Telmisartan/Amlodipine: Single-pill combination in hypertension.. - (Page 658)

658 Frampton a low potential for interactions between telmisartan and drugs metabolized by CYP isoenzymes.[8] 3.1 Drug Interactions Undesirable consequences of RAAS blockade that have been reported in susceptible patients, especially those receiving combinations of medications that inhibit this system, include hypotension, syncope, hyperkalaemia and acute renal failure.[10] The EU summary of product characteristics (SPC)[10] states that dual blockade of the RAAS (e.g. by adding an ACE inhibitor to an ARB) is not recommended in patients with already controlled BP and should be limited to individually defined cases with close monitoring of renal function. With specific reference to the use of the drug in the setting of CVD prevention, concomitant administration of telmisartan with ramipril is not recommended in patients represented in the ONTARGET trial[10] (see sections 4.1, 6 and 7). Combining telmisartan with other products that may also provoke hyperkalaemia (e.g. potassium supplements, potassium-sparing diuretics, ACE inhibitors, NSAIDs [including cyclo-oxygenase-2 selective inhibitors], heparin, immunosuppressives [ciclosporin or tacrolimus] and trimethoprim) increases the risk of this condition occurring.[10] The risk is particularly high in combination with potassium supplements and potassium-sparing diuretics; therefore, concomitant use of telmisartan and these products is not recommended.[10] Caution is recommended when coadministering an ARB (e.g. telmisartan) with an NSAID, as the latter may reduce the antihypertensive effect of the former. Additionally, this combination may cause further deterioration of renal function in some patients in whom renal function is already compromised.[10] Caution is also advised when initiating telmisartan in patients who may be volume depleted as a result of prior high-dose diuretic (thiazide or loop) therapy, and therefore are at increased risk of hypotension.[10] 4. Therapeutic Efficacy The efficacy of telmisartan in preventing cardiovascular events in individuals at high vasª 2011 Adis Data Information BV. All rights reserved. cular risk has been evaluated in three large, randomized, double-blind, multinational trials, namely the pivotal ONTARGET study (n = 25 620 randomized patients; section 4.1) and the supporting TRANSCEND (n = 5926; section 4.2) and PRoFESS (n = 20 332; section 4.3) studies. The design and results of the main ONTARGET[68,69,77-79] and TRANSCEND[70,71,77-79] trials have been published in full, as have those of the PRoFESS trial.[75,80,81] The protocols for three ONTARGET and/or TRANSCEND substudies assessing arterial stiffness,[82] cardiac structure[83] and sexual function[84] have also been described in detail. To date, findings from the ONTARGET cardiac magnetic resonance imaging (MRI) substudy[85] and ONTARGET/ TRANSCEND-erectile dysfunction substudy[86] are available; however, the erectile dysfunction substudy results are not discussed in this article. 4.1 ONTARGET The ONTARGET trial was a noninferiority comparison of telmisartan 80 mg once daily and ramipril 10 mg once daily for the prevention of cardiovascular events in high-risk patients with CVD or diabetic end-organ damage, but without heart failure.[68] The inclusion/exclusion criteria for this study are listed in table III. Ramipril 10 mg/day was chosen as the comparator following the demonstration in the HOPE study that this ACE inhibitor, at this dosage, significantly reduced the incidence of the combined primary endpoint of cardiovascular death, non-fatal MI and non-fatal stroke compared with placebo in a broad range of high-risk patients who did not have a low ejection fraction or heart failure (14.0% vs 17.8%; relative risk 0.78, 95% CI 0.70, 0.86; p < 0.001)[87-89] The ONTARGET trial included a third arm: combined treatment with telmisartan 80 mg once daily plus ramipril 10 mg once daily.[68] However, the EU SPC[10] does not recommend the use of this combination in patients represented in this trial (see section 3.1); hence, findings for combination therapy are not discussed in this section, although they are briefly described in section 7. Drugs 2011; 71 (6)

Table of Contents for the Digital Edition of Telmisartan/Amlodipine: Single-pill combination in hypertension..

Telmisartan/Amlodipine: Single-pill combination in hypertension..
Contents
Abstract
Introduction
Pharmacodynamic Properties
Anti-Inflammatory Effects
Endothelial Effects
Metabolic Effects
Cardiovascular Effects
Renal Effects
Cerebrovascular Effects
Pharmacokinetic Properties
Drug Interactions
Therapeutic Efficacy
ONTARGET
TRANSCEND
PRoFESS
Pooled Analyses of the TRANSCEND and PRoFESS studies
Tolerability
Comparisons with Placebo

Telmisartan/Amlodipine: Single-pill combination in hypertension..