Safety & Tolerability
Learn about the safety and
tolerability of RAVICTI
aAn uncontrolled, open-label study was conducted in 16 children less than 2 months of age to assess transition to RAVICTI over a period of 7 days, followed by monthly assessment of ammonia control and hyperammonemic crises over a 24-month period. Ammonia values across different laboratories were normalized to a common normal pediatric range of 28 to 57 μmol/L.1
bSixteen, 14, 12, 6, and 3 patients completed 1, 3, 6, 12, and 18 months of treatment, respectively (median exposure of 10 months [range, 2 to 20 months]).1
cSuccessful transition was defined as no signs and symptoms of hyperammonemia and a venous ammonia value less than 100 μmol/L.1
dUncontrolled, open-label studies were conducted to assess monthly ammonia control and hyperammonemic crises with RAVICTI in pediatric patients 2 months to less than 2 years of age (study 4/4E, study 5, and study 6). Patients in study 5 previously participated in study 4/4E. A total of 17 pediatric patients with UCDs 2 months to less than 2 years of age participated in the studies. Ammonia values across different laboratories were normalized to a common normal pediatric range of 28 to 57 μmol/L.1
eNine, 7, and 3 patients completed 1, 3, and 6 months of treatment, respectively (mean and median exposure of 4 and 5 months, respectively).1
fSuccessful transition was defined as no signs and symptoms of hyperammonemia and a venous ammonia value less than 100 μmol/L.1
gThe efficacy of RAVICTI in pediatric patients 2 to 17 years of age was evaluated in 2 fixed-sequence, open-label, NaPBA-to-RAVICTI crossover studies (studies 3 and 4). Study 3 was 7 days in duration and study 4 was 10 days in duration. These studies compared blood ammonia levels of patients on RAVICTI with venous ammonia levels of patients on NaPBA in 26 pediatric patients between 2 months and 17 years of age. The AUC0–24h for blood ammonia in 11 pediatric patients 6 to 17 years of age (study 3) and 11 pediatric patients 2 to 5 years of age (study 4) were similar between treatments.1
hLong-term (12-month), uncontrolled, open-label studies were conducted to assess monthly ammonia control and hyperammonemic crises. In 2 studies, a total of 26 pediatric patients 6 to 17 years of age were enrolled, and all but 1 had been converted from NaPBA to RAVICTI. Ammonia values across different laboratories were normalized to a common normal range of 9 to 35 μmol/L.1
iA randomized, double-blind, active-controlled, crossover, noninferiority study compared RAVICTI with NaPBA by evaluating venous ammonia levels in patients with UCDs who had been on NaPBA prior to enrollment. Forty-four patients were randomized 1:1 to receive either NaPBA for 2 weeks then RAVICTI for 2 weeks, or RAVICTI for 2 weeks then NaPBA for 2 weeks. RAVICTI was noninferior to NaPBA with respect to the AUC0–24h for ammonia.1
jA long-term (12-month), uncontrolled, open-label study was conducted to assess monthly ammonia control and hyperammonemic crises. A total of 51 adult patients were in the study and all but 6 had been converted from NaPBA to RAVICTI. Ammonia values across different laboratories were normalized to a common normal range of 9 to 35 μmol/L.1
Learn about the safety and
tolerability of RAVICTI
Review the patient treatment profile and
administration features of RAVICTI
References: 1. RAVICTI (glycerol phenylbutyrate) Oral Liquid [prescribing information] Horizon. 2. Berry SA, Longo N, Diaz GA, et al. Safety and efficacy of glycerol phenylbutyrate for management of urea cycle disorders in patients aged 2 months to 2 years. Mol Genet Metab. 2017;122(3):46-53. doi:10.1016/j.ymgme.2017.09.002 3. Longo N, Holt RJ. Glycerol phenylbutyrate for the maintenance treatment of patients with deficiencies in enzymes of the urea cycle. Exp Opin Orphan Drugs. 2017;5(12):999-1010. doi:10.1080/21678707.2017.1405807. 4. Lee B, Diaz GA, Rhead W, et al. Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder. Genet Med. 2015;17(7):561-568. doi:10.1038/gim.2014.148 5. Lichter-Konecki U, Diaz GA, Merritt JL II, et al. Ammonia control in children with urea cycle disorders (UCDs); phase 2 comparison of sodium phenylbutyrate and glycerol phenylbutyrate. Mol Genet Metab. 2011;103(4):323-329. doi:10.1016/j.ymgme.2011.04.013 6. Smith W, Diaz GA, Lichter-Konecki U, et al. Ammonia control in children ages 2 months through 5 years with urea cycle disorders: comparison of sodium phenylbutyrate and glycerol phenylbutyrate. J Pediatr. 2013;162(6):1228-1234.e1. doi:10.1016/j.jpeds.2012.11.084 7. Diaz GA, Krivitzky LS, Mokhtarani M, et al. Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Hepatology. 2013;57(6):2171-2179. doi:10.1002/hep.26058 8. Diaz GA, Schulze A, Longo N, et al. Long-term safety and efficacy of glycerol phenylbutyrate for the management of urea cycle disorder patients. Mol Genet Metab. 2019;127(4):336-345. doi:10.1016/j.ymgme.2019.07.004 9. Data on File. Horizon, April 2017.
RAVICTI (glycerol phenylbutyrate) Oral Liquid is indicated for use as a nitrogen-binding agent for chronic management of patients with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or supplementation alone. RAVICTI must be used with dietary protein restriction and, in some cases, dietary supplements (e.g. essential amino acids, arginine, citrulline, protein-free calorie supplements).
The most common adverse reactions reported in clinical trials (at least 10% of patients) were:
Please see Full Prescribing Information.
RAVICTI (glycerol phenylbutyrate) Oral Liquid is indicated for use as a nitrogen-binding agent for chronic management of patients with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or supplementation alone. RAVICTI must be used with dietary protein restriction and, in some cases, dietary supplements (e.g. essential amino acids, arginine, citrulline, protein-free calorie supplements).
The most common adverse reactions reported in clinical trials (at least 10% of patients) were:
Please see Full Prescribing Information.