• Xywav is the brand (trade) name for a fixed mixture of 4 oxybate salts, namely: calcium oxybate, magnesium oxybate, potassium oxybate, and sodium oxybate (gamma-hydroxybutyrate). Xywav may be used to treat idiopathic hypersomnia or narcolepsy, a sleep disorder characterized by excessive daytime sleepiness.
• Experts aren't sure exactly how Xywav works in the treatment of narcolepsy. Sodium oxybate is thought to be metabolized to a neurotransmitter called GABA which then binds to GABA_B 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).
• Xywav 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.

• 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 for use in adults and children aged 7 years or older.
• May also be used to treat idiopathic hypersomnia in adults. This sleep disorder is characterized by chronic excessive daytime sleepiness with symptoms such as severe sleep inertia, sleep drunkenness (difficulty waking with frequent reentries into sleep, confusion and irritability), non-restorative nighttime sleep, cognitive impairment, or long and unrefreshing naps.
• Side effects with Xywav are more common on starting treatment and tend to resolve or diminish with time. Overall, side effects with Xyvaw were reported less often in people who had been switched for Xyrem compared with those who had not been taking Xyrem.
• Each prescription of Xywav includes one bottle of Xywav with an attached press-in bottle adaptor, an oral measuring device (plastic syringe), and a Medication Guide. The pharmacy provides two empty containers with child-resistant caps with each Xywav shipment.
• Taking Xywav 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.
• Xywav is not a narcotic. Narcotics bind to opioid receptors in the brain and include substances such as codeine, oxycodone, and morphine.
• Xywav is available as an oral solution.
• It is considered safe to dispose of Xywav down the sanitary sewer.
• Xywav contains the same amount of oxybate as Xyrem, but because this comes as a mixture of calcium, magnesium, and potassium oxybate salts, as well as sodium oxybate, the total daily sodium dose is lower.
• Xywav contains 92% less sodium than sodium oxybate (Xyrem). Xywav is considered a lower sodium alternative to Xyrem and may be more suitable for people on a low salt diet or who are at risk of high blood pressure than Xyrem because Xyrem contains 1640mg of sodium per 9g dose. The AHA recommends no more than 2,300 mg of sodium a day with an aim of reducing salt intake to less than 1,500 mg per day. Xywav only contains 131mg sodium in a daily 9g dose.
• Doctors can initiate Xywav at the same dose and regimen as Xyrem in people transitioning from Xyrem to Xywav.

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:

• Headache, nausea, dizziness, decreased appetite, parasomnias (complex movements or abnormal behaviors during sleep), anxiety, diarrhea, excessive sweating, and vomiting are the most common side effects reported. Tremor, muscle spasms, feeling drunk and suicidal thoughts have also been reported.
• In children, the most common side effects include bedwetting, nausea, headache, vomiting, weight decrease, decreased appetite, and dizziness.
• Xywav is a controlled substance. When used legitimately to treat narcolepsy, Xywav 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.
• Xywav can cause physical dependence and craving for it when it is not taken as directed.
• Sleepwalking has been reported in approximately 6% of people taking Xywav. This may increase their risk of injury.
• Even at recommended dosages, significant respiratory depression and altered levels of consciousness have been reported with Xywav. Overdosage may cause seizures, respiratory depression, decreased consciousness, coma, or death.
• Xywav may not be suitable for some people including those with a history of depression, anxiety, psychosis, aggression, high blood pressure, heart disease, liver, or kidney problems.
• Xywav may also not be suitable for people with sleep apnea or sleep-related breathing disorders as Xywav may increase the risk of severe apneas or oxygen desaturation. Sleep-related disorders are more prevalent in obese patients and postmenopausal women.
• Xywav should not be used in combination with sedative-hypnotics, with alcohol, or in people with succinic semialdehyde dehydrogenase deficiency.
• Xywav may increase thoughts about suicide.
• The usual starting dose of Xywav in adults is 4.5 grams (g) per night, given in two divided doses: 2.25 g at bedtime and 2.25 g taken two and a half to four hours later. The dosage is usually increased by up to 1.5g per night per week (as a split dose: 0.75mg followed by 0.75mg 2.5 to 4 hours later), until the usual maintenance dose of 6g to 9g at night is reached. Recommended dosages in children depend on their weight. Some people may achieve a better response with unequal doses at bedtime and 2.5 to 4 hours later.
• Doctors must enroll in the Xywav REMS program to prescribe Xywav. To become certified, doctors must complete a one-time enrollment and be familiar with the Xywav prescribing information. This includes knowing how to screen for alcohol or substance abuse, interacting medicines, or medical conditions that may not be compatible with Xywav use.
• Xywav can only be dispensed from the central certified pharmacy. This is the only pharmacy that can supply and distribute Xywav across the United States.
• Xywav has a high potential for abuse and contains sodium oxybate which is also known as the street name of GHB, a known street drug of abuse. However, there are differences in purity between GHB which is sold on the street, and GHB that is contained in Xywav.
• The use of Xywav during pregnancy is not recommended. Animal studies showed decreased postnatal viability, weight gain, and increased stillbirths at 1000 mg/kg/day doses given throughout pregnancy and lactation. The FDA has not assigned a pregnancy category to Xywav. Xywav is passed into breastmilk and women taking Xywav should not breastfeed.
• No generic form of Xywav is currently available.

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

• Take Xywav exactly as directed by your doctor. The usual starting dose of Xywav in adults is 4.5 grams (g) per night, split into two doses: 2.25 g at bedtime and 2.25 g taken two and a half to four hours later. 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 Xywav and you should wait at least 2 hours after eating before you take your dose.
• The total nightly dosage of Xywav 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 Xywav 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 Xywav it lasts for 24 hours. Throw it away if you have not consumed it during this time. It is considered safe to dispose of Xywav down the sanitary sewer.
• Once the first dose of Xywav has been taken, the person should lie down immediately and remain in bed. Xywav may cause patients to fall asleep abruptly (often within 5 minutes of taking Xywav) without first feeling drowsy. You may need to set an alarm to awaken for the second dose. If you miss the second dose, skip that dose, and do not take Xywav until the next night. Never take two Xywav doses at one time.
• Avoid alcohol while you are taking Xywav because 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 Xywav, 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.
• Xywav can only be prescribed by doctors enrolled in the Xyrem REMS Program.
• The prescription for Xywav 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 Xywav; provides an overnight delivery service (includes Saturdays) - but only the patient or a designated adult can sign for delivery; and follows up your prescription with a nurse case manager two days after delivery who can answer any questions.
• Before prescribing Xywav, your doctor will screen you for alcohol or substance abuse or other medical conditions that may prohibit the use of Xywav. They should also provide you with a Xywav REMS Program Patient Quick Start Guide. You will also need to complete a one-time enrollment in the Xywav REMS Program Patient Enrollment Form and be able to answer patient questions about usage, storage, the risks associated with Xywav, and where to obtain it from.
• When Xywav 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 Xywav 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.
• Xywav 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.
• Xywav is not a narcotic but it still has a high potential for abuse and serious side effects. Xywav is available only from a certified pharmacy under a special program called the Xywav REMS Program. Your doctor must be registered in the program to prescribe this medicine for you.
• Few pregnant women have been given Xywav. This means data on its effects during pregnancy are limited and it is not recommended during pregnancy. If you inadvertently become pregnant while taking Xywav, tell your doctor immediately.
• Store Xywav out of the refrigerator at room temperature 20°C to 25°C (68°F to 77°F). Occassionally lower and higher temperature excursions are permitted between 15°C and 30°C (59°F and 86°F).

• It takes on average about 1.3 hours for Xywav to reach its maximum concentration when taken on an empty stomach.
• High-fat meals reduce the maximum blood level of sodium oxybate by approximately 33%, and total exposure by about 16%.
• Xywav significantly reduced the mean number of cataplexy attacks after two weeks of dosing in a study that enrolled 201 patients. The Epworth Sleepiness Scale (ESS) score also decreased significantly. In a study that investigated the effects of Xywav in children, those randomized to receive placebo experienced far worse cataplexy and narcolepsy overall compared to those receiving Xyrem.

Medicines that interact with Xywav may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with Xywav. 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 Xywav 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
• hydroxyzine
• 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
• sodium oxybate
• medications used to treat mental illness, such as aripiprazole, clozapine, and thioridazine.

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

If initiating Xywav in somebody already on a stable dose of divalproex, a lower starting dosage of Xywav is recommended.

Xywav does not significantly affect hepatic enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A at dosages much higher than recommended, so is unlikely to interact with medications metabolized by these enzymes.

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