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Telmichek is an angiotensin II receptor blocker indicated for:
Telmichek is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents [seeClinical Studies (14.1)].
Telmichek is indicated for 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.
High risk for cardiovascular events can be evidenced by a history of coronary artery disease, peripheral arterial disease, stroke, transient ischemic attack, or high-risk diabetes (insulin-dependent or non-insulin dependent) with evidence of end-organ damage . MICARDIS can be used in addition to other needed treatment (such as antihypertensive, antiplatelet or lipid-lowering therapy) .
Studies of Telmichek 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-trying the ACE inhibitor after the cough resolves.
Use of Telmichek with an ACE inhibitor is not recommended .
|Indication||Starting Dose||Dose Range|
|Hypertension (2.1)||40 mg once |
|40 to 80 mg once |
Risk Reduction (2.2)
|80 mg once |
|80 mg once |
Dosage must be individualized. The usual starting dose of Telmichek tablets is 40 mg once a day. Blood pressure response is dose-related over the range of 20 to 80 mg .
Most of the antihypertensive effect is apparent within 2 weeks and maximal reduction is generally attained after 4 weeks. When additional blood pressure reduction beyond that achieved with 80 mg Telmichek is required, a diuretic may be added.
No initial dosage adjustment is necessary for elderly patients or patients with renal impairment, including those on hemodialysis. Patients on dialysis may develop orthostatic hypotension; their blood pressure should be closely monitored.
Telmichek tablets may be administered with other antihypertensive agents.
Telmichek tablets may be administered with or without food.
The recommended dose of Telmichek tablets is 80 mg once a day and can be administered with or without food. It is not known whether doses lower than 80 mg of Telmichek are effective in reducing the risk of cardiovascular morbidity and mortality.
When initiating Telmichek therapy for cardiovascular risk reduction, monitoring of blood pressure is recommended, and if appropriate, adjustment of medications that lower blood pressure may be necessary.
Telmichek is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis or angioedema) to Telmichek or any other component of this product .
Pregnancy Category D
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Telmichek as soon as possible .
In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients, symptomatic hypotension may occur after initiation of therapy with Telmichek. Either correct this condition prior to administration of Telmichek, or start treatment under close medical supervision with a reduced dose.
If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.
Hyperkalemia may occur in patients on ARBs, particularly in patients with advanced renal impairment, heart failure, on renal replacement therapy, or on potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes or other drugs that increase potassium levels. Consider periodic determinations of serum electrolytes to detect possible electrolyte imbalances, particularly in patients at risk.
As the majority of Telmichek is eliminated by biliary excretion, patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Initiate Telmichek at low doses and titrate slowly in these patients .
As a consequence of inhibiting the renin-angiotensin-aldosterone system, anticipate changes in renal function in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure or renal dysfunction), treatment with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar results have been reported with Telmichek .
In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen were observed. There has been no long term use of Telmichek in patients with unilateral or bilateral renal artery stenosis, but anticipate an effect similar to that seen with ACE inhibitors.
As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function (including acute renal failure) have been reported. Dual blockade of the renin-angiotensin-aldosterone system (e.g., by adding an ACE-inhibitor to an angiotensin II receptor antagonist) should include close monitoring of renal function.
The ONTARGET trial enrolled 25,620 patients ≥55 years old with atherosclerotic disease or diabetes with end-organ damage, randomizing them to Telmichek only, ramipril only, or the combination, and followed them for a median of 56 months. Patients receiving the combination of Telmichek and ramipril did not obtain any additional benefit compared to monotherapy, but experienced an increased incidence of renal dysfunction (e.g., acuterenal failure) compared with groups receiving Telmichek alone or ramipril alone. Concomitant use of Telmichek and ramipril is not recommended.
The following adverse reaction is described elsewhere in labeling:
Renal dysfunction upon use with ramipril
To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at (800) 542-6257 or (800) 459-9906TTY, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Because clinical studies are conducted under widely varying conditions, adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
MICARDIS has been evaluated for safety in more than 3700 patients, including 1900 treated for over 6 months and more than 1300 for over one year. Adverse experiences have generally been mild and transient in nature and have infrequently required discontinuation of therapy.
In placebo-controlled trials involving 1041 patients treated with various doses of Telmichek (20 to 160 mg) monotherapy for up to 12 weeks, the overall incidence of adverse events was similar to that in patients treated with placebo.
Adverse events occurring at an incidence of ≥1% in patients treated with Telmichek and at a greater rate than in patients treated with placebo, irrespective of their causal association, are presented in Table 1.
Table 1 Adverse Events Occurring at an Incidence of ≥1% in Patients Treated with Telmichek and at a Greater Rate Than Patients Treated with Placebo
|Upper respiratory tract infection||7||6|
In addition to the adverse events in the table, the following events occurred at a rate of ≥1% but were at 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. Discontinuation of therapy because of adverse events was required in 2.8% of 1455 patients treatedwith Telmichek tablets and 6.1% of 380 placebo patients in placebo-controlled clinical trials.
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 Telmichek in 6 placebo-controlled trials was identical to that noted for placebo-treated patients (1.6%).
In addition to those listed above, adverse events that occurred in more than 0.3% of 3500 patients treated with Telmichek monotherapy in controlled or open trials are listed below. It cannot be determined whether these events were causally related to Telmichek tablets:
Autonomic Nervous System : impotence, increased sweating, flushing; Body as a Whole : allergy, fever, leg pain, malaise; Cardiovascular : palpitation, dependent edema, angina pectoris, tachycardia, leg edema, abnormal ECG; CNS : insomnia, somnolence, migraine, vertigo, paresthesia, involuntary muscle contractions, hypoesthesia; Gastrointestinal : flatulence, constipation, gastritis, vomiting, dry mouth, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache, non-specific 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 disorder; and Special Senses : abnormal vision, conjunctivitis, tinnitus, earache.
During initial clinical studies, a single case of angioedema was reported (among a total of 3781 patients treated).
Clinical Laboratory Findings
In placebo-controlled clinical trials, clinically relevant changes in standard laboratory test parameters were rarely associated with administration of Telmichek tablets.
Hemoglobin: A greater than 2 g/dL decrease in hemoglobin was observed in 0.8% Telmichek patients compared with 0.3% placebo patients. No patients discontinued therapy because of anemia.
Creatinine: A 0.5 mg/dL rise or greater in creatinine was observed in 0.4% Telmichek patients compared with 0.3% placebo patients. One telmisartan-treated patient discontinued therapy because of increases in creatinine and blood urea nitrogen.
Liver Enzymes: Occasional elevations of liver chemistries occurred in patients treated with Telmichek; all marked elevations occurred at a higher frequency with placebo. No telmisartan-treated patients discontinued therapy because of abnormal hepatic function.
Cardiovascular Risk Reduction
Because common adverse reactions were well characterized in studies of Telmichek in hypertension, only adverse events leading to discontinuation and serious adverse events were recorded in subsequent studies of Telmichek for cardiovascular risk reduction. In TRANSCEND (N=5926, 4 years and 8 months of follow-up), discontinuations for adverse events were 8.4% on Telmichek and 7.6% on placebo. The only serious adverse events at least 1% more common on Telmichek than placebo were intermittent claudication (7% vs 6%) and skin ulcer (3% vs 2%).
The following adverse reactions have been identified during post-approval use of Telmichek. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Telmichek.
The most frequent spontaneously reported events include: headache, dizziness, asthenia, coughing, nausea, fatigue, weakness, edema, face edema, lower limb edema, angioneurotic edema, urticaria, hypersensitivity, sweating increased, erythema, chest pain, atrial fibrillation, congestive heart failure, myocardial infarction, blood pressure increased, hypertension aggravated, hypotension (including postural hypotension), hyperkalemia, syncope, dyspepsia, diarrhea, pain, urinary tract infection, erectile dysfunction, back pain, abdominal pain, muscle cramps (including leg cramps), myalgia, bradycardia, eosinophilia, thrombocytopenia, uric acid increased, abnormal hepatic function/liver disorder, renal impairment including acute renal failure, anemia, increased CPK, anaphylactic reaction, tendon pain (including tendonitis, tenosynovitis), drug eruption (toxic skin eruption mostly reported as toxicoderma, rash, and urticaria), hypoglycemia (in diabetic patients), and angioedema (with fatal outcome).
Rare cases of rhabdomyolysis have been reported in patientsreceiving angiotensin II receptor blockers, including Telmichek.
Digoxin : When Telmichek was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. Therefore, monitor digoxin levels when initiating, adjusting, and discontinuing Telmichek for the purpose of keeping the digoxin level within the therapeutic range.
Lithium : Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists including Telmichek. Therefore, monitor serum lithium levels during concomitant use.
Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including Telmichek, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving Telmichek and NSAID therapy.
The antihypertensive effect of angiotensin II receptor antagonists, including Telmichek may be attenuated by NSAIDs including selective COX-2 inhibitors.
Ramipril and Ramiprilat : Co-administration of Telmichek 80 mg once daily and ramipril 10 mg once daily to healthysubjects increases steady-state Cmax and AUC of ramipril 2.3- and 2.1-fold, respectively, and Cmax and AUC of ramiprilat 2.4- and 1.5-fold, respectively. In contrast, Cmax and AUC of Telmichek decrease by 31% and 16%, respectively. When co-administering Telmichek and ramipril, the response may be greater because of the possibly additive pharmacodynamic effects of the combined drugs, and also because of the increased exposure to ramipril and ramiprilat in the presence of Telmichek. Concomitant use of Telmichek and ramipril is not recommended.
Other Drugs : Co-administration of Telmichek did not result in a clinically significant interaction with acetaminophen, amlodipine, glyburide, simvastatin, hydrochlorothiazide, warfarin, or ibuprofen. Telmichek is not metabolized by the cytochrome P450 system and had no effects in vitro on cytochrome P450 enzymes, except for some inhibition of CYP2C19. Telmichek is not expected to interact with drugs that inhibit cytochrome P450 enzymes; it is also not expected to interact with drugs metabolized by cytochrome P450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by CYP2C19.
Pregnancy Category D. .
Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Telmichek as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.
In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Telmichek, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Telmichek for hypotension, oliguria, and hyperkalemia .
It is not known whether Telmichek is excreted in human milk, but Telmichek was shown to be present in the milk of lactating rats. Because of the potential for adverse effects on the nursing infant, decide whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
Safety and effectiveness in pediatric patients have not been established .
Of the total number of patients receiving Telmichek in hypertension clinical studies, 551 (19%) were 65 to 74 years of age and 130 (4%) were 75 years or older. No overall differences in effectiveness and safety were observed in these patients compared to younger patients and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Of the total number of patients receiving Telmichek in the cardiovascular risk reduction study (ONTARGET), the percentage of patients ≥65 to <75 years of age was 42%; 15% of patients were ≥75 years old. No overall differences in effectiveness and safety were observed in these patients compared to younger patients and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Monitor carefully and uptitrate slowly in patients with biliary obstructive disorders or hepatic insufficiency .
Limited data are available with regard to overdosage in humans. The most likely manifestation of overdosage with Telmichek tablets would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmichek is not removed by hemodialysis.
Telmichek is a non-peptide angiotensin II receptor (type AT1) antagonist.
Telmichek is chemically described as 4'-[(1,4'-dimethyl-2'-propyl [2,6'-bi-1H-benzimidazol]-1'-yl)methyl]-[1,1'-biphenyl]-2-carboxylic acid. Its empirical formula is C33H30N4O2, its molecular weight is 514.63, and its structural formula is:
Telmichek is a white to slightly yellowish solid. It is practically insoluble in water and in the pH range of 3 to 9, sparingly soluble in strong acid (except insoluble in hydrochloric acid), and soluble in strong base.
Telmichek is available as tablets for oral administration, containing 20 mg, 40 mg or 80 mg of Telmichek. The tablets contain the following inactive ingredients: sodium hydroxide, meglumine, povidone, sorbitol, and magnesium stearate. Telmichek tablets are hygroscopic and require protection from moisture.
Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme. Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effectsthat include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmichek blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the 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.
There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Telmichek 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 Telmichek does not inhibit ACE (kininase II), it does not affect the response to bradykinin. Whether this difference has clinical relevance is not yet known. Telmichek 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 Telmichek on blood pressure.
In normal volunteers, a dose of Telmichek 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 Telmichek to healthy subjects and repeated administration to hypertensive patients. The once-daily administration of up to 80 mg Telmichek to healthy subjects did not influence plasma aldosterone concentrations. In multiple dose studies with hypertensive patients, there were no clinically significantchanges in electrolytes (serum potassium or sodium), or in metabolic function (including serum levels of cholesterol, triglycerides, HDL, LDL, glucose, or uric acid).
In 30 hypertensive patients with normal renal function treated for 8 weeks with Telmichek 80 mg or Telmichek 80 mg in combination with hydrochlorothiazide 12.5 mg, there were no clinically significant changes from baseline in renal blood flow, glomerular filtration rate, filtration fraction, renovascular resistance, or creatinine clearance.
Following oral administration, peak concentrations (Cmax) of Telmichek are reached in 0.5 to 1 hour after dosing. Food slightly reduces the bioavailability of Telmichek, 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 Telmichek is dose dependent. At 40 and 160 mg the bioavailability was 42% and 58%, respectively. The pharmacokinetics of orally administered Telmichek are nonlinear over the dose range 20 to 160 mg, with greater than proportional increases of plasma concentrations (Cmax and AUC) with increasing doses. Telmichek shows bi-exponential decay kinetics with a terminal elimination half life of approximately 24 hours. Trough plasma concentrations of Telmichek with once daily dosing are about 10% to 25% of peak plasma concentrations. Telmichek has an accumulation index in plasma of 1.5 to 2.0 upon repeated once daily dosing.
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 Telmichek is approximately 500 liters indicating additional tissue binding.
Metabolism and Elimination
Following either intravenous or oral administration of 14C-labeled Telmichek, 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).
Telmichek 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 andurine. 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 Telmichek.
Total plasma clearance of Telmichek is >800 mL/min. Terminal half-life and total clearance appear to be independent of dose.
No dosage adjustment is necessary in patients with decreased renal function. Telmichek is not removed from blood by hemofiltration .
In patients with hepatic insufficiency, plasma concentrations of Telmichek are increased, and absolute bioavailability approaches 100% .
Plasma concentrations of Telmichek are generally 2 to 3 times higher in females than in males. In clinical trials, however, no significant increases in blood pressure response or in the incidence of orthostatic hypotension were found in women. No dosage adjustment is necessary.
The pharmacokinetics of Telmichek do not differ between the elderly and those younger than 65 years .
Telmisartan pharmacokinetics have not been investigated in patients <18 years of age.
There was no evidence of carcinogenicity when Telmichek was administered in the diet to mice and rats for up to 2 years. The highest doses administered to mice and rats (100 mg/kg/day) are, on a mg/m2 basis, about 59 and 13 times, respectively, the maximum recommended human dose (MRHD) of Telmichek. These same doses have been shown to provide average systemic exposures to Telmichek >100 times and >25 times, respectively, the systemic exposure in humans receiving the MRHD (80 mg/day).
Genotoxicity assays did not reveal any telmisartan-related effects at either the gene or chromosome level. These assays included bacterial mutagenicity tests with Salmonella and E. coli (Ames), a gene mutation test with Chinese hamster V79 cells, a cytogenetic test with human lymphocytes, and a mouse micronucleus test.
No drug-related effects on the reproductive performance of male and female rats were noted at 100 mg/kg/day (the highest dose administered), about 13 times, on a mg/m2 basis, the MRHD oftelmisartan. This dose in the rat resulted in an average systemic exposure (telmisartan AUC as determined on day 6 of pregnancy) at least 50 times the average systemic exposure in humans at the MRHD (80 mg/day).
There is no clinical experience with the use of Telmichek tablets in pregnant women. No teratogenic effects were observed when Telmichek was administered to pregnant rats at oral doses of up to 50mg/kg/day and to pregnant rabbits at oral doses up to 45 mg/kg/day. In rabbits, embryolethality associated with maternal toxicity (reduced body weight gain and food consumption) was observed at 45 mg/kg/day [about 12 times the maximum recommended human dose (MRHD) of 80 mg on a mg/m2 basis]. In rats, maternally toxic (reduction in body weight gain and food consumption) Telmichek doses of 15 mg/kg/day (about 1.9 times the MRHD on a mg/m2 basis), administered during late gestation and lactation, were observed to produce adverse effects in neonates, including reduced viability, low birth weight, delayed maturation, and decreased weight gain. Telmichek has been shown tobe present in rat fetuses during late gestation and in rat milk. The no observed effect doses for developmental toxicity in rats and rabbits, 5 and 15 mg/kg/day, respectively, are about 0.64 and 3.7 times, on a mg/m2 basis,the maximum recommended human dose of Telmichek (80 mg/day).
The antihypertensive effects of Telmichek have been demonstrated in six principal placebo-controlled clinical trials, studying a range of 20 to 160 mg; one of these examined the antihypertensive effects of Telmichek and hydrochlorothiazide in combination. The studies involved a total of 1773 patients with mild to moderate hypertension, 1031 of whom were treated with Telmichek. Following once dailyadministration of Telmichek, the magnitude of blood pressure reduction from baseline after placebo subtraction was approximately (SBP/DBP) 6-8/6 mmHg for 20 mg, 9-13/6-8 mmHg for 40 mg, and 12-13/7-8 mmHg for 80 mg. Larger doses (up to 160 mg) did not appear to cause a further decrease in blood pressure.
Upon initiation of antihypertensive treatment with Telmichek, blood pressure was reduced after the first dose, with a maximal reduction by about 4 weeks. With cessation of treatment with Telmichek tablets,blood pressure gradually returned to baseline values over a period of several days to one week. During long term studies (without placebo control) the effect of Telmichek appeared to be maintained for up to at least one year. The antihypertensive effect of Telmichek is not influenced by patient age, gender, weight, or body mass index. Blood pressure response in black patients (usually a low-renin population) is noticeably less than that in Caucasian patients. This has been true for most, but not all, angiotensin II antagonists and ACE inhibitors.
In a controlled study, the addition of Telmichek to hydrochlorothiazide produced an additional dose-related reduction in blood pressure that was similar in magnitude to the reduction achieved with Telmichek monotherapy. Hydrochlorothiazide also had an added blood pressure effect when added to Telmichek.
The onset of antihypertensive activity occurs within 3 hours after administration of a single oral dose. At doses of 20, 40, and 80 mg, the antihypertensive effect of once daily administration of Telmichek ismaintained for the full 24-hour dose interval. With automated ambulatory blood pressure monitoring and conventional blood pressure measurements, the 24-hour trough-to-peak ratio for 40 to 80 mg doses of Telmichek was 70 to 100% for bothsystolic and diastolic blood pressure. The incidence of symptomatic orthostasis after the first dose in all controlled trials was low (0.04%).
There were no changes in the heart rate of patients treated with Telmichek in controlled trials.
Support for use to reduce therisk of cardiovascular events was obtained in a pair of studies. Both enrolledsubjects age ≥55 years, at high cardiovascular risk as evidenced by coronary artery disease (75%), diabetesmellitus (27%) accompanied with end-organ damage (e.g., retinopathy, leftventricular hypertrophy, and, in ONTARGET only, macro- or microalbuminuria),stroke (16%), peripheral vascular disease (13%), or transient ischemic attack(4%). Patients without a history of intolerance to ACE inhibitors enteredONTARGET, and those with such a history, usually cough (90%), entered TRANSCEND,but patients with >1+ proteinuria on dipstick were excluded from TRANSCEND. For both ONTARGET and TRANSCEND trials, the primary4-component composite endpoint was death from cardiovascular causes, myocardialinfarction, stroke, and hospitalization for heart failure. The secondary3-component composite endpoint was death from cardiovascular causes, myocardialinfarction, and stroke.
ONTARGET was a randomized, active-controlled, multinational,double-blind study in 25,620 patients who were randomized to Telmichek 80 mg,ramipril 10 mg, or their combination. The population studied was 73%male, 74% Caucasian, 14% Asian, and 57% were 65 years of age or older. Baseline therapy included acetylsalicylic acid (76%), lipid lowering agents(64%), beta-blockers (57%), calcium channel blockers (34%), nitrates (29%), anddiuretics (28%). The mean duration of follow up was about 4 years and 6months. During the study, 22.0% (n=1878) of Telmichek patientsdiscontinued the active treatment, compared to 24.4% (n=2095) of ramiprilpatients and 25.3% (n=2152) of telmisartan/ramipril patients.
TRANSCEND randomized patientsto Telmichek 80 mg (n=2954) or placebo (n=2972). The mean duration of followup was 4 years and 8 months. Thepopulation studied was 57% male, 62% Caucasian, 21% Asian, and 60% were 65years of age or older. Baseline therapy included acetylsalicylic acid(75%), lipid lowering agents (58%), beta-blockers (58%), calcium channelblockers (41%), nitrates (34%) and diuretics (33%). During the study, 17.7%(n=523) of Telmichek patients discontinued the active treatment, compared to19.4% (n=576) of placebo patients.
The results for the TRANSCENDtrial are summarized in Table 2, and the results for ONTARGET are summarized inTable 3, below:
| *The primary endpoint was defined as the time to first event. In case of multiple simultaneous events, all individual events were considered; the sum of patients with individual outcomes may exceed the number of patients with composite (primary or secondary) outcomes. |
**For individual components of the primary composite endpoints, all events, regardless whether or not they were the first event, were considered. Therefore, they are more than the first events considered for the primary or secondary composite endpoint.
|Telmichek vs. Placebo |
| No. of Events |
Telmichek / Placebo
| Hazard Ratio |
|*Composite of CV death, myocardial infarction, stroke, or hospitalization for heart failure||465 (15.7%) / 504 (17.0%)||0.92 (0.81 – 1.05)||0.2129|
|*Composite of CV death, myocardial infarction, or stroke||384 (13.0%) / 440 (14.8%)||0.87 (0.76 – 1.00)||0.0483|
|Individual components of the primary composite endpoint|| No. of Events |
Telmichek / Placebo
| Hazard Ratio |
|**All non-fatal MI||114 (3.9%) / 145 (4.9%)||0.79 (0.62 – 1.01)||0.0574|
|**All non-fatal strokes||112 (3.8%) / 136 (4.6%)||0.83 (0.64 – 1.06)||0.1365|
|Telmichek vs. Ramipril |
| No. of Events |
Telmisartan / Ramipril
| Hazard Ratio |
|Composite of CV death, myocardial infarction, stroke, or hospitalization for heart failure||1423 (16.7%) / 1412 (16.5%)||1.01 (0.93 – 1.10)|
|Composite of CV death, myocardial infarction, or stroke||1190 (13.9%) / 1210 (14.1%)||0.99 (0.90 – 1.08)|
Althoughthe event rates in ONTARGET were similar on Telmichek and ramipril, theresults did not unequivocally rule out that Telmichek may not preserve ameaningful fraction of the effect of ramipril in reducing cardiovascular events. However, theresults of both ONTARGET and TRANSCEND do adequately support Telmichek beingmore effective than placebo would be in this setting, particularly for the end pointof time to cardiovascular death, myocardial infarction, or stroke.
In ONTARGET, there was noevidence that combining ramipril and Telmichek reduced the risk of death fromcardiovascular causes, myocardial infarction, stroke, or hospitalization for heartfailure greater than ramipril alone; instead, patients who received thecombination of ramipril and Telmichek in ONTARGET experienced an increasedincidence of clinically important renal dysfunction (e.g., acute renal failure)compared to patients receiving Telmichek or ramipril alone.
Multiple sub-group analysesdid not demonstrate any differences in the 4-component composite primaryendpoint based on age, gender, or ethnicity for either ONTARGET or TRANSCENDtrial.
Telmichek is available as white or off-white, uncoated tablets containing Telmichek 20 mg, 40 mg, or 80 mg. Tablets are marked with the BOEHRINGER INGELHEIM logo on one side, and on the other side, with either 50H, 51H, or 52H for the 20 mg, 40 mg, and 80 mg strengths, respectively. Tablets are provided as follows:
Telmichek tablets 20 mg are round and individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0039-37).
Telmichek tablets 40 mg are oblong shaped and individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0040-37).
Telmichek tablets 80 mg are oblong shaped and individually blister-sealed in cartons of 30 tablets as 3 x 10 cards (NDC 0597-0041-37).
Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). Tablets should not be removed from blisters until immediately before administration.
See FDA-approved Patient Labeling
Female patients of childbearing age should be told about the consequences of exposure to Telmichek during pregnancy. Discuss treatment options with women planning to become pregnant. Patients should be asked to report pregnancies to their physicians as soon as possible .
Boehringer Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA
Licensed from: Boehringer Ingelheim International GmbH, Ingelheim, Germany
Copyright 2012 Boehringer Ingelheim International GmbH
ALL RIGHTS RESERVED
Read this Patient Information before you start taking Telmichek tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.
What is the most important information I should know about Telmichek tablets?
Telmichek can cause harm or death to an unborn baby. Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant. If you get pregnant while taking Telmichek, tell your doctor right away.
What is Telmichek?
Telmichek is a prescription medicine used:
It is not known if Telmichek is safe and effective in children.
Who should not take Telmichek?
You should not take Telmichek tablets if you are allergic (hypersensitive) to the active ingredient (telmisartan) or any of the other ingredients listed at the end of this leaflet.
What should I tell my doctor before taking Telmichek tablets?
Before you take Telmichek tablets, tell your doctor if you:
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.
Telmichek may affect the way other medicines work, and other medicines may affect how Telmichek works. Especially tell your doctor if you take:
Know the medicines you take. Keep a list of them and show it to your doctor or pharmacist when you get a new medicine.
How should I take Telmichek tablets?
What are the possible side effects of Telmichek tablets?
Telmichek tablets may cause serious side effects, including:
Rare, serious allergic reactions may happen. Tell your doctor right away if you get any of these symptoms:
The most common side effects of Telmichek tablets include:
These are not all the possible side effects with Telmichek tablets. Tell your doctor if you have any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Telmichek tablets?
Keep Telmichek tablets and all medicines out of the reach of children.
General information about Telmichek tablets
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Telmichek tablets for a condition for which it was not prescribed. Do not give MICARDIStablets to other people, even if they have the same condition you have. It may harm them.
This Patient Information leaflet summarizes the most important information about Telmichek tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor forinformation about Telmichek tablets that is written for health professionals.
For more information, call Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257, or (TTY) 1-800-459-9906.
What are the ingredients in Telmichek tablets?
Active Ingredient: Telmichek
Inactive Ingredients: sodium hydroxide, meglumine, povidone, sorbitol, and magnesium stearate
What is High Blood Pressure (Hypertension)?
Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too much. Telmichek tablets can help your blood vessels relax so your blood pressure is lower. High blood pressure makes the heart work harder to pump blood throughout the body and causes damage to the blood vessels. If high blood pressure is not treated, it can lead to stroke, heart attack, heart failure, kidney failure, and vision problems.
What is Cardiovascular Risk?
Patients older than 55 years of age who have been diagnosed with blood vessel disease in the heart, legs, or brain (coronary, peripheral, or cerebral vascular disease) or diabetes with end organ damage (for example: kidney, heart, and brain) are at higher risk of cardiovascular events (for example: death from cardiovascular causes, stroke, and/or heart attack).
How to open the blister:
1. Tear (You may also use scissors to tear the blister apart)
2. Peel (Peel off the paper layer from the aluminum foil)
3. Push (Push the tablet through the foil)
Boehringer Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA
Licensed from: Boehringer Ingelheim International GmbH, Ingelheim, Germany
Copyright 2012 Boehringer Ingelheim International GmbH
ALL RIGHTS RESERVED
Revised: January 2012
Tear the blister apart Peel off the paper layer from the aluminum foil Push (Push the tablet through the foil)
Depending on the reaction of the Telmichek after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Telmichek not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Telmichek addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology