What to Know About Xywav

Treatment for Symptoms of Narcolepsy

Xywav (calcium, magnesium, potassium, and sodium oxybates) is a brand name prescription drug. It was approved by the Food and Drug Administration in July 2020 to treat narcolepsy symptoms in adults and children ages 7 and older.

Narcolepsy is a chronic sleep disorder that causes overwhelming daytime sleepiness, interrupted sleep, and cataplexy—sudden, brief episodes of muscle weakness or paralysis that occur while a person is awake.

Xywav is available as an oral solution taken by mouth, twice per night. There is currently no generic form of Xywav. A generic drug is an exact copy of a brand name drug that usually costs less than the brand name. 

narcolepsy

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Uses

Xywav is FDA approved for people with narcolepsy. People with this condition fall asleep during regular activities, including driving and talking. Narcolepsy can range from mild to severe. In cases where it is severe, it negatively affects work, school, social activities, and an affected person’s overall health and well-being.

According to the Narcolepsy Network, narcolepsy affects 1 in every 2,000 Americans.

Narcolepsy is a lifelong health problem. Fortunately, it doesn’t get worse as you age. Symptoms might improve with time, but you will always have symptoms to some degree.

Some of the most common symptoms include excessive daytime sleepiness, cataplexy, sleep paralysis, and hallucinations. All people with this condition will experience excessive daytime sleepiness, but only up to 25% will experience all four major symptoms.

Xywav has been approved to treat two of the most common symptoms of narcolepsy: excessive daytime sleepiness and cataplexy.

Cataplexy

This symptom can cause physical changes from slurred speech to weakness or paralysis of several or all the muscles. Episodes of cataplexy may last up to a few minutes. Cataplexy may also cause weakness of the small muscles, such as the eyelids.

Sometimes, muscle weakness can be so severe it can cause a person to collapse. Some people experience a few episodes of cataplexy yearly, while others will have several episodes a day. Not everyone with narcolepsy will have episodes of cataplexy.

Xywav has been approved by the FDA to treat cataplexy in adults and children with narcolepsy and studies have shown it to be effective for managing cataplexy. Phase 3 studies of Xywav for treating cataplexy were published in late-2020 in the journal SLEEP. These studies found Xywav led to significant differences in the weekly frequency of cataplexy attacks.

In this study of adults, people talking Xywav were compared to other adults taking a placebo (a treatment with no active drug). The study participants initially were treated with Xywav for 12 weeks with increasing doses until researchers determined the correct dose.

After that, participants were given a corrected, consistent dose for two more weeks. For the next two weeks after that, study participants either continued on the same dosage of Xywav or received a placebo.

Cataplexy attacks while using Xywav averaged around 8.9 to 9 attacks per week. But for adults who received the placebo, attacks ranged from 7.2 per week to 18.7 per week.

Excess Daytime Sleepiness

Xywav has also been approved for treating excessive daytime sleepiness (EDS) in adults and children with narcolepsy. People with EDS experience a strong need to sleep that may occur suddenly while they are awake.

EDS affects every single person with narcolepsy. EDS also causes people to feel sleepy and tired all the time and this happens even if they have slept eight or more hours the night before. Research has found Xywav is effective in managing EDS in people with narcolepsy.

In the previously mentioned 2020 study published in the journal, SLEEP, people with narcolepsy took Xywav for up to 12 weeks until the correct dosage was determined. For another two weeks, they were given a consistent dose of Xywav, and then for the last two weeks, the study participants either continued using Xywav or were given a placebo.

The researchers relied on the Epworth Sleepiness Scale (ESS) to measure symptoms of EDS. Scores of ESS range from 0 to 24, and the higher the number, the sleepier a person is throughout their day. ESS scores averaged around 13.6 in people who took Xywav throughout the study and ranged from 12.6 to 15.6 for the people taking the placebo towards the end of the study.

Xywav for Children

While Xywav is approved for use in children who experience symptoms of cataplexy or excessive daytime sleepiness with narcolepsy, there have not been any studies done to determine the effectiveness of Xywav for children.

However, labeling for Xywav compares it to another narcolepsy drug called Xyrem (sodium oxybate). Xyrem, much like Xywav, contains sodium oxybate as an active ingredient. Xywav is a modified version of Xyrem with 92% less sodium.

One study on Xyrem—according to the labeling for Xywav—shows children were given increasing doses for up to 10 weeks until the correct dosage was reached. Once dosage was determined, the children were given two weeks of consistent dosing of Xyrem. After that, for another two weeks, half of the group of children continued on the Xyrem while the other half was put on a placebo. 

The study found the average number of cataplexy attacks in the children while taking Xyrem averaged 3.5 attacks to 3.8 attacks weekly. The children who were using the placebo had a range of 4.7 attacks to 21.3 attacks per week. ESS scores (on a scale of 0 to 24) were 8 to 9 with the Xyrem. They increased to 11 to 12 in the children who were using the placebo at the end of the study.

Off-Label Use

Xywav has been used to treat idiopathic hypersomnia (IH) but its use is considered off-label. IH is a neurologic disorder that causes excessive daytime sleepiness despite a person getting a full night’s sleep. IH is similar to narcolepsy in that people with the condition experience excessive sleepiness, but IH doesn’t cause the other serious symptoms of narcolepsy.

Off-label use means that a particular drug is being used for an unapproved condition for an unapproved age group, dosage, or administration. Off-label drugs need to be submitted to the FDA for review with clinical data and other information, showing the drug is safe and effective for the intended use.

When the FDA determines that a drug is safe for off-label use, this doesn’t mean the drug doesn’t have side effects, it just means it has decided that the benefits outweigh the risks of using a particular drug.

Xyrem was previously found to improve daytime sleepiness in people with IH to the same degree as in people who narcolepsy. It was also found to improve sleep inertia significantly in people with IH.

Sleep Inertia

Sleep inertia is a transitional stage between sleeping and being awake. It is marked by impaired function, feelings of drowsiness and disorientation, and a desire to go back to sleep.

Xywav clinical trials for idiopathic hypersomnia were completed in late 2020 and the manufacturer plans to seek the FDA’s approval for use in managing excessive daytime sleepiness in IH in 2021.

Before Taking

Before taking Xywav, you should tell your doctor if you are allergic to sodium oxybate or if you have other allergies.

You should also let your doctor know if you have a history of metabolic conditions, liver disease, breathing problems, including sleep apnea, a personal or family history of drug or alcohol abuse, mood or mental health concerns, including depression and suicidal thoughts or attempts.

Your doctor also needs to know if you have other sleep disorders and the medications you are taking for those. Lastly, they need to know about all other medications, over-the-counter medicines, vitamins, and herbal supplements you or a child take.

Dosage

Xywav should be taken according to the instructions given to you by your healthcare provider. This is extremely important because Xywav can lead to drug tolerance. Drug tolerance means that you will experience a diminished response to a drug after you have used it repeatedly and your body adapts to it.

Xywav may also cause dependence, which is where the body needs the drug to feel normal. Both tolerance and dependence can lead to misuse of Xywav.

Preparation

Xywav comes as a solution that needs to be diluted in water. Once diluted, it can be taken by mouth. It is taken in two doses, the first taken when you go to bed, and the second dose 2.5 to 4 hours later.

The Xywav solution comes in containers to dilute the solution and a syringe to measure the dosage. Both doses can be prepared at bedtime.

To prepare the solution, you would start by using the syringe to dose the correct amount of medication. You then place the solution into the empty container and add a 1/4 cup of water to the solution.

The second dose is prepared the same way. The diluted solution should be taken within 24 hours and any solution that remains after 24 hours should be thrown out.

How To Take

You should take the first dose at least two hours after your last meal for the day and when you are getting ready for bed. The second dose is taken 2.5 to 4.0 hours later. You will need to set an alarm to wake up and take the second dose. Take your medication while sitting up in bed, and then lie down after the dose.

According to the labeling information, you should avoid activities that might be considered dangerous within the first six hours of taking a dose of Xywav. This includes driving. Talk to your doctor about when you should take Xywav and what activities you will need to avoid. Do what you can not to miss doses.

You should not take Xywav with food. It should be taken at least two hours after eating. This is because taking it with food might affect the way the drug is absorbed and lead to the medication being less effective.

Storage

Xywav can be stored at room temperature. It should be kept in a tightly sealed container. Any solution that has been diluted should be taken within 24 hours. After that, it should be discarded.

Side Effects

The side effects of Xywav may differ in adults versus children. For more information on the side effects of Xywav, talk to your doctor. They can also offer some ideas on managing side effects.

Common Side Effects

The most common side effects of Xywav in adults include:

  • Headaches
  • Nausea
  • Vomiting
  • Decreased appetite
  • Parasomnia— a sleep disorder that causes abnormal behavior while sleeping
  • Abnormal dreams
  • Sleepwalking
  • Diarrhea
  • Sweating
  • Anxiety

Side effects in children taking Xywav might include:

  • Bedwetting
  • Nausea
  • Headache
  • Vomiting
  • Weight loss
  • Decreased appetite
  • Dizziness

Most of these side effects will go away within a few days to weeks after starting the drug. If they don’t go away or become severe, talk to your doctor. They may suggest changing the dosage or taking a different treatment.

Severe Side Effects

You should call your doctor if you experience severe side effects. Call 911 if you or a child experience symptoms that appear life-threatening or if you think there is a medical emergency.

Severe side effects associated with Xywav might include:

  • Breathing problems: This might include trouble breathing, sleep apnea, or slowed breathing. If you already have sleep apnea, lung problems, or breathing problems, you are more likely to experience breathing problems while using Xywav.
  • Mental health problems: This might include confusion, hallucinations (seeing or hearing things that are not real), abnormal thinking, anxiety, feeling upset for no reason, depression, thoughts of harming yourself or others, increased tiredness, and concentration problems. Call your doctor if you or your child are feeling or are considering self-harm or harming others.
  • Sleepwalking: This could lead to an injury. Sleepwalking is more common in children, but your doctor should know about sleepwalking regardless of a person's age.
  • Allergic reaction to Xywav: Symptoms of a drug reaction might include a skin rash or hives, fever, wheezing, and shortness of breath. Some people might experience a serious reaction called anaphylaxis that could lead to a tightening of the airways and throat, trouble breathing, reduced blood pressure, seizures, and other serious symptoms. These types of reactions to Xywav are rare.

Warnings and Interactions

Some people should not take Xywav. This includes people who are pregnant or who are breastfeeding. Researchers do not know if it is safe for a pregnant person to take Xywav and the animal studies conducted by the manufacturer showed an increased risk for stillbirth and growth problems in offspring.

While animal studies aren’t a predictor of what will happen in people, you should let your doctor know if you are pregnant or planning on becoming pregnant while using Xywav. They might suggest you take something else until after you give birth.

It is unknown whether Xywav is safe while breastfeeding. Sodium oxybate, an active ingredient in Xywav, can pass to breastmilk, which means a breastfed child can be exposed to the drug. Additionally, the effects of Xywav on a breastfed child are unknown.

If you are breastfeeding let your doctor know before starting Xywav. They may suggest another treatment while you are breastfeeding.

Many medications can interact with Xywav. According to the manufacturer's labeling, this may include Divalproex sodium and other central nervous system (CNS) depressants.

Divalproex Sodium

Divalproex sodium is a drug used to treat seizures. It may cause you to have too much Xywav in your body and increase your risk for serious side effects, including breathing troubles and decreased alertness.

Other CNS Depressants

Xywav belongs to a class of drugs called CNS depressants that reduce the activity of the central nervous system. If you are taking CNS depressants, your doctor needs to know because these drugs can affect breathing rate, blood pressure, and alertness. They can also cause seizures, lead to coma, and can be fatal.

The FDA has issued a boxed warning for CNS depressants with Xywav. A boxed warning is the most serious warning the FDA gives. Make sure you let your doctor know what other medications you take so they can determine what other CNS depressants you might be having.

Specific CNS depressants that should not be taken with Xywav include:

  • Sleep medications like Ambien (zolpidem), Lunesta (eszopiclone), and Ramelteon (rozerem)
  • Drugs called benzodiazepines used to treat mood and sleep disorders like Xanax (alprazolam) and Valium (diazepam)
  • Barbiturates also used to treat sleep and mood disorders, including Amytal (amobarbital)

Other medications that might be considered CNS depressants should not be taken and may include:

  • Some pain medications, including oxycodone, fentanyl, and morphine
  • Muscle relaxers including Soma (carisoprodol)
  • Antidepressants or antipsychotic medications
  • Illegal drugs like heroin

If you take any of these medications, make sure you let your doctor know. 

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Article Sources
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