Byetta (exenatide) - Renal Failure
FDA notified healthcare professionals of revisions to the prescribing information for Byetta (exenatide) to include information on post-marketing reports of altered kidney function, including acute renal failure and insufficiency. Byetta, an incretin-mimetic, is approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
From April 2005 through October 2008, FDA received 78 cases of altered kidney function (62 cases of acute renal failure and 16 cases of renal insufficiency), in patients using Byetta. Some cases occurred in patients with pre-existing kidney disease or in patients with one or more risk factors for developing kidney problems. Labeling changes include:
•Information regarding post-market reports of acute renal failure and insufficiency, highlighting that Byetta should not be used in patients with severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease.
•Recommendations to healthcare professionals that caution should be applied when initiating or increasing doses of Byetta from 5 mcg to 10 mcg in patients with moderate renal impairment (creatinine clearance 30 to 50 ml/min).
•Recommendations that healthcare professionals monitor patients carefully for the development of kidney dysfunction, and evaluate the continued need for Byetta if kidney dysfunction is suspected while using the product.
•Information about kidney dysfunction in the patient Medication Guide to help patients understand the benefits and potential risks associated with Byetta.
Read the complete MedWatch 2009 safety summary, including a link to the Healthcare Professional information sheet, at:
http://www.fda.gov/Safety/ MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalPro ducts/ucm188703.htm
Tuesday, November 3, 2009
Long-Term Use of Trimethoprim-Sulfamethoxazole May Reduce UTIs in At-Risk Children
Long-Term Use of Trimethoprim-Sulfamethoxazole May Reduce UTIs in At-Risk Children
October 29, 2009 — Use of long-term, low-dose trimethoprim-sulfamethoxazole may reduce urinary tract infections in at-risk children, according to the results of a study reported in the October 29 issue of the New England Journal of Medicine.
"Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking," write Jonathan C. Craig, MB, ChB, PhD, from University of Sydney in Sydney, Australia, and colleagues from the Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric Reflux and Normal Renal Tracts (PRIVENT) Investigators. "This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children."
Children younger than 18 years with at least 1 microbiologically proven urinary tract infection were randomly selected to receive either daily trimethoprim-sulfamethoxazole suspension (2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The main endpoint of the study was symptomatic, microbiologically confirmed urinary tract infection, based on intent-to-treat analyses with the use of time-to-event data.
Although planned sample size was 780, a total of 576 children (64% girls) were recruited and randomly selected from December 1998 to March 2007. At study entry, median age was 14 months; 71% were enrolled after the first diagnosis of urinary tract infection, and 42% had known vesicoureteral reflux, which was grade 3 or higher in 53% of these participants.
Of 288 patients in the antibiotic group, urinary tract infection developed in 36 (13%) during the study vs 55 (19%) of 288 patients in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 - 0.93; P= .02 by the log-rank test).
Lower absolute risk for urinary tract infection in the antibiotic group (6 percentage points) appeared to be consistent across all subgroups of patients (P ≥ .20 for all interactions).
"Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children," the study authors write. "The treatment effect appeared to be consistent but modest across subgroups."
Limitations of this study include lower recruitment than planned, study not designed to estimate the effect of trimethoprim-sulfamethoxazole on the progression of renal damage, and inability to determine the incremental effect of trimethoprim-sulfamethoxazole vs circumcision.
"Since the rate of adverse events did not differ between the two study groups and the risk of infections other than urinary tract infection that were severe enough to require the use of antibiotics was lower in the antibiotic group, it would be reasonable for clinicians to recommend the use of trimethoprim-sulfamethoxazole in children who are at high risk for infection or whose index infection was severe," the study authors conclude. "In children who have had a single symptomatic urinary tract infection, prophylaxis with trimethoprim-sulfamethoxazole should be considered but not routinely recommended. The modest size of the benefit and the possibility of rare but serious complications from the use of trimethoprim-sulfamethoxazole, such as the Stevens-Johnson syndrome, suggest that the drug should not be used prophylactically in children who have never had a symptomatic urinary tract infection (e.g., those with congenital hydronephrosis or siblings with reflux)."
In an accompanying editorial, Alejandro Hoberman, MD, from the Children's Hospital of Pittsburgh in Pittsburgh, Pennsylvania, and Ron Keren, MD, MPH, from the Children's Hospital of Philadelphia in Philadelphia, Pennsylvania, note that the time-to-event analysis showed that the effect of long-term antibiotics was not sustained, and the number of children who would need to have been treated to prevent 1 infection was relatively large.
"Given the modest overall effect size, a one-size-fits-all approach may not be appropriate," Drs. Hoberman and Keren write. "The need to detect vesicoureteral reflux is probably the most important issue facing parents and clinicians....Early diagnosis and treatment of urinary tract infection and treatment of dysfunctional voiding, which predisposes many children to urinary tract infection, are likely to go a long way toward preventing long-term renal damage."
The National Health and Medical Research Council of Australia, the Financial Markets Foundation for Children of Australia, and a private donation by J.T. Honan of the Manildra Group supported this study. The study authors and editorialists have disclosed no relevant financial relationships.
N Engl J Med. 2009;361:1748-1759, 1804-1806.
October 29, 2009 — Use of long-term, low-dose trimethoprim-sulfamethoxazole may reduce urinary tract infections in at-risk children, according to the results of a study reported in the October 29 issue of the New England Journal of Medicine.
"Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking," write Jonathan C. Craig, MB, ChB, PhD, from University of Sydney in Sydney, Australia, and colleagues from the Prevention of Recurrent Urinary Tract Infection in Children with Vesicoureteric Reflux and Normal Renal Tracts (PRIVENT) Investigators. "This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children."
Children younger than 18 years with at least 1 microbiologically proven urinary tract infection were randomly selected to receive either daily trimethoprim-sulfamethoxazole suspension (2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The main endpoint of the study was symptomatic, microbiologically confirmed urinary tract infection, based on intent-to-treat analyses with the use of time-to-event data.
Although planned sample size was 780, a total of 576 children (64% girls) were recruited and randomly selected from December 1998 to March 2007. At study entry, median age was 14 months; 71% were enrolled after the first diagnosis of urinary tract infection, and 42% had known vesicoureteral reflux, which was grade 3 or higher in 53% of these participants.
Of 288 patients in the antibiotic group, urinary tract infection developed in 36 (13%) during the study vs 55 (19%) of 288 patients in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 - 0.93; P= .02 by the log-rank test).
Lower absolute risk for urinary tract infection in the antibiotic group (6 percentage points) appeared to be consistent across all subgroups of patients (P ≥ .20 for all interactions).
"Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children," the study authors write. "The treatment effect appeared to be consistent but modest across subgroups."
Limitations of this study include lower recruitment than planned, study not designed to estimate the effect of trimethoprim-sulfamethoxazole on the progression of renal damage, and inability to determine the incremental effect of trimethoprim-sulfamethoxazole vs circumcision.
"Since the rate of adverse events did not differ between the two study groups and the risk of infections other than urinary tract infection that were severe enough to require the use of antibiotics was lower in the antibiotic group, it would be reasonable for clinicians to recommend the use of trimethoprim-sulfamethoxazole in children who are at high risk for infection or whose index infection was severe," the study authors conclude. "In children who have had a single symptomatic urinary tract infection, prophylaxis with trimethoprim-sulfamethoxazole should be considered but not routinely recommended. The modest size of the benefit and the possibility of rare but serious complications from the use of trimethoprim-sulfamethoxazole, such as the Stevens-Johnson syndrome, suggest that the drug should not be used prophylactically in children who have never had a symptomatic urinary tract infection (e.g., those with congenital hydronephrosis or siblings with reflux)."
In an accompanying editorial, Alejandro Hoberman, MD, from the Children's Hospital of Pittsburgh in Pittsburgh, Pennsylvania, and Ron Keren, MD, MPH, from the Children's Hospital of Philadelphia in Philadelphia, Pennsylvania, note that the time-to-event analysis showed that the effect of long-term antibiotics was not sustained, and the number of children who would need to have been treated to prevent 1 infection was relatively large.
"Given the modest overall effect size, a one-size-fits-all approach may not be appropriate," Drs. Hoberman and Keren write. "The need to detect vesicoureteral reflux is probably the most important issue facing parents and clinicians....Early diagnosis and treatment of urinary tract infection and treatment of dysfunctional voiding, which predisposes many children to urinary tract infection, are likely to go a long way toward preventing long-term renal damage."
The National Health and Medical Research Council of Australia, the Financial Markets Foundation for Children of Australia, and a private donation by J.T. Honan of the Manildra Group supported this study. The study authors and editorialists have disclosed no relevant financial relationships.
N Engl J Med. 2009;361:1748-1759, 1804-1806.
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