Teli 40/Teli 80

Teli 40/Teli 80

telmisartan

Manufacturer:

Cadila Pharma

Distributor:

Ambica

Marketer:

Macropharma Corp
Full Prescribing Info
Contents
Telmisartan.
Description
Each tablet of Teli 40 contains telmisartan 40 mg.
Each tablet of Teli 80 contains telmisartan 80 mg.
Teli also contains the following excipients: Povidone (K25), meglumine, sodium hydroxide, mannitol (E421), magnesium stearate.
Action
Pharmacotherapeutic Group: Angiotensin II antagonists, plain. ATC Code: C09CA07.
Pharmacology: Pharmacodynamics: Mechanism of Action: 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 characterized 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 (ACE, kininase II), the enzyme which also degrades bradykinin. Therefore, it is not expected to potentiate bradykinin-mediated adverse effects.
In human, an telmisartan 80-mg dose almost completely inhibits the angiotensin II evoked blood pressure increase. The inhibitory effect is maintained over 24 hrs and still measurable up to 48 hrs.
Clinical Efficacy and Safety: Treatment of Essential Hypertension: After the 1st dose of telmisartan, the antihypertensive activity gradually becomes evident within 3 hrs. The maximum reduction in blood pressure is generally attained 4-8 weeks after the start of treatment and is sustained during long-term therapy.
The antihypertensive effect persists constantly over 24 hrs after dosing and includes the last 4 hrs before the next dose as shown by ambulatory blood pressure measurements. This is confirmed by trough to peak ratios consistently >80% seen after doses of 40 and 80 mg of telmisartan in placebo controlled clinical studies. There is an apparent trend to a dose relationship to a time to recovery of baseline systolic blood pressure (SBP). In this respect data, concerning diastolic blood pressure (DBP) are inconsistent.
In patients with hypertension, telmisartan reduces both systolic and diastolic blood pressure without affecting pulse rate. The contribution of the Teli's diuretic and natriuretic effect to its hypotensive activity has still to be defined. The antihypertensive efficacy of telmisartan is comparable to that of agents representative of other classes of antihypertensive medicinal products (demonstrated in clinical trials comparing telmisartan to amlodipine, atenolol, enalapril, hydrochlorothiazide and lisinopril).
Upon abrupt cessation of treatment with telmisartan, blood pressure gradually returns to pretreatment values over a period of several days without evidence of rebound hypertension.
The incidence of dry cough was significantly lower in patients treated with telmisartan than in those given ACE inhibitors in clinical trials directly comparing the 2 antihypertensive treatments.
Cardiovascular (CV) Prevention: Ongoing telmisartan alone and in combination with ramipril global endpoint trial (ONTARGET) compared the effects of telmisartan, ramipril and the combination of telmisartan and ramipril on CV outcomes in 25,620 patients ≥55 years with a history of coronary artery disease, stroke, transient ischemic attack (TIA), peripheral arterial disease or type 2 diabetes mellitus accompanied by evidence of end-organ damage (eg, retinopathy, left ventricular hypertrophy, macro- or microalbuminuria), which is a population at risk for CV events.
Patients were randomized to 1 of the 3 following treatment groups: Telmisartan 80 mg (n=8,542), ramipril 10 mg (n=8,576) or the combination of telmisartan 80 mg plus ramipril 10 mg (n=8,502) and followed for a mean observation time of 4.5 years.
Telmisartan showed a similar effect to ramipril in reducing the primary composite endpoint of CV death, non-fatal myocardial infarction (MI), non-fatal stroke or hospitalization for congestive heart failure (CHF). The incidence of the primary endpoint was similar in the telmisartan (16.7%) and ramipril (16.5%) groups. The hazard ratio for telmisartan versus ramipril was 1.01 (97.5% CI 0.93-1.1, p (non-inferiority)=0.0019 at a margin of 1.13).
The all-cause mortality rate was 11.6% and 11.8% among telmisartan and ramipril treated patients, respectively.
Telmisartan was found to be similarly effective to ramipril in the prespecified secondary endpoint of CV death, non-fatal MI and non-fatal stroke [0.99 (97.5% CI 0.9-1.08), p (non-inferiority)=0.0004], the primary endpoint in the reference study the heart outcomes prevention evaluation study (HOPE), which had investigated the effect of ramipril versus placebo.
TRANSCEND randomized ACE-I intolerant patients with otherwise similar inclusion criteria as ONTARGET to telmisartan 80 mg (n=2954) or placebo (n=2972), both given on top of standard care. The mean duration of follow up was 4 years and 8 months. No statistically significant difference in the incidence of the primary composite endpoint (CV death, non-fatal MI, non-fatal stroke or hospitalization for CHF) was found [15.7% in the telmisartan and 17% in the placebo groups with a hazard ratio of 0.92 (95% CI 0.81-1.05, p=0.22)]. There was evidence for a benefit of telmisartan compared to placebo in the prespecified secondary composite endpoint of CV death, non-fatal MI and non-fatal stroke [0.87 (95% CI 0.76-1, p=0.048)]. There was no evidence for benefit on CV mortality (hazard ratio 1.03, 95% CI 0.85-1.24).
Cough and angioedema were less frequently reported in patients treated with telmisartan than in patients treated with ramipril, whereas hypotension was more frequently reported with telmisartan.
Combining telmisartan with ramipril did not add further benefit over ramipril or telmisartan alone. Cardiovascular mortality and all cause mortality were numerically higher with the combination. In addition, there was a significantly higher incidence of hyperkalemia, renal failure, hypotension and syncope in the combination arm. Therefore, the use of a combination of telmisartan and ramipril is not recommended in this population.
In the prevention regimen for effectively avoiding second strokes (PRoFESS) trial in patients ≥50 years, who recently experienced stroke, an increased incidence of sepsis was noted for telmisartan compared with placebo, 0.7% versus 0.49% [RR 1.43 (95% confidence interval 1-2.06)]; the incidence of fatal sepsis cases was increased for patients taking telmisartan (0.33%) versus patients taking placebo (0.16%) [RR 2.07 (95% confidence interval 1.14-3.76)]. The observed increased occurrence rate of sepsis associated with the use of telmisartan may be either a chance finding or related to a mechanism not currently known.
Teli 80: Angiotensin II is formed from angiotensin I in a reaction catalyzed by ACE (kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal absorption of sodium. Telmisartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectivity blocking the binding of angiotensin II to the AT1 receptor in many tissues eg, vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis. There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis.
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. Whether this difference has clinical relevance is not yet known, 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.
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 hrs after administration, plasma concentrations are similar whether telmisartan is taken fasting or with food.
Linearity/Nonlinearity: The small reduction in area under the plasma concentration-time curve (AUC) is not expected to cause a reduction in the therapeutic efficacy. There is no linear relationship between doses and plasma levels. Maximum plasma concentration (Cmax) and to a lesser extent AUC increase disproportionately at doses >40 mg.
Distribution: Telmisartan is largely bound to plasma protein (>99.5%), mainly albumin and α1-acid glycoprotein. The mean steady-state apparent volume of distribution (Vdss) is approximately 500 L.
Metabolism: Telmisartan is metabolized by conjugation to the glucuronide of the parent compound. No pharmacological activity has been shown for the conjugate.
Elimination: Telmisartan is characterized by biexponential decay pharmacokinetics with a terminal elimination half-life (t½) of >20 hrs. The Cmax and to a smaller extent, the 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 IV) administration, telmisartan is nearly exclusively excreted with the feces, mainly as unchanged compound. Cumulative urinary excretion is <1% of dose. Total plasma clearance (Cltot) is high (approximately 1,000 mL/min) compared with hepatic blood flow (about 1,500 mL/min).
Special Populations: 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 t½ 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 t½ is not changed in patients with hepatic impairment.
Teli 80: General: Following oral administration, Cmax of telmisartan are reached in 0.5-1 hr after dosing. Food slightly reduces the bioavailability of telmisartan, with a reduction in the AUC of about 6% with the 80-mg tablet and about 20% after a 160-mg dose. The absolute bioavailability of telmisartan is dose-dependent. At 40 mg 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 biexponential decay kinetics with a terminal elimination t½ of approximately 24 hrs. Trough plasma concentrations of telmisartan with once daily dosing are about 10-25% of Cmax. Telmisartan has an accumulation index in plasma of 1.5-2 upon repeated once-daily dosing.
Metabolism and Elimination: Following either IV 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 in active acyl 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 (CYP450) isoenzyme are not involved in the metabolism of telmisartan. Total plasma clearance of telmisartan is >800 mL/min. Terminal t½ and total clearance appear to be independent of dose.
Distribution: Telmisartan is highly bound to plasma proteins (>99.5%), mainly albumin and α1-acid glycoprotein. Plasma protein-binding is constant over the concentration range achieved with recommended doses. The volume of distribution for telmisartan is approximately 500 L indicating additional tissue binding.
Toxicology: Preclinical Safety Data: In preclinical safety studies, doses producing exposure comparable to that in the clinical therapeutic range caused reduced red cell parameters (erythrocytes, hemoglobin, hematocrit), changes in renal hemodynamics (increased blood urea nitrogen and creatinine), as well as increased serum potassium in normotensive animals. In dogs, renal tubular dilation and atrophy were observed. Gastric mucosal injury (erosion, ulcers or inflammation) also was noted in rats and dogs. These pharmacologically-mediated undesirable effects, known from preclinical studies with both ACE inhibitors and angiotensin II receptor antagonists, were prevented by oral saline supplementation.
In both species, increased plasma renin activity and hypertrophy/hyperplasia of the renal juxtaglomerular cells were observed. These changes, also a class effect of ACE inhibitors and other angiotensin II receptor antagonists, do not appear to have clinical significance.
No clear evidence of a teratogenic effect was observed, however at toxic levels of telmisartan an effect on the postnatal development of the offsprings eg, lower body weight and delayed eye opening, was observed.
There was no evidence of mutagenicity and relevant clastogenic activity in in vitro studies and no evidence of carcinogenicity in rats and mice.
Indications/Uses
Hypertension: Treatment and management of essential hypertension in adults.
Cardiovascular (CV) Prevention: Reduction of CV morbidity in patients with: Manifestation of atherothrombotic CV disease (history of coronary heart disease, stroke or peripheral arterial disease) or type 2 diabetes mellitus with documented target organ damage.
Dosage/Direction for Use
Dosage must be individualized. Blood pressure response is dose related over the range of 20-80 mg.
Essential Hypertension: Usual Effective Dose: 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 eg, 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 4-8 weeks after the start of treatment.
Cardiovascular Prevention: Recommended Dose: 80 mg once daily. It is not known whether doses telmisartan <80 mg are effective in reducing CV morbidity.
When initiating telmisartan therapy for the reduction of CV morbidity, close monitoring of blood pressure is recommended and if appropriate adjustment of medications that lower blood pressure may be necessary.
Special 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 hemodialysis. 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.
Administration: Telmisartan tablets are for once-daily oral administration and should be taken with liquid, with or without food.
Precautions to be Taken Before Handling or Administering Teli 40/Teli 80: Telmisartan should be kept in the sealed blister due to the hygroscopic property of the tablets. Tablets should be taken out of the blister shortly before administration.
Overdosage
There is limited information available with regard to overdose in humans.
Symptoms: The most prominent manifestations of telmisartan overdose were hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation, dizziness, increase in serum creatinine,and acute renal failure have also been reported.
Treatment: 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.
Contraindications
Hypersensitivity to telmisartan or to any of the excipients of Teli 40/Teli 80.
Second and 3rd trimesters of pregnancy. Biliary obstructive disorders. Severe hepatic impairment.
Use in pregnancy: The use of angiotensin II receptor antagonists is not recommended during the 1st trimester of pregnancy. The use of angiotensin II receptor antagonists is contraindicated during the 2nd and 3rd trimesters of pregnancy.
There are no adequate data from the use of telmisartan in pregnant women. Studies in animals have shown reproductive toxicity .
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the 1st trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. While there is no controlled epidemiological data on the risk with angiotensin II receptor antagonists, similar risks may exist for this class of drugs. 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.
Exposure to angiotensin II receptor antagonist therapy during the 2nd and 3rd trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia).
Should exposure to angiotensin II receptor antagonists have occurred from the 2nd trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for hypotension.
Special Precautions
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.
Hepatic Impairment: Telmisartan is not to be given to patients with cholestasis, biliary obstructive disorders or severe hepatic impairment (see Contraindications) 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.
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.
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.
Intravascular Hypovolemia: Symptomatic hypotension, especially after the 1st dose of telmisartan, may occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhea 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, hyperkalemia 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 [eg, 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 (eg, patients with severe CHF or underlying renal disease, including renal artery stenosis), treatment with medicinal products that affect this system eg, telmisartan has been associated with acute hypotension, hyperazotemia, 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.
Hyperkalemia: The use of medicinal products that affect the renin-angiotensin-aldosterone system may cause hyperkalemia.
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, hyperkalemia 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 hyperkalemia to be considered are: Diabetes mellitus, renal impairment, age (>70 years). Combination with ≥1 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 hyperkalemia are salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs (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 (eg, infectious diseases), cellular lysis (eg, acute limb ischemia, rhabdomyolysis, extend trauma).
Close monitoring of serum potassium in at risk patients is recommended (see Interactions).
Mannitol: This medicinal product contains mannitol (E421). Patients with rare hereditary problems of fructose intolerance should not take Teli tablets.
Ethnic Differences: As observed for ACE 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 ischemic cardiopathy or ischemic CV disease could result in a MI or stroke.
Effects on the Ability to Drive or Operate Machinery: No studies on the effects on the ability to drive and use machines have been performed. However, when driving vehicles or operating machinery it should be taken into account that dizziness or drowsiness may occasionally occur when taking antihypertensive therapy.
Impairment of Fertility: In preclinical studies, no effects of telmisartan on male and female fertility were observed.
Use in lactation: Because no information is available regarding the use of telmisartan during breastfeeding, telmisartan is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant.
Use in children: Telmisartan is not recommended for use in children <18 years due to a lack of data on safety and efficacy.
Use In Pregnancy & Lactation
Use in pregnancy: The use of angiotensin II receptor antagonists is not recommended during the 1st trimester of pregnancy. The use of angiotensin II receptor antagonists is contraindicated during the 2nd and 3rd trimesters of pregnancy.
There are no adequate data from the use of telmisartan in pregnant women. Studies in animals have shown reproductive toxicity.
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the 1st trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. While there is no controlled epidemiological data on the risk with angiotensin II receptor antagonists, similar risks may exist for this class of drugs. 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.
Exposure to angiotensin II receptor antagonist therapy during the 2nd and 3rd trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalemia).
Should exposure to angiotensin II receptor antagonists have occurred from the 2nd trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for hypotension.
Use in lactation: Because no information is available regarding the use of telmisartan during breastfeeding, telmisartan is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant.
Adverse Reactions
Summary of the Safety Profile: Serious adverse drug reactions include anaphylactic reaction and angioedema which may occur rarely (<1 cases/1,000 patients) and acute renal failure.
The overall incidence of adverse events reported with telmisartan (41.4%) was usually comparable to placebo (41.4% vs 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 CV 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 3 clinical long-term studies including 21,642 patients treated with telmisartan for the reduction of CV morbidity for up to 6 years.
Tabulated Summary of Adverse Reactions: 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).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See table.)

Click on icon to see table/diagram/image

Description of Selected Adverse Reactions: Sepsis: 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.
Hypotension: This adverse drug reaction was reported as common in patients with controlled blood pressure who were treated with telmisartan for the reduction of CV morbidity on top of standard care.
Abnormal Hepatic Function/Liver Disorder: Most cases of abnormal hepatic function/liver disorder from post-marketing experience occurred in Japanese patients. Japanese patients are more likely to experience these adverse reactions.
Teli 80: Least as Frequent in the Placebo Group: Influenza-like symptoms, dyspepsia, myalgia, urinary tract infection, abdominal pain, headache, dizziness, pain, fatigue, coughing, hypertension, chest pain, nausea and peripheral edema. The incidence of adverse events was not dose-related and did not correlate with gender, age or race of patients. The incidence of cough occurring with telmisartan in 6 palcebo-controlled trials was identical to that noted for placebo-treated patients (1.6%). In addition, it cannot be determined whether these events were casually related to telmisartan tablets: Autonomic Nervous System: Impotence, increased sweating, flushing.
Body as a Whole: Fever, leg pain, malaise.
Cardiovascular: Palpitation, dependent edema, angina pectoris, tachycardia, leg edema, abnormal ECG.
Central Nervous System: Insomnia, somnolence, migraine, vertigo, paresthesia, involuntary muscle contractions, hypesthesia.
Gastrointestinal: Flatulence, constipation, gastritis, vomiting, dry mouth, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache, nonspecific gastrointestinal disorders.
Metabolic: Gout, hypercholesterolemia, diabetes mellitus.
Musculoskeletal: Arthritis, arthralgia, leg cramps.
Psychiatric: Anxiety, depression, nervousness.
Resistance Mechanism: Infection, fungal infection, abscess, otitis media.
Respiratory: Asthma, bronchitis, rhinitis, dyspnea, epistaxis.
Skin: Dermatitis, rash, eczema, pruritus.
Urinary: Micturition frequency, cystitis.
Vascular: Cerebrovascular disorders.
Special Senses: Abnormal vision, conjunctivitis, tinnitus, earache. During initial clinical studies, a single case of angioedema was reported (among a total of 3,781 patients treated).
Drug Interactions
Interaction Studies have only been Performed in Adults: As with other medicinal products acting on the renin-angiotensin-aldosterone system, telmisartan may provoke hyperkalemia . The risk may increase in case of treatment combination with other medicinal products that may also provoke hyperkalemia [salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs (including selective COX-2 inhibitors), heparin, immunosuppressives (cyclosporin or tacrolimus) and trimethoprim].
The occurrence of hyperkalemia 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 eg, telmisartan, attenuate diuretic induced potassium loss. Potassium-sparing diuretics eg, 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 hypokalemia, 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 ACE 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: Nonteroidal Anti-Inflammatory Medicinal Products: NSAIDs (ie, 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 (eg, dehydrated patients or elderly patients with compromised renal function), the co-administration of angiotensin II receptor antagonists and agents that inhibit cyclo-oxygenase 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 1 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 eg, 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.
Teli 80: Digoxin: When telmisartan was co-administered with digoxin, median increases in digoxin Cmax (49%) and in trough concentration (20%) were observed. It is therefore recommended that digoxin levels be monitored when initiating, adjusting and discontinuing telmisartan to avoid possible over- or under-digitalization.
Warfarin: Telmisartan administered for 10 days slightly decreased the mean warfarin trough plasma concentration; this decrease did not result in a change in international normalized ratio (INR).
Other Drugs: Co-administration of telmisartan did not result in a clinically significant interaction with acetaminophen, amlodipine, glibenclamide, simvastatin, hydrochlorothiazide or ibuprofen. Telmisartan is not metabolized by the CYP450 system and had no effects in vitro on CYP450 enzymes, except for some inhibition of CYP2C19. Telmisartan is not expected to interact with drugs that inhibit CYP450 enzymes; it is also not expected to interact with drugs metabolized by CYP450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by CYP2C19.
Incompatibilities: Not applicable.
Caution For Usage
Special Precautions for Disposal and Other Handling: No special requirements.
Storage
Store below 30°C. Protect from moisture.
Shelf-Life: 24 months.
ATC Classification
C09CA07 - telmisartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
Presentation/Packing
Teli 40: Tab 40 mg (white to off white, oval, uncoated, biconvex, plain on both sides, length: 12.3 mm, width: 6.4 mm) x 30's.
Teli 80: Tab 80 mg (white to off white, oval, uncoated, biconvex, plain on both sides, length: 15.4 mm, width: 8.1 mm) x 30's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in