Instructions for Telmista H 80 film-coated tablets 80mg + 12.5mg blister No. 28
Composition
active ingredients: telmisartan, hydrochlorothiazide;
1 tablet contains 40 mg of telmisartan and 12.5 mg of hydrochlorothiazide or 80 mg of telmisartan and 12.5 mg of hydrochlorothiazide, or 80 mg of telmisartan and 25 mg of hydrochlorothiazide;
excipients: meglumine, sodium hydroxide, povidone, lactose monohydrate, sorbitol (E 420), magnesium stearate, mannitol (E 421), mannitol DC (E 421), hydroxypropylcellulose, colloidal anhydrous silica, sodium stearyl fumarate, red iron oxide (E 172) - for Telmista H 40, Telmista H 80 tablets, yellow iron oxide (E 172) - for Telmista HD 80 tablets.
Dosage form
Pills.
Main physicochemical properties:
Telmista H 40: white to almost white or pinkish-white on one side and pinkish-marble on the other side, two-layer, biconvex, oval tablets.
Telmista H 80: white to almost white or pinkish-white on one side and pinkish-marble on the other side, two-layer, biconvex, oval tablets.
Telmista HD 80: white to yellowish-white on one side and yellow-marble on the other side, two-layer, biconvex, oval tablets.
Pharmacotherapeutic group
Angiotensin II antagonists and diuretics. ATC code C09D A07.
Pharmacological properties
Pharmacodynamics.
The fixed combination of telmisartan/hydrochlorothiazide is a combination of the angiotensin II receptor antagonist telmisartan and the thiazide diuretic hydrochlorothiazide. The combination of these components exhibits an additive antihypertensive effect, reducing blood pressure to a greater extent than either component alone. Telmisartan/hydrochlorothiazide, when administered once daily within therapeutic doses, results in an effective and slow reduction in blood pressure.
Mechanism of action
Telmisartan is effective when administered orally and is a specific antagonist of angiotensin II receptors (AT1 subtype). Having a very high affinity for this receptor subtype, telmisartan displaces angiotensin II from its binding to AT1 receptors. It does not exhibit any partial agonist effect on AT1 receptors. Telmisartan binds selectively to AT1 receptors. The binding is long-lasting. Telmisartan does not exhibit affinity for other receptors, including AT2 and other less characterized 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 the level of aldosterone in the blood plasma. Telmisartan does not inhibit human plasma renin and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (ACE) (kinase II), the enzyme that also degrades bradykinin. Therefore, potentiation of bradykinin-mediated side effects is not expected.
The drug at a dose of 80 mg almost completely inhibits the hypertensive effect of angiotensin II in humans. The effect of the drug lasts for more than 24 hours and is observed for up to 48 hours.
Hydrochlorothiazide is a thiazide diuretic. The mechanism of antihypertensive action of thiazide diuretics is not yet fully understood. Thiazide diuretics affect the mechanism of electrolyte reabsorption in the renal tubules, thereby directly increasing the excretion of sodium and chloride in approximately equivalent volumes. Due to the diuretic effect of hydrochlorothiazide, plasma volume decreases, plasma renin activity increases, aldosterone secretion increases with a corresponding increase in urinary potassium and bicarbonate excretion and a decrease in serum potassium. Perhaps through blockade of the renin-angiotensin-aldosterone system (RAAS), the concomitant use of telmisartan helps to reverse the potassium loss associated with these diuretics. When using hydrochlorothiazide, the onset of diuresis occurs after 2 hours, the maximum effect is achieved after approximately 4 hours, while the action lasts for approximately 6-12 hours.
Clinical efficacy and safety
After the first dose of telmisartan, antihypertensive activity gradually manifests itself within 3 hours. The maximum reduction in blood pressure is observed 4-8 weeks after the start of treatment and is maintained during long-term therapy. The hypotensive effect is maintained continuously for 24 hours after taking the drug, including the last 4 hours before taking the next dose. This is confirmed by measuring blood pressure at the point of maximum effect and immediately before taking the next dose (the ratio of the lowest to the highest values is above 80% after taking doses of 40 and 80 mg of telmisartan in placebo-controlled clinical studies).
In patients with arterial hypertension, telmisartan reduces both systolic and diastolic blood pressure without affecting pulse rate. The antihypertensive efficacy of telmisartan is comparable to that of other classes of antihypertensive drugs (demonstrated in clinical trials comparing telmisartan with amlodipine, atenolol, enalapril, hydrochlorothiazide, losartan and lisinopril).
The effect of telmisartan on mortality and cardiovascular morbidity is still unknown.
Epidemiological studies have shown that long-term treatment with hydrochlorothiazide reduces the risk of cardiovascular morbidity and mortality.
The effect of the fixed combination of telmisartan/hydrochlorothiazide on mortality and cardiovascular disease is unknown.
Non-melanoma skin cancer (NMSC)
Available epidemiological data have demonstrated an association between cumulative dose of hydrochlorothiazide and NMSR.
Pharmacokinetics.
Concomitant use of hydrochlorothiazide and telmisartan does not affect the pharmacokinetics of either drug in healthy volunteers.
Absorption
Telmisartan. After oral administration, the maximum concentration of telmisartan (Cmax) is reached after 0.5-1.5 hours. The absolute bioavailability of telmisartan at a dose of 40 mg and 160 mg is 42% and 58%, respectively. Food slightly reduces the bioavailability of telmisartan, the decrease in the area under the concentration-time curve (AUC) for telmisartan varies from approximately 6% (40 mg dose) to approximately 19% (160 mg dose). 3 hours after administration of the drug, the concentration in the blood plasma is the same and does not depend on how telmisartan is taken - on an empty stomach or with food. It is believed that a small decrease in AUC does not cause a decrease in therapeutic efficacy. Telmisartan does not accumulate in the blood plasma to a significant extent with repeated administration.
Hydrochlorothiazide: After oral administration of the telmisartan/hydrochlorothiazide combination, Cmax of hydrochlorothiazide is reached after 1-3 hours. Due to the cumulative renal excretion of hydrochlorothiazide, the absolute bioavailability is approximately 60%.
Distribution
Telmisartan: Telmisartan is highly bound to plasma proteins (>99.5%), mainly to albumin and alpha-1-acid glycoprotein. The volume of distribution is approximately 500 L, indicating extensive tissue binding.
Hydrochlorothiazide. Hydrochlorothiazide is 68% bound to plasma proteins, with a volume of distribution of 0.83–1.14 L/kg.
Biotransformation
Telmisartan is metabolized by conjugation to form a pharmacologically inactive acylglucuronide. The glucuronide of the parent compound is the only metabolite identified in humans. After a single dose of 14C-labeled telmisartan, the glucuronide represents approximately 11% of the measured radioactivity in plasma. Cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.
Hydrochlorothiazide: Not metabolized in humans.
Breeding
Telmisartan. After intravenous or oral administration of 14C-labeled telmisartan, the majority of the dose (>97%) is excreted in the faeces via biliary excretion. Only a small amount was recovered in the urine. The total plasma clearance of telmisartan after oral administration is >1500 ml/min. The terminal half-life is more than 20 hours.
Hydrochlorothiazide is excreted almost entirely unchanged in the urine. Approximately 60% of an oral dose is excreted unchanged within 48 hours. Renal clearance is approximately 250-300 ml/min. The terminal half-life is 10-15 hours.
Linearity/nonlinearity
Telmisartan: The pharmacokinetics of orally administered telmisartan are non-linear in the dose range of 20 to 160 mg with a more than proportional increase in plasma concentrations (Cmax and AUC) with increasing doses.
Hydrochlorothiazide exhibits linear pharmacokinetics.
Special categories of patients
Elderly patients: The pharmacokinetics of telmisartan do not differ between elderly patients and patients under 65 years of age.
Gender. Telmisartan plasma concentrations are generally 2-3 times higher in women than in men. However, clinical studies have shown that the rate of blood pressure reduction in women is not significantly increased, nor is the incidence of orthostatic hypotension. No dose adjustment is necessary. Women tend to have higher hydrochlorothiazide concentrations than men, but this is of no clinical significance.
Patients with renal impairment. Renal excretion does not affect the elimination of telmisartan. Based on limited experience in patients with mild to moderate renal impairment (creatinine clearance 30-60 ml/min, mean approximately 50 ml/min), no dose adjustment is necessary for these patients. Telmisartan is not removed by haemodialysis. In patients with renal insufficiency, the elimination rate of hydrochlorothiazide is reduced. In typical studies, the half-life of hydrochlorothiazide is increased in patients with a mean creatinine clearance of 90 ml/min. In patients with a removed or absent kidney, the half-life is approximately 34 hours.
Patients with hepatic impairment: Pharmacokinetic studies in patients with hepatic impairment have shown an increase in absolute bioavailability of almost 100%. The elimination half-life is not altered in these patients.
Indication
Arterial hypertension.
Telmisartan 80 mg/hydrochlorothiazide 25 mg is indicated for use in adult patients whose blood pressure is not adequately controlled on Telmisartan 80 mg/hydrochlorothiazide 12.5 mg, or in adult patients whose blood pressure has previously been stabilised on telmisartan and hydrochlorothiazide alone.
Contraindication
Hypersensitivity to the active substance or to any of the components of the drug.
Hypersensitivity to other sulfonamide derivatives (hydrochlorothiazide is a sulfonamide derivative).
Pregnancy and planning pregnancy (see sections "Special instructions" and "Use during pregnancy or breastfeeding").
Cholestatic and biliary obstructive disorders.
Severe liver dysfunction.
Anuria, severe renal impairment (creatinine clearance < 30 ml/min).
Refractory hypokalemia/hyponatremia, hypercalcemia.
Breastfeeding period.
Symptomatic hyperuricemia (gout).
Children's age (up to 18 years).
The concomitant use of telmisartan/hydrochlorothiazide with aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency (GFR <60 ml/min/1.73 m2) (see sections “Interaction with other medicinal products and other types of interactions” and “Special precautions for use”).
Interaction with other medicinal products and other types of interactions
Lithium. Reversible increases in serum lithium concentrations and toxicity have been reported with concomitant use of lithium with ACE inhibitors. Rare cases of such interactions have been reported with angiotensin II receptor antagonists (including telmisartan/hydrochlorothiazide). Concomitant use of lithium and Telmisartan H, Telmisartan HD is not recommended (see section 4.4). If the efficacy of this combination has been proven with concomitant use, careful monitoring of serum lithium levels is recommended.
Medicinal products associated with potassium loss and hypokalaemia (e.g. other potassium-sparing diuretics, laxatives, corticosteroids, adrenocorticotropic hormone (ACTH), amphotericins, carbenoxolones, penicillin G sodium, salicylic acid and derivatives) When these medicinal products are used together with the combination of hydrochlorothiazide/telmisartan, monitoring of plasma potassium levels is recommended. These medicinal products may potentiate the effect of hydrochlorothiazide on plasma potassium levels (see section 4.4).
Medicinal products that may increase sodium levels and cause hyperkalaemia (e.g. medicinal products that inhibit the renin-angiotensin system, potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, ciclosporin or other medicinal products such as heparin sodium) When these medicinal products are used together with the combination of hydrochlorothiazide/telmisartan, monitoring of potassium levels in the blood plasma is recommended. Based on experience with other medicinal products that inhibit the renin-angiotensin system, the simultaneous use of these medicinal products may lead to increases in serum potassium and is therefore not recommended (see section 4.4).
Medicinal products that cause disturbances in serum potassium levels. It is recommended to periodically monitor serum potassium levels and perform ECGs when using Telmisartan H, Telmisartan HD with the following medicinal products that cause disturbances in serum potassium levels (e.g. digitalis glycosides, antiarrhythmics) and medicinal products that stimulate ventricular fibrillation (including some antiarrhythmics), hypokalemia, which is a provoking factor for ventricular fibrillation:
Class Ia antiarrhythmic drugs (e.g. quinidine, hydroquinidine, disopyramide);
Class III antiarrhythmic drugs (e.g. amiodarone, sotalol, dofetilide, ibutilide);
some antipsychotics (e.g. thioridazine, chlorpromazine, levopromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol);
others (e.g., bepridil, cisapride, diphemanil, erythromycin IV, halofantrine, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine IV).
Digitalis glycosides: Thiazide-induced hypokalemia or hypomagnesemia may precipitate digitalis-induced cardiac arrhythmias (see section 4.4).
Digoxin: Concomitant administration of telmisartan with digoxin has been associated with an increase in mean peak (49%) and trough (20%) plasma digoxin concentrations. Digoxin levels should be monitored at the start of treatment, during dose adjustments and when telmisartan therapy is discontinued to maintain digoxin levels within therapeutic ranges.
Clinical data have shown that dual blockade of the RAAS using a combination of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher incidence of adverse reactions such as hypotension, hyperkalemia and decreased renal function (up to acute renal failure) compared with the use of a single RAAS-acting agent (see sections "Pharmacological properties", "Contraindications" and "Special instructions for use").
Antidiabetic medicinal products (oral agents and insulin): Dose adjustment of the antidiabetic medicinal product may be required (see section 4.4).
Metformin: Metformin should be used with caution due to the risk of lactic acidosis when used concomitantly with hydrochlorothiazide.
Cholestyramine and colestipol resins. The absorption of hydrochlorothiazide is reduced in the presence of anion exchange resins.
Non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs (acetylsalicylic acid at anti-inflammatory doses, COX-2 inhibitors, non-selective NSAIDs) may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics and the antihypertensive effect of angiotensin II receptor antagonists. In some patients with impaired renal function (in dehydrated patients or elderly patients with impaired renal function), the concomitant use of angiotensin II receptor antagonists and agents that inhibit cyclooxygenase may cause deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be used with caution, especially in elderly patients. After initiation of therapy with the combination of drugs and periodically thereafter, patients should be adequately hydrated and renal function should be closely monitored.
In one study, concomitant administration of telmisartan and ramipril resulted in a 2.5-fold increase in the AUC and Cmax of ramipril and ramiprilat. The clinical significance of this observation remains unknown.
Vasopressor amines (e.g., noradrenaline). The effect of vasopressor amines may be reduced.
Non-depolarizing skeletal muscle relaxants (e.g. tubocurarine). The effects of non-depolarizing skeletal muscle relaxants may be potentiated by hydrochlorothiazide.
Medicines used to treat gout (e.g. probenecid, sulfinpyrazone and allopurinol) Dosage adjustment of uric acid-lowering drugs may be necessary as hydrochlorothiazide may increase serum uric acid levels. The dose of probenecid or sulfinpyrazone may need to be increased. Concomitant use of thiazides may increase the incidence of hypersensitivity reactions to allopurinol.
Calcium salts: Thiazide diuretics may increase serum calcium levels due to decreased excretion. If calcium supplements or calcium-sparing drugs (e.g. vitamin D therapy) are required, serum calcium levels should be monitored and the dose adjusted accordingly.
Beta-blockers and diazoxide: The hyperglycemic effects of beta-blockers and diazoxide may be potentiated by thiazides.
Anticholinergic drugs (e.g. atropine, biperiden) may increase the bioavailability of thiazide diuretics by increasing gastrointestinal motility and the rate of gastric emptying.
Amantadine: Thiazides may increase the risk of side effects caused by amantadine.
Cytotoxic drugs (e.g. cyclophosphamide, methotrexate) Thiazides may reduce the renal excretion of cytotoxic drugs and enhance their myelosuppressive effect.
Based on their pharmacological properties, baclofen and amifostine are expected to potentiate the hypotensive effects of all antihypertensive drugs, including telmisartan. In addition, orthostatic hypotension may be exacerbated by alcohol, barbiturates, narcotics or antidepressants.
Salicylates: When using high doses of salicylates, hydrochlorothiazide may enhance their toxic effects on the central nervous system.
Methyldopa: Isolated cases of hemolytic anemia have been reported with concomitant use of hydrochlorothiazide and methyldopa.
Cyclosporine: Concomitant use of cyclosporine may increase hyperuricemia and increase the risk of complications such as gout.
Effects of medicinal products on laboratory test results: Due to their effect on calcium metabolism, thiazides may interfere with the results of parathyroid function tests (see section 4.4).
Carbamazepine: Clinical and biological monitoring is necessary due to the risk of symptomatic hyponatremia.
Iodinated contrast media: Diuretic-induced dehydration increases the risk of acute renal failure, especially with high doses of iodinated contrast media. Patients should be rehydrated prior to administration of iodinated contrast media.
Amphotericin B (for parenteral administration), corticosteroids, ACTH and stimulant laxatives. Hydrochlorothiazide increases electrolyte imbalance, mainly hypokalemia.
Application features
Pregnancy: Angiotensin II receptor antagonists are contraindicated during pregnancy. Patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.8).
Hepatic impairment. Telmisartan H, Telmisartan HD should not be administered to patients with cholestasis, biliary obstructive disorders or severe hepatic insufficiency (see section "Contraindications"), since telmisartan is excreted mainly with bile. In these patients, a decrease in the clearance of telmisartan in the liver is expected. Telmisartan H, Telmisartan HD should be used with caution in patients with impaired liver function or progressive liver disease, since this drug can cause intrahepatic cholestasis, and even minor changes in water-salt balance can lead to hepatic coma. There is no clinical experience with the use of telmisartan/hydrochlorothiazide in patients with hepatic insufficiency.
Renal hypertension: There is an increased risk of severe hypotension and renal failure when drugs that affect the RAAS are used in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.
Renal impairment and kidney transplantation. Telmisartan/hydrochlorothiazide is contraindicated in patients with severe renal impairment (creatinine clearance <30 ml/min) (see section "Contraindications"). There is no experience with the use of Telmisartan H, Telmisartan HD in patients with severe renal impairment or with a recent kidney transplant. There is limited experience in patients with mild to moderate renal impairment, therefore periodic monitoring of serum potassium, creatinine and uric acid levels is recommended. Azotemia associated with thiazide diuretics may occur in patients with impaired renal function.
Intravascular volume depletion. Symptomatic hypotension, especially after the first dose, may occur in patients who are volume and/or sodium depleted by diuretic therapy, dietary salt restriction, diarrhea, or vomiting. Such conditions should be corrected before administration of Telmisartan H, Telmisartan HD.
Double blockade of RAAS.
There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (up to acute renal failure).
Therefore, dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see sections 5.1 and 5.2).
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 prescribed simultaneously in patients with diabetic nephropathy.
Other conditions requiring stimulation of the RAAS: In patients whose vascular tone and renal function depend primarily on the activity of the RAAS (e.g., patients with congestive heart failure or severe renal disease, including renal artery stenosis), the use of other drugs that affect the RAAS may be associated with acute hypotension, hyperazotemia, oliguria, and rarely, acute renal failure (see section 4.8).
Primary aldosteronism: Patients with primary aldosteronism generally do not respond to antihypertensive drugs that act by blocking the renin-angiotensin system, and the use of this medicinal product in such patients is therefore not recommended.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: As with other vasodilators, special caution is required when treating patients with aortic and mitral valve stenosis or obstructive hypertrophic cardiomyopathy.
Electrolyte imbalance. All patients receiving diuretics should have their serum electrolytes measured periodically. Thiazides, including hydrochlorothiazide, may cause electrolyte imbalance (hypokalemia, hyponatremia, and hypochloremic alkalosis), which may occur in the presence of diarrhea and vomiting. Symptoms of electrolyte imbalance include dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting (see Adverse Reactions).
Hypokalaemia: Although thiazide diuretics may cause hypokalaemia, concomitant treatment with telmisartan may reduce diuretic-induced hypokalaemia. The risk of hypokalaemia is greatest in patients with cirrhosis of the liver, in patients with significant diuresis, in patients receiving inadequate oral electrolytes and in patients receiving concomitant therapy with corticosteroids or ACTH (see section 4.5).
Hyperkalemia. Conversely, hyperkalemia may occur due to antagonism of angiotensin II (AT1) receptors by telmisartan, a component of Telmisartan. However, clinically significant hyperkalemia due to Telmisartan has not been documented, and risk factors for hyperkalemia include renal insufficiency and/or heart failure and diabetes mellitus. Potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes should be administered with caution with Telmisartan (see section 4.5).
Hyponatremia and hypochloraemic alkalosis. There is no evidence that Telmisartan H, Telmisartan HD will reduce or prevent diuretic-induced hyponatremia. Chloride deficiency is generally mild and usually does not require treatment.
Hypercalcemia: Thiazides may reduce urinary calcium excretion and cause a transient and minor increase in serum calcium in the absence of known disorders of calcium metabolism. Significant hypercalcemia may be a sign of latent hyperparathyroidism. Thiazides should be discontinued before parathyroid function tests are performed.
Hypomagnesemia: Thiazides have been shown to increase urinary magnesium excretion, which may lead to hypomagnesemia (see Interactions with other medicinal products and other forms of interaction).
Sorbitol and lactose monohydrate. The medicinal product contains lactose monohydrate and sorbitol, therefore patients with hereditary fructose intolerance and/or hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Race: As with other angiotensin II receptor antagonists, telmisartan is likely to be less effective in lowering blood pressure in black patients, presumably because of the greater prevalence of low-renin states in this hypertensive population.
Others: As with any antihypertensive drug, a significant decrease in blood pressure in patients with ischemic cardiopathy or in patients with myocardial ischemia may lead to myocardial infarction or stroke.
General: Hypersensitivity reactions to hydrochlorothiazide are more likely to occur in patients with a history of allergy or bronchial asthma, but are more likely in patients with a history of such conditions. Exacerbation or activation of systemic lupus erythematosus (SLE) has been reported with the use of thiazide diuretics, including hydrochlorothiazide.
Photosensitivity reactions have been reported with thiazide diuretics (see section 4.8). If photosensitivity reactions occur during treatment, discontinuation of the drug is recommended. If repeated use of diuretics is considered necessary, it is recommended to protect exposed areas from sunlight or artificial ultraviolet radiation.
Choroidal effusion, acute myopia and secondary angle-closure glaucoma. Hydrochlorothiazide, like sulfonamides, may cause hypersensitivity reactions and, as a consequence, choroidal effusion with visual field defect, acute transient myopia and acute angle-closure glaucoma.
Symptoms include sudden onset of decreased visual acuity or eye pain and usually occur within hours to weeks of starting treatment. Untreated acute angle-closure glaucoma may lead to irreversible vision loss. Hydrochlorothiazide should be discontinued as soon as possible. Urgent medical treatment, including surgery, may be required if intraocular pressure remains uncontrolled. Risk factors for acute angle-closure glaucoma may include a history of sulphonamide or penicillin allergy.
In two epidemiological studies based on the Danish National Cancer Registry, an increased risk of NSCLC (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) was observed with increasing cumulative dose of hydrochlorothiazide. The photosensitizing effect of hydrochlorothiazide may be a mechanism for the development of NSCLC.
Patients taking hydrochlorothiazide should be informed of the risk of NMSC and should regularly examine their skin for new lesions and promptly report any suspicious skin lesions. Preventive measures, such as limiting exposure to sunlight and ultraviolet light, are possible. Patients should be advised to take adequate protection from such exposure to minimize the risk of skin cancer. Suspicious skin lesions should be investigated promptly, including histological examination of a biopsy specimen. Hydrochlorothiazide should also be reconsidered in patients with a history of NMSC (see section 4.8).
Acute respiratory toxicity
Very rare cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS), have been reported following the administration of hydrochlorothiazide. Pulmonary oedema usually develops within minutes to hours of administration of hydrochlorothiazide. Initial symptoms include dyspnoea, fever, worsening pulmonary function and hypotension. If ARDS is suspected, telmisartan/hydrochlorothiazide should be discontinued and appropriate treatment should be initiated. Hydrochlorothiazide should not be given to patients who have previously experienced an acute respiratory infection after taking hydrochlorothiazide.
The drug may affect the results of some laboratory tests:
the drug may reduce the level of protein-bound iodine in blood plasma;
Treatment with the drug should be discontinued before laboratory testing to assess parathyroid function;
The drug is capable of increasing the concentration of free bilirubin in the blood serum.
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 the use of this drug, its use should be immediately discontinued and replaced with another drug approved for use in pregnant women.
There are no data on the use of the combination of telmisartan/hydrochlorothiazide in pregnant women.
Epidemiological evidence of the risk of teratogenicity following use of inhibitors during the first trimester of pregnancy is not conclusive, but a small increase in risk cannot be excluded.
Treatment with angiotensin II receptor antagonists during the second and third trimesters of pregnancy is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia). If angiotensin II receptor antagonists are used from the second trimester of pregnancy, ultrasound monitoring of renal function and skull is recommended. Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for hypotension (see sections 4.3 and 4.4). There is limited experience with the use of hydrochlorothiazide during pregnancy, especially during the first trimester.
Hydrochlorothiazide crosses the placental barrier. Given the pharmacological mechanism of action of hydrochlorothiazide, use of the drug during the II and III trimesters may impair fetal-placental perfusion and lead to intrauterine and neonatal effects such as jaundice, fetal electrolyte imbalance, and thrombocytopenia.
Hydrochlorothiazide should not be used in edema, pregnancy-induced hypertension, or late toxicosis due to the risk of decreased plasma volume and placental hypoperfusion without
