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Xyrem: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Oct 12, 2022.

1. How it works

  • Xyrem is a brand (trade) name for sodium oxybate which is the sodium salt of gamma-hydroxybutyrate (GHB). Xyrem may be used to treat narcolepsy, a sleep disorder characterized by excessive daytime sleepiness.
  • The exact way Xyrem works for narcolepsy is not known but it is thought to be metabolized to a neurotransmitter called GABA which then binds to GABAB and GHB receptors. This leads to changes in the activity of the brain, enhancing delta waves which are a type of high-amplitude brain wave generally associated with slow-wave sleep (during the third stage of sleep).
  • Xyrem belongs to the class of medicines known as central nervous system (CNS) depressants. CNS depressants slow down brain activity, which makes them useful for treating sleep disorders.

2. Upsides

  • May be used to treat cataplexy or excessive daytime sleepiness (EDS) in patients with narcolepsy. Cataplexy is sudden, uncontrollable muscle weakness or paralysis that occurs during the day and is often triggered by strong emotions, such as laughter.
  • Approved to treat adults and children aged 7 years or older.
  • Taking Xyrem at night improves the quality and quantity of deep sleep, which reduces the number of sleeping periods during the day. This improves the symptoms of narcolepsy.
  • Xyrem is not a narcotic. Narcotics bind to opioid receptors in the brain and include substances such as codeine, oxycodone, and morphine.
  • Xyrem is available as an oral solution.
  • A generic of Xyrem is available through the Xyrem REMS program under the name of sodium oxybate.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Nausea, dizziness, bloating, headache, urinary issues, loud snoring, unusual wake gain or loss, balance problems, back pain, increased sweating, vomiting or abdominal pain, dry mouth, abnormal dreams, seeing, hearing, or feeling things that are not there, sleepiness, tremor, thoughts of killing oneself, tingling of the hands or feet, unusual weight gain or loss are the most commonly reported side effects.
  • Xyrem can cause physical dependence and craving for it when it is not taken as directed.
  • People taking a higher dose of Xyrem (eg, 9 g/day) are more likely to report feeling drunk.
  • Sleepwalking has been reported in approximately 6% of people taking Xyrem. This may increase their risk of injury.
  • Overdosage may cause seizures, respiratory depression, decreased consciousness, coma, or death.
  • Xyrem may not be suitable for some people including those with a history of depression, anxiety, psychosis, aggression, high blood pressure, heart disease, or kidney problems.
  • Xyrem may also not be suitable for people with sleep apnea or sleep-related breathing disorders as Xyrem may increase the risk of severe apneas or oxygen desaturation. Sleep-related disorders are more prevalent in obese patients and postmenopausal women.
  • Xyrem should not be used in combination with sedative-hypnotics, with alcohol, or in people with succinic semialdehyde dehydrogenase deficiency.
  • Xyrem may increase thoughts about suicide.
  • People with liver disease only need to take half the recommended dose of Xyrem but this is still administered as two divided doses at night.
  • Xyrem contains sodium, and this needs to be taken into account by people on a low-salt diet, with high blood pressure, heart failure, or with kidney disease who need to calculate their daily salt intake. Every 4.5g of Xyrem contains 820mg of sodium.
  • The usual starting dose of Xyrem in adults is 4.5 grams (g) per night increasing to a usual maintenance dose of 6g to 9g at night. Recommended dosages in children depend on their weight.
  • Doctors must enroll in the Xyrem REMS program to prescribe Xyrem. To become certified, doctors must complete a one-time enrollment and be familiar with the Xyrem prescribing information. This includes knowing how to screen for alcohol or substance abuse, interacting medicines, or medical conditions that may not be compatible with Xyrem use.
  • Xyrem can only be dispensed from the central certified pharmacy. This is the only pharmacy that can supply and distribute Xyrem across the United States.
  • Xyrem is a controlled substance. When used legitimately to treat narcolepsy, Xyrem is a class III controlled substance. When misused, either by people who have legitimately obtained it or those who have obtained it illegally, it is considered a class I controlled substance, and penalties are severe.
  • Xyrem has a high potential for abuse and is also known as the street name of GHB. However, there are differences in purity between GHB which is sold on the street, and GHB which is manufactured as Xyrem.
  • The use of Xyrem during pregnancy is not recommended. Although animal studies did not show an increased risk of birth defects, there was an increased number of stillbirths and post-birth deaths in baby rats. The FDA has not assigned a pregnancy category to Xyrem.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

  • Xyrem is a schedule III controlled substance when prescribed to treat narcolepsy; however, there is a high risk of abuse associated with it and people who misuse it or sell it to other people are subject to severe schedule I penalties. Xyrem is taken at night which decreases the risk of somebody with narcolepsy falling asleep during the day. Nausea is one of the most common reasons for discontinuation.

5. Tips

  • Take Xyrem exactly as directed by your doctor. The usual starting dose of Xyrem in adults is 4.5 grams (g) per night increasing to a usual maintenance dose of 6g to 9g at night. Recommended dosages in children depend on their weight and your doctor will advise you on the initial dose for your child.
  • Food may interfere with the absorption of sodium oxybate. Wait at least 2 hours after eating before you take your dose.
  • The total nightly dosage of Xyrem is divided into two doses and both doses are taken at night. You should prepare both doses before bedtime. Just before you drink the first dose, dilute it with approximately ¼ cup (approximately 60 mL) of water in the empty pharmacy containers provided. Take the first nightly dose of Xyrem at least 2 hours after eating then take the second nightly dose 2.5 to 4 hours after the first dose. Once you have diluted Xyrem it lasts for 24 hours. Throw it away if you have not consumed it during this time. It is considered safe to dispose of Xyrem down the sanitary sewer.
  • Each dose should be taken while you are lying in bed and you should lie down immediately after taking a dose. Remain in bed following ingestion of each dose because Xyrem may cause patients to fall asleep abruptly without first feeling drowsy (often within 5 to 15 minutes). You may need to set an alarm to wake yourself up to take the next dose. If you miss the second dose, just skip it and do not take Xyrem again until the next night. Never take both Xyrem doses at one time.
  • Avoid alcohol during treatment, as it may add increase the risk of serious side effects such as respiratory depression, low blood pressure, fainting, coma, and even death. Do not drive, operate machinery, or perform hazardous tasks for at least six hours after taking sodium oxybate, and until you know how the medication affects you.
  • Tell your doctor about any other medications you take, including those brought from a grocery or drug store, such as vitamins and herbs.
  • If you develop any severe side effects such as difficulty breathing, balance issues, confusion, fainting, or start to think about suicide, see your doctor straight away.
  • If you are on a low-salt diet, have high blood pressure, heart failure, or kidney disease then you need to take into account how much sodium Xyrem contains when calculating your daily salt intake. Every 4.5g of Xyrem contains 820mg of sodium. Sodium is another name for salt. To put the sodium content of Xyrem into context, a teaspoon of table salt contains about 2300mg of sodium. The American Heart Association recommends no more than 2300mg of sodium a day although it recommends people strive towards an ideal limit of no more than 1500mg per day.
  • Xyrem can only be prescribed by doctors enrolled in the Xyrem REMS Program.
  • The prescription for Xyrem can only be filled by the central certified pharmacy, not your local pharmacy. This is the only pharmacy in the United States permitted to fill the prescription and send it directly to patients. This pharmacy also allows the patient access to a pharmacist 24 hours a day, 7 days a week to answer questions about Xyrem; provides an overnight delivery service (includes Saturdays) but only the patient or a designated adult can sign for the delivery; follows up your prescription with a nurse case manager two days after delivery to answer questions.
  • Before prescribing Xyrem, your doctor will screen you for alcohol or substance abuse or other medical conditions that may prohibit the use of Xyrem. They should also provide you with a Xyrem REMS Program Patient Quick Start Guide. You will also need to complete a one-time enrollment in the Xyrem REMS Program Patient Enrollment Form and be able to answer patient questions about usage, storage, the risks associated with Xyrem, and where to obtain it from.
  • When Xyrem is used for medicinal purposes, such as narcolepsy, it is classified as a Schedule III controlled substance under the Controlled Substances Act. However, even if you obtain Xyrem for medicinal use, but then misuse it or offer it to anybody else to use, then it is considered a Schedule I controlled substance and illicit use is subject to Schedule I penalties which are severe.
  • Xyrem has a high potential for abuse because it can cause changes in the activity of the brain and can also cause changes in your breathing, even at regular dosages or if you are taking other interacting medicines. Fatal side effects, such as breathing problems, seizures, loss of consciousness, or death can occur if you misuse this medicine, take it with alcohol, or take it with other drugs that cause drowsiness or slow your breathing.
  • Xyrem is not a narcotic but it still has a high potential for abuse and serious side effects. Xyrem is available only from a certified pharmacy under a special program called the Xyrem REMS Program. Your doctor must be registered in the program to prescribe this medicine for you.
  • Few pregnant women have been given Xyrem (sodium oxybate). This means data on its effects during pregnancy are limited and it is not recommended during pregnancy. If you inadvertently become pregnant while taking Xyrem, tell your doctor immediately.
  • Store Xyrem out of the refrigerator at room temperature 25°C (77°F).

6. Response and effectiveness

Approximately 10% of patients discontinue Xyrem because of adverse reactions compared with 2.8% of patients receiving a placebo (an inactive pill). The most common adverse reaction leading to discontinuation was nausea (2.8%) and discontinuation was most likely to happen during the first few weeks of treatment.

7. Interactions

Medicines that interact with Xyrem may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Xyrem. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Xyrem include:

  • amyl nitrate
  • anti-anxiety medications such as alprazolam, diazepam, or oxazepam (all sedative-hypnotics and CNS depressants are contraindicated)
  • anticonvulsants such as carbamazepine or divalproex
  • antidepressants, such as amitriptyline, imipramine, nortriptyline
  • antihistamines that cause sedation, such as azatadine or diphenhydramine
  • barbiturates
  • bupropion
  • cannabidiol
  • cannabis
  • diuretics, such as bendroflumethiazide and furosemide
  • duloxetine
  • heart medications, such as amlodipine, atenolol, or bisoprolol
  • gabapentin
  • ketamine
  • minoxidil
  • monoamine oxidase inhibitors, such as selegiline, isocarboxazid, or phenelzine
  • opioid analgesics such as codeine, fentanyl, oxycodone, or morphine
  • muscle relaxants such as cyclobenzaprine
  • sleeping pills, such as eszopiclone or zolpidem
  • medications used to treat mental illness, such as aripiprazole, clozapine, and thioridazine.

Alcohol should not be taken with Xyrem because it can lead to dangerous side effects such as respiratory depression which may increase the risk of death.

Reduce the dosage of Xyrem by at least 20% if divalproex sodium needs to be started in a person already taking a stable dose of Xyrem. If initiating Xyrem in somebody already on a stable dose of divalproex, a lower starting dosage of Xyrem is recommended.

Note that this list is not all-inclusive and includes only common medications that may interact with Xyrem. You should refer to the prescribing information for Xyrem for a complete list of interactions.


Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Xyrem only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Revision date: October 12, 2022.