Instructions for use Hipotel tablets 40 mg blister No. 28
Composition
active ingredient: telmisartan;
1 tablet contains telmisartan 20 mg, 40 mg or 80 mg;
excipients: sodium hydroxide, meglumine, mannitol (E 421), crospovidone, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: white or almost white round biconvex tablets.
Pharmacotherapeutic group
Simple angiotensin II antagonists. ATC code C09C A07.
Pharmacological properties
Pharmacodynamics.
Mechanism of action.
Telmisartan is a specific and potent angiotensin II receptor (type AT1) antagonist. Telmisartan displaces angiotensin II with very high affinity at the binding sites of the AT1 receptor subtype, which are responsible for the activity of angiotensin II. Telmisartan does not have any partial agonist effect at the AT1 receptor. Telmisartan selectively binds
AT1 receptor. Binding is long-lasting. Telmisartan shows no affinity for other receptors, including AT2 and other, less studied AT receptors. The functional role of these receptors is unknown, as is the effect of their possible "overstimulation" by angiotensin II, the level of which increases under the influence of telmisartan. Telmisartan reduces plasma aldosterone levels. Telmisartan does not inhibit renin in human plasma, does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kininase II), an enzyme that also destroys bradykinin. Therefore, potentiation of bradykinin-associated side effects should not be expected.
In humans, telmisartan at a dose of 80 mg almost completely inhibits the increase in blood pressure caused by angiotensin II. The blocking effect is maintained for 24 hours and remains significant for up to 48 hours.
Pharmacokinetics.
Absorption. Absorption of telmisartan is rapid, although the amounts absorbed vary. The mean absolute bioavailability of telmisartan is approximately 50%. When telmisartan is administered with food, the decrease in the area under the plasma concentration-time curve (AUC) for telmisartan ranges from approximately 6% (40 mg) to 19% (160 mg). Three hours after administration, plasma concentrations are similar whether telmisartan is taken on an empty stomach or with food.
Linearity/non-linearity. A small decrease in AUC is not expected to result in a decrease in therapeutic efficacy. There is no linear relationship between dose and plasma levels. Cmax and, to a lesser extent, AUC increase disproportionately at doses above 40 mg.
Distribution: Telmisartan is highly bound to plasma proteins (>99.5%), mainly to albumin and alpha-1 acid glycoprotein. The mean volume of distribution (Vss) is approximately 500 l.
Metabolism: Telmisartan is metabolized by conjugation to the glucuronide of the parent compound. The pharmacological activity of the conjugate has not been established.
Elimination: Telmisartan exhibits biexponential pharmacokinetics with a terminal half-life of >20 hours. Maximum plasma concentration (Cmax) and, to a lesser extent, AUC increase disproportionately with dose. There is no evidence of clinically significant accumulation of telmisartan at recommended doses. Plasma concentrations were higher in women than in men, without any corresponding effect on efficacy.
After oral administration, telmisartan is almost completely excreted in the faeces, mainly as unchanged compound. Cumulative renal excretion is < 1% of the dose. Total plasma clearance (Cltot) is high (approximately 1000 ml/min) compared to hepatic blood flow (approximately 1500 ml/min).
Special categories of patients.
Children: The results of pharmacokinetic studies in children are generally consistent with those obtained in adults and confirm the non-linearity of telmisartan, in particular for Cmax.
Gender: Plasma concentrations Cmax and AUC are approximately 3- and 2-fold higher in women than in men, respectively.
Elderly patients: The pharmacokinetics of telmisartan do not differ between the elderly and those under 65 years of age.
Patients with renal impairment. In patients with mild to moderate and severe renal impairment, a 2-fold increase in plasma concentrations was observed. However, in patients with renal impairment undergoing dialysis, low plasma concentrations were observed. Telmisartan is highly bound to plasma proteins in subjects with renal impairment and cannot be removed by dialysis. The elimination half-life is not altered in patients with renal impairment.
Patients with hepatic impairment: Pharmacokinetic studies in patients with hepatic impairment have shown an increase in absolute bioavailability to approximately 100%. The elimination half-life is not altered in patients with hepatic insufficiency.
Indication
Hypertension.
Treatment of essential hypertension in adults.
Prevention of cardiovascular diseases.
Reducing the incidence of cardiovascular disease in patients with:
- manifest atherothrombotic cardiovascular disease (history of ischemic heart disease, stroke or peripheral arterial disease);
- type II diabetes mellitus with documented target organ damage.
Contraindication
- pregnant women or women planning to become pregnant (see sections (Special instructions for use", "Use during pregnancy or breastfeeding");
- obstructive biliary disorders;
- severe liver dysfunction;
- childhood (up to 18 years old).
The concomitant use of telmisartan and aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see sections “Interaction with other medicinal products and other forms of interaction” and “Pharmacological properties”).
Interaction with other medicinal products and other types of interactions
Digoxin.
When telmisartan and digoxin were co-administered, mean increases in peak plasma digoxin concentrations (by 49%) and trough concentrations (by 20%) were observed. Digoxin levels should be monitored at the start of treatment, in case of dose adjustment and discontinuation of telmisartan, to maintain them within the therapeutic range.
As with other drugs that inhibit the renin-angiotensin system, telmisartan may induce hyperkalemia (see section 4.4). The risk may be increased by concomitant treatment with other drugs that may also induce hyperkalemia (salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressants (ciclosporin or tacrolimus) and trimethoprim).
The incidence of hyperkalemia depends on the associated risk factors. The risk increases with the above therapeutic combinations. The risk is particularly high in combination with potassium-sparing diuretics and in combination with potassium-containing salt substitutes. The combination with ACE inhibitors or NSAIDs, for example, is less risky if the precautions for use are strictly observed.
Concomitant use is not recommended.
Potassium-sparing diuretics or potassium supplements. Angiotensin II receptor antagonists such as telmisartan attenuate diuretic-induced potassium loss. Potassium-sparing diuretics such as spironolactone, eplerenone, triamterene or amiloride, potassium supplements or potassium-containing salt substitutes may lead to significant increases in serum potassium. If concomitant use is indicated because of documented hypokalaemia, they should be used with caution, with frequent monitoring of serum potassium.
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, including telmisartan. If the combination is considered necessary, serum lithium levels should be closely monitored during concomitant use.
Concomitant use requires caution.
Nonsteroidal anti-inflammatory drugs: NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory doses, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the combination of angiotensin II receptor antagonists and cyclooxygenase inhibitors may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, this combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated; in addition, renal function should be monitored after initiation of combination therapy and periodically thereafter.
There is evidence that the combined administration of telmisartan and ramipril leads to a 2.5-fold increase in AUC0-24 and Cmax of ramipril and ramiprilat. The clinical significance of this observation is unknown.
Diuretics (thiazide or loop diuretics): Pre-treatment with high doses of diuretics such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic) may lead to volume depletion and a risk of hypotension when initiating treatment with telmisartan.
This should be taken into account when used concomitantly.
Other antihypertensive agents: The blood pressure-lowering effect of telmisartan may be enhanced by concomitant use of other antihypertensive agents.
Clinical data have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher incidence of adverse events such as hypotension, hyperkalemia and decreased renal function (including acute renal failure) compared with the use of a single RAAS-acting agent (see sections 4.4, 4.3 and 5.1).
Based on the pharmacological properties of baclofen and amifostine, it can be expected that these drugs may potentiate the hypotensive effect of all antihypertensive drugs, including telmisartan. In addition, orthostatic hypotension may be exacerbated by alcohol, barbiturates, narcotics, and antidepressants.
Corticosteroids (systemic use). Decreased antihypertensive effect.
Application features
Pregnancy.
Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued angiotensin II receptor antagonist therapy is considered essential for the patient planning pregnancy, she should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.8).
Liver failure.
Hipotel should not be prescribed to patients with cholestasis, obstructive diseases of the bile ducts and severe hepatic insufficiency (see section "Contraindications"), since telmisartan is excreted mainly with bile. In such patients, a decrease in hepatic clearance of telmisartan can be expected.
Hipotel should be administered with caution to patients with mild to moderate hepatic impairment.
Renovascular hypertension: There is an increased risk of severe hypotension and renal failure when patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney are treated with drugs that affect the renin-angiotensin-aldosterone system.
Renal impairment and kidney transplantation. When Hipotel is prescribed to patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended. There is no experience with the use of telmisartan in patients with a recent kidney transplantation.
Intravascular volume depletion. Symptomatic hypotension, especially after the first dose of Hypotel, may occur in patients with reduced intravascular volume and/or sodium levels resulting from diuretic therapy, dietary salt restriction, diarrhea, or vomiting. Such conditions, especially intravascular volume and/or sodium depletion, should be corrected before administration of Hypotel.
Dual blockade of the renin-angiotensin-aldosterone system.
There is evidence that concomitant use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure).
Therefore, dual blockade through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see sections 4.5 and 5.1).
If dual blockade is considered absolutely necessary, it should only be performed under specialist supervision and with continuous close monitoring of renal function, electrolytes and blood pressure.
ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Other conditions requiring stimulation of the renin-angiotensin-aldosterone system.
In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or severe renal disease, including renal artery stenosis), the use of telmisartan with other medicinal products that affect the renin-angiotensin-aldosterone system has been associated with acute hypotension, hyperazotemia, oliguria, and rarely acute renal failure (see section 4.8).
Primary hyperaldosteronism: Patients with primary hyperaldosteronism generally do not respond to antihypertensive drugs that act by blocking the renin-angiotensin system. Therefore, the use of telmisartan in these patients is not recommended.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy. As with other vasodilators, the drug should be administered with extreme caution to patients diagnosed with aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.
Diabetic patients treated with insulin or antidiabetic drugs.
Hypoglycemia may develop in such patients during treatment with telmisartan. Appropriate blood glucose monitoring should be considered in such patients. Dosage adjustment of insulin or antidiabetic medicinal products may be necessary if indicated.
Hyperkalemia: Hyperkalemia may occur during the entire course of treatment with drugs that affect the renin-angiotensin-aldosterone system.
In the elderly, in patients with renal insufficiency, diabetes, in patients who are being treated concurrently with other drugs that may cause an increase in potassium levels, and/or in patients with concomitant diseases, hyperkalemia can be fatal.
Before considering the concomitant use of medicinal products that inhibit the renin-angiotensin system, the benefit-risk ratio should be weighed.
The main risk factors for developing hyperkalemia that you need to pay attention to are:
- Diabetes, renal failure, age (over 70 years).
- Combination therapy with one or more other medicinal products that affect the renin-angiotensin system and/or potassium supplements. Medicinal products or therapeutic classes of medicinal products that may induce hyperkalaemia include salt substitutes containing potassium, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressants (ciclosporin or tacrolimus) and trimethoprim.
- Concomitant diseases, especially dehydration, acute cardiac decompensation, metabolic acidosis, worsening of renal function, acute deterioration of renal status (e.g. infectious diseases), cellular lysis (e.g. acute limb ischemia, acute skeletal muscle necrosis, extensive trauma).
Patients at risk should undergo careful monitoring of serum potassium concentrations (see section “Interaction with other medicinal products and other types of interactions”).
Ethnic differences: As with all angiotensin II receptor antagonists, telmisartan is apparently less effective in lowering blood pressure in black patients than in non-blacks. This may be due to a higher prevalence of low-renin states in black hypertensive patients.
Others: As with any other antihypertensive agent, a significant decrease in blood pressure in patients with ischemic cardiopathy or ischemic cardiovascular disease may lead to myocardial infarction or stroke.
Use during pregnancy or breastfeeding
Pregnancy.
The drug is contraindicated for use in pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment with this drug, its use should be discontinued immediately and, if necessary, replaced with another drug approved for use in pregnant women (see sections "Contraindications" and "Special Instructions").
There are no adequate data from the use of telmisartan in pregnant women.
Epidemiological evidence of a teratogenic risk following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive, but a small increased risk cannot be excluded. Although there are no controlled epidemiological data on the risk of teratogenicity with angiotensin II receptor antagonists, similar risks may exist for this class of medicinal products. When planning pregnancy, patients should be changed in good time to another antihypertensive treatment which has an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately and, if appropriate, alternative therapy should be started.
The use of angiotensin II receptor antagonists during the second and third trimesters of pregnancy is known to induce human fetotoxicity (renal impairment, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia). If exposure to angiotensin II receptor antagonists has been initiated from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken angiotensin II receptor antagonists should be closely monitored for hypotension (see sections 4.3 and 4.4).
Breast-feeding.
Because no information is available regarding the use of telmisartan during breast-feeding, Telmisartan is not recommended. Alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
Fertility.
In preclinical studies, no effect of telmisartan on male or female fertility was observed.
Ability to influence reaction speed when driving vehicles or other mechanisms
When driving a car or operating machinery, it is necessary to take into account the possibility of dizziness or hypersomnia during antihypertensive therapy, including the drug Hipotel.
Method of administration and doses
The usual effective dose is 40 mg daily. Some patients may find a daily dose of 20 mg sufficient. If the desired blood pressure is not achieved, the dose of telmisartan can be increased to 80 mg once daily. Alternatively, telmisartan can be given in combination with thiazide diuretics, such as hydrochlorothiazide, which has been shown to provide additional blood pressure lowering when used with telmisartan. When considering increasing the dose, it should be borne in mind that the maximum antihypertensive effect is generally achieved 4–8 weeks after initiation of treatment.
Prevention of cardiovascular diseases.
The recommended dose is 80 mg once daily. The efficacy of telmisartan at doses lower than
80 mg in the prevention of cardiovascular disease is unknown.
When initiating treatment with telmisartan for the prevention of cardiovascular diseases, it is recommended to monitor blood pressure and, if necessary, adjust the dose of blood pressure-lowering drugs.
Special patient groups
Kidney dysfunction.
Experience in patients with renal insufficiency or patients undergoing haemodialysis is limited. In such patients it is recommended to start treatment with a low dose of 20 mg (see section 4.4).
There is no need for dose adjustment for patients with mild to moderate renal impairment.
The concomitant use of telmisartan and aliskiren in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) is contraindicated (see section "Contraindications").
Hepatic impairment. Hypotel is contraindicated in patients with severe hepatic impairment.
For patients with mild or moderate hepatic impairment, the daily dose should not exceed 40 mg once daily (see section "Special warnings and precautions for use").
Elderly patients: No dose adjustment is required for elderly patients.
Method of application.
Take Hipotel once a day orally with sufficient liquid, with/or without food.
Store the tablets in a sealed blister to protect from moisture. The tablets should be removed from the blister immediately before use.
Children.
The safety and efficacy of Hipotel in children (under 18 years of age) have not been studied.
Overdose
Limited information on human overdose.
Symptoms: The most significant manifestations of telmisartan overdose were hypotension and tachycardia; bradycardia, dizziness, increased serum creatinine concentration and acute renal failure have also been reported.
Therapy. Telmisartan is not removed by hemodialysis. Patients should be closely monitored and receive symptomatic and supportive therapy. Therapy depends on the time of drug administration and the severity of symptoms. Recommended measures include induction of vomiting and/or gastric lavage. Activated charcoal may be used in the treatment of overdose. Serum electrolytes and creatinine levels should be monitored frequently. If hypotension occurs, the patient should be placed on his back and assistance should be provided to rapidly replenish the volume of fluid and salt in the body.
Adverse reactions
Infections and infestations: upper respiratory tract infections, including pharyngitis and sinusitis; urinary tract infections, including cystitis; sepsis, including fatal outcomes.
From the blood and lymphatic system: anemia, thrombocytopenia, eosinophilia.
Immune system disorders: hypersensitivity, anaphylactic reaction.
Metabolic disorders: hyperkalemia, hypoglycemia (in patients with diabetes).
Mental disorders: depression, insomnia, anxiety.
Nervous system: syncope, drowsiness.
On the part of the organs of vision: visual impairment.
From the side of the organs of hearing, vestibular apparatus: vertigo.
Cardiac: bradycardia, tachycardia.
Vascular disorders: arterial hypotension, orthostatic hypotension.
Respiratory, thoracic and mediastinal disorders: dyspnea, cough, interstitial lung disease.
On the part of the digestive tract: abdominal pain, diarrhea, dyspepsia, flatulence, vomiting, discomfort in the stomach area, dry mouth, dysgeusia.
Hepatobiliary system: liver dysfunction/hepatic disorders.
Skin and subcutaneous tissue disorders: increased sweating, itching, rash, erythema, angioedema (including fatal), drug dermatitis, toxic dermatitis, eczema, urticaria.
Musculoskeletal and connective tissue disorders: myalgia, back pain (e.g. sciatica), muscle cramps, arthralgia, pain in extremities, tendon pain (symptoms similar to tendinitis).
From the urinary system: renal dysfunction, including acute renal failure.
General disorders: chest pain, asthenia (weakness), flu-like symptoms.
Laboratory data: increased creatinine in the blood, increased uric acid in the blood, increased liver enzymes, increased creatine phosphokinase (CPK) in the blood, decreased hemoglobin.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 ºC in the original packaging.
Keep out of reach of children.
Packaging
10 tablets in a blister; 3 blisters in a cardboard box.
14 tablets in a blister; 2 or 4 or 6 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
"KUSUM FARM" LLC.
Location of the manufacturer and its business address
Ukraine, 40020, Sumy, Skryabina St., 54.
