Arbitel

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ARBITEL (ARBITEL)

Composition:

Active substance: telmisartan;

1 tablet contains 20 mg, or 40 mg, or 80 mg of telmisartan;

Excipients: mannite (E 421), meglumine, sodium hydroxide, povidone (K-30), crospovidone (type A), magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties:

20 mg tablets: white or almost white, round uncoated tablets, approximately 7.0 mm in diameter, flat with beveled edges, engraved with "T" on one side and "20" on the other;

40 mg tablets: white or almost white, oval biconvex uncoated tablets, 12.0 mm × 6.0 mm, engraved with "T40" on one side and smooth on the other;

80 mg tablets: white or almost white, capsule-shaped biconvex uncoated tablets, 16.0 mm × 8.0 mm, engraved with "T80" on one side and smooth on the other.

Pharmacotherapeutic group. Simple angiotensin II receptor blockers.

ATC code C09C A07.

Pharmacological Properties

Pharmacodynamics

Mechanism of Action

Telmisartan is a specific and potent oral angiotensin II receptor (type AT1) blocker. Telmisartan binds with very high affinity to the AT1 subtype of angiotensin II receptors, displacing angiotensin II from its binding sites responsible for angiotensin II activity. Telmisartan exhibits no partial agonistic activity at the AT1 receptor. It selectively binds to the AT1 receptor, and this 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 fully understood, nor is the effect of their potential stimulation by angiotensin II, whose levels increase with telmisartan. Telmisartan reduces plasma aldosterone levels. It does not reduce plasma renin levels and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kininase II), the enzyme also responsible for bradykinin degradation. 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 arterial blood pressure induced by angiotensin II. The blocking effect persists for 24 hours and remains noticeable up to 48 hours.

Pharmacokinetics

Absorption. Telmisartan is rapidly absorbed, but the extent of absorption 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–∞) decreases by approximately 6% (40 mg) to 19% (160 mg). However, three hours after administration, plasma concentrations are similar to those observed when telmisartan is taken without food.

Linearity / Non-linearity. The slight reduction 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 of the parent compound to glucuronide. 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 is no evidence of clinically relevant accumulation of telmisartan with repeated administration at recommended doses. Plasma concentrations are higher in women than in men, without a corresponding impact on efficacy.

After oral (and intravenous) administration, telmisartan is almost entirely 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. The 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 steady-state telmisartan levels in children and adolescents and investigation of age-related differences. Although the study was too small to reliably assess pharmacokinetics in children under 12 years of age, the results generally align with data obtained in adults and confirm the non-linearity of telmisartan, particularly for Cmax.

Gender. 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 significantly between elderly patients and those under 65 years of age.

Patients with Renal Impairment. In patients with mild to moderate and severe renal impairment, plasma concentrations were approximately doubled. However, in patients with renal impairment undergoing dialysis, lower plasma concentrations were observed. Telmisartan is highly protein-bound in patients with renal impairment and is not dialyzable. The elimination half-life of telmisartan 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 of telmisartan 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 (history of ischemic heart disease, stroke, or peripheral artery disease);
• Type 2 diabetes with documented target organ damage.

Contraindications

• Hypersensitivity to the components of the drug;
• 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 products in patients with diabetes mellitus or renal dysfunction (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, median increases in digoxin plasma peak 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 levels within the therapeutic range.

Like other drugs that inhibit the renin-angiotensin-aldosterone system (RAAS), telmisartan may provoke hyperkalemia (see section "Special precautions"). The risk may increase when used concomitantly with other agents that may also cause hyperkalemia (potassium-containing salt substitutes, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (ACEIs), 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 with potassium-sparing diuretics and in combination with potassium-containing salt substitutes. The combination with ACE inhibitors or NSAIDs is less risky provided that the relevant precautions 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, such combination 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 nonselective 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 possible acute kidney injury, which is usually reversible. Therefore, such combinations should be used cautiously, especially in the elderly. Patients should receive adequate hydration; consideration should be given to monitoring renal function after initiation and periodically after discontinuation of concomitant therapy.

In one study, concomitant administration of telmisartan and ramipril resulted in a 2.5-fold increase in AUC0–24 and Cmax 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 an increased risk 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 by concomitant use of 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 kidney injury), compared to using a single RAAS-acting agent (see sections "Special precautions", "Contraindications", and "Pharmacodynamics").

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.

Corticosteroids (systemic use)

Reduction of antihypertensive effect.

Special precautions for use

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

Hepatic impairment. ARBITEL must not be administered 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.

ARBITEL should be used with caution 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 of a single functioning kidney when treated with drugs affecting the RAAS.

Renal impairment and kidney transplantation. Periodic monitoring of serum potassium and creatinine levels is recommended in patients with renal dysfunction receiving ARBITEL. 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 volume and/or sodium levels. Symptomatic hypotension, particularly after the first dose of ARBITEL, may occur in patients with reduced intravascular volume and/or sodium levels, such as those resulting from intensive diuretic therapy, a low-salt diet, or diarrhea and vomiting. These conditions should be corrected prior to administration of ARBITEL. Sodium levels and/or intravascular fluid volume should be normalized before initiating treatment.

Dual blockade of the RAAS

Evidence indicates that concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of hypotension, hyperkalemia, and decreased renal function (including acute renal failure).

Therefore, dual blockade by combining ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended (see sections "Pharmacological properties" and "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, electrolytes, and blood pressure.

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

Other conditions requiring RAAS activity

In patients whose vascular tone and renal function primarily depend on RAAS activity (e.g., patients with severe congestive heart failure or significant renal disease, including renal artery stenosis), administration of ARBITEL together with other medicinal products affecting the RAAS may lead to acute hypotension, hyperazotemia, oliguria, and rarely, acute renal failure (see section "Adverse reactions").

Primary hyperaldosteronism. Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs acting via blockade of the renin-angiotensin system (RAS). Therefore, the use of telmisartan in these patients is not recommended.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy. As with other vasodilators, ARBITEL should be administered with caution to patients diagnosed with aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy.

Diabetic patients treated with insulin or antidiabetic medicinal products. Hypoglycemia may develop during telmisartan treatment 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.

Hyperkalemia. Medicinal products affecting the RAAS may cause hyperkalemia.

In elderly patients, patients with renal impairment, diabetes mellitus, concomitant diseases, and in patients receiving other medicinal products that may increase potassium levels, hyperkalemia may lead to fatal outcomes.

The benefit-risk ratio should be carefully evaluated before considering concomitant use of medicinal products that suppress the RAAS.

Key risk factors for hyperkalemia to consider:

• diabetes mellitus, renal impairment, age over 70 years;
• combination therapy with one or more other RAAS-affecting drugs and/or potassium-containing dietary supplements. Medicinal products or therapeutic groups that may provoke hyperkalemia include potassium-containing salt substitutes, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, heparin, immunosuppressants (cyclosporine or tacrolimus), and trimethoprim;
• intercurrent events, particularly dehydration, acute heart failure, metabolic acidosis, worsening renal function, acute deterioration of kidney function (e.g., due to infections), and cell lysis (e.g., acute limb ischemia, 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. As observed with ACE inhibitors, telmisartan and other angiotensin II receptor blockers are less effective in reducing blood pressure in patients of black race compared to patients of other races. This may be explained by the higher prevalence of low-renin states among black patients with arterial hypertension.

Ischemic heart disease

As with other antihypertensive agents, excessive reduction of blood pressure in patients with ischemic heart disease or ischemic cardiopathy may lead to myocardial infarction or stroke.

Intestinal angioedema

Cases of intestinal angioedema have been reported in patients taking angiotensin II receptor blockers (see section "Adverse reactions"). These patients presented with abdominal pain, nausea, vomiting, and diarrhea. Symptoms resolved after discontinuation of angiotensin II receptor blockers. If intestinal angioedema is diagnosed, telmisartan should be discontinued and appropriate monitoring initiated until complete resolution of symptoms.

Mannitol. The medicinal product contains mannitol (E 421). This medicinal product may have a mild laxative effect.

Use during pregnancy or breastfeeding

Pregnancy

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

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

Epidemiological evidence of teratogenic risk associated with the use of ACE inhibitors during the first trimester of pregnancy has not been conclusive, but a small increased risk cannot be excluded. Although there are no controlled epidemiological data on the teratogenic risk of angiotensin II receptor antagonists, similar risks may exist for this class of medicinal products. When pregnancy is planned, the drug should be replaced in advance with another antihypertensive agent with an established safety profile for use during pregnancy. Upon confirmation of pregnancy, treatment with angiotensin II receptor antagonists must be discontinued immediately, and alternative therapy should be initiated if necessary.

It is known that the use of angiotensin II receptor antagonists during the second and third trimesters of pregnancy causes fetotoxicity in humans (renal dysfunction, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, hypotension, hyperkalemia). If angiotensin II receptor antagonists are administered starting from the second trimester of pregnancy, ultrasound monitoring of fetal renal function and skull ossification is recommended. Infants whose mothers have taken angiotensin II receptor antagonists must be closely monitored for arterial hypotension (see sections "Contraindications" and "Special precautions").

Lactation

Due to the lack of information on the use of telmisartan during lactation, ARBITEL is not recommended for use in breastfeeding women. Alternative treatment with a better-established safety profile is preferred, especially when breastfeeding a newborn or preterm infant.

Fertility

Preclinical studies have not shown any effect of telmisartan on fertility in males or females.

Ability to influence the reaction rate while driving or operating machinery

When driving vehicles or operating machinery, one should consider the possibility of dizziness or hypersomnia occurring during antihypertensive therapy, including treatment with ARBITEL.

Dosage and Administration

Arterial Hypertension Treatment

The usual effective dose of ARBITEL is 40 mg once daily. In some patients, a daily dose of ARBITEL 20 mg may be sufficient. If blood pressure is not adequately controlled, the dose may be increased to 80 mg once daily. Alternatively, telmisartan may be co-administered with thiazide diuretics such as hydrochlorothiazide, which provide an additional antihypertensive effect when used in combination with telmisartan. When considering dose escalation, it should be noted that the maximal antihypertensive effect is achieved within 4–8 weeks after initiation of treatment.

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 ARBITEL therapy for the prevention of cardiovascular events, careful monitoring of blood pressure is recommended, and the dosage of antihypertensive medications should be adjusted as needed.

Special Patient Groups

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 (see section "Special Warnings and Precautions for Use"). Dose adjustment is not required in patients with mild to moderate renal impairment.

Hepatic Impairment. ARBITEL is contraindicated in patients with severe hepatic impairment.

In 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").

Elderly Patients. Dose adjustment is not required.

Administration

ARBITEL should be taken orally once daily with sufficient fluid, independent of food intake.

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

Pediatric Population

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

Current available data are presented in the "Pharmacokinetics" section; however, no dosage recommendations can be made.

Overdose

Information regarding telmisartan overdose is limited.

Symptoms. The most prominent symptoms reported with telmisartan overdose include hypotension and tachycardia. Bradycardia, dizziness, elevated serum creatinine levels, and acute renal failure have also been reported.

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

Adverse Reactions

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

The overall incidence of adverse reactions in patients with arterial hypertension during controlled clinical trials receiving telmisartan was generally comparable to that with placebo (41.4% vs. 43.9%). The frequency of adverse reactions was independent of 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 with arterial hypertension.

The overall incidence of adverse reactions in patients with arterial hypertension during controlled clinical trials receiving telmisartan was generally comparable to that with placebo (41.4% vs. 43.9%). The frequency of adverse reactions was independent of 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 with arterial hypertension.

Adverse effects are listed below with frequency categories defined as follows: very common (≥1/10); common (from 1/100 to <1/10); uncommon (from 1/1,000 to <1/100); rare (from 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, including cystitis; upper respiratory tract infections, including pharyngitis and sinusitis;

rare – sepsis, including fatal cases¹.

Blood and lymphatic system disorders:

uncommon – anaemia;

rare – eosinophilia, thrombocytopenia.

Immune system disorders:

rare – hypersensitivity, anaphylactic reactions.

Metabolism and nutrition disorders:

uncommon – hyperkalaemia;

rare – hypoglycaemia (in patients with diabetes mellitus), hyponatraemia.

Cardiac disorders:

uncommon – bradycardia;

rare – tachycardia.

Psychiatric disorders:

uncommon – insomnia, depression;

rare – anxiety.

Nervous system disorders:

uncommon – syncope;

rare – somnolence.

Eye disorders:

rare – visual disturbances.

Ear and labyrinth disorders:

uncommon – vertigo.

Vascular disorders:

uncommon – arterial hypotension², orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders:

uncommon – dyspnoea, cough;

very rare – interstitial lung disease⁴.

Gastrointestinal disorders:

uncommon – abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting;

rare – dry mouth, abdominal discomfort, dysgeusia.

Hepatobiliary disorders:

rare – hepatic function abnormalities / hepatic 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 renal failure.

General disorders:

uncommon – chest pain, asthenia (weakness);

rare – influenza-like symptoms.

Investigations:

uncommon – increased blood creatinine;

rare – decreased haemoglobin levels, increased blood uric acid, increased liver enzymes, increased blood creatine phosphokinase.

^{1, 2, 3, 4} – See section "Adverse Reactions. Description of selected adverse reactions".

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 a process not yet understood.

Hypotension. This adverse reaction was commonly observed in patients with controlled blood pressure who were treated with telmisartan for cardiovascular risk reduction in addition to standard therapy.

Hepatic function abnormalities / hepatic disorders. According to post-marketing data, most cases of hepatic function abnormalities / hepatic disorders were observed in patients of Japanese nationality. Patients of Japanese nationality may be more susceptible to these adverse reactions.

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

Intestinal angioedema

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

Reporting of adverse reactions

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

Shelf life. 3 years.

Storage conditions. No special storage conditions required. Keep out of reach of children.

Packaging. 10 tablets in a blister; 3 blisters in a cardboard box.

7 tablets in a blister; 2 or 4 blisters in a cardboard box.

14 tablets in a blister; 1, 2, 4, or 7 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Micro Labs Limited.

Manufacturer's address and location of business operations

Plot No. S.155 – S.159 and N1, Verna Industrial Estate, Phase III and Phase IV, Verna Salcette, In-403 722, India.