Original
Difference between the frequencies of antisecretory drug prescriptions in users of buffered vs. enteric-coated low-dose aspirin therapies
Hiroko Hachiken, Ai Murai, Kyoichi Wada, Takeshi Kuwahara, Kouichi Hosomi and Mitsutaka Takada
Price
42.00 $
Volume 51 p. 807 - 815
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 51 – No. 10/2013 (807-815)
Difference between the frequencies of antisecretory drug prescriptions in users of buffered vs. enteric-coated low-dose aspirin therapies
Hiroko Hachiken1, Ai Murai1, Kyoichi Wada2, Takeshi Kuwahara2, Kouichi Hosomi1 and Mitsutaka Takada1
1Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, and 2Department of Pharmacy, National Cerebral and Cardiovascular Center, Osaka, Japan
Objective: To provide further insights on the risks of gastrointestinal (GI) complications in individuals using low-dose aspirin (LDA), we investigated the concomitant use of LDA and antisecretory drugs. Additionally, we examined the frequency distributions of prescribing sequences for LDA and antisecretory drugs. Methods: Data from a computerized prescription order entry system was analyzed at the National Cerebral and Cardiovascular Center of Japan. LDA use in combination with H2-receptor antagonists (H2RAs) and proton pomp inhibitors (PPIs) was examined over the period from January 2001 to December 2010. Prescription sequence symmetry analyses were used to identify LDA-induced H2RAs or PPIs users. Results: In December 2010, PPIs accounted for 9.9% of the prescriptions for buffered LDA users and 16.1% of those for enteric-coated LDA users. Incident use of PPIs occurred more frequently among enteric-coated LDA users than buffered LDA users (17.6% vs. 11.0%, respectively). Prescription sequence symmetry analyses of PPI use revealed significant associations with enteric-coated LDA use, resulting in adjusted sequence ratios of 1.82 (95%CI, 1.11 – 3.03) and 1.87 (95% CI, 1.26 – 2.83) at intervals of 182 and 365 days, respectively. Enteric-coated LDA users tended to initiate PPI therapy on the same date more frequently than buffered LDA users (35.1% vs. 10.8%, respectively). Conclusions: Our findings do not support the notion that entericcoated LDA products confer a lower risk for GI complications than buffered formulations, but may conversely imply that the risk of GI complications associated with buffered LDA is lower than that of enteric-coated LDA.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kinki University
577-8502, 3-4-1, Kowakae,
Higashi-osaka, Osaka, 577-8502, Japan
Email: [email protected]
Original
Difference in risk of gastrointestinal complications between users of enteric-coated and buffered low-dose aspirin
Mitsutaka Takada, Mai Fujimoto, and Kouichi Hosomi
Price
42.00 $
Volume 52 p. 181 - 191
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 3/2014 (181-191)
Difference in risk of gastrointestinal complications between users of enteric-coated and buffered low-dose aspirin
Mitsutaka Takada, Mai Fujimoto, and Kouichi Hosomi
Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, Osaka, Japan
Objective: Difference in the risk of gastrointestinal (GI) complications between users of enteric-coated and buffered low-dose aspirin (LDA) is unclear. The purpose of the study is to examine the difference in risk of GI damage between enteric-coated and buffered LDA products. Methods: A large and chronologically organized receipt database constructed by a database vendor was utilized. Prescription and event sequence symmetry analysis was used to identify the risk of LDA-induced GI complications over the period from January 2005 to July 2011. LDA use in combination with H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) was examined by prescription sequence symmetry analysis. Likewise, symmetry analysis was undertaken to evaluate the association between the diagnosis of GI disease and the prescription of LDA products. Results: In July 2011, enteric-coated LDA users were more frequently co-administered PPIs than buffered LDA users (25.4% vs. 14.4%). Prescription sequence symmetry analysis of acid inhibitor use found no significant associations with enteric-coated LDA use and buffered LDA use. The event sequence symmetry analysis of ulcer, gastritis and duodenitis, and melena found significant associations with entericcoated LDA use, with adjusted sequence ratios (ASRs) of 1.58 (1.23 – 2.06), 1.30 (1.03 – 1.65), and 14.38 (2.19 – 607.95), respectively, at the 6-month interval. At the 12-month interval, analysis of ulcers and melena found significant associations for enteric-coated LDA users, with ASRs of 1.39 (1.13 – 1.73) and 20.83 (3.33 – 863.25), respectively. Conclusions: Our findings do not support that there is no difference in the risk of GI complications between enteric-coated LDA and buffered LDA, but rather may imply that the risk of GI complications associated with enteric-coated LDA is higher than that with buffered LDA.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kinki University
577-8502, 3-4-1, Kowakae,
Higashi-osaka, Osaka 577-8502, Japan
Email: [email protected]
Original
Statin-associated lower urinary tract symptoms: data mining of the public version of the FDA adverse event reporting system, FAERS
Mai Fujimoto, Kouichi Hosomi, and Mitsutaka Takada
Price
42.00 $
Volume 52 p. 259 - 266
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 4/2014 (259-266)
Statin-associated lower urinary tract symptoms: data mining of the public version of the FDA adverse event reporting system, FAERS
Mai Fujimoto, Kouichi Hosomi, and Mitsutaka Takada
Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, Osaka, Japan
Objective: To examine the association between statin use and the risk of lower urinary tract symptoms (LUTS) in reports submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) between 2004 and 2011. Methods: Relevant reports in the FAERS were identified and analyzed. The reporting odds ratio (ROR) was used to detect spontaneous report signals, calculated using the case/non-case method. Cases were identified by the presence of reports of an adverse drug reaction (ADR) in which statins were the suspected drug. Non-cases were all the reports of the same reactions induced by drugs other than statins. The reporting odds ratio (ROR) and 95% confidential interval (CI) was calculated as a measure of disproportionality. Results: A total of 44,959,104 drug-reaction pairs was found in 2,681,739 reports. Significant RORs were found for both voiding (ROR; 1.16, 95% CI; 1.10 – 1.23) and storage symptoms (ROR; 1.25, 95% CI; 1.20 – 1.30). Analysis of individual statins showed that rosuvastatin, atorvastatin, and lovastatin had significant disproportionality for voiding symptoms, while simvastatin, rosuvastatin, pravastatin, atorvastatin, pitavastatin, and lovastatin had significant disproportionality for storage symptoms. Of the four voiding symptoms, significant RORs were found for urine flow decrease and dysuria. Of the four storage symptoms, significant RORs were found for pollakiuria and nocturia. No fundamental differences in disproportionality were observed between genders. Conclusions: Analysis of the FAERS database showed small but reliable signals for LUTS in statin users. The mechanism responsible for these reactions is unknown. However, these adverse events should be monitored closely.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kinki University
3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan
Email: [email protected]
Original Research
Association of statin use with storage lower urinary tract symptoms (LUTS): data mining of prescription database
Mai Fujimoto, Tomoya Higuchi, Kouichi Hosomi, and Mitsutaka Takada
Price
42.00 $
Volume 52 p. 762 - 769
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 9/2014 (762-769)
Association of statin use with storage lower urinary tract symptoms (LUTS): data mining of prescription database
Mai Fujimoto, Tomoya Higuchi, Kouichi Hosomi, and Mitsutaka Takada
Division of Clinical Drug Informatics, School of Pharmacy, Kinki University, Osaka, Japan
Objective: The efficacy and safety of statins have been studied in a number of clinical trials and epidemiological studies. In recent years, the Medicine and Healthcare Products Regulatory Agency (MHRA) has assessed the evidence available on the following adverse reactions associated with the use of statins: sleep disturbances, memory loss, micturition disorders (problems with urination), sexual disturbances, depression, and interstitial pneumopathy. However, the association between statin use and the risk of these adverse reactions remains unclear. To examine the association between statin use and the risk of lower urinary tract symptoms (LUTS) or the disorder causing LUTS, we carried out data mining using a prescription database. Methods: A large organized database of prescriptions constructed by a database vendor was used in the study. Symmetry analysis was used to identify the risk of LUTS after using statins over the period January 2006 to August 2013. Statin use in combination with drugs administered for storage LUTS was examined by prescription sequence symmetry analysis (PSSA). Results: A significant association between statins and drugs for storage LUTS was found, with adjusted sequence ratios (ASRs) of 1.21 (95% CI, 1.00 – 1.46), 1.19 (95% CI, 1.04 – 1.38), and 1.17 (95% CI, 1.05 – 1.30) for intervals of 91, 182, and 365 days, respectively. In the analyses of individual statins, significant associations were found only for pravastatin. Significant associations with individual drugs for storage LUTS were found for solifenacin succinate with ASRs of 1.36 (95% CI, 1.02 – 1.81), 1.48 (95% CI, 1.19 – 1.84), and 1.47 (95% CI, 1.25 – 1.73) for intervals of 91, 182, and 365 days, for flavoxate hydrochloride with an ASR of 1.56 (95% CI, 1.13 – 2.17) at an interval of 182 days, and for oxybutynin hydrochloride with ASRs of 2.06 (95% CI, 1.11 – 3.94) and 1.71 (95% CI, 1.09 – 2.72) at intervals of 182 and 365 days. Significant associations with gender were found only in females with ASRs of 1.25 (95% CI, 1.04 – 1.51) and 1.23 (95% CI, 1.07 – 1.41) at intervals of 182 and 365 days, respectively. Conclusions: Analysis of the prescription database showed significant association for storage LUTS in statin users.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kink University
577-8502, 3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan
Email: [email protected]
Original
Long-term impact of therapeutic drug monitoring on the risk of hypoglycemia in HOCM patients on cibenzoline therapy
Yutaro Mukai, Kyoichi Wada, Mai Fujimoto, Kouichi Hosomi, Takeshi Kuwahara, Mitsutaka Takada
Price
42.00 $
Volume 54 p. 795 - 803
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 54 – No. 10/2016 (795-803)
Long-term impact of therapeutic drug monitoring on the risk of hypoglycemia in HOCM patients on cibenzoline therapy
Yutaro Mukai1,2, Kyoichi Wada1,2, Mai Fujimoto3, Kouichi Hosomi3, Takeshi Kuwahara1,2, Mitsutaka Takada2,3
1Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, Osaka, 2Division of Cardiovascular Drugs and Therapy, Kindai University Graduate School of Pharmacy, Higashi-osaka, and 3Division of Clinical Drug Informatics, Kindai University School of Pharmacy, Higashi-osaka, Japan
Objective: The purpose of this study was to evaluate the long-term impact of therapeutic drug monitoring (TDM) services on the risk of hypoglycemia in cibenzoline therapy. In addition, we evaluated the impact of changes in clinical setting or patient background on the risk of hypoglycemia in patients receiving cibenzoline. Methods: TDM services for cibenzoline have been performed at the Japan National Cerebral and Cardiovascular Center since March 1998. A case-control study was performed from September 2012 to February 2013, and the calculated risk of hypoglycemia associated with cibenzoline use was compared with data from our previous studies, which were performed ~ 15 years ago. Results: A significantly increased risk for hypoglycemia was observed for users of cibenzoline (adjusted OR: 2.6; 95% CI: 1.5 – 4.7). In an additional analysis, the calculated risk was slightly reduced (adjusted OR; 2.1, 95% CI; 1.1 – 3.8) and hypertrophic obstructive cardiomyopathy (HOCM) was identified as a possible risk factor for hypoglycemia (adjusted OR: 4.7, 95% CI: 1.8 – 12.3). There was a significant difference in the mean level of cibenzoline between outpatients with and without HOCM (360.5 ± 166.9 ng/mL vs. 276.4 ± 136.3 ng/mL). An inverse relationship was observed between the percentage of outpatients whose cibenzoline serum level had been measured and their risk of hypoglycemia. Conclusions: Consistent TDM services for cibenzoline have contributed to a reduced risk of hypoglycemia associated with cibenzoline therapy. Patients with HOCM have a higher risk of developing hypoglycemia. Clinicians should therefore carefully monitor serum glucose levels in patients with HOCM taking cibenzoline.
Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
Kindai University School of Pharmacy
577-8502, 3-4-1, Kowakae, Higashi-osaka,
Osaka, 577-8502, Japan
Email: takada@
phar.kindai.ac.jp
Original
Circadian pharmacokinetics and limited sampling strategy of everolimus in heart transplant patients
Yuka Terada, Kyoichi Wada, Sachi Matsuda, Takeshi Kuwahara, Atsufumi Kawabata, Mitsutaka Takada, Takuya Watanabe, Seiko Nakajima, Takuma Sato, Osamu Seguchi, Masanobu Yanase, Norihide Fukushima, Takeshi Nakatani
Price
42.00 $
Volume 55 (2017) p. 1 - 8
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 1/2017 (1-8)
Circadian pharmacokinetics and limited sampling strategy of everolimus in heart transplant patients
Yuka Terada1#2#3, Kyoichi Wada1#3, Sachi Matsuda1, Takeshi Kuwahara1#3, Atsufumi Kawabata2, Mitsutaka Takada3, Takuya Watanabe4, Seiko Nakajima4, Takuma Sato4, Osamu Seguchi4, Masanobu Yanase4, Norihide Fukushima4, Takeshi Nakatani4
1Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, 2Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, 3Division of Cardiovascular Drugs and Therapy, Kindai University Graduate School of Pharmacy, Higashi-Osaka, and 4Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Objective: To evaluate circadian changes in everolimus (EVL) pharmacokinetics and to identify the time point of blood sampling with the strongest correlation with the area under the blood concentration-time curve (AUC) of EVL in heart transplant patients. Methods: Heart transplant patients receiving the same dose of EVL twice a day were reviewed. In 28 patients enrolled, whole blood samples were collected before (C0), and 1, 2, 4, 6, 8, and 12 hours after each administration of EVL. Blood concentrations of EVL were compared between active (9:00 AM to 9:00 PM) and resting periods (9:00 PM to 9:00 AM). Results: AUC0–4h, peak concentration (Cmax), Cmax/minimum concentration, and peak-trough fluctuation in the resting period were significantly lower than those in the active period (p = 0.008, 0.017, 0.022, and 0.011, respectively). Half-life and mean residence time were significantly longer in the resting period than in the active period (p = 0.002 and 0.002, respectively). AUC0–12h in the active period was similar (p = 0.154) and correlated with that in the resting period (r2 = 0.93). Two-point blood samplings, C0 and C2, correlated more strongly with AUC0–12h for EVL, compared with C0 alone (0.92 vs. 0.79, respectively, for r2 in the active period). Conclusions: EVL pharmacokinetics showed circadian changes, suggesting delayed absorption and decreased metabolic activity at rest. However, the circadian changes did not affect AUC0–12h. A 2-time-point model that included C0 and C2 was more accurate for predicting the AUC0–12h of EVL than C0 alone in heart transplant patients.
Correspondence to:
Kyoichi Wada, PhD
Department of
Pharmacy
National Cerebral and Cardiovascular Center
5-7-1 Fujishirodai, Suita 565-8565, Japan
Email: [email protected]
Original Research
Angiotensin receptor blockers and the risk of cancer: data mining of a spontaneous reporting database and a claims database
Mai Fujimoto, Migiwa Kanou, Kouichi Hosomi, Mitsutaka Takada
Price
42.00 $
Volume 55 (2017) p. 295 - 303
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 4/2017 (295-303)
Angiotensin receptor blockers and the risk of cancer: data mining of a spontaneous reporting database and a claims database
Mai Fujimoto, Migiwa Kanou, Kouichi Hosomi, Mitsutaka Takada
Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Osaka, Japan
Objective: The aim of this study was to examine the associations between angiotensin receptor blockers (ARBs) and the risk of 10 major cancers by employing different pharmacoepidemiological assessments. Materials & methods: Data from the first quarter of 2004 through 2012 were downloaded from the US Food and Drug Administration Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR) and information component (IC) were used to detect the signals. Furthermore, symmetry analysis was applied to the claims database to identify the risk of cancer after using ARBs from January 2005 to July 2013. Results: Significant inverse associations were found for all cancer types assessed as a whole (ROR: 0.78, 95% confidence interval (CI): 0.75 – 0.80; IC: –0.36, 95% CI: –0.40 to –0.31) in the analyses of FAERS database. Likewise, significant inverse association was found for all cancer types assessed as a whole (adjusted sequence ratio: 0.89, 95% CI: 0.82 – 0.96) in claims database. In addition, a significantly decreased risk for breast cancer and increased risks for pancreatic and prostate cancer were found in patients treated with ARBs in the analyses of individual cancers. Conclusions: Significant inverse association was found between ARB use and all cancer types assessed as a whole. However, in the analyses of individual cancers, the risks of ARB-induced cancer may differ according to cancer site. It may be reasonable to assume that the risks of ARB-induced cancer may differ according to cancer site.
Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kindai University
577-8502, 3-4-1, Kowakae, Higashi-osaka,
Osaka, 577-8502, Japan
Email: takada@
phar.kindai.ac.jp
Case
Report
Use of rifabutin to treat tuberculosis in a cardiac transplant recipient: A case report
Maya Takayoshi, Kyoichi Wada, Yuka Terada, Sachi Matsuda, Kazuki Nakagita, Akira Oita, Mitsutaka Takada, Aki Shionoiri, Haruki Sunami, Seiko Nakajima, Kensuke Kuroda, Takuma Sato, Osamu Seguchi, Masanobu Yanase, and Norihide Fukushima
Price
42.00 $
Volume 56 (2018) p. 184 - 188
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 56 – No. 4/2018 (184-188)
Use of rifabutin to treat tuberculosis in a cardiac transplant recipient: A case report
Maya Takayoshi1, Kyoichi Wada1#2, Yuka Terada1, Sachi Matsuda1, Kazuki Nakagita1#2, Akira Oita1, Mitsutaka Takada2, Aki Shionoiri3, Haruki Sunami3, Seiko Nakajima3, Kensuke Kuroda3, Takuma Sato3, Osamu Seguchi3, Masanobu Yanase3, and Norihide Fukushima3
1Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, 2Division of Cardiovascular Drugs and Therapy, Kindai University Graduate School of Pharmacy, Higashi-Osaka, and 3Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
Objective: Tuberculosis is an important concern following organ transplantation. Unfortunately, several antituberculosis drugs interact with immunosuppressants. This report describes our experience with rifabutin (RBT) in the treatment of acute tuberculosis in a cardiac transplant recipient. Case: A 61-year-old cardiac transplant recipient developed tuberculosis meningitis during treatment of miliary tuberculosis. RBT was given for 27 days concomitantly with cyclosporine (CsA). CsA concentrations at 0 hour (C0) decreased within 3 days of starting RBT. The serum concentration-curve from 0 to 12 hours (AUC0–12h)/dose 7 days after starting RBT therapy decreased by 28%, compared to the values before RBT therapy. The apparent clearance at both 7 and 21 days after starting RBT therapy was 1.4 times higher than before RBT therapy. Conclusion: RBT has fewer drug-drug interactions than rifampin and should be preferentially used for the treatment of tuberculosis in transplant patients treated with CsA. Close monitoring of CsA blood concentration during RBT therapy minimized the risk of under- or over-immunosuppression in a cardiac transplant patient.
Correspondence to:
Kyoichi Wada, PhD
Department of Pharmacy
National Cerebral and Cardiovascular Center
5-7-1,
Fujishirodai, Suita, 565-8565, Japan
Email: [email protected]
Case
Report
Effect of fluconazole on the pharmacokinetics of everolimus and tacrolimus in a heart transplant recipient: Case report
Kazuki Nakagita, Kyoichi Wada, Yuka Terada, Sachi Matsuda, Nobue Terakawa, Akira Oita, and Mitsutaka Takada
Price
42.00 $
Volume 56 (2018) p. 270 - 276
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 56 – No. 6/2018 (270-276)
Effect of fluconazole on the pharmacokinetics of everolimus and tacrolimus in a heart transplant recipient: Case report
Kazuki Nakagita1#2, Kyoichi Wada1#2, Yuka Terada1, Sachi Matsuda1, Nobue Terakawa1, Akira Oita1, and Mitsutaka Takada2
1Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, and 2Division of Cardiovascular Drugs and Therapy, Kindai University Graduate School of Pharmacy, Higashi-Osaka, Osaka, Japan
Objective: Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR) and has been used in combination with calcineurin inhibitors (tacrolimus and cyclosporine) to prevent allograft rejection following organ transplantation. In heart transplant recipients, everolimus should be maintained at a target blood concentration of 3 – 8 ng/mL, in combination with reduced-dose calcineurin inhibitors and therefore, requires strict monitoring. Fluconazole, an azole antifungal agent, affects blood concentration of tacrolimus by inhibiting the cytochromes P450 (CYP) 3A4 and 3A5. Therefore, to avoid overexposure during everolimus-azole cotreatment, the dose of everolimus should be reduced. However, the mechanism of interaction between everolimus and fluconazole remains unclear. Case report: We report the case of a heart transplant recipient who experienced a 2.8-fold increase in everolimus clearance and a 3.5-fold increase in everolimus dosage, following withdrawal of fluconazole therapy. The clearance and dosage of tacrolimus increased 4.7- and 3.0-fold, respectively. Conclusion: The concentrations of everolimus and tacrolimus should be carefully monitored when administered concomitantly with fluconazole to heart transplant recipients. The patient in this case had a CYP3A5*1/*3 genotype, and CYP3A5 constituted the metabolic pathway. Therefore, concomitant use of fluconazole might have a relatively small impact on everolimus and tacrolimus pharmacokinetics in this case.
Correspondence to:
Kyoichi Wada, PhD
Department of
Pharmacy
National Cerebral and Cardiovascular Center
5-7-1 Fujishirodai,
Suita 565-8565, Japan
Email: [email protected]
Original Research
Risk of malignant lymphoma in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs and methotrexate
Ryo Inose, Kouichi Hosomi, Katsuyuki Takahashi, Satoshi Yokoyama, and Mitsutaka Takada
Price
42.00 $
Volume 57 (2019) p. 63 - 72
Abstract
Risk of malignant lymphoma in patients with rheumatoid arthritis treated with biological disease-modifying antirheumatic drugs and methotrexate
Ryo Inose1, Kouichi Hosomi2, Katsuyuki Takahashi1, Satoshi Yokoyama2, and Mitsutaka Takada2
1Department of Pharmacy, Osaka City University Hospital, and 2Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Osaka, Japan
Objective: This study investigated whether using biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignant lymphoma in patients with rheumatoid arthritis undergoing methotrexate therapy using spontaneous adverse reaction databases in different countries. Materials and methods: Patient data were acquired from the US Food and Drug Administration’s Adverse Event Reporting System (FAERS), the Japanese Adverse Drug Event Report (JADER), and the Canada Vigilance Adverse Reaction Online Database (CVARD) from the first quarter of 2004 to the end of 2015. Data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignant lymphoma in patients receiving methotrexate therapy. Results: The FAERS subset data indicated a significant association between Hodgkin lymphoma and methotrexate with infliximab (reporting odds ratio (ROR): 8.28. 95% CI: 5.70 – 12.02; information component (IC): 2.04, 95% CI: 1.59 – 2.49). In addition, signal scores suggested that methotrexate with infliximab (ROR: 3.26. 95% CI: 2.68 – 3.98; IC: 1.31, 95% CI: 1.04 – 1.58) was significantly associated with non-Hodgkin lymphoma (NHL). The CVARD subset data also indicated a significant association between NHL and methotrexate with infliximab (ROR: 22.82. 95% CI: 5.02 – 103.78; IC: 1.77, 95% CI: 0.13 – 3.41). However, the JADER subset data revealed no significant associations. Conclusion: The present study shows that using infliximab further increases the risk of malignant lymphoma in patients receiving methotrexate therapy.
Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
Kindai University School of Pharmacy
3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan
Email: takada@
phar.kindai.ac.jp
Original Research
Adherence to guidelines for antiulcer drug prescription in patients receiving low-dose aspirin therapy in Japan
Makiko Iwasawa, Keiko Sagami, Satoshi Yokoyama, Kouichi Hosomi, and Mitsutaka Takada
Price
42.00 $
Volume 57 (2019) p. 197 - 206
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 57 – No. 4/2019 (197-206)
Adherence to guidelines for antiulcer drug prescription in patients receiving low-dose aspirin therapy in Japan
Makiko Iwasawa1, Keiko Sagami2, Satoshi Yokoyama2, Kouichi Hosomi2, and Mitsutaka Takada2
1Division of Drug Information, School of Pharmacy, Kitasato University, Sagamihara, Kanagawa, and 2Division of Clinical Drug Informatics, School of Pharmacy,
Kindai University, Higashi-osaka-city, Osaka, Japan
Objective: Prevalence of guideline adherence for antiulcer drug prescription in patients receiving low-dose aspirin (LDA) therapy was examined and the association of risk factors with the adherence was assessed. Materials and methods: A retrospective cohort study using a population-based longitudinal healthcare database was conducted. Claims data between January 2005 and April 2016 were analyzed. A total of 3,079 patients were included in the study. The selected patients taking LDA were divided into two categories: those taking and those not taking antiulcer drugs in an inpatient setting. Additionally, they were classified into four groups according to the time antiulcer therapy was initiated. The risk factors for ulcer, such as history of gastrointestinal injuries; age ≥ 65 years; and concomitant use of anticoagulants, antiplatelets, oral corticosteroids, and nonsteroidal anti-inflammatory drugs except aspirin, were assessed. Results: A total of 3,079 patients were included in the study. The rate of LDA patients using antiulcer drugs was 65.2%, with the strongest single factor associated with the use of antiulcer drugs being the concomitant use of corticosteroids. Among the LDA patients not taking antiulcer drugs, 66.8% had more than one risk factor. Irrespective of the use of concomitant treatment with antiulcer drug prior to hospital admission, 78.3% of the LDA patients continued their home regimen after hospital admission. Conclusion: Our results showed that the requirement of antiulcer therapy is not routinely evaluated at hospital admission, and antiulcer drugs for patients with ulcer risks are under-prescribed. Developing strategies to screen gastrointestinal risk factors at hospital admission is required to improve the guideline adherence for LDA-induced ulcer.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kindai University
577-8502, 3-4-1, Kowakae, Higashi-osaka,
Osaka, 577-8502, Japan
Email: takada@
phar.kindai.ac.jp
Original
Voriconazole trough concentration and hepatotoxicity in patients with low serum albumin
Atsushi Hirata, Keisuke Noto, Ryosuke Ota, Satoshi Yokoyama, Kouichi Hosomi, Mitsutaka Takada, and Hiroshi Matsuoka
Price
42.00 $
Volume 57 (2019) p. 135 - 143
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 57 – No. 3/2019 (135-143)
Voriconazole trough concentration and hepatotoxicity in patients with low serum albumin
Atsushi Hirata1, Keisuke Noto1, Ryosuke Ota1, Satoshi Yokoyama2, Kouichi Hosomi2, Mitsutaka Takada2, and Hiroshi Matsuoka1
1Department of Pharmacy, Kindai University Nara Hospital, and
2Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Japan
Objective: We aimed to investigate the relationship between voriconazole (VRCZ) trough concentrations and hepatotoxicity and to evaluate whether the recommended trough concentration is adequate in our clinical setting. Materials and methods: A retrospective study was performed to investigate the relationship between serum VRCZ concentrations and the development of hepatotoxicity at the Kindai University Nara Hospital. Patients treated with VRCZ from March 2010 to January 2018 were identified from the medical records. A total of 42 patients (mean age of 61.9 ± 16.9 years; 33 males and 9 females) were enrolled in this study. Results: Hepatotoxicity developed in 28.6% (12/42) of patients treated with VRCZ, and 91.7% (11/12) of these patients developed hepatotoxicity within 3 weeks after initiating the treatment. Significantly increased aspartate aminotransferase (AST; p < 0.001), alkaline phosphatase (ALP; p < 0.001), and alanine aminotransferase (p = 0.001) levels were observed after the initiation of VRCZ therapy. In addition, significant positive correlations between AST and VRCZ trough concentrations (p = 0.017) and between ALP and VRCZ trough concentrations (p = 0.012) were observed. VRCZ trough concentration was identified as a significant independent risk factor for hepatotoxicity (adjusted odds ratio: 1.611, 95% confidence interval: 1.131 – 2.579, p = 0.006), and the cutoff serum trough concentration was calculated to be 4.2 μg/mL. Conclusion: VRCZ-induced hepatotoxicity should be noted in the early stages of therapy. A sustained VRCZ trough concentration of ~ < 4.2 μg/mL is recommended to prevent hepatotoxicity in patients with low serum albumin levels.
This study was conducted in the Department of Pharmacy, Nara Hospital, Japan.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kindai University
3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan
Email:
takada@
phar.kindai.ac.jp
Original Research
Comparison of CYP3A5*3 genotyping assays for personalizing immunosuppressive therapy in heart transplant patients
Takaya Uno, Kyoichi Wada, Sachi Matsuda, Yuka Terada, Akira Oita, Mitsutaka Takada, Masanobu Yanase, and Norihide Fukushima
Price
42.00 $
Volume 57 (2019) p. 315 - 322
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 57 – No. 6/2019 (315-322)
Comparison of CYP3A5*3 genotyping assays for personalizing immunosuppressive therapy in heart transplant patients
Takaya Uno1#2#3, Kyoichi Wada1#3, Sachi Matsuda1, Yuka Terada1#3, Akira Oita1, Mitsutaka Takada2#3, Masanobu Yanase4, and Norihide Fukushima4
1Department of Pharmacy, National Cerebral and Cardiovascular Center, 2Division of Clinical Drug Informatics, Faculty of Pharmacy, 3Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, and 4Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
Objective: This study aimed to compare a novel point-of-care assay that involves a flap endonuclease reaction performed using GTS-7000® to a conventional assay that involves DNA sequencing performed using 3130xl Genetic Analyzers*. Materials and methods: This study enrolled 74 patients who underwent heart transplantation at the National Cerebral and Cardiovascular Center between May 2004 and October 2016. Each patient was genotyped as cytochrome P450 (CYP) 3A5*1/*1, CYP3A5*1/*3, or CYP3A5*3/*3. Quantitative and qualitative comparison between the two assays was carried out. Results: Four patients were genotyped as CYP3A5*1/*1, 25 as CYP3A5*1/*3, and 45 as CYP3A5*3/*3. Genotyping results of the point-of-care method were completely consistent with those of the conventional method. The total analysis time of the point-of-care method was shorter than that of the conventional method (~ 1.5 vs. 7.5 h). However, the cost of the point-of-care method was higher than that of the conventional method (~ 21 vs. 17 US$). Conclusion: Compared with a laboratory-based assay, the point-of-care assay that utilizes GTS-7000® is accurate and rapid despite being slightly more expensive. Further trials using this assay are warranted.Correspondence to:
Norihide Fukushima, PhD
Department of Transplant Medicine
National Cerebral and Cardiovascular Center
5-7-1, Fujishirodai, Suita, Osaka, 565-8565, Japan
Email: [email protected]
Original
Relationship between the blood concentrations of tacrolimus and voriconazole in hematopoietic stem cell transplant recipients
Ryosuke Ota, Atsushi Hirata, Keisuke Noto, Satoshi Yokoyama, Kouichi Hosomi, Mitsutaka Takada, and Hiroshi Matsuoka
Price
42.00 $
Volume 57 (2019) p. 561 - 566
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 57 – No. 11/2019 (561-566)
Relationship between the blood concentrations of tacrolimus and voriconazole in hematopoietic stem cell transplant recipients
Ryosuke Ota1, Atsushi Hirata1, Keisuke Noto1, Satoshi Yokoyama2, Kouichi Hosomi2, Mitsutaka Takada2, and Hiroshi Matsuoka1
1Department of Pharmacy, Kindai University Nara Hospital, Ikoma, Nara, and
2Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-osaka, Osaka, Japan
Objective: We aimed to clarify the drug interaction between tacrolimus and voriconazole and investigate the relationship between blood concentrations of tacrolimus and voriconazole in hematopoietic stem cell transplantation (HSCT) patients.
Materials and methods: A retrospective study was conducted to investigate the relationship between blood concentration of tacrolimus and that of voriconazole at the Kindai University Nara Hospital. Patients who received HSCT and tacrolimus and were prescribed voriconazole for the prevention or treatment of aspergillosis from April 2010 to July 2018 were identified from the medical records. A total of 13 patients (administration route of tacrolimus: intravenously in 6 patients, orally in 7 patients) were enrolled in the present study.
Results: No significant correlation was observed between the blood concentration/dose (C/D) ratio of tacrolimus and the blood concentration of voriconazole (r = 0.38; p = 0.402; y = 102.8x + 928.1). However, a significant correlation was observed between the C/D ratio of tacrolimus and the blood concentration of voriconazole in the intravenous-administration group (r = 0.94; p = 0.0048; y = 421.9x + 810.5). Meanwhile, no significant correlation was observed in the oral-administration group (r = 0.43; p = 0.34; y = 7.9x + 719).
Conclusion: The C/D ratio of tacrolimus was significantly correlated with the blood concentration of voriconazole when tacrolimus was intravenously administered. There was a difference in the mechanism of drug interaction between tacrolimus and voriconazole depending on the administration routes.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kindai University
3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan
Email:
[email protected]
Original
Association between malignancy and methotrexate and biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis
Ryo Inose, Natsue Hashimoto, Kouichi Hosomi, Satoshi Yokoyama, and Mitsutaka Takada
Price
42.00 $
Volume 58 (2020) p. 131 - 138
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 3/2020 (131-138)
Association between malignancy and methotrexate and biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis
Ryo Inose1, Natsue Hashimoto2, Kouichi Hosomi2, Satoshi Yokoyama2, and Mitsutaka Takada2
1Department of Pharmacy, Osaka City University Hospital, and 2Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Osaka, Japan
Objective: This study was aimed at investigating the risk of malignancies in rheumatoid arthritis patients treated with methotrexate (MTX), and whether the addition of biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignancies in patients receiving MTX therapy, by using data from a spontaneous adverse reaction database.
Materials: Patient data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2015 were analyzed.
Methods: A data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignancies in patients receiving MTX therapy.
Results: MTX showed significant associations with all malignancies except liver cancer. bDMARDs showed significant associations with stomach cancer, colorectal cancer, prostate cancer, ovarian cancer, malignant melanoma, and lung cancer. In addition, bDMARD use increased the risk of breast, ovarian, and lung cancers in rheumatoid arthritis patients receiving MTX therapy.
Conclusion: MTX use was significantly associated with various malignancies. Moreover, concomitant use of bDMARDs further increased the risk of breast, ovarian, and lung cancers in MTX-treated patients with rheumatoid arthritis.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
Kindai University School of Pharmacy
3-4-1, Kowakae, Higashi-osaka, Osaka, 577-8502, Japan
Email: takada@
phar.kindai.ac.jp
Original Research
Influence of co-initiation of antiulcer drugs on persistence and adherence to low-dose aspirin: A retrospective cohort study using a Japanese claims database
Makiko Iwasawa, Keiko Sagami, Satoshi Yokoyama, Kouichi Hosomi, and Mitsutaka Takada
Price
42.00 $
Volume 58 (2020) p. 214 - 222
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 4/2020 (214-222)
Influence of co-initiation of antiulcer drugs on persistence and adherence to low-dose aspirin: A retrospective cohort study using a Japanese claims database
Makiko Iwasawa1, Keiko Sagami2, Satoshi Yokoyama2, Kouichi Hosomi2, and Mitsutaka Takada2
1Division of Clinical Pharmacy (Laboratory of Drug Information) and Research and Education Center for Clinical Pharmacy, School of Pharmacy, Kitasato University, Kanagawa, and 2Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Osaka, Japan
Objective: The purpose of this study was to examine whether co-initiation of antiulcer drugs (AUDs) and low-dose aspirin (LDA) therapy is beneficial for good adherence to LDA therapy.
Materials and methods: A retrospective cohort study was conducted using the JMDC claims database. Patients for whom LDA therapy was newly initiated between January 2005 and April 2016 were selected from the JMDC database. The selected patients were divided into LDA and LDA+AUD groups and were followed up from the first prescription of LDA or LDA+AUD until the earliest of the following events: discontinuation or the end of the observation period. Unadjusted and multivariable Cox proportional hazards models controlling for all demographic and clinical characteristics were applied to examine whether the addition of an AUD to LDA improved adherence. A 1 : 1 propensity score matching analysis was conducted to balance confounders between the two groups.
Results: After the propensity score matching analysis, 4,089 patients were matched in each therapy group. The Kaplan-Meier curves for the rate of LDA continuation showed a sharp decline just after the initiation of LDA therapy. A significant difference was observed in the incidence of LDA therapy discontinuation between the LDA+AUD and LDA groups (HR: 0.87, 95% CI: 0.82 – 0.92), and the median duration of LDA therapy in the LDA+AUD and LDA groups were 18 and 11 months (log-rank test: p < 0.0001), respectively.
Conclusion: The therapy persistence rate in the LDA+AUD group was significantly higher than that in the LDA group.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kindai University
577-8502, 3-4-1, Kowakae, Higashi-osaka,
Osaka, 577-8502, Japan
Email: takada@
phar.kindai.ac.jp
Original
Relationship between serum calcium and creatinine in hematopoietic stem cell transplantation patients treated with foscarnet
Ryosuke Ota, Atsushi Hirata, Keisuke Noto, Satoshi Yokoyama, Kouichi Hosomi, Mitsutaka Takada, and Hiroshi Matsuoka
Price
42.00 $
Volume 58 (2020) p. 274 - 281
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 5/2020 (274-281)
Relationship between serum calcium and creatinine in hematopoietic stem cell transplantation patients treated with foscarnet
Ryosuke Ota1, Atsushi Hirata1, Keisuke Noto1, Satoshi Yokoyama2, Kouichi Hosomi2, Mitsutaka Takada2, and Hiroshi Matsuoka1
1Department of Pharmacy and 2Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashiosaka, Osaka, Japan
Objective: The relationship between serum creatinine and calcium (Ca) was investigated in hematopoietic stem cell transplantation (HSCT) patients treated with foscarnet.
Materials and methods: A retrospective study was performed to investigate the development of foscarnet-induced renal dysfunction in patients who received HSCT from April 2010 to November 2018 at the Kindai University Nara Hospital. A total of 80 patients were identified from the medical records, and 42 patients who met the inclusion criteria were enrolled in this study. Renal dysfunction was classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.
Results: A significant inverse relationship was observed between serum creatinine and Ca levels (r = –0.372; p < 0.0001; y = –0.537x + 9.268). A separate analysis divided into renal dysfunction and non-renal dysfunction groups showed that there was a significant relationship between serum creatinine and Ca levels in the renal dysfunction group (r = –0.531; p < 0.0001; y = –0.617x + 9.239) but not in the non-renal dysfunction group (r = –0.011; p = 0.561; y = –0.023x + 8.934). The optimal cutoff for the minimum Ca level was calculated to be 8.1 mg/mL.
Conclusion: A significant inverse relationship was observed between serum creatinine and Ca levels in HSCT patients with foscarnet-induced renal dysfunction. Foscarnet-induced renal dysfunction should be noted if Ca levels fall below 8.1 mg/dL. Monitoring Ca levels may be useful for detecting renal dysfunction at early stages in patients treated with foscarnet.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kindai University
3-4-1, Kowakae Higashi-osaka, Osaka 577-5802, Japan
Email:
[email protected]
Original Research
Polypharmacy in three different spontaneous adverse drug event databases
Takayuki Mabuchi, Kouichi Hosomi, Satoshi Yokoyama, and Mitsutaka Takada
Price
42.00 $
Volume 58 (2020) p. 601 - 607
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 11/2020 (601-607)
Polypharmacy in three different spontaneous adverse drug event databases
Takayuki Mabuchi1#3, Kouichi Hosomi1#2, Satoshi Yokoyama1#2, and Mitsutaka Takada1#2
1Division of Clinical Drug Informatics, Kindai University Graduate School of Pharmacy, 2Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, and 3Maruzen Pharmacy, Osaka, Japan
Objective: Polypharmacy has become a major problem in medical care worldwide, including in Japan. The purpose of this study was to investigate the current situation of polypharmacy using different spontaneous adverse drug event report databases.
Materials and methods: A retrospective data analysis was performed using reports from 2007 to 2015 from three different spontaneous adverse drug event report databases: the Japanese Adverse Drug Event Report (JADER) constructed by the Pharmaceuticals and Medical Devices Agency in Japan, the US Food and Drug Administration (FDA) Adverse Drug Event Reporting System (FAERS) constructed by the FDA in the United States, and the Canada Vigilance Adverse Reaction Online Database (CVARD) constructed by the government of Canada. Polypharmacy trends during the study period were investigated.
Results: The mean numbers of drugs per report in the JADER, FAERS, and CVARD databases during the study period were 6.62, 3.76, and 3.44, respectively. The mean number of drugs per report increased with age in all three databases, with a peak at ages 70 – 79 years in all three databases (7.0 drugs for JADER, 4.7 drugs for FAERS, and 4.2 drugs for CVARD).
Conclusion: Adverse event reports were more likely to develop in the patients treated through polypharmacy. Polypharmacy in Japan should be improved to prevent adverse events. Additionally, the patients aged ≥ 80 years tended to develop adverse events even if the number of prescribed drugs was relatively small. Therefore, polypharmacy should be noted in these patients to prevent adverse events.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
School of Pharmacy, Kindai University
3-4-1, Kowakae, Higashi-osaka, Osaka,
577-8502, Japan
Email: takada@
phar.kindai.ac.jp
Original
Relationship between serum bepridil concentration and corrected QT interval
Kazuki Matsui, Yutaro Mukai, Kota Sakakura, Kyoichi Wada, Tsutomu Nakamura, Atsufumi Kawabata, Nobue Terakawa, Naoki Hayakawa, Kengo Kusano, Kouichi Hosomi, Satoshi Yokoyama, and Mitsutaka Takada
Price
42.00 $
Volume 59 (2021) p. 63 - 70
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 59 – No. 1/2021 (63-70)
Relationship between serum bepridil concentration and corrected QT interval
Kazuki Matsui1#2#3, Yutaro Mukai3, Kota Sakakura3, Kyoichi Wada4, Tsutomu Nakamura4, Atsufumi Kawabata2, Nobue Terakawa3, Naoki Hayakawa3, Kengo Kusano5, Kouichi Hosomi6#7, Satoshi Yokoyama6#7, and Mitsutaka Takada1#6#7
1Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, 2Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Higashi-Osaka, 3Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, 4Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, 5Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, 6Division of Clinical Drug Informatics, Kindai University Graduate School of Pharmacy, and 7Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, Higashi-Osaka, Japan
Objective: Bepridil prolongs the QT interval and can induce torsade de pointes. Although increased bepridil concentration may be a primary cause of prolonged QT, the relationship between serum bepridil concentration and prolonged QT remains unclear. We investigated the relationship between serum bepridil concentration and the corrected QT (QTc) interval in patients treated with bepridil.
Materials and methods: A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. Patients with atrial fibrillation who were treated with bepridil from January 2014 to December 2015 were enrolled in the study. Serum bepridil concentrations and electrocardiogram data collected more than 21 days after the initiation of bepridil were used for analysis.
Results: A total of 60 patients were included in this study. There was a significant difference in mean QTc interval before and after initiation of bepridil (p < 0.0001). A significant relationship was observed between bepridil dose (p = 0.014) or serum bepridil concentration (p < 0.001) and QTc interval. Additionally, a significant relationship was observed between serum bepridil concentration and ΔQTc (p = 0.034). In the study, 4 patients developed QTc prolongation ≥ 500 ms after the initiation of bepridil. Serum bepridil concentration in this group was significantly higher compared with the group that did not display prolonged QTc (973 ± 651 vs. 526 ± 310 ng/mL, p = 0.01).
Conclusion: This study revealed that the QTc interval was significantly associated with serum bepridil concentration. Serum bepridil concentration beyond a therapeutic range may be a critical risk factor for developing QTc prolongation.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical Drug Informatics
Kindai University Graduate School of Pharmacy
Higashi-Osaka, Osaka, 577-8502, Japan
Email:
takada@
phar.kindai.ac.jp
Original
Relationship between polypharmacy and adverse events
Takayuki Mabuchi, Kouichi Hosomi, Satoshi Yokoyama, and Mitsutaka Takada
Price
42.00 $
Volume 59 (2021) p. 353 - 357
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 59 – No. 5/2021 (353-357)
Relationship between polypharmacy and adverse events
Takayuki Mabuchi1#3, Kouichi Hosomi1#2, Satoshi Yokoyama1#2, and Mitsutaka Takada1#2
1Division of Clinical Drug Informatics, Kindai University Graduate School of Pharmacy, 2Division of Clinical Drug Informatics, School of Pharmacy, Kindai University, and 3Maruzen Pharmacy, Osaka, Japan
A retrospective data analysis was performed to investigate the association between polypharmacy and adverse events using three different spontaneous adverse event reporting system databases. Multivariate logistic regression analyses were performed to investigate the association between the number of drugs and adverse events, including hepatic disorders, renal disorders, hypersensitivity, and extrapyramidal syndrome. The results showed that the risk of hepatic and renal disorders increased with the number of drugs. Thus, decreasing the number of drugs may reduce the risk of hepatic and renal disorders. Furthermore, attention should be given to specific drugs that may cause hypersensitivity and extrapyramidal syndrome.Correspondence to:
Mitsutaka Takada, PhD
Division of Clinical
Drug Informatics
School of Pharmacy, Kindai University
3-4-1, Kowakae, Higashi-osaka
Osaka, 577-8502, Japan
Email: takada@
phar.kindai.ac.jp
