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Drug details for : XYREM 500 mg/ml oral solution
| Drug class description : | Other Nervous System Drugs |
| Generic Name : | Sodium Oxybate |
| Drug description : | Oral solution. The oral solution is clear to slightly opalescent. |
| Presentation : | One ml Xyrem contains 500 mg of sodium oxybate. |
| Indications : | Treatment of cataplexy in adult patients with narcolepsy. |
| Adult Dosage : | Treatment should be initiated by and remain under the guidance of a physician experienced in the treatment of sleep disorders. Due to the well known potential of abuse of sodium oxybate, physicians should evaluate patients for a history of drug abuse (See Special Precautions). The recommended starting dose is 4.5 g/day sodium oxybate (9 ml Xyrem) divided into two equal doses of 2.25 g/dose (4.5 ml/dose). The dose should be titrated to effect based on efficacy and tolerability (See Special Precautions) up to a maximum of 9 g/day divided into two equal doses of 4.5g/dose (9ml/dose) by adjusting up or down in dose increments of 1.5 g/day (i.e. 0.75 g/dose or 1.5 ml/dose). A minimum of two weeks is recommended between dosage increments. The dose of 9g/day should not be exceeded due to the possible occurrence of severe symptoms at doses of 18 g/day or above (See Special Precations). A 10ml measuring syringe and two 90 ml dosing cups are provided with Xyrem. Each dose of Xyrem must be diluted with 60 ml of water in the dosing cup prior to ingestion. Single doses of 4.5g should not be given unless the patient has been titrated previously to that dose level. Because food significantly reduces the bioavailability of sodium oxybate, patients should eat at least several (2-3) hours before taking the first dose of Xyrem at bedtime. Patients should always observe the same timing of dosing in relation to meals. Using Xyrem Xyrem should be taken orally upon getting into bed and again between 2.5 to 4 hours later. It is recommended that both doses of Xyrem should be made up at the same time upon retiring to bed. Xyrem is provided for use with a graduated measuring syringe and dosing cup with child resistant cap. Each measured dose of Xyrem must be dispensed into the dosing cup and diluted with 60 ml of water prior to ingestion. Discontinuation of Xyrem The discontinuation effects of sodium oxybate have not been systematically evaluated in controlled clinical trials (See Special Precautions). If the patient stops medication for more than 14 consecutive days, titration should be restarted from the lowest dose Patients with hepatic impairment The starting dose should be halved in patients with hepatic impairment, and response to dose increments monitored closely (See Special Precautions). Patients with renal impairment Patients with impaired renal function should consider a dietary recommendation to reduce sodium intake (See Special Precautions). |
| Child Dosage : | Safety and effectiveness in children and adolescents has not been established, therefore use in patients under 18 years of age is not recommended. |
| Elderly Dosage : | Elderly patients should be monitored closely for impaired motor and/or cognitive function when taking sodium oxybate (See Special Precautions). |
| Contra Indications : | Hypersensitivity to sodium oxybate or to any of the excipients. Sodium oxybate is contraindicated in patients with succinic semialdehyde dehydrogenase deficiency. Sodium oxybate is contraindicated in patients being treated with opioids or barbiturates. |
| Special Precautions : | Xyrem has the potential to induce respiratory depression Abuse potential and dependance The active substance in Xyrem is sodium oxybate, which is as the sodium salt of gamma hydroxybutyrate (GHB), a CNS depressant active substance with well known abuse potential. Physicians should evaluate patients for a history of drug abuse and follow such patients closely. There have been case reports of dependence after illicit use of GHB at frequent repeated doses (18 to 250 g/day) in excess of the therapeutic dose range. Whilst there is no clear evidence of emergence of dependence in patients taking sodium oxybate at therapeutic doses, this possibility cannot be excluded. CNS depression The combined use of alcohol or any CNS depressant drug with sodium oxybate may result in potentiation of the CNS-depressant effects of sodium oxybate. Therefore, patients should be warned against the use of alcohol in conjunction with sodium oxybate. Patients with porphyria Sodium oxybate is considered to be unsafe in patients with porphyria because it has been shown to be porphyrogenic in animals or in-vitro systems. Respiratory depression Sodium oxybate also has the potential to induce respiratory depression. Apnoea and respiratory depression have been observed in a fasting healthy subject after a single intake of 4.5g (twice the recommended starting dose). Patients should be questioned regarding signs of CNS or respiratory depression. Special caution should be observed in patients with an underlying respiratory disorder. Approximately 80% of patients who received sodium oxybate during clinical trials maintained CNS stimulant use. Whether this affected respiration during the night is unknown. Before increasing the sodium oxybate dose (See Adult Dosage), prescribers should be aware that sleep apnoea occurs in up to 50% of patients with narcolepsy. Benzodiazepines Given the possibility of increasing the risk of respiratory depression, the concomitant use of benzodiazepines and Xyrem should be avoided. Neuropsychiatric events Patients may become confused while being treated with sodium oxybate. If this occurs, they should be evaluated fully, and appropriate intervention considered on an individual basis. Other neuropsychiatric events include psychosis, paranoia, hallucinations, and agitation. The emergence of thought disorders and/or behavioural abnormalities when patients are treated with sodium oxybate requires careful and immediate evaluation. The emergence of depression when patients are treated with sodium oxybate requires careful and immediate evaluation. Patients with a previous history of a depressive illness and/or suicide attempt should be monitored especially carefully for the emergence of depressive symptoms while taking sodium oxybate. If a patient experiences urinary or faecal incontinence during sodium oxybate therapy, the prescriber should consider pursuing investigations to rule out underlying aetiologies. Sleepwalking has been reported in patients treated in clinical trials with sodium oxybate. It is unclear if some or all of these episodes correspond to true somnambulism (a parasomnia occurring during non-REM sleep) or to any other specific medical disorder. The risk of injury or self-harm should be borne in mind in any patient with sleepwalking. Therefore, episodes of sleepwalking should be fully evaluated and appropriate interventions considered. Sodium intake Patients taking sodium oxybate will have an additional daily intake of sodium that ranges from 0.75g (for a 4.5g/day (9ml) Xyrem dose) to 1.6g (for a 9g/day (18ml) Xyrem dose). A dietary recommendation to reduce sodium intake should be carefully considered in the management of patients with heart failure, hypertension or compromised renal function. (See Adult Dosage). Patients with compromised liver function Patients with compromised liver function will have an increased elimination half-life and systemic exposure to sodium oxybate. The starting dose should therefore be halved in such patients, and response to dose increments monitored closely (Adult Dosage). Elderly There is very limited experience with sodium oxybate in the elderly. Therefore, elderly patients should be monitored closely for impaired motor and/or cognitive function when taking sodium oxybate. Childhood and adolescence Safety and effectiveness in children and adolescents has not been established, therefore use in patients under 18 years of age is not recommended. Epileptic patients Seizures have been observed in patients treated with sodium oxybate. In patients with epilepsy, the safety and efficacy of sodium oxybate has not been established, therefore use is not recommended. Rebound effects and withdrawal syndrome The discontinuation effects of sodium oxybate have not been systematically evaluated in controlled clinical trials. In some patients, cataplexy may return at a higher frequency on cessation of sodium oxybate therapy, however this may be due to the normal variability of the disease. Although the clinical trial experience with sodium oxybate in narcolepsy/cataplexy patients at therapeutic doses does not show clear evidence of a withdrawal syndrome, in rare cases, events such as insomnia, headache, anxiety, dizziness, sleep disorder, somnolence, hallucination, and psychotic disorders were observed after GHB discontinuation. |
| Interactions : | The combined use of alcohol with sodium oxybate may result in potentiation of the central nervous system-depressant effects of sodium oxybate. Patients should be warned against the use of any alcoholic beverages in conjunction with sodium oxybate. Sodium oxybate should not be used in combination with sedative hypnotics or other CNS depressants. Drug interaction studies in healthy adults demonstrated no pharmacokinetic interactions between sodium oxybate and protriptyline hydrochloride (an antidepressant), zolpidem tartrate (a hypnotic), and modafinil (a stimulant). However, pharmacodynamic interactions with these drugs have not been assessed. The co-administration of omeprazole (a drug that alters gastric pH) has no clinically significant effect on the pharmacokinetics of sodium oxybate. The dosage of sodium oxybate therefore does not require adjustment when given concomitantly with proton pump inhibitors. Studies in vitro with pooled human liver microsomes indicate that sodium oxybate does not significantly inhibit the activities of the human isoenzymes. Since sodium oxybate is metabolised by GHB dehydrogenase there is a potential risk of an interaction with drugs that stimulate or inhibit this enzyme (e.g. valproate, phenytoin or ethosuximide). No interaction studies have been conducted in human subjects Sodium oxybate has been administered concomitantly with CNS stimulant agents in approximately 80 % of patients in clinical studies. Whether this affected respiration during the night is unknown. Antidepressants have been used in the treatment of cataplexy. A possible additive effect of antidepressants and sodium oxybate cannot be excluded. The rate of adverse events have increased when sodium oxybate is co-administered with tricyclic antidepressants. Pregnancy and lactation: Pregnancy Animal studies have shown no evidence of teratogenicity but embryolethality was seen in both rat and rabbit studies. There are no adequate data on the use of sodium oxybate during the first trimester of pregnancy. Limited data from pregnant patients during second and third trimester indicate no malformative nor foeto/neonatal toxicity of sodium oxybate. Sodium oxybate is not recommended during pregnancy Lactation It is not known whether sodium oxybate is excreted into breast milk. Breastfeeding is not recommended when treating with Xyrem. |
| Adverse Reactions : | The most commonly reported adverse drug reactions are sleep disorder, dizziness, nausea, and headache, all occurring in 10 % to 25 % of patients. Frequency estimate: very common > 1/10); common > 1/100 to < 1/10); uncommon > 1/1000 to < 1/100); rare > 1/10,000 to < 1/1000); very rare (< 1/10,000) Immune system disorders: Common: hypersensitivity Metabolism and nutrition disorders: Common: anorexia Psychiatric disorders: Very common: sleep disorder Common: abnormal dreams, abnormal thinking, confusion, disorientation, nightmares, sleepwalking, depression, hallucination, agitation Uncommon: psychosis, paranoia Nervous system disorders: Very common: dizziness, headache Common: sleep paralysis, somnolence, tremor, amnesia Uncommon: myoclonus, convulsion Eye disorders: Common: blurred vision Respiratory, thoracic and mediastinal disorders: Rare: respiratory depression Gastrointestinal disorders: Very common: nausea (the frequency of nausea is higher in women than men) Common: vomiting, upper abdominal pain, diarrhoea, Uncommon: faecal incontinence Skin and subcutaneous tissue disorders: Common: sweating, rash Uncommon: urticaria Musculoskeletal, connective tissue and bone disorders: Common: muscle cramps Renal and urinary disorders: Common: enuresis nocturna General disorders and administration site conditions: Common: asthenia, fatigue, feeling drunk Investigations: Common: blood pressure increased In some patients, cataplexy may return at a higher frequency on cessation of sodium oxybate therapy, however this may be due to the normal variability of the disease. Although the clinical trial experience with sodium oxybate in narcolepsy/cataplexy patients at therapeutic doses does not show clear evidence of a withdrawal syndrome, in rare cases, adverse events such as insomnia, headache, anxiety, dizziness, sleep disorder, somnolence, hallucination, and psychotic disorders were observed after GHB discontinuation. |
| Manufacturer : | UCB Pharm |
| Drug Availability : | (POM) |
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