Hipotel

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT HYPOTEL (HYPOTEL®)

Composition:

Active substance: telmisartan;

One tablet contains 40 mg or 80 mg of telmisartan;

Excipients: sodium hydroxide, meglumine, mannitol (E 421), crospovidone, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white, round, biconvex tablets.

Pharmacotherapeutic group. Angiotensin II receptor blockers (single preparations).

ATC code: C09CA07.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action. Telmisartan is a specific and effective oral angiotensin II receptor (type AT1) blocker.

Telmisartan, with very high affinity, displaces angiotensin II from its binding sites on the AT1 receptor subtype responsible for the activity of angiotensin II.

Telmisartan does not exhibit any partial agonistic effect on the AT1 receptor. Telmisartan selectively binds to the AT1 receptor. The binding is long-lasting. Telmisartan has no affinity for other receptors, including AT2 and other less-characterized AT receptors. The functional role of these receptors is not known, nor is the effect of their possible stimulation by angiotensin II, whose levels increase with telmisartan. Telmisartan reduces plasma aldosterone levels. Telmisartan does not reduce plasma renin levels and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kininase II), an enzyme that also degrades bradykinin. Therefore, potentiation of bradykinin-mediated adverse effects is not expected.

In humans, telmisartan at a dose of 80 mg almost completely inhibits the increase in blood pressure induced by angiotensin II. The blocking effect persists for 24 hours and remains detectable up to 48 hours.

Pharmacokinetics.

Absorption. Telmisartan is rapidly absorbed, but the amount absorbed is variable. The mean absolute bioavailability of telmisartan is approximately 50%. When telmisartan is administered with food, the area under the concentration-time curve (AUC0–∞) for telmisartan decreases by approximately 6% (40 mg) to 19% (160 mg). Three hours after administration, plasma concentrations are the same as when telmisartan is taken without food.

Linearity/non-linearity. The slight decrease in AUC is not considered to reduce therapeutic efficacy. There is no linear relationship between dose and plasma concentration. Cmax and, to a lesser extent, AUC increase disproportionately at doses above 40 mg.

Distribution. Telmisartan is highly bound to plasma proteins (> 99.5%), primarily to albumin and alpha-1 acid glycoprotein. The mean volume of distribution (Vss) at steady state is approximately 500 L.

Metabolism. Telmisartan is metabolized via conjugation to the glucuronide of the parent compound. The pharmacological activity of the conjugate has not been established.

Elimination. Telmisartan exhibits a biexponential pharmacokinetic profile with a terminal elimination half-life > 20 hours. Maximum plasma concentration (Cmax) and, to a lesser extent, the area under the plasma concentration-time curve (AUC) increase disproportionately with dose. There are no data indicating clinically relevant accumulation of telmisartan with repeated administration at recommended doses. Plasma concentrations were higher in women than in men, without a corresponding effect on efficacy.

After oral (and intravenous) administration, telmisartan is almost completely excreted in feces, primarily as unchanged compound. Cumulative renal excretion accounts for < 1% of the dose. Total plasma clearance (Cltot) is high (approximately 1000 mL/min) compared to hepatic blood flow (about 1500 mL/min).

Special patient populations.

Children. Pharmacokinetics of two doses of telmisartan were evaluated as a secondary objective in hypertensive patients (n = 57) aged 6 to < 18 years after administration of telmisartan at doses of 1 mg/kg or 2 mg/kg for 4 weeks of treatment. Pharmacokinetic objectives included determination of telmisartan levels at steady state in children and adolescents and investigation of age-related differences. Although the study was too small to provide reliable assessment of pharmacokinetics in children under 12 years of age, the results overall are consistent with data in adults and confirm the non-linearity of telmisartan, particularly for Cmax.

Gender. Plasma Cmax and AUC concentrations in women are approximately 3 and 2 times higher, respectively, than in men.

Elderly patients. The pharmacokinetics of telmisartan do not differ between elderly patients and patients under 65 years of age.

Patients with renal impairment. In patients with mild, moderate, and severe renal impairment, plasma concentrations increased by approximately 2-fold. However, in dialysis-dependent patients, lower plasma concentrations were observed. Telmisartan has high plasma protein binding in patients with renal impairment and is not dialyzable. The elimination half-life is not altered in patients with renal impairment.

Patients with hepatic impairment. Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute bioavailability to approximately 100%. The elimination half-life is not changed in patients with hepatic impairment.

Clinical characteristics.

Indications.

Hypertension.

For the treatment of essential hypertension in adults.

Prevention of cardiovascular diseases.

For reducing cardiovascular morbidity in adult patients with:

• Established atherothrombotic cardiovascular disease (history of ischemic heart disease, stroke, or peripheral artery disease);
• Type 2 diabetes mellitus with documented target organ damage.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product (see section "Composition");

• Pregnancy or planned pregnancy (see sections "Special precautions", "Use during pregnancy or breastfeeding");
• Obstructive biliary disorders;
• Severe hepatic impairment;
• Pediatric use (under 18 years of age).

Concomitant use of telmisartan and aliskiren-containing medicinal products is contraindicated in patients with diabetes mellitus or renal impairment (eGFR < 60 mL/min/1.73 m²) (see sections "Pharmacological properties" and "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Digoxin.

When telmisartan and digoxin were administered concomitantly, median increases in digoxin plasma peak concentrations (by 49%) and trough concentrations (by 20%) were observed. Monitoring of digoxin levels should be performed at the initiation of treatment, during dose adjustment, and upon discontinuation of telmisartan to maintain levels within the therapeutic range.

Like other agents that inhibit the renin-angiotensin-aldosterone system (RAAS), telmisartan may provoke hyperkalemia (see section "Special precautions"). The risk may be increased when used concomitantly with other agents that may also cause hyperkalemia (potassium-containing salt substitutes, potassium-sparing diuretics, angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor blockers, nonsteroidal anti-inflammatory drugs [NSAIDs, including selective COX-2 inhibitors], heparin, immunosuppressants [cyclosporine or tacrolimus], and trimethoprim).

Cases of hyperkalemia depend on associated risk factors. The risk increases with the above-mentioned therapeutic combinations. The risk is particularly high when combined with potassium-sparing diuretics or potassium-containing salt substitutes. Combination with ACE inhibitors or NSAIDs is considered less risky provided that application recommendations are strictly followed.

Concomitant use not recommended.

Potassium-sparing diuretics or potassium supplements. Angiotensin II receptor blockers, such as telmisartan, reduce potassium loss induced by diuretics. Potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene, or amiloride), potassium-containing dietary supplements, or potassium-containing salt substitutes may lead to a significant increase in serum potassium concentration. If concomitant use is indicated due to documented hypokalemia, these agents should be used with caution and serum potassium levels should be monitored frequently.

Lithium. Concomitant use of lithium with ACE inhibitors and angiotensin II receptor blockers, including telmisartan, has been associated with reversible increases in serum lithium concentrations and lithium toxicity. If use of this combination is necessary, careful monitoring of serum lithium levels is recommended.

Concomitant use requiring caution.

Nonsteroidal anti-inflammatory drugs (NSAIDs). 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 blockers.

In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of angiotensin II receptor blockers and agents that inhibit cyclooxygenase may lead to further deterioration of renal function, including potentially acute renal failure, which is usually reversible.

Therefore, this combination should be used with caution, particularly in elderly patients. Patients should receive adequate hydration; consideration should be given to monitoring renal function after initiation of concomitant therapy and periodically thereafter.

In one study, concomitant administration of telmisartan and ramipril resulted in a 2.5-fold increase in AUC_0–24 and C_max of ramipril and ramiprilat. The clinical significance of this finding is unknown.

Diuretics (thiazide or loop diuretics). Prior treatment with high doses of diuretics such as furosemide (a loop diuretic) or hydrochlorothiazide (a thiazide diuretic) may lead to dehydration and the development of hypotension at the start of telmisartan therapy.

Concomitant use requiring attention.

Other antihypertensive agents. The ability of telmisartan to lower blood pressure may be enhanced when used concomitantly with other antihypertensive agents.

Clinical data have shown that dual blockade of the renin-angiotensin-aldosterone system (RAAS) by combining ACE inhibitors, angiotensin II receptor blockers, or aliskiren is associated with a higher incidence of adverse effects such as hypotension, hyperkalemia, and decreased renal function (including acute renal failure), compared to treatment with a single agent acting on the RAAS (see sections "Pharmacodynamics", "Contraindications", and "Special precautions").

Due to the pharmacological properties of baclofen and amifostine, an enhanced hypotensive effect of all antihypertensive agents, including telmisartan, may be expected. Additionally, orthostatic hypotension may be exacerbated by alcohol consumption, barbiturates, narcotics, and antidepressants.

Corticosteroids (systemic use). Reduction of antihypertensive effect.

Special precautions for use.

Pregnancy. Angiotensin II receptor blockers must not be initiated during pregnancy. If continuation of angiotensin II receptor blocker therapy is not considered essential in a woman planning pregnancy, she should switch to an alternative antihypertensive treatment with an established safety profile during pregnancy. Angiotensin II receptor blockers must be discontinued immediately upon confirmation of pregnancy, and alternative therapy should be initiated if necessary (see sections "Contraindications" and "Use during pregnancy or breastfeeding").

Hepatic impairment. Xipotel must not be prescribed to patients with cholestasis, obstructive biliary disorders, or severe hepatic impairment (see section "Contraindications"), as telmisartan is primarily excreted via bile. Hepatic clearance of telmisartan is reduced in patients with these conditions.

Telmisartan should be used with caution in patients with mild to moderate hepatic impairment.

Renovascular hypertension. There is an increased risk of severe arterial hypotension and renal failure in patients with bilateral renal artery stenosis or stenosis of the renal artery of a solitary functioning kidney when treated with drugs affecting the renin-angiotensin-aldosterone system.

Renal impairment and kidney transplantation. Periodic monitoring of serum potassium and creatinine levels is recommended in patients with impaired renal function receiving telmisartan. There is no experience with the use of telmisartan in patients who have recently undergone kidney transplantation.

Telmisartan is not removed from blood by hemofiltration and is not dialyzable.

Patients with reduced intravascular volume and/or reduced sodium levels. Symptomatic hypotension, particularly after the first dose of telmisartan, may occur in patients with reduced intravascular volume and/or reduced sodium levels, for example due to intensive diuretic therapy, a salt-restricted diet, or diarrhoea. Such conditions should be corrected prior to initiating Xipotel therapy. Prior to starting telmisartan treatment, sodium levels and/or intravascular fluid volume should be normalized.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS). Evidence indicates that concomitant use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of hypotension, hyperkalaemia, and reduced renal function (up to acute renal failure).

Therefore, dual blockade of the RAAS by combining ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

If dual blockade is considered absolutely necessary, it should be performed only under specialist supervision and with continuous, careful monitoring of renal function, electrolyte levels, and blood pressure.

ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Other conditions requiring renin-angiotensin-aldosterone system activity. In patients in whom vascular tone and renal function primarily depend on renin-angiotensin-aldosterone system activity (such as patients with severe congestive heart failure or significant renal disease, including renal artery stenosis), treatment with drugs affecting this system, such as telmisartan, may lead to acute hypotension, hyperazotaemia, oliguria, and rarely, acute renal failure (see section "Adverse reactions").

Primary hyperaldosteronism. Patients with primary hyperaldosteronism generally do not respond to antihypertensive drugs acting via blockade of the renin-angiotensin system. Therefore, telmisartan is not recommended for these patients.

Stenosis of aortic and mitral valves, obstructive hypertrophic cardiomyopathy. Like other vasodilators, the medicinal product should be used with caution in patients diagnosed with aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy.

Diabetic patients treated with insulin or antidiabetic medicinal products. Hypoglycaemia may occur in diabetic patients treated with insulin or antidiabetic medicinal products during telmisartan therapy. Blood glucose levels should be monitored in such patients, and dosage adjustments of insulin or antidiabetic medicinal products may be necessary.

Hyperkalaemia. Medicinal products affecting the renin-angiotensin-aldosterone system may cause hyperkalaemia.

In elderly patients, patients with renal impairment, diabetic patients, patients receiving other medicinal products that may increase potassium levels, and/or patients with concomitant diseases, hyperkalaemia may lead to fatal outcomes.

The benefit-risk ratio should be carefully considered before combining medicinal products that inhibit the renin-angiotensin system.

Key risk factors for hyperkalaemia to consider:

• Diabetes mellitus, renal impairment, age over 70 years.
• Combination therapy with one or more other agents affecting the renin-angiotensin-aldosterone system and/or potassium-containing dietary supplements. Medicinal products or therapeutic groups that may provoke hyperkalaemia include potassium-containing salt substitutes, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor blockers, non-steroidal anti-inflammatory drugs (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressants (cyclosporine or tacrolimus), and trimethoprim.
• Intercurrent conditions such as dehydration, acute heart decompensation, metabolic acidosis, worsening of renal function, sudden deterioration of kidney function (e.g., due to infections), and cellular lysis (e.g., acute limb ischaemia, acute skeletal muscle necrosis, extensive trauma).

Patients at risk require close monitoring of serum potassium concentration (see section "Interaction with other medicinal products and other forms of interaction").

Ethnic differences. Observations have shown that telmisartan and other angiotensin II receptor blockers are clearly less effective in lowering blood pressure in black patients compared to other racial groups, similar to angiotensin-converting enzyme inhibitors. This may be explained by the higher prevalence of low-renin states in black patients with arterial hypertension.

Ischaemic heart disease. As with other antihypertensive agents, excessive reduction in blood pressure in patients with ischaemic heart disease or ischaemic cardiomyopathy may lead to myocardial infarction or stroke.

Angioedema of the intestine. Cases of intestinal angioedema have been reported in patients receiving angiotensin II receptor blockers (see section "Adverse reactions"). These patients experienced abdominal pain, nausea, vomiting, and diarrhoea. Symptoms resolved after discontinuation of angiotensin II receptor blockers. If intestinal angioedema is diagnosed, telmisartan should be discontinued and appropriate monitoring initiated until complete symptom resolution.

Content. This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially sodium-free.

Use during pregnancy or breastfeeding.

Pregnancy.

There are no adequate data on the use of telmisartan in pregnant women.

Animal studies have shown toxic effects of telmisartan on reproductive function.

Epidemiological evidence of teratogenic risk associated with the use of angiotensin-converting enzyme (ACE) inhibitors during the first trimester of pregnancy has been inconclusive, but a small increased risk cannot be ruled out. Although there are no controlled epidemiological data on the teratogenic risk of angiotensin II receptor blockers, similar risks may exist with this class of medicinal products. If continued treatment with angiotensin II receptor blockers is necessary, the drug should be replaced in advance with another antihypertensive agent with an established safety profile for use during pregnancy when planning pregnancy. Upon confirmation of pregnancy, treatment with angiotensin II receptor blockers must be stopped immediately and, if necessary, alternative therapy should be initiated.

It is known that the use of angiotensin II receptor blockers during the second and third trimesters of pregnancy causes fetal toxicity in humans (renal dysfunction, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, hypotension, hyperkalemia).

If angiotensin II receptor blockers are started from the second trimester of pregnancy, ultrasound evaluation of fetal renal function and skull ossification is recommended.

Infants born to mothers who have taken angiotensin II receptor blockers should be closely monitored for signs of arterial hypotension (see sections "Contraindications" and "Special precautions").

Breast-feeding period.

Due to the lack of information on the use of telmisartan during breast-feeding, this medicinal product is not recommended for administration to women who are breast-feeding. Alternative therapy with a better-established safety profile is preferred, especially when breast-feeding a newborn or preterm infant.

Fertility.

Preclinical studies have not shown any effect of telmisartan on male or female fertility.

Ability to influence reaction speed when driving or operating machinery.

When driving or operating machinery, one should consider the possible occurrence of syncope or vertigo during antihypertensive therapy, including treatment with the drug Hypotel.

Method of Administration and Dosage.

Arterial Hypertension Treatment

The usual effective dose of telmisartan is 40 mg once daily. Some patients may achieve adequate blood pressure control with a daily dose of 20 mg telmisartan (use other dosage forms with appropriate strength). If blood pressure is not adequately controlled, the dose of telmisartan may be increased to 80 mg once daily. When considering dose escalation, it should be noted that the maximum antihypertensive effect is achieved within 4–8 weeks after initiation of therapy (see section "Pharmacological Properties. Pharmacodynamics").

Alternatively, telmisartan may be prescribed in combination with thiazide diuretics, such as hydrochlorothiazide, which provide additional blood pressure-lowering effects when used concomitantly with telmisartan.

Cardiovascular Disease Prevention

The recommended dose is 80 mg once daily. The efficacy of telmisartan at doses lower than 80 mg for cardiovascular disease prevention is unknown.

When initiating telmisartan therapy to reduce cardiovascular morbidity, careful monitoring of blood pressure is recommended, with dose adjustments of antihypertensive medications as needed.

Elderly Patients. Dose adjustment is not required for elderly patients.

Renal Impairment. Experience with telmisartan in patients with renal insufficiency or those undergoing hemodialysis is limited. Such patients should be started on the lowest initial dose of telmisartan, 20 mg (use other dosage forms with appropriate strength; see section "Special Warnings and Precautions for Use"). Dose adjustment is not required in patients with mild to moderate renal impairment.

Telmisartan is not removed from blood by hemofiltration and is not dialyzable.

Hepatic Impairment. Hypotel is contraindicated in patients with severe hepatic impairment (see section "Contraindications").

For patients with mild or moderate hepatic impairment, the daily dose of telmisartan should not exceed 40 mg once daily (see section "Special Warnings and Precautions for Use").

Method of Administration

Telmisartan tablets should be taken orally once daily, independent of food intake. Tablets should be swallowed whole with sufficient liquid.

Storage and Handling Precautions

Telmisartan should be stored in sealed blisters to protect from moisture. Tablets should be removed from the blister immediately before administration.

Pediatric Population

The safety and efficacy of Hypotel in children (under 18 years of age) have not been established.

Current available data are presented in the subsections "Pharmacokinetics" and "Pharmacodynamics", but no dosage recommendations can be provided.

Overdose

Information on telmisartan overdose in humans is limited.

Symptoms. The most prominent symptoms of telmisartan overdose were hypotension and tachycardia; bradycardia, dizziness, increased serum creatinine concentration, and acute renal failure have also been reported.

Treatment. Telmisartan is not removed from the body by hemofiltration and is not dialyzable. Patients should be closely monitored and receive symptomatic and supportive treatment. Management depends on the time since overdose and severity of symptoms. Induction of emesis and/or gastric lavage may be considered. Activated charcoal may be administered. Serum electrolytes and creatinine levels should be monitored frequently. In case of arterial hypotension, the patient should be placed in the supine position and treated with rapid volume and salt repletion.

Adverse Reactions

Serious adverse reactions, including anaphylactic reaction and angioedema, are possible in isolated cases (frequency ≥ 1/10,000 to <1/1,000); acute renal failure has also been observed.

The overall frequency of adverse reactions in patients with arterial hypertension during controlled clinical trials in the telmisartan treatment group was generally comparable to that in the placebo group (41.4% vs. 43.9%). The frequency of adverse reactions did not depend on dose, patient sex, age, or race. The safety profile of telmisartan in patients who received the drug for cardiovascular disease prevention was consistent with the safety profile observed in patients treated for arterial hypertension.

The adverse reactions listed below are based on results from controlled clinical studies in hypertensive patients and post-marketing reports. This list also includes serious adverse reactions and those leading to discontinuation of the drug during three long-term clinical trials involving 21,642 patients who received telmisartan for cardiovascular disease prevention over a period of up to six years.

Adverse reactions are listed according to frequency: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000).

Within each category, adverse reactions are listed in order of decreasing severity.

Infections and infestations:

uncommon — urinary tract infections, cystitis; upper respiratory tract infections, including pharyngitis and sinusitis;

rare — sepsis, including fatal cases1.

Blood and lymphatic system disorders:

uncommon — anemia;

rare — eosinophilia, thrombocytopenia.

Immune system disorders:

rare — anaphylactic reaction, hypersensitivity.

Metabolism and nutrition disorders:

uncommon — hyperkalemia;

rare — hypoglycemia (in patients with diabetes mellitus), hyponatremia.

Psychiatric disorders:

uncommon — insomnia, depression;

rare — anxiety.

Nervous system disorders:

uncommon — syncope;

rare — somnolence.

Eye disorders:

rare — vision impairment.

Ear and labyrinth disorders:

uncommon — vertigo.

Cardiac disorders:

uncommon — bradycardia;

rare — tachycardia.

Vascular disorders:

uncommon — arterial hypotension2, orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders:

uncommon — dyspnea, cough;

very rare — interstitial lung disease4.

Gastrointestinal disorders:

uncommon — abdominal pain, diarrhea, dyspepsia, flatulence, vomiting;

rare — dry mouth, abdominal discomfort, dysgeusia.

Hepatobiliary disorders:

rare — liver function abnormalities/liver disorders3.

Skin and subcutaneous tissue disorders:

uncommon — pruritus, increased sweating, rash;

rare — angioedema (including fatal cases), eczema, erythema, urticaria, drug dermatitis, toxic dermatitis.

Musculoskeletal and connective tissue disorders:

uncommon — back pain (e.g., sciatica), muscle cramps, myalgia;

rare — arthralgia, limb pain, tendon pain (symptoms similar to tendinitis).

Renal and urinary disorders:

uncommon — renal function impairment (including acute kidney injury).

General disorders:

uncommon — chest pain, asthenia (weakness);

rare — influenza-like symptoms.

Laboratory findings:

uncommon — increased blood creatinine levels; rare — decreased hemoglobin levels, increased blood uric acid levels, increased liver enzyme levels, increased blood creatine phosphokinase levels.

1, 2, 3, 4 See detailed descriptions in the section “Description of selected adverse reactions” below.

Description of selected adverse reactions

Sepsis. In the PRoFESS trial, a higher incidence of sepsis was observed in patients receiving telmisartan compared to those receiving placebo. This may be due to chance or may reflect an as yet unknown underlying process.

Hypotension. This adverse reaction was frequently observed in patients with controlled blood pressure who received telmisartan for reduction of cardiovascular risk in addition to standard therapy.

Liver function abnormalities / liver disorders. According to post-marketing data, most cases of liver function abnormalities / liver disorders occurred in patients of Japanese nationality. These patients appear to be more susceptible to these adverse reactions.

Interstitial lung disease. Cases of interstitial lung disease have been reported during the post-marketing period in temporal association with telmisartan use. However, a causal relationship has not been established.

Intestinal angioedema. Cases of intestinal angioedema have been reported in patients receiving angiotensin II receptor blockers (see section “Special precautions”).

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, as well as patients or their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in the original packaging.

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister; 3 blisters in a cardboard pack.

14 tablets in a blister; 2, 4, or 6 blisters in a cardboard pack.

Prescription status.

Prescription only.

Manufacturer.

LLC "KUSUM PHARM".

Manufacturer's location and address of business activity.

54 Skryabina Street, Sumy, Sumy region, 40020, Ukraine.

or

Manufacturer.

LLC "GLEDFARM LTD".

Manufacturer's location and address of business activity.

54 Hryhorii Davydovskoho Street, Sumy, Sumy region, 40020, Ukraine.