XYREM SIDE EFFECTS
- Generic Name: sodium oxybate
- Brand Name: Xyrem
- Drug Class: CNS Depressants
SIDE EFFECTS
The following clinically significant adverse reactions appear in other sections of the labeling:
- CNS depression
- Abuse and Misuse
- Respiratory Depression and Sleep-Disordered Breathing
- Depression and Suicidality
- Other Behavioral or Psychiatric Adverse Reactions
- Parasomnias
- Use in Patients Sensitive to High Sodium Intake
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.
Adult Patients
Xyrem was studied in three placebo-controlled clinical trials (Trials N1, N3, and N4, described in Sections 14.1 and 14.2) in 611 patients with narcolepsy (398 subjects treated with Xyrem, and 213 with placebo). A total of 781 patients with narcolepsy were treated with Xyrem in controlled and uncontrolled clinical trials.
Section 6.1 and Table 4 present adverse reactions from three pooled, controlled trials (N1, N3, N4) in patients with narcolepsy.
Adverse Reactions Leading to Treatment Discontinuation
Of the 398 patients with narcolepsy treated with Xyrem, 10.3% of patients discontinued because of adverse reactions compared with 2.8% of patients receiving placebo. The most common adverse reaction leading to discontinuation was nausea (2.8%). The majority of adverse reactions leading to discontinuation began during the first few weeks of treatment.
Commonly Observed Adverse Reactions in Controlled Clinical Trials
The most common adverse reactions (incidence ≥5% and twice the rate seen with placebo) in patients treated with Xyrem were nausea, dizziness, vomiting, somnolence, enuresis, and tremor.
Adverse Reactions Occurring at an Incidence of 2% or Greater
Table 1 lists adverse reactions that occurred at a frequency of 2% or more in any treatment group for three controlled trials and were more frequent in any Xyrem treatment group than with placebo. Adverse reactions are summarized by dose at onset. Nearly all patients in these studies initiated treatment at 4.5 g per night. In patients who remained on treatment, adverse reactions tended to occur early and to diminish over time.
Table 1 Adverse Reactions Occurring in ≥2% of Adult Patients and More Frequently with Xyrem than Placebo in Three Controlled Trials (N1, N3, N4) by Body System and Dose at Onset
| Adverse Reaction | Placebo (n=213) % |
Xyrem 4.5g (n=185) % |
Xyrem 6g (n=258) % |
Xyrem 9g (n=178) % |
| ANY ADVERSE REACTION | 62 | 45 | 55 | 70 |
| GASTROINTESTINAL DISORDERS | ||||
| Nausea | 3 | 8 | 13 | 20 |
| Vomiting | 1 | 2 | 4 | 11 |
| Diarrhea | 2 | 4 | 3 | 4 |
| Abdominal pain upper | 2 | 3 | 1 | 2 |
| Dry mouth | 2 | 1 | 2 | 1 |
| GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS | ||||
| Pain | 1 | 1 | <1 | 3 |
| Feeling drunk | 1 | 0 | <1 | 3 |
| Edema peripheral | 1 | 3 | 0 | 0 |
| MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS | ||||
| Cataplexy | 1 | 1 | 1 | 2 |
| Muscle spasms | 2 | 2 | <1 | 2 |
| Pain in extremity | 1 | 3 | 1 | 1 |
| NERVOUS SYSTEM DISORDERS | ||||
| Dizziness | 4 | 9 | 11 | 15 |
| Somnolence | 4 | 1 | 3 | 8 |
| Tremor | 0 | 0 | 2 | 5 |
| Disturbance in attention | 0 | 1 | 0 | 4 |
| Paresthesia | 1 | 2 | 1 | 3 |
| Sleep paralysis | 1 | 0 | 1 | 3 |
| PSYCHIATRIC DISORDERS | ||||
| Disorientation | 1 | 1 | 2 | 3 |
| Irritability | 1 | 0 | <1 | 3 |
| Sleepwalking | 0 | 0 | 0 | 3 |
| Anxiety | 1 | 1 | 1 | 2 |
| RENAL AND URINARY DISORDERS | ||||
| Enuresis | 1 | 3 | 3 | 7 |
| SKIN AND SUBCUTANEOUS TISSUE DISORDERS | ||||
| Hyperhidrosis | 0 | 1 | 1 | 3 |
Dose-Response Information
In clinical trials in narcolepsy, a dose-response relationship was observed for nausea, vomiting, paresthesia, disorientation, irritability, disturbance in attention, feeling drunk, sleepwalking, and enuresis. The incidence of all these reactions was notably higher at 9 g per night.
In controlled trials in narcolepsy, discontinuations of treatment due to adverse reactions were greater at higher doses of Xyrem.
Pediatric Patients (7 Years Of Age And Older)
In the pediatric clinical trial (Trial N5), 104 patients aged 7 to 17 years (37 patients aged 7 to 11 years; 67 patients aged 12 to 17 years) with narcolepsy received Xyrem for up to one year. This study included an open-label safety continuation period in which eligible patients received Xyrem for up to an additional 2 years. The median and maximum exposure across the entire study were 371 and 987 days, respectively.
Adverse Reactions Leading to Treatment Discontinuation
In the pediatric clinical trial, 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
- Depression and Suicidality
- Other Behavioral or Psychiatric Adverse Reactions
- Parasomnias
The overall adverse reaction profile of Xyrem in the pediatric clinical trial was similar to that seen in the adult clinical trial program.
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of Xyrem. 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.
SRC: NLM .