Telmista AM pills 5mg+40mg, 28pcs

Composition

For 1 tablet:

First layer

Active ingredient:  telmisartan 40.00 mg

Auxiliary substances:  meglumine, sodium hydroxide, povidone K 30, lactose monohydrate, sorbitol, iron oxide yellow dye (E 172), magnesium stearate, sodium stearyl fumarate

Second layer

Active ingredient:  amlodipine bezylate 6.94 mg, equivalent to amlodipine 5.00 mg

Auxiliary substances:  mannitol, colloidal silicon dioxide, stearic acid

Pharmacological action

Pharmacotherapeutic group:

antihypertensive combined agent (slow calcium channel blocker + angiotensin II receptor antagonist).

ATX Code:

C09DB04

Pharmacological properties

Pharmacodynamics

The combined preparation Telmista ® AM contains two antihypertensive substances with a complementary effect, which makes it possible to control blood pressure (BP) in patients with arterial (essential) hypertension: angiotensin II receptor antagonist (ARA II) – telmisartan and slow calcium channel blocker (BMCC), dihydropyridine derivative-amlodipine.

The combination of these substances has an additive antihypertensive effect, reducing blood pressure to a greater extent than each component separately. The combined drug, which includes amlodipine and telmisartan, taken once a day, leads to an effective and sustained reduction in blood pressure for 24 hours.

Amlodipine

Amlodipine is a dihydropyridine derivative and belongs to the BMCC class. Inhibits the transmembrane transfer of calcium ions to cardiomyocytes and smooth muscle cells of the vascular wall.

The antihypertensive effect of amlodipine is due to a direct relaxing effect on the smooth muscle cells of the vascular wall, which leads to a decrease in peripheral vascular resistance and a decrease in blood pressure.

In patients with arterial hypertension, taking amlodipine once a day provides a clinically significant reduction in blood pressure within 24 hours. The antihypertensive effect develops slowly, and therefore, the development of acute arterial hypotension is uncharacteristic.

In patients with arterial hypertension and normal renal function, the use of therapeutic doses of amlodipine resulted in a decrease in renal vascular resistance, an increase in glomerular filtration rate (GFR) and effective plasma flow in the kidneys without changing filtration or proteinuria.

Amlodipine has no adverse metabolic effects and does not affect the concentration of plasma lipids. In this regard, the drug can be used in patients with concomitant bronchial asthma, diabetes mellitus and gout.

The use of amlodipine in patients with heart failure is not accompanied by a negative inotropic effect (exercise tolerance does not decrease, the left ventricular ejection fraction does not decrease).

Telmisartan

Telmisartan-specific ARA II (type AT1), effective when taken orally. It has a high affinity for the AT1 subtype of angiotensin II receptors, through which the action of angiotensin II is realized. Displaces angiotensin II from binding to the receptor, without having an agonist effect on this receptor. Telmisartan binds only to the AT1 receptor subtype of angiotensin II. The relationship is long-term. It has no affinity for other receptors, including the AT2 receptor. Reduces the concentration of aldosterone, does not inhibit the activity of renin in blood plasma and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (ACE) or kininase II, an enzyme that also breaks down bradykinin. Therefore, an increase in bradykinin-induced adverse reactions (HP) is not expected.

At a dose of 80 mg, telmisartan completely blocks the hypertensive effect of angiotensin II. The onset of antihypertensive action is noted within 3 hours after the first use of telmisartan. The effect of the drug persists for 24 hours and remains significant for up to 48 hours. A pronounced antihypertensive effect usually develops 4-8 weeks after regular use.

Telmisartan reduces systolic and diastolic blood pressure in patients with arterial hypertension, without affecting the heart rate (HR).

In the case of abrupt withdrawal of telmisartan, blood pressure gradually returns to its original level without the development of “withdrawal”syndrome.

The incidence of dry cough was significantly lower in patients treated with telmisartan compared with ACE inhibitors.

Two large randomized controlled trials, ONTARGET (The Global Endpoints Study for telmisartan Monotherapy and in Combination with ramipril) and VA NEPHRON-D (The Veterans Affairs Nephropathy in diabetes study conducted by the US Department of Veterans Affairs), examined the use of a combination ACE inhibitor simultaneously with ARA II. The ONTARGET study was a study conducted in patients with a history of cardiovascular or cerebrovascular diseases, or type 2 diabetes mellitus with confirmed target organ damage. The VA NEPHRON-D study was a study in patients with type 2 diabetes mellitus and diabetic nephropathy.

These studies did not show a significant positive effect on renal and/or cardiovascular outcomes and mortality, while there was an increased risk of hyperkalemia, acute renal failure (ARF), and/or hypotension compared to monotherapy. Given the similar pharmacodynamic properties, these results are also relevant for other ACE and ARA II inhibitors.

Therefore, ACE inhibitors and ARA II inhibitors should not be used simultaneously in patients with diabetic nephropathy.

The ALTITUDE Study (Aliskiren Application Study in Patients with type 2 Diabetes Mellitus with assessment of cardiovascular and Renal endpoints) was a study designed to test the benefit of adding aliskiren to standard treatment with an ACE inhibitor or ARA II in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease, or both. The study was terminated prematurely due to an increased risk of adverse outcomes. Cardiovascular death and stroke were more frequently reported in the aliskiren group than in the placebo group, and adverse events (AES) and serious adverse events (SES) (hyperkalemia, hypotension, and impaired renal function) were more frequently reported in the aliskiren group than in the placebo group. There is a difference in plasma concentrations of telmisartan in men and women. The values of maximum concentration (Cmax) and area under the pharmacokinetic curve “concentration-time” (AUC) were approximately 3 and 2 times higher in women compared to men, respectively, without significant effect on efficacy.

Pharmacokinetics

Fixed-dose combination of amlodipine and telmisartan

The magnitude and rate of absorption of amlodipine and telmisartan when used as part of a combined drug does not significantly differ from that when used as monopreparations.

Amlodipine

Suction

Amlodipine is well absorbed when taken orally in therapeutic doses and reaches Cmax in 6-12 hours. Absolute bioavailability is 64-80%. Food intake does not affect the bioavailability of amlodipine.

Distribution

The volume of distribution is approximately 21 l / kg. The results of in vitro studies showed that approximately 97.5% of circulating amlodipine binds to plasma proteins.

Metabolism

Amlodipine is largely (approximately 90%) metabolized in the liver to form inactive metabolites.

Deduction

Elimination of amlodipine from blood plasma occurs in two phases, with a half-life (T 1/2) of approximately 30-50 hours. A stable concentration in the blood plasma is achieved after constant use of the drug for 7-8 days. Amlodipine is excreted by the kidneys both unchanged (10%) and as metabolites (60%).

Telmisartan

Suction

When taken orally, telmisartan is rapidly absorbed from the gastrointestinal tract (GIT). Absolute bioavailability – 50%. When taken simultaneously with food, the decrease in AUC ranges from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg).3 hours after oral use, the plasma concentration becomes similar to that of telmisartan on an empty stomach.

Distribution

Binding to plasma proteins >99.5% (mainly albumin and alpha-1-acid glycoprotein). The average apparent volume of distribution at equilibrium is 500 liters.

Metabolism

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

Removal

of T 1/2 is more than 20 hours. The Cmax and, to a lesser extent, AUC values increase disproportionately to the dose. There is no evidence of clinically significant accumulation of telmisartan. It is excreted through the intestines in unchanged form, excretion by the kidneys-less than 1%. Total plasma clearance is high (approximately 1000 ml / min) compared to hepatic blood flow (approximately 1500 ml / min).

Special patient groups

Elderly patients

In elderly patients, there is a tendency to decrease the clearance of amlodipine, which leads to an increase in AUC and T 1/2.

The pharmacokinetics of telmisartan in elderly patients and young patients do not differ.

Renal impairment

The pharmacokinetics of amlodipine do not change significantly in patients with impaired renal function.

Telmisartan binds to plasma proteins and is not removed by hemodialysis in patients with renal insufficiency. The concentration of telmisartan in the blood plasma in patients with renal insufficiency is doubled. However, in patients undergoing hemodialysis, lower concentrations of telmisartan are observed, T 1/2 does not change.

Impaired liver function

In patients with hepatic insufficiency, the clearance of amlodipine decreased, which led to an increase in the AUC value by about 40-60%.

Pharmacokinetic studies conducted in patients with impaired liver function have shown that the absolute bioavailability of telmisartan increases to almost 100%. T 1/2, in patients with impaired liver function does not change.

Indications

Arterial hypertension (for patients whose blood pressure is insufficiently controlled by amlodipine or telmisartan in monotherapy).

Arterial hypertension (for patients who are indicated for combination therapy). Patients with hypertension receiving amlodipine and telmisartan as separate tablets as a replacement for this therapy.

Use during pregnancy and lactation

Telmista ® AM is contraindicated during pregnancy and lactation.

Special studies of the combined drug amlodipine and telmisartan during pregnancy and lactation have not been conducted. The effects associated with taking individual components of the drug are described below.

Pregnancy

Amlodipine

The limited data available on the effects of amlodipine or other BMCs do not indicate any adverse effects on the fetus. However, there may be a risk of slowing down labor.

Telmisartan

The use of ARA II is contraindicated during pregnancy. If pregnancy is diagnosed, telmisartan should be discontinued immediately. If necessary, alternative therapy should be used.

Preclinical studies of telmisartan did not reveal teratogenic properties, but established the presence of fetotoxicity. It is known that the use of ARA II during the second and third trimesters of pregnancy has a fetotoxic effect (decreased renal function, oligohydramnion, slowing of ossification of the fetal skull), and neonatal toxicity (renal failure, hypotension and hyperkalemia) is also observed.

When planning pregnancy, ARA II should be replaced with other antihypertensive agents with an established pregnancy safety profile (unless continued use of ARA II is considered necessary).

If ARA II is used during pregnancy, then, starting from the second trimester of pregnancy, ultrasound is recommended to monitor kidney function and the condition of the fetal skull.

Newborns whose mothers received ARA II should be carefully monitored for the development of hypotension.

Breast-feeding period

Amlodipine

Amlodipine is excreted in human breast milk. In women suffering from pregnancy-related hypertension and receiving amlodipine at an initial dosage of 5 mg per day, the average milk / plasma ratio for amlodipine concentration was 0.85 among 31 nursing women. The dosage of the drug was adjusted if necessary (the average daily dose of amlodipine and the dose depending on body weight were 6 mg and 98.7 mcg / kg, respectively). The estimated daily dose of amlodipine received by an children through breast milk is 4.17 mcg/kg.

The use of amlodipine during breastfeeding is contraindicated. If it is necessary to use Telmista® AM during lactation, stop breastfeeding.

Telmisartan

Special studies on the excretion of telmisartan in breast milk in women have not been conducted. Animal studies have shown that telmisartan is excreted in the milk of lactating animals. Taking into account possible adverse reactions, the decision to continue breast-feeding or discontinue therapy should be made taking into account its significance for the mother.

Impact on fertility

Studies of the effect on human fertility have not been conducted.

Biochemical changes in the sperm head were found in some patients treated with BMCC. However, there are currently insufficient clinical data regarding the potential effect of amlodipine on fertility. In a rat study, undesirable effects on male fertility were identified.

Contraindications

• Hypersensitivity to amlodipine and / or telmisartan, as well as to any of the excipients (see the section “Composition”),
• Hypersensitivity to other dihydropyridine derivatives.
• Fructose and galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.
• Pregnancy.
• Breast-feeding period.
• Age up to 18 years (efficacy and safety have not been established).
• Obstructive diseases of the biliary tract.
• Severe arterial hypotension (systolic blood pressure less than 90 mm Hg).
• Obstruction of the left ventricular exit tract (including severe aortic stenosis).
• Hemodynamically unstable heart failure after acute myocardial infarction.
• Shock (including cardiogenic shock).
• Severe hepatic impairment (Child-Pugh class C).
• Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 of body surface area).
• Concomitant use with ACE inhibitors in patients with diabetic nephropathy.

With caution in

Chronic heart failure (CHF) in non-ischemic etiology of III-IV functional class NYHA classification, coronary heart disease (CHD) with severe obstructive coronary artery disease, acute myocardial infarction (within 1 month after), unstable angina, aortic stenosis, mitral stenosis, idiopathic hypertrophic obstructive cardiomyopathy (HACMP), hypotension, sick sinus syndrome node (marked tachycardia, bradycardia), concurrent use with inhibitors or inducers of CYP3A4 (see section “Interaction with other drugs”), bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney, impaired renal function of mild and moderate severity, condition after kidney transplantation (experience of missing), and decreased volume of circulating blood (BCC) on the background of the preceding use of diuretics, limit the consumption of salt, diarrhoea or vomiting, hyponatremia, hyperkalemia, impaired liver function of mild and moderate severity.

Side effects

The most common symptoms include dizziness and peripheral edema. Serious syncope can occur in rare cases (less than 1 case per 1000 patients).

HP was based on the experience with the use of telmisartan and amlodipine, used as monotherapy, and in their simultaneous application submitted in accordance with the classification of the HP world health organization (who): very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), including individual messages, the unknown frequency (frequency cannot be estimated based on available data).

HP is distributed across organs and systems according to the MedDRA classification.

System-organ class	Undesirable reaction	Amlodipine + telmisartan	Amlodipine	Telmisartan
Infectious and parasitic diseases	Urinary tract infections (including cystitis)	–	–	Infrequently
	Upper respiratory tract infections, including pharyngitis and sinusitis	—		Infrequently
	Sepsis, including fatal	cases–		Rarely
	Cystitis	Rarely	—
Disorders of the blood and lymphatic system	Anemia	—		Infrequently
	Eosinophilia	—		Rarely
	Leukopenia	–	Very rare	–
	Thrombocytopenia	–	Very rare	Rarely
Immune system disorders	Hypersensitivity	–	Very rare	Rarely
	Anaphylactic reaction	—		Rarely
Metabolic and nutritional disorders	Hyperkalemia	—		Infrequently
	Hypoglycemia (in patients with diabetes mellitus).	–	–	Rarely
	Hyperglycemia	–	Very rare	–
Mental disorders	Mood lability	–	Infrequently	–
	Confusion of knowledge	–	Rarely	–
	Depression	Rarely	—
	Worry	Rarely	—
	Insomnia	Rarely	—
Nervous system disorders	Vertigo	Often	—
	Drowsiness	Infrequently	—
	Migraines	Infrequently	—
	Headache	Infrequently	—
	Paresthesia	Infrequently	—
	Fainting	Rarely	—
	Peripheral neuropathy	Rarely	—
	Hypesthesia	Rarely	—
	Dysgeusia	Rarely	—
	Tremor	Rarely	—
	Extrapyramidal syndrome	–	Very rare	–
Visual disturbances	Visual impairments	–	Infrequently	Rarely
Hearing disorders and labyrinth disorders	Tinnitus	–	Infrequently	–
	Vertigo	Infrequently	—
Cardiac disorders	Bradycardia	Infrequently	—
	Palpitation sensation	Infrequently	—
	Tachycardia	—		Rarely
	Myocardial infarction	–	Very rare	–
	Cardiac arrhythmias	–	Very rarely	–
	Ventricular tachycardia	–	Very rare	–
	Atrial fibrillation	–	Very rare	–
Vascular disorders	Arterial hypotension	Infrequently	—
	Orthostatic hypotension	Infrequently	—
	The feeling of “tides”	Infrequently	—
	Vasculitis	–	Very rare	–
Respiratory, thoracic and mediastinal disorders	Shortness of breath	Rarely	Infrequently	Infrequently
	Rhinitis	–	Infrequently	–
	Cough	Infrequently	—
	Interstitial lung disease	Very rarely	—
Disorders of the digestive system	Changing the rhythm of defecation	–	Infrequently	–
	Flatulence	—		Infrequently
	Abdominal pain	Infrequently	—
	Diarrhea	Infrequently	—
	Nausea	Infrequently	—
	Vomiting	Rarely	—
	Gum hypertrophy	Rarely	—
	Dryness of the oral mucosa	Rarely	—
	Stomach discomfort	—		Rarely
	Pancreatitis	–	Very rare	–
	Gastritis	–	Very rare	–
Liver and biliary tract disorders	Liver function disorders	–	–	Rarely
	Liver pathology	—		Rarely
	Hepatitis	–	Very rare	–
	Jaundice	–	Very rare	–
	Increased activity of “hepatic” transaminases (mainly reflecting cholestasis)	–	Very rare	–
Skin and subcutaneous tissue disorders	Hyperhidrosis	–	Infrequently	Infrequently
	Alopecia	–	Infrequently	–
	Magenta	–	Infrequently	–
	Changing skin color	–	Infrequently	–
	Pruritus of the skin	Infrequently	—
	Angioedema (fatal)	–	–	Rarely
	Drug rash	—		Rarely
	Toxic rash	—		Rarely
	Eczema	Rarely	—
	Erythema	Rarely	—
	Angioedema	–	Very rare	–
	Urticaria	–	Very rare	Rarely
	Photosensitization reactions	–	Very rare	–
	Erythema multiforme	–	Very rare	–
	Stevens-Johnson Syndrome	–	Very rare	–
	Exfoliative dermatitis	–	Very rare	–
	Toxic epidermal necrolysis	–	Frequency unknown	–
Musculoskeletal and connective tissue disorders	Arthralgia	Infrequently	—
	Muscle spasms (calf muscle spasms)	Infrequently	—
	Myalgia	Infrequently	—
	Pain in the lower extremities	Rarely	—
	Back pain	Rarely	—
	Tendon pain (tendinitis-like symptoms)	–	–	Rarely
Kidney and urinary tract disorders	Violation of urination	–	Infrequently	–
	Pollakiuria (rapid urination).	–	Infrequently	–
	Impaired renal function, including	acute renal failure–		Infrequently
	Nocturia	Rarely	—
Genital and breast disorders	Gynecomastia	–	Infrequently	–
	Erectile dysfunction	Infrequently	—
General disorders and disorders at the injection site	Peripheral edema	Is Often	—
	Pain	–	Infrequently	–
	Asthenia	Infrequently	—
	Chest pain	Infrequently	—
	Fatigue	Infrequently	—
	Edema	Infrequently	—
	Malaise	–	Rarely	–
	Flu-like syndrome	—		Rarely
Laboratory and instrumental data	Weight gain	–	Infrequently	–
	Weight	loss–	Infrequently	–
	Increased creatinine concentration in blood plasma	—		Infrequently
	Increased activity of “liver” enzymes in blood plasma	Infrequently	—
	Increased creatine phosphokinase (CPK) activity in blood plasma	—		Rarely
	Reduced hemoglobin	—		Rarely
	Increased uric acid concentration in blood plasma	Rarely	—

Additional information about individual components

HP previously reported with the use of one of the components of the drug (amlodipine or telmisartan) may increase with the use of their combination, even if they were not observed in clinical studies or in the post-marketing period.

Additional information about the component combination

Peripheral edema – a dose-dependent response to amlodipine-was observed less frequently in patients who received a combination of amlodipine and telmisartan than in patients who received amlodipine alone.

Interaction

No interactions between amlodipine and telmisartan have been identified in clinical trials. Special studies of drug interactions of the combination of amlodipine and telmisartan with other drugs have not been conducted.

Combination of active ingredients

Other antihypertensive agents

When used concomitantly with other antihypertensive drugs, the antihypertensive effect of Telmista® AM may be enhanced.

Drugs that can reduce blood pressure

Certain medications, such as baclofen, amifostin, antipsychotics, and antidepressants, can be expected to enhance the antihypertensive effects of all antihypertensive agents, including the combination drug Telmista® AM, due to their pharmacological properties. In addition, orthostatic hypotension may increase with the use of ethanol.

Corticosteroids (systemic use)

It is possible to reduce the antihypertensive effect.

Amlodipine

Concomitant use requiring precautionary measures

Inhibitors of the CYP3A4 isoenzyme

When co-administered with an inhibitor of the CYP3A4 isoenzyme (erythromycin) in young patients and with diltiazem in elderly patients, the concentration of amlodipine in blood plasma increased by 22% and 50%, respectively. However, the clinical significance of this observation is not clear.

It cannot be excluded that more active inhibitors of the CYP3A4 isoenzyme (such as ketoconazole, itraconazole, ritonavir) may increase the concentration of amlodipine in blood plasma to a greater extent than diltiazem. Amlodipine should be used with caution concomitantly with inhibitors of the CYP3A4 isoenzyme. However, no undesirable effects associated with this interaction were observed.

Inducers of the CYP3A4 isoenzyme

With the simultaneous use of known inducers of the CYP3A4 isoenzyme, the concentration of amlodipine in blood plasma can vary. Therefore, it is necessary to monitor blood pressure and adjust the dose during and after concomitant treatment, especially with powerful inducers of the CYP3A4 isoenzyme (for example, rifampicin, St. John’s wort preparations).

Grapefruit and grapefruit juice

Concomitant use of 240 ml of grapefruit juice with a single oral dose of 10 mg amlodipine in 20 healthy volunteers did not significantly affect the pharmacokinetic properties of amlodipine.

Concomitant use of Telmista ® AM with grapefruit or grapefruit juice is not recommended, as in some patients, as a result of increased bioavailability of amlodipine, the antihypertensive effect may increase.

Amiodarone and quinidine

Although no negative inotropic effects were usually observed when studying amlodipine, however, some BMCs may increase the severity of the negative inotropic effects of antiarrhythmic drugs that cause prolongation of the QT interval.

Concomitant use to be considered

Tacrolimus

There is a risk of increased concentrations of tacrolimus when it is co-administered with amlodipine, but the pharmacokinetic mechanism of this interaction is not fully understood. To avoid tacrolimus toxicity, the use of amlodipine in patients receiving tacrolimus requires monitoring tacrolimus concentrations and adjusting the tacrolimus dose when necessary.

Cyclosporine

No studies of drug interactions between cyclosporine and amlodipine were conducted in healthy volunteers or in other populations, with the exception of patients who underwent kidney transplantation, who showed a variable increase in the residual concentration of cyclosporine (on average 0-40%). Consideration should be given to monitoring cyclosporine concentrations in kidney transplant patients receiving amlodipine, and reducing cyclosporine doses if necessary.

Simvastatin

Concomitant use of amlodipine with simvastatin at a dose of 80 mg resulted in an increase in simvastatin exposure by up to 77% compared to simvastatin monotherapy. Therefore, the dose of simvastatin should not exceed 20 mg per day.

Calcium supplements

Calcium supplements can reduce the effect of BMCC.

Lithium preparations

Concomitant use of BMCC (no data available for amlodipine) with lithium preparations may increase the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Other medications

The safety of concomitant use of amlodipine with digoxin, warfarin, atorvastatin, sildenafil, antacid drugs (aluminum hydroxide, magnesium hydroxide, simethicone), cimetidine, antibiotics and oral hypoglycemic drugs has been established.

When amlodipine and sildenafil were co-administered, each drug was shown to have an independent antihypertensive effect.

Concomitant use of amlodipine with cimetidine did not significantly affect the pharmacokinetics of amlodipine. Concomitant use of amlodipine with atorvastatin, digoxin, warfarin or cyclosporine did not significantly affect the pharmacokinetics or pharmacodynamics of these drugs.

Mammalian mechanistic target inhibitors for rapamycin (mTOR)

mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are substrates of the CYP3A isoenzyme. Amlodipine is a weak inhibitor of the CYP3A4 isoenzyme. When used concomitantly with mTOR inhibitors, amlodipine may increase their exposure

Telmisartan

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

Dual blockade of the RAAS (for example, concomitant use of ACE inhibitors or aliskiren, a direct renin inhibitor with ARA II) is not recommended due to possible renal impairment (including acute renal failure).

Concomitant use of ARA II with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to severe renal insufficiency (GFR less than 60 ml/min / 1.73 m2 of body surface area) and is not recommended in other patients.

Concomitant use of ACE inhibitors and ARA II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Simultaneous use is not recommended

Potassium-sparing diuretics and salt substitutes containing potassium

ARA II drugs, such as telmisartan, reduce potassium loss caused by the use of diuretics. The use of potassium-sparing diuretics, such as spironolactone, eplerenone, triamterene or amiloride, potassium preparations or potassium-containing salt substitutes, can lead to a significant increase in serum potassium. If their simultaneous use is necessary due to the presence of registered hypokalemia, then treatment should be carried out with caution and with frequent monitoring of the potassium content in the blood serum. If concomitant use is indicated due to documented hypokalemia, these medications should be used with caution and serum potassium levels should be monitored regularly.

Lithium preparations

There was a reversible increase in the concentration of lithium in blood plasma, accompanied by toxic phenomena, when taking ACE inhibitors. In rare cases, such changes have been reported with the appointment of ARA II, in particular, telmisartan. With simultaneous use of lithium and ARA II preparations, it is recommended to determine the concentration of lithium in blood plasma.

Other antihypertensive agents

It is possible to increase the antihypertensive effect. In one study, the combined use of telmisartan and ramipril resulted in a 2.5-fold increase in AUC0-24 and Cmax of ramipril and ramiprilate. The clinical significance of this interaction has not been established.

Concomitant use requiring precautionary measures

Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (in doses used as an anti-inflammatory agent), cyclooxygenase-2 (COE-2)inhibitors and non-selective NSAIDs can reduce the severity of the antihypertensive effect of ARA II.

In some patients with renal insufficiency (for example, patients with dehydration or elderly patients with renal insufficiency), concomitant use of ARA II and medications that inhibit COX activity may lead to additional deterioration of renal function, including the possible development of acute renal failure; these effects are usually reversible. Therefore, this combination should be used with caution, especially in elderly patients. Patients should be adequately hydrated, and renal function should be monitored after starting concomitant use of these medications and periodically thereafter.

Concomitant use that Digoxin should be considered

When telmisartan was co-administered with digoxin, an increase in the median digoxin Cmax (49%) and the residual digoxin concentration (20%) was observed. Plasma digoxin concentrations should be monitored during initiation, dose adjustment, and discontinuation of telmisartan.

How to take it, course of use and dosage

Inside,1 time a day, regardless of the meal time.

Telmista ® AM may be prescribed:

• patients receiving the same doses of amlodipine and telmisartan as separate tablets, for ease of therapy and increased adherence to treatment;
• patients in whom the use of amlodipine alone or telmisartan alone does not lead to adequate blood pressure control. Patients taking amlodipine at a dose of 10 mg, who have symptoms that limit the use of the drug, for example, peripheral edema, can be transferred to Telmista® AM at a dose of 5 mg + 40 mg 1 time per day, which will reduce the dose of amlodipine, but will not reduce the overall expected antihypertensive effect.
• for the treatment of arterial hypertension: therapy may begin with the use of Telmista ® AM in cases where it is assumed that achieving blood pressure control with any one drug is unlikely. The usual starting dose of Telmista ® AM is 5 mg + 40 mg once daily. Patients who need a more significant reduction in blood pressure can start taking Telmista ® AM at a dose of 5 mg + 80 mg once a day.

If an additional reduction in blood pressure is required after at least 2 weeks of treatment, the dose of Telmista® AM can be gradually increased to a maximum dose of 10 mg + 80 mg once a day.

Telmista ® AM can be used together with other antihypertensive drugs.

Special patient groups

Impaired renal function

In patients with impaired renal function, including patients on hemodialysis, changes in the dosage regimen are not required. Amlodipine and telmisartan are not removed from the body during hemodialysis.

Liver function disorders

In patients with mild to moderate hepatic impairment (Child-Pugh Class A and B), Telmista® AM should be used with caution. The dose of telmisartan should not exceed 40 mg once a day.

Elderly patients

When using Telmista® AM in elderly patients, no dose adjustment is required.

Children and adolescents under 18 years of age

Telmista AM should not be prescribed to children and adolescents under 18 years of age, as there are no data on the efficacy and safety of amlodipine and telmisartan in these groups of patients, both in monotherapy and in combination therapy.

Overdose

Symptoms

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

Amlodipine – a marked decrease in blood pressure with the possible development of reflex tachycardia and symptoms of excessive peripheral vasodilation (risk of severe and persistent hypotension, including shock and death).

Telmisartan – tachycardia, possibly bradycardia, dizziness, increased serum creatinine, acute renal failure.

Treatment

Hemodialysis is ineffective, and amlodipine and telmisartan are not removed from the body during it.

Monitoring of the patient’s condition is required, and therapy should be symptomatic and supportive.

Intravenous use of calcium gluconate may be useful to relieve calcium channel blockage.

Such methods of overdose treatment as inducing vomiting, gastric lavage, the use of activated charcoal, placing the patient in a “lying position with raised legs” and the introduction of plasma-substituting solutions in the case of a pronounced decrease in blood pressure can be used.

Special instructions

Amlodipine

Cardiovascular diseases

The efficacy and safety of amlodipine in hypertensive crisis has not been established.

In acute myocardial infarction, the use of amlodipine is possible only after stabilization of hemodynamic parameters.

In rare cases, patients with CHD (especially those with severe obstructive coronary artery disease) have experienced an increase in the frequency, duration, and/or severity of angina attacks after starting BMCC or after increasing their dosage.

Although BMCC should generally be used with caution in patients with CHF, amlodipine has not been shown to increase mortality or cardiovascular events in patients with CHF in short – and long-term clinical trials. In patients with non-ischemic CHF (NYHA functional class III and IV), there was an increase in the incidence of pulmonary edema, despite the absence of signs of heart failure progression, when amlodipine was used.

Aortic stenosis, mitral stenosis, HOCMP

As with all vasodilating drugs, amlodipine should be used with caution in patients with aortic stenosis, mitral stenosis, or HOCMP. In patients with left ventricular outflow tract obstruction (including severe aortic stenosis), the drug is contraindicated.

Withdrawal syndrome

Despite the absence of “withdrawal” syndrome in BMCC, it is advisable to stop treatment with amlodipine by gradually reducing the dose of the drug. Amlodipine does not prevent the development of “withdrawal” syndrome when abruptly stopping taking beta-blockers.

Peripheral edema

Mild to moderate peripheral edema was the most common adverse event reported with amlodipine in clinical trials. The frequency of peripheral edema increases with increasing dose (when using amlodipine at a dose of 2.5 mg,5 mg and 10 mg per day, edema occurred in 1.8%,3% and 10.8% of patients, respectively). Peripheral edema associated with the use of amlodipine should be carefully differentiated from symptoms of progressive left ventricular heart failure.

Impaired liver function

No controlled studies have been conducted in patients with hepatic impairment. In a small number of patients with mild to moderate hepatic insufficiency, an increase in the T 1/2 of amlodipine was noted. Patients with hepatic insufficiency should be monitored by a doctor if necessary for the use of amlodipine. In some cases (for example, in moderate hepatic insufficiency), a lower initial dose of amlodipine (2.5 mg per day) is recommended.

Elderly patients

In elderly patients, T 1/2 may increase and clearance of amlodipine may decrease. In clinical trials, the incidence of AE in patients aged >65 years was approximately 6% higher than in younger patients. There is no need to change the dose of amlodipine, but more careful monitoring of patients in this category is necessary.

Other things

During therapy with amlodipine, it is necessary to monitor body weight and consumption of table salt, and the appointment of an appropriate diet is indicated.

It is necessary to maintain dental hygiene and follow up with a dentist (to prevent soreness, bleeding and gum hyperplasia).

Telmisartan

Pregnancy

The use of ARA II should not be initiated during pregnancy. Unless continued treatment is considered necessary, these medications should be replaced with alternative antihypertensive medications that have a proven safety profile for use during pregnancy in patients planning pregnancy. If pregnancy is diagnosed, treatment with ARA II should be stopped immediately, and alternative treatment should be initiated if necessary.

Renovascular arterial hypertension

Patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney who are taking medications that affect the RAAS have an increased risk of developing severe hypotension and renal failure.

Double blockade of the RAAS

There is evidence that concomitant use of ACE inhibitors, ARA II or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS by the combined use of ACE inhibitors, ARA II or aliskiren is not recommended.

If double blockade of the RAAS is considered necessary, it should only be performed under the supervision of a specialist and subject to careful monitoring of renal function, electrolyte concentrations and blood pressure.

Concomitant use of ARA II with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to severe renal insufficiency (GFR less than 60 ml/min / 1.73 m2 of body surface area) and is not recommended in other patients.

Concomitant use of ACE inhibitors and ARA II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Other conditions characterized by RAAS activation

In cases of dependence of vascular tone and renal function mainly on the activity of RAAS (for example, in patients with CHF or kidney diseases, including renal artery stenosis), the use of drugs that affect it may be accompanied by the development of acute arterial hypotension, hyperazotemia, oliguria, and, in rare cases, acute renal failure.

Liver failure

Telmisartan should not be used in patients with cholestasis, biliary tract obstruction, or severe hepatic impairment (Child-Pugh Class C), as telmisartan is mainly excreted in the bile. It is assumed that the hepatic clearance of telmisartan is reduced in such patients.

Primary hyperaldosteronism

In patients with primary hyperaldosteronism, antihypertensive drugs, the mechanism of action of which is to inhibit the RAAS, are usually ineffective. Thus, the use of telmisartan in such cases is not recommended.

Diabetes mellitus

In patients with diabetes mellitus with an additional cardiovascular risk (i. e., with concomitant CHD), the risk of fatal myocardial infarction and sudden cardiovascular death may be increased when treated with antihypertensive agents such as ARA II and ACE inhibitors.

When using telmisartan in patients with diabetes mellitus receiving insulin or other hypoglycemic drugs, hypoglycemia may occur. Therefore, appropriate monitoring of blood glucose levels should be considered in these patients; dose adjustment of insulin or hypoglycemic medications may be necessary, if necessary.

Hyperkalemia

Hyperkalemia may occur during treatment with medications that affect the RAAS, especially in the presence of impaired renal function and/or heart failure. Hyperkalemia can be fatal in elderly patients, in patients with renal insufficiency, in patients with diabetes mellitus, in patients who are simultaneously receiving other medications that may increase serum potassium, and/or in patients with intercurrent events.

Before considering the possibility of concomitant use of drugs that affect the RAAS, it is necessary to assess the benefit-risk ratio. The main risk factors for hyperkalemia are:

• diabetes mellitus, impaired renal function, age (>70 years);>
• combination with one or more other medications that affect the RAAS and/or dietary supplements containing potassium. Medicinal products or therapeutic classes of drugs that can trigger the development of hyperkalemia, is a salt containing potassium, potassium-sparing diuretics, ACE inhibitors, ARA II, NSAIDs (including selective COX-2 inhibitors), heparin, immunosuppressants (ciclosporin or tacrolimus) and trimethoprim;
• intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis, worsening of renal function, sudden worsening of the renal condition (e. g. infectious diseases), cellular lysis (e. g., limb ischemia, rhabdomyolysis, extensive trauma).

In these patients, the serum potassium content should be carefully monitored.

Amlodipine + telmisartan

Liver failure

Telmista AM should be used with caution in patients with hepatic insufficiency.

Impaired renal function and conditions after kidney transplantation

There is no experience of using a combined drug containing amlodipine and telmisartan in patients who have recently undergone kidney transplantation. Amlodipine and telmisartan are not removed by hemodialysis. Periodic monitoring of serum potassium and creatinine levels is recommended for patients with impaired renal function.

Reduced BCC and / or hyponatremia

Due to restriction of salt intake, intensive diuretic therapy, diarrhea or vomiting, symptomatic hypotension may develop, especially after taking the first dose of the drug. Such conditions require correction before using Telmista ® AM. If hypotension occurs while using Telmista ® AM, the patient should be placed on his back and, if necessary, intravenous saline solution should be administered. Treatment can be continued after blood pressure stabilizes.

Aortic and mitral valve stenosis, HOCMP

In patients with aortic or mitral stenosis or with HOCMP, the use of Telmista ® AM, as well as other vasodilators, requires special caution.

Unstable angina, acute myocardial infarction

There are no data on the use of Telmista® AM in patients with unstable angina, in the acute period and within one month after a myocardial infarction.

Other things

A marked decrease in blood pressure in patients with ischemic cardiomyopathy or CHD can lead to the development of myocardial infarction or stroke.

Telmista ® AM is effective in the treatment of patients of the black race (in this population, plasma renin activity is usually reduced).

Special information on excipients

The composition of Telmista ® AM, along with other excipients, includes sorbitol and lactose monohydrate (see the section “Composition”), and therefore its use is contraindicated in patients with fructose intolerance, galactose, lactase deficiency, glucose-galactose malabsorption syndrome.

Influence on the ability to drive vehicles and mechanisms

Studies of the effect on the ability to drive vehicles and mechanisms have not been conducted. However, it should be taken into account that NRS such as fainting, drowsiness, or dizziness may occur during treatment. Therefore, care should be taken when driving vehicles or mechanisms. If patients experience these sensations, they should avoid performing such potentially dangerous actions as driving vehicles or mechanisms.

Form of production

Tablets,5 mg + 40 mg,5 mg + 80 mg,10 mg + 40 mg,10 mg + 80 mg.

7 or 10 tablets in a blister of combined OPA/Al/PVC material and aluminum foil.

4,8 or 12 blisters (7 tablets each), or 3,6 or 9 blisters (10 tablets each) together with the instructions for use are placed in a cardboard pack.

Storage conditions

At a temperature not exceeding 25 °C, in the original blister. Keep out of reach of children.

Shelf

life is 3 years. Do not use the drug after the expiration date.

Active ingredient

Amlodipine, Telmisartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets