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PubMedDate not supplied

Comparison of a fixed-dose combination of 40 mg telmisartan plus 12.5 mg hydrochlorothiazide with 40 mg telmisartan in the control of mild to moderate hypertension.

This study investigated whether a fixed-dose combination of 40 mg of the angiotensin II antagonist telmisartan plus 12.5 mg of the diuretic hydrochlorothiazide (HCTZ) was superior to 40 mg telmisartan in patients with mild to moderate hypertension who failed to respond adequately to 40 mg telmisartan monotherapy. One hundred forty-six patients were withdrawn before randomization. Nonresponders (n = 327) were double blind and randomized to 40 mg telmisartan + 12.5 mg HCTZ (n = 160) or 40 mg telmisartan (n = 167). After 8 weeks of treatment, 40 mg telmisartan + 12.5 mg HCTZ lowered diastolic blood pressure (DBP) by an additional 3.5 mm Hg (P <.01) and systolic blood pressure (SBP) by 7.4 mm Hg (P <.01) compared with 40 mg telmisartan. Most of the additional effect of the combination was seen after 4 weeks of treatment. At week 8, blood pressure was normalized (SBP <140 mm Hg and DBP <90 mm Hg) in 51.6% of patients on 40 mg telmisartan + 12.5 mg HCTZ compared with 23.5% on 40 mg telmisartan (P <.05). The combination of 40 mg telmisartan + 12.5 mg HCTZ normalized DBP in 64.8% of patients, whereas 40 mg telmisartan normalized DBP in 40.1% (P <.05). SBP decreased by > or =10 mm Hg from baseline in 63.5% of patients receiving the fixed-dose combination compared with 42.6% of those receiving 40 mg telmisartan (P <.05). Both treatments were well tolerated. Adverse events were predominantly mild, transient, and considered unrelated to therapy. These findings indicate that a fixed-dose combination of 40 mg telmisartan + 12.5 mg HCTZ is clinically and statistically superior to 40 mg telmisartan in patients with mild to moderate hypertension failing to respond to 40 mg telmisartan alone.

Adult↗

PubMed2001

Telmisartan plus hydrochlorothiazide versus telmisartan or hydrochlorothiazide monotherapy in patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: Recent surveys reveal continuing deficiencies in the awareness, treatment, and control of hypertension. In many cases, failure to achieve blood pressure targets may be attributable to the use of antihypertensive monotherapy. OBJECTIVES: This study was undertaken to identify combinations of telmisartan, a new oral angiotensin II type 1-receptor antagonist, and hydrochlorothiazide (HCTZ) that might provide greater antihypertensive efficacy than monotherapy with either agent in the treatment of mild to moderate hypertension. It also examined the dose-response surface for the 2 drugs alone and in combination. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that employed all cells of a 4 x 5 factorial design. After a 4-week, single-blind, placebo run-in period, men and women between 18 and 80 years of age with mild to moderate hypertension (defined as mean supine diastolic blood pressure [DBP] between 95 and 114 mm Hg during the last 2 weeks of the placebo run-in period and systolic blood pressure [SBP] between 114 and 200 mm Hg immediately before randomization) were eligible to enter the 8-week, double-blind, double-dummy treatment period. Study comparisons were between once-daily telmisartan monotherapy (20, 40, 80, or 160 mg), HCTZ monotherapy (6.25, 12.5, or 25 mg), 12 combinations of these telmisartan/HCTZ doses, and placebo. The focus was on 2 combinations: telmisartan 40 mg/HCTZ 12.5 mg and telmisartan 80 mg/HCTZ 12.5 mg. The primary efficacy variable was change in supine trough DBP from baseline to the last evaluable measurement during double-blind treatment. Plasma renin activity and safety parameters, including treatment-emergent adverse events, physical findings, electrocardiograms, and serum electrolyte levels (which are known to increase with HCTZ treatment), were also assessed. RESULTS: Of 1293 patients screened, 818 (63.3%) were enrolled at 47 centers. Of these 818, 749 (91.6%) completed the study. The intent-to-treat population (randomized with > or = 1 postrandomization blood pressure measurement) consisted of 807 patients (98.7%). Telmisartan 80 mg/HCTZ 12.5 mg significantly decreased mean supine trough SBP/DBP by 23.9/14.9 mm Hg, a benefit of 8.5/3.4 mm Hg compared with telmisartan 80 mg and of 17.0/7.6 mm Hg compared with HCTZ 12.5 mg (both comparisons, P < 0.01). Telmisartan 40 mg/HCTZ 12.5 mg significantly reduced mean supine SBP by 18.8 mm Hg, a benefit of 6.6 mm Hg compared with telmisartan 40 mg and 11.9 mm Hg compared with HCTZ 12.5 mg (both, P < 0.01). This same combination significantly reduced mean supine DBP by 12.6 mm Hg, a benefit of 5.3 mm Hg compared with HCTZ 12.5 mg (P < 0.01), but was not significantly different from telmisartan 40 mg. Telmisartan 80 mg/HCTZ 12.5 mg was significantly more effective than telmisartan 40 mg/HCTZ 12.5 mg in reducing mean supine DBP and SBP (both, P < 0.05). The response surface and responder analyses confirmed the additive antihypertensive efficacy of the combination of telmisartan and HCTZ. All regimens were well tolerated. CONCLUSIONS: Once-daily telmisartan 80 mg/HCTZ 12.5 mg was effective and well tolerated when used to reduce SBP and DBP in patients with mild to moderate hypertension. In addition to enhancing efficacy, this combination protected against potassium depletion, a common side effect of thiazide monotherapy.

Adolescent↗

PubMed2001

Efficacy and tolerability of a fixed-dose combination of telmisartan plus hydrochlorothiazide in patients uncontrolled with telmisartan monotherapy.

The antihypertensive effects of a telmisartan 80 mg/hydrochlorothiazide (HCTZ) 12.5 mg fixed-dose combination and telmisartan 80 mg monotherapy were compared in patients with a history of mild-to-moderate essential hypertension and inadequate BP control (DBP > or = 90 mm Hg) following 8 weeks of telmisartan monotherapy. At the end of this period, 491 patients (62.9% men; mean age 55.3 years) whose DBP was > or = 90 mm Hg were double-blind randomised to once-daily telmisartan 80 mg/HCTZ 12.5 mg (n = 246) or telmisartan 80 mg (n = 245). Trough (24 h post-dose) clinic BP was measured after 4 and 8 weeks of double-blind therapy. At the end of double-blind treatment, patients receiving telmisartan 80 mg/HCTZ 12.5 mg had significant additional decrements in clinic SBP/DBP over telmisartan 80 mg of -5.7/-3.1 mm Hg (P < 0.01). Most of the additional effect occurred during the first 4 weeks of treatment. The proportion of patients with normalised BP (SBP < 140 mm Hg and DBP < 90 mm Hg) was significantly greater in the telmisartan 80 mg/HCTZ 12.5 mg group than the telmisartan 80 mg group (41.5%vs 26.1%;P < 0.05). Both treatments were well tolerated. The incidence of adverse events was similar except for diarrhoea, which occurred more frequently in the telmisartan 80 mg/HCTZ 12.5 mg group, and oedema, which occurred more frequently in the telmisartan group. Our results indicate that a telmisartan 80 mg/HCTZ 12.5 mg fixed-dose combination confers significant additional BP reductions compared with continuation of telmisartan monotherapy in non-responders.

Adult↗

PubMed2004

Angiotensin II receptor antagonist telmisartan in isolated systolic hypertension (ARAMIS) study: efficacy and safety of telmisartan 20, 40 or 80 mg versus hydrochlorothiazide 12.5 mg or placebo.

OBJECTIVE: To identify telmisartan doses that are more effective than placebo and non-inferior to hydrochlorothiazide (HCTZ) 12.5 mg, and are well tolerated, in lowering systolic blood pressure (SBP) in patients with isolated systolic hypertension (ISH). PATIENTS AND METHODS: A 2-4-week single-blind placebo run-in was followed by randomization of 1039 patients (age 36-84 years) with ISH [seated SBP 150-179 mmHg and seated diastolic blood pressure (DBP) < 90 mmHg] to once-daily double-blind treatment with telmisartan 20, 40 or 80 mg, HCTZ 12.5 mg, or placebo. The change in seated trough SBP after 6 weeks compared with baseline was the primary end point. Secondary end points were the percentage achieving the target fall in SBP and the change from baseline in seated trough DBP. Incidence and severity of adverse events and physical examination and laboratory parameters were monitored for the safety evaluation. RESULTS: Baseline demographics in telmisartan 20 mg (n = 206), 40 mg (n = 210), 80 mg (n = 207), HCTZ 12.5 mg (n = 205) and placebo (n = 211) treatment groups were comparable: (mean +/- SD) age, 63.0 +/- 10.9 years; SBP, 162.9 +/- 8.1 mmHg; and DBP 83.4 +/- 5.0 mmHg. No previous antihypertensive therapy had been received by 66% of the patients. Mean reductions in seated trough SBP (adjusted for baseline and country) were: telmisartan 20 mg, 15.6 mmHg (n = 204); 40 mg, 17.9 mmHg (n = 209); and 80 mg, 16.9 mmHg (n = 205), compared with placebo, 11.4 mmHg (n = 208), and HCTZ 12.5 mg, 15.7 mmHg (n = 204). The target fall in seated trough SBP (< or =140 mmHg or reduction by > or =20 mmHg) was achieved in 46.6% (telmisartan 20 mg), 51.7% (telmisartan 40 mg), 53.9% (telmisartan 80 mg), 27.4% (placebo) and 42.7% (HCTZ 12.5 mg); the response rate was significantly higher for telmisartan 80 mg than for HCTZ 12.5 mg (P = 0.03). All-causality adverse events occurred in 19.9, 17.6 and 20.3% receiving telmisartan 20, 40 and 80 mg, respectively; 20.9% receiving placebo and 22.0% receiving HCTZ 12.5 mg. No drug-related serious adverse events occurred. CONCLUSIONS: All doses of telmisartan (20-80 mg) were significantly superior to placebo in reducing SBP in patients with ISH and clinically comparable to HCTZ 12.5 mg. Tolerability of telmisartan was similar to that of placebo.

Adult↗

PubMed2003

The telmisartan programme of research tO show Telmisartan End-organ proteCTION (PROTECTION) programme.

Angiotensin-II receptor blockers (ARBs) have been shown to provide stroke, cardiac and renal protection in high-risk hypertensive patients. Telmisartan is a powerful and selective ARB that provides sustained blood pressure reduction for a full 24 h after a single dose and continues to protect against circadian blood pressure surges in the critical early morning hours. The objective of the Programme of Research tO show Telmisartan End-organ proteCTION (PROTECTION) is to measure the end-organ protective effects of telmisartan in patients at high risk of renal, cardiac and vascular damage. An extensive series of clinical trials is being conducted to compare telmisartan with valsartan, losartan, amlodipine and ramipril in patients at increased risk of end-organ damage. Nine clinical studies will examine the effects of telmisartan in about 5000 hypertensive patients with isolated systolic hypertension, type 2 diabetes, obesity, left ventricular hypertrophy or renal disease. All of the studies will be conducted using state-of-the-art technology, including such techniques as ambulatory blood pressure monitoring and magnetic resonance imaging. This programme will also investigate the effects of an ARB on key surrogate markers of organ tissue damage. This series of trials will characterize the end-organ protective effects of telmisartan in hypertensive patient populations at high risk of clinical events.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2004

Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, myocardial infarction, stroke, heart failure, need for revascularization, nephropathy, and diabetes and its complications. Although angiotensin-II receptor blockers (ARBs) have been less extensively evaluated, theoretically they may have "protective" effects similar to those of ACE inhibitors, but with better tolerability. Currently, there is uncertainty about the role of ARBs when used alone or in combination with an ACE inhibitor in high-risk populations with controlled hypertension. OBJECTIVES: Primary objectives of the ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) are to determine if the combination of the ARB telmisartan and the ACE inhibitor ramipril is more effective than ramipril alone, and if telmisartan is at least as effective as ramipril. The Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) will determine if telmisartan is superior to placebo in patients who are intolerant of ACE inhibitors. The primary outcome for both trials is the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. METHOD: High-risk patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage are being recruited and followed for 3.5 to 5.5 years in 2 parallel, randomized, double-blind clinical trials. PROGRESS: Recruitment from 730 centers in 40 countries for ONTARGET (n = 25,620) was completed in July 2003. For TRANSCEND, 5776 patients (out of a projected total of 6000) have been recruited (by May 10, 2004). Baseline patient characteristics are comparable to the Heart Outcomes Prevention Evaluation (HOPE) trial, the basis of the design of the current study, confirming that patients are at high-risk.

Aged↗

PubMedDate not supplied

The telmisartan renoprotective study from incipient nephropathy to overt nephropathy--rationale, study design, treatment plan and baseline characteristics of the incipient to overt: angiotensin II receptor blocker, telmisartan, Investigation on Type 2 Diabetic Nephropathy (INNOVATION) Study.

We planned the INNOVATION study to determine whether telmisartan, an angiotensin-2-receptor blocker, delays the progression of renal disease from incipient nephropathy to overt nephropathy in hypertensive or normotensive Japanese patients with type 2 diabetes mellitus. The INNOVATION study is a randomized, double-blind, placebo-controlled trial. Eligible patients must have incipient nephropathy (defined as a urinary albumin to creatinine ratio of 100-300 mg/g creatinine) and a serum creatinine concentration of < 1.5 mg/dl for men and < 1.3 mg/dl for women. Patients who need treatment with angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors are excluded. Eligible patients are randomly assigned to three groups: telmisartan titrated to 40 mg; telmisartan titrated to 80 mg; or placebo. The primary endpoint is the time from baseline visit to first detection of overt nephropathy (defined by a urinary albumin to creatinine ratio that is > 300 mg/g creatinine and 30% higher than the baseline on at least two consecutive visits). A total of 1855 patients have been enrolled from 160 study centres. In 527 randomized patients (28.4% of the enrolled patients), mean (SD) urinary albumin to creatinine ratio and serum creatinine concentration at baseline were 173.3 (47.2) mg/g creatinine and 0.78 (0.19) mg/dl. Sixty-eight per cent of the patients had hypertension at baseline. Mean (SD) systolic and diastolic blood pressures at baseline were 137.1 (14.6) and 77.5 (10.3) mmHg. The INNOVATION study will determine whether telmisartan, an angiotensin II receptor blocker, provides clinical benefits in hypertensive or normotensive patients with diabetes mellitus and diabetic nephropathy.

Aged↗

PubMed1999

The incidence of cough: a comparison of lisinopril, placebo and telmisartan, a novel angiotensin II antagonist. Telmisartan Cough Study Group.

Dry cough is a troublesome side-effect associated with certain antihypertensive agents that act by modulating aspects of the renin-angiotensin-aldosterone system. The incidence of dry cough associated with two of these therapies, the novel All receptor antagonist telmisartan and the ACE inhibitor lisinopril, was assessed in a multicentre, randomised, parallel-group, double-blind, placebo-controlled, 8-week study of 88 patients with mild to moderate hypertension who previously demonstrated ACE inhibitor-related cough. Patients received either telmisartan 80 mg, lisinopril 20 mg, or placebo once daily. Cough incidence, measured at each visit by a self-administered symptom assessment questionnaire, was significantly higher with lisinopril (60%) than with telmisartan (15.6%) or placebo (9.7%). A visual analogue scale demonstrated a similar trend for cough frequency. Thus the incidence of cough with telmisartan 80 mg is significantly less than that seen with lisinopril 20 mg and is comparable to placebo.

Adolescent↗

PubMed2000

Dose response and safety of telmisartan in patients with mild to moderate hypertension.

This randomized, double-blind, double-dummy, placebo-controlled, parallel-group study evaluated the dose-response relationship of telmisartan in 207 patients with mild to moderate hypertension (diastolic blood pressure [DBP] 100 to 114 mmHg). After a 28-day placebo run-in period, patients were randomized to 28 days of once-daily, double-blind, double-dummy treatment with telmisartan 40, 80, or 120 mg; enalapril 20 mg; or placebo. Blood pressure (BP) was manually recorded for 12 hours after the first dose and after 24 hours at baseline (Day 0), Day 1, and Day 28 of double-blind treatment. Pharmacokinetic and pharmacodynamic parameters were assessed from telmisartan plasma concentrations. All doses of telmisartan and enalapril significantly reduced BP compared with placebo (p < or = 0.01). Mean +/- SE reductions in supine DBP after 28 days of treatment ranged between 7.9 +/- 1.3 mmHg and 9.8 +/- 1.3 mmHg in the telmisartan groups, 9.6 +/- 1.3 mmHg with enalapril, and 1.5 +/- 1.3 mmHg with placebo. Mean +/- SE reductions in supine systolic blood pressure (SBP) were between 10.0 +/- 2.2 mmHg and 15.5 +/- 2.2 mmHg with telmisartan versus 10.2 +/- 2.1 mmHg with enalapril; placebo increased supine SBP by 3.5 +/- 2.1 mmHg. The BP reductions after 4 weeks of treatment with telmisartan were no different from those achieved with enalapril. No significant linear trend in BP reduction was evident among telmisartan doses. Reductions in SBP and DBP were maintained over the 24-hour period at Day 28. Treatment did not affect supine heart rate. Trough/peak DBP ratios were > or = 85% for all telmisartan doses versus 65% for enalapril. High interpatient variability in telmisartan plasma concentrations was observed. For example, mean +/- SD values for Cmax were 159 +/- 104 ng/mL for telmisartan 40 mg, 693 +/- 606 ng/mL for telmisartan 80 mg, and 1635 +/- 1406 ng/mL for telmisartan 120 mg. Plasma concentration-effect analyses indicated that the antihypertensive effects of telmisartan 40, 80, and 120 mg are at the plateau region of the concentration-response curve. All active treatments were well tolerated, with tolerability profiles similar to placebo, and telmisartan did not produce any clinically relevant first-dose effects. These data confirm the antihypertensive efficacy and placebo-like tolerability of telmisartan.

Adolescent↗

PubMed2000

Pharmacokinetics and safety of intravenous and oral telmisartan 20 mg and 120 mg in subjects with hepatic impairment compared with healthy volunteers.

The pharmacokinetics and safety of telmisartan were assessed in subjects with hepatic impairment in a single-center, open-label study. Single oral doses of telmisartan 20 mg and 120 mg, separated by a washout period of 14 days, were given to 12 hepatically impaired subjects and 12 healthy subjects. In 5 hepatically impaired subjects who received both oral doses, a single i.v. infusion of telmisartan 120 mg was later administered. After oral dosing, the pharmacokinetic profile of telmisartan was characterized by rapid absorption and disposition kinetics and a slow terminal elimination phase with mean half-lives of 27 to 42 hours. The maximum plasma concentration and area under the telmisartan plasma concentration-time curve (AUC0-infinity) increased in hepatically impaired subjects compared with healthy volunteers 6.4-fold and 2.7-fold, respectively, for telmisartan 20 mg and 3.2-fold and 3.1-fold, respectively, for telmisartan 120 mg. Maximum plasma concentrations and AUC0-infinity after i.v. infusion were markedly elevated compared with values obtained from other studies conducted in healthy volunteers. Hepatic impairment resulted in an apparent increase in the absolute bioavailability of telmisartan, and total clearance following oral and i.v. administration was significantly reduced compared with healthy volunteers. Plasma protein binding of telmisartan was > or = 99.5% in hepatically impaired and healthy subjects and was not changed when compared to healthy subjects. Oral and i.v. telmisartan were well tolerated in both the hepatically impaired and the healthy; headache was the most common potentially telmisartan-related adverse event. Changes in vital signs and clinical laboratory parameters were transient and of no clinical relevance. The good tolerability of telmisartan in hepatically impaired patients demonstrated in this study, the proven sustained blood pressure control in hypertensive patients, and the increased exposure in patients with hepatic dysfunction suggest that effective treatment of hypertensive patients with impaired hepatic function would be achieved even with the lowest dose of telmisartan available. The increased bioavailability of telmisartan suggests that lower doses of telmisartan should be considered when the drug is administered to patients with hepatic impairment.

Administration, Oral↗

PubMed2002

Long-term exposure to telmisartan as monotherapy or combination therapy: efficacy and safety.

This multicentre, open-label extension study to four controlled trials involved 888 patients with mild-to-moderate primary hypertension. Patients received telmisartan 40-80 mg once daily with add-on hydrochlorothiazide (HCTZ; 12.5-25 mg) if necessary and/or other antihypertensives to achieve diastolic blood pressure (DBP) control (<90 mmHg). Treatment continued for up to 4 years. At treatment end, 578 (65.1%) patients were on telmisartan monotherapy, 106 (11.9%) were on telmisartan + HCTZ 12.5 mg, 101 (11.4%) were on telmisartan + HCTZ 25 mg, and 103 (11.6%) were on telmisartan + another antihypertensive + HCTZ. Overall, 84.4% (746/884) patients achieved DBP control. The highest proportion of responders was in the telmisartan monotherapy (40 or 80 mg) treatment category (89.0% 1,511/574 patients]). The mean change in systolic blood pressure (SBP)/DBP from the previous trial baseline to last available trough was -21.2/-17.3 mmHg with telmisartan alone, -24.6/-16.7 mmHg with telmisartan + HCTZ, and - 18.7/-14.9 mmHg with telmisartan + another antihypertensive +/- HCTZ. Most adverse events were of mild-to-moderate intensity and unrelated to treatment. The proportions of patients discontinuing the study due to adverse events, by treatment at onset, were 7.3% (65/888) with telmisartan monotherapy, 6.6% (20/304) with telmisartan + HCTZ and 2.9% (3/103) with telmisartan + another antihypertensive +/- HCTZ. There were 15 deaths during the study, but none was considered drug related. Thus, telmisartan alone or in combination with other antihypertensives achieved and maintained clinically relevant reductions in DBP and SBP. This long-term analysis supports the favourable efficacy and safety profile of telmisartan both as monotherapy and in combination with other antihypertensive drugs.

Adult↗

PubMed2005

Transepithelial transport of telmisartan in caco-2 monolayers.

Telmisartan is the most recently marketed angiotensin II type 1 receptor antagonist. Drug-drug interactions involving transporters can directly affect the therapeutic safety and efficacy of many important drugs. In clinical practice, telmisartan is coadministered with many kinds of drugs. However, little is known about the contribution of transporters to the intestinal transport of telmisartan. The aim of this study was to determine the transport mechanism of telmisartan across intestinal epithelial cells. In the presence of an inwardly directed proton gradient, the apical-to-basal transport of telmisartan was greater than basal-to-apical transport. Thus, we focused on the uptake mechanism of telmisartan across brush-border membranes. The uptake of telmisartan by Caco-2 cells was shown to be energy- and proton-dependent. Although some monocarboxylates inhibited the uptake of telmisartan, L-lactic acid, which is a typical substrate of the monocarboxylate transporter (MCT) 1-MCT4, did not affect the uptake of telmisartan. Preloading of acetic acid enhanced the uptake of telmisartan, showing a trans-stimulation effect. These results suggest that the carrier-mediated transport system is involved in the uptake of telmisartan by Caco-2 cells and that the apical-localized transport system is similar to MCTs, but not MCT1-MCT4. It is possible that telmisartan reduce the absorption of coadministered drugs by sharing the MCTs. Since MCTs have an important role in the intestinal absorption of pharmacologically active compounds, it is important to be aware of the potential of telmisartan-drug interactions involving MCTs and to act in order to prevent undesirable and harmful consequences.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2001

Inhibitory effect of telmisartan on the blood pressure response to angiotensin II challenge.

Telmisartan is a new angiotensin receptor antagonist possessing potent, selective, and insurmountable inhibitory activity specific to the angiotensin II type 1 (AT 1 ) receptor. The current study was performed to determine the inhibition of the angiotensin II pressor response by telmisartan in 48 healthy volunteers challenged with hypertension-inducing doses of i.v. angiotensin II. Subjects were challenged with this dose of angiotensin II at intervals between 0.25 and 48 h after double-blind single-dose oral administration of telmisartan 20 mg (n = 12), 40 mg (n = 12), or 80 mg (n = 12) or placebo (n = 12) in parallel groups. Diastolic and systolic blood pressure and pulse rate were recorded continuously using a servophotoplethysmograph. Urine samples were collected during the study for urinalysis. Tolerability of telmisartan, in comparison with placebo, was also monitored throughout the study. Telmisartan 20-80 mg dose dependently inhibited the increase in diastolic and systolic blood pressure induced by angiotensin II. Telmisartan 40 mg produced 80.1% maximum inhibition, and with 80 mg 89.6% maximum inhibition of diastolic blood pressure was achieved. Inhibition was apparent after 0.3-1.1 h and was still observed 48 h after administration for all telmisartan doses. The inhibitory effect of telmisartan 20, 40, and 80 mg, 48 h after dosing was significantly greater than that of placebo. A > 25% inhibition of the angiotensin II response on diastolic blood pressure was detected until 26.9, 35.4, and 40.5 h, respectively, after telmisartan 20 mg, 40 mg, and 80 mg. Anti-clockwise hysteresis was observed, indicating a delay and longer persistence of effect than to be expected from the plasma concentration-time course. The slow dissociation of telmisartan from the receptor probably contributed to this hysteresis. The incidence of adverse events was comparable in telmisartan-and placebo-treated subjects and was not dose dependent. In conclusion, telmisartan 40 mg provides rapid-onset, well-tolerated, and near-maximal inhibition of angiotensin II-induced hypertension, with maintenance of the inhibitory effect for 48 h.

Adult↗

PubMedDate not supplied

Pharmacokinetics of orally and intravenously administered telmisartan in healthy young and elderly volunteers and in hypertensive patients.

A series of studies was conducted in healthy young males and healthy elderly males or females to evaluate the pharmacokinetic profile of telmisartan. In addition, two phase-II clinical trials assessed the pharmacokinetics and the safety of telmisartan in mild-to-moderate hypertensive patients. Telmisartan was given as a single oral (1-160 mg) or intravenous (10-160 mg) dose to young males. In another multiple-dose study, telmisartan 320 mg was administered orally once daily for 7 days to healthy young male subjects. Elderly subjects received oral telmisartan (20 and 120 mg) once daily for 7 days. Telmisartan doses of 10, 20, 40, 80, 120 and 160 mg were taken once daily by mild-to-moderate hypertensive patients for 7 days. Additionally, oral telmisartan (40, 80 or 120 mg) was administered once daily for 28 days to hypertensive subjects. Following oral dosing, median time to maximum plasma telmisartan concentration was 0.5 - 2 h, with maximum plasma concentrations increasing disproportionately with dose. By contrast, plasma concentrations were directly related to the intravenous dose. Steady state was observed after 5-7 days of once-daily administration, and there was no clinically relevant accumulation at 28 days. The plasma concentration-time profiles were similar in all study groups and were characterized by fast absorption and a rapid biexponential decline after the peak plasma concentration, with a prolonged terminal elimination phase (> 20 h in healthy and hypertensive subjects). Telmisartan was well tolerated, with a low incidence of drug-related adverse events. The most frequent event was headache, which also occurred in placebo-treated control subjects. No changes in heart rate, electrocardiograms or clinical chemistry were detected following receipt of telmisartan. The study thus shows that high systemic levels of telmisartan, which are well tolerated, can be attained in healthy adults of any age and in hypertensive subjects. The long terminal elimination half-life makes telmisartan suitable for once-daily dosing and contributes to the sustained efficacy over the full 24-h dosing interval.

Administration, Oral↗

PubMed2001

Telmisartan: a review of its use in hypertension.

UNLABELLED: Telmisartan is an angiotensin II receptor antagonist that is highly selective for type 1 angiotensin II receptors. It was significantly more effective than placebo in large (n >100), double-blind, randomised, multicentre clinical trials in patients with mild to moderate hypertension. Telmisartan 20 to 160 mg once daily produced mean reductions in supine trough systolic blood pressure and diastolic blood pressure of up to 15.5 and 10.5 mm Hg, respectively. Maximum blood pressure reduction occurred with a dosage of 40 to 80 mg/day. Telmisartan 40 to 120 mg/day was as effective as amlodipine 5 to 10 mg/day or atenolol 50 to 100 mg/day in dose-titration studies. Telmisartan 20 to 160 mg/day was generally similar in efficacy to enalapril 5 to 20 mg/day or lisinopril 10 to 40 mg/day in both titration-to-response and other studies. Hydrochlorothiazide was coadministered in most of the titration-to-response studies if patients remained hypertensive. Telmisartan 80 mg/day was more effective than submaximal dosages of losartan (50 mg/day) or valsartan (80 mg/day) and was as effective as a fixed-dose combination of losartan 50 mg plus hydrochlorothiazide 12.5 mg over the last 6 hours of the dosage interval and the whole 24-hour postdose interval. In patients with severe hypertension, telmisartan 80 to 160 mg/day was as effective as enalapril 20 to 40 mg/day (both agents could be titrated and combined sequentially with hydrochlorothiazide 25 mg and amlodipine 5 mg). The addition of hydrochlorothiazide to telmisartan was more effective than each agent alone at lowering blood pressure in patients with hypertension. Telmisartan was well tolerated in patients with mild to moderate hypertension and was significantly less likely to cause persistent, dry cough than lisinopril. CONCLUSION: Telmisartan is an effective antihypertensive agent with a tolerability profile similar to that of placebo. Comparative data have shown telmisartan to be as effective as other major classes of antihypertensive agents at lowering blood pressure. Compared with lisinopril, telmisartan is associated with a significantly lower incidence of dry, persistent cough. Therefore, telmisartan is a useful therapeutic option in the management of patients with hypertension.

Angiotensin II↗

PubMed2026

Telmisartan-based monotherapy and combination regimens for blood pressure control in adults with hypertension: a systematic review, meta-analysis, and GRADE assessment.

PURPOSE: To evaluate the efficacy, safety, and certainty of evidence for telmisartan-based antihypertensive regimens in adults with hypertension. METHODS: This systematic review and meta-analysis followed PRISMA 2020. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL were searched from inception to 2026. Eligible studies enrolled adults with hypertension and compared telmisartan monotherapy or telmisartan-containing combinations with placebo, usual care, non-telmisartan antihypertensive agents, or alternative telmisartan-based regimens. Continuous outcomes were pooled as mean differences (MDs) and dichotomous outcomes as risk ratios (RRs), both with 95% confidence intervals (CIs), using random-effects models, with additional subgroup analyses conducted by comparator type. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated using GRADE. RESULTS: Twenty-five included reports (24 unique trials, since two reports present secondary outcomes from the same underlying trial) involving 6,521 participants were included, spanning placebo-controlled, usual-care-controlled, active-comparator, and telmisartan-combination-versus-telmisartan-monotherapy designs. Telmisartan-based therapy significantly reduced office systolic blood pressure (MD - 6.39 mm Hg; 95% CI - 7.86 to - 4.93; low certainty) and office diastolic blood pressure (MD - 4.88 mm Hg; 95% CI - 6.67 to - 3.09; low certainty), although the magnitude of effect was comparator-dependent. Based on only two trials, 24-h ambulatory systolic blood pressure (MD - 7.16 mm Hg; 95% CI - 10.61 to - 3.72) and ambulatory diastolic blood pressure (MD - 4.42 mm Hg; 95% CI - 6.36 to - 2.48) were reduced with moderate certainty. Telmisartan-based regimens improved blood pressure response (RR 1.68; 95% CI 1.31 to 2.16; moderate certainty) but not blood pressure control achievement (RR 1.44; 95% CI 0.92 to 2.24; very low certainty). Overall adverse events, dizziness, and headache were comparable (very low to low certainty), while edema was less frequent with telmisartan-based therapy (RR 0.33; 95% CI 0.15 to 0.73; moderate certainty). CONCLUSION: Telmisartan-based regimens, particularly fixed-dose and multidrug combinations, effectively reduce office and ambulatory blood pressure and improve blood pressure response, with broadly comparable short-term safety and less edema. These effect sizes are comparator-dependent, and certainty of evidence for absolute blood pressure control achievement and for major adverse events is very low; heterogeneity, limited long-term data, and a predominance of Asian-population trials warrant cautious interpretation pending larger, higher-quality, and more geographically diverse confirmatory studies.

Humans↗

PubMed1999

Disposition and chemical stability of telmisartan 1-O-acylglucuronide.

Telmisartan 1-O-acylglucuronide, the principal metabolite of telmisartan in humans, was characterized in terms of chemical stability and the structure of its isomerization products was elucidated. In addition, pharmacokinetics of telmisartan 1-O-acylglucuronide were assessed in rats after i.v. dosing. Similar to other acylglucuronides, telmisartan 1-O-acylglucuronide and diclofenac 1-O-acylglucuronide, which was used for comparison, showed the formation of different isomeric acylglucuronides on incubation in aqueous buffer. The isomeric acylglucuronides of telmisartan consisted of the 2-O-, 3-O-, and 4-O-acylglucuronides (alpha,beta-anomers). First order degradation half-lives of 26 and 0. 5 h were observed on incubation in buffer of pH 7.4 for the 1-O-acylglucuronides of telmisartan and diclofenac, respectively. This indicated that the 1-O-acylglucuronide of telmisartan was among the most stable acylglucuronides reported to date. The high stability of telmisartan 1-O-acylglucuronide was confirmed by in vitro experiments that indicated only very low covalent binding of telmisartan acylglucuronide to human serum albumin but a considerable amount of covalently bound radioactivity with the acylglucuronide of diclofenac. After i.v. dosing to rats, telmisartan 1-O-acylglucuronide was rapidly cleared from plasma with a clearance of 180 ml/min/kg, compared with 15.6 ml/min/kg for the parent compound. Because telmisartan 1-O-acylglucuronide exhibited a comparably high chemical stability together with a high clearance that resulted in low systemic exposure, the amount of covalent binding to proteins should be negligible compared with other frequently used drugs, such as furosemide, ibuprofen, or salicylic acid.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2006

A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring.

BACKGROUND: Blood pressure (BP) has a circadian pattern with a morning surge that is associated with an increased risk of acute coronary and cerebrovascular events. In a prospective, randomized, open-label, blinded-endpoint, parallel-group, multicenter, forced-titration study of telmisartan and ramipril, the efficacy of both drugs on mean ambulatory diastolic BP (DBP) and systolic BP (SBP) during the last 6 h of a 24-h dosing interval was evaluated. METHODS: After screening and a single-blind run-in phase, 812 adults with mild-to-moderate hypertension (defined as a mean seated DBP > or =95 mm Hg and < or =109 mm Hg and a 24-h ABPM mean DBP 7 > or = 85 mm Hg) were randomized to the open-label, 14-week, forced-titration, active-treatment phase as follows: telmisartan 40 mg/80 mg/80 mg (n = 405) or ramipril 2.5 mg/5 mg/10 mg (n = 407), once daily in the morning. The primary efficacy variable was change from baseline in the last 6-h mean DBP and SBP at 8 and 14 weeks as assessed by ambulatory BP monitoring (ABPM). Secondary efficacy variables were changes from baseline in BP control during each of the 24-h periods and in-clinic trough cuff BP. RESULTS: Telmisartan 80 mg was superior to ramipril 5 mg and 10 mg in change from baseline in the last 6-h ABPM mean DBP and SBP at both 8 and 14 weeks (both P < .0001), respectively. At 14 weeks, the adjusted mean change from baseline in DBP for telmisartan 80 mg was -8.8 mm Hg compared with that for ramipril 10 mg of -5.4 mm Hg (P < .0001). For SBP, the adjusted mean change from baseline for telmisartan 80 mg was -12.7 mm Hg compared with that for ramipril 10 mg of -7.9 mm Hg (P < .0001). At 14 weeks, telmisartan 80 mg also yielded superior reductions from baseline in trough cuff BP compared with ramipril 10 mg (DBP: -11.0 mm Hg v -7.8 mm Hg, respectively; SBP: -14.3 mm Hg v -9.1 mm Hg, respectively; both P < .0001). Measures of 24-h BP control favored telmisartan 80 mg versus ramipril 10 mg (P < .0001), as did other secondary ABPM endpoints during the daytime, night-time, and morning periods. Treatment-related adverse events were uncommon; patients treated with ramipril had a higher incidence of cough than those treated with telmisartan (10.1% v 1.5%, respectively). CONCLUSIONS: Telmisartan 80 mg was consistently more effective than ramipril 10 mg in reducing both DBP and SBP during the last 6 h of the dosing interval, a measure of the early morning period when patients are at greatest risk of life-threatening cardiovascular and cerebrovascular events. Telmisartan 80 mg was also more effective than ramipril 10 mg in reducing BP throughout the entire 24-h dosing interval. Both drugs were well tolerated.

Adult↗