Telmisar/Telmisar 80

Telmisar: Each film-coated tablet contains: Telmisartan USP 40 mg.
Telmisar 80: Each film-coated tablet contains: Telmisartan USP 80 mg.
Excipients q.s.
Excipients/Inactive Ingredients: Colour: Titanium Dioxide BP.

Pharmacological Classification: Angiotensin II Receptor Blocker.
Pharmacology: Telmisartan is an orally active and specific angiotensin II receptor (type AT1) antagonist. Telmisartan displaces angiotensin II with very high affinity from its binding site at the AT1 receptor subtype, which is responsible for the known actions of angiotensin II. Telmisartan does not exhibit any partial agonist activity at the AT1 receptor. Telmisartan selectively binds the AT1 receptor. The binding is long-lasting. Telmisartan does not show affinity for other receptors, including AT2 and other less characterised AT receptors. The functional role of these receptors is not known, nor is the effect of their possible overstimulation by angiotensin II, whose levels are increased by Telmisartan. Plasma aldosterone levels are decreased by Telmisartan. Telmisartan does not inhibit human plasma renin or block ion channels. Telmisartan does not inhibit angiotensin converting enzyme (kininase II), the enzyme which also degrades bradykinin. Therefore, it is not expected to potentiate bradykinin-mediated adverse effects.
Pharmacokinetics: Absorption: Absorption of Telmisartan is rapid although the amount absorbed varies. The mean absolute bioavailability for Telmisartan is about 50%. When Telmisartan is taken with food, the reduction in the area under the plasma concentration-time curve (AUC0-) of Telmisartan varies from approximately 6% (40 mg dose) to approximately 19% (160 mg dose). By 3 hours after administration, plasma concentrations are similar whether Telmisartan is taken fasting or with food.
Linearity/Non-Linearity: The small reduction in AUC is not expected to cause a reduction in the therapeutic efficacy. There is no linear relationship between doses and plasma levels. Cmax and to a lesser extent AUC increase disproportionately at doses above 40 mg.
Distribution: Telmisartan is largely bound to plasma protein (>99.5%), mainly albumin and alpha-1 acid glycoprotein. The mean steady state apparent volume of distribution (Vdss) is approximately 500 L.
Biotransformation: Telmisartan is metabolised by conjugation to the glucuronide of the parent compound. No pharmacological activity has been shown for the conjugate.
Elimination: Telmisartan is characterised by biexponential decay pharmacokinetics with a terminal elimination half-life of >20 hours. The maximum plasma concentration (Cmax) and, to a smaller extent, the area under the plasma concentration-time curve (AUC), increase disproportionately with dose. There is no evidence of clinically relevant accumulation of Telmisartan taken at the recommended dose. Plasma concentrations were higher in females than in males, without relevant influence on efficacy.
After oral (and intravenous) administration, Telmisartan is nearly exclusively excreted with the faeces, mainly as unchanged compound. Cumulative urinary excretion is <1 % of dose. Total plasma clearance (Cl_tot) is high (approximately 1,000 mL/min) compared with hepatic blood flow (about 1,500 mL/min).
Special Populations: Paediatric Population: The pharmacokinetics of two doses of Telmisartan were assessed as a secondary objective in hypertensive patients (n = 57) aged 6 to < 18 years after taking Telmisartan 1 mg/kg or 2 mg/kg over a four-week treatment period. Pharmacokinetic objectives included the determination of the steady-state of Telmisartan in children and adolescents, and investigation of age related differences. Although the study was too small for a meaningful assessment of the pharmacokinetics of children under 12 years of age, the results are generally consistent with the findings in adults and confirm the non-linearity of Telmisartan, particularly of Cmax.
Gender Effects: Differences in plasma concentrations were observed, with Cmax and AUC being approximately 3- and 2-fold higher, respectively, in females compared to males.
Elderly Patients: The pharmacokinetics of Telmisartan do not differ between the elderly and those younger than 65 years.
Patients with Renal Impairment: In patients with mild to moderate and severe renal impairment, doubling of plasma concentrations was observed. However, lower plasma concentrations were observed in patients with renal insufficiency undergoing dialysis. Telmisartan is highly bound to plasma protein in renal-insufficient patients and cannot be removed by dialysis. The elimination half-life is not changed in patients with renal impairment.
Patients with Hepatic Impairment: Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute bioavailability up to nearly 100%. The elimination half-life is not changed in patients with hepatic impairment.

For the treatment of hypertension and cardiovascular risk reduction in patients unable to take Angiotensin-Converting Enzyme (ACE) Inhibitors.

Route of Administration: Oral.
Treatment of Essential Hypertension: The usually effective dose is 40 mg once daily. Some patients may already benefit at a daily dose of 20 mg. In cases where the target blood pressure is not achieved, the dose of Telmisartan 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.
Cardiovascular Prevention: The recommended dose is 80 mg once daily. It is not known whether doses lower than 80 mg of Telmisartan are effective in reducing cardiovascular morbidity.
When initiating Telmisartan therapy for the reduction of cardiovascular morbidity, close monitoring of blood pressure is recommended, and if appropriate adjustment of medications that lower blood pressure may be necessary. Telmisartan may be taken with or without food.
Special Patient Populations: Renal Impairment: No posology adjustment is required for patients with mild to moderate renal impairment. Limited experience is available in patients with severe renal impairment or haemodialysis. A lower starting dose of 20 mg is recommended in these patients.
Hepatic impairment: In patients with mild to moderate hepatic impairment, the posology should not exceed 40 mg once daily.
Elderly: No dose adjustment is necessary for elderly patients.
Paediatric Patients: Telmisartan is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.

There is limited information available with regard to overdose in humans.
Symptoms: 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.
Treatment: Telmisartan is not removed by haemodialysis. 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.

Renovascular Hypertension: There is an increased risk of severe hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with medicinal products that affect the renin-angiotensin-aldosterone system.
Intravascular Hypovolaemia: Symptomatic hypotension, especially after the first dose of Telmisartan, may occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea, or vomiting. Such conditions should be corrected before the administration of Telmisartan. Volume and/or sodium depletion should be corrected prior to administration of Telmisartan.
Dual Blockade of the Renin-Angiotensin-Aldosterone System: As a consequence of inhibiting the renin-angiotensin-aldosterone system, hypotension, syncope, hyperkalaemia, and changes in renal function (including acute renal failure) have been reported in susceptible individuals, especially if combining medicinal products that affect this system. Dual blockade of the renin-angiotensin-aldosterone system (e.g. by adding an ACE-inhibitor to an angiotensin II receptor antagonist) is therefore not recommended in patients with already controlled blood pressure and should be limited to individually defined cases with close monitoring of renal function.
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.
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 in 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, immunosuppressives (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 diseases), cellular lysis (e.g. acute limb ischemia, rhabdomyolysis. Close monitoring of serum potassium in at risk patients is recommended.
Sorbitol: This medicinal product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take Telmisartan.
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.
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.
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.
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.

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 overall incidence of adverse events reported with Telmisartan (41.4%) was usually comparable to placebo (43.9%) in controlled trials in patients treated for hypertension. The incidence of adverse events was not dose related and showed no correlation with gender, age or race of the patients. The safety profile of Telmisartan in patients treated for the reduction of cardiovascular morbidity was consistent with that obtained in hypertensive patients. The adverse drug reactions listed as follows have been accumulated from controlled clinical trials in patients treated for hypertension and from post-marketing reports. The listing also takes into account serious adverse events and adverse events leading to discontinuation reported in three clinical long-term studies including 21642 patients treated with Telmisartan for the reduction of cardiovascular morbidity for up to six years.
Adverse Reactions Have Been Ranked Under Headings of Frequency Using the Following Convention: 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), Not Known: (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Infections and Infestations: Uncommon: Upper respiratory tract infection including pharyngitis and sinusitis, urinary tract infection including cystitis.
Not Known: Sepsis including fatal outcome.
Blood and the Lymphatic System Disorders: Uncommon: Anaemia.
Rare: Thrombocytopenia.
Not Known: Eosinophilia.
Immune System Disorders: Rare: Hypersensitivity.
Not Known: Anaphylactic reaction.
Metabolism and Nutrition Disorders: Uncommon: Hyperkalaemia.
Psychiatric Disorders: Uncommon: Depression, insomnia.
Rare: Anxiety.
Nervous System Disorders: Uncommon: Syncope.
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.
Gastrointestinal Disorders: Uncommon: Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting.
Rare: Stomach discomfort, dry mouth.
Hepato-Biliary Disorders: Rare: Abnormal hepatic function (Liver disorder).
Skin and Subcutaneous Tissue Disorders: Uncommon: Hyperhidrosis, pruritus, rash.
Rare: Erythema, angioedema, drug eruption, toxic skin eruption, eczema.
Not Known: Urticaria.
Musculoskeletal and Connective Tissue Disorders: Uncommon: Myalgia, back pain (e.g. sciatica), muscle spasms.
Rare: Arthralgia, pain in extremity.
Not Known: 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.
Investigations: Uncommon: Blood creatinine increased.
Rare: Blood uric acid increased, hepatic enzyme increased, blood creatine phosphokinase increased, haemoglobin decreased in the PRoFESS trial, an increased incidence of sepsis was observed with Telmisartan compared with placebo. The event may be a chance finding or related to a mechanism currently not known.
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.

Interaction studies have only been performed in adults. 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, Angiotensin-Converting Enzyme (ACE) inhibitors, angiotensin II receptor antagonists, Non-Steroidal Anti-Inflammatory Medicinal Products (Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)), including selective (Cyclooxygenase (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 with 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 concentrations 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.
Concomitant Use Requiring Caution: Non-Steroidal Anti-Inflammatory Medicinal Products: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, Cyclooxygenase (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. In one study the co-administration of Telmisartan and ramipril led to an increase of up to 2.5 fold in the AUC0-24 and Cmax of ramipril and ramiprilat. The clinical relevance of this observation is not known.
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.
Other antihypertensive agents: The blood pressure lowering effect of Telmisartan can be increased by concomitant use of other antihypertensive medicinal products. 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 at temperatures not exceeding 30°C. Protect from light.

Angiotensin II Antagonists

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

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