Uses, Dosage, Side Effects, Interactions, Warning

WARNINGS

Included as part of the “PRECAUTIONS” Section

PRECAUTIONS

Fetal Toxicity

Telmisartan

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of
pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting
oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential
neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When
pregnancy is detected, discontinue MICARDIS HCT as soon as possible.

Hydrochlorothiazide

Thiazides cross the placental barrier and appear in cord blood. Adverse reactions include fetal or
neonatal jaundice and thrombocytopenia [see Use In Specific Populations].

Hypotension In Volume-Or Salt-Depleted Patients

In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g.,
those being treated with high doses of diuretics), symptomatic hypotension may occur after initialization
of treatment with MICARDIS HCT. Correct volume or salt depletion prior to administration of
MICARDIS HCT.

Impaired Renal Function

Changes in renal function including acute renal failure can be caused by drugs that inhibit the reninangiotensin
system and by diuretics. Patients whose renal function may depend in part on the activity of
the renin-angiotensin system (e.g., patients with renal artery stenosis, chronic kidney disease, severe
congestive heart failure, or volume depletion) may be at particular risk of developing oliguria,
progressive azotemia, or acute renal failure on MICARDIS HCT. Monitor renal function periodically in
these patients. Consider withholding or discontinuing therapy in patients who develop a clinically
significant decrease in renal function on MICARDIS HCT.

Electrolytes And Metabolic Disorders

Drugs, including telmisartan, that inhibit the renin-angiotensin system can cause hyperkalemia,
particularly in patients with renal insufficiency, diabetes, or combination use with other angiotensin
receptor blockers or ACE inhibitors and the concomitant use of other drugs that raise serum potassium
levels [see DRUG INTERACTIONS].

Hydrochlorothiazide can cause hypokalemia and hyponatremia. Thiazides have been shown to increase
the urinary excretion of magnesium; this may result in hypomagnesemia. Hypomagnesemia can result in
hypokalemia which may be difficult to treat despite potassium repletion. Monitor serum electrolytes
periodically.

In controlled trials using the telmisartan/hydrochlorothiazide combination treatment, no patient
administered 40 mg/12.5 mg, 80 mg/12.5 mg, or 80 mg/25 mg experienced a decrease in potassium ≥1.4
mEq/L, and no patient experienced hyperkalemia.

Hydrochlorothiazide decreases urinary calcium excretion and may cause elevations of serum calcium.

Hydrochlorothiazide may alter glucose tolerance and raise serum levels of cholesterol and
triglycerides.

Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide
therapy. Because telmisartan decreases uric acid, telmisartan in combination with hydrochlorothiazide
attenuates the diuretic-induced hyperuricemia.

Hypersensitivity Reaction

Hydrochlorothiazide

Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of
allergy or bronchial asthma, but are more likely in patients with such a history [see CONTRAINDICATIONS].

Acute Myopia And Secondary Angle-Closure Glaucoma

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient
myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or
ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure
glaucoma can lead to permanent vision loss. The primary treatment is to discontinue
hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be
considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angleclosure
glaucoma may include a history of sulfonamide or penicillin allergy.

Systemic Lupus Erythematosus

Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus
erythematosus.

Postsympathectomy Patients

The antihypertensive effects of hydrochlorothiazide may be enhanced in the postsympathectomy patient.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).

Pregnancy

Advise female patients of childbearing age about the consequences of exposure to MICARDIS HCT
during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to
report pregnancies to their physicians as soon as possible [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].

Lactation

Advise nursing women not to breastfeed during treatment with MICARDIS HCT [see Use In Specific Populations].

Symptomatic Hypotension And Syncope

Advise patients that lightheadedness can occur, especially during the first days of therapy, and to report
it to their healthcare provider. Inform patients that inadequate fluid intake, excessive perspiration,
diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of
lightheadedness and possible syncope. Advise patients to contact their healthcare provider if syncope
occurs [see WARNINGS AND PRECAUTIONS].

Potassium Supplements

Advise patients not to use potassium supplements or salt substitutes that contain potassium without
consulting the prescribing healthcare provider [see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].

Acute Myopia And Secondary Angle-Closure Glaucoma

Advise patients to discontinue MICARDIS HCT and seek immediate medical attention if they experience
symptoms of Acute Myopia or Secondary Angle-Closure Glaucoma [see WARNINGS AND PRECAUTIONS].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Telmisartan And Hydrochlorothiazide

No carcinogenicity, mutagenicity, or fertility studies have been conducted with the combination of
telmisartan and hydrochlorothiazide.

Telmisartan

There was no evidence of carcinogenicity when telmisartan was administered in the diet to mice and rats
for up to 2 years. The highest doses administered to mice (1000 mg/kg/day) and rats (100 mg/kg/day)
are, on a mg/m² basis, about 59 and 13 times, respectively, the maximum recommended human dose
(MRHD) of telmisartan. These same doses have been shown to provide average systemic exposures to
telmisartan >100 times and >25 times, respectively, the systemic exposure in humans receiving the
MRHD of telmisartan (80 mg/day).

Genotoxicity assays did not reveal any telmisartan-related effects at either the gene or chromosome
level. These assays included bacterial mutagenicity tests with Salmonella and E. coli (Ames), a gene
mutation test with Chinese hamster V79 cells, a cytogenetic test with human lymphocytes, and a mouse
micronucleus test.

No drug-related effects on the reproductive performance of male and female rats were noted at 100
mg/kg/day (the highest dose administered), about 13 times, on a mg/m² basis, the MRHD of telmisartan.
This dose in the rat resulted in an average systemic exposure (telmisartan AUC as determined on day 6
of pregnancy) at least 50 times the average systemic exposure in humans at the MRHD (80 mg/day).

Hydrochlorothiazide

Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology
Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female
mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to
approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for
hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella
typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster
Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell
chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive
lethal trait gene. Positive test results were obtained in the in vitro CHO Sister Chromatid Exchange
(clastogenicity) assay, in the Mouse Lymphoma Cell (mutagenicity) assay, and in the Aspergillus nidulans non-disjunction assay.

Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies
wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively,
prior to mating and throughout gestation.

Use In Specific Populations

Pregnancy

Risk Summary

MICARDIS HCT can cause fetal harm when administered to a pregnant woman. Use of drugs that act on
the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal
function and increases fetal and neonatal morbidity and death (see Clinical Considerations). Most
epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first
trimester have not distinguished drugs affecting the renin-angiotensin system from other
antihypertensive agents. Studies in rats and rabbits with telmisartan showed fetotoxicity only at
maternally toxic doses (see Data). When pregnancy is detected, discontinue MICARDIS HCT as soon as
possible.

The estimated background risk of major birth defects and miscarriage for the indicated population is
unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In
the U.S. general population, the estimated background risk of major birth defects and miscarriage in
clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes,
premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum
hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine
death. Pregnant women with hypertension should be carefully monitored and managed accordingly.

Fetal/Neonatal adverse reactions

Telmisartan

Use of drugs that act on the RAS in the second and third trimesters of pregnancy can result in the
following: oligohydramnios, reduced fetal renal function leading to anuria and renal failure, fetal lung
hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual
case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system
for a particular patient, apprise the mother of the potential risk to the fetus.

In patients taking MICARDIS HCT during pregnancy, perform serial ultrasound examinations to assess
the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. If
oligohydramnios is observed, discontinue MICARDIS HCT, unless it is considered lifesaving for the
mother. Patients and physicians should be aware, however, that oligohydramnios may not appear until
after the fetus has sustained irreversible injury.

Closely observe infants with histories of in utero exposure to MICARDIS HCT for hypotension,
oliguria, and hyperkalemia. If oliguria or hypotension occurs, support blood pressure and renal
perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and
replacing renal function [see Use In Specific Populations].

Hydrochlorothiazide

Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or
neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults.

Data

Animal Data

MICARDIS HCT

A developmental toxicity study was performed in rats with telmisartan/hydrochlorothiazide doses of
3.2/1.0, 15/4.7, 50/15.6, and 0/15.6 mg/kg/day. Although the two higher dose combinations appeared to
be more toxic (significant decrease in body weight gain) to the dams than either drug alone, there did
not appear to be an increase in toxicity to the developing embryos.

Telmisartan

No teratogenic effects were observed when telmisartan was administered to pregnant rats at oral doses
of up to 50 mg/kg/day and to pregnant rabbits at oral doses of up to 45 mg/kg/day. In rabbits, embryo
lethality associated with maternal toxicity (reduced body weight gain and food consumption) was
observed at 45 mg/kg/day (approximately 12 times the maximum recommended human dose [MRHD] of
80 mg on a mg/m²basis). In rats, maternally toxic (reduced body weight gain and food consumption)
telmisartan doses of 15 mg/kg/day (approximately 1.9 times the MRHD on a mg/m² basis), administered
during late gestation and lactation, were observed to produce adverse effects in neonates, including
reduced viability, low birth weight, delayed maturation, and decreased weight gain. The no-observed
effect doses for developmental toxicity in rats and rabbits, 5 and 15 mg/kg/day, respectively, are
approximately 0.64 and 3.7 times, respectively, on a mg/m² basis, the MRHD of telmisartan (80 mg/day).

Hydrochlorothiazide

Studies in which hydrochlorothiazide was administered to pregnant mice and rats during their respective
periods of major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively (about 600 and
400 times the MRHD), provided no evidence of harm to the fetus.

Thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the
maternal plasma. Hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion. It
accumulates in the amniotic fluid, with reported concentrations up to 19 times that in umbilical vein
plasma. Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or
thrombocytopenia. Since they do not prevent or alter the course of EPH (Edema, Proteinuria,
Hypertension) gestosis (pre-eclampsia), these drugs should not be used to treat hypertension in pregnant
women. The use of hydrochlorothiazide for other indications (e.g., heart disease) in pregnancy should
be avoided.

Lactation

Risk Summary

There is no information regarding the presence of MICARDIS HCT or telmisartan in human milk, the
effects on the breastfed infant or the effects on milk production. Limited published studies report that
hydrochlorothiazide is present in human milk. However, there is insufficient information to determine
the effects of hydrochlorothiazide on the breastfed infant or the effects of hydrochlorothiazide on milk
production. Telmisartan is present in the milk of lactating rats. (see Data). Because of the potential for
serious adverse reactions in the breastfed infant including hypotension, hyperkalemia and renal
impairment, advise a nursing woman not to breastfeed during treatment with MICARDIS HCT.

Data

Telmisartan was present in the milk of lactating rats at concentrations 1.5 to 2 times those found in
plasma from 4 to 8 hours after administration.

Pediatric Use

Safety and effectiveness of MICARDIS HCT in pediatric patients have not been established.

Neonates With A History Of In Utero Exposure To MICARDIS HCT

If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions
or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal
function.

Geriatric Use

In the controlled clinical trials (n=1017), approximately 20% of patients treated with
telmisartan/hydrochlorothiazide were 65 years of age or older, and 5% were 75 years of age or older.
No overall differences in effectiveness and safety of telmisartan/hydrochlorothiazide were observed in
these patients compared to younger patients. Other reported clinical experience has not identified
differences in responses between the elderly and younger patients, but greater sensitivity of some older
individuals cannot be ruled out. In general, dose selection for an elderly patient should be cautious,
usually starting at the low end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal or cardiac function and of concomitant diseases or other drug therapy.

Use In Patients With Hepatic Impairment

Patients with biliary obstructive disorders or hepatic insufficiency should initiate treatment under close
medical supervision using the 40 mg/12.5 mg combination.

Telmisartan

As the majority of telmisartan is eliminated by biliary excretion, patients with biliary obstructive
disorders or hepatic insufficiency can be expected to have reduced clearance and higher blood levels.

Hydrochlorothiazide

Minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired
hepatic function or progressive liver disease.

Use In Patients With Renal Impairment

Safety and effectiveness of MICARDIS HCT in patients with severe renal impairment (CrCl ≤30
mL/min) have not been established. In patients with severe renal impairment, MICARDIS HCT tablets
are not recommended. No dose adjustment is required in patients with mild (CrCl 60 to 90 mL/min) or
moderate (CrCl 30 to 60 mL/min) renal impairment.

Micardis – Uses, Side Effects, Interactions

How does this medication work? What will it do for me?

Telmisartan belongs to a class of medications known as angiotensin II receptor antagonists. These medications reduce blood pressure by blocking the actions of a chemical (angiotensin II) that causes blood vessels to constrict or tighten. It is used to treat mild-to-moderate high blood pressure.

When blood pressure is allowed to remain high for a long time, the blood vessels of the heart, kidneys, and brain may become damaged. This puts a person at increased risk for heart attack and stroke as well as kidney failure and blindness. Keeping blood pressure in the normal range can reduce the risk for these conditions.

Telmisartan is also used to reduce the risk of death caused by a heart attack or stroke, for people who cannot use another type of medication called angiotensin-converting enzyme inhibitor.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

40 mg
Each white, oblong-shaped, uncoated tablet, marked with the Boehringer Ingelheim logo on one side, and on the other side, with “51H”, contains telmisartan 40 mg. Nonmedicinal ingredients: magnesium stearate, meglumine, povidone, sodium hydroxide, and sorbitol.

80 mg
Each white, oblong-shaped, uncoated tablet, marked with the Boehringer Ingelheim logo on one side, and on the other side, with “52H”, contains telmisartan 80 mg. Nonmedicinal ingredients: magnesium stearate, meglumine, povidone, sodium hydroxide, and sorbitol.

How should I use this medication?

The recommended adult dose of telmisartan is 80 mg once a day at approximately the same time each day, with or without food. It will take about 2 weeks for reductions in blood pressure to become noticeable and another 2 weeks until the full effects of the medication are realized. People with reduced liver function are usually given 40 mg once daily to start.

It is important to take this medication regularly and to follow your doctor’s instructions regarding blood pressure monitoring to ensure that you are getting the maximum benefit from the medication.

If you miss a dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

Store telmisartan at normal room temperature in a dry place (not in the bathroom) and keep it out of the reach of children. Do not remove tablets from their blister-pack until you are ready to take them.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take telmisartan if you:

• are allergic to telmisartan or to any of the ingredients of the medication
• have experienced angioedema as a reaction to any angiotensin receptor blocker (ARB)
• are pregnant or plan to become pregnant
• are breast-feeding
• have diabetes or kidney disease and are taking the medication aliskiren
• are allergic to certain sugars (fructose and/or sorbitol intolerant)

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent. The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• abdominal pain
• anxiety
• back or leg pain
• constipation
• diarrhea
• difficulty sleeping
• dizziness
• drowsiness
• dry mouth
• eczema or skin rash
• gas
• headache
• heartburn
• joint pain
• muscle cramps or spasms
• nausea
• nervousness
• rash
• tiredness
• upper respiratory tract infection (such as colds or sinus infections)
• upset stomach
• vomiting

Although most of these side effects listed below don’t happen very often, they could lead to serious problems if you do not check with your doctor or seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• chest pain
• dizziness, fainting, or lightheadedness
• symptoms of low blood sugar (e.g., cold sweat, cool pale skin, headache, fast heartbeat, weakness)
• shortness of breath
• signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
• signs of kidney problems (e.g., decreased urination, nausea, vomiting, swelling of the feet and ankles)
• signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
• signs of too much potassium in the body (e.g., irregular heartbeat, muscle weakness, generally feeling unwell)
• swelling of ankles, feet, or hands
• symptoms of a urinary tract infection (e.g., pain when urinating, urinating more often than usual, low back or flank pain)
• unexplained muscle pain, tenderness, or weakness
• vision changes

Stop taking the medication and seek immediate medical attention if any of the following occur:

• signs of a serious blood infection (e.g., chills, confusion, fever or low body temperature, shakiness, irregular heartbeat)
• signs of a serious allergic reaction (e.g., swelling of face, lips, tongue, or throat; hives; difficulty breathing)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

Drowsiness/reduced alertness: Telmisartan may cause drowsiness or dizziness, affecting your ability to drive or operate machinery. Avoid these and other hazardous tasks until you have determined how this medication affects you.

Kidney disease: Telmisartan may affect kidney function, especially for people who already have kidney problems. Taking this medication along with the medication aliskiren or an angiotensin-converting enzyme inhibitor (ACEI) further increases the risk of kidney problems. If you have reduced kidney function or kidney disease, renal artery stenosis (narrowing of blood vessels in the kidneys), or congestive heart failure, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience symptoms of decreased kidney function, such as puffy hands, face or feet, high blood pressure, unusual muscle cramping, or darkened urine, contact your doctor as soon as possible.

Liver disease: Telmisartan is removed from the body by the liver. On rare occasions, it may cause liver problems. If you have liver disease or decreased liver function, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience symptoms of liver problems such as fatigue, feeling unwell, loss of appetite, nausea, yellowing of the skin or whites of the eyes, dark urine, pale stools, abdominal pain or swelling, and itchy skin, contact your doctor immediately.

Low blood pressure: If you have orthostatic hypotension (a sudden drop in blood pressure caused by standing up, which may lead to fainting), you should be cautious while taking telmisartan, as it can worsen the condition. The first time this medication is taken, it may cause dizziness, lightheadedness, or fainting. This may be reduced by taking the medication in a sitting position and being careful to rise slowly to a standing position. The dizziness usually improves after the first dose, but if the medication is stopped and then started again, it may reappear. Your doctor may also adjust the dose.

Potassium levels: This medication may affect potassium levels in the blood, especially when used for heart failure, or when taken with other medications called ACE inhibitors, aliskiren, or diuretics such as spironolactone. Your doctor will monitor your potassium levels while on this medication. Avoid using salt substitutes that contain potassium while you are taking telmisartan.

Pregnancy: Telmisartan may cause severe harm to an unborn fetus and should not be taken during pregnancy. If you discover you are pregnant while taking this medication, stop taking the medication and tell your doctor at once.

Breast-feeding: It is not known if telmisartan passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of using this medication have not been established for children.

What other drugs could interact with this medication?

There may be an interaction between telmisartan and any of the following:

• aldesleukin
• aliskiren
• alpha-blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin)
• amifostine
• amphetamines (e.g., dextroamphetamine, lisdexamfetamine)
• angiotensin-converting enzyme inhibitors (ACEIs; captopril, enalapril, ramipril)
• other angiotensin receptor blockers (ARBs; e.g., candesartan, irbesartan, losartan)
• antipsychotics (e.g., clozapine, olanzapine, quetiapine, risperidone)
• barbiturates (e.g., secobarbital, phenobarbital)
• beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
• brimonidine
• celecoxib
• calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
• clonidine
• cyclosporine
• dexmethylphenidate
• digoxin
• dipyridamole
• diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
• drospirenone
• duloxetine
• eplerenone
• guanfacine
• heparin
• hydralazine
• isosorbide dinitrate or isosorbide mononitrate
• levodopa
• lithium
• low molecular weight heparins (e.g., dalteparin, enoxaparin, tinzaparin)
• methyldopa
• methylphenidate
• minoxidil
• monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
• nitroglycerin
• nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., naproxen, ibuprofen)
• obinutuzumab
• pentoxifylline
• phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
• potassium supplements or medications that increase potassium in the blood
• rituximab
• selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, paroxetine, sertraline)
• sodium phosphates
• tacrolimus
• tizanidine
• tolcapone
• tolvaptan
• trimethoprim
• yohimbine

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2021. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Micardis

Telmisartan tablets info. Micardis Telmisartan info – Patient

About telmisartan

Telmisartan is an angiotensin receptor blocker (also called an angiotensin-II receptor antagonist (A2RA)). It is used to treat high blood pressure (hypertension). People with high blood pressure often do not feel unwell but, if left untreated, high blood pressure can harm the heart and damage blood vessels.

Telmisartan works by blocking the effect of a natural chemical made in your bloodstream, called angiotensin II. Angiotensin II causes your blood vessels to narrow, so by blocking this effect, telmisartan allows your blood vessels to relax and widen. As this happens, the pressure within your blood vessels is reduced. This also makes it easier for your heart to pump blood around your body.

Telmisartan is also used to help prevent heart attacks and strokes in people who may be at risk of these because of other medical conditions, such as diabetes.

Telmisartan is also available in a combination tablet with another medicine used to reduce high blood pressure, called hydrochlorothiazide. Taking combination tablets like this can help reduce the number of tablets you need to take each day.

Before taking telmisartan

Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you start taking telmisartan it is important that your doctor or pharmacist knows:

• If you are pregnant, trying for a baby or breastfeeding.
• If you have kidney problems or if you have a blockage of the artery which supplies blood to your kidneys.
• If you have liver problems.
• If you have any problems with your heart valves or heart muscle.
• If you have high blood sugar levels (diabetes).
• If you are taking any other medicines. This includes any medicines you are taking which are available to buy without a prescription, as well as herbal and complementary medicines.
• If you have ever had an allergic reaction to a medicine.

How to take telmisartan

• Before you start this treatment, read the manufacturer’s printed information leaflet from inside the pack. The leaflet will give you more information about telmisartan and a full list of possible side-effects from taking it.
• Take telmisartan exactly as your doctor has told you to. It is usual to take one tablet a day, although there are several strengths of tablet available. The usual starting dose for high blood pressure is 20-40 mg each day, although your doctor may decide to increase your dose after a few weeks. If you are taking telmisartan to reduce your risk of a heart attack or stroke, the usual dose is 80 mg each day
• Each time you collect a prescription, check to make sure it is the strength of tablet that you are expecting.
• Try to take telmisartan at the same time of day each day. This will help you to remember to take it regularly.
• You can take telmisartan before or after meals.
• If you forget to take a dose, take it as soon as you remember. If you do not remember until the following day, skip the missed dose. Do not take two doses together to make up for a forgotten dose.

Getting the most from your treatment

• Try to keep your regular appointments with your doctor. This is so your progress can be monitored. Your doctor will want you to have some blood tests from time to time to check on your kidneys, and also how much potassium is in your blood.
• If you buy any medicines, check with a pharmacist that they are suitable to take with telmisartan. This is because some anti-inflammatory painkillers (such as aspirin and ibuprofen) may interfere with the way telmisartan works, and also may increase the risk of side-effects.
• It is very important that you follow any dietary and lifestyle advice that you may have been given by your doctor, such as eating a healthy diet, not smoking, and taking regular exercise.
• If you drink alcohol, ask your doctor for advice about drinking while you are on telmisartan. Alcohol will increase the risk of you feeling dizzy or faint and may not be recommended for you.
• Do not use salt substitutes which contain potassium while you are taking these tablets. This is because they increase the amount of potassium in your blood and this can cause problems.
• If you are having an operation or dental treatment, tell the person carrying out the treatment that you are taking telmisartan. This is because telmisartan taken with an anaesthetic may make your blood pressure drop too low.
• Treatment with telmisartan is usually long-term unless you experience an adverse effect. Continue to take it unless you are advised otherwise by your doctor.

If you are also taking hydrochlorothiazide in combination with this medicine

• Studies have suggested that taking higher doses of hydrochlorothiazide for long periods of time may increase the risk of certain skin cancers.
• Tell your doctor if you have ever been treated for skin cancer before.
• Tell your doctor about any new or changed moles or worrying marks on your skin.
• Use a sunscreen in strong sunlight. Do not use sunbeds.

Can telmisartan cause problems?

Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. Side-effects from telmisartan are uncommon and usually improve as your body adjusts to the new medicine, but you should speak with your doctor or pharmacist if any of the following side-effects continue or become troublesome.

Important: if you develop any swelling of your mouth or face, speak with your doctor or go to your local accident and emergency department straightaway. These are signs of an allergic reaction.

If you experience any other symptoms which you think may be due to this medicine, speak with your doctor or pharmacist.

How to store telmisartan

• Keep all medicines out of the reach and sight of children.
• Store in a cool, dry place, away from direct heat and light.

Important information about all medicines

Micardis (telmisartan) dosing, indications, interactions, adverse effects, and more

Effect of telmisartan vs. ramipril on ‘dipping’ status and blood pressure variability: pooled analysis of the PRISMA studies

Telmisartan shows greater SBP reduction and higher SI in all four dipper subgroups

In this retrospective analysis of data pooled from the two PRISMA studies,^{5, 6} a comparison of the changes from baseline in SBP at different intervals during the 24-h monitoring period demonstrated that telmisartan resulted in significantly greater SBP reductions in all four dipper subgroups compared with ramipril. Telmisartan treatment was also associated with a greater reduction in the EMBPS in the extreme dipper and dipper subgroups, a similar change in the non-dipper subgroup and a lower SBP rise in the riser subgroup compared with ramipril.

The SI, a measure of the homogeneity of BP reduction by antihypertensive treatment, was significantly higher in each dipper subgroup in patients treated with telmisartan compared with ramipril. The SI was ⩾1 in the extreme dippers, dippers and non-dipper subgroups of patients treated with telmisartan. Although the SI was <1 in the riser subgroup following telmisartan treatment, it was higher than that observed for ramipril (0.89 vs. 0.74, respectively). As a high SI (⩾1) has been reported to be associated with positive changes in carotid artery wall thickness,¹⁰ the higher SI demonstrated by the long-acting drug, telmisartan, in this current analysis may provide some cardiovascular (CV) benefit. For the extreme dippers, non-dippers and riser subgroups, who are already at a higher risk of CVD, a more homogenous BP might help to reduce their risks.

Change of dipping pattern on treatment

Classification of patients based on dipping pattern is poorly reproducible and this limits the usefulness of this concept in treating single patients. In an observational study of 414 untreated hypertensive patients, it was seen that in a quarter of patients, the initial dipping pattern was changed on repeat ABPM assessment after 4 weeks. The change was more prominent in the extreme dipper and non-dipper subgroups.¹¹ In another observational study of hypertensive and normotensive patients over a period of 1 year, 44% of patients had variable dipping status, with normal night-time BP in patients who perceived their sleep quality to be good.¹² Similarly, in the Study on Ambulatory Monitoring of Pressure and Lisinopril Evaluation (SAMPLE) study, variability in dipper status was observed in 35–40% of patients with essential hypertension and left ventricular hypertrophy.¹³ These results highlight significant intra-subject variability in the diurnal fluctuations in ambulatory BP and dipper status, suggesting that assessments based on a single ABPM cannot be taken as independent predictors of increased CV risk. Repeated ABPMs were better able to predict an ‘abnormal’ nocturnal profile correctly as a part of the risk stratification.¹⁴

However, in spite of limitations related to intra-subject dipping status variability, it has been shown that abnormal circadian patterns of BP, especially nocturnal hypertension or non-dipper status, is associated with CVD risk.¹⁵ The Coronary Artery Risk Development in Young Adults (CARDIA) study demonstrated that failure of the night-time SBP to dip sufficiently, or excessive dipping of the night-time SBP, is associated with the presence of coronary artery calcium 10–15 years later.¹⁶ A study of 900 middle-aged men and women demonstrated that those with a non-dipping nocturnal BP profile had an increased mean intima-media thickness in the carotid artery (P<0.01), an indication of early atherosclerosis.¹⁷ The reverse-dipping (riser) pattern of nocturnal BP is also an independent risk factor for CVD.^{18, 19, 20} A meta-analysis of 3648 patients from four prospective studies revealed that the dipping pattern and the night/day BP ratio significantly and independently predicted mortality and CV events in hypertensive patients without a history of major CV disease; the incidence of CV events was highest in patients in the riser (or reverse dipper) category.²¹

In the prospective, observational Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, the risk of CV events was significantly increased in non-dippers and reverse dippers among 3012 initially untreated hypertension patients followed up over a period of 8.44 years.²² Similarly, in a cross-sectional study of 376 patients with hypertension, left and right ventricular structure and diastolic function were found to be significantly more impaired with the non-dippers and the reverse dippers compared with others,²³ and pulse wave velocity was significantly higher in reverse dippers compared with dippers and non-dippers in untreated patients with hypertension.²⁴ Hence, it would be highly undesirable for an antihypertensive agent to cause patients to move from the dipper category to any of the other three categories.

This retrospective analysis showed a significant treatment effect on dipper status in favor of telmisartan compared with ramipril. The odds ratio, and sensitivity analysis, indicated a stronger tendency toward dipping in patients treated with telmisartan compared with ramipril. This is expected to protect patients on telmisartan from CVD. The greater tendency for dipping observed with telmisartan vs. ramipril is predominantly driven by the smaller proportion at the end point of non-dippers and risers/reverse dippers with telmisartan treatment than with ramipril treatment. Transition between dipper categories following treatment might be expected due to a greater efficacy of the antihypertensive drug on the daytime BP compared with the night-time BP (resulting from a <24 h duration of effect), which would make the difference between the wake and sleep BPs smaller; thus, the patient’s dipper category would change, possibly from dipper to non-dipper or riser. However, telmisartan, a long-acting drug with a high trough:peak ratio, has greater efficacy on early morning BP (falling into the last 6 h of the dosing interval) compared with ramipril,^{5, 6} which may help to maintain normal dipping status or improve the dipping status to normal. Indeed, in this analysis, only 0.9% of patients treated with telmisartan moved from the dipper to riser group, compared with 3.7% treated with ramipril. Similarly, more patients on telmisartan treatment improved from non-dipper category at baseline to dipper category at end point. Of the risers/reverse dippers at baseline, more patients on ramipril than telmisartan remained in the same category at end point. Similar proportions of patients on either treatment improved from extreme dipper category at baseline to dipper category at end point. Consistent with this finding, the mean percentage change from baseline to end point in SBP during sleep time also decreased in the extreme dipper category on either treatment.

The extreme dipper profile is commonly associated with a larger early morning SBP surge. Importantly, telmisartan treatment was associated with significantly greater reductions from baseline in the NTL, EMM, and morning surge SBPs compared with ramipril in patients with an early morning SBP surge ⩾35 mm Hg, suggesting that it provides more effective BP control in these high-risk patients. A very high or very low EMBPS is reported to be associated with CV events. A meta-analysis of individual data from more than 5000 patients randomly recruited from eight different countries and followed up for an average of 10 years showed an EMBPS ⩾37.0 mm Hg to be a significant and independent predictor of mortality and CV events,²⁵ while in normotensive and well-controlled hypertensive elderly followed up for a period of 5 years, an EMBPS ⩾34 mm Hg was found to be associated with CV events.²⁶ Further studies also show that those individuals who experience a high EMBPS have a higher incidence of cerebrovascular events and higher CV mortality.^{8, 27} In contrast, in a recent study in 3012 initially untreated white patients with essential hypertension followed up for a period of 8.44 years, a blunted EMBPS (⩽9.5 mm Hg) was found to be an independent predictor of CV events.²²

Ideally, antihypertensive agents should provide smooth and sustained BP control over the full 24-h circadian cycle.²⁸ Maintaining efficacy during the trough period can be difficult as many antihypertensive agents are taken once daily in the morning, so a longer duration of action would be expected to provide benefits in terms of reducing the EMBPS.²⁹ Telmisartan, with its long duration of action, may help to maintain normal dipping status or improve the dipping status to normal, and to reduce BP variability during the early morning hours, the critical period of the morning surge.

In conclusion, studies have shown that BP variability adds to the prediction of CV events beyond average BP levels. This seems especially true for dipping pattern and the EMBPS, which means that the analysis of the effects of antihypertensive treatment can no longer be limited to average BP levels. In this retrospective analysis of two studies of identical design, telmisartan normalizes the circadian BP pattern to a dipper profile in a larger proportion of patients than ramipril and reduces EMBPS in high-risk patients. This can be expected to reduce the incidence of CV events, although a potential benefit of improved BP variability beyond average BP lowering may take longer to materialize. Further evidence is needed from long-term prospective trials and observational studies on the potential benefits of a normalized circadian profile on CV outcomes.

Blood pressure drug Micardis cuts heart risk: study

CHICAGO (Reuters) – The blood pressure drug Micardis was as effective in preventing serious heart problems in high-risk patients as certain older drugs, but with fewer side effects, international researchers said on Monday.

The Boehringer Ingelheim drug Micardis, or telmisartan, is typically used in patients with heart failure, but the study found it worked as well as the ACE inhibitor ramipril, marketed in the United States as Altace by King Pharmaceuticals Inc.

“We have one more alternative to use,” said Dr. Salim Yusuf of McMaster University in Ontario, Canada. “This is probably key for the 20 to 30 percent of people who don’t tolerate an ACE inhibitor,” said Yusuf, who presented the study at a meeting of the American College of Cardiology in Chicago.

Telmisartan is an angiotensin receptor blocker, or ARB. Ramipril is an angiotensin converting enzyme, or ACE, inhibitor. Both act on a compound called angiotensin in different ways to regulate blood pressure.

A team of international researchers compared the drugs in a study of more than 25,620 patients with heart disease or diabetes and other heart risk factors, but not heart failure.

Telmisartan and ramipril alone worked equally well to reduce cardiovascular death, stroke, heart attack or hospitalization for heart failure, but telmisartan was easier to tolerate than ramipril, with fewer patients experiencing cough or other side effects.

Micardis is the first ARB to be shown to have heart benefits in patients who do not have heart disease. But since the drug is more costly than the typical ACE inhibitor, the study may not change practice, doctors said.

“The newer drug is certainly not better,” said Dr. Steven Nissen, a cardiologist from the Cleveland Clinic.

“The drugs were equivalent in the trial, which means that the same results can be achieved with an ACE inhibitor,” Nissen said in an interview. “I think most physicians will choose the drugs that are generically available,” he said.

The study, published online in the New England Journal of Medicine, also tested to see if Micardis combined with an ACE inhibitor might work even better. But the researchers found the combination caused a number of negative side-effects in patients who do not have heart failure.

Yusuf said the findings mean doctors need to be careful not to use both drugs in patients. “What was even more important was adding the two together could cause harm,” he said.

Editing by Maggie Fox; Editing by Gary Hill

Diabetes Clinic

About Micardis

Micardis (telmisartan) is a white, oblong-shaped, uncoated tablet containing either 40 mg or 80 mg of telmisartan as the active ingredient. In addition, Micardis tablets contain the following nonmedicinal ingredients: magnesium stearate, meglumine, povidone, sodium hydroxide and sorbitol.

If you are on a special diet, or if you are allergic to any substance, ask your doctor or pharmacist whether any of these ingredients may cause a problem.

Why has Your Doctor Prescribed Micardis?

Your doctor has prescribed Micardis tablets for your high blood pressure, also known as hypertension.

What is Blood Pressure?

Blood pressure is the pressure of the blood on an arterial wall which is pumped by the heart to all parts of your body. Your blood pressure might change depending on your level of activity, stress or excitement, and other such factors.

What is High Blood Pressure (Hypertension)?

High blood pressure increases the workload of the heart and arteries. If this condition continues for a long time, damage to the blood vessels of the brain, heart and kidneys can occur, and may eventually result in a stroke, heart failure or kidney failure. High blood pressure also increases the risk of heart attacks. Reducing your blood pressure decreases your risk of developing these illnesses.

How do you Know if you Have High Blood Pressure?

To detect high blood pressure, it is recommended that you have your blood pressure checked regularly by your doctor, as there may be no symptoms associated with high blood pressure.

Why Should you be Treated?

High blood pressure if left untreated, could lead to stroke, heart attack, heart failure, kidney failure or blindness.

How Does Micardis Work?

Angiotensin II is a naturally occurring hormone in the human body that causes the blood vessels to constrict, thus affecting the blood pressure. Micardis lowers blood pressure by specifically blocking the action of angiotensin II, and thus relaxing the blood vessels and as a result blood pressure is lowered.

What you Should Tell Your Doctor Before you use Micardis?

You should tell your doctor the following before you use Micardis:

• If you have any allergies.
• If you are pregnant or intend to become pregnant. When used in pregnancy during the second and third trimester, drugs like Micardis can cause fetal injury or death.
• If you are breast-feeding. It is not known whether telmisartan can pass into human milk, therefore do not breast-feed during treatment.
• If you have any other health problems, including kidney or liver disease.
• If you are taking any other medication, including diuretics, herbal preparations or any other medications you can buy without a prescription.

How to Take Micardis

The recommended dose of Micardis (telmisartan) is 80 mg once daily. It may be taken with or without food, but it should be taken the same way each day. You should follow any other direction that your doctor has given you for the treatment and/or monitoring of your condition.

What Happens if a Dose is Missed?

Try to take your dose at the same time each day, preferably in the morning. However, if you have forgotten to take your dose during the day, carry on with the next one at the usual time. Do not double dose.

What to do in Case of Overdose

If you experience dizziness and/or fainting, contact your doctor immediately so that medical attention may be given promptly.

Additional Notes to Remember

• Micardis has been prescribed to treat your condition. Do not give it to other people.
• Do not take any other medication without your doctor’s advice. Tell any other doctor, dentist or pharmacist with whom you consult that you are using Micardis.
• In case of overdosage, consult your doctor immediately.
• Keep out of the reach of children.
• Consult you doctor immediately if you become pregnant while using Micardis. Drugs like Micardis can cause fetal injury or death.
• Like any drug product, Micardis may cause some unwanted effects along with good effects. The most common adverse events in patients treated with Micardis tablets as compared to placebo were: headache, upper respiratory tract infection, dizziness, pain and diarrhea. Tell your doctor or pharmacist promptly about these or any other unusual symptoms.
• If you develop an allergic reaction involving swelling of the face, lips and/or tongue, stop taking Micardis and contact your physician immediately.
• If you have any other questions about Micardis, contact your doctor or pharmacist.

How Should Micardis be Stored?

Micardis tablets should be stored at room temperature (15 to 30°C). Tablets should not be removed from blisters until immediately prior to administration. Avoid excessive heat and avoid moisture. Keep out of reach of children and pets.

Mikardis – an effective means of blood pressure control

On July 18, at the 18th Scientific Congress of the European Society of Hypertension and the 22nd Scientific Congress of the International Society of Hypertension, held in Berlin (Germany), the results of two new studies were presented that showed the benefits of using the drug Mikardis ^® (Telmisartan) in combination with amlodipine and hydrochlorothiazide.
In one study, Mikardis ^® (telmisartan) was used in combination with amlodipine, in another – as a fixed combination with hydrochlorothiazide at a dose of 25 mg. These studies have confirmed that the therapy of arterial hypertension, based on the use of telmisartan, in patients at risk of cardiovascular events provides powerful and long-term control of blood pressure, even in patients with hypertension that is difficult to treat [1-5].

Commenting on the research findings, Professor Thomas Unger, Director of the Institute of Pharmacology at the Charite Medical University (Berlin) , stated: “Blood pressure control is a challenge that usually requires more than just antihypertensive drugs.It has been proven that telmisartan is not only effective in lowering blood pressure, but also has a protective effect in patients at high risk of cardiovascular disease. Two new studies show that the combination of telmisartan with other antihypertensive drugs – amlodipine and hydrochlorothiazide, which have a different mechanism of action – may reduce the risk of myocardial infarction and stroke.

The combination of telmisartan and amlodipine provides an effective decrease in blood pressure throughout the day
The study involved 1461 patients who were prescribed telmisartan (a modern angiotensin II receptor blocker) and amlodipine.Study participants were randomized to receive therapy with telmisartan 0 (placebo), 20, 40, 80 mg and amlodipine 0 (placebo), 2.5; 5 or 10 mg [1].
After 8 weeks of therapy, a significant decrease in blood pressure was noted for all target combinations (telmisartan 40 or 80 mg plus amlodipine 5 or 10 mg, p <0.05). The greatest decrease in blood pressure (-26.4 / -20.1 mm Hg) and the highest level of blood pressure control (76.5% of patients) were shown in the group of patients who received 80 mg of telmisartan and 10 mg of amlodipine [1 ].In addition, combinations of drugs in different dosages were equally well tolerated by patients [4].
A follow-up study, which included 562 patients, showed that the combination of telmisartan and amlodipine provides complete blood pressure control for 24 hours. To confirm this, patients underwent daily ambulatory blood pressure monitoring. Of particular importance is the fact that pressure control persisted in the early morning hours, since it is at this time of day that the lack of blood pressure control increases the risk of myocardial infarction and stroke.The antihypertensive effect of this combination was twice as high as compared with monotherapy with one of the drugs [2].

Fixed combination of telmisartan 80 mg and hydrochlorothiazide 25 mg: benefits for patients with poorly responsive arterial hypertension
The second long-term study involved patients with essential hypertension who previously failed to achieve adequate blood pressure control. Study participants received a fixed combination therapy of telmisartan 40 mg / hydrochlorothiazide 25 mg (n = 321) or telmisartan 80 mg / hydrochlorothiazide 12.5 mg (n = 318) [5].
After 24 weeks of treatment with a combination of telmisartan 80 mg / hydrochlorothiazide 25 mg, the number of patients reached the target blood pressure, namely diastolic blood pressure <90 mm Hg. Art., increased from 52.4 to 71.4% [5]. Most often, the achievement of target blood pressure levels was observed at the 4th week of therapy and persisted throughout the study. At the end of the study, the majority of patients (85.6%) did not need additional antihypertensive drugs.The therapy was well tolerated by all patients, as in the first study [5].
It should be added that the European Commission recently approved the use of the fixed combination telmisartan 80 mg / hydrochlorothiazide 25 mg in patients with difficult to treat hypertension, as well as in patients in whom taking lower doses of the telmisartan / hydrochlorothiazide combination does not lead to adequate blood pressure control …

ONTARGET ^® Study – evidence of good tolerability and cardiovascular protective properties of telmisartan
Telmisartan is the only angiotensin II receptor blocker with proven effective antihypertensive action and cardiovascular protective properties in a wide population of vascular patients with high cardiovascular risk [6].Earlier at ACC 2008, the first results of the ONTARGET ^® study were presented. They showed that telmisartan has protective properties similar to ramipril (formerly the gold standard) in reducing cardiovascular deaths, myocardial infarction, stroke and hospitalizations due to congestive heart failure in a wide population of high-risk patients. In addition, the results of the study indicate a better tolerance of telmisartan compared with ramipril [6].
Telmisartan also has a more pronounced hypotensive effect compared to angiotensin receptor blockers such as losartan [7] and valsartan [8]. In addition, telmisartan has been proven to lower blood pressure no less effectively than antihypertensive drugs of other classes, such as enalapril, lisinopril, ramipril, amlodipine and atenolol [9-13].
In conclusion, we note that today cardiovascular diseases are the leading cause of disability worldwide.Cardiovascular disease is the leading cause of death, causing more than 17.5 million deaths annually [14]. Every year 7.6 million people die from myocardial infarction and 5.7 million from stroke [4]. It is assumed that by 2020 the annual mortality from cardiovascular diseases will reach 25 million people [15, 16].

About Telmisartan (Micardis ^® / Kinzal ^® / Pritor ^® )
Telmisartan belongs to the class of angiotensin II receptor blockers.The drug is approved for the treatment of hypertension of varying severity. To study the protective properties of telmisartan, more than 58 thousand patients have been included in the current clinical programs ONTARGET, PROTECTION and PRoFESS.
Telmisartan was discovered and developed by Boehringer Ingelheim. Under the trademarks Micardis ^® and MicardisPlus ^® (combination with hydrochlorothiazide), the drug is presented in 84 countries of the world, including the USA, Japan and European countries.In some markets telmisartan is promoted in conjunction with other companies: Astellas Pharma Inc. in Japan, Bayer HealthCare and GlaxoSmithKline in Europe.
Astellas Pharma Inc. promotes telmisartan under the brand name Micardis ^® , Bayer HealthCare under the brand name Kinzalmono ^® , Kinzalkomb ^® (combination with hydrochlorothiazide). Pritor ^® and PritorPlus ^® are marketed in Europe and are also co-produced by GlaxoSmithKline.

About ONTARGET
The ONTARGET Clinical Trials Program consists of two randomized, double-blind controlled trials: the main ONTARGET study, the results of which were presented on March 31, 2008, and the parallel TRANSCEND study (Telmisartan Randomized Assessment Study in ACE-I INtolerant subjects with cardiovascular Disease), the results of which are also expected this year [6].
In the ONTARGET study, patients were divided into three treatment groups: telmisartan 80 mg, ramipril 10 mg, and a combination of telmisartan 80 mg and ramipril 10 mg.
In the TRANSCEND study, patients were divided into two treatment groups: telmisartan 80 mg or placebo; the drug was prescribed in addition to standard antihypertensive therapy, which did not include angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers [6, 17].
The ONTARGET research program included patients over the age of 55 years with a history of coronary heart disease, stroke, recent transient ischemic attack, peripheral vascular disease or diabetes mellitus with target organ damage (presence of microalbuminuria or hypertrophy of the left ventricular walls) [17].

The endpoint in the
ONTARGET study consisted of four components: cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure. The study did not include patients with ACE inhibitor intolerance (in this case, the patient was included in the TRANSCEND study).
The ONTARGET program is sponsored by Boehringer Ingelheim, and in some countries, Bayer HealthCare and GlaxoSmithKline are involved.

About Boehringer Ingelheim
Boehringer Ingelheim is one of the 20 leading pharmaceutical companies in the world. The company is headquartered in Ingelheim (Germany) and manages 137 offices in 47 countries, employing 47 thousand workers. Since its founding in 1885, the company has been owned by the same family and has been engaged in the discovery, research, production and sale of products of high therapeutic value in medicine and veterinary medicine.
In 2007net profit of the company
Boehringer Ingelheim totaled € 10.9 billion, with a fifth of its revenue in the largest sales segment, prescription drugs, invested in new drug development.

Additional information: www.news-ontarget.com,
www.ontarget-telmisartan.com,
www.micardis.com

Literature
1. Littlejohn T. et al. Superior antihypertensive efficacy of the combination of telmisartan and amlodipine versus respective monotherapies in patients with hypertension: results of a factorial design study.Poster presented at 18th Scientific Meeting of the European Society of Hypertension and the 22nd Scientific Meeting of the International Society of Hypertension; Berlin, Germany, June 18 2008.
2. Littlejohn T. et al. Telmisartan and amlodipine combination therapy is powerful at lowering 24 hour blood pressure: findings of an ABPM substudy in hypertensive patients. Poster presented at 18th Scientific Meeting of the European Society of Hypertension and the 22nd Scientific Meeting of the International Society of Hypertension; Berlin, Germany, June 16 2008.
3. Littlejohn T. et al. Telmisartan and amlodipine combination provides an effective treatment option for patients with moderate or severe hypertension: subanalysis from a factorial design study Poster presented at 18th Scientific Meeting of the European Society of Hypertension and the 22nd Scientific Meeting of the International Society of Hypertension; Berlin, Germany, June 18 2008.
4. Littlejohn T. et al. Effect of telmisartan addition to amlodipine on reduction of incidence of peripheral edema and orthostatic BP changes: safety analysis.Poster presented at 18th Scientific Meeting of the European Society of Hypertension and the 22nd Scientific Meeting of the International Society of Hypertension; Berlin, Germany, June 18 2008.
5. Neldam S. et al. Efficacy and safety of telmisartan 80mg / HCTZ 25mg fixed-dose combination, alone or with other antihypertensive medications, during open-label, long-term treatment. Poster presented at 18th Scientific Meeting of the European Society of Hypertension and the 22nd Scientific Meeting of the International Society of Hypertension; Berlin, Germany, June 18 2008.
6. The ONTARGET investigators. N Eng J Med 2008; 358 (15): 1547-1959.
7. Mallion J.M. J Hum Hypertens 1999; 13: 657-664.
8. Lacourciere Y. et al. Blood Press Monit 2004; 9: 203-210.
9. Parati G.F. et al. Presented at the Annual Meeting of the European Society of Hypertension. June 2006, Madrid, Spain.
10. Neutel J.M. et al. Am J Ther 1999; 6: 161-166.
11. Freytag F. et al. Clin Ther 2001; 23: 108-123.
12. Lacourciere Y. et al.Blood Press Monit 1998; 3: 295-302.
13. Williams B. et al. Br J Hypertens 2006; 24: 193-200.
14. World Health Organization, Fact Sheet 317: Cardiovascular Diseases February 2007. http://www.who.int/mediacentre/factsheets/fs317/en/index.html (Accessed June 2008)
15. Murray C. J. L., Lopez A. D. eds. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. Cambridge; Harvard University Press 2001.
16. Primary Prevention of Ischemic Stroke. A Guideline From the American Heart Association / American Stroke Association Stroke Council. Stroke 2006; 37: 1583-1633.
17. The ONTARGET / TRANSCEND Investigators. Am Heart J 2004; 148 (1): 52-61.

Translation from English Olga Tatarenko

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26.09.2021

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Mildronate® is a supra nosological preparation for comorbid patients

The problem of multimorbidity and comorbidity of swelling is of increasing urgency, so that the increase in the number of patients from ≥5 patients with ailments for a 10-day period is 16%.Comorbid pathologies are often promoted by the middle of individuals from heart-vascular disease (CVD), sprouting in representatives of young adult groups. The introduction of comorbid patients to a high frequency of the use of a combined treatment for the improvement of the general indicators of the skin from obvious ailments, so that the need for an one-hour consumption of a significant drug is necessary. For the solution of the problem of polypragmacy, one of the promising directions may be called supra-nosological pharmacotherapy….

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90,000 more than just lowering blood pressure – the topic of a scientific article on clinical medicine

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hypertension

LECTURE Volume 17, No. 2/2011

Micardis in daily clinical practice: more than just lowering blood pressure

A.O. Konradi

Federal State Institution “Federal Center for Heart, Blood and Endocrinology named after V.A. Almazov “Ministry of Health and Social Development of the Russian Federation, St. Petersburg, Russia

Konradi A.O. – Deputy Director of the Federal State Institution “FTSSKE im. V.A. Almazov “on scientific work, doctor of medical sciences, professor. Contact information: Federal State Institution “Federal Center for Heart, Blood and Endocrinology named afterV.A. Almazov “Ministry of Health and Social Development of the Russian Federation, st. Akkuratova, 2, St. Petersburg, Russia, 197341. Tel .: 8 (812) 702-33-37. E-mail: [email protected] (Alexandra Olegovna Konradi).

Keywords: blockade of the renin-angiotensin system, prognosis, organoprotection, telmisartan.

Telmisartan in everyday clinical practice:

More than blood pressure lowering

A.O. Konradi

Almazov Federal Heart, Blood and Endocrinology Center, St Petersburg, Russia

Corresponding author: Almazov Federal Heart, Blood and Endocrinology Center, 2 Akkuratov st., St Petersburg, Russia, 197341. Phone: 8 (812) 702-33-37. E-mail: [email protected] (Alexandra O. Konradi, MD, PhD, Professor, the Assistant Director for Research, the Head of the Hypertension Research Department at Almazov Federal Heart, Blood and Endocrinology Center, the President of Antihypertensive League) …

Key words: renin-angiotensin system blockade, prognosis, organoprotection, telmisartan.

Received: 20.04.11. and accepted for publication: 04.24.11.

Introduction

The role of the renin-angiotensin system (RAS) in the pathogenesis of many cardiovascular diseases and their complications is indisputable.The physiology of this system has been known for over 100 years, and since the time when Tigerstedt [1] first showed in 1898 that rabbit kidney bark extract has a prohypertensive effect, our understanding of the significance of circulating and especially tissue ASD has expanded significantly. The activation of this system is accompanied by vasoconstriction, stimulation of hypertrophy and fibrosis of the myocardium and vascular wall. Stimulation of intracellular signaling pathways leads to unfavorable processes of remodeling of the structures of blood vessels, heart, kidneys and an increase in vascular stiffness.

The beneficial effect of blocking RAS is also clearly shown for various conditions, such as arterial hypertension (AH), postinfarction remodeling of the left ventricle (LV), chronic heart failure, stroke, as well as various stages of kidney damage in AH and diabetes mellitus (DM) [2 ]. The long history of the clinical use of angiotensin-converting enzyme (ACE) inhibitors, and subsequently angiotensin II receptor blockers (ARB II), has gradually formed a modern balanced understanding of the place of each group of drugs in blocking ASD and the realization of the clinical effect of such an effect.More problematic is still

, the question remains about the combined use of these groups of drugs, as well as about the place of direct renin inhibitors, which are still under study.

Blocking ASD has great advantages in a number of pathologies, in particular for providing organoprotection in the therapy of hypertension [2-3]. It has now been proven that the use of angiotensin II receptor antagonists, in particular telmisartan, causes a reverse development of left ventricular hypertrophy (LVH), myocardial fibrosis, vascular wall remodeling, atherosclerotic lesions, and also contributes to the restoration of endothelial function.In general, if we consider the treatment of hypertension, especially in the early stages, not only as a symptomatic decrease in blood pressure (BP), but as an attempt to prevent or cause regression of pathological remodeling of the cardiovascular system, then patients should be treated with the obligatory use of blockade of the effects of angiotensin II ( ATP). It is no coincidence that ARB IIs were chosen to conduct the only research on the prevention of hypertension – TROPHY [4]. The pronounced organoprotective effect and excellent tolerance of ARB II today determine their rapid growth in the frequency of prescriptions in the world, and in some countries, the issue of their over-the-counter dispensing along with statins is being considered in the range of

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programs for primary and secondary prevention of cardiovascular diseases.

However, a number of the effects of blockade of ASD when using ARB II go beyond not only lowering blood pressure, but also beyond organoprotection. We are talking about the anti-atherosclerotic effect, about the prevention of the development of diabetes, about the prevention of rhythm disturbances, in particular atrial fibrillation, as well as about the total reduction of cardiovascular risk. Telmisartan (Mikardis 80 mg) is the first and only ARB II in Russia that has officially registered indications not only for “Arterial hypertension”, but also for “Reduction of cardiovascular morbidity and mortality in patients aged 55 years and older with a high risk of cardiovascular diseases “.

In this regard, the purpose of this review is not only to summarize the data on the features of the antihypertensive and organoprotective action of Mikardis, but also to summarize its effects on the effect on general and cardiovascular morbidity and mortality.

Brief pharmacological characteristics of Telmisartan (Mikardis)

Micardis provides stable, but reversible binding to receptors for ATP type 1 and has the highest affinity for these receptors among all ARB II available for clinical use today.At the same time, Mikardis has minimal affinity for the second type of receptors, as well as other receptors involved in the regulation of blood pressure.

A feature of Mikardis is its high lipophilicity, due to which good penetration into organs and tissues and blocking of tissue effects of ATP is achieved. Another distinctive feature is the long half-life (up to 24 hours), which ensures the smoothness of the antihypertensive effect and the absence of withdrawal syndrome.The duration of the effect underlies the elimination of the adverse effects of morning rises in blood pressure [3].

Another important feature of the telmisartan molecule, which has been actively discussed in the literature over the past 10 years, is its ability to modulate the so-called PPARy receptors, which are now regarded as the most important therapeutic target in the treatment of metabolic syndrome and obesity and the prevention of diabetes mellitus. Activation of PPARy receptors also leads to an increase in adiponectin levels, anti-inflammatory and antioxidant effects, inhibition of proliferation and a decrease in the risk of atherosclerosis.The effect of stimulating these receptors has been described for other members of the class, but for telmisartan it has been proven at significantly lower concentrations, which today has become a widely discussed advantage of Mikardis and formed the basis for explaining many “pleotropic” effects [3].

The longest half-life, the maximum volume of distribution in tissues and the highest degree of PPARy receptor activation allowed for

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list Mikardis as a second generation ARB II and call it a “bridge” to the creation of a fundamentally new class of drugs with multiple effects [2].

Antihypertensive activity – comparison with other drug classes and with other ARBs II

Among all ARBs II, Micardis has the largest evidence base in terms of the number of observations in relation to various comparisons with other drugs.Long listing of these studies and their detailed analysis within the framework of this review does not make sense. Based on the general thesis that the antihypertensive activity of most modern antihypertensive drugs is comparable to each other, it should be noted that according to the office changes in blood pressure and its daily monitoring in a number of studies telmisartan surpassed losartan, eprosartan and valsartan in its activity [5-7]. no comparison with irbesartan was carried out, and comparison with olmesartan gave conflicting results (weaker antihypertensive effect, but more significant decrease in the morning rise in blood pressure) [8].

Comparison with ACE inhibitors has been carried out more widely, in particular, in such studies as PRISMA I and II [9], which showed advantages over ramipril in terms of lowering blood pressure. In smaller studies, a greater effect was shown in comparison with comparable doses of perindopril, lisinopril [10-11]. Like all ARBs II, telmisartan was better tolerated in all studies than ACE inhibitors.

Most studies comparing the effects of telmisartan with calcium antagonists and beta-blockers have shown a comparable effect in reducing blood pressure, the same is true for diuretics [12-14].

Telmisartan and organoprotection

Left ventricular hypertrophy

Plasma ATP levels are closely related to the severity of LVH. The data available today indicate that regression of LVH leads to a twofold decrease in the risk of mortality and, of course, is an important task in the treatment of patients with essential hypertension (HD). In addition to influencing the prognosis, a decrease in LVH is accompanied by a number of beneficial consequences: an improvement in LV systolic function, an improvement in the parameters of diastolic filling, a change in the balance of the autonomic nervous system towards its normalization, as well as restoration of baroreflex sensitivity, a decrease in the number of ventricular arrhythmias and an increase in coronary reserve [15 ].

With the advent of ARB II, great hopes were pinned on drugs in this group in terms of cardioprotective effects. Within the framework of the large LIFE study (more than 9000 patients), which was mainly aimed at analyzing the prognosis of hypertensive patients with losartan therapy in comparison with atenolol, also

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Figure 1.Effect of various drugs on left ventricular hypertrophy

Note: LVMI – left ventricular myocardial mass index; BAB – beta-blockers; ACE inhibitors – angiotensin converting enzyme inhibitors; ARA – angiotensin II receptor antagonists.

, LVH regression was assessed, and undeniable benefits were noted for ARB II [16]. Long-term results of this study showed a decrease in the risk of sudden death among those individuals who achieved a decrease in LVH on the background of losartan therapy [17].A 2003 meta-analysis (Fig. 1) once again put this class of drugs in first place for efficacy in the treatment of LVH [18], which identified LVH as one of the indications for ARB II in the 2007 European Society guidelines [19].

The results of our studies comparing the effects of various drugs showed that the most significant relative reduction in myocardial mass was achieved in the groups of patients who received the ATP receptor antagonist telmi-sartan (Fig.2).

The effects of telmisartan on LVH have been compared with diuretics (shown to be superior to hydrochlorothiazide), beta-blockers (more effective than carvedilol) [20].

It should be borne in mind that the dynamics of the LV mass index, of course, does not reflect the entire complex of structural changes in the myocardium under the influence of drug therapy.

rapies.Most drugs that reduce LV mass do not have the ability to reverse fibrosis, which leads to a relative increase in collagen content in the heart muscle [21]. In this respect, theoretically, drugs with antagonistic activity against fibrosis factors – ACE inhibitors and aldosterone antagonists, as well as ARB II – should have advantages. In this aspect, the most convincing data were obtained in the course of experimental work.

Vascular stiffness and endothelial dysfunction

RAS is also critical in the development of vascular remodeling.Experimental studies have shown that when modeling renovascular hypertension, pronounced hypertrophy of vascular cells is observed, while in genetic AH, wall remodeling without pronounced hypertrophy is more characteristic [22]. ATP is produced in the vascular wall in large quantities due to the local RAS system and directly stimulates hypertrophy of smooth muscle cells, as well as the production of fibroblast growth factor transforming

Figure 2.Dynamics of the left ventricular myocardial mass index in the groups of patients receiving therapy with various classes of antihypertensive drugs

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growth factors 1-beta, responsible for the transformation of fibroblasts into myofibroblasts and the production of collagen in them [22].It also activates the production of endothelin. ATP also activates platelet growth factor synthesis in [22]. LTP not only activates collagen production, but also interacts with the collagenase system that degrades it. It can also be an inducer of vascular cell apoptosis, which is an invariable attribute of vascular remodeling.

ATII stimulates hyperplasia, hypertrophy, as well as pro- and anti-apoptotic effects and is a regulator of the production of numerous growth factors: endothelin-1, platelet growth factor, fibroblast growth factor, insulin-like factor and TGF-P1.

RAS, especially local, takes an active part in the development of endothelial dysfunction and acceleration of the processes of atherosclerosis in the vascular wall. Excess ATII leads to increased oxidative stress, increased synthesis of chemoattractants and adhesion molecules that stimulate inflammation. In addition, prothrombotic (induction of tissue plasminogen inhibitor, platelet aggregation) and proliferative action of ATII are realized. Later, LTP takes part in the processes of destabilization and rupture of atherosclerotic plaques, along with systemic pathological vascular remodeling.

Taking into account the role of ASD in the pathogenesis of vascular wall remodeling and due to the accumulated data, blockers of this system are considered drugs with the maximum ability to induce regression of changes in vessels in hypertension [23]. A number of studies have shown that telmisartan therapy reduces the stiffness of the vascular wall (the speed of propagation of the pulse wave). This effect is shown both for patients with hypertension and diabetes mellitus [24-25], both with therapy for 3 weeks, and with longer periods of treatment.

There are many potential mechanisms by which telmisartan is able to improve endothelial function: a decrease in the production of free radicals, a decrease in atherosclerotic damage, inhibition of inflammation, and a decrease in insulin resistance. The most striking clinical evidence of the beneficial effect was a study comparing telmisartan with ramipril (TRENDY) [26], in which both drugs contributed to the restoration of endothelial function.

Interestingly, the improvement of endothelial function for telmisartan has been shown in various vascular regions, in particular, it has recently been demonstrated that treatment with telmisartan leads to an improvement in vascular reactivity and an increase in walking distance in patients with obliterating atherosclerosis of the vessels of the lower extremities [27]. Moreover, telmisartan therapy has been shown to increase the number of circulating endothelial progenitor cells in patients with coronary artery disease and normal blood pressure (in a double-blind study) [28].

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Telmisartan and renoprotection

The mechanism of the positive effects of RAS blockade on renal damage also lies in the plane of hemodynamic effects – a decrease in perfusion pressure and anti-inflammatory and antioxidant properties. The nephroprotective effect of telmisartan, closely associated with an improvement in endothelial function, was shown in the already mentioned TRENDY study [26], in which telmisartan treatment reduced albuminuria and led to an increase in renal blood flow and a decrease in renal resistance.The DETAIL study [29], which demonstrated the benefits of telmi-sartan in reducing both micro- and macroalbuminuria in diabetes mellitus, is also considered a classic. Moreover, in the AMADEO study [30] tel-misartan was shown to reduce albuminuria more significantly than losartan.

The final chord in the chain of studies on the effects of telmisartan on the renal continuum was the VIVALDI study [31], in which 80 mg of telmisartan had an effect comparable to valsartan at a dose of 160 mg in reducing albuminuria, dynamics of glomerular filtration rate or changes in plasma creatinine levels.A series of these successful studies have identified the current indications for the prescription of telmisartan, including the delay in nephropathy in diabetes mellitus.

Telmisartan and cardiovascular prognosis

Thanks to the ONTARGET study [32], which includes two independent programs – ONTARGET and TRANSCEND [33], telmisartan has become the most well-studied member of its class in terms of its effect on various types of rigid endpoints, including all cardiovascular diseases and mortality from various causes.While the results of these studies cannot be called a class II victory over ACE inhibitors, and the results of these studies raised more questions than they answered with regard to their use, the release of the results of these largest clinical trials marked the beginning of the use of ARB II, namely telmisartan. as a drug with the ability to prevent CVD. Based on the results of the ONTARGET study, we can still state today that telmisartan is the only ARB II that has a cardioprotective effect in high-risk patients, and, being no less effective than ramipril, has significantly better tolerability.

Conclusion

Thus, the pharmacological uniqueness of telmisartan (Mikardis) provides its stronger and longer antihypertensive effect in comparison with other drugs, including sartans. It has also been proven that Mikardis has both significant renoprotective and cardioprotective effects and is able to reduce cardiovascular mortality.

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This opens up new prospects for the use of Mi-Cardis 80 mg not only as an effective agent for the treatment of grade 1-2 hypertension as monotherapy, but also for the recognition of Mikardis as a basic drug in the combination therapy of hypertension, diabetes mellitus and in the treatment of high-risk patients [34].In other words, the effect of prescribing Mikardis 80 mg is measured today not only in millimeters of mercury, but also in the number of lives saved, which is the most important strategy in the treatment of patients in our daily practice.

Literature

1. Tigerstedt R., Bergman P.G. Nierre und Kreislauf // Skand. Arch. Physiol. – 1898. – Vol. 8. – P. 223-271.

2.Kurtz T.W., Klein U. Next generation multifunctional angiotensin receptor blockers // Hypertens. Res. – 2009. – Vol. 32, No. 10. – P. 826-834.

3. Galzerano D., Capogrosso C., Di Michele S. et al. New standards in hypertension and cardiovascular risk management: focus on telmisartan // Vasc. Health Risk Manag. – 2010. – Vol. 6. – P. 113-33.

4. Nesbitt S.D., Julius S., Leonard D., Egan B. M., Grozinski M., TROPHY study investigators. Is low-risk hypertension fact or fiction? Cardiovascular risk profile in the TROPHY study // Am. J. Hypertens. – 2005. – Vol. 18, No. 7. – P. 980-985.

5. Derosa G., Ragonesi P., Mugellini A., Ciccarelli L., Fogari R. Effects of telmisartan compared with eprosartan on blood pressure control, glurose metabolism and lipid profile in hypertensive, type II diabetic patients: a randomized, double -blind, placebo-controlled 12-month study // Hypertens.64.

6. Mallion J.M., Siche J.P., Lacourciere Y, the telmisartan blood pressure monitoring group. ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension // J. Hum. Hypertens. – 1999. – Vol. 13, No. 10. – P. 657-664.

7. Smith D.H., Cramer M.J., Neutel J.M., Hettiarachchi R., Koval S. Comparison of telmisartan versus losartan: meta-analysis of titration-to-response studies // Blood Press. Monit. – 2003. – Vol. 8, No. 3. – P. 111-117.

8. Sasaki T., Noda Y, Yasuoka Y. et al. Comparison of the effects of telmisartan and olmesartan on home blood pressure, glucose, and lipid profiles in patients with hypertension, chronic heart failure, and metabolic syndrome // Hypertens. Res. – 2008. – Vol. 31, No. 5. – P. 921-929.

9. Lacourciere Y., Neutel J.M., Davidai G., Koval S. A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring // Am. J. Hyper-tens. – 2006. – Vol. 19. – P. 104-112.

10. Nalbantgil I., Nalbantgil S., Ozerkan F. et al. The efficacy of telmis-artan compared with perindopril in patients with mild-to-moderate hypertension // Int.J. Clin. Pract. – 2004. – Vol. 58, No. 145. – P. 50-54.

11. Neutel J.M., Frishman W.H., Oparil S., Papademitriou V., Guthrie G. Comparison of telmisartan with lisinopril in patients with mild-to-moderate hypertension // Am. J. Ther. – 1999. – Vol. 6, No. 3. – P. 161-166.

12. Galzerano D., Tammaro P., del Viscovo L. et al. Three-dimensional echocardiographic and magnetic resonance assessment of the effect of telmisartan compared with carvedilol on left ventricular mass a multicenter, randomized, longitudinal study // Am.J. Hypertens. – 2005. – Vol. 18, no. 12, Pt. 1. – P. 1563-1569.

13. Lacourciere Y., Lenis J., Orchard R. et al. A comparison of the efficacy and duration of action of the angiotensin II receptor blocker telm-isartan to amlodipine // Blood Press. Monit. – 1998. – Vol. 3, No. 5. – P. 295-302.

14. Derosa G., Cicero A. F. G., Bertone G. et al. Comparison of the effects of telmisartan and nifedipine gastrointestinal therapeutic system on blood pressure control, glucose metabolism, and the lipid profile in patients with type 2 diabetes mellitus and mild hypertension: a 12-month, randomized, double-blind study // Clin.Ther. – 2004. – Vol. 26, No. 8. – P. 1228-1236.

15. Dahlof B., Pennert K., Hansson L. Reversal of left ventricular hypertrophy in hypertensive patients – a metaanalysis of 109 treatment studies // Am. J. Hypertens. – 1992. – Vol. 5, No. 2. – P. 95-110.

16. Dahlof B., Zanchetti A., Diez J. et al. Effects of losartan and atenolol on left ventricular mass and neurohormonal profile in patients with essential

LECTURE Volume 17, No. 2/2011

hypertension and left ventricular hypertrophy // J.Hypertens. – 2002. – Vol. 20, No. 9. – P. 1855-1864.

17. Wachtell K., Okin P.M., Olsen M.H. et al. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE Study // Circulation. – 2007. – Vol. 116, No. 7. – P. 700-705.

18. Klingbeil A.U., Schneider M., Martus P., Messerli F.H., Schmie-der R.E. A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension // Am.J. Med. – 2003. – Vol. 115, No. 1. – P. 41-46.

19. Mansia G., De Backer G., Dominiczak A. et al. European Society of Hypertension; European Society of Cardiology. 2007 ESH-ESC Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) // Blood Press. – 2007. – Vol. 16, no. 3.- P. 135-232.

20. Galzerano D., Tammaro P., Cerciello A. et al. Freehand threedimensional echocardiographic evaluation of the effect of telmisartan compared with hydrochlorothiazide on left ventricular mass in hypertensive patients with mild-to-moderate hypertension: a multicenter study // J. Hum. Hypertens. – 2004. – Vol. 18, No. 1. – P. 53-59.

21. Weber K.T., Sun G., Campbell S.E. Structural remodeling of the heart by fibrosis tissue: the role of circulating hormones and locally produced peptides // Eur. Heart J. – 1995. – Vol. 16, Suppl. l. – P. 80-85.

22. Rosendorff C. Vascular hypertrophy in hypertension: role of the renin-angiotensin system // Mt. Sinai. J. Med. – 1998. – Vol. 65, No. 2. – P. 108-117.

23. Chrysant S.G. Vascular remodeling: the role of angiotensin converting enzyme inhibitors // Am.Heart J. – 1998. – Vol. 135, No. 2, Pt. 2. – P. S21-S30.

24. Asmar R., Gosse P., Topouchian J., N’tela G., Dudley A., Shepherd G. L. Effects of telmisartan on arterial stiffness in type 2 diabetes patients with essential hypertension // J. Renin Angiotensin Aldosterone Syst. – 2002. – Vol. 3, No. 3. – P. 176-180.

25. Uchida H., Nakamura Y., Kaihara M. et al. Practical efficacy of telmisartan for decreasing morning home blood pressure and pulse wave velocity in patients with mild-to-moderate hypertension // Hypertens.Res. – 2004. – Vol. 27, No. 8. – P. 545-550.

26. Schmieder R.E., Delles C., Mimran A., Fauvel J.P., Ruilope L.M. Impact of telmisartan versus ramipril on renal endothelial function in patients with hypertension and type 2 diabetes // Diabetes Care. – 2007. – Vol. 30, No. 6. – P. 1351-1356.

27. Zankl A. R., Ivandic B., Andrassy M. et al. Telmisartan improves absolute walking distance and endothelial function in patients with peripheral artery disease // Clin.Res. Cardiol. – 2010. – Vol. 99, No. 12. – P. 787-794.

28. Wago T., Yoshimoto T., Akaza I. et al. Improvement of endothelial function in patients with hypertension and type 2 diabetes after treatment with telmisartan // Hypertens. Res. – 2010. – Vol. 33, No. 8. – P. 796-801.

29. Bakris G., Burgess E., Weir M., Davidai G., Koval S., AMADEO Study Investigators. Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy // Kidney Int.- 2008. – Vol. 74, No. 3. – P. 364-369.

30. Symeonides P., Koulouris S., Triantafyllou K. et al. Favorable pleiotropic effects of ramipril and telmisartan on vascular endothelium of diabetics // J. Am. Coll. Cardiol. – 2005. – Vol. 45, Suppl. A. – P. 428A109.

31. Galle J., Schwedhelm E., Pinnetti S., Boger R.H., Wanner C. Antiproteinuric effects of angiotensin receptor blockers: telmisartan versus valsartan in hypertensive patients with type 2 diabetes mellitus and overt nephropathy // Nephrol.Dial. Transplant. – 2008. – Vol. 23, No. 10. – P. 3174-3183.

32. Yusuf S., Teo K. K., Pogue J. et al. ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events // N. Engl. J. Med. – 2008. – Vol. 358, no. 15 – P. 1547-1559.

33. Yusuf S., Teo K., Anderson C. et al., TRANSCEND Investigators, Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomized controlled trial / / Lancet.- 2008. – Vol. 372, No. 9644. – P. 1174-1183.

34. Galzerano D., Capogrosso C., Di Michele S. et al. New standards in hypertension and cardiovascular risk management: focus on telmisartan // Vasc. Health Risk Manag. – 2010. – Vol. 6. – P. 113-133.

A

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Study of the pharmacokinetics and bioequivalence of the two-component drug Telzap AM ® (telmisartan / amlodipine) and co-administered monocomponent drugs Mikardis ® (telmisartan) and Norvask ® (amlodipine) with the participation of healthy volunteers | Kubesh

1.Ettehad D, Emdin C. A., Kiran A., Anderson S. G., Callender M. B., Emberson J., Chalmers J., Rodgers A., Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016; 387 (10022): 957-967.

2. Neutel J. M. The role of combination therapy in the management of hypertension. Nephrol Dial Transplant. 2006; 21 (6): 1469-1473.

3.Gupta A. K., Arshad S., Poulter N. R. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension. 2010; 55 (2): 399-407.

4. Shekhyan G. G., Yalymov A. A., Shchikota A. M., Zadionchenko V. S., Varentsov S. I. Combination of telmisartan and amlodipine in the treatment of arterial hypertension. Systemic hypertension. 2014; 11 (1): 64–72.

5.Ushkalova E.A., Zyryanov S.K., Ushkalova A.V. Reproduced drugs and features of their regulation. Neurology, Neuropsychiatry, Psychosomatics. 2016; 8 (3): 82–87.

6. Mironov AN Guidelines for the examination of medicines. T. I. M .: Grif i K., 2013.280 p.

7. Rules for conducting bioequivalence studies of medicinal products of the Eurasian Economic Union.2016.

8. Zhang P., Zhang Y., Chen X., Li R., Yin J., Zhong D. Pharmacokinetics of telmisartan in healthy Chinese subjects after oral administration of two dosage levels. Arzneimittelforschung. 2006.56 (8): 569-573.

9. Kang WY, Seong SJ, Ohk B., Gwon M., Kim BK, La S., Kim H., Cho S., Yoon Y., Yang H., Lee HW Pharmacokinetic and bioequivalence study of a telmisartan / S-amlodipine fixed-dose combination (CKD-828) formulation and coadministered telmisartan and S-amlodipine in healthy subjects.Drug Design, Development and Therapy. 2018; 12: 545–553.

10. Paramanindita AS, Harahap Y., Prasaja B., Wijayanti TR, Lusthom W., Sofiah RE, Sandra M., Trisari Y. A Bioequivalence Study of Two Telmisartan 80 mg Tablets in Healthy Indonesian Subjects: An Open Label, Three -way, Three-period, Partial Replicate Crossover Study. Drug Development and Industrial Pharmacy. 2020: 1-25.

11.EMA / 576613/2010 Committee for Medicinal Products for Human Use (CHMP) assessment report on telmisartan / amlodipine. Available at: https://www.ema.europa.eu/en/documents/assessment-report/twynsta-epar-public-assessment-report_en.pdf.

12. Meredith P. A., Elliott H. L. Clinical pharmacokinetics of amlodipine. Clinical pharmacokinetics. 1992; 22 (1): 22–31.

13.Abernethy D. R. The pharmacokinetic profile of amlodipine. American heart journal. 1989; 118 (5): 1100-1103.

14. Kaynak M. S., Bogacz A., Stelmasinski M., Sahin S. Bioavailability File: Amlodipine. FABAD Journal of Pharmaceutical Sciences. 2011; 36 (4): 207-222.

Clinical study Hypertension: Triatec 10 mg, Triatec HCT 5, Lasix 25, Mikardis 80 mg, Mikardis plus 80 / 12.5, Catapresan TTS 2, Norvasc 10 mg, Triatec 5 mg, Pluscor – Clinical Trials Registry

Takeda introduces Edarbi

to the Russian market

Many patients currently receiving ARB treatment do not achieve sustained reductions in blood pressure.This means that they still have a high risk of developing complications from the cardiovascular system and damage to the target organs of hypertension. Takeda’s Edarbi® will improve blood pressure control in these patients.

Globally, 51% of strokes and 45% of deaths from coronary heart disease are associated with high systolic blood pressure1. Moreover, even a moderate decrease in blood pressure is associated with a significant decrease in cardiovascular mortality, including from heart attacks and strokes.As shown by the results of large observational studies, a decrease in systolic blood pressure by only 5 mm Hg. Art. reduces the risk of death from stroke by 14%, from ischemic heart disease by 9%, the risk of total mortality by 7% 2.3.

According to epidemic studies, about 40% of the population in Russia currently suffers from arterial hypertension4.5, while 69.5% of patients are taking antihypertensive drugs, 27.3% of them are effectively treated, and blood pressure is controlled at the target level of 23.2% patients 6.The demand for effective therapeutic solutions in this area remains very high.

Azilsartan medoxomil is a prodrug. After oral administration, it turns into the pharmacologically active metabolite azilsartan. The drug provides a rapid decrease in blood pressure that persists for 24 hours, including in the early morning, when the risk of adverse cardiovascular events, such as stroke or myocardial infarction, is greatest1, 7.

The efficacy of Edarbi has been confirmed by a large amount of data from seven phase III clinical trials, which include more than 6,000 patients with arterial hypertension8.Comparative clinical studies have shown that, according to ambulatory and 24-hour blood pressure monitoring, azilsartan medoxomil lowers blood pressure more effectively than the commonly used ARBs, olmesartan medoxomil9,10 and valsartan10,11, as well as ramipril (an ACE inhibitor) 12.

Edarbi is currently marketed in 47 countries. Now it will be available to doctors and patients in Russia as well.

Andrey Potapov, General Director of Takeda Russia: “Diseases of the cardiovascular system are one of the main causes of death in our country.The demand of patients and the healthcare system for new effective drugs in this area remains very high. Our portfolio includes a range of products designed to treat cardiovascular diseases and prevent complications associated with them. The emergence of Edarbi will allow us to bring new therapeutic solutions to the Russian market. Takeda, the company that launched the first ARB over 30 years ago, continues to optimize this class of already well-established medicines.Since no two patients are alike, a wide range of treatment options are needed to ensure that each patient is treated according to their specific needs. ”

Edarbi entered the market in October 2014 and will initially be available in 40 mg and 80 mg tablets.

¹ World Health Organization. Global health risks: mortality and burden of disease attributable to selected major risks. http: // www.who.int/healthinfo/global_burden_disease/GlobalHealthRisks_report_full.pdf. Published 2009. Accessed January 15, 2014.
² Whelton PK, et al. JAMA. 2002; 288: 1882-1888.
³ Stalmer R. Hypertension. 1991; 17 (Suppl 1): I16-I20.
⁴ Diagnostics and treatment of arterial hypertension. Clinical guidelines. Ministry of Health of the Russian Federation. Moscow, 2013.http: //www.gipertonik.ru/files/recommendation/Recommendations_hypertension.docx
⁵ Shalnova S.B., Kukushkin S., Manoshkina E. et al. Arterial hypertension and adherence to therapy. Doctor. 2009; 12: 39-42
⁶ Russian Medical Society for Arterial Hypertension (RMAH), All-Russian Scientific Society of Cardiology (VNOK). Diagnostics and treatment of arterial hypertension. Russian recommendations (fourth revision). Systemic hypertension 2010; 3: 5-26.
⁷ White WB. Importance of aggressive blood pressure lowering when it may matter most. Am J Cardiol.2007; 100: 10J-16J.
⁸ Azilsartan medoxomil Summary of Product Characteristics.
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002293/WC500119204.pdf. Accessed January 15, 2014.
⁹ Bakris GL, Sica D, Weber M et al. The comparative effects of azilsartan medoxomil and olmesartan on ambulatory and clinic blood pressure. J Clin Hypertens. 2011; 13 (2): 81–88.
¹⁰ White WB, Weber MA, Sica D et al. Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and 2 hypertension.Hypertension. 2011; 57: 413-420.
¹¹ Sica D, White WB, Weber MA. Comparison of the novel angiotensin II receptor blocker azilsartan medoxomil vs valsartan by ambulatory blood pressure monitoring. J Clin Hypertens. 2011; 13: 467–472.
¹² Bonner G, Bakris GL, Sica D et al. Comparison of antihypertensive efficacy of the new angiotensin receptor blocker azilsartan medoxomil with ramipril. J Hypertens. 2010; 28: e283.

90,000 when is it better to drink – in the morning or in the evening?

Timing of high blood pressure medication is very important – it can be life-saving.

A medicine for the night?

Recently, Spanish doctors stated that pressure pills work better if taken at night. They came to this conclusion as a result of a study in which 19 thousand people participated.

– Patients who took the medication at night had significantly lower blood pressure both during the night and during the day than in patients who took the medication in the morning. We concluded that taking evening blood pressure medications halved the risk of heart attacks and strokes, ”said study leader Ramon Germida, .

Still, the pill works better in the morning

The study of Spanish colleagues was called into question by a German specialist, director of the department of cardiology at the Frankfurt University Hospital Andreas Seicher. He was critical of such statements and recommended to stop antihypertensive drugs in the evening.

– Today, more people suffer from high blood pressure due to stress.And during the day, they are more likely to be exposed to similar situations. Therefore, hypertensive patients will be better protected during the day if they take medication in the morning, the specialist is sure.

Time must be calculated correctly

Against this background, each patient should consult with their cardiologist about choosing an individual time of day for taking high blood pressure pills.

The best way to determine individual recommendations is by measuring performance.To do this, a diary is started, in which the current blood pressure is recorded, which is measured every 30 minutes for 24 hours.

Earlier, “Kubanskie Novosti” told how to properly monitor your blood pressure.

indications and contraindications, composition and dosage – Pharmacy Mos