Xywav

Narcolepsy

Xywav is used to treat symptoms of narcolepsy in adults and children 7 years of age and older. It is specifically indicated for:

• Cataplexy: This is a sudden, temporary loss of muscle tone or weakness that is often triggered by strong emotions like laughter, surprise, or anger.
• Excessive Daytime Sleepiness: This is a condition where a person feels an overwhelming urge to sleep during the day, regardless of how much sleep they received at night.

Idiopathic Hypersomnia

Xywav is also approved for use in adults with idiopathic hypersomnia. This sleep disorder causes people to feel very sleepy during the day despite getting a normal or long amount of sleep at night. It can also cause extreme difficulty waking up from sleep, often referred to as sleep inertia or sleep drunkenness.

This medication is a central nervous system depressant. It is formulated with a blend of oxybate salts that provides a lower sodium content compared to some other similar treatments, which may be beneficial for patients who need to limit their sodium intake for heart health or other medical reasons.

Mechanism of Action

Xywav is a central nervous system depressant. While the exact way it works to treat narcolepsy and idiopathic hypersomnia is not fully understood, it is believed to produce its effects by interacting with certain receptors in the brain.

Interaction with GABA Receptors

The active ingredient in Xywav is oxybate. Scientists believe that oxybate works by binding to GABA-B receptors on neurons in the brain. GABA is a naturally occurring chemical messenger (neurotransmitter) that helps regulate nerve activity and promotes relaxation and sleep.

Effects on Sleep

By acting on these receptors, Xywav is thought to help improve the overall quality and structure of sleep. Its primary effects include:

• Improving nighttime sleep: It helps consolidate sleep and may increase the amount of deep sleep a person gets during the night.
• Reducing daytime symptoms: By improving the quality of sleep at night, the medication helps reduce excessive daytime sleepiness and the frequency of cataplexy (sudden muscle weakness) in people with narcolepsy.

Because Xywav is a potent depressant, it significantly slows down brain activity. This is why it is taken at night and why it is important to be in bed immediately after taking a dose.

Common Side Effects

Many people using Xywav experience mild to moderate side effects. These often include:

• Nausea and vomiting
• Headache
• Dizziness or lightheadedness
• Increased sweating
• Decreased appetite
• Diarrhea
• Dry mouth
• Tremors or shakiness
• Anxiety

Serious Side Effects

While less common, some side effects can be severe and require immediate medical attention. Contact a healthcare provider right away if you experience:

• Breathing problems: Slowed or shallow breathing, or periods where breathing stops during sleep (sleep apnea).
• Mental health changes: New or worsening depression, anxiety, confusion, hallucinations, or thoughts of self-harm.
• Sleep behaviors: Sleepwalking, or performing activities while asleep that you do not remember later, such as eating or talking.
• Allergic reactions: Swelling of the face, lips, or tongue, or difficulty breathing.
• Incontinence: Bedwetting or loss of bladder control during sleep.

Because Xywav is a central nervous system depressant, it can cause extreme drowsiness. It should not be taken with alcohol or other sedating medications, as this increases the risk of dangerous side effects.

Boxed Warning: CNS Depression and Abuse

Xywav is a form of gamma-hydroxybutyrate (GHB). Because of the risks of central nervous system (CNS) depression and abuse or misuse, it is only available through a restricted program called the Xywav REMS. Serious side effects can include respiratory depression, coma, or death. Because of these risks, the medication is strictly controlled.

Contraindications

Xywav must not be taken with alcohol or sedative-hypnotic medications, such as benzodiazepines. Using these substances together increases the risk of profound sedation and respiratory failure. It is also contraindicated in individuals with succinic semialdehyde dehydrogenase deficiency, a rare metabolic disorder.

Respiratory and CNS Depression

Xywav can slow or stop breathing. This risk is higher in people who have underlying respiratory issues, such as sleep apnea or chronic obstructive pulmonary disease (COPD). Because the medication causes profound sedation, it should be taken while in bed. Users should not engage in activities requiring mental alertness, such as driving or operating heavy machinery, for at least six hours after taking a dose.

Mental Health and Behavioral Effects

Some people taking Xywav may experience changes in mood or behavior. Monitoring is recommended for the following:

• Depression and Suicidal Thoughts: There is an increased risk of depression, anxiety, or thoughts of self-harm while taking this medication.
• Psychosis: Symptoms such as hallucinations, paranoia, or agitation may occur.
• Parasomnias: Complex sleep behaviors like sleepwalking, sleep-eating, or performing other tasks while asleep have been reported. These behaviors can lead to serious injury.

Sodium and Mineral Content

While Xywav contains significantly less sodium than sodium oxybate (Xyrem), it still contains a combination of sodium, potassium, calcium, and magnesium. Individuals on a salt-restricted diet or those with heart failure, hypertension, or kidney disease should be aware of the total mineral content.

Pregnancy

There are no adequate and well-controlled studies of Xywav in pregnant women. It is currently unknown whether the medication can cause fetal harm or affect reproductive capacity. In animal studies where high doses of oxybate were administered, researchers observed increased stillbirths and decreased pup survival and body weight. Xywav should be used during pregnancy only if the potential benefit clearly outweighs the potential risk to the fetus.

Breastfeeding

The active ingredient in Xywav is excreted in human milk. Because the medication is a central nervous system depressant, there is a concern that it could cause serious side effects in a nursing infant, such as:

• Excessive sleepiness
• Slow or shallow breathing
• Decreased muscle tone

Healthcare providers typically recommend monitoring the infant closely for these signs if a mother continues to take Xywav while breastfeeding. Some patients may choose to discontinue nursing or the medication after consulting with their doctor.

Clinical Considerations

If you are pregnant, planning to become pregnant, or breastfeeding, it is essential to talk to your healthcare provider. They can help evaluate the risks of the medication versus the risks of leaving symptoms of narcolepsy or idiopathic hypersomnia untreated during this time.

Dosage Forms

Xywav is supplied as a clear to slightly opalescent oral solution. This liquid medication is intended to be diluted with water before it is swallowed.

FDA Approval and Indications

Xywav (calcium, magnesium, potassium, and sodium oxybates) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy. It is also approved for the treatment of idiopathic hypersomnia (IH) in adults.

Boxed Warning

Xywav carries a Boxed Warning, the FDA's most serious type of warning, regarding the following risks:

• Central Nervous System (CNS) Depression: Xywav can cause severe breathing problems and a decrease in consciousness, even at recommended doses.
• Abuse and Misuse: The active ingredient in Xywav is a form of gamma-hydroxybutyrate (GHB), which is associated with serious adverse reactions including seizures, respiratory depression, and death.

REMS Program and Distribution

Because of these risks, Xywav is only available through a restricted distribution program called the XYWAV and XYREM REMS. Under this program:

• Prescribers must be certified in the program.
• The medication is only dispensed by a central pharmacy that is certified in the program.
• Patients must be enrolled in the program and educated on the risks of the medication.

Controlled Substance Status

Xywav is classified as a Schedule III controlled substance. However, because it contains GHB, the penalties for illegal use, possession, or distribution are those associated with Schedule I substances.

Safety Communications

The FDA has issued safety communications warning that Xywav must not be taken with alcohol or other CNS depressant medications, as this combination significantly increases the risk of profound sedation, respiratory depression, and death.

Specialty Pharmacy Distribution

Xywav is not available at standard retail pharmacies. It is distributed exclusively through a central specialty pharmacy as part of a restricted program called the XYWAV and XYREM REMS. This program is required by the FDA to ensure the medication is used safely. The specialty pharmacy coordinates the delivery of the medication and works with patients to manage the billing and insurance process.

Insurance and Prior Authorization

Most insurance plans, including private insurance and government programs like Medicare, may cover Xywav. However, insurance providers often require a prior authorization process. This means a healthcare provider must submit documentation to the insurance company to confirm that the medication is medically necessary before coverage is approved. The final out-of-pocket cost depends on the specific terms of the patient's insurance plan, such as deductibles and copayment tiers.

Financial Assistance Options

Several options may be available to help reduce the cost of Xywav:

• Copay Savings Programs: Eligible patients with commercial (private) insurance may be able to use a copay savings card to lower their monthly out-of-pocket expenses.
• Patient Assistance Programs: For individuals who are uninsured or meet specific financial criteria, the manufacturer may offer programs that provide the medication at a reduced cost or for free.

Patients are encouraged to speak with the specialty pharmacy or a benefits coordinator to obtain specific pricing information and explore available support options.