If you or someone in your household has narcolepsy, you know how much this condition can affect daily life.
People with narcolepsy have fragmented nighttime sleep and extreme sleepiness during the day. This leads to “sleep attacks,” where people with narcolepsy fall asleep suddenly, sometimes even while doing an activity or having a conversation. These symptoms can make it difficult to work or learn.
Some people with narcolepsy also have cataplexy, which refers to sudden, brief loss of muscle control. For example, your head may drop to the side. These attacks are often triggered by strong emotions, such as laughter or excitement.
One medicine used for narcolepsy is Xyrem (sodium oxybate). Xyrem is FDA-approved to treat excessive daytime sleepiness (EDS) or cataplexy in adults and children aged 7 or older with narcolepsy.
Below are common questions and answers to help you understand more about Xyrem, how it works, and what to discuss with your health care provider.
How Does Xyrem Work for Narcolepsy?
Xyrem contains sodium oxybate, which is also called gamma-hydroxybutyrate (GHB). GHB acts on GABA-B receptors in the brain and alters the release of certain brain chemicals. This slows down activity in the central nervous system, which quickly causes strong drowsiness and puts you in a deep sleep. Xyrem is taken at night to help improve nighttime sleep, which is thought to reduce symptoms the next day.
How Do I Take Xyrem?
Xyrem is a liquid medicine that is taken by mouth at night while you are in bed. You will prepare two doses before bedtime by adding water to dilute the medicine. Your pharmacy will provide instructions, special containers, and measuring tools to prepare the medicine safely.
Your health care provider will tell you how much Xyrem to take. Typically, your total nightly dose is split into two doses.
- The first dose is taken at bedtime while you are in bed, at least two hours after eating.
- The second dose is taken 2.5-4 hours later (consider setting an alarm).
Xyrem causes strong drowsiness very quickly (often within 5-15 minutes), so it must be taken only once you are in bed for the night and ready to go to sleep.
For adults, the typical starting dose is 4.5 grams (g) per night. Your health care provider may increase your dose slowly if your daytime sleepiness or cataplexy continues. The dose is usually adjusted each week in small steps until symptoms improve. The maximum total nightly dose is 9 g per night.
For children, the starting and maximum dosage of Xyrem are much lower and depend on their body weight. Their health care provider will slowly increase the dose based on how the child responds. It may also be adjusted over time as the child grows.
Always check with your health care provider before making changes.
How Was Xyrem Studied for Cataplexy in Adults With Narcolepsy?
Two clinical studies, Trial N1 and Trial N2, tested the effect of Xyrem for cataplexy in adults with narcolepsy. In both studies, the main goal was to measure changes in the number of cataplexy attacks.
Most people in these studies were also taking stimulant medicines for narcolepsy to help them stay awake during the day. Only those on a stable stimulant dose for narcolepsy could join. These studies did not include people who had other conditions or factors that could affect sleep or make participation unsafe. This included anyone with sleep apnea, other causes of daytime sleepiness, unstable medical conditions, seizure or certain psychiatric conditions, substance use concerns, or abnormal lab or heart test results. People taking certain medicines, working night or rotating shifts, or who were pregnant or could become pregnant were also not allowed to join the study.
Trial N1 included 136 adults who had moderate to severe cataplexy. At baseline (meaning before the study began), these people were having frequent cataplexy attacks, with a median 21 attacks per week (median is the middle value in a set of numbers). The average age was 43 years. Most people (91.2%) were Caucasian, 6.6% were African American, 0.7% were Asian, and 1.5% identified as other races.
- People in the study were randomly assigned to take Xyrem (3 g, 6 g, or 9 g) or a placebo (containing no medicine) each night for four weeks. No one knew which one they were getting. Daytime sleepiness and symptom severity were measured at clinic visits, and people kept daily diaries to track cataplexy attacks and other symptoms.
In Trial N2, researchers tested whether Xyrem continued to work after taking it for a while. The study included 55 adults who had already been taking Xyrem for 7-44 months. People were randomly assigned to continue their usual Xyrem dose (3-9 g per night) or switch to a placebo for two weeks.
Results:
In Trial N1, Xyrem 6 g and 9 g nightly doses significantly reduced the number of cataplexy attacks compared with placebo. The 3-g dose had little effect.
In Trial N2, people who switched from Xyrem to placebo had a big increase in cataplexy attacks (median increase of 21 attacks in two weeks), while those who stayed on Xyrem had no increase. Benefits were similar in people taking 6 g or 9 g per night.
Together, these studies show that Xyrem reduces the number of cataplexy attacks in adults with narcolepsy and that it keeps working long-term. Note that most people in these studies were also taking stimulant medicines, so it was not always possible to determine Xyrem’s effects independently of stimulants. Your results may differ from what was seen in clinical studies.
How Was Xyrem Studied for Excessive Daytime Sleepiness in People With Narcolepsy?
Two additional studies, Trial N3 and Trial N4, tested the effect of Xyrem for excessive daytime sleepiness in people 16 years and older with narcolepsy.
In these studies, researchers used various symptom rating tools to measure effectiveness.
- Epworth Sleepiness Scale (ESS): This questionnaire measures how likely a person is to fall asleep during everyday activities, such as reading, watching TV, or other common scenarios. A higher total score (on a scale of 0-24) means more severe sleepiness.
- Clinical Global Impression of Change (CGI-C): This 7-point scale is used to rate how much a person’s symptoms have improved or worsened over time. People were rated by comparing their current symptoms to how severe their symptoms were before the trial started.
- Maintenance of Wakefulness Test (MWT): This test measures how long someone can stay awake during the day. A person sits in a quiet room for several short sessions and tries to stay awake. Each session ends after 20 minutes if they stay awake or after 10 minutes if they fall asleep. Their final score is the average time they stayed awake, with higher times showing better alertness.
Trial N3 included 228 people with moderate to severe daytime sleepiness. People’s ages ranged from 16 to 75 (average, 40.5). Most people (196) were Caucasian, 25 were of African descent, two were Asian, two were Hispanic, and two identified as other races/ethnicities. At baseline, people had high daytime sleepiness scores (ESS scores between 17 and 19, on a scale of 0-24).
- People were randomly assigned to take placebo or Xyrem at doses of 4.5 g, 6 g, or 9 g per night for eight weeks. Most people (78%) continued taking stimulant medicines to help them stay awake during the day, but antidepressant medicines were stopped before the study.
Trial N4 included 222 people with moderate to severe narcolepsy symptoms.
- All people started the study while taking a stable dose of a stimulant medicine called modafinil for at least a month. They were then randomly assigned to one of four groups: placebo, Xyrem only, modafinil only, or Xyrem plus modafinil. Those taking Xyrem used 6 g nightly for four weeks, then 9 g nightly for another four weeks. People in the placebo or Xyrem-only groups stopped taking modafinil, while those in the modafinil-only and Xyrem-plus-modafinil groups continued their usual dose of modafinil.
Results:
In Trial N3, people taking Xyrem saw significant improvements after eight weeks of treatment.
- The group taking 6 g per night had a 2-point reduction in sleepiness score (ESS), while those taking the 9-g dose had a 5-point reduction. A lower score means less severe sleepiness.
- More than half (52%-64%) of the people taking Xyrem (6-9 g per night) rated their change in daytime and nighttime symptoms as “very much improved” or “much improved.”
- Those taking the highest dosage (9 g per night) could stay awake longer during the day, with a median increase of 10+ minutes on the MWT.
In Trial N4, people taking Xyrem could stay awake slightly longer during the day. By week 8, people taking Xyrem (alone or with modafinil) had improved MWT scores (0.5-2.7 minutes increase on average) compared with placebo.
Together, these studies show that Xyrem can reduce daytime sleepiness in people with narcolepsy. Your results may differ from what was seen in clinical studies. Talk with your health care provider about what to expect while taking Xyrem.
How Was Xyrem Studied in Children With Narcolepsy?
A clinical study tested the effectiveness of Xyrem in children and adolescents aged 7-17 with narcolepsy. Trial N5 included 106 people with cataplexy and excessive daytime sleepiness. Everyone had a history of at least 14 cataplexy attacks in a typical two-week period before starting treatment. About half the children and adolescents in the study were taking a stable dose of a stimulant.
Some people entered the study already taking Xyrem, while others were new to it. After reaching a stable Xyrem dose, 63 people were randomly assigned to continue Xyrem or switch to placebo. No one knew which one they were taking.
The study measured how often cataplexy attacks happened, how severe they were, how sleepy people felt during the day, and how their overall narcolepsy symptoms changed. Researchers used child-friendly versions of the same rating scales used in adult studies.
Results:
Children who continued Xyrem had fewer weekly cataplexy attacks than those who switched to placebo. Improvements were also seen in overall ratings of symptom severity. Those who switched to placebo had worsening daytime sleepiness and more frequent cataplexy.
These findings support the effectiveness of Xyrem in children with narcolepsy. While results can vary, a health care provider can help determine if Xyrem is a good option for your child.
What Are the Benefits of Xyrem, and When Will I See Them?
Across various studies, many adults and children with narcolepsy saw benefits while taking Xyrem, such as the following.
- Fewer cataplexy attacks
- Reduced daytime sleepiness
- Improved ability to stay awake
- Better overall ratings of narcolepsy symptoms (by clinicians and people in the studies)
In studies, improvements were seen within weeks of starting treatment and continued with ongoing use. As mentioned, real-life experiences can vary from study results. Tell your health care provider if you feel Xyrem is not helping.
What Is the Difference Between Xyrem and Xywav?
Xyrem and Xywav are both prescription medicines used to treat symptoms of narcolepsy. Both are made by the same company and contain the same active ingredient (oxybate), but they differ in sodium content.
Xyrem contains 550 milligrams (mg) to 1,640 mg of sodium in each dose, with more sodium in higher doses. Xywav has very little sodium in comparison. For instance, the maximum dose (9 g) of Xywav has about 1,500 mg less sodium than the same dose of Xyrem.
Consuming too much sodium can increase blood pressure and worsen heart disease. If you need to limit your sodium intake, your health care provider may ask you to take Xywav instead of Xyrem.
Is It Safe to Take Xyrem?
Xyrem can be safe when it is taken exactly as prescribed, but it does come with serious risks that you should understand. Xyrem slows down the central nervous system, which means it can cause strong drowsiness and, in some cases, slowed or difficult breathing. For this reason, it must never be taken with alcohol or other medicines that make you sleepy, such as painkillers (opioids) or sleep aids. Combining these can greatly increase the risk of dangerous side effects. If you must take a medicine that makes you sleepy (if you need surgery, for example), your health care provider may temporarily stop your Xyrem treatment.
Xyrem also has potential for misuse, which means taking a medicine in a way other than how it was prescribed. Xyrem is only available through a special safety program. Some people may have serious side effects, such as breathing problems during sleep, unusual nighttime behaviors such as sleepwalking, and mood changes, including suicidal thoughts or behaviors. (This is not a full list of side effects.)
When used correctly, with the right monitoring and safety precautions, Xyrem can be safe to take for many. Your health care provider will work with you to weigh the potential benefits against the risks and decide whether Xyrem is the right choice for you or your child.
Is There Any Xyrem Cost Assistance Available?
A cost assistance program for Xyrem is available from the drugmaker. It may reduce the amount you need to pay. Whether you qualify to enroll may depend on what type of insurance you have or if you are uninsured.
Visit this website for more information about Xyrem costs and copay savings. You can also call 833-533-5299 to connect with a representative for financial support information and other resources.
