Telsartan AM Tablets 10 mg+80 mg, 28 pcs.

Pharmacodynamics

Combination drug, contains two hypotensive agents with complementary action, which allows to control blood pressure (BP) in patients with arterial (essential) hypertension: The angiotensin II receptor antagonist (ARA II) – telmisartan, and the “slow” calcium channel blocker (CMCB), a dihydropyridine derivative – amlodipine.

The combination of these substances has an additive antihypertensive effect, reducing BP to a greater extent than each individual component. The combination of amlodipine and telmisartan, taken once daily, results in effective and sustained BP reduction within 24 h.

Amlodipine

Amlodipine is a dihydropyridine derivative and belongs to the class of BMCCs. It inhibits transmembrane entry of calcium ions into cardiomyocytes and vascular smooth muscle cells. The mechanism of antihypertensive action of amlodipine is related to direct relaxant effect on vascular smooth muscle cells, which leads to decrease of peripheral vascular resistance and blood pressure.

In patients with arterial hypertension once daily use of amlodipine provides clinically significant BP reduction for 24 hours. Orthostatic arterial hypotension is not typical during amlodipine administration due to slow onset of drug action.

In patients with arterial hypertension and normal renal function, amlodipine at therapeutic doses resulted in decreased renal vascular resistance, increased glomerular filtration rate and effective renal blood flow, without changes in filtration or proteinuria.

Amlodipine does not lead to any metabolic adverse effects or changes in plasma lipid content and is therefore suitable for use in patients with bronchial asthma, diabetes and gout. The use of amlodipine in patients with heart failure is not accompanied by negative inotropic effect (exercise tolerance is not reduced, left ventricular ejection fraction is not reduced).

Telmisartan

Telmisartan is a 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. It displaces angiotensin II from binding to the receptor, having no agonist effect against this receptor. Telmisartan binds only to the AT1 subtype of angiotensin II receptor. The binding is long-lasting. It has no affinity for other receptors, including the AT2 receptor. Reduces aldosterone concentration in blood, does not inhibit plasma renin activity and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (ACE) or kininase II, an enzyme that also degrades bradykinin. Therefore, an increase in bradykinin-induced adverse reactions is not expected.

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

Telmisartan reduces systolic and diastolic BP in patients with arterial hypertension without affecting heart rate (HR).

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

Pharmacokinetics

The rate and degree of absorption of the combined drug amlodipine and telmisartan are equivalent to the bioavailability of telmisartan and amlodipine when used as separate tablets.

Amlodipine

Absorption

After oral administration of amlodipine at therapeutic doses Cmax in plasma is reached after 6-12 hours. Absolute bioavailability ranges from 64% to 80%. Food intake has no effect on the bioavailability of amlodipine.

Distribution

The volume of distribution of amlodipine is approximately 21 l/kg. In in vitro studies have shown that in patients with arterial hypertension approximately 97.5% of circulating amlodipine is bound to plasma proteins.

Metabolism

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

Excretion

Excretion of amlodipine from blood plasma is biphasic. The elimination half-life (T1/2) is approximately 30-50 hours. Stable plasma concentrations are achieved after 7-8 days of continuous drug administration. Amlodipine is excreted by the kidneys both as unchanged (10%) and as metabolites (60%).

Telmisartan

Absorption

When taken orally it is rapidly absorbed from the gastrointestinal tract (GIT). Bioavailability is 50%. If it is taken simultaneously with food the area under pharmacokinetic curve “concentration-time” (AUC) is reduced from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). Three hours after ingestion, plasma concentrations level off, regardless of ingestion.

Distribution

Binding to plasma proteins is 99.5%, mainly to albumin and alpha-1 glycoprotein. Mean apparent volume of distribution in equilibrium is 500 l.

Metabolism

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

Excretion

T1/2 is more than 20 hours. The maximum concentration (Cmax) in blood plasma and, to a lesser extent, AUC increases disproportionately to the dose. There is no evidence of clinically significant cumulation of telmisartan. It is excreted unchanged in the intestine, renal excretion is less than 2%. Total plasma clearance is high (900 ml/min) compared to hepatic blood flow (approximately 1500 ml/min).

Special patient groups

There is a difference in plasma concentrations of telmisartan in men and women. Cmax and AUC were approximately 3 and 2 times higher in women compared to men, respectively, with no significant effect on efficacy.

Elderly

Telmisartan pharmacokinetics in elderly and younger patients do not differ. Amlodipine clearance tends to decrease in elderly patients, resulting in increased AUC and T1/2.

Renal dysfunction

In patients with renal impairment, telmisartan T1/2 is not altered and lower plasma telmisartan concentrations are observed. Amlodipine pharmacokinetics in patients with impaired renal function is not significantly altered. Amlodipine and telmisartan are not eliminated from the body by hemodialysis.

Hepatic impairment

Pharmacokinetic studies conducted in patients with hepatic impairment have shown that the absolute bioavailability of telmisartan increases to almost 100%. T1/2 in patients with hepatic impairment does not change. In patients with hepatic impairment the clearance of amlodipine was decreased, resulting in an increase in AUC of approximately 40-60%.

Indications

Active ingredient

Composition

How to take, the dosage

Interaction

Special Instructions

Contraindications

Side effects

Unwanted reactions expected based on experience of use are presented according to the WHO classification of adverse reactions. Their frequency is defined as follows: very common (>1/10 appointments); common (1/10-1/100 appointments); infrequent (1/100-1/1000 appointments); rare (1/1 000-1/10 000 appointments); very rare (<1/10 000 appointments); unknown (frequency of adverse reaction could not be determined from available data).

The adverse reactions were classified by organ and system according to MedDRA terms.

Infectious and parasitic diseases: infrequent – urinary tract infections1; upper respiratory tract infections1; rare – cystitis2; sepsis, including fatal.including fatal1.

Mental disorders: rare – depression2, anxiety2, insomnia2; frequency unknown – mood lability3, confusion3.

Nervous system disorders: Frequent – dizziness2; infrequent – drowsiness2, migraine2, headache2, paresthesia2; rarely, decreased sensitivity or resistance to external factors2 , impaired taste2 , syncope2 , tremor2, peripheral neuropathy2; frequency unknown – extrapyramidal disorders3.

Immune system disorders: rare – anaphylactic reaction1 , hypersensitivity1 ; frequency unknown – hypersensitivity3.

Visual organ: rare – visual disturbances1; frequency unknown – decreased vision3.

Hearing organ and labyrinth disorders: infrequent – vertigo2; frequency unknown – tinnitus3.

Cardiac disorders: Infrequent – bradycardia2, palpitations2; rare – tachycardia1; frequency unknown – myocardial infarction3, arrhythmia3, ventricular tachycardia3, atrial fibrillation3.

Vascular disorders: infrequent – marked decrease in BP2, orthostatic hypotension2.

Respiratory system disorders: Infrequent – cough2, shortness of breath1; frequency unknown – shortness of breath3, rhinitis3.

Gastrointestinal side: Infrequent – abdominal pain2, diarrhea2, nausea2, flatulence1, increased liver enzyme activity2; rarely, vomiting2, dyspepsia2, stomach discomfort1; frequency unknown- changes in defecation rhythm3, pancreatitis3, gastritis3.

Liver and biliary tract disorders: Rarely, impaired liver function1; frequency unknown, hepatitis3, jaundice3, increased liver transaminase activity, mainly reflecting cholestasis3.

Skin and subcutaneous tissue disorders: Infrequent – skin itching2, hyperhidrosis1; rare – eczema2, erythema2, skin rash2, drug rash1, toxic rash1, angioedema1, urticaria1; frequency unknown – hyperhidrosis3; angioedema3; urticaria3, alopecia3, purpura3, skin discoloration3, erythema multiforme>3 , exfoliative dermatitis3 , Stevens-Johnson syndrome3, photosensitization reaction3, vasculitis3.

Skeletal, muscular and connective tissue disorders: Infrequent – arthralgia2, muscle spasms (calf muscle cramps)2, myalgia2; rarely, pain in the lower extremities2, tendon pain (tendinitis-like symptoms)1, back pain2.

Kidney and urinary tract side: Rarely, nycturia2; frequency unknown, renal dysfunction, including acute renal failure1, urinary disorders3, rapid urination3.

Genital and breast disorders: infrequent – erectile dysfunction2; frequency unknown – gynecomastia3.

General disorders and disorders at the site of administration: Frequent – peripheral edema2; infrequent – asthenia (weakness)2, chest pain2, increased fatigue2, edema2, feeling of blood rush to face2; rarely, malaisesup>2, flu-like syndrome1, gum hypertrophy2, dry oral mucosasup>2; frequency unknown – pain3, weight gain3, weight loss3.

Laboratory and instrumental findings: Infrequent – hyperkalemia1, anemia1, increased blood creatinine concentration1; rare: increase in uric acid concentration in blood2, increase in CPK activity in blood1, decrease in Hb1, anemiasup>1, hypoglycemia (in patients with diabetes1, eosinophilia1, thrombocytopenia1; frequency unknown – thrombocytopenia3, leukopenia3, hyperglycemia3.

Additional information regarding individual components

Adverse reactions previously reported with one component of the drug (amlodipine or telmisartan) may be increased with their combination, even if they were not observed in clinical trials or during the post-registration period.

Particular information about the combination of components

Peripheral edema, a dose-dependent adverse reaction of amlodipine, was observed less frequently in patients who received a combination of telmisartan and amlodipine than in patients who received amlodipine alone.

1Unwanted reactions expected based on experience with telmisartan.

2Unwanted reactions expected based on experience with concomitant use of telmisartan and amlodipine.

3Unwanted reactions expected based on experience with amlodipine.

Overdose

Pregnancy use

Similarities