XYWAV calcium, magnesium, potassium, and sodium oxybates .5 g/mL; .5 g/mL; .5 g/mL; .5 g/mL Solution, 180 mL — NDC 68727-150-01 (Billing 68727-0150-01)

1 INDICATIONS AND USAGE XYWAV is a central nervous system depressant indicated for the treatment of: • Cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy ( 1.1 ). • Idiopathic Hypersomnia (IH) in adults ( 1.2 ).

1.1Narcolepsy XYWAV is indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy.

1.2Idiopathic Hypersomnia XYWAV is indicated for the treatment of idiopathic hypersomnia (IH) in adults.

2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for complete dosing instructions ( 2.1 - 2.7 ). Dosage for Adult Patients with Narcolepsy • Initiate dosage at 4.5 g per night orally, divided into two doses ( 2.1 ). • Titrate to effect in increments of up to 1.5 g per night per week ( 2.1 ). • Recommended dosage range: 6 g to 9 g per night orally, divided into two doses ( 2.1 ). • Doses may be divided equally or unequally and the first dose taken at bedtime and the second dose taken 2.5 to 4 hours later ( 2.1 ).

Dosage for Pediatric Patients with Narcolepsy (7 Years of Age and Older) • The recommended starting dosage, titration regimen, and maximum total nightly dosage are based on body weight (2.2 ). Dosage for Adult Patients with Idiopathic Hypersomnia • XYWAV can be administered as a twice or once nightly regimen in adults ( 2.3 ). • Twice nightly: Initiate dosage at 4.5 g or less per night orally, divided into two doses. Titrate to effect in increments of up to 1.5 g per night per week, up to 9 g total nightly dose ( 2.3 ). • Once nightly: Initiate dosage at 3 g or less per night orally, as one dose.

Titrate to effect in increments of up to 1.5 g per night per week, up to 6 g total nightly dose ( 2.3 ). Important Administration Information • Administer XYWAV at least 2 hours after eating ( 2.4 ). • Prepare XYWAV prior to bedtime; dilute with approximately ¼ cup of water in pharmacy-provided containers ( 2.4 ). • Take XYWAV while in bed and lie down after dosing ( 2.4 ). For Patients Transitioning from Xyrem to XYWAV: Initiate at the same dose and regimen as Xyrem (gram for gram).

Titrate as needed based on efficacy and tolerability ( 2.5 ). Patients with Hepatic Impairment Recommended starting dosage is one-half of the original dosage per night administered orally, divided into two doses ( 2.6 ).

2.1Dosing Information in Adult Patients with Narcolepsy The recommended starting dosage is 4.5 grams (g) per night administered orally, divided into two doses: 2.25 g at bedtime and 2.25 g taken 2.5 to 4 hours later (see Table 1). Increase the dosage by up to 1.5 g per night per week (e.g., 0.75 g at bedtime and 0.75 g taken 2.5 to 4 hours later), to the recommended dosage range of 6 g to 9 g per night. The dosage may be gradually titrated based on efficacy and tolerability.

Some patients may achieve better responses with unequal doses at bedtime and 2.5 to 4 hours later. Doses higher than 9 g per night have not been studied and ordinarily should not be administered. Table 1: Recommended Adult XYWAV Dosage Regimen (g = grams) Note: Some patients may achieve better responses with unequal nightly doses at bedtime and 2.5 to 4 hours later.

If a Patient’s Total Nightly Dosage Is: Take at Bedtime: Take 2.5 to 4 Hours Later: 4.5 g per night 2.25 g 2.25 g 6 g per night 3 g 3 g 7.5 g per night 3.75 g 3.75 g 9 g per night 4.5 g 4.5 g

2.2Dosing Information in Pediatric Patients with Narcolepsy For pediatric patients 7 years of age and older, XYWAV is administered orally twice per night. The recommended starting pediatric dosage, titration regimen, and maximum total nightly dosage are based on patient weight, as specified in Table 2. The dosage may be gradually titrated based on efficacy and tolerability.

Doses higher than 9 g per night have not been studied and ordinarily should not be administered. Table 2: Recommended XYWAV Dosage for Patients 7 Years of Age and Older* * For patients who sleep more than 8 hours per night, the first nightly dose of XYWAV may be given at bedtime or after an initial period of sleep. ** If XYWAV is used in patients 7 years of age and older who weigh less than 20 kg, a lower starting dosage, lower maximum weekly dosage increases, and lower total maximum nightly dosage should be considered.

Note: Some patients may achieve better responses with unequal nightly doses at bedtime and 2.5 to 4 hours later. Patient Weight Initial Dosage Maximum Weekly Dosage Increase Maximum Recommended Dosage Take at B… [Excerpted — this section continues on DailyMed.]

3 DOSAGE FORMS AND STRENGTHS XYWAV is a clear to slightly opalescent oral solution at a total salt concentration of 0.5 g per mL. Each mL contains 0.5 g of total salts present as 0.234 g calcium oxybate, 0.096 g magnesium oxybate, 0.13 g potassium oxybate, and 0.04 g sodium oxybate (equivalent to 0.413 g total oxybate). Oral solution: 0.5 g/mL total salts (equivalent to 0.413 g/mL of oxybate) ( 3 )

17 PATIENT COUNSELING INFORMATION Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Central Nervous System Depression Inform patients and/or caregivers that XYWAV can cause central nervous system depression, including respiratory depression, hypotension, profound sedation, syncope, and death. Instruct patients not to engage in activities requiring mental alertness or motor coordination, including operating hazardous machinery, for at least 6 hours after taking XYWAV.

Instruct patients and/or their caregivers to inform their healthcare providers of all the medications they take [see Warnings and Precautions ( 5.1 )]. Abuse and Misuse Inform patients and/or caregivers that the active ingredient of XYWAV is gamma-hydroxybutyrate (GHB), which is associated with serious adverse reactions with illicit use and abuse [see Warnings and Precautions ( 5.2 )]. XYWAV and XYREM REMS XYWAV is available only through a restricted program called the XYWAV and XYREM REMS [see Warnings and Precautions ( 5.3 )].

Inform the patient and/or caregiver of the following notable requirements: • XYWAV is dispensed only by the central pharmacy • XYWAV will be dispensed and shipped only to patients enrolled in the XYWAV and XYREM REMS XYWAV is available only from the central pharmacy participating in the program. Therefore, provide patients and/or caregivers with the telephone number and website for information on how to obtain the product. Alcohol or Sedative Hypnotics Advise patients and/or caregivers that alcohol and other sedative hypnotics should not be taken with XYWAV [see Contraindications ( 4 )] .

Sedation Inform patients and/or caregivers that the patient is likely to fall asleep quickly after taking XYWAV (often within 5 and usually within 15 minutes), but the time it takes to fall asleep can vary from night to night. The sudden onset of sleep, including in a standing position or while rising from bed, has led to falls complicated by injuries, in some cases requiring hospitalization [see Adverse Reactions ( 6.2 )] . Instruct patients and/or caregivers that the patient should remain in bed following ingestion of each dose.

Instruct patients and/or caregivers that the patient should not take a subsequent nightly dose until at least 2.5 to 4 hours after the previous dose [see Dosage and Administration ( 2.4 )] . Administration Instructions Inform patients to administer XYWAV at least 2 hours after eating. Inform patients and/or caregivers of patients taking XYWAV twice nightly, that the total nightly dosage of XYWAV is divided into two doses [see Dosage and Administration ( 2.4 )] .

Inform patients if their nightly dose requires multiple draws. Instruct patients on how to perform the draws from the bottle. Respiratory Depression and Sleep-Disordered Breathing Inform patients that XYWAV may impair respiratory drive, especially in patients with compromised respiratory function, and may cause apnea [see Warnings and Precautions ( 5.4 )] .

Depression and Suicidality Instruct patients and/or caregivers to contact a healthcare provider immediately if the patient develops depressed mood, markedly diminished interest or pleasure in usual activities, significant change in weight and/or appetite, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, or suicidal ideation [see Warnings and Precautions ( 5.5 )] . Other Behavioral or Psychiatric Adverse Reactions Inform patients and/or caregivers that XYWAV can cause behavioral or psychiatric adverse reactions, including confusion, anxiety, and psychosis.

Instruct them to notify their healthcare provider if any of these types of symptoms occur [see Warnings and Precautions ( 5.6 )]. Sleepwalking Instruct patients and/or caregivers that XYWAV has been associated with sleepwalking and other behaviors during sleep, and to contact their healthcare provider if this… [Excerpted — this section continues on DailyMed.]

MEDICATION GUIDE XYWAV ® (ZYE wave) (calcium, magnesium, potassium, and sodium oxybates) oral solution, CIII Read this Medication Guide carefully before you start or your child starts taking XYWAV, and each time you get or your child gets a refill. There may be new information. This information does not take the place of talking to your doctor about your or your child’s medical condition or treatment.

What is the most important information I should know about XYWAV? • XYWAV is a central nervous system (CNS) depressant. Taking XYWAV with other CNS depressants, such as medicines used to make you or your child fall asleep, including opioid analgesics, benzodiazepines, sedating antidepressants, antipsychotics, sedating anti-epileptic medicines, general anesthetics, muscle relaxants, alcohol, or street drugs, may cause serious medical problems, including: o trouble breathing (respiratory depression) o low blood pressure (hypotension) o changes in alertness (drowsiness) o fainting (syncope) o death Ask your doctor if you are not sure if you are, or your child is, taking a medicine listed above. • XYWAV is a federal controlled substance (CIII).

The active ingredient of XYWAV is a form of gamma-hydroxybutyrate (GHB) that is also a federal controlled substance (CI). Abuse of illegal GHB, either alone or with other CNS depressants, may cause serious medical problems, including: o seizure o trouble breathing (respiratory depression) o changes in alertness (drowsiness) o coma o death Call your doctor right away if you have or your child has any of these serious side effects. • Anyone who takes XYWAV 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 XYWAV.

Those activities should not be done until you know how XYWAV affects you or your child. • Keep XYWAV in a safe place to prevent abuse and misuse. Selling or giving away XYWAV 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, XYWAV is available only by prescription, and filled through the central pharmacy in the XYWAV and XYREM REMS.

You or your child must be enrolled in the XYWAV and XYREM REMS to receive XYWAV. For information on how to receive XYWAV, visit www.XYWAVXYREMREMS.com . Before you receive or your child receives XYWAV, your doctor or pharmacist will make sure that you understand how to take XYWAV safely and effectively.

If you have any questions about XYWAV, ask your doctor or call the XYWAV and XYREM REMS at 1-866-997-3688. What is XYWAV? XYWAV is a prescription medicine used to treat: • the following symptoms in people 7 years of age or older with narcolepsy: o sudden onset of weak or paralyzed muscles (cataplexy), or o excessive daytime sleepiness (EDS) • idiopathic hypersomnia (IH) in adults It is not known if XYWAV is safe and effective in children less than 7 years of age with narcolepsy.

It is not known if XYWAV is safe and effective in children with IH. Do not take XYWAV 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 XYWAV, tell your doctor about all medical conditions, including if you or your child: • have a history of drug abuse. • have short periods of not breathing while sleeping (sleep apnea). • has trouble breathing or has lung problems.

You or your child may have a higher chance of having serious breathing problems when taking XYWAV. • have or had depression or has tried to harm yourself or themselves. You or your child should be watched carefully for new symptoms of depression. • has or had behavior or other psychiatric problems such as: o anxiety o feeling more suspicious (paranoia) o acting aggressive o seeing or… [Excerpted — this section continues on DailyMed.]

INSTRUCTIONS FOR USE XYWAV ® (ZYE wave) (calcium, magnesium, potassium, and sodium oxybates) oral solution, CIII This Instructions for Use contains information on how to take XYWAV. Read this Instructions for Use carefully before you (or your child) start taking XYWAV and each time you (or your child) get a refill. There may be new information.

This information does not take the place of talking to your doctor about your (or your child’s) medical condition or treatment. Important Information: • Your doctor and pharmacist will provide instructions to take XYWAV 2 times a night or 1 time a night. o For 2 times a night, you will need to split your (or your child’s) prescribed XYWAV dose into 2 separate pharmacy containers for mixing. o For 1 time a night, you will use the dosing syringe to draw up your prescribed XYWAV dose and empty the dose into 1 pharmacy container for mixing.

You will only need 1 pharmacy container to prepare your dose. • You (or your child) should take XYWAV while in bed. Lie down immediately after taking XYWAV and remain in bed afterwards. • You will need to mix XYWAV with water before you take or give your child the dose. • Safely store the prepared XYWAV doses and take within 24 hours after mixing. If the prepared dose was not taken within this time, throw the mixture away.

See “Throwing away (disposing of) XYWAV” section below for instructions about how to safely throw away XYWAV. • The pharmacy container(s) may be rinsed out with water and emptied into the sink drain. Supplies you will need for mixing and taking (or giving your child) XYWAV. See Figure A: • Bottle of XYWAV medicine • Dosing syringe for measuring and dispensing the XYWAV dose • Measuring cup that is able to measure about ¼ cup of water (not provided with the XYWAV shipment) • 1 or 2 empty pharmacy containers with child-resistant caps for mixing, storing, and taking the XYWAV doses • Alarm clock if you take XYWAV 2 times a night (not pictured) • Medication Guide Note: If you or your child are prescribed XYWAV 2 times a night, see the instructions for 2 times a night dosing.

If you are prescribed XYWAV 1 time a night, see the instructions for 1 time a night dosing. 2 times a night dosing Step 1. Setup • Take the XYWAV bottle, syringe, and pharmacy containers out of the shipping box. • Take the syringe out of the plastic wrapper.

Use only the syringe provided with the XYWAV prescription. • Fill a measuring cup (not provided) with about ¼ cup of water available for mixing your (or your child’s) dose. • Make sure the pharmacy containers are empty. • Open both pharmacy containers by holding the tab under the cap and turning counterclockwise (to the left). See Figure B Figure B • Remove the tamper evident band by pulling at the perforations and then remove the child-resistant bottle cap from the XYWAV bottle by pushing down while turning the cap counterclockwise.

See Figure C Figure C Step 2. Prepare the first XYWAV dose (prepare before bedtime) Place the XYWAV bottle on a hard, flat surface and grip the bottle with one hand. Firmly press the syringe into the center opening of the bottle with the other hand.

See Figure D Figure D Pull back on the plunger until the medicine flows into the syringe and the liquid level is lined up with the marking on the syringe that matches your or your child’s dose. See Figure E Figure E Note: The XYWAV medicine will not flow into the syringe unless you keep the bottle upright. Figure F shows an example of drawing up a 2.25 g dose of XYWAV.

Figure G shows an example if an air space forms when drawing up the medicine. Note: If an air space forms between the plunger and the liquid when drawing up the medicine, line up the liquid level with the marking on the syringe that matches your (or your child’s) dose. See Figure G Figure F Figure G • After you draw up the first divided dose, remove the syringe from the opening of the XYWAV bottle. • Empty all of the medicine from the syringe into one of the provided empty ph… [Excerpted — this section continues on DailyMed.]