The following clinically significant adverse reactions appear in other sections of the labeling: ● CNS Depression [see Warnings and Precautions (5.1) ] ● Abuse and Misuse [see Warnings and Precautions (5.2) ] ● Respiratory Depression and Sleep-Disordered Breathing [see Warnings and Precautions (5.4) ] ● Depression and Suicidality [see Warnings and Precautions (5.5) ] ● Other Behavioral or Psychiatric Adverse Reactions [see Warnings and Precautions (5.6) ] ● Parasomnias [see Warnings and Precautions (5.7) ] ● Use in Patients Sensitive to High Sodium Intake [see Warnings and Precautions (5.8) ] Most common adverse reactions in adults (incidence ≥ 5% and greater than placebo) reported for any dose of LUMRYZ were nausea, dizziness, enuresis, headache, and vomiting ( 6.1 ).
Most common adverse reactions for pediatric patients (≥ 5%) in a study with immediate-release sodium oxybate were nausea, enuresis, vomiting, headache, weight decreased, decreased appetite, dizziness, and sleepwalking ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Avadel CNS Pharmaceuticals, LLC at 1-888-828-2335 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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. Adult Patients LUMRYZ was studied in one placebo-controlled trial (Study 1) [see Clinical Studies (14.1) ] in 212 patients with narcolepsy (107 patients treated with LUMRYZ and 105 with placebo).
Adverse Reactions Leading to Treatment Discontinuation In Study 1, 15.9% of patients treated with LUMRYZ discontinued because of adverse reactions, compared to 1.9% of patients receiving placebo. The most common adverse reaction leading to discontinuation was dizziness (4.7%). For LUMRYZ, 5.6% of patients discontinued due to adverse reactions on 4.5 g, 4.1% on 6 g, 4.5% on 7.5 g, and 3.9% on 9 g dose. Most Common Adverse Reactions The most common adverse reactions (incidence ≥5% and greater than placebo) reported for any dose of LUMRYZ were nausea, dizziness, enuresis, headache, and vomiting.
Adverse Reactions Occurring at an Incidence of 2% or Greater Table 2 lists adverse reactions occurring in 2% or more of LUMRYZ-treated patients on any individual dose and at a rate greater than placebo-treated patients in Study 1. Table 2: Adverse Reactions Occurring in 2% or More of LUMRYZ-Treated Adult Patients and Greater than for Placebo-Treated Patients in Study 1 Adverse Reaction Placebo (N=105) % LUMRYZ 4.5 g (N=107) % LUMRYZ 6 g (N=97) % LUMRYZ 7.5 g (N=88) % LUMRYZ 9 g (N=77) % Gastrointestinal Disorders Vomiting 2 3 3 6 5 Nausea 3 6 8 7 1 Investigations Weight Decreased 0 1 0 0 4 Metabolism and Nutritional Disorders Decreased Appetite 0 4 4 3 3 Nervous System Disorders Dizziness 0 6 4 6 5 Somnolence 1 0 1 2 4 Headache 6 7 5 6 0 Psychiatric Disorders Enuresis 0 2 4 9 9 Anxiety 1 3 1 3 1 Somnambulism 0 1 2 0 0 Dose-Response Information In the clinical trial in adult patients with narcolepsy, a dose-response relationship was observed for enuresis and somnolence.
Additional Adverse Reactions Adverse reactions observed in clinical studies with immediate-release sodium oxybate (≥2%), but not observed in Study 1 at a frequency of higher than 2%, and which may be relevant for LUMRYZ: diarrhea, abdominal pain upper, dry mouth, pain, feeling drunk, peripheral edema, cataplexy, muscle spasms, pain in extremity, tremor, disturbance in attention, paresthesia, sleep paralysis, disorientation, irritability, and hyperhidrosis.
Pediatric Patients (7 Years of Age and Older) The safety of LUMRYZ for the treatment of cataplexy or excessive daytime sleepiness in pediatric patients 7 years of age and older with narcolepsy is supported by an adequate and well-controlled trial of immediate-release sodium oxybate [see Clinical Studies (14.2) ] . Below is a display of adverse reactions of immediate-release sodium oxybate in this adequate and well-controlled trial.
In this trial, 104 patients aged 7 to 17 years (37 patients aged 7 to 11 years; 67 patients aged 12 to 17 years) with narcolepsy received immediate-release sodium oxybate for up to one year. This trial included an open-label safety continuation period in which eligible patients received immediate-release sodium oxybate for up to an additional 2 years. The median and maximum exposure across the entire trial were 371 and 987 days, respectively.
Adverse Reactions Leading to Treatment Discontinuation In the pediatric clinical trial with immediate-release sodium oxybate, 7 of 104 patients reported adverse reactions that led to withdrawal from the study (hallucination, tactile; suicidal ideation; weight decreased; sleep apnea syndrome; affect lability; anger, anxiety, depression; and headache). Adverse Reactions in the Pediatric Clinical Trial The most common adverse reactions (≥5%) were nausea (20%), enuresis (19%), vomiting (18%), headache (17%), weight decreased (13%), decreased appetite (9%), dizziness (8%), and sleepwalking (6%).
Additional information regarding safety in pediatric patients appears in the following sections: ● Respiratory Depression and Sleep-Disordered Breathing [see Warnings and Precautions (5.4) ] ● Depression and Suicidality [see Warnings and Precautions (5.5) ] ● Other Behavioral or Psychiatric Adverse Reactions [see Warnings and Precautions (5.6) ] ● Parasomnias [see Warnings and Precautions (5.7) ] The overall adverse reaction profile of immediate-release sodium oxybate in the pediatric clinical trial was similar to that seen in the adult clinical trial with immediate-release sodium oxybate.
The safety profile in pediatric patients with LUMRYZ is expected to be similar to that of adult patients treated with LUMRYZ and to that of pediatric patients treated with immediate-release sodium oxybate.
6.2Postmarketing Experience
The following adverse reactions have been identified during postapproval use of sodium oxybate. 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: Arthralgia, decreased appetite, fall*, fluid retention, hangover, headache, hypersensitivity, hypertension, memory impairment, nocturia, panic attack, vision blurred, and weight decreased. *The sudden onset of sleep in patients taking sodium oxybate, including in a standing position or while rising from bed, has led to falls complicated by injuries, in some cases requiring hospitalization.
