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Fulltext Role of febuxostat in retarding progression of diabetic kidney disease with asymptomatic hyperuricemia: A 6-months open-label, randomized controlled trial

Mukri MNA, Kong WY, Mustafar R, Shaharir SS, Shah SA, Abdul Gafor AH, et al.

EXCLI J, 2018;17:563-575.
PMID: 30108461 DOI: 10.17179/excli2018-1256

Introduction: Hyperuricemia is associated with chronic kidney disease (CKD) progression and poor cardiovascular outcomes. We studied the effect of febuxostat on estimated glomerular filtration rate (eGFR), proteinuria and monitored the safety profile of the medication.
Material and Methods: This is a prospective open-label, randomized study in CKD stage 3 and 4 patients with diabetic nephropathy and asymptomatic hyperuricemia. Patients were randomized into febuxostat 40 mg daily and no treatment group using block randomization method and were followed up for 6 months. Their usual care for diabetes mellitus, hypertension and dyslipidemia were continued in the study. Blood and urine investigations were monitored at baseline, 3 months and 6 months.
Results: The eGFR in febuxostat group was stabilized at 6 months with no significant reduction [26.2 (IQR 14.30) at baseline to 26.3 (IQR 15.2) ml/min/1.73 m2]. Whereas, there was a significant reduction of the eGFR in no treatment group from 28.2 (IQR 17.9) to 27.6 (IQR 19.3) ml/min/1.73 m2 (p value < 0.01). We found the HbA1c (glycosylated hemoglobin) was significantly increased in febuxostat group from 7.2 ± 0.5 % at baseline to 7.6 ± 1.4 at 6 months (p value 0.04) but no significant change of HbA1c in the no treatment group. Proteinuria level was unchanged in both groups. The commonest adverse event was joint pain.
Conclusions: Febuxostat was able to preserve eGFR in CKD patients with diabetic nephropathy and this effect was beyond glycemic control. Increment of HbA1c level in febuxostat group needs further larger trials.
Study site: Chronic kidney disease clinic, Hospital Canselor Tuanku Muhriz, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia

Matched MeSH terms: Febuxostat*
A new Febuxostat-Telmisartan Drug-Drug Cocrystal for Gout-Hypertension Combination Therapy

Ganesan T, Muthudoss P, Voguri RS, Ghosal S, Ann EYC, Kwok J, et al.

J Pharm Sci, 2022 Dec;111(12):3318-3326.
PMID: 36028135 DOI: 10.1016/j.xphs.2022.08.022

Drug-drug cocrystalllization is a novel mechanism for effective pharmacological combination therapy. In this work, we have demonstrated the preparation of a drug-drug cocrystal of a hypertension drug (Telmisartan; TEL) with a hyperuricemia drug (Febuxostat; FEB) in 1:1 molar ratio using a solvent evaporation method for the first time. Generally, a multi-component system may yield either a eutectic, salt, and/or a cocrystal. This study adopted a methodical orthogonal framework to analyze the final solid form. A single crystal X-ray structural investigation revealed the formation of a heterosynthon with carboxylic and benzimidazole groups of FEB and TEL, respectively, in the triclinic P-1 space group. ΔpKa of the heterosynthon is ∼1.5, hence, based on the empirical rules, a salt-cocrystal continuum is hypothesized. Further, attenuated total reflectance Fourier transform infrared (ATR-FTIR), and Raman spectroscopy were employed to corroborate the hydrogen bond formation in the heterosynthon (-N---H-O-), which confirmed the propensity for cocrystal formation. An accelerated stability study and an in vitro biorelevant dissolution study of the cocrystal were performed, which demonstrated that it is physiochemically stable, but it resulted in a slower dissolution rate when compared with plain drugs.

Matched MeSH terms: Febuxostat
Fulltext Successful febuxostat desensitization in a patient with febuxostat hypersensitivity: A Malaysian experience

Sulaiman N, Othman AZ, Shahril NS, Abdul Rashid AM, Md Noh MSF

SAGE Open Med Case Rep, 2017;5:2050313X17749080.
PMID: 29318019 DOI: 10.1177/2050313X17749080

Over the years, allopurinol has been widely used as the preferred choice of urate lowering therapy in patients with gout. However, its role in patients with renal impairment is limited; and adverse reactions are well documented. Febuxostat, a newer oral non-purine xanthine oxidase inhibitor has been proven in several trials to be more effective and tolerable compared to allopurinol and may be used in patients with renal impairment. Here, we describe a case of successful febuxostat desensitization in a patient with a history of allopurinol- and febuxostat-induced adverse cutaneous reaction, as well as the protocol utilized.

Matched MeSH terms: Febuxostat
Fulltext A single-centre experience of febuxostat as a second-line urate-lowering therapy

Ong SG, Ding HJ

Malays Fam Physician, 2021 Mar 25;16(1):50-55.
PMID: 33948142 DOI: 10.51866/oa0892

Introduction: The purpose of this study was to describe the local experience in terms of drug efficacy and safety using a new xanthine oxidase inhibitor, febuxostat, as a second-line urate-lowering therapy (ULT) in gout patients with normal renal function and chronic kidney disease.
Methods: This cross-sectional study included all gout patients who attended the rheumatology clinic from January 2013 to June 2018 and had received febuxostat as a second-line ULT. Analysis focused on the proportion of gout patients who achieved target serum urate (sUA) of <360 μmol/L, duration taken to achieve target sUA, and febuxostat dosage at achievement of target sUA. Safety assessments included comparison of serum creatinine, estimated glomerular filtration rate (eGFR), and serum alanine aminotransferase (ALT) at baseline, at achievement of target sUA, and at 12-monthly intervals.
Results: Majority (90.9%) of patients achieved target sUA. Median duration required to achieve target sUA was 5.5 months with IQR (interquartile range) of 8.5. Five (22.7%) patients achieved target sUA within one month of therapy with febuxostat 40 mg per day. Eleven (55%) patients achieved target sUA within six months and 16 (80%) by 12 months. Equal proportion of patients achieved target sUA with febuxostat 40 mg per day and 80 mg per day, respectively. There was no significant difference in the changes in serum creatinine level, eGFR and ALT from baseline and at achievement of target sUA, nor at 12-monthly intervals throughout the duration of febuxostat therapy. Apart from three patients who developed hypersensitivity reactions to febuxostat, no other adverse events were reported.
Conclusion: A significant proportion of gout patients with CKD managed to achieve target sUA with a lower dose of febuxostat at 40 mg per day and it is reasonable to maintain this dose for up to six months before considering dose escalation.

Matched MeSH terms: Febuxostat
Fulltext The use of febuxostat for gout in Hospital Tengku Ampuan Afzan (HTAA) Kuantan. [Abstract]

Abdullah H

International Medical Journal Malaysia, 2017;16(11):50.
MyJurnal

Introduction: Febuxostat is a non-purine-selective oral xanthine oxidase inhibitor drug, and is an alternative to Allopurinol to lower serum uric acid in gout patients. It is probably more effective than Allopurinol, however, its use is limited because of its cost and availability. Allopurinol has been the mainstay treatment for gout for about 50 years. However, its use has been associated with allergic reactions especially in patients with renal impairment.The objective of this study was to describe HTAA Rheumatology Unit experiences with Febuxostat in the management of gout.
Materials and method: Case records belonging to 6 patients who had been started on Febuxostat between January 2012 and January 2017 were analysed.
Results: The majority of patients on Febuxostat were males (83.3%) as well as Malays (83.3%). About 66.7% of patients had already developed mild to moderate chronic kidney disease (GFR between 30-89 mL/min) due to multifactorial causes by the time they were started on Febuxostat. Also 33% of patients had mild liver impairment (ALT & AST < 1.5 ULN) due to fatty liver prior to Febuxostat. All patients had been started on Febuxostat due to allergic reactions to Allopurinol. All patients were on Febuxostat 40 mg once a day. Following Febuxostat, a significant decrease in the uric acid levels much closer to the target level i.e. less than 360 µmol/L were achieved in all patients. Only 1 patient (16.7%) developed a side effect i.e. ALT > 1.5 ULN while the rest tolerated the drug very well.
Conclusion: Although the number of patients analysed was small, Febuxostat was shown to be very effective and safe for use in patients with gout even with concomitant mild to moderate renal impairment. Serum uric acid levels reduced significantly while on the lowest dose of 40 mg once a day.

Matched MeSH terms: Febuxostat
Fulltext Use of newly available febuxostat in a case of chronic tophaceous gout contraindicated to allopurinol and probenecid

Abdullah H, Asmahan MI, Rosman A

Med J Malaysia, 2012 Feb;67(1):125-6.
PMID: 22582566 MyJurnal

Urate lowering therapy in this country has mainly been achieved by the use of allopurinol and probenecid. A new xanthine oxidase inhibitor called febuxostat has been approved in 2009 for treatment of hyperuricaemia in gout. In this report, we describe the management of a patient with chronic tophaceous gout using febuxostat. The reduction in serum uric acid to target levels was rapid, and the tophi size had also reduced significantly while on therapy. There was no unwanted side effect observed during the therapy. Therefore, febuxostat would be a useful alternative drug in the treatment of hyperuricaemia in gout patients who have contraindications to allopurinol and probenecid.
Study site: Rheumatology clinic, Selayang Hospital, Kuala Lumpur, Malaysia

Matched MeSH terms: Febuxostat