Telsartan

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TELMISARTAN (TELSARTAN)

Composition:

Active substance: telmisartan;

One tablet contains telmisartan 40 mg or 80 mg;

Excipients: meglumine, sodium hydroxide, povidone, polysorbate 80, mannitol (E 421), magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets from white to almost white in color, uncoated, capsule-shaped, with imprints “T” and “L” on both sides of the break line on one side and the imprint “40” (for 40 mg tablets) or “80” (for 80 mg tablets) on the other side.

Pharmacotherapeutic group. Simple preparations of angiotensin II antagonists.

ATC code C09C A07.

Pharmacological properties.

Pharmacodynamics.

Telmisartan is a specific oral angiotensin II receptor antagonist (type AT1). With high affinity, telmisartan displaces angiotensin II from its binding site on the AT1 receptor subtype responsible for angiotensin II effects. Telmisartan does not exhibit any partial agonist activity at the AT1 receptor. Telmisartan selectively binds to the AT1 receptor for a prolonged period. The drug shows no 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 potential overstimulation by angiotensin II, whose levels are increased by telmisartan. Telmisartan reduces plasma aldosterone levels. Telmisartan does not inhibit human plasma renin, nor does it block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (ACE) (kininase II), which also degrades bradykinin. Therefore, an increase in bradykinin-related adverse reactions is not expected.

In humans, telmisartan at a dose of 80 mg almost completely inhibits the blood pressure-elevating effect of angiotensin II. The inhibitory effect lasts beyond 24 hours and is still evident up to 48 hours.

Clinical efficacy and safety

Treatment of essential hypertension

After the first dose of telmisartan, antihypertensive effects gradually begin to appear within 3 hours. Maximum reduction in blood pressure is usually achieved within 4–8 weeks of starting therapy and is maintained during long-term treatment.

The antihypertensive effect remains consistent over 24 hours after dosing, including the last 4 hours before the next dose, as demonstrated by ambulatory blood pressure monitoring. This has been repeatedly confirmed by residual-to-peak effect ratios exceeding 80% following 40 mg and 80 mg doses of telmisartan in placebo-controlled clinical trials. There is a clear dose- and time-dependent relationship regarding the recovery of baseline systolic blood pressure (SBP). Data regarding diastolic blood pressure (DBP) are conflicting.

In patients with arterial hypertension, telmisartan reduces both systolic and diastolic blood pressure, without affecting pulse rate. The contribution of diuretic and natriuretic effects of the drug to its antihypertensive activity has not yet been established. The efficacy of telmisartan in lowering blood pressure is comparable to that of other antihypertensive agents from different drug classes (clinical studies comparing telmisartan with amlodipine, atenolol, enalapril, hydrochlorothiazide, and lisinopril are available).

Upon abrupt discontinuation of telmisartan therapy, blood pressure gradually returns to pre-treatment levels over several days, without evidence of rebound hypertension.

In clinical trials with direct comparison of two antihypertensive drugs, cases of dry cough were significantly less frequent with telmisartan than with ACE inhibitors.

Pharmacokinetics.

Absorption

Telmisartan is rapidly absorbed, although the extent of absorption varies. The mean value of absolute bioavailability of telmisartan is approximately 50%. Administration with food reduces the area under the concentration-time curve (AUC0–∞) by 6% (at a 40 mg dose) to approximately 19% (at a 160 mg dose). Three hours after administration, plasma concentrations of telmisartan are similar whether taken fasting or with food.

Linearity/non-linearity

The slight reduction in AUC is not expected to diminish therapeutic effect. There is no linear relationship between dose and plasma concentration of the drug. Maximum 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 average volume of distribution at steady state (Vdss) is approximately 500 L.

Metabolism

Telmisartan is metabolized via conjugation of the parent compound to glucuronide; the conjugate has no pharmacological activity.

Elimination

Telmisartan exhibits a biexponential pharmacokinetic profile with a terminal half-life exceeding 20 hours. Cmax and, to a lesser extent, AUC increase disproportionately with dose. There is no evidence of clinically significant accumulation of telmisartan with recommended dose administration. Plasma concentrations are higher in women than in men, without a significant impact on efficacy.

After oral administration, telmisartan is almost entirely excreted in feces, primarily in unchanged form. Cumulative urinary excretion accounts for <1% of the dose. Total plasma clearance (CLtot) is high (approximately 1000 mL/min), compared to hepatic blood flow (approximately 1500 mL/min).

Special patient populations

Effect of gender

When comparing female and male patients, differences in plasma concentrations were observed, with Cmax and AUC approximately 3 and 2 times higher, respectively, in women.

Elderly patients

Telmisartan pharmacokinetics do not differ significantly between elderly patients and those under 65 years of age.

Patients with renal impairment

In patients with mild, moderate, and severe renal impairment, plasma concentrations approximately double. However, lower plasma concentrations were observed in dialysis-dependent patients with renal failure. In patients with renal failure, telmisartan is highly bound to plasma proteins and therefore cannot be effectively removed by dialysis. The elimination half-life is not altered in patients with renal impairment.

Patients with hepatic impairment

Pharmacokinetic studies in patients with hepatic impairment demonstrated an increase in absolute bioavailability to nearly 100%. The elimination half-life is not altered in patients with hepatic impairment.

Clinical characteristics.

Indications.

Hypertension.

Treatment of essential hypertension in adults.

Prevention of cardiovascular disease.

Reduction of cardiovascular morbidity in patients with:

• established atherothrombotic cardiovascular disease (ischemic heart disease, stroke or peripheral artery disease in medical history);
• 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.

Pregnant women or women planning to become pregnant (see sections "Special warnings and precautions for use" and "Use during pregnancy or breastfeeding").

Biliary obstruction.

Severe hepatic impairment.

Children and adolescents (under 18 years of age).

Concomitant use of telmisartan and aliskiren-containing 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 are used concomitantly, mean increases in peak digoxin plasma concentrations (by 49%) and trough concentrations (by 20%) have been observed. Monitoring of digoxin levels should be performed at the initiation of treatment, during dose adjustments, and upon discontinuation of telmisartan to maintain digoxin levels within the therapeutic range.

As with other agents that inhibit the renin-angiotensin-aldosterone system (RAAS), telmisartan may provoke hyperkalaemia (see section "Special warnings and precautions for use"). The risk may increase when used in combination with other agents that may also cause hyperkalaemia (potassium-containing salt substitutes, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, heparin, immunosuppressants (cyclosporine or tacrolimus), and trimethoprim).

Cases of hyperkalaemia depend on associated risk factors. The risk increases with the above-mentioned therapeutic combinations. The risk is particularly high with potassium-sparing diuretics and with potassium-containing salt substitutes. Combination with ACE inhibitors or NSAIDs is less risky provided that the relevant precautions are strictly observed.

Concomitant use is not recommended

Potassium-sparing diuretics or potassium supplements

Angiotensin II receptor antagonists, such as telmisartan, reduce diuretic-induced potassium loss. 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 hypokalaemia, patients should use these agents with caution and serum potassium levels should be monitored frequently.

Lithium

During concomitant use of lithium with ACE inhibitors and angiotensin II receptor antagonists, including telmisartan, reversible increases in serum lithium concentrations and lithium toxicity have been observed. If use of such a combination is necessary, careful monitoring of serum lithium levels is recommended.

Concomitant use requires caution

Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs (e.g., acetylsalicylic acid at anti-inflammatory doses, COX-2 inhibitors, and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.

In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with renal impairment), concomitant use of angiotensin II receptor antagonists and agents that inhibit cyclooxygenase may lead to further deterioration in renal function, including possible acute renal failure, which is usually reversible. Therefore, such combinations should be used with caution, particularly in elderly patients. Patients should be adequately hydrated. Renal function should be monitored 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 AUC0–24 and Cmax for ramipril and ramiprilat. The clinical significance of this observation is unknown.

Diuretics (thiazides or loop diuretics)

Prior treatment with high doses of diuretics such as furosemide (a loop diuretic) or hydrochlorothiazide (a thiazide diuretic) may lead to volume depletion (dehydration) and increase the risk of developing arterial hypotension at the start of telmisartan therapy.

Should be considered during concomitant use

Other antihypertensive agents

The ability of telmisartan to lower blood pressure may be enhanced by concomitant use of other antihypertensive agents.

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

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

Glucocorticoids (systemic use)

Reduction of antihypertensive effect.

Special precautions for use.

Pregnancy. Angiotensin II receptor antagonists must not be initiated during pregnancy. Women of childbearing potential who are prescribed this medicinal product should be informed that it may affect the fetus and should be consistently reminded of the necessity for immediate medical consultation once pregnancy is confirmed. Patients planning pregnancy should switch to an alternative antihypertensive therapy with an established safety profile during pregnancy. Angiotensin II receptor antagonists must be discontinued immediately upon confirmation of pregnancy, and alternative treatment should be initiated if necessary (see sections "Contraindications" and "Use during pregnancy or breastfeeding").

Hepatic impairment

Telmisartan is contraindicated in patients with cholestasis, obstructive biliary disorders, or severe hepatic impairment, as telmisartan is primarily excreted via bile. Reduced hepatic clearance of telmisartan may be expected in such patients. Telmisartan may be used with caution only in patients with mild to moderate hepatic impairment.

Renovascular hypertension

There is an increased risk of severe hypotension and renal failure in patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney when treated with medicinal products affecting the RAAS.

Renal impairment and kidney transplantation

Periodic monitoring of serum potassium and creatinine levels is recommended during telmisartan treatment in patients with renal impairment. There is no experience with the use of telmisartan in patients after recent kidney transplantation.

Intravascular hypovolemia

Symptomatic hypotension, particularly after the first dose of telmisartan, may occur in patients with reduced fluid volume and/or sodium, resulting from active diuretic therapy, dietary salt restriction, diarrhea, or vomiting. Such conditions should be corrected prior to initiating telmisartan. Intravascular fluid volume and/or sodium levels should be normalized before starting telmisartan.

Dual blockade of the RAAS

Due to inhibition of the RAAS in susceptible individuals, especially when combining medicinal products affecting this system, cases of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) have been observed. Dual blockade of the RAAS (e.g., adding ACE inhibitors to angiotensin II receptor antagonists) is not recommended in patients whose blood pressure is already controlled; it should be restricted to specifically defined cases with careful monitoring of renal function (see sections "Pharmacodynamics" and "Interaction with other medicinal products and other forms of interaction").

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

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

Other conditions with RAAS activation

In patients whose vascular tone and renal function primarily depend on RAAS activity (e.g., patients with severe congestive heart failure or renal disease, including renal artery stenosis), treatment with medicinal products affecting this system, such as telmisartan, has been associated with acute hypotension, hyperazotemia, oliguria, or acute renal failure, which occurred rarely (see section "Adverse reactions").

Primary hyperaldosteronism

Patients with primary hyperaldosteronism generally do not respond to antihypertensive medicinal products that suppress the renin-angiotensin system. Therefore, the use of telmisartan is not recommended.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy

As with other vasodilators, the drug should be administered with caution in patients with aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.

Patients with diabetes mellitus treated with insulin or antidiabetic medicinal products

Hypoglycemia may develop during treatment with telmisartan in such patients. Blood glucose levels should be monitored in these patients, and this should be taken into account when adjusting the dose of insulin or antidiabetic medicinal products.

In patients with diabetes mellitus and cardiovascular risk (patients with diabetes and concomitant coronary artery disease), the risk of fatal myocardial infarction and sudden cardiovascular death may be higher when treated with antihypertensive agents such as angiotensin II receptor antagonists and ACE inhibitors. Patients with diabetes mellitus may have asymptomatic concomitant coronary artery disease and thus remain undiagnosed. Patients with diabetes mellitus should be carefully evaluated, e.g., by stress testing, to detect and treat concomitant coronary artery disease before initiating treatment with this medicinal product.

Hyperkalemia

The use of medicinal products affecting the RAAS may cause hyperkalemia. In elderly patients, patients with renal impairment, diabetes mellitus, patients receiving other medicinal products that may increase potassium levels, and/or patients with intercurrent illnesses, hyperkalemia may be fatal.

The benefit-risk ratio should be assessed before deciding on concomitant use of medicinal products affecting the RAAS.

Main risk factors for hyperkalemia:

• Diabetes mellitus, renal dysfunction, age >70 years.
• Combination with other medicinal products affecting the RAAS and/or use of potassium-containing supplements. Medicinal products that may provoke hyperkalemia include potassium-containing salt substitutes, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs (including selective COX-2 inhibitors), heparin, immunosuppressants (cyclosporine or tacrolimus), and trimethoprim.
• Intercurrent conditions, particularly dehydration, acute heart failure, metabolic acidosis, worsening renal function, sudden deterioration of renal status (e.g., infections), and cellular lysis (e.g., acute limb ischemia, rhabdomyolysis, severe trauma).

Careful monitoring of potassium levels is recommended in patients belonging to risk groups.

Ethnic differences

ACE inhibitors, telmisartan, and other angiotensin II receptor antagonists are less effective in lowering blood pressure in patients of Black race compared to other racial groups, likely because hypertensive patients of Black race more frequently have low renin levels.

Other

With the use of any antihypertensive agent, excessive reduction in blood pressure in patients with ischemic heart disease or ischemic cerebrovascular disease may lead to myocardial infarction or stroke.

Angioedema of the intestine

Cases of intestinal angioedema have been reported in patients taking angiotensin II receptor blockers (see section "Adverse reactions"). These patients experienced abdominal pain, nausea, vomiting, and diarrhea. Symptoms resolved after discontinuation of angiotensin II receptor blockers. If intestinal angioedema is diagnosed, treatment with the medicinal product TELMISARTAN should be discontinued and appropriate monitoring initiated until symptoms completely resolve.

Use during pregnancy or breastfeeding.

Pregnancy.

The medicinal product is contraindicated in pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment with this product, its use must be discontinued immediately and, if necessary, replaced with another medicinal product permitted for use during pregnancy (see sections "Contraindications" and "Special precautions").

There are no adequate data on the use of telmisartan in pregnant women. Animal studies indicate reproductive toxicity.

Therapy with angiotensin II receptor antagonists should not be initiated during pregnancy.

Women of childbearing potential who are prescribed treatment with this medicinal product must be informed that the drug may affect the fetus, and they should be consistently reminded of the need to seek immediate medical advice as soon as pregnancy is confirmed. If therapy with angiotensin II antagonists is considered necessary and the patient is planning pregnancy, it is recommended to replace the treatment with antihypertensive therapy with an established safety profile during pregnancy. If pregnancy is confirmed during treatment with this drug, its use must be discontinued immediately and appropriate alternative therapy initiated.

It is known that the use of angiotensin II receptor antagonists during pregnancy causes fetal and neonatal toxicity in humans (cases of fetal and neonatal death, oligohydramnios, intrauterine growth restriction, fetal and neonatal hypotension, impaired renal function, renal failure, hyperkalemia, cranial hypoplasia, hypotension, limb contractures/craniofacial deformities/pulmonary hypoplasia—possibly caused by oligohydramnios—have been reported in pregnant patients treated with drugs of this class). If exposure to angiotensin II receptor antagonists during pregnancy has occurred, it is recommended to consult a physician and perform ultrasound assessment of fetal renal function and skull bones. Newborns whose mothers have taken angiotensin II receptor antagonists must be closely monitored for signs of arterial hypotension (see sections "Contraindications" and "Special precautions").

Breastfeeding period.

Due to lack of information on the use of telmisartan during breastfeeding, this medicinal product is not recommended during lactation. Alternative treatment with a better-established safety profile is preferred, especially when breastfeeding newborns or preterm infants.

Fertility.

Preclinical data show no effect of the drug on fertility in males or females.

Ability to influence reaction rate while driving or operating machinery.

When driving vehicles or operating machinery, one should consider the possibility of dizziness or hypersomnia associated with antihypertensive therapy, including the use of the drug Telsartan.

Dosage and Administration

Telmisartan tablets are recommended to be taken orally once daily with liquid, regardless of food intake.

Due to the hygroscopic properties of the tablets, telmisartan should be stored in the closed blister pack.

The tablets should be removed from the blister pack immediately before administration.

Treatment of essential arterial hypertension

The usual effective dose of the drug is 40 mg once daily. Some patients may achieve a therapeutic effect with a dose of 20 mg daily. If the target blood pressure cannot be achieved, the dose of telmisartan may be increased to the maximum dose of 80 mg daily.

Alternatively, telmisartan may be used in combination with thiazide diuretics such as hydrochlorothiazide, which can additionally lower blood pressure when used together with telmisartan. When deciding on increasing the dose, it should be taken into account that the maximum antihypertensive effect is usually achieved within 4 to 8 weeks after initiation of therapy.

Prevention of cardiovascular disease

The recommended dose is 80 mg once daily. It is not known whether telmisartan doses lower than 80 mg are effective in reducing cardiovascular morbidity.

Careful monitoring of blood pressure is recommended at the beginning of telmisartan therapy for cardiovascular risk reduction, and appropriate adjustment of antihypertensive medications may be required.

Special populations

Renal impairment

Patients with mild to moderate renal impairment do not require dose adjustment. Experience in patients with severe renal impairment and in patients undergoing hemodialysis is limited. For these patients, a lower initial dose of telmisartan 20 mg is recommended (see section "Special instructions").

Hepatic impairment

Telmisartan is contraindicated in patients with severe hepatic impairment.

Patients with mild to moderate hepatic impairment should not exceed a dose of 40 mg once daily (see section "Special instructions").

Elderly patients

Dose adjustment in elderly patients is not required.

Children

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

Overdose.

Information regarding overdose with telmisartan in humans is limited.

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

Treatment. Telmisartan is not removed from the body by hemodialysis. Close monitoring and symptomatic and supportive therapy should be administered. Treatment depends on the time elapsed since ingestion of the overdose and the severity of symptoms. Recommended measures include induction of emesis and/or gastric lavage. Activated charcoal may be beneficial in treating overdose. Serum electrolytes and creatinine levels should be monitored frequently. If hypotension occurs, the patient should be placed in a supine position, and prompt measures to restore fluid and electrolyte balance should be initiated.

Adverse Reactions

Adverse reactions are categorized by frequency as follows: 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 frequency group, adverse reactions are listed in order of decreasing severity.

Infections and infestations:

Uncommon: upper respiratory tract infections, including pharyngitis and sinusitis; urinary tract infections, including cystitis;

Rare: sepsis, including fatal outcomes¹.

Blood and lymphatic system disorders:

Uncommon: anemia;

Rare: thrombocytopenia, eosinophilia.

Immune system disorders:

Rare: hypersensitivity, anaphylactic reaction.

Metabolism and nutrition disorders:

Uncommon: hyperkalemia;

Rare: hypoglycemia (in diabetic patients).

Psychiatric disorders:

Uncommon: depression, insomnia;

Rare: anxiety.

Nervous system disorders:

Uncommon: syncope;

Rare: somnolence.

Eye disorders:

Rare: visual disturbance.

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 disease³.

Gastrointestinal disorders:

Uncommon: abdominal pain, diarrhea, dyspepsia, flatulence, vomiting;

Rare: gastric discomfort, dry mouth, dysgeusia.

Hepatobiliary disorders:

Rare: liver function abnormalities/liver disorders⁴.

Skin and subcutaneous tissue disorders:

Uncommon: increased sweating, pruritus, rash;

Rare: erythema, angioedema (including fatal outcomes), urticaria, drug rash, toxic dermatitis, eczema.

Musculoskeletal and connective tissue disorders:

Uncommon: myalgia, back pain (e.g., sciatica), muscle cramps;

Rare: arthralgia, limb pain, tendon pain (symptoms similar to tendinitis).

Renal and urinary disorders:

Uncommon: renal function impairment, including acute renal failure.

General disorders:

Uncommon: chest pain, asthenia (weakness);

Rare: influenza-like symptoms.

Laboratory findings:

Uncommon: increased blood creatinine;

Rare: increased blood uric acid, elevated liver enzymes, increased blood creatine phosphokinase (CPK), decreased hemoglobin.

Description of selected adverse reactions

Intestinal angioedema

Cases of intestinal angioedema have been reported following administration of angiotensin II receptor blockers (see section "Special precautions").

¹ Sepsis

An increased incidence of sepsis was observed in clinical trials with telmisartan compared to placebo. This finding may be coincidental or related to a mechanism not yet known.

² Arterial hypotension

This adverse reaction has been reported as common in patients with controlled blood pressure who were treated with telmisartan for cardiovascular risk reduction in addition to standard therapy.

³ Interstitial lung disease

Cases of interstitial lung disease have been reported during post-marketing use of telmisartan. However, a causal relationship has not been established.

⁴ Liver function abnormalities/Liver disorders

Most cases of liver function abnormalities/liver disorders were reported during the post-marketing period in Japanese patients. Japanese patients appear to experience these adverse reactions more frequently than others.

Shelf life. 3 years.

Storage conditions. Store in the original packaging, out of reach of children, at a temperature not exceeding 25°C.

Packaging. 10 tablets per blister; 1 or 3 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer. Dr. Reddy’s Laboratories Ltd, FTO – II

Manufacturer's address.

Survey Nos. 42R, 43, 44R, 45R, 46R, 53, 54, 83, Bachupally, Bachupally Mandal, Medchal Malkajgiri District – 500090, Telangana State, India

Adverse reactions or lack of efficacy with this medicinal product should be reported via phone:

+38 044 207 51 97 or +38 050 414 39 39, or by email: [email protected] (available 24/7).