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The interaction of tramadol with ondansetron or droperidol on antinociception can be antagonistic or additive, depending on the type of stimuli. Both anti-emetics antagonize the anti-transit effects of tramadol. The results demonstrate antagonism between tramadol and the two anti-emetics for analgesia and inhibition of gastrointestinal transit, supporting previous clinical studies.

BackgroundPatients with hypertension and cardiovascular disease (CVD), diabetes, or chronic kidney disease (CKD) usually require two or more antihypertensive agents to achieve blood pressure (BP) goals.MethodsThe efficacy/safety of olmesartan (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg versus the component dual-combinations (OM 40/AML 10 mg, OM 40/HCTZ 25 mg, and AML 10/HCTZ 25 mg) was evaluated in participants with diabetes, CKD, or chronic CVD in the Triple Therapy with Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients Study (TRINITY). The primary efficacy end point was least squares (LS) mean reduction from baseline in seated diastolic BP (SeDBP) at week 12. Secondary end points included LS mean reduction in SeSBP and proportion of participants achieving BP goal (<130/80 mm Hg) at week 12 (double-blind randomized period), and LS mean reduction in SeBP and BP goal achievement at week 52/early termination (open-label period).ResultsAt week 12, OM 40/AML 10/HCTZ 25 mg resulted in significantly greater SeBP reductions in participants with diabetes (−37.9/22.0 mm Hg vs −28.0/17.6 mm Hg for OM 40/AML 10 mg, −26.4/14.7 mm Hg for OM 40/HCTZ 25 mg, and −27.6/14.8 mm Hg for AML 10/HCTZ 25 mg), CKD (−44.3/25.5 mm Hg vs −39.5/23.8 mm Hg for OM 40/AML 10 mg, −25.3/17.0 mm Hg for OM 40/HCTZ 25 mg, and −33.4/20.6 mm Hg for AML 10/HCTZ 25 mg), and chronic CVD (−37.8/20.6 mm Hg vs −31.7/18.2 mm Hg for OM 40/AML 10 mg, −30.9/17.1 mm Hg for OM 40/HCTZ 25 mg, and −27.5/16.1 mm Hg for AML 10/HCTZ 25 mg) (P<0.05 for all subgroups vs dual-component treatments). BP goal achievement was greater for participants receiving triple-combination treatment compared with the dual-combination treatments, and was achieved in 41.1%, 55.0%, and 38.9% of participants with diabetes, CKD, and chronic CVD on OM 40/AML 10/HCTZ 25 mg, respectively. At week 52, there was sustained BP lowering with the OM/AML/HCTZ regimen. Overall, the triple combination was well tolerated.ConclusionsIn patients with diabetes, CKD, or chronic CVD, short-term (12 weeks) and long-term treatment with OM 40/AML 10/HCTZ 25 mg was well tolerated, lowered BP more effectively, and enabled more participants to reach BP goal than the corresponding 2-component regimens.Trial Identification NumberNCT00649389

Registered at ClinicalTrials.gov as NCT00649389.

This 12-week, multicenter, randomized, double-blinded, 4-arm study in 440 patients with moderate to severe hypertension compared ambulatory blood pressure (ABP) responses with a triple-combination regimen (olmesartan medoxomil [OM] 40 mg, amlodipine besylate [AML] 10 mg, and hydrochlorothiazide [HCTZ] 25 mg) and its component dual-combination regimens at similar doses. At week 12, the triple combination resulted in a greater reduction in mean 24-hour systolic and diastolic blood pressure ()30.3 ⁄)18.0 mm Hg) compared with the 3 dual-combination regimens (OM 40 mg ⁄AML 10 mg:)23.5 ⁄)13.9, OM 40 mg ⁄HCTZ 25 mg: )23.9 ⁄)14.5, and AML 10 mg ⁄HCTZ 25 mg: )18.5 mm Hg ⁄)10.7 mm Hg; P<.0001 each). Greater efficacy was also found during daytime and nighttime hours and during the last 6, 4, or 2 hours of the dosing interval. 1 Achieving this level of control typically requires the use of !2 classes of antihypertensive drugs 2-4 that have complementary mechanisms of action. Ideal combinations should also incorporate component drugs with sufficient durations of action in order to reduce the morning surge in BP and the early morning peak in myocardial infarction and stroke. [5][6][7] In order to study such effects, it is necessary to use ambulatory BP monitoring (ABPM), which not only distinguishes sustained hypertension from white-coat hypertension, but also allows the study of diurnal variation and true 24-hour drug efficacy. 2,7-11The Triple Therapy With Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients Study (TRINITY) demonstrated that a 3-drug regimen of olmesartan medoxomil (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg reduced office seated DBP (SeDBP) and SBP (SeSBP) to a greater degree and achieved a higher rate of BP goal attainment than any of the 3 component dual-combinations. 12 The objective of this prespecified TRINITY substudy was to compare 24-hour BP patterns and control rates at baseline and week 12 in a nested subgroup. Specific measured variables included mean daytime (8 AM-4 PM) and nighttime (10 PM-6 AM) BP values, with additional comparisons among treatments during the final 6, 4, and 2 hours of the dosing interval. METHODS Study DesignMethods for TRINITY have previously been described in detail.12 This multicenter (N=317), randomized, double-blind, 12-week, parallel-group study compared the triple-combination regimen (OM 40 mg ⁄AML 10 mg ⁄HCTZ 25 mg) with its component dual-combination regimens in patients with moderate to severe hypertension. To be eligible for randomization, all patients had to be 18 years or older and had to have a mean SeBP !140 ⁄100 mm Hg (SeSBP !140 mm Hg and SeDBP !100 mm Hg) or SeBP !160 ⁄90 mm Hg (SeSBP !160 mm Hg and SeDBP !90 mm Hg) at two consecutive visits during the washout period. Excluded were patients with secondary hypertension, recent ( 6 months) cerebrovascular or coronary artery disease, New York Heart Association class III or IV heart failure, uncontrolled diabetes (defined as glycated hemog...

Most patients with hypertension require combination therapy in order to achieve blood pressure (BP) goals. This 40-week open-label extension of the 12-week double-blind Triple Therapy With Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hypertensive Patients Study (TRINITY) evaluated the efficacy and safety of triplecombination treatments with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide (OM ⁄ AML ⁄ HCTZ) in 2112 participants with moderate to severe hypertension. Following 2 weeks of initial treatment with OM 40 ⁄ AML 5 ⁄ HCTZ 12.5 mg, participants not achieving BP goal were titrated to OM 40 ⁄ AML 5 ⁄ HCTZ 25 mg or OM 40 ⁄ AML 10 ⁄ HCTZ 12.5 mg on a randomized basis. At week 16, participants who did not achieve BP goal were further titrated to OM 40 ⁄ AML 10 ⁄ HCTZ 25 mg. At the end of the study, 44.5% to 79.8% of participants reached BP goal and the mean BP decreased from 168.6 ⁄ 100.7 mm Hg (baseline BP at randomization) to 125.0 to 136.8 mm Hg ⁄ 77.8 to 82.5 mm Hg, depending on treatment. Longterm treatment with OM ⁄ AML ⁄ HCTZ was well tolerated and effective with no new safety concerns.

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