Xyrem

Approved Indications

Xyrem is a central nervous system depressant used to manage specific symptoms in patients 7 years of age and older who have been diagnosed with narcolepsy. It is primarily prescribed for two conditions:

• Cataplexy: This is a sudden, temporary loss of muscle tone or strength. These episodes are often triggered by strong emotions, such as laughter, anger, or surprise, and can cause a person to become weak or collapse.
• Excessive Daytime Sleepiness (EDS): This involves a persistent feeling of sleepiness and an inability to stay awake or alert during the day, regardless of the amount of sleep obtained at night.

The medication is intended to help reduce the frequency of cataplexy attacks and improve daytime alertness in those living with narcolepsy.

Mechanism of Action

The exact mechanism by which Xyrem works to treat narcolepsy is not fully known. It is a central nervous system depressant that is thought to act on certain neurotransmitters in the brain, specifically gamma-aminobutyric acid (GABA). It is believed that its effects are mediated through GABA-B receptors during sleep.

Impact on Sleep Architecture

Xyrem helps regulate the sleep-wake cycle by changing how the brain moves through different stages of sleep. Its primary functions include:

• Increasing Slow-Wave Sleep: It promotes deeper, more restorative stages of sleep that are often fragmented in people with narcolepsy.
• Reducing Nighttime Disruptions: By consolidating sleep, it helps prevent frequent awakenings throughout the night.
• Managing Daytime Symptoms: By improving the quality of rest at night, the medication helps reduce excessive daytime sleepiness and the occurrence of cataplexy (sudden loss of muscle strength).

Because the medication significantly slows brain activity, it is typically taken in two doses: one at bedtime and another several hours later to maintain its effect throughout the night.

Common Side Effects

Many people using Xyrem experience mild to moderate side effects. These may include:

• Nausea and vomiting
• Dizziness or lightheadedness
• Headache
• Bedwetting
• Diarrhea
• Decreased appetite and weight loss
• Tremors or shaking
• Pain in the arms or legs
• Feeling unusually sleepy or tired during the day

Serious Side Effects

Some side effects can be severe and require immediate medical attention. Contact a healthcare provider right away if you experience:

• Breathing problems: This includes slow or shallow breathing, or sleep apnea (where breathing stops for short periods during sleep).
• Mental health changes: New or worsening depression, anxiety, confusion, hallucinations, or unusual thoughts.
• Thoughts of self-harm: Any thoughts of hurting yourself or suicidal actions.
• Sleepwalking: Walking or performing other activities while asleep, which can lead to injuries.
• Allergic reactions: Signs such as hives, rash, or swelling of the face, tongue, or throat.
• Seizures: Sudden, uncontrolled electrical disturbances in the brain.

Boxed Warning: CNS Depression and Abuse

Xyrem can cause severe central nervous system (CNS) depression, which may lead to respiratory distress, coma, or death. Because sodium oxybate is a form of gamma-hydroxybutyrate (GHB), it has a high potential for abuse and misuse. Due to these risks, Xyrem is only available through a restricted distribution program called the Xyrem REMS.

Contraindications

Xyrem must not be used in combination with alcohol or sedative-hypnotic medications (such as benzodiazepines). Using these together increases the risk of life-threatening respiratory depression. It is also contraindicated for individuals with succinic semialdehyde dehydrogenase deficiency, a rare metabolic disorder.

Mental Health and Behavioral Effects

This medication may cause significant changes in mood or behavior. Healthcare providers monitor for the following:

• Depression or worsening of existing mood disorders
• Suicidal thoughts or behaviors
• Confusion, anxiety, or agitation
• Hallucinations or psychosis

Sleep-Related Issues

Xyrem can cause breathing problems during sleep, including sleep apnea and decreased oxygen levels. It is also associated with parasomnias, such as sleepwalking (somnambulism), which can result in accidental injury. Any new or unusual sleep behaviors should be reported to a healthcare provider.

Sodium Content Warning

Xyrem contains a high amount of sodium in each dose. This is a critical precaution for individuals with medical conditions that require restricted salt intake, such as heart failure, hypertension, or kidney disease.

General Precautions

Because Xyrem causes rapid onset of sleep and significant impairment, it should only be taken while in bed. Individuals should not engage in hazardous activities requiring mental alertness, such as driving or operating machinery, for at least six hours after taking a dose.

Pregnancy

There are no adequate and well-controlled studies regarding the use of Xyrem in pregnant women. In animal studies, high doses of the medication were associated with decreased fetal weight and increased risks, though these findings may not directly apply to humans. It is important to talk with a healthcare provider about the risks and benefits if you are pregnant or planning to become pregnant while taking this medication.

Breastfeeding

Xyrem is known to pass into breast milk. The impact on a nursing infant and on milk production is not well established. If you are breastfeeding while taking this medication, you should monitor your infant for potential side effects, such as:

• Increased sleepiness or sedation
• Trouble breathing
• Changes in feeding patterns or poor weight gain

Decisions regarding breastfeeding while using Xyrem should be made in consultation with a healthcare professional to weigh the benefits of breastfeeding against the potential risks to the infant.

Available Forms

Xyrem is available as an oral solution. This liquid medication is clear to slightly opalescent and is intended for oral administration.

The product is supplied in a bottle with a child-resistant cap. It is packaged with a measuring syringe and dosing cups to facilitate the preparation and administration of the liquid.

FDA Approval and Indications

The U.S. Food and Drug Administration (FDA) approved Xyrem (sodium oxybate) to treat cataplexy and excessive daytime sleepiness in patients 7 years of age and older with narcolepsy.

Boxed Warning

Xyrem carries a boxed warning, the FDA's most serious warning, because it is a central nervous system (CNS) depressant and has the potential for abuse and misuse. The active ingredient in Xyrem is a form of gamma-hydroxybutyrate (GHB). Misuse of GHB is associated with serious safety risks, including seizures, coma, and death. Even at recommended doses, Xyrem can cause severe breathing problems and loss of consciousness.

REMS Program

Because of these risks, Xyrem is only available through a restricted distribution program called the Xyrem REMS (Risk Evaluation and Mitigation Strategy). This program requires that:

• Healthcare providers who prescribe the drug must be specially certified.
• The medication is only dispensed by a designated central pharmacy.
• Patients and caregivers receive education on the risks and the importance of safe storage to prevent accidental ingestion or misuse.

Controlled Substance Status

Xyrem is classified as a Schedule III controlled substance for medical use. The FDA has issued safety communications warning that Xyrem should not be used with alcohol or other drugs that cause sleepiness or slow breathing, as this combination can lead to life-threatening respiratory depression.

Risk of Misuse and Abuse

Xyrem contains sodium oxybate, which is the sodium salt of gamma-hydroxybutyrate (GHB). GHB is a substance with a known history of abuse and is associated with severe adverse reactions. Because of the risk of misuse, Xyrem is classified as a controlled substance and is only available through a restricted distribution program called a REMS (Risk Evaluation and Mitigation Strategy).

Serious Safety Concerns

Misusing Xyrem or taking it in ways not prescribed can lead to life-threatening complications. These risks are increased if the medication is combined with alcohol or other drugs that cause drowsiness. Serious effects of misuse include:

• Severe breathing problems (respiratory depression)
• Seizures
• Changes in alertness or loss of consciousness
• Coma or death

Dependence and Withdrawal

Xyrem can be habit-forming, and patients may develop a physical or psychological dependence on the medication. If the drug is stopped abruptly after long-term use, withdrawal symptoms may occur. These symptoms can include:

• Anxiety and agitation
• Insomnia
• Tremors
• Increased heart rate and blood pressure
• Hallucinations or confusion

To minimize the risk of addiction and dependence, it is essential to follow the prescribed dosing schedule exactly and never share the medication with others. Healthcare providers will monitor patients for signs of misuse or abuse during treatment.