Xyrem

Xyrem (sodium oxybate) is used to treat cataplexy (sudden onset of weak or paralyzed muscles) or excessive daytime sleepiness (EDS) in adults and children 7 years and older with narcolepsy. It is an oral solution taken twice at night.

Xyrem has dual classification as a controlled substance. When used legitimately for medical purposes, it's classified as Schedule III. However, when misused, either by patients or those obtaining it illegally, it's treated as Schedule I, which carries severe legal penalties, including imprisonment and heavy fines.

Xyrem contains sodium oxybate, also known as gamma-hydroxybutyrate (GHB), which is a known street drug of abuse. Because of the potential for abuse and serious side effects, Xyrem is available only from a certified pharmacy under a special program called Xywav and Xyrem REMS. You and your healthcare provider must be registered in the program and understand the risks and benefits of this medicine.

Xyrem gained FDA approval on July 17, 2002. A generic is available under the name sodium oxybate.

Read the Instructions for Use in the Xyrem Package Insert for detailed instructions on how to take Xyrem.

• Take or give Xyrem exactly as your doctor tells you to take or give it.
• Xyrem can cause physical dependence and craving for the medicine when it is not taken as directed.
• Never change the Xyrem dose without talking to your doctor.

Xyrem can cause you to fall asleep very quickly without feeling drowsy.

• Some people fall asleep within 5 minutes, and most fall asleep within 15 minutes.
• The time it takes to fall asleep might be different from night to night.
• Falling asleep quickly, including while standing or while getting up from bed, has led to falls with injuries that have required some people to be hospitalized.

Xyrem is taken at night, divided into 2 doses.

• Adults: Take the first Xyrem dose at bedtime while you are in bed and lie down immediately. Take the second Xyrem dose 2½ to 4 hours after the first Xyrem dose. You may want to set an alarm clock to make sure you wake up to take the second Xyrem dose. You should remain in bed after taking the first and second doses of Xyrem.
• Children: Give the first Xyrem dose at bedtime or after an initial period of sleep, while your child is in bed, and have them lie down immediately. Give the second Xyrem dose 2½ to 4 hours after the first Xyrem dose. You may want to set an alarm clock to make sure you wake up to give the second Xyrem dose. Your child should remain in bed after taking the first and second doses of Xyrem.

If you miss or your child misses the second Xyrem dose, skip that dose and do not take or give Xyrem again until the next night. Never take or give two Xyrem doses at 1 time.

Wait at least 2 hours after eating before taking Xyrem.

You or your child should see your doctor every 3 months for a check-up while taking Xyrem. Your doctor should check to see if Xyrem is helping to lessen your or your child’s symptoms and if you feel or your child feels any side effects while taking Xyrem.

If you take or your child takes too much Xyrem, call your doctor or go to the nearest hospital emergency roomright away.

Xyrem carries a Boxed Warning for Central Nervous System (CNS) depression, abuse, and misuse.

Central Nervous System Depression

Xyrem is a central nervous system (CNS) depressant. Taking Xyrem with other CNS depressants such asmedicines used to make you or your child fall asleep, including opioid analgesics, benzodiazepines, sedatingantidepressants, antipsychotics, sedating anti-epileptic medicines, general anesthetics, muscle relaxants,alcohol or street drugs may cause serious medical problems, including:

• Trouble breathing (respiratory depression)
• Low blood pressure (hypotension)
• Changes in alertness (drowsiness)
• Fainting (syncope)
• Death.

Xyrem is a federally controlled substance (CIII, Schedule 3). The active ingredient of Xyrem is a form of gamma-hydroxybutyrate (GHB), which is also a federally controlled substance (Schedule I). Abuse of illegal GHB, either alone or with other CNS depressants, may cause serious medical problems, including:

• Seizures
• Trouble breathing (respiratory depression)
• Changes in alertness (drowsiness)
• Coma
• Death.

Call your doctor right away if you or your child has any of these serious side effects. Ask your doctor if you are not sure if you are taking a medicine listed above.

Residual Drowsiness

Anyone who takes Xyrem should not do anything that requires them to be fully awake or is dangerous, including driving a car, using heavy machinery, or flying an airplane, for at least 6 hours after taking Xyrem. Those activities should not be done until you know how Xyrem affects you or your child.

Abuse and Misuse

Keep Xyrem in a safe place to prevent abuse and misuse. Selling or giving away Xyrem may harm others and is against the law. Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines, or street drugs.

Because of the risk of CNS depression, abuse, and misuse, Xyrem is only available by prescription and filled through the central pharmacy in the Xyrem REMS Program.

• Before you receive or your child receives Xyrem, your doctor or pharmacist will make sure that you understand how to take Xyrem safely and effectively. If you have any questions about Xyrem, ask your doctor or call the Xyrem REMS Program at 1-866-997-3688.

Do not take Xyrem if you or your child:

• Takes other sleep medicines or sedatives (medicines that cause sleepiness)
• Drinks alcohol
• Has a rare problem called succinic semialdehyde dehydrogenase deficiency.

Before taking Xyrem, tell your healthcare provider about all medical conditions, including if you or your child:

• Has short periods of not breathing while sleeping (sleep apnea)
• Snores, has trouble breathing, or has lung problems. You or your child may have a higher chance of having serious breathing problems when taking Xyrem
• Have or have had depression or have tried to harm yourself or others. You or your child should be watched carefully for new symptoms of depression.
• Has or had behavior or other psychiatric problems such as: Anxiety Seeing or hearing things that are not real (hallucinations) Feeling more suspicious (paranoia) Being out of touch with reality (psychosis) Acting aggressive Agitation.
• Have liver problems
• Are on a salt-restricted diet. Xyrem contains a lot of sodium (salt) and may not be right for you or your child
• Have high blood pressure
• Have heart failure
• Have kidney problems
• Is pregnant or planning to become pregnant
• Is breastfeeding or planning to breastfeed.

Pregnancy

It is not known if Xyrem can harm your unborn baby.

Breastfeeding

Xyrem passes into breast milk. You and your doctor should decide if you or your child will take Xyrem or breastfeed.

Common side effects

The most common side effects of Xyrem are:

• Nausea
• Sleepiness
• Dizziness
• Vomiting
• Bedwetting
• Tremor (in adults).

In children, headache, decreased appetite, and weight loss were also common.

Side effects may increase when taking higher doses of Xyrem.

Serious side effects and warnings

Xyrem may cause the following other serious side effects:

• Central Nervous System (CNS) depression, abuse, and misuse. See Important Information above.
• Breathing Problems. Xyrem may cause breathing problems, such as:

• Slower breathing Trouble breathing Short periods of not breathing while sleeping (sleep apnea).

People with pre-existing breathing or lung problems are at higher risk of breathing problems when they take Xyrem.

• Mental Health Problems. Mental health problems have been reported with Xyrem, including:

• Confusion Seeing or hearing things that are not real (hallucinations) Unusual or disturbing thoughts (abnormal thinking) Feeling anxious or upset Depression Thoughts of killing yourself or trying to kill yourself.

Call your doctor right away if you have, or your child has symptoms of mental health problems.

• Sleepwalking. Sleepwalking can cause injuries. Call your doctor if you start or your child starts sleepwalking. Your doctor should check you or your child.

Notes:

These are not all the possible side effects of Xyrem. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Xyrem (sodium oxybate) is a form of GHB used to treat narcolepsy. It works by binding to GABA-B and GHB receptors in the brain, which helps deepen and consolidate nighttime sleep, particularly slow-wave sleep. This improved sleep quality reduces excessive daytime sleepiness. It also significantly decreases cataplexy episodes (sudden muscle weakness). Due to its short half-life, Xyrem is taken in two nightly doses.

Xyrem (sodium oxybate) belongs to the drug class called central nervous system (CNS) depressants.

The recommended starting dosage in people with liver disease is one-half of the original dosage per night, administered orally, divided into two doses.

Adult Dose of Xyrem for Cataplexy or EDS in Narcolepsy

• Initial: 4.5 grams orally per night, divided into two doses (2.25 grams at bedtime and another 2.25 grams taken 2.5 to 4 hours later).
• Increase the dosage by 1.5 grams per night (0.75 grams per dose) at weekly intervals.
• Recommended dosage range: 6 grams to 9 grams orally per night (divided into 2 doses).

Child 7+ Dose of Xyrem for Cataplexy or EDS in Narcolepsy

• The dosage of Xyrem for children is based on body weight.
• See the Xyrem Prescribing Information for the full recommended Pediatric dosages for Xyrem.

Dose of Xyrem for Cataplexy or EDS in Narcolepsy in those with Liver Impairment

• Half the initial dosage per night, divided into two doses.

Xywav is a low-sodium alternative to Xyrem, approved in 2020 after concerns about the high sodium content of Xyrem potentially contributing to heart disease, high blood pressure, or kidney disease (see What is the difference between Xywav vs Xyrem?).

Lumryz is an extended-release version of sodium oxybate taken once at night (see What is the difference between Lumryz vs Xyrem?).

Tell your doctor about all the medicines you or your child takes, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

• Xyrem should not be taken in combination with sedative hypnotics or with alcohol.

Especially, tell your doctor if you take or your child takes other medicines to help you or your child sleep (sedatives). Know the medicines you take or your child takes. Keep a list of them to show your doctor and pharmacist when you get, or your child gets a new medicine

Tell your doctor if you or your child takes divalproex sodium. Your doctor may need to lower the starting dose of Xyrem.

Store Xyrem in the original bottle or in pharmacy containers with child-resistant caps provided by the pharmacy.

• Get emergency medical help right away if a child who has not been prescribed Xyrem drinks Xyrem.
• Store Xyrem between 68°F and 77°F (20°C and 25°C).

All Xyrem solutions prepared after dilution should be taken within 24 hours. When you have finished using a Xyrem bottle:

• Empty any unused Xyrem down the sink drain
• Cross out the label on the Xyrem bottle with a marker
• Place the empty Xyrem bottle in the trash
• Keep Xyrem and all medicines out of the reach of children and pets.

Keep Xyrem and all medicines out of the reach of children and pets.

Active ingredients: sodium oxybate 0.5 g per mL (0.5 g/mL of sodium oxybate equivalent to 0.413 g/mL of oxybate).

Inactive ingredients: purified water and malic acid.

Available as Xyrem oral solution, 0.5 g per mL, in a 180 mL bottle with a child-resistant cap.

Xyrem is manufactured by Jazz Pharmaceuticals, Inc., Palo Alto, CA 94306.