Description
Pharmacological action
Combined antihypertensive drug, which includes an angiotensin II receptor antagonist telmisartan and a thiazide diuretic hydrochlorothiazide. The simultaneous use of these components leads to a more pronounced antihypertensive effect than the use of each of them separately.
Telmisartan is a specific angiotensin II receptor antagonist. It has a high affinity for the AT1 receptor subtype of angiotensin II, through which the action of angiotensin II is realized. Telmisartan displaces angiotensin II from its binding to the receptor, lacking the action of an agonist in relation to this receptor. Telmisartan only binds to the AT1 receptor subtype of angiotensin II. Binding is continuous. Telmisartan does not have an affinity for other receptors (including AT2 receptors) of angiotensin. The functional significance of these receptors, as well as the effect of their possible excessive stimulation with angiotensin II, the concentration of which increases with the appointment of telmisartan, has not been studied. Telmisartan leads to a decrease in the concentration of aldosterone in the blood, does not inhibit renin in blood plasma and does not block ion channels. Telmisartan does not inhibit ACE (kininase II), an enzyme that also breaks down bradykinin, so no increase in side effects caused by bradykinin is expected.
In patients with arterial hypertension, telmisartan at a dose of 80 mg completely blocks the hypertensive effect of angiotensin II. The onset of antihypertensive action is noted within 3 hours after the first oral administration of telmisartan. The effect lasts for 24 hours and remains significant up to 48 hours. A pronounced antihypertensive effect usually develops after 4 weeks of regular use.
In patients with arterial hypertension, telmisartan reduces systolic and diastolic blood pressure without affecting heart rate.
In the case of abrupt cancellation of telmisartan, blood pressure gradually returns to baseline without the development of withdrawal syndrome.
Hydrochlorothiazide is a thiazide diuretic whose diuretic effect is associated with impaired reabsorption of sodium, chlorine, potassium, magnesium, water ions in the distal nephron, which delays the excretion of calcium ions, uric acid. It has antihypertensive properties, the hypotensive effect develops due to the expansion of arterioles. Virtually no effect on the normal level of blood pressure.
Excretion of electrolytes and water begins about 2 hours after administration, the maximum effect is achieved in 3-6 hours and lasts for 6-12 hours. The antihypertensive effect is achieved within 3-4 days of treatment and lasts for 1 week after completion of the drug. With prolonged treatment, a decrease in blood pressure is achieved by using lower doses than necessary for the diuretic effect. A decrease in blood pressure is accompanied by a slight increase in glomerular filtration rate, vascular resistance of the renal bed and plasma renin activity.
Hydrochlorothiazide with a single dose in high doses leads to a decrease in plasma volume, glomerular filtration rate, renal blood flow, and mean blood pressure. With prolonged use in small doses, the blood plasma volume remains reduced, while the minute volume and glomerular filtration rate return to the initial level preceding the start of treatment. Mean arterial pressure and systemic vascular resistance remain reduced. Thiazide diuretics can interfere with the production of breast milk.
The maximum antihypertensive effect of the combination telmisartan + hydrochlorothiazide is usually achieved 4-8 weeks after the start of treatment.
Indications
Arterial hypertension (with ineffective telmisartan or hydrochlorothiazide as monotherapy).
Contraindications
Obstructive biliary tract diseases severe hepatic impairment (Child-Pugh class C) severe renal impairment (CC <30 ml / min) refractory hypokalemia, hypercalcemia, simultaneous use with aliskiren in patients with diabetes mellitus and diabetes mellitus GFR <60 ml / min / 1.73 m2) age up to 18 years of pregnancy lactation (breastfeeding) hypersensitivity to telmisartan, hydrochlorothiazide or other sulfonamide derivatives. Caution: bilateral renal artery stenosis or stenosis of a single kidney artery, impaired liver function or progressive liver disease (Child-Pugh class A and B), a decrease in BCC due to previous diuretic therapy, restriction of salt intake, diarrhea or vomiting hyperkalemia condition after kidney transplantation (no experience with application) chronic heart failure III-IV FC according to NYHA classification aortic and mitral valve stenosis idiopathic hypertrophic subaortic stenosis hypertrophic obstructive cardiomyopathy diabetes mellitus primary aldosteronism gout with cornea glaucoma and glaucoma ) Use during pregnancy and lactation Use during pregnancy and lactation (breastfeeding) is contraindicated. Special instructions In some patients, renal function (including acute renal failure) is impaired due to the suppression of RAAS activity, especially with the simultaneous administration of drugs acting on this system. Therefore, therapy accompanied by a similar double blockade of RAAS (for example, when an ACE inhibitor or direct renin inhibitor, aliskiren, is added to angiotensin II receptor antagonist blockers), should be carried out strictly individually and with regular monitoring of renal function (including periodic monitoring of serum potassium and creatinine). The use of thiazide diuretics in patients with impaired renal function can lead to azotemia. Periodic monitoring of renal function is recommended. In patients with bilateral renal artery stenosis or arterial stenosis of the only functioning kidney, with drugs that affect RAAS, the risk of developing severe arterial hypotension and renal failure is increased. In patients with impaired liver function or progressive liver disease, this combination should be used with caution, since even small changes in the water-electrolyte balance can contribute to the development of hepatic coma. In patients with diabetes, a change in the dose of insulin or hypoglycemic agents for oral administration may be required. During the treatment with thiazide diuretics, latent diabetes mellitus may manifest. In some cases, with the use of thiazide diuretics, the development of hyperuricemia and exacerbation of the course of gout are possible. In patients with diabetes mellitus and additional cardiovascular risk, for example, in patients with diabetes mellitus and coronary heart disease, the use of drugs that reduce blood pressure, such as angiotensin II receptor antagonists or ACE inhibitors, may increase the risk of fatal myocardial infarction and sudden cardiac -vascular death. In patients with diabetes, coronary heart disease can be asymptomatic and therefore may be undiagnosed. Before using this combination for the detection and treatment of coronary artery disease, appropriate diagnostic studies should be carried out, including test with physical activity. Hydrochlorothiazide, being a sulfonamide derivative, can cause an idiosyncratic reaction in the form of acute transient myopia and acute angle-closure glaucoma. Symptoms of these disorders are an unexpected decrease in visual acuity or eye pain, which in typical cases occurs within a few hours to several weeks after the start of the drug. If untreated, acute angle-closure glaucoma can lead to vision loss. The main treatment is to discontinue hydrochlorothiazide as quickly as possible. It must be borne in mind that if intraocular pressure remains uncontrolled, emergency conservative or surgical treatment may be required. Risk factors for the development of acute angle-closure glaucoma include a history of allergies to sulfonamides or penicillin. Thiazide diuretics, incl. hydrochlorothiazide, can cause disturbances in the water-electrolyte balance and the acid-base state (hypokalemia, hyponatremia and hypochloremic alkalosis). Signs of concern for these disorders are dry oral mucosa, thirst, general weakness, drowsiness, anxiety, myalgia or convulsive twitching of the calf muscles (crumpi), muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, and such gastrointestinal intestinal disorders like nausea or vomiting. During treatment with this combination, periodic monitoring of serum electrolytes is necessary. When using this combination, the risk of hypokalemia is more likely in patients with liver cirrhosis, with increased diuresis, while maintaining a salt-free diet, as well as in the case of the simultaneous use of gluco- and mineralocorticoids or corticotropin, renal and / or heart failure and sugar are risk factors for hyperkalemia diabetes. Thiazide diuretics can reduce the excretion of calcium by the kidneys and cause (in the absence of obvious disturbances in calcium metabolism) a transient and slight increase in serum calcium. More severe hypercalcemia may be a sign of latent hyperparathyroidism. Before assessing the function of the parathyroid glands, thiazide diuretics should be discontinued. Thiazide diuretics have been shown to increase kidney excretion of magnesium, which can lead to hypomagnesemia. In patients with coronary heart disease, the use of any antihypertensive agent, in the case of an excessive decrease in blood pressure, can lead to myocardial infarction or stroke. There are reports of the development of SLE with thiazide diuretics. This combination, if necessary, is used in combination with other antihypertensive agents. Dysfunction of the liver with the appointment of telmisartan in most cases was observed in residents of Japan. This combination is less effective in patients of the Negroid race. Effect on the ability to drive vehicles and mechanisms During treatment, the possibility of developing dizziness and drowsiness should be considered, which requires caution. Composition 1 tab. telmisartan 80 mg hydrochlorothiazide 12.5 mg Excipients: meglumine, sodium hydroxide, povidone K30, lactose monohydrate, sorbitol, magnesium stearate, mannitol, mannitol (E421) DC, hyprolose, silicon dioxide colloidal yellow, ferric acid, yellow E172). Dosage and administration Take orally 1 time / day. A single dose of telmisartan + hydrochlorothiazide combination is between 40 mg / 12.5 mg and 80 mg / 25 mg. In patients with severe arterial hypertension, the maximum daily dose of telmisartan is 160 mg / day. This dose was effective and well tolerated. In patients with impaired liver function of mild to moderate degree (class A and B on the Child-Pugh scale), this combination should not be used in a daily dose of more than 40 mg / 12.5 mg. Side effects of From the respiratory system: respiratory distress syndrome (including pneumonia and pulmonary edema), shortness of breath. From the cardiovascular system: arrhythmias, tachycardia, bradycardia, marked decrease in blood pressure (including orthostatic hypotension). From the nervous system: syncope / fainting, paresthesia, sleep disturbances, insomnia, dizziness, anxiety, depression, increased irritability, headache. From the digestive system: diarrhea, dry oral mucosa, flatulence, abdominal pain, constipation, vomiting, gastritis, decreased appetite, anorexia, hyperglycemia, hypercholesterolemia, pancreatitis, impaired liver function, jaundice (hepatocellular or cholestatic,). From the skin: increased sweating. From the musculoskeletal system: back pain, muscle cramps, myalgia, arthralgia, spasms of the calf muscles, arthrosis, tendonitis-like symptoms, chest pain. From the hemopoietic system: iron deficiency anemia, aplastic anemia, hemolytic anemia, thrombocytopenia, eosinophilia, leukopenia, neutropenia / agranulocytosis, thrombocytopenia. From the urinary system: renal failure, including acute renal failure, interstitial nephritis, glucosuria. On the part of the sensory organs: visual impairment, transient blurred vision, xanthopsia, acute angle-closure glaucoma, acute myopia. From the reproductive system: impotence. Infections: sepsis, including fatal cases, upper respiratory tract infections (bronchitis, pharyngitis, sinusitis), urinary tract infections (including cystitis), salivary gland inflammation. From the side of metabolism: increased plasma creatinine concentration, increased liver enzyme activity, increased CPK activity, increased blood uric acid concentration, hypertriglyceridemia, hypokalemia, hyperkalemia, hyponatremia, hyperuricemia, a decrease in BCC, hypoglycemia (in patients with diabetes mellitus), impaired glucose tolerance, a decrease in hemoglobin in the blood. Allergic reactions: angioedema (including fatal cases), erythema, pruritus, rash, anaphylactic reactions, eczema, drug rash, toxic epidermal necrolysis, lupus-like reactions, exacerbation or exacerbation of symptoms of systemic lupus erythematosus, necrotizing vascular system photosensitivity reaction, relapse of systemic lupus erythematosus, vasculitis. Other: flu-like syndrome, fever, weakness. Drug Interactions Telmisartan Other antihypertensive drugs – an increase in the hypotensive effect is possible. Lithium preparations – a reversible increase in the concentration of lithium in the blood, accompanied by toxic effects, has rarely been observed. With the simultaneous use of lithium preparations and angiotensin II receptor antagonists, it is recommended to determine the blood lithium content of NSAIDs, including acetylsalicylic acid in doses used as anti-inflammatory drugs, COX-2 inhibitors and non-selective NSAIDs – it is possible to develop acute renal failure in patients with reduced BCC . Drugs that affect RAAS may have a synergistic effect. In patients receiving NSAIDs and telmisartan, bcc should be compensated at the beginning of treatment and a kidney function test should be performed. Decreased effect of antihypertensive drugs such as telmisartan, by inhibiting the vasodilating effect of prostaglandins, it was noted with co-treatment with NSAIDs. With the simultaneous use of telmisartan with ibuprofen or paracetamol, no clinically significant effect was detected. Digoxin – an increase in the average concentration of digoxin in blood plasma by an average of 20% (in one case, by 39%). With the simultaneous administration of telmisartan and digoxin, it is advisable to periodically determine the concentration of digoxin in the blood. Hydrochlorothiazide Ethanol, barbiturates, opioid analgesics – risk of orthostatic hypotension. Hypoglycemic drugs for oral administration and insulin – dose adjustment of hypoglycemic agents for oral and insulin administration may be required. Metformin – there is a risk of developing lactic acidosis. Colestyramine and colestipol – in the presence of anionic exchange resins, the absorption of hydrochlorothiazide is impaired. Cardiac glycosides – the risk of developing hypokalemia or hypomagnesemia caused by thiazide diuretics, the development of arrhythmias caused by cardiac glycosides is increased. Pressor amines (e.g. norepinephrine) – possibly weakening the effect of pressor amines. Non-depolarizing muscle relaxants (e.g. tubocurarine chloride) – hydrochlorothiazide may enhance the effect of non-depolarizing muscle relaxants Anti-gout agents – may increase the concentration of uric acid in the blood serum, therefore, a dose change of uricosuric agents may be required. The use of thiazide diuretics increases the incidence of hypersensitivity reactions to allopurinol. Calcium preparations – thiazide diuretics can increase serum calcium due to a decrease in its excretion by the kidneys. If you want to use calcium preparations, you should regularly monitor the calcium content in the blood and, if necessary, change the dose of calcium preparations. Beta-blockers and diazoxide – thiazide diuretics can increase the hyperglycemia caused by beta-blockers and diazoxide M-anticholinergics (e.g., atropine, biperidine) – decrease gastrointestinal motility, increase bioavailability of thiazide diuretics. Amantadine – Thiazide diuretics may increase the risk of unwanted effects caused by amantadine. Cytotoxic agents (for example, cyclophosphamide, methotrexate) – a decrease in renal excretion of cytotoxic agents and an increase in their myelosuppressive effect. NSAIDs – combined use with thiazide diuretics can lead to a decrease in diuretic and antihypertensive effect. Means that lead to the elimination of potassium and hypokalemia (for example, diuretics that remove potassium, laxatives with gluco- and mineralocorticoids corticotropin amphotericin B carbenoxolone benzylpenicillin, derivatives of acetylsalicylic acid) – increased hypokalemic effect. Hypokalemia caused by hydrochlorothiazide is offset by the potassium-sparing effect of telmisartan. Potassium-sparing diuretics, potassium preparations, other drugs that can increase the potassium content in blood serum (for example, heparin) or replace sodium in sodium chloride with potassium salts – hyperkalemia may develop. Periodic monitoring of potassium in the blood plasma is recommended in cases when the combination of telmisartan + hydrochlorothiazide is used simultaneously with drugs that can cause hypokalemia, as well as with drugs that can increase serum potassium. Active ingredient Telmisartan, hydrochlorothiazide Pharmacy terms Prescription lekarstvennaja form tablets
