Switching Therapy from Variable-Dose Multiple Pill to Fixed-Dose Single-Pill Combinations of Angiotensin II Receptor Blockers and Thiazides for Hypertension

Sakima, Atsushi; Ohshiro, Kazuiku; Nakada, Seigo; Yamazato, Masanobu; Kohagura, Kentaro; Nakamoto, Minori; Tana, Takeshi; Ohya, Yusuke

doi:10.3109/10641963.2010.549260

Cited by 8 publications

(3 citation statements)

References 27 publications

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“…The combination therapy improves patient compliance, simplifies the regimen by reducing the number of drugs and the frequency of dosing, reduces costs, and may produce a superior blood pressure lowering effect in some patients. 17 , 18 Therefore, the combination of fimasartan, amlodipine, and rosuvastatin is expected to be effective against both hypertension and dyslipidemia and to inhibit the development of cardiovascular disease. In this study, we aimed to compare the pharmacokinetics (PK) and safety profiles of fixed-dose combination (FDC) of fimasartan, amlodipine, and rosuvastatin with the co-administration of the three drugs in healthy male subjects.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of fimasartan, amlodipine, and rosuvastatin using partial replicated design in healthy adult subjects

Ghim

Park

et al. 2018

DDDT

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ObjectiveThe aim of this study was to compare the pharmacokinetics (PK) and safety profiles of a fixed-dose combination (FDC) formulation of fimasartan, amlodipine, and rosuvastatin with the co-administration of the two products by using a replicated crossover study design in healthy male subjects.ResultsThis was an open-label, randomized, three-sequence, three-period replicated crossover study in healthy male subjects. The replicated crossover design was done because of high coefficient of variation of PK parameter for fimasartan, that is, >30%. With a 14 days washout period, an FDC tablet containing 60 mg fimasartan, 10 mg amlodipine, and 20 mg rosuvastatin was administered only once, and separate formulations of fimasartan/amlodipine 60 mg/10 mg FDC tablet and 20 mg rosuvastatin tablet administered twice. Blood samples were collected up to 72 hours following drug administration. The plasma concentrations of fimasartan, amlodipine, and rosuvastatin were measured by liquid chromatography tandem mass spectrometry. Safety was assessed by evaluating vital signs, clinical laboratory parameters, physical examinations, and medical interviews.ResultsThe geometric mean ratios and 90% confidence intervals (CIs) for the maximum plasma concentration (Cmax) and area under the curve from time zero to the last measurable sampling time (AUCt) were 1.0776 (0.9201–1.2622) and 0.9978 (0.9538–1.0439) for fimasartan, 1.0038 (0.9782–1.0301) and 1.0055 (0.9828–1.0288) for amlodipine, and 1.0006 (0.9290–1.0776) and 0.9986 (0.9532–1.0461) for rosuvastatin, respectively. A total of 22 adverse events (AEs) were reported by 60 subjects; there were no significant differences in the incidence of AEs between the two groups.ConclusionThe 90% CI of the Cmax of fimasartan was within the widened acceptance limit, ln(0.6984)–ln(1.4319). The 90% CIs of the other PK parameters for drugs were between ln(0.8) and ln(1.25). These results suggest that the FDC formulation is pharmacokinetically bioequivalent and has a similar safety profile, to the co-administration of its three constituent drugs.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of fimasartan, amlodipine, and rosuvastatin using partial replicated design in healthy adult subjects

Ghim

Park

et al. 2018

DDDT

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“…Reflecting the clinical evidence, including the findings of the ACCOMPLISH study [4], an angiotensin-receptor blocker (ARB) together with a calcium-channel blocker (CCB) is the combination most frequently prescribed to Japanese hypertensive patients [5,6]. For patients who have comorbidities such as hyperlipidemia, diabetes, and chronic renal disease, more aggressive treatment, with the addition of thiazide diuretics (i.e., hydrochlorothiazide or HCTZ) is provided to achieve therapeutic goals [7]. Because those patients need to take multiple medications in a day, the complex regimen often affects the patients’ adherence to the treatments.…”

Section: Introductionmentioning

confidence: 99%

Economic impact of switching to fixed-dose combination therapy for Japanese hypertensive patients: a retrospective cost analysis

Akazawa

Fukuoka²

2013

BMC Health Serv Res

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BackgroundThe prescription of fixed-dose combinations (FDC) of antihypertensive drugs has increased rapidly since the relaxation of the prescription-term restriction.In this study, we used the opportunity of this policy change in Japan as an instrument to assess the causal impact of switching to FDC on hypertensive treatment costs.MethodsClaims data from 64 community pharmacies located in Tokyo were used to identify hypertensive patients under continuous treatment with angiotensin-receptor blockers (ARBs). Patients switching to FDC between December 2010 and April 2011 were compared to patients who did not receive FDC (control group). Changes in annual antihypertensive drug costs were compared using a difference-in-differences approach to adjust for patient characteristics and use of concomitant medication. Subpopulation analyses were also performed, taking into account pre-index treatment patterns and prescribers’ characteristics.ResultsThere were 542 patients who switched to FDC and 9664 patients in the control group. No significant differences were observed between the 2 groups, except for antihypertensive drug use patterns before the policy change and prescribers’ characteristics. The switch to FDC was associated with an annual saving of 10,420 yen (US$112.0) in antihypertensive drug costs. Approximately 20% of the FDC patients, however, switched from ARB alone, and their drug costs increased by 2376 yen (US$25.5).ConclusionsFor hypertensive patients who required ARB-based combination therapy, switching to FDC drugs had a significant cost-saving effect. However, the policy change of relaxing the prescription-term restriction could encourage aggressive treatment, i.e., switching to a combination therapy from monotherapy, regardless of medical conditions. Further research is required to evaluate the possible negative aspects of FDC drugs.

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“…3 Fixeddose combinations have the advantage of delivering multiple treatments in a single dosage form and have been shown to improve both adherence to treatment and achievement of BP targets. 4 A fixed-dose combination of losartan potassium 50 mg (L50), an angiotensin II receptor blocker, and hydrochlorothiazide 12.5 mg (H12.5), a thiazide diuretic, was approved as PREMINENT LD (Merck, Whitehouse Station, NJ, USA) in Japan in 2006. The higher-dose combination of losartan 100 mg (L100)/H12.5 (MK-0954A) has also been approved as PREMINENT HD (Merck) in Japan in 2013.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of losartan 100 mg/hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension: two randomized, controlled trials

Rakugi

Tsuchihashi

Shimada³

et al. 2014

Hypertens Res

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Two randomized studies were designed to assess the safety, tolerability and efficacy of losartan 100 mg (L100) plus hydrochlorothiazide 12.5 mg (H12.5) in a single fixed-dose combination. In one study, subjects received losartan 50 mg (L50) plus H12.5 during an 8-week filter period. They were then randomized to either L100/H12.5 or L50/H12.5 for another 8 weeks, followed by L100/H12.5 for 44 weeks. The primary end point was safety of L100/H12.5 for 52 weeks. In the second study, subjects received L100 during an 8-week filter period. Subjects were then randomized to receive either L100/H12.5 or L100 for a further 8 weeks. The primary end point was change from baseline in sitting diastolic blood pressure (SiDBP) at week 8. Safety was assessed throughout both studies. L100/H12.5 reduced SiDBP and sitting systolic blood pressure (SiSBP) at 8 weeks, and when compared with L100, the differences were statistically significant for both measures (P<0.001). L100/H12.5 reductions SiDBP for 8 weeks were comparable to L50/H12.5. The efficacy of L100/H12.5 was maintained to week 52. Drug-related adverse events with an incidence ⩾ 2% in the L100/H12.5 group during the 52-week extension period were an increase in aspartate aminotransferase and in blood uric acid. Additionally, mean uric acid levels were reduced by 0.57 mg dl(-1) from baseline with long-term treatment with L100/H12.5 in subjects whose baseline uric acid level was >7.0 mg dl(-1). In conclusion, L100/H12.5 was shown to be more effective than L100 at reducing SiDBP and SiSBP and showed good tolerability in Japanese patients with essential hypertension.

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Switching Therapy from Variable-Dose Multiple Pill to Fixed-Dose Single-Pill Combinations of Angiotensin II Receptor Blockers and Thiazides for Hypertension

Cited by 8 publications

References 27 publications

Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of fimasartan, amlodipine, and rosuvastatin using partial replicated design in healthy adult subjects

Pharmacokinetic comparison of a fixed-dose combination versus concomitant administration of fimasartan, amlodipine, and rosuvastatin using partial replicated design in healthy adult subjects

Economic impact of switching to fixed-dose combination therapy for Japanese hypertensive patients: a retrospective cost analysis

Efficacy and safety of losartan 100 mg/hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension: two randomized, controlled trials

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