Telinstar (Tablets) Instructions for Use

Marketing Authorization Holder

Krka d.d., Novo mesto (Slovenia)

ATC Code

C09DA07 (Telmisartan and diuretics)

Active Substances

Indapamide (Rec.INN registered by WHO)

Telmisartan (Rec.INN registered by WHO)

Dosage Forms

	Telinstar	Modified-release tablets 1.5 mg+40 mg
		Modified-release tablets 1.5 mg+80 mg

Dosage Form, Packaging, and Composition

Modified-release tablets

10 pcs. – blisters (3 pcs.) – cardboard packs (30 pcs.) – Prescription only
10 pcs. – blisters (6 pcs.) – cardboard packs (60 pcs.) – Prescription only
10 pcs. – blisters (9 pcs.) – cardboard packs (90 pcs.) – Prescription only
7 pcs. – blisters (12 pcs.) – cardboard packs (84 pcs.) – Prescription only
7 pcs. – blisters (4 pcs.) – cardboard packs (28 pcs.) – Prescription only
7 pcs. – blisters (8 pcs.) – cardboard packs (56 pcs.) – Prescription only

Modified-release tablets

10 pcs. – blisters (3 pcs.) – cardboard packs (30 pcs.) – Prescription only
10 pcs. – blisters (6 pcs.) – cardboard packs (60 pcs.) – Prescription only
10 pcs. – blisters (9 pcs.) – cardboard packs (90 pcs.) – Prescription only
7 pcs. – blisters (12 pcs.) – cardboard packs (84 pcs.) – Prescription only
7 pcs. – blisters (4 pcs.) – cardboard packs (28 pcs.) – Prescription only
7 pcs. – blisters (8 pcs.) – cardboard packs (56 pcs.) – Prescription only

Clinical-Pharmacological Group

Antihypertensive drug

Pharmacotherapeutic Group

Agents acting on the renin-angiotensin system; angiotensin II receptor antagonists (ARBs) in combination with diuretics

Pharmacological Action

A combined antihypertensive drug containing the angiotensin II receptor antagonist Telmisartan and the thiazide-like diuretic indapamide. The simultaneous use of these components results in 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 angiotensin II AT₁ receptor subtype, through which the action of angiotensin II is mediated. Telmisartan displaces angiotensin II from binding to the receptor, having no agonist action on this receptor. Telmisartan binds only to the angiotensin II AT₁ receptor subtype. The binding is long-lasting. Telmisartan has no affinity for other angiotensin receptors (including AT₂ receptors). The functional significance of these receptors, as well as the effect of their possible excessive stimulation by 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 plasma renin and does not block ion channels. Telmisartan does not inhibit ACE (kininase II), an enzyme that also breaks down bradykinin, so an increase in bradykinin-mediated side effects is not expected.

In patients with arterial hypertension, Telmisartan at a dose of 80 mg completely blocks the hypertensive effect of angiotensin II. The onset of the antihypertensive effect is noted within 3 hours after the first oral intake of telmisartan. The effect persists for 24 hours and remains significant for 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 case of abrupt withdrawal of telmisartan, blood pressure gradually returns to baseline without the development of withdrawal syndrome.

Indapamide is a sulfonamide derivative. In its pharmacological properties, it is close to thiazide diuretics. Indapamide inhibits the reabsorption of sodium ions in the cortical segment of the loop of Henle, which leads to an increase in the renal excretion of sodium and chloride ions, and to a lesser extent potassium and magnesium ions, thereby enhancing diuresis and reducing blood pressure.

Pharmacokinetics

The simultaneous use of indapamide and telmisartan does not affect the pharmacokinetics of each of the drug components.

Telmisartan

When taken orally, it is rapidly absorbed from the gastrointestinal tract. Bioavailability is approximately 50%. C_max of telmisartan is reached within 0.5-1.5 hours after application. When taken with food, the decrease in AUC ranges from 6% (when used at a dose of 40 mg) to 19% (when used at a dose of 160 mg). Three hours after oral administration, the plasma concentration levels out, regardless of food intake. Plasma protein binding is significant (more than 99.5%), mainly with albumin and α₁-glycoprotein. V_d is approximately 500 L. Telmisartan is metabolized by conjugation with glucuronic acid. Metabolites are pharmacologically inactive. T_1/2 is more than 20 hours. It is excreted through the intestine unchanged, renal excretion is less than 2%. Total plasma clearance is high (about 900 ml/min).

Pharmacokinetic studies in patients with hepatic insufficiency showed an increase in absolute bioavailability to almost 100%. In hepatic insufficiency, T_1/2 does not change.

Indapamide

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract, C_max in plasma is reached after 1-2 hours. Plasma protein binding is 79%. It is widely distributed in the body. Does not accumulate.

T_1/2 is 18 hours. It is excreted by the kidneys mainly in the form of metabolites, 5% unchanged.

Indications

Arterial hypertension (for patients who are indicated for combined therapy with telmisartan and indapamide).

ICD codes

Dosage Regimen

Take orally once daily in the morning, with or without food. Swallow the tablet whole with a sufficient amount of liquid; do not chew or crush.

Initiate therapy with the 1.5 mg + 40 mg strength for most patients. The dose may be increased to the 1.5 mg + 80 mg strength if additional blood pressure control is required.

Prescribe this combination only to patients whose blood pressure is adequately controlled with the individual components, telmisartan and indapamide, taken concurrently. The selected dose must correspond to the doses previously established during separate administration.

For patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), do not exceed the 1.5 mg + 40 mg dose. The drug is contraindicated in severe hepatic impairment (Child-Pugh class C).

In patients with mild to moderate renal impairment (CrCl ≥30 ml/min), no initial dose adjustment is necessary. The drug is contraindicated in severe renal impairment (CrCl <30 ml/min).

For elderly patients, no dose adjustment is required, but assess renal function before and during treatment. Monitor plasma creatinine levels, calculated with consideration for age, weight, and sex.

Regularly monitor blood pressure, serum electrolytes (potassium, sodium), creatinine, and uric acid levels, particularly within the first few weeks of treatment and after dose adjustments.

If blood pressure is not sufficiently controlled with this combination, consider adding another antihypertensive agent from a different class.

Adverse Reactions

Respiratory system disorders respiratory distress syndrome (including pneumonia and pulmonary edema), dyspnea.

Cardiovascular system disorders arrhythmia, tachycardia, bradycardia, marked decrease in blood pressure (including orthostatic hypotension).

Nervous system disorders: syncope/fainting, paresthesia, sleep disorders, insomnia, dizziness, anxiety, depression, increased excitability, headache.

Digestive system disorders: diarrhea, dryness of the oral mucosa, flatulence, abdominal pain, constipation, vomiting, gastritis, decreased appetite, anorexia, hyperglycemia, hypercholesterolemia, pancreatitis, impaired liver function, jaundice (hepatocellular or cholestatic), dyspepsia.

Skin disorders increased sweating.

Musculoskeletal system disorders back pain, muscle spasms, myalgia, arthralgia, calf muscle cramps, arthrosis, tendinitis-like symptoms, chest pain.

Hematopoietic system disorders iron deficiency anemia, aplastic anemia, hemolytic anemia, thrombocytopenia, eosinophilia, leukopenia, neutropenia/agranulocytosis, thrombocytopenia.

Urinary system disorders renal failure, including acute renal failure, interstitial nephritis, glucosuria.

Sense organ disorders visual impairment, transient blurred vision, xanthopsia, acute angle-closure glaucoma, acute myopia.

Reproductive system disorders impotence.

Infections sepsis, including fatal cases, upper respiratory tract infections (bronchitis, pharyngitis, sinusitis), urinary tract infections (including cystitis), inflammation of the salivary glands.

Metabolism and nutrition disorders: increased plasma creatinine concentration, increased liver enzyme activity, increased CPK activity, increased blood uric acid concentration, hypertriglyceridemia, hypokalemia, hyperkalemia, hyponatremia, hyperuricemia, decreased blood volume, hypoglycemia (in patients with diabetes mellitus), impaired glucose tolerance, decreased blood hemoglobin level.

Allergic reactions angioedema (including fatal cases), erythema, skin itching, rash, anaphylactic reactions, eczema, drug rash, toxic epidermal necrolysis, lupus-like reactions, exacerbation or intensification of systemic lupus erythematosus symptoms, necrotizing vasculitis, systemic vasculitis, photosensitivity reaction, recurrence of systemic lupus erythematosus, vasculitis.

Other flu-like syndrome, fever, weakness.

Contraindications

Hypersensitivity to telmisartan, indapamide, other sulfonamide derivatives and/or to any of the excipients included in the used drug; pregnancy and breastfeeding; severe hepatic impairment (Child-Pugh class C) and hepatic encephalopathy; severe renal impairment; hypokalemia; obstructive biliary tract diseases; simultaneous use of telmisartan 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; simultaneous use with ACE inhibitors in patients with diabetic nephropathy.

With caution: bilateral renal artery stenosis or stenosis of the artery of a single kidney; impaired liver function or progressive liver disease (Child-Pugh class A and B); decreased blood volume due to previous diuretic therapy, salt restriction, diarrhea or vomiting; hyperkalemia; condition after kidney transplantation (no experience of use); chronic heart failure NYHA class III-IV; stenosis of the aortic and mitral valve; idiopathic hypertrophic subaortic stenosis; hypertrophic obstructive cardiomyopathy; diabetes mellitus; primary aldosteronism; gout; angle-closure glaucoma (due to the presence of indapamide in the composition).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated for use in patients with severe hepatic impairment (Child-Pugh class C). In patients with mild to moderate hepatic impairment (Child-Pugh classes A and B), the dose of the combination components should not exceed 1.5 mg + 40 mg once a day.

Use in Renal Impairment

Contraindicated for use in patients with severe renal impairment (CC < 30 ml/min) in patients on hemodialysis.

For patients with mild to moderate renal impairment, dose adjustment is not required. However, thiazide and thiazide-like diuretics are fully effective only in patients with normal renal function or with minimal impairment.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

In elderly patients, dose adjustment is not required, but plasma creatinine concentration is calculated taking into account age, weight and sex.

The drug can be used in elderly patients with normal renal function or with minimal impairment.

Special Precautions

In some patients, due to the suppression of the RAAS activity, especially with the simultaneous use of drugs acting on this system, renal function is impaired (including acute renal failure). Therefore, therapy accompanied by such dual blockade of the RAAS (for example, when adding an ACE inhibitor or a direct renin inhibitor – aliskiren to angiotensin II receptor antagonists) should be carried out strictly individually and with regular monitoring of renal function (including periodic monitoring of serum potassium and creatinine levels).

When prescribing thiazide and thiazide-like diuretics to patients with impaired liver function, especially in case of water-electrolyte imbalance, hepatic encephalopathy may develop, which can progress to hepatic coma. In this case, the use of diuretics should be stopped immediately.

Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine concentration in adults is below 25 mg/l or 220 µmol/l). In elderly patients, plasma creatinine levels are calculated taking into account age, weight and sex.

It should be taken into account that at the beginning of treatment, patients may experience a decrease in GFR due to hypovolemia, which, in turn, is caused by the loss of water and sodium ions while taking diuretic drugs. As a result, the concentration of urea and creatinine in the blood plasma may increase. Such transient functional renal failure is of no clinical significance in patients with normal renal function, but may worsen pre-existing renal failure before the start of treatment.

Cases of photosensitivity reactions have been reported while taking thiazide and thiazide-like diuretics. If photosensitivity reactions occur while taking this drug, it is recommended to discontinue treatment. If re-administration of this drug is considered necessary, it is recommended to protect exposed areas of the body exposed to sunlight or artificial UV radiation.

Before starting treatment with this drug, it is necessary to determine the sodium content in the blood plasma. During administration, this indicator should be regularly monitored. Constant monitoring of sodium content is necessary, because the initial decrease in plasma sodium content may be asymptomatic; more frequent monitoring is indicated for patients with liver cirrhosis and elderly persons. Any diuretic drug can cause hyponatremia, sometimes leading to extremely serious consequences. Hyponatremia combined with hypovolemia can cause dehydration and orthostatic hypotension. Concomitant decrease in plasma chloride levels can lead to secondary compensatory metabolic alkalosis: the frequency of development and severity of this effect are insignificant.

During therapy with thiazide and thiazide-like diuretics, the main risk is a decrease in plasma potassium levels and the development of hypokalemia. Hypokalemia can cause muscle disorders. Cases of rhabdomyolysis have been reported, mainly against the background of severe hypokalemia. It is necessary to prevent the development of hypokalemia (≤ 3.4 mmol/l) in patients at increased risk: elderly patients, debilitated and/or receiving combined drug therapy, patients with liver cirrhosis, peripheral edema and ascites, patients with coronary artery disease and heart failure. Hypokalemia in such patients enhances the cardiotoxicity of cardiac glycosides and increases the risk of arrhythmias.

Patients with a prolonged QT interval on the ECG, both congenital and drug-induced, are at risk. Hypokalemia, like bradycardia, is a condition that contributes to the development of severe arrhythmias, in particular polymorphic ventricular tachycardia of the “torsades de pointes” type, which can be fatal.

In all the cases described above, it is necessary to monitor the plasma potassium content more often than usual. The first determination of plasma potassium ions should be performed in the first week from the start of treatment. If hypokalemia occurs, appropriate treatment should be prescribed. Hypokalemia associated with hypomagnesemia may be resistant to treatment unless serum magnesium levels are corrected.

It has been shown that thiazides and thiazide-like diuretics, including indapamide, increase the renal excretion of magnesium, which can lead to hypomagnesemia.

Thiazide and thiazide-like diuretics can reduce the renal excretion of calcium and lead to a slight and temporary increase in plasma calcium levels. True hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism.

Diuretic drugs should be discontinued before testing parathyroid function.

During treatment, it is important to monitor blood glucose concentration.

In patients with hyperuricemia, the risk of gout attacks may increase.

Athletes should note that indapamide, which is part of this combination, may give a positive result during doping control.

Sulfonamides and their derivatives can cause an idiosyncratic reaction leading to the development of choroidal effusion with visual field defect, transient myopia and acute secondary angle-closure glaucoma. If symptoms appear, it is necessary to stop taking the thiazide/thiazide-like diuretic as soon as possible. If intraocular pressure remains uncontrolled, emergency drug treatment or surgery may be required. A risk factor for the development of acute angle-closure glaucoma is: a history of an allergic reaction to sulfonamides or penicillin.

In patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney, when using drugs that affect the RAAS, the risk of developing severe arterial hypotension and renal failure increases.

In patients with impaired liver function or progressive liver disease, this combination should be used with caution, since even minor changes in water and electrolyte balance can contribute to the development of hepatic coma.

In patients with coronary artery disease, the use of any antihypertensive agent, in case of excessive blood pressure reduction, can lead to myocardial infarction or stroke.

Effect on the ability to drive vehicles and mechanisms

During treatment, the possibility of developing dizziness and drowsiness should be taken into account, which requires caution.

Drug Interactions

Telmisartan

Other antihypertensive agents – enhancement of the hypotensive effect is possible.

Lithium preparations – a reversible increase in lithium concentration in the blood, accompanied by toxic phenomena, has rarely been observed. With the simultaneous use of lithium preparations and angiotensin II receptor antagonists, it is recommended to determine the lithium content in the blood;

NSAIDs, including acetylsalicylic acid in doses used as an anti-inflammatory agent, COX-2 inhibitors and non-selective NSAIDs – possible development of acute renal failure in patients with reduced blood volume. Drugs affecting the RAAS may have a synergistic effect. In patients receiving NSAIDs and Telmisartan, blood volume should be compensated and renal function should be investigated at the beginning of treatment. A reduction in the effect of antihypertensive agents, such as Telmisartan, through inhibition of the vasodilating effect of prostaglandins has been observed with concomitant treatment with NSAIDs. No clinically significant effect was detected with the simultaneous use of telmisartan with ibuprofen or paracetamol.

Digoxin – an increase in the average plasma concentration of digoxin by an average of 20% (in one case by 39%) was noted. When telmisartan and digoxin are co-administered, it is advisable to periodically determine the blood concentration of digoxin.

Indapamide

With the simultaneous use of indapamide with calcium preparations, the development of hypercalcemia is possible due to a decrease in the excretion of calcium ions in the urine.

With the simultaneous use of indapamide with cardiac glycosides, corticosteroids, the risk of developing hypokalemia increases.

With the simultaneous use of indapamide and agents that can cause hypokalemia (amphotericin B, gluco- and mineralocorticoids, tetracosactide, laxatives that stimulate intestinal peristalsis), the risk of developing hypokalemia increases.

With the simultaneous use of indapamide with tricyclic antidepressants (including imipramine), the hypotensive effect is enhanced and the risk of developing orthostatic hypotension increases (additive effect).

With the simultaneous use of indapamide with astemizole, bepridil, erythromycin (IV), pentamidine, sultopride, terfenadine, vincamine, quinidine, disopyramide, amiodarone, bretylium tosilate, sotalol, there is a risk of developing torsades de pointes arrhythmia.

With simultaneous use with baclofen, the hypotensive effect is enhanced.

With the simultaneous use of indapamide with halofantrine, the likelihood of cardiac arrhythmias (including ventricular torsades de pointes arrhythmia) increases.

With the simultaneous use of indapamide with lithium carbonate, the risk of developing the toxic effect of lithium increases against the background of a decrease in its renal clearance.

With the simultaneous use of indapamide with metformin, the appearance of lactic acidosis is possible, which is apparently associated with the development of functional renal failure caused by the action of diuretics (mainly “loop” diuretics).

With the simultaneous use of indapamide with cyclosporine, an increase in plasma creatinine content is possible, which is observed even with normal water and sodium ion content.

Dehydration while taking diuretics increases the risk of developing acute renal failure, especially when using iodine-containing X-ray contrast agents in high doses. Fluid loss must be compensated before administration.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.