Horizon Pharma plc Announces the U.S. Patent and Trademark Office Issuance of an Additional Notice of Allowance With Claims Covering RAVICTI(R) (Glycerol Phenylbutyrate) Oral Liquid - Seite 2

• In patients less than 2 months of age
• In patients who develop or have known hypersensitivity to phenylbutyrate

WARNINGS AND PRECAUTIONS:

• Phenylacetate (PAA), the major metabolite of RAVICTI, may be toxic at levels ≥500 µg/mL. Reduce RAVICTI dosage if symptoms of neurotoxicity, including vomiting, nausea, headache, somnolence, confusion, or sleepiness are present in the absence of high ammonia or other intercurrent illnesses.
• Low or absent pancreatic enzymes or intestinal disease resulting in fat malabsorption may result in reduced or absent digestion of RAVICTI and/or absorption of phenylbutyrate and reduced control of plasma ammonia. Monitor ammonia levels closely.
• RAVICTI should be used with caution in patients who are pregnant or planning to become pregnant. Based on animal data it may cause fetal harm. A voluntary patient registry will include evaluation of pregnancy outcomes in patients with UCDs. For more information regarding the registry program, visit www.ucdregistry.com or call 1-855-823-2592
• Caution should be exercised when administering RAVICTI to nursing mothers, as breastfeeding is not recommended with maternal use of RAVICTI. It is not known whether RAVICTI or its metabolites are present in breast milk

ADVERSE REACTIONS:

• Adverse reactions occurring in ≥10% of adult patients during short-term treatment (n=44, 4 weeks) with RAVICTI were diarrhea, flatulence, and headache.
• Adverse reactions occurring in ≥10% of adult patients during long-term treatment (n=51, 12 months) with RAVICTI were nausea, vomiting, diarrhea, decreased appetite, hyperammonemia, dizziness, headache, and fatigue.
• Adverse events occurring in ≥10% of pediatric patients during long-term treatment (n=26, 12 months) with RAVICTI were upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite, hyperammonemia, 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 PAGN and PAA

About Urea Cycle Disorders (UCDs)
Urea Cycle Disorders or UCDs are inherited metabolic diseases caused by a deficiency of one of the enzymes or transporters that constitute the urea cycle. The urea cycle involves a series of biochemical steps in which ammonia, a potent neurotoxin, is converted to urea, which is excreted in the urine. UCD patients may experience episodes where they get symptoms from the ammonia in their blood being excessively high -- called hyperammonemic crises -- which may result in irreversible brain damage, coma or death. UCD symptoms may first occur at any age depending on the severity of the disorder, with more severe defects presenting earlier in life.