RESUMO
BACKGROUND: Colonoscopy may be one of the most frequent elective procedures in older adults and is associated with a low occurrence of complications. However, reduction of risks attributable to the bowel preparation may be achieved with the use of effective and safer products. AIM: The aim of this study was to examine the incidence of treatment-emergent adverse events (TEAEs) associated with SUPREP(®) [oral sulfate solution (OSS)] and other common prescription bowel preparations (non-OSS). METHODS: This real-world, observational study used de-identified health insurance claims and laboratory results to identify TEAEs in the 3 months following screening colonoscopy in adults with a prescription for a bowel preparation in the prior 60 days. The unadjusted and adjusted (controlling for patient risk factors) cumulative incidences of TEAEs were estimated using Kaplan-Meier and Poisson regression, respectively. RESULTS: Among patients ≥45 years, the overall cumulative incidence was significantly lower (p < 0.001) in the OSS cohort than in the non-OSS cohort (unadjusted: 2.31 vs. 2.89 %; adjusted: 1.61 vs. 1.95 %), with significantly lower acute cardiac conditions (1.56 vs. 1.90 %; p < 0.001), renal failure/other serious renal diseases (OSS: 0.21 %, non-OSS: 0.32 %; p < 0.001), and serum electrolyte abnormalities (OSS: 0.39 %, non-OSS: 0.49 %; p = 0.017). There were no significant differences between cohorts in death, seizure disorders, aggravation of gout, and ischemic colitis. Results were similar in the adjusted cumulative incidences. CONCLUSIONS: In actual use, the overall cumulative incidence of TEAEs was significantly lower in the OSS cohort, demonstrating that OSS is as safe as, or possibly safer than, non-OSS prescription bowel preparations.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Arritmias Cardíacas/induzido quimicamente , Catárticos/efeitos adversos , Colonoscopia , Eletrólitos/efeitos adversos , Desequilíbrio Hidroeletrolítico/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Adolescente , Adulto , Arritmias Cardíacas/epidemiologia , Colite Isquêmica/induzido quimicamente , Colite Isquêmica/epidemiologia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Gota/induzido quimicamente , Gota/epidemiologia , Cardiopatias/induzido quimicamente , Cardiopatias/epidemiologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Nefropatias/induzido quimicamente , Nefropatias/epidemiologia , Pessoa de Meia-Idade , Fosfatos/efeitos adversos , Polietilenoglicóis/efeitos adversos , Vigilância de Produtos Comercializados , Estudos Retrospectivos , Convulsões/induzido quimicamente , Convulsões/epidemiologia , Sulfatos/efeitos adversos , Desequilíbrio Hidroeletrolítico/epidemiologia , Adulto JovemRESUMO
The pharmacokinetics (PK) of an oral sulfate solution (OSS) for bowel cleansing preparation was studied. OSS (30 g of sulfate) was split between 2 doses, 12 hours apart. Safety measures included electrocardiography, vital signs, adverse events, hematology, blood chemistry, and urinalysis. Six adult patients with moderate renal disease (MRD), 6 with mild-moderate hepatic disease (M/MHD), and 6 normal healthy volunteers (NHVs) completed the study. Adverse events were mild to moderate in severity and were mainly limited to headache and expected gastrointestinal symptoms. Serum sulfate levels were highly variable at all times, even after adjusting for baseline. Sulfate was higher in MRD in comparison to the other groups. The C(max) and AUC were higher in the patients, but no statistically significant differences emerged. Sulfate levels returned to predose values within 54 hours after dosing. No electrolyte disturbances occurred. Urinary sulfate excretion was approximately 20% of the dose. OSS was well tolerated. The types and severity of adverse events were similar to those seen in large phase III trials. While patients with MRD had elevated sulfate, the levels were less than those in renal failure and did not alter biochemical parameters that are associated with hypersulfatemia.
Assuntos
Catárticos/administração & dosagem , Catárticos/farmacocinética , Colo/efeitos dos fármacos , Colonoscopia , Nefropatias/metabolismo , Hepatopatias/metabolismo , Sulfatos/administração & dosagem , Sulfatos/farmacocinética , Administração Oral , Adulto , Idoso , Área Sob a Curva , Estudos de Casos e Controles , Catárticos/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Eletrólitos/metabolismo , Feminino , Cefaleia/induzido quimicamente , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Soluções Farmacêuticas/administração & dosagem , Índice de Gravidade de Doença , Sulfatos/efeitos adversos , Irrigação Terapêutica , Sinais Vitais/efeitos dos fármacosRESUMO
An oral sulfate salt solution (OSS), under development as a bowel cleansing agent for colonoscopy in humans, is studied in rats and dogs. In rats, amaximumpractical oral OSS dose (5 g/kg/d) is compared with an oral sodium phosphate (OSP) solution, both at about 7 times the clinical dose. OSS induces the intended effects of loose stools and diarrhea. In rats, higher urine sodium and potassium accompany higher clearance rates, considered adaptive to the osmotic load of OSS. OSS for 28 days is well tolerated in rats and dogs. In contrast, OSP causes increased mortality, reduced body weight and food consumption, severe kidney tubular degeneration, and calcium phosphate deposition in rats. These are accompanied by mineralization in the stomach and aorta, along with cardiac and hepatic degeneration and necrosis. The greater safety margin of OSS over OSP at similarmultiples of the clinical dose indicates its suitability for human use.
Assuntos
Colonoscopia , Rim/efeitos dos fármacos , Fosfatos/toxicidade , Sulfatos/toxicidade , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Cálcio/sangue , Creatinina/metabolismo , Cães , Feminino , Rim/patologia , Masculino , Potássio/urina , Ratos , Sódio/sangue , Sódio/urinaRESUMO
BACKGROUND: Hyperphosphatemia underlies development of hyperparathyroidism, osteodystrophy, extraosseous calcification, and is associated with increased mortality in hemodialysis patients. METHODS: To determine whether calcium acetate or sevelamer hydrochloride best achieves recently recommended treatment goals of phosphorus =5.5 mg/dL and Ca x P product =55 mg(2)/dL(2), we conducted an 8-week randomized, double-blind study in 100 hemodialysis patients. RESULTS: Comparisons of time-averaged concentrations (weeks 1 to 8) demonstrated that calcium acetate recipients had lower serum phosphorus (1.08 mg/dL difference, P= 0.0006), higher serum calcium (0.63 mg/dL difference, P < 0.0001), and lower Ca x P (6.1 mg(2)/dL(2) difference, P= 0.022) than sevelamer recipients. At each week, calcium acetate recipients were 20% to 24% more likely to attain goal phosphorus [odds ratio (OR) 2.37, 95% CI 1.28-4.37, P= 0.0058], and 15% to 20% more likely to attain goal Ca x P (OR 2.16, 95% CI 1.20-3.86, P= 0.0097). Transient hypercalcemia occurred in 8 of 48 (16.7%) calcium acetate recipients, all of whom received concomitant intravenous vitamin D. By regression analysis hypercalcemia was more likely with calcium acetate (OR 6.1, 95% CI 2.8-13.3, P < 0.0001). Week 8 intact PTH levels were not significantly different. Serum bicarbonate levels were significantly lower with sevelamer hydrochloride treatment (P < 0.0001). CONCLUSION: Calcium acetate controls serum phosphorus and calcium-phosphate product more effectively than sevelamer hydrochloride. Cost-benefit analysis indicates that in the absence of hypercalcemia, calcium acetate should remain the treatment of choice for hyperphosphatemia in hemodialysis patients.