Telswift

Telmisartan.

Composition: Telswift 40 (Telmisartan Tablets 40 mg): Each uncoated tablet contains: Telmisartan BP/Ph. Eur. 40 mg.
Excipients q.s.
Telswift 80 (Telmisartan Tablets 80 mg): Each uncoated tablet contains: Telmisartan BP/Ph. Eur. 80 mg.
Excipients q.s.
Properties: Telmisartan belongs to a group of medicines called angiotensin II receptor antagonists. It blocks the effect of angiotensin II so that the blood vessels relax, and the blood pressure is lowered. Telmisartan is 4'-[[4-Methyl-6-(1-methyl-1H-benzimidazol-2-yl)-2-propyl-1H-benzimidazol-1-yl] methyl] biphenyl-2-carboxylic acid. The empirical formula of Telmisartan is C33H30N4O2 and its molecular weight is 514.6.

Pharmacotherapeutic group: Angiotensin II receptor (type AT1) antagonist. ATC Code: C09CA07.
Pharmacology: Pharmacodynamics and Mechanism of Action: Telmisartan blocks the vasoconstrictor and aldosterone secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis.
Telmisartan has much greater affinity ( > 3,000 fold) for the AT1 receptor than for the AT2 receptor. Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because telmisartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Telmisartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.
Blockade of the angiotensin II receptor inhibits the negative regulatory feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and angiotensin II circulating levels do not overcome the effect of telmisartan on blood pressure.
Pharmacodynamics: A dose of telmisartan 80 mg inhibited the pressor response to an intravenous infusion of angiotensin II by about 90% at peak plasma concentrations with approximately 40% inhibition persisting for 24 hours.
Plasma concentration of angiotensin II and plasma renin activity (PRA) increased in a dose-dependent manner after single administration of telmisartan and repeated administration to hypertensive patients. The once-daily administration for up to 80 mg telmisartan did not influence plasma aldosterone concentrations. After multiple dose, there were no clinically significant changes in electrolytes (serum potassium or sodium), or in metabolic function (including serum levels of cholesterol, triglycerides, HDL, LDL, glucose, or uric acid).
Pharmacokinetics and Drug Metabolism: Absorption: Following oral administration, peak concentration (Cmax) of telmisartan are reached in 0.5-1 hour after dosing. Food slightly reduces the bioavailability of telmisartan, with a reduction in the area under the plasma concentration-time curve (AUC) of about 6% with the 40 mg tablet and about 20% after a 160 mg dose. The absolute bioavailability of telmisartan is dose dependent. At 40 and 160 mg the bioavailability was 42% and 58%, respectively. The pharmacokinetics of orally administered telmisartan are nonlinear over the dose range 20-160 mg, with greater than proportional increases of plasma concentrations (Cmax and AUC) with increasing doses. Telmisartan shows bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours. Through plasma concentrations of telmisartan with once daily dosing are about 10% to 25% of peak plasma concentrations. Telmisartan has an accumulation index in plasma of 1.5 to 2.0 upon repeated once daily dosing.
Distribution: Telmisartan is highly bound to plasma proteins (> 99.5%), mainly albumin and 1-acid glycoprotein. Plasma protein binding is constant over the concentration range achieved with recommended doses. The volume of distribution for telmisartan is approximately 500 liters, indicating additional tissue binding.
Metabolism and Elimination: Following either intravenous or oral administration of ¹⁴C-labeled telmisartan, most of the administered dose (> 97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively).
Telmisartan is metabolized by conjugation to form a pharmacologically inactive acyl glucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. After a single dose, the glucuronide represents approximately 11% of the measured radioactivity in plasma. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.
Total plasma clearance of telmisartan is > 800 mL/min. Terminal half-life and total clearance appear to be independent of dose.
Special Populations: Pediatric: Telmisartan pharmacokinetics have not been investigated in patients < 18 years of age.
Geriatric: The pharmacokinetics of telmisartan do not differ between the elderly and those younger than 65 years.
Gender: Plasma concentrations of telmisartan are generally 2-3 times higher in females than in males, however, no significant increases in blood pressure response or in the incidence of orthostatic hypotension were found in women. No dosage adjustment is necessary.
Renal insufficiency: Renal excretion does not contribute to the clearance of telmisartan. With mild-to-moderate renal impairment (creatinine clearance of 30-80 mL/min, mean clearance approximately 50 mL/min), no dosage adjustment is necessary with decreased renal function. Telmisartan is not removed from blood by haemodialysis.
Hepatic insufficiency: In patients with hepatic insufficiency, plasma concentrations of telmisartan are increased, and absolute bioavailability approaches 100%.

Hypertension: Treatment of essential hypertension in adults.
Cardiovascular risk reduction: Telmisartan is indicated for the reduction of the risk of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years of age or older at high risk of developing major cardiovascular events who are unable to take ACE inhibitors.
Studies of Telmisartan in this setting do not exclude that it may not preserve a meaningful fraction of the effect of the ACE inhibitor to which it was compared. Consider using the ACE inhibitor first, and, if it is stopped for cough only, consider re-typing the ACE inhibitor after the cough resolves.
Use of telmisartan with an ACE inhibitor is not recommended.

Treatment of essential hypertension: The recommendation dose is 40 mg once daily. In cases where the target blood pressure is not achieved, telmisartan dose can be increased to a maximum of 80 mg once daily. Alternatively, telmisartan may be used in combination with thiazide-type diuretics such as hydrochlorothiazide, which has been shown to have an additive blood pressure lowering effect with telmisartan. When considering raising the dose, it must be borne in mind that the maximum antihypertensive effect is generally attained four to eight weeks after the start of treatment.
In patients with severe hypertension treatment with telmisartan at doses up to 160 mg alone and in combination with hydrochlorothiazide 12.5 - 25 mg was daily was well tolerated and effective.
Cardiovascular prevention: The recommended dose of Telmisartan tablet is 80 mg once daily and can be administered with or without food. It is not known whether doses lower than 80 mg of telmisartan are effective in reducing cardiovascular morbidity and mortality.
When initiating Telmisartan tablet therapy for cardiovascular risk reduction, monitoring of blood pressure is recommended, and if appropriate adjustment of medications that lower blood pressure may be necessary.
Telmisartan tablet may be taken with or without food.
Special populations: Renal impairment: No posology adjustment is required for patients with renal impairment, including those on haemodialysis. Telmisartan is not removed from blood by hemofiltration.
Hepatic impairment: In patients with mild to moderate hepatic impairment the posology should not exceed 40 mg once daily.
Elderly patients: No dose adjustment is necessary.
Children and adolescents: The safety and efficacy of Telmisartan tablet for use in children below 18 years have not been established.
Method of administration: Telmisartan tablets may be taken with or without food.
Route of Administration: Oral.

The most prominent manifestations of telmisartan overdose were hypotension and tachycardia; bradycardia, dizziness, increase in serum creatinine, and acute renal failure have also been reported.
Telmisartan is not removed by hemodialysis. The patient should be closely monitored, and the treatment should be symptomatic and supportive. Management depends on the time since ingestion and the severity of the symptoms. Suggested measures include induction of emesis and/or gastric lavage. Activated charcoal may be useful in the treatment of overdosage. Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patient should be placed in a supine position, with salt and volume replacement given quickly.

Hypersensitivity to the active substance or to any of the excipients.
Second and third trimesters of pregnancy.
Biliary obstructive disorders.
Severe hepatic impairment.
The concomitant use of Telmisartan with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²).

Renovascular hypertension: There is an increased risk of severe hypotension and renal insufficiency when patients with bilateral renal artery stenosis of the artery to a single functioning kidney are treated with medicinal products that affect the renin-angiotensin-aldosterone system.
Intravascular hypovolaemia.
Dual Blockade of the Renin-angiotensin-aldosterone System: There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended. If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close 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 stimulation of the renin-angiotensin-aldosterone system: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with medicinal products that affect this system such as telmisartan has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute renal failure.
Primary aldosteronism: Patients with primary aldosteronism generally will not respond to antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. Therefore, the use of telmisartan is not recommended.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Diabetic patients treated with insulin or antidiabetics: In these patients hypoglycaemia may occur under telmisartan treatment. Therefore, in these patients an appropriate blood glucose monitoring should be considered; a dose adjustment of insulin or antidiabetics may be required, when indicated.
Hyperkalaemia: The use of medicinal products that affect the renin-angiotensin-aldosterone system may cause hyperkalaemia.
In the elderly, in patients with renal insufficiency, in diabetic patients, in patients concomitantly treated with other medicinal products that may increase potassium levels, and/or patients with intercurrent events, hyperkalaemia may be fatal. Before considering the concomitant use of medicinal products that affect the renin-angiotensin-aldosterone system, the benefit risk ratio should be evaluated.
The main risk factors for hyperkalaemia to be considered are: Diabetes mellitus, renal impairment, age (>70 years).
Combination with one or more other medicinal products that affect the renin-angiotensin-aldosterone system and/or potassium supplements. Medicinal products or therapeutic classes of medicinal products that may provoke hyperkalaemia are salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppresives (cyclosporin or tacrolimus), and trimethoprim.
Intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis, worsening of renal function, sudden worsening of the renal condition (e.g. infectious disease), cellular lysis (e.g. acute limb ischemia, rhabdomyolysis, extend trauma).
Close monitoring of serum potassium in at risk patients is recommended.
Ethnic differences: As observed for angiotensin converting enzyme inhibitors, telmisartan and the other angiotensin II receptor antagonists are apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of higher prevalence of low-renin states in the black hypertensive population.
Other: As with any antihypertensive agent, excessive reduction of blood pressure in patients with ischaemic cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke.
Renal impairment and kidney transplantation: When Telmisartan is used in patients with impaired renal function, periodic monitoring of potassium and creatinine serum levels is recommended. There is no experience regarding the administration of Telmisartan in patients with recent kidney transplantation.
Hepatic impairment: Telmisartan is not to be given to patients with cholestasis, biliary obstructive disorders or severe hepatic impairment since telmisartan is mostly eliminated with the bile. These patients can be expected to have reduced hepatic clearance for telmisartan. Telmisartan should be used only with caution in patients with mild to moderate hepatic impairment.
Use in Pregnancy: Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started.

The use of angiotensin II receptor antagonists is not recommended during the first trimester of pregnancy. The use of angiotensin II receptor antagonists is contraindicated during the second and third trimesters of pregnancy. Because no information is available regarding the use of telmisartan during breast-feeding, Telmisartan is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

Infections and infestations: Uncommon: Urinary tract infection including cystitis, upper respiratory tract infection including pharyngitis and sinusitis. Rare: Sepsis including fatal outcome.
Blood and the lymphatic system disorders: Uncommon: Anaemia. Rare: Eosinophilia, thrombocytopenia.
Immune system disorders: Rare: Anaphylactic reaction, hypersensitivity.
Metabolism and nutrition disorders: Uncommon: Hyperkalaemia. Rare: Hypoglycaemia (in diabetic patients).
Psychiatric disorders: Uncommon: Insomnia, depression. 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: Hypotension, orthostatic hypotension.
Respiratory, thoracic and mediastinal disorders: Uncommon: Dyspnoea, cough. Very rare: Interstitial lung disease.
Gastrointestinal disorders: Uncommon: Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting. Rare: Dry mouth, stomach discomfort, dysgeusia.
Hepato-biliary disorders: Rare: Hepatic function abnormal/liver disorder.
Skin and subcutaneous tissue disorders: Uncommon: Pruritus, hyperhidrosis, rash. Rare: Angioedema (also with fatal outcome), eczema, erythema, urticaria, drug eruption, toxic skin eruption.
Musculoskeletal and connective tissue disorders: Uncommon: Back pain (e.g. sciatica), muscle spasms, myalgia. Rare: Arthralgia, pain in extremity, tendon pain (tendinitis like symptoms).
Renal and urinary disorders: Uncommon: Renal impairment including acute renal failure.
General disorders and administration site conditions: Uncommon: Chest pain, asthenia (weakness). Rare: Influenza-like illness.
Description of selected adverse reactions: Sepsis: An increased incidence of sepsis was observed. The event may be a chance finding or related to a mechanism currently not known.
Hypotension: This adverse reaction was reported as common in patients with controlled blood pressure who were treated with telmisartan for the reduction of cardiovascular morbidity on top of standard care.
Interstitial lung disease: Cases of interstitial lung disease have been reported from post-marketing experience in temporal association with the intake of telmisartan. However, a causal relationship has not been established.
Hepatic function abnormal/liver disease: Most cases of hepatic function abnormal/liver disorder from post-marketing experience occurred in Japanese patients. Japanese patients are more likely to experience these adverse reactions.

Aliskiren: Do not co-administer Aliskiren with Telmisartan in patients with diabetes. Avoid the use of Aliskiren with Telmisartan in patients with renal impairment (GFR <60 mL/min).
Digoxin: When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentrations (20%) were observed. When initiating, adjusting, and discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic range.
As with other medicinal products acting on the renin-angiotensin-aldosterone system, telmisartan may provoke hyperkalaemia. The risk may increase in case of treatment combination with other medicinal products that may also provoke hyperkalaemia (salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non steroidal anti-inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressives (cyclosporin or tacrolimus), and trimethoprim).
The occurrence of hyperkalaemia depends on associated risk factors. The risk is increased in case of the previously-mentioned treatment combinations. The risk is particularly high in combination with potassium sparing-diuretics, and when combined with salt substitutes containing potassium. A combination the ACE inhibitors or NSAIDs, for example, presents a lesser risk provided that precautions for use are strictly followed.
Concomitant use not recommended: Potassium sparing diuretics or potassium supplements: Angiotensin II receptor antagonists such as telmisartan, attenuate diuretic induced potassium loss. Potassium sparing diuretics e.g. spironolactone, eplerenone, triamterene, or amiloride, potassium supplements, or potassium-containing salt substitutes may lead to a significant increase in serum potassium. If concomitant use is indicated because of documented hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.
Lithium: Reversible increases in serum lithium concentration and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors, and with angiotensin II receptor antagonists, including telmisartan. If use of the combination proves necessary, careful monitoring of serum lithium levels is recommended. Lithium should not be used with diuretics, the use of lithium with telmisartan is not recommended.
Concomitant use requiring caution: Non-Steroidal Anti-inflammatory Agents including Selective Cyclooxygenase-2 inhibitors (COX-2 inhibitors): NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect of angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the co-administration of angiotensin II receptor antagonists and agents that inhibit cyclooxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter.
Diuretics (thiazide or loop diuretics): Prior treatment with high dose diuretics such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic) may result in volume depletion, and in a risk of hypotension when initiating therapy with telmisartan.
To be taken into account with concomitant use: Ramipril: Concomitant use of Telmisartan and Ramipril is not recommended.
Other antihypertensive agents: The blood pressure lowering effect of telmisartan can be increased by concomitant use of other antihypertensive medicinal products.
The dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent.
Based on their pharmacological properties it can be expected that the following medicinal products may potentiate the hypotensive effects of all antihypertensives including telmisartan: Baclofen, amifostine. Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics, or antidepressants.
Corticosteroids (systemic route): Reduction of the antihypertensive effect.

Store below 30°C. Protect from moisture.

Angiotensin II Antagonists

C09CA07 - telmisartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.

B