Xyrem: Some Questions and Misperceptions
In the past the only medications available for treating the symptoms of narcolepsy were medications that had been developed to treat other conditions or disorders. Stimulants such as Dextroamphetamine (Dexedrine) and Methylphenidate (Ritalin) developed to treat hyperactivity and attention deficit disorder in children has been prescribed to help daytime sleepiness in people with narcolepsy. Tri-cyclic anti-depressants were found to effectively help curb or control cataplexy and other REM related symptoms of narcolepsy. The use of medications for a purpose other than what the drug is officially approved for is called “off-label” use and is not uncommon particularly in conditions or disorders where patient populations are small.
In recent years several new medications have been developed and approved specifically for treating the symptoms of narcolepsy. Modafinil (Provigil) was first approved in 1997 for treating excessive daytime sleepiness in people with narcolepsy. More recently it has also gained approval for treating sleepiness in other disorders such as sleep apnea and shift work sleep disorder. Sodium Oxybate (Xyrem), the most recently approved new medication for patients with narcolepsy was approved for the treatment of cataplexy in July of 2002. Recent clinical trials have also demonstrated Xyrem’s effectiveness in treating the symptom of daytime sleepiness. A supplemental new drug application will be filed with the FDA to gain approval for this indication as well.
Although a number of people with narcolepsy have reported tremendous success with Xyrem’s treating their cataplexy and other symptoms of narcolepsy, a number of patients and doctors alike have remained hesitant to try this new treatment. The following section raises some of the most common questions or stumbling blocks that come up in queries from people with narcolepsy or the physicians treating them. The questions are followed with answers from some of the leading clinicians treating patients with narcolepsy or patients who have taken Xyrem successfully for some period of time.
Q. I’m not willing to stop taking my current cataplexy medication before trying the Xyrem. Rebound cataplexy is too difficult and disruptive to my life. I’m doing OK; I will stick with what I have taken for years.
Although patients who enrolled in the clinical trials were required to withdraw from their cataplexy medications in order to comply with the study protocol it certainly is not necessary for one to stop their existing cataplexy medication in order to start taking Xyrem. In the initial clinical trials patients were withdrawn from their cataplexy medications in order to compare a person’s cataplexy at “baseline” verses while on the new medication or placebo. Now that the drug is approved, prescribing doctors can start a patient on Xyrem and slowly wean them from their previous cataplexy medications as the Xyrem begins to work to control symptoms of cataplexy. A person may still experience some mild rebound cataplexy while slowly weaning from the old medications (it is hard to avoid entirely due to the nature of anti-depressants), but generally this rebound cataplexy will be mild and less severe as the Xyrem works to help lessen the rebound.
– Dr. Richard K. Bogan,
Q. I’m afraid to try Xyrem, isn’t that the “date-rape” drug or a “party” drug?
I can fully understand the fear that comes with trying Xyrem because I had that fear myself in the beginning. However, the way to overcome fear is to talk about it. In my experience I wanted to talk with other people already taking the medication. I spoke with people face to face in my narcolepsy support group as well as other people through the phone and internet. I also spoke with more than one doctor. My family/support system was another avenue I used to talk about my fears and choices. After speaking with these different groups of people I began to feel more at ease in taking the medication.
In terms of the date rape drug or party drug, many medications are misused recreationally. I knew my experience would be carefully monitored by a physician. If someone at a party gives you a drug, no one knows where the drug comes from. When a doctor prescribes a medication, the dosage and quality are controlled.
– Nicole Cortichiato, Xyrem user for 5 years.
Q. I have high blood pressure and I was told that the salt content of Xyrem would make my high blood pressure worse.
The salt content of Xyrem is fairly high and for persons sensitive to salt this might be a valid concern. Salt sensitivity varies amongst patients with high blood pressure. A person shouldn’t assume they will not tolerate Xyrem due to it’s salt content and therefore should not preclude at least a brief trial of the drug to assess it’s effectiveness on a individual basis.
– Dr. Wynne Chen,
Sodium content of Xyrem – information provided by Orphan Medical
Sodium oxybate is 18.25% sodium. This means that for every 100gm of sodium oxybate, there is approximately 18gm of sodium. Xyrem is a 50% w/v sodium oxybate solution (500mg/ml) in USP purified water with a sodium concentration of 91mg/ml (s ee table for dose equivalents) . Patients on sodium-restricted diets should consult with their physician prior to initiating sodium oxybate therapy.
NOTE: Daily Recommended Value (DRV) = 2400 mg
Q. I’m told that I need to take the medication while in bed because it will take effect immediately. The idea of anything taking effect so quickly scares me. Will I have time to lie down comfortably?
The Xyrem can and does take effect fairly quickly but it isn’t instantaneous. It is important to take the medication and get into bed. In my experience the Xyrem will fully take affect and cause me to be in a deep sleep approximately 20 minutes after taking. Some nights it will take effect more quickly and other nights it seems to take a little longer, so it’s always a good idea to take it when fully ready for bed and either in or near bed.
I was told that the Xyrem will put me into such a deep sleep that I won’t wake up. Isn’t this dangerous? What if there is a fire or an emergency?
On a long term basis, I have rarely found this to be a problem. Most patients get partially used to the sleep inducing effect of XYREM and can still wake up if an emergency or a strong external stimulation occurs. Additionally, for some patients with narcolepsy-cataplexy, insomnia is so pronounced without treatment that even with XYREM sleep is not as deep as anticipated. But of course, every patient is different, may react atypically to the medication, and these guidelines cannot be generalized.
– Dr. Emmanuel Mignot,
Q. When taking Xyrem two doses are needed throughout the night. I’m not sure I want to have to wake up in the middle of the night to take a second dose.
Most patients feel that the benefits of treatment outweigh this inconvenience. In fact, because of the short half life, many patients easily wake spontaneously to take the second dose and only occasionally require an alarm clock to take the second dose.
– Dr. Neil Feldman,
Q. I was told that if you drink alcohol you can’t take Xyrem.
Both alcohol and sodium oxybate (Xyrem) are sedating and impair cognition. Accordingly, it is reasonable to avoid mixing the two. This leaves open the question of how soon after drinking alcohol, and how much alcohol, is it safe to take oxybate, and vice versa. Unfortunately, there is no scientific data from controlled trials to provide guidance. The half-life for oxybate is so short, an hour or less, that drinking three ounces of wine or an equivalent amount of another alcoholic beverage, six hours or more after or six hours or more before taking a therapeutic dose of oxybate may be safe. Reducing the interval between drinking alcohol and taking oxybate, or increasing the amount consumed of either, should be done with caution, if at all.
– Dr. Michael Biber, MA
Q. I heard that Xyrem is a highly addictive drug and that withdrawal can be deadly. I’m not sure I want to be taking anything so dangerous.
Reports of addiction and withdrawal following long-term abuse of street forms of GHB have caused concerns about physical dependence from sodium Oxybate; however, the therapeutic administration of sodium oxybate (Xyrem) for up to 44 months has not cause withdrawal upon abrupt discontinuation.
A study of 55 patients who had taken Xyrem long-term were asked to abruptly withdraw treatment. There was no evidence of a withdrawal phenomenon at the therapeutic doses studied. Additionally, no rebound insomnia was noted.
When similar compounds are used as drugs of abuse there have been reported cases of difficult withdrawal reaction. When used as a drug of abuse typically doses are many times higher than doses prescribed to patients with narcolepsy.
– Information from Clinical Trial results reports.
Q. I’ve heard that Xyrem has side effects of nausea, bed-wetting, and sleep walking. I’m not sure that taking the drug will be worth these complications.
In most cases Xyrem is well tolerated and absent of side effects. The reported side effects can occur but the incidence is small and careful titration and following instructions will minimize adverse events. Most often side effects of incontinence, sleep walking and nausea will disappear with continued treatment. If side effects persist a patient may have to weigh the pros and cons of continued use.
– Dr. Neil Feldman,
This article was published in the Winter 2005 issue of The Network, a newsletter published exclusively for members of Narcolepsy Network, Inc., 631B Ten Rod Road, North Kingstown, RI 02852 Tel. 1-888-292-6522. This newsletter may not be posted to any website in whole or in part without the express permission of Narcolepsy Network.