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 effect of angiotensin II. The onset of the antihypertensive effect is noted within 3 hours after the first oral intake of telmisartan. The effect of the drug persists for 24 hours and remains significant for up to 48 hours. A pronounced antihypertensive effect usually develops after 4 weeks of regular use of the drug.

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

In case of abrupt withdrawal of telmisartan, blood pressure gradually returns to baseline without the development of withdrawal syndrome.

A study with telmisartan evaluated cases of cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, or hospitalization due to chronic heart failure. A reduction in cardiovascular morbidity and mortality was proven in patients at high cardiovascular risk (with coronary artery disease, stroke, peripheral artery disease, or diabetes mellitus with concomitant target organ damage, such as retinopathy, left ventricular hypertrophy, history of macro- or microalbuminuria) over the age of 55 years.

Hydrochlorothiazide is a thiazide diuretic. Thiazide diuretics affect the reabsorption of electrolytes in the renal tubules, directly increasing the excretion of sodium and chlorides (in approximately equivalent amounts). The diuretic effect of hydrochlorothiazide leads to a decrease in circulating blood volume, an increase in plasma renin activity, an increase in aldosterone secretion and is accompanied by an increase in the content of potassium and bicarbonates in the urine, and as a result, a decrease in the content of potassium in the blood plasma. With the simultaneous use of telmisartan, there is a tendency to stop the loss of potassium caused by these diuretics, presumably due to the blockade of the RAAS.

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

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

The maximum antihypertensive effect of MicardisPlus^® is usually achieved 4-8 weeks after the start of treatment.

Pharmacokinetics

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

Telmisartan

Absorption

When taken orally, it is rapidly absorbed from the gastrointestinal tract. Bioavailability is approximately 50%. C_max of telmisartan is reached within 0.5-1.5 hours after application. When taken simultaneously with food, the decrease in AUC ranges from 6% (when used at a dose of 40 mg) to 19% (when used at a dose of 160 mg). After 3 hours of oral administration, the plasma concentration levels off, regardless of food intake.

Distribution

Binding to plasma proteins is significant (more than 99.5%), mainly with albumin and α₁-glycoprotein. V_d is approximately 500 L.

Metabolism

Telmisartan is metabolized by conjugation with glucuronic acid. The metabolites are pharmacologically inactive.

Excretion

T_1/2 is more than 20 hours. It is excreted through the intestines unchanged, renal excretion is less than 2%. Total plasma clearance is high (about 900 ml/min).

Pharmacokinetics in special clinical cases

A difference in plasma concentrations of telmisartan is observed between men and women. In women, C_max and AUC were approximately 3 and 2 times higher, respectively, than in men (without a significant effect on efficacy). However, no enhancement of the hypotensive effect is observed in women.

The pharmacokinetics of telmisartan in elderly patients does not differ from that in young patients. No dose adjustment is required.

Changing the dose of telmisartan in patients with renal failure is not required, including patients on hemodialysis. Telmisartan is not removed by hemodialysis.

Pharmacokinetic studies in patients with hepatic insufficiency showed an increase in absolute bioavailability to almost 100%. In hepatic insufficiency, T_1/2 does not change.

Hydrochlorothiazide

Absorption

After oral administration of MicardisPlus^®, C_max of hydrochlorothiazide is reached within 1-3 hours. Absolute bioavailability is estimated by cumulative renal excretion of hydrochlorothiazide and is about 60%.

Distribution

Binds to plasma proteins by 64%. V_d – 0.8±0.3 L/kg.

Metabolism and excretion

It is not metabolized in the human body and is excreted in the urine almost unchanged. About 60% of the orally administered dose is eliminated within 48 hours. Renal clearance is about 250-300 ml/min. T_1/2 – 10-15 hours.

Pharmacokinetics in special clinical cases

A difference in plasma concentrations is observed between men and women. In women, there is a tendency for a clinically significant increase in the plasma concentration of hydrochlorothiazide.

In patients with impaired renal function, the excretion rate of hydrochlorothiazide is reduced. Studies conducted in patients with a creatinine clearance of 90 ml/min showed that the T_1/2 of hydrochlorothiazide increases. In patients with reduced renal function, T_1/2 is about 34 hours.

Indications

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

ICD codes

Open the list of ICD codes

ICD-10 code	Indication
I10	Essential [primary] hypertension

ICD-11 code	Indication
BA00.Z	Essential hypertension, unspecified

Dosage Regimen

The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen.

MicardisPlus^® should be taken orally once a day, regardless of meals.

MicardisPlus^® 40/12.5 mg can be prescribed to patients in whom the use of the drug Micardis^® at a dose of 40 mg or hydrochlorothiazide does not lead to adequate blood pressure control.

MicardisPlus^® 80/12.5 mg can be prescribed to patients in whom the use of the drug Micardis^® at a dose of 80 mg or MicardisPlus^® 40/12.5 mg does not lead to adequate blood pressure control.

In patients with severe arterial hypertension, the maximum daily dose of telmisartan is 160 mg/day. This dose was effective and well tolerated.

In mild to moderate renal impairment, no change in the dose of the drug is required. In such patients, renal function should be monitored (with creatinine clearance >30 ml/min).

In patients with mild to moderate hepatic impairment (Child-Pugh class A and B), MicardisPlus^® should not be used at a daily dose of more than 40/12.5 mg.

No change in the dosage regimen is required for elderly patients.

Adverse Reactions

From the respiratory system respiratory distress syndrome (including pneumonia and pulmonary edema)³⁾, dyspnea³⁾.

From the cardiovascular system arrhythmias³⁾, tachycardia³⁾, bradycardia¹⁾, pronounced decrease in blood pressure (including orthostatic hypotension)³⁾.

From the central nervous system: syncope/fainting³⁾, paresthesia³⁾, sleep disorders³⁾, insomnia³⁾, dizziness³⁾, anxiety³⁾, depression³⁾, increased excitability²⁾, headache²⁾.

From the digestive system: diarrhea³⁾, dryness of the oral mucosa³⁾, flatulence³⁾, abdominal pain³⁾, constipation³⁾, vomiting³⁾, gastritis³⁾, decreased appetite²⁾, anorexia²⁾, hyperglycemia²⁾, hypercholesterolemia²⁾, pancreatitis²⁾, impaired liver function³⁾, jaundice (hepatocellular or cholestatic)²⁾, dyspepsia^1),2),3).

From the skin increased sweating³⁾.

From the musculoskeletal system back pain³⁾, muscle spasms³⁾, myalgia³⁾, arthralgia³⁾, calf muscle cramps³⁾, arthrosis¹⁾, tendinitis-like symptoms¹⁾, chest pain³⁾.

From the hematopoietic system iron deficiency anemia¹⁾, aplastic anemia²⁾, hemolytic anemia²⁾, thrombocytopenia¹⁾, eosinophilia¹⁾, leukopenia²⁾, neutropenia/agranulocytosis²⁾, thrombocytopenia²⁾.

From the urinary system renal failure^1),2), including acute renal failure¹⁾, interstitial nephritis²⁾, glucosuria²⁾.

From the sense organs visual impairment³⁾, transient blurred vision³⁾, xanthopsia²⁾, acute angle-closure glaucoma²⁾, acute myopia²⁾.

From the reproductive system impotence³⁾.

Infections sepsis, including fatal cases¹⁾, upper respiratory tract infections (bronchitis, pharyngitis, sinusitis)^1),3), urinary tract infections (including cystitis)¹⁾, inflammation of the salivary glands²⁾.

Metabolic disorders increased plasma creatinine concentration³⁾, increased activity of liver enzymes³⁾, increased activity of creatine phosphokinase³⁾, increased concentration of uric acid in the blood³⁾, hypertriglyceridemia²⁾, hypokalemia^2),3), hyperkalemia ¹⁾, hyponatremia^2),3), hyperuricemia³⁾, decreased circulating blood volume²⁾, hypoglycemia (in patients with diabetes mellitus)¹⁾, impaired glucose tolerance²⁾, decreased hemoglobin level in the blood¹⁾.

Allergic reactions angioedema (including fatal cases)³⁾, erythema³⁾, skin itching³⁾, rash³⁾, anaphylactic reactions^1),2), eczema¹⁾, drug rash^1),2), toxic epidermal necrolysis^1),2), lupus-like reactions²⁾, exacerbation or intensification of symptoms of systemic lupus erythematosus³⁾, necrotizing vasculitis²⁾, systemic vasculitis²⁾, photosensitivity reaction²⁾, recurrence of systemic lupus erythematosus²⁾, vasculitis²⁾.

Other flu-like syndrome³⁾, fever²⁾, weakness^1),2).

¹⁾ – expected based on the experience of using telmisartan.

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

³⁾ – side effects that were not observed in clinical studies with the simultaneous use of telmisartan and hydrochlorothiazide, but are expected during the use of the drug MicardisPlus^®.

Contraindications

Obstructive diseases of the biliary tract;
Severe liver dysfunction (Child-Pugh class C);
Severe renal impairment (creatinine clearance <30 ml/min);
Refractory hypokalemia, hypercalcemia;
Simultaneous use with aliskiren in patients with diabetes mellitus and renal failure (GFR <60 ml/min/1.73 m²);
Hereditary fructose intolerance (the drug contains sorbitol);
Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome;
Age under 18 years (safety and efficacy not established);
Pregnancy;
Lactation period (breastfeeding);
Hypersensitivity to the active substance or auxiliary components of the drug or other sulfonamide derivatives.

With caution

Bilateral renal artery stenosis or stenosis of the artery of a single kidney;
Impaired liver function or progressive liver disease (Child-Pugh class A and B);
Decreased circulating blood volume due to previous diuretic therapy, salt restriction, diarrhea or vomiting;
Hyperkalemia;
Condition after kidney transplantation (no experience of use);
Chronic heart failure NYHA functional class III-IV;
Aortic and mitral valve stenosis;
Idiopathic hypertrophic subaortic stenosis;
Hypertrophic obstructive cardiomyopathy;
Diabetes mellitus;
Primary aldosteronism;
Gout;
Angle-closure glaucoma (due to the presence of hydrochlorothiazide in the composition).

Experience of use in patients with renal failure (creatinine clearance >30 ml/min) is limited but does not confirm the development of renal side effects; no dose adjustment is required.

Use in Pregnancy and Lactation

The use of the drug MicardisPlus^® is contraindicated during pregnancy.

Telmisartan

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

The use of angiotensin II receptor antagonists in the second and third trimesters of pregnancy is contraindicated. In preclinical studies of telmisartan, no teratogenic effects were identified, but fetotoxicity was established. It is known that exposure to angiotensin II receptor antagonists in the second and third trimesters of pregnancy causes fetotoxicity in humans (decreased renal function, oligohydramnios, delayed skull ossification), as well as neonatal toxicity (renal failure, hypotension, hyperkalemia). Patients planning pregnancy should be prescribed alternative therapy. If treatment with angiotensin II receptor antagonists was carried out in the second trimester of pregnancy, ultrasound of the kidneys and skull bones of the fetus is recommended.

Newborns whose mothers received angiotensin II receptor antagonists should be carefully monitored for arterial hypotension.

Hydrochlorothiazide

Experience with hydrochlorothiazide during pregnancy, especially in the first trimester, is limited. Hydrochlorothiazide crosses the placental barrier. Considering the pharmacological mechanism of action of hydrochlorothiazide, it is assumed that its use in the second and third trimesters of pregnancy may impair fetoplacental perfusion and cause changes in the embryo and fetus such as jaundice, electrolyte imbalance, and thrombocytopenia. Hydrochlorothiazide should not be used for pregnancy-related edema, pregnancy-related arterial hypertension, or during pre-eclampsia, because there is a risk of reduced plasma volume and reduced placental perfusion, and there is no beneficial effect in these clinical situations.

Hydrochlorothiazide should not be used to treat essential hypertension in pregnant women, except in those rare situations where other types of treatment cannot be used.

Therapy with MicardisPlus^® is contraindicated during breastfeeding.

In experimental studies in animals, no effect of telmisartan and hydrochlorothiazide on fertility was observed.

No studies on the effect on human fertility have been conducted.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction (Child-Pugh class C).

The drug should be prescribed with caution in cases of impaired liver function or progressive liver disease (Child-Pugh class A and B).

In patients with mild to moderate hepatic impairment (Child-Pugh class A and B), MicardisPlus^® should not be used at a daily dose exceeding 40/12.5 mg.

Use in Renal Impairment

Contraindicated in severe renal impairment (CrCl <30 ml/min).

The drug should be prescribed with caution in cases of bilateral renal artery stenosis or stenosis of the artery to a single kidney, impaired renal function, and status after kidney transplantation.

For mild to moderate renal impairment, no dose adjustment of the drug is required. In such patients, renal function should be monitored (with CrCl >30 ml/min).

Pediatric Use

The drug is contraindicated for use in children and adolescents under 18 years of age, because data on efficacy and safety in this category of patients are lacking.

Geriatric Use

No dose adjustment is required for elderly patients.

Special Precautions

Conditions contributing to increased RAAS activity

In some patients, due to suppression of RAAS activity, especially with the simultaneous use of drugs acting on this system, renal function may be impaired (including acute renal failure). Therefore, therapy accompanied by such dual blockade of the RAAS (for example, when adding an ACE inhibitor 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 serum potassium and creatinine levels).

The use of thiazide diuretics in patients with impaired renal function may lead to azotemia. Periodic monitoring of renal function is recommended.

Renovascular hypertension

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

Hepatic impairment

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

Effect on metabolism and endocrine gland function

In patients with diabetes mellitus, adjustment of the dose of insulin or oral hypoglycemic agents may be required. During therapy with thiazide diuretics, latent diabetes mellitus may become manifest.

In some cases, the use of thiazide diuretics may lead to the development of hyperuricemia and exacerbation of gout.

Diabetes mellitus

In patients with diabetes mellitus and additional cardiovascular risk, for example, in patients with diabetes mellitus and coronary artery disease, when using blood pressure-lowering drugs such as angiotensin II receptor antagonists or ACE inhibitors, the risk of fatal myocardial infarction and sudden cardiovascular death may be increased. In patients with diabetes mellitus, coronary artery disease may be asymptomatic and therefore may be undiagnosed. Before starting MicardisPlus^®, appropriate diagnostic tests, including an exercise test, should be performed to detect 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 are sudden decrease in visual acuity or eye pain, which typically occur within hours to weeks after starting the drug. If left untreated, acute angle-closure glaucoma can lead to vision loss. The main treatment is to discontinue hydrochlorothiazide as soon as possible. It should be kept 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 allergy to sulfonamides or penicillin.

Water and electrolyte balance disorders

When using MicardisPlus^®, as with diuretic therapy, periodic monitoring of serum electrolytes is necessary.

Thiazide diuretics, including Hydrochlorothiazide, can cause disturbances in water and electrolyte balance and acid-base status (hypokalemia, hyponatremia, and hypochloremic alkalosis). Signs suggestive of these disturbances include dry oral mucosa, thirst, general weakness, drowsiness, restlessness, myalgia or muscle cramps, muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, and gastrointestinal disturbances such as nausea or vomiting.

The use of thiazide diuretics may lead to hypokalemia, but concurrently used Telmisartan may increase blood potassium levels. The risk of hypokalemia is most increased in patients with liver cirrhosis, with increased diuresis, while on a salt-free diet, as well as in case of simultaneous use of glucocorticoids and mineralocorticoids or corticotropin. Telmisartan, which is part of MicardisPlus^®, on the contrary, may lead to hyperkalemia due to antagonism of angiotensin II receptors (subtype AT₁). Although clinically significant hyperkalemia has not been reported with the use of MicardisPlus^®, it should be taken into account that risk factors for its development include renal and/or heart failure and diabetes mellitus.

There is no data that MicardisPlus^® can reduce or prevent diuretic-induced hyponatremia. Hypochloremia is usually minor and does not require treatment.

Thiazide diuretics can reduce renal calcium excretion and cause (in the absence of obvious calcium metabolism disorders) a transient and slight increase in serum calcium levels. More pronounced hypercalcemia may be a sign of latent hyperparathyroidism. Thiazide diuretics should be discontinued before assessing parathyroid function.

Thiazide diuretics have been shown to increase renal magnesium excretion, which can lead to hypomagnesemia.

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

There are reports of systemic lupus erythematosus developing with the use of thiazide diuretics.

MicardisPlus^® can, if necessary, be used concomitantly with other antihypertensive agents.

Liver function disorders when prescribing telmisartan were observed mostly in Japanese residents.

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

Effect on the ability to drive vehicles and operate machinery

No specific clinical studies have been conducted to assess the effect of MicardisPlus^® on the ability to drive vehicles and operate machinery requiring increased attention. However, when driving vehicles and engaging in potentially hazardous activities, the possibility of dizziness and drowsiness should be taken into account, which requires caution.

Overdose

No cases of overdose have been identified. Possible symptoms of overdose consist of symptoms from the individual components of the drug.

Symptoms of telmisartan overdose: marked decrease in blood pressure, tachycardia, bradycardia.

Symptoms of hydrochlorothiazide overdose: disturbances in blood water and electrolyte balance (hypokalemia, hypochloremia), decreased blood volume, which can lead to muscle spasms and/or exacerbate cardiovascular disorders (arrhythmias caused by concomitant use of cardiac glycosides or some antiarrhythmic agents).

Treatment: symptomatic therapy, hemodialysis is not effective. The extent of hydrochlorothiazide removal during hemodialysis has not been established. Regular monitoring of serum electrolytes and creatinine is necessary.

Drug Interactions

Telmisartan

When telmisartan is used concomitantly with:

other antihypertensive agents, an enhancement of the antihypertensive effect is possible. In one study, when telmisartan and ramipril were used in combination, an increase in AUC_0-24 and C_max of ramipril and ramiprilat by 2.5 times was observed. The clinical significance of this interaction has not been established. Analysis of adverse events leading to treatment discontinuation and analysis of serious adverse events obtained during the clinical study found that cough and angioedema were more frequently observed during therapy with ramipril, while arterial hypotension was more frequent during therapy with telmisartan. Cases of hyperkalemia, renal failure, arterial hypotension, and syncope were observed significantly more often with the concomitant use of telmisartan and ramipril;
lithium preparations, a reversible increase in blood lithium concentration accompanied by toxic phenomena was noted with the use of ACE inhibitors. In rare cases, similar changes have been reported with the prescription of angiotensin II receptor antagonists, in particular, telmisartan. When lithium preparations and angiotensin II receptor antagonists are used concomitantly, it is recommended to monitor blood lithium levels;
NSAIDs, including acetylsalicylic acid in doses used as an anti-inflammatory agent, COX-2 inhibitors and non-selective NSAIDs, may cause the development of acute renal failure in patients with reduced blood volume. Drugs affecting the RAAS may have a synergistic effect. In patients receiving NSAIDs and Telmisartan, blood volume should be compensated and renal function should be investigated at the start of treatment. A reduction in the effect of antihypertensive agents such as Telmisartan, through inhibition of the vasodilatory effect of prostaglandins, has been observed with concomitant treatment with NSAIDs. No clinically significant effect was detected when telmisartan was used concomitantly with ibuprofen or paracetamol;
digoxin, warfarin, hydrochlorothiazide, glibenclamide, simvastatin and amlodipine, no clinically significant interaction was detected. An increase in the average plasma concentration of digoxin by an average of 20% (in one case by 39%) was noted. When telmisartan and digoxin are prescribed concomitantly, it is advisable to periodically determine the blood concentration of digoxin.

Hydrochlorothiazide

When used concomitantly with

ethanol, barbiturates or opioid analgesics, there is a risk of orthostatic hypotension;
oral hypoglycemic agents and insulin, adjustment of the dose of oral hypoglycemic agents and insulin may be required;
metformin, there is a risk of lactic acidosis;
cholestyramine and colestipol – in the presence of anion exchange resins, the absorption of hydrochlorothiazide is impaired;
cardiac glycosides, the risk of hypokalemia or hypomagnesemia caused by thiazide diuretics, and the development of arrhythmias caused by cardiac glycosides, increases;
pressor amines (e.g., norepinephrine), a weakening of the effect of pressor amines is possible;
non-depolarizing muscle relaxants (e.g., tubocurarine chloride), Hydrochlorothiazide may enhance the effect of non-depolarizing muscle relaxants;
antigout agents, the concentration of uric acid in the blood serum may increase and therefore dose adjustments of uricosuric agents may be required. The use of thiazide diuretics increases the frequency of hypersensitivity reactions to allopurinol;
calcium preparations – thiazide diuretics may increase serum calcium levels due to reduced renal excretion. If calcium preparations are required, blood calcium levels should be regularly monitored and, if necessary, the dose of calcium preparations should be adjusted;
beta-blockers and diazoxide, thiazide diuretics may enhance the hyperglycemia caused by beta-blockers and diazoxide;
m-cholinoblockers (e.g., atropine, biperiden) – decreased gastrointestinal motility, increased bioavailability of thiazide diuretics;
amantadine, thiazide diuretics may increase the risk of adverse effects caused by amantadine;
cytotoxic agents (e.g., cyclophosphamide, methotrexate) – decreased renal excretion of cytotoxic agents and enhancement of their myelosuppressive effect;
NSAIDs – concomitant use with thiazide diuretics may lead to a reduction in the diuretic and antihypertensive effect;
agents that lead to potassium loss and hypokalemia (e.g., potassium-excreting diuretics, laxatives; glucocorticoids and mineralocorticoids; corticotropin; amphotericin B; carbenoxolone; benzylpenicillin, acetylsalicylic acid derivatives) – enhancement of the hypokalemic effect. Hypokalemia caused by hydrochlorothiazide is compensated by the potassium-sparing effect of telmisartan;
potassium-sparing diuretics, potassium preparations, other agents capable of increasing serum potassium levels (e.g., heparin) or replacement of sodium in table salt with potassium salts, hyperkalemia may develop. Periodic monitoring of plasma potassium levels is recommended in cases where MicardisPlus^® is used concomitantly with drugs that can cause hypokalemia, as well as with drugs that can increase serum potassium levels.

Storage Conditions

The drug should be stored in a dry place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.

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