RAVICTI SIDE EFFECTS
SIDE EFFECTS
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Assessment of adverse reactions was based on exposure of 45 adult patients (31 female and 14 male) with UCD subtype deficiencies of ornithine transcarbamylase (OTC, n=40), carbamoyl phosphate synthetase (CPS, n=2), and argininosuccinate synthetase (ASS, n=1) in a randomized, double-blind, active-controlled (RAVICTI vs sodium phenylbutyrate), crossover, 4-week study (Study 1) that enrolled patients 18 years of age and older. One of the 45 patients received only sodium phenylbutyrate prior to withdrawing on day 1 of the study due to an adverse reaction.
The most common adverse reactions (occurring in at least 10% of patients) reported during short-term treatment with RAVICTI were diarrhea, flatulence, and headache. Table 1 summarizes adverse reactions occurring in 2 or more patients treated with RAVICTI or sodium phenylbutyrate (incidence of at least 4% in either treatment arm).
Table 1: Adverse Reactions Reported in 2 or More Adult Patients with UCDs (at least 4% in Either Treatment Arm) in Study 1
| Number (%) of Patients in Study 1 | ||
| Sodium Phenylbutyrate (N = 45) |
RAVICTI (N = 44) |
|
| Diarrhea | 3 (7) | 7 (16) |
| Headache | 4 (9) | 6 (14) |
| Flatulence | 1 (2) | 6 (14) |
| Abdominal pain | 2 (4) | 3 (7) |
| Vomiting | 2 (4) | 3 (7) |
| Decreased appetite | 2 (4) | 3 (7) |
| Fatigue | 1 (2) | 3 (7) |
| Dyspepsia | 3 (7) | 2 (5) |
| Nausea | 3 (7) | 1 (2) |
| Dizziness | 4 (9) | 0 |
| Abdominal discomfort | 3 (7) | 0 |
Other Adverse Reactions
RAVICTI has been evaluated in 77 patients with UCDs (51 adult and 26 pediatric patients ages 2 years to 17 years) in 2 open-label long-term studies, in which 69 patients completed 12 months of treatment with RAVICTI (median exposure = 51 weeks). During these studies there were no deaths.
Adverse reactions reported in at least 10% of adult patients were nausea, vomiting, diarrhea, decreased appetite, dizziness, headache, and fatigue.
Adverse reactions reported in at least 10% of pediatric patients ages 2 years to 17 years were upper abdominal pain, rash, nausea, vomiting, diarrhea, decreased appetite, and headache.
RAVICTI has been evaluated in 17 patients with UCDs ages 2 months to less than 2 years in 3 open-label studies. The median exposure was 6 months (range 0.2 to 20 months). Adverse reactions reported in at least 10% of pediatric patients aged 2 months to less than 2 years were neutropenia, vomiting, constipation, diarrhea, pyrexia, hypophagia, cough, nasal congestion, rhinorrhea, rash, and papule.
RAVICTI has been evaluated in 16 patients with UCDs less than 2 months of age (age range 0.1 to 2 months, median age 0.5 months) in a single, open-label study. The median exposure was 10 months (range 2 to 20 months). Adverse reactions reported in at least 10% of pediatric patients aged less than 2 months were vomiting, rash, gastroesophageal reflux, increased hepatic enzymes, feeding disorder (decreased appetite, hypophagia), anemia, cough, dehydration, metabolic acidosis, thrombocytosis, thrombocytopenia, neutropenia, lymphocytosis, diarrhea, flatulence, constipation, pyrexia, lethargy, and irritability/agitation.
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of RAVICTI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:
- Abnormal body odor, including from skin, hair and urine
- Retching and gagging
- Dysgeusia or burning sensation in mouth
SRC: NLM .