Twice-Daily Cysteamine Bitartrate Therapy for Children with Cystinosis

Dohil, Ranjan; Fidler, Meredith C.; Gangoiti, Jon A.; Kaskel, Frederick J.; Schneider, Jerry A.; Barshop, Bruce A.

doi:10.1016/j.jpeds.2009.07.016

Cited by 50 publications

(64 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The initial sample size calculation and the predetermined noninferiority margin (0.3 nmol 1/2 cystine/mg protein) were based on a study from the University of California at San Diego study (15) of weekly steady-state serial measures of WBC cystine levels from seven patients treated with Cystagon followed by treatment with an entericcoated cysteamine bitartrate (EC-Cysteamine).…”

Section: Statistical Analysesmentioning

confidence: 99%

“…There is evidence that failure to adhere to this strict Q6H dosing regimen results in more rapid deterioration of kidney function as WBC cystine levels rise (13). A small pilot trial suggested that a delayed-release Q12H formulation of cysteamine, EC-Cysteamine, was able to maintain WBC cystine levels comparable with the marketed immediaterelease Q6H formulation (15,16).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Randomized Controlled Crossover Trial with Delayed-Release Cysteamine Bitartrate in Nephropathic Cystinosis

Langman

Greenbaum

Sarwal

et al. 2012

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

SummaryBackground and objectives Immediate-release cysteamine bitartrate (Cystagon; Mylan Pharmaceuticals, Canonsburg, PA) may prevent or delay kidney transplantation and other serious outcomes in patients with cystinosis, but has never been subjected to a prospective clinical trial. Cystagon efficacy requires strict lifelong dosing every 6 hours. Such a dosing schedule and Cystagon-associated side effects are often cited by patients as reasons for nonadherence. Design, setting, participants, & measurementsThis open-label, randomized, controlled, crossover trial was powered to show that a new delayed-release formulation of cysteamine bitartrate, RP103, taken every 12 hours, was noninferior to Cystagon for maintenance of white blood cell (WBC) cystine at levels associated with optimal outcomes in the disease.Results Forty-three patients were randomized. Using a mixed-effects statistical analysis model, the least-squares mean peak value of WBC cystine level was 0.6260.05 nmol 1/2 cystine/mg protein after 12 hours under RP103 and 0.5460.05 nmol 1/2 cystine/mg protein after 6 hours under Cystagon, a difference of 0.0860.04 nmol 1/2 cystine/mg protein (95.8% confidence interval, 0-0.16). The average steady-state total daily dose of RP103 was 82% of the incoming steady-state total daily dose of Cystagon. There were three-fold more gastrointestinal side effects compared with using Cystagon.Conclusions A new delayed-release Q12H formulation of cysteamine bitartrate is not inferior to the Q6H formulation (Cystagon) in maintaining low WBC cystine levels in patients with cystinosis but at a lower total daily dose.

show abstract

Section: Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Randomized Controlled Crossover Trial with Delayed-Release Cysteamine Bitartrate in Nephropathic Cystinosis

Langman

Greenbaum

Sarwal

et al. 2012

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…With early and diligent therapy, cystinosis patients can prevent or delay most of the non-renal complications and extend their lives into a fourth or fifth decade, live independently and some women have borne children (5,9). The renal damage is continuous however, and decline is inevitable (5).…”

Section: Introductionmentioning

confidence: 99%

“…Cysteamine causes a range of side effects, and this is largely due to the high dose which is required as much of the drug is lost to first-pass metabolism (9). High blood levels must be achieved, as a large proportion of the administered drug will bind to circulating proteins, and cannot be up taken by the cells (10,11).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Suppository formulations as a potential treatment for nephropathic cystinosis

Buchan

Kay

Matthews

et al. 2012

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Pharmacokinetic Studies of Cysteamine Bitartrate Delayed‐Release

Dohil

Rioux

2013

Clinical Pharm in Drug Dev

Self Cite

View full text Add to dashboard Cite

A twice-daily microsphere formulation of cysteamine bitartrate has been developed for cystinosis and other potential applications. To date, there are no published pharmacokinetic data for cysteamine bitartrate delayed-release in healthy adults. Three randomized open-label, crossover studies to determine the effects of fasting, high fat, and carbohydrate meals on the bioavailability of cysteamine bitartrate delayed-release (600 mg) administered in capsule or sprinkle form to healthy adults. Adverse events were monitored. Fifty-eight adults were studied. Cysteamine absorption (AUC0-24 hours ) was the same for capsule and sprinkle forms during all meal/fasting states. The AUC0-24 hours for capsules while fasted, 30 and 120 minutes before a carbohydrate meal and during a high fat meal were 6,313 ± 329, 4,616 ± 878, 6,691 ± 669, 2,572 ± 295 minutes × µM, respectively, and the mean Cmax values were 29.4 ± 1.7, 20.7 ± 4.9, 31.6 ± 3.0, and 10.9 ± 1.7 µM, respectively. The mean Tmax following fasting and high fat meal were about 3 and 6 hours, respectively. Minor transient GI adverse events occurred. Cysteamine bitartrate delayed-release capsule and sprinkle forms are bioequivalent and optimal absorption occurs during fasting state. High fat diet reduces drug absorption, increases the Tmax and should be avoided at the time of drug ingestion. Cysteamine bitartrate delayed-release (RP103) is best ingested >30 minutes before a carbohydrate-rich meal.

show abstract

Twice-Daily Cysteamine Bitartrate Therapy for Children with Cystinosis

Cited by 50 publications

References 17 publications

A Randomized Controlled Crossover Trial with Delayed-Release Cysteamine Bitartrate in Nephropathic Cystinosis

A Randomized Controlled Crossover Trial with Delayed-Release Cysteamine Bitartrate in Nephropathic Cystinosis

Suppository formulations as a potential treatment for nephropathic cystinosis

Pharmacokinetic Studies of Cysteamine Bitartrate Delayed‐Release

Contact Info

Product

Resources

About