Low Dose Combination Antihypertensive Therapy Additional Efficacy Without Additional Adverse Effects?

MacConnachie, A.M.; Maclean, Derek

doi:10.2165/00002018-199512020-00001

Cited by 23 publications

(13 citation statements)

References 21 publications

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“…An alternative strategy for improving blood pressure control is to combine 2 or more drugs with different but complementary mechanisms of action. Combination therapy (at lower doses of each drug) may result in fewer adverse effects and enhanced patient efficacy plus compliance [17,50]. Normalization of blood pressure has been achieved in up to 80% of patients treated with different combination therapies [11,22,30,31].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Pharmacokinetic Interaction between Candesartan Cilexetil and Felodipine

Abib¹,

Duarte²,

Oliveira³

et al. 2011

JBB

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The study was performed to evaluate the pharmacokinetic interaction of test formulation of candesartan 16 mg tablet and felodipine extended release 5 mg tablet together in a combination package, comparing with the fasting period intake of commercial formulations of both Atacand® 16 mg tablet and Splendil® extended release 5 mg tablet (Test formulation and reference formulation from AstraZeneca, Brazil) in 36 volunteers of both sexes. The study was conducted open with randomized three period crossover design and a one week wash out period. The candesartan and felodipine were analyzed by LC-MS-MS. The mean ratio of parameters C max and AUC 0-t and 90% confidence intervals of correspondents were calculated to determine the pharmacokinetic interaction. Geometric mean of candesartan exposure together in a combination package felodipine individual percent ratio was 102.51% AUC 0-t and 110.40% for C max . The 90% confidence intervals were 90.00 -116.77% and 93.94 -129.74%, respectively. Geometric mean of felodipine exposure together in a combination package candesartan individual percent ratio was 102.69% AUC 0-t and 96.17% for C max . The 90% confidence intervals were 89.46 -117.88% and 82.07 -112.69%, respectively. The major variable in this respect, AUC, was not signicantly affected by felodipine and candesartan with concomitant administration. The Cmax of candesartan was not signicantly affected by co-administration of felodipine. Based on these data and in presence in the market of isolated candersatana and felodipino formularizations used in combination in medical practice, it is concluded that there are no risk with concomitant administration between felodipine and candesartan.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the Pharmacokinetic Interaction between Candesartan Cilexetil and Felodipine

Abib¹,

Duarte²,

Oliveira³

et al. 2011

JBB

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“…Average prescribed daily dose of thiazides (equivalent to 37 mg hydrochlorothiazide) was well above the recommended daily dose for hypertension in the elderly (12.5 mg). Excessive thiazide dosing should be avoided, since most adverse effects are dose‐dependent [28]. Thiazides may have been prescribed in higher doses for heart failure or ankle oedema.…”

Section: Discussionmentioning

confidence: 99%

Prescription patterns of diuretics in Dutch community‐dwelling elderly patients

Kraaij

Jansen

Gier

et al. 1998

Brit J Clinical Pharma

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Aims To describe age-and gender-related prescription patterns of diuretics in community-dwelling elderly, and to compare diuretics to other cardiovascular (CV) medications. Methods Cross-sectional study of patient-specific prescription data derived from a panel of 10 Dutch community pharmacies. Determination of proportional prescription rates and prescribed daily dose (PDD) of diuretics, cardiac glycosides, nitrates, angiotensin converting enzyme (ACE) inhibitors, b-adrenoceptor blockers, and calcium channel blockers in all 5326 patients aged 65 years or older dispensed CV medications between August 1st, 1995 and February 1st, 1996. Results Diuretics were prescribed to 2677 of 5326 patients (50.3%), 1325 patients (24.9%) using thiazides and 1198 patients (22.5%) using loop diuretics. Prescription rates of loop diuretics increased from 15.1% in patients aged 65-74 years to 37.2% in patients aged 85 years or older. Rates also increased for digoxin and nitrates. Rates for thiazide diuretics remained unchanged with age; rates for b-adrenoceptor blockers, ACE inhibitors and calcium channel blockers declined with age. Thiazides were prescribed to 30.1% of women compared with 16% of men ( P<0.001). Average PDD was 135±117% of defined daily dose (DDD) for loop diuretics, and highest for bumetanide (245±2.01% of DDD, equivalent to 2.5±2.0 mg). Average PDD was 74±40% of DDD for thiazides, and highest for chlorthalidone (100±49% of DDD, equivalent to 25±12 mg). Conclusions Important characteristics of diuretic usage patterns in this elderly population were a steep increase in loop diuretic use in the oldest old, a large gender difference for thiazide use, and high prescribed doses for thiazides.

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“…Furthermore, the pharmacologic action of one drug of the combination may attenuate an AE of the other. 8 Reduced frequency and severity of AEs may contribute to improved patient compliance, resulting in a greater number of patients at goal BP and subsequently reducing mortality and morbidity.…”

Section: Rationale For Combination Therapymentioning

confidence: 99%

Patients with uncontrolled hypertension or concomitant hypertension and benign prostatic hyperplasia

Zusman

2004

Clinical Cardiology

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Summary: At optimal doses, individual antihypertensive agents lower blood pressure (BP) by an average of 10 mmHg. Many patients with hypertension, including those with stage 3 hypertension, target organ damage, or those at high risk for cardiovascular events and/or adverse effects of high-dose monotherapy, are likely to require combination antihypertensive drug treatment to achieve the recommended systolic/diastolic BP (< 140/90 mmHg). Two studies, a placebo-controlled, double-blind trial (n = 70) and a community-based, open-label trial (n = 491) investigated the antihypertensive efficacy of doxazosin, a long-acting selective ␣ 1 -adrenoceptor blocker, as add-on therapy for uncontrolled hypertension with other antihypertensive medications and in patients with concomitant benign prostatic hyperplasia (BPH) and treated but inadequately controlled hypertension, respectively. The addition of doxazosin to baseline antihypertensive medication(s) significantly lowered BP and had a significantly positive effect on the serum lipid profile. In patients with concomitant BPH, doxazosin significantly improved all BPH symptom scores, regardless of initial symptom severity. Add-on doxazosin sufficiently reduced systolic/diastolic BP such that many patients whose hypertension was previously uncontrolled by other antihypertensive medications were able to reach goal BP (< 140/90 mmHg). Doxazosin as add-on therapy was well tolerated. In conclusion, doxazosin as add-on therapy improves BP control in hypertensive patients not at goal BP and improves lower urinary tract symptoms in patients with concomitant BPH.

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Low Dose Combination Antihypertensive Therapy Additional Efficacy Without Additional Adverse Effects?

Cited by 23 publications

References 21 publications

Evaluation of the Pharmacokinetic Interaction between Candesartan Cilexetil and Felodipine

Evaluation of the Pharmacokinetic Interaction between Candesartan Cilexetil and Felodipine

Prescription patterns of diuretics in Dutch community‐dwelling elderly patients

Patients with uncontrolled hypertension or concomitant hypertension and benign prostatic hyperplasia

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