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RAVICTI® (glycerol phenylbutyrate)
Chronic management of patients with urea cycle disorders (UCDs) whose age >2 years and who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. RAVICTI must be used with dietary protein restriction and, in some cases, dietary supplements.
It is contraindicated in patient less than 2 month of age or breast feeding.
It is also contraindicated in hypersensitive to RAVICTI or its metabolites (phenylbutyric acid [PBA], phenylacetic acid [PAA], and phenylacetylglutamine [PAGN]).
Patients > 2 months and < 2 years of Age : the safety and efficacy of RAVICTI in this age group have not been established.
1. Switching From Sodium Phenylbutyrate to RAVICTI Patients:
Switching from sodium phenylbutyrate to RAVICTI should receive the dosage of RAVICTI that contains the same amount of phenylbutyric acid. The conversion is as follows: Total daily dosage of RAVICTI (mL) = total daily dosage of sodium phenylbutyrate tablets (g) x 0.86.
2. Initial Dosage in Phenylbutyrate-Naïve Patients :
The recommended dosage range, based upon body surface area, in patients naïve to phenylbutyrate (PBA) is 4.5 to 11.2 mL/m2/day (5 to 12.4 g/m2/day). For patients with some residual enzyme activity who are not adequately controlled with protein restriction, the recommended starting dosage is 4.5 mL/m2/day. In determining the starting dosage of RAVICTI in treatment-naïve patients, consider the patient’s residual urea synthetic capacity, dietary protein requirements, and diet adherence. Dietary protein is approximately 16% nitrogen by weight. Given that approximately 47% of dietary nitrogen is excreted as waste and approximately 70% of an administered PBA dose will be converted to urinary phenylacetylglutamine (U-PAGN), an initial estimated RAVICTI dose for a 24-hour period is 0.6 mL RAVICTI per gram of dietary protein ingested per 24-hour period. The total daily dosage should not exceed 17.5 mL.
3. Dosage Adjustment and Monitoring :
During treatment with RAVICTI, patients should be followed clinically and with plasma ammonia levels to determine the need for dosage titration. Closely monitor plasma ammonia levels during treatment with RAVICTI and when changing the dosage of RAVICTI. The methods used for measuring plasma ammonia levels vary among individual laboratories and values obtained using different assay methods may not be interchangeable. Normal ranges and therapeutic target levels for plasma ammonia depend upon the assay method used by the individual laboratory. During treatment with RAVICTI, refer to the assay-specific normal ranges and to the therapeutic target ranges for plasma ammonia.(190)
Oral liquid: 1.1 g/mL
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Most common adverse reactions (≥10%) in adults are: diarrhea, flatulence, and headache.
Drug interactions:
Corticosteroids, valproic acid, or haloperidol: May increase plasma ammonia level; monitor ammonia levels closely.
Probenecid: May affect renal excretion of metabolites of RAVICTI, including phenylacetylglutamine (PAGN) and PAA.
CYP3A4 Substrates with narrow therapeutic index (e.g., alfentanil, quinidine, cyclosporine): RAVICTI may decrease exposure; monitor for decreased efficacy of the narrow therapeutic index drug.
Midazolam: Decreased exposure; monitor for suboptimal effect of midazolam.
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190. Susan A Berry, Uta Lichter-Konecki, George A Diaz, Shawn E McCandless, William Rhead, Wendy Smith, Cynthia Lemons, Sandesh C S Nagamani, Dion F Coakley, Masoud Mokhtarani, Bruce F Scharschmidt, Brendan Lee. Glycerol phenylbutyrate treatment in children with urea cycle disorders: pooled analysis of short and long-term ammonia control and outcomes. Clinical Trial Mol Genet Metab . 2014 May;112(1):17-24. doi: 10.1016/j.ymgme.2014.02.007.
