Talk:Sodium oxybate/Archive 1

Archive 1

Off-label and European usage?

Is there any information on this drug's current or future availability for off-label in the USA? Proponents see GHB as a safe, non-toxic, borderline wonder drug, with dozens of potential uses including: treatments for depression, anxiety, obesity, alcoholism, drug abuse/dependence, insomnia, ADHD, bipolar disorder, social anxiety disorder and many others. However, the DEA really seems to fear this compound because of its media-fueled notoriety, so despite its being Schedule III, it's tightly controlled. Information on the European use of GHB, whatever name it goes by there would be very informative, and would help tone down the danger rhetoric currently making up a large part of the article. Kel - Ex-web.god 13:51, 26 October 2007 (UTC)

Kel, I'm a GHB sympathizer but I wrote this article with as strict NPOV as I was able. The sources of the claims made here are clearly cited, and as you note the problem is that there isn't any information representing the other side of the debate. You'd need to funnel in info from credentialed experts in biology, pharmacology, public policy, or similar fields. Probably that info would be more useful on the main GHB page, anyway -- it's just bald-faced reefer madness over there. I figured I'd make a small contribution here, rather than wading into that maelstrom.

I'm not aware of the status of GHB in Europe. I agree that the information would be useful, though! Inhumandecency 20:54, 27 October 2007 (UTC)

You're right, and I apologize if my comment insinuated that you weren't remaining NPOV. I actually agree with everything you just said. I guess we're caught in a catch-22, as credentialed experts willing o say something positive about the substance are rare. I guess that's just the nature of the beast. It also doesn't help that even the Xyrem's own prescribing information is packed, if not consumed, with the reefer madness rhetoric you spoke of. Add to that the ridiculous cost, support program and central pharmacy thing, and it's clear the powers that be don't want the substance out there, even as a prescription.

As for GHB's status in Europe, I'm pretty sure it's banned for recreational use n more than a few countries. WHat I'm hoping someone will add is its use and status as a prescribed medicine. Rare as it may be, the US occasionally takes cues from European medicine trends, and any information of novel uses for existing compounds couldn't hurt. I have lots of anecdotal evidence of GHB being used to spectacular effect for the conditions mentioned above, but nothing citable, hence its absence. Anyway, good job on the article. :) Kel - Ex-web.god 08:05, 5 November 2007 (UTC)

ATC Code

Xyrem falls within N07XX04 —Preceding unsigned comment added by 208.74.209.161 (talk) 13:11, 18 July 2008 (UTC)

Done, thanks --ἀνυπόδητος (talk) 17:19, 14 January 2013 (UTC)

Two articles?

Is it really necessary to have two separate articles about the exact same chemical Xyrem™ and gamma-Hydroxybutyric acid? This had also been done with the Morphine and MSIR articles (and since been merged). --- W5WMW (talk) 00:17, 6 April 2010 (UTC)

In this case, I think it is best to have two separate articles because of the length of the GHB article. There is sufficient length in each article to keep them separate. --Tea with toast (talk) 06:06, 6 April 2010 (UTC)

-I have to disagree, the Xyrem™ article should be merged with the gamma-Hydroxybutyric acid article. As a medical professional, I have found that patients often rely upon Wikipedia as an initial source of information about medications, and I find the Xyrem™ article incomplete without the mechanism of action information discussed in the gamma-Hydroxybutyric acid page. (talk)

I have address your concern about the mechanism of action by creating a section that links to the content found in the GHB article so that it is more accessible to patients. I still believe it is best to keep that articles separate since Xyrem has it's own history that is separate from GHB. I think it would be more difficult for patients to find the information they need if this article was merged with GHB. --Tea with toast (talk) 19:37, 4 December 2010 (UTC)

Xyrem should most definitely be a separate article from GHB. GHB has the odd distinction of being both a schedule 1 and schedule 3 substance, with Xyrem being the approved schedule 3 use (even though it is a GHB salt). --98.70.56.46 (talk) 20:45, 19 October 2011 (UTC)

Xyrem is Sodium Oxybate. GHB, whilst most frequently encountered in the form of the sodium salt (NaGHB) version, can also be synthesised to other forms, such as potassium GHB (kGHB). That's why there is a need for two articles. — Preceding unsigned comment added by 83.168.50.235 (talk) 10:01, 7 November 2013 (UTC)

(Side) Effects

Pretty well the entire section under "Side effects" is very badly organized/written.

Data on abuse, dependance and withdrawal; while quite interesting is hardly a side effect.

I'm doubtful pregnancy effects should be under "side effects" (generally many things that are normally done are bad while pregnant).

There is no mention of central apneas, by far the most common side-effect of Xyrem/Sodium oxybate/GHB (at least in medical use).

There is no mention of increased N3 sleep, by far the greatest measurable effect of Xyrem/Sodium oxybate/GHB. — Preceding unsigned comment added by 207.172.210.101 (talk) 09:08, 18 September 2015 (UTC)

Update XYREM Package Insert link

I am an employee of Synchrony Healthcare Communications, Inc. (Synchrony). Synchrony is an agent acting on behalf of Jazz Pharmaceuticals plc (Jazz), and my intent is to correct misinformation about Jazz products in a truthful and non-misleading manner. All of the edits that I request are made with the knowledge and approval of Jazz.

I suggest updating the Xyrem package insert link in the External links section. The current link is no longer active due to updates made to the package insert. The current Xyrem package insert can be found at: https://www.xyrem.com/prescribing-information.pdf

Jipeuxer83 (talk) 14:49, 5 January 2016 (UTC)Jipeuxer83

 Done. -- Ed (Edgar181) 21:51, 5 January 2016 (UTC)

Request edit for updated bioavailability and protein binding data

I am an employee of Synchrony Healthcare Communications, Inc. (Synchrony). Synchrony is an agent acting on behalf of Jazz Pharmaceuticals plc (Jazz), and my intent is to correct misinformation about Jazz products in a truthful and non-misleading manner. All of the edits that I request are made with the knowledge and approval of Jazz. The information regarding the bioavailability and protein binding data of Xyrem on the sodium oxybate Wikipedia article is inaccurate. I suggest making updates according to the data found in the 2015 Xyrem Package Insert.

The current Xyrem package insert can be found at: https://www.xyrem.com/prescribinginformation.pdf

Under the pharmacokinetic data section, please update the bioavailability of Xyrem to 88% and protein binding to <1%. These data can be supported by section 12.3 Pharmacokinetics, subsection Absorption, in the Xyrem Package Insert, which states “Following oral administration, sodium oxybate is absorbed rapidly across the clinical dose range, with an absolute bioavailability of about 88%” and subsection Distribution, which states “At sodium oxybate concentrations ranging from 3 mcg/mL to 300 mcg/mL, less than 1% is bound to plasma proteins.”

References

Jipeuxer83 (talk) 15:09, 12 January 2016 (UTC)Jipeuxer83

 Done. -- Ed (Edgar181) 14:18, 20 January 2016 (UTC)

Request edit for updated distribution section

I am an employee of Synchrony Healthcare Communications, Inc. (Synchrony). Synchrony is an agent acting on behalf of Jazz Pharmaceuticals plc (Jazz), and my intent is to correct misinformation about Jazz products in a truthful and non-misleading manner. All of the edits that I request are made with the knowledge and approval of Jazz.

In April 2015, the Xyrem Package Insert was updated to reflect the Food and Drug Administration’s (FDA) approval of the Xyrem Risk Evaluation and Mitigation Strategy (REMS) Program. The Xyrem REMS Program replaces the Risk Management Plan for Xyrem that was called the Xyrem Success Program.

I suggest making edits to the distribution section of the sodium oxybate Wikipedia article in order to reflect the current terminology. The current Xyrem package insert can be found at: https://www.xyrem.com/prescribing-information.pdf

The following edits are suggested to reflect the terminology that was updated in the Xyrem Package Insert in April 2015:

A number of measures have been put in place by sodium oxybate's manufacturers to ensure that it is used safely and appropriately. For example, in the US sodium oxybate requires a prescription and can only be obtained through a restricted distribution program, called the (delete “Xyrem Success Program”: this pertains to the program previously in place. Replace with text: “Xyrem REMS Program using the central pharmacy that is specially certified.” ).

This restricted distribution program is required by the FDA as part of a (please delete from “Risk Management Program” through bullet “Detailed patient surveillance”. This details the program previously in place, which has now been updated to a new program. Please replace text with:

“Risk Evaluation and Mitigation Strategy (REMS) to manage known or potential serious risks to ensure the benefits of Xyrem outweigh the risks.

The required components of the Xyrem REMS Program include:

• Healthcare providers who prescribe Xyrem are specially certified
• Xyrem will be dispensed and shipped only to patients who are enrolled in the Xyrem
• REMS Program with documentation of safe use conditions

Xyrem will be dispensed only by the specially certified central pharmacy”)

References

Jipeuxer83 (talk) 23:08, 25 January 2016 (UTC)Jipeuxer83

Updates to Adverse Events Section

I am an employee of Synchrony Healthcare Communications, Inc (Synchrony). Synchrony is an agent acting on behalf of Jazz Pharmaceuticals plc (Jazz), and my intent is to correct misinformation about Jazz products in a truthful and non-misleading manner. All of the edits that I request are made with the knowledge and approval of Jazz. I suggest making edits to the adverse effects section in order to reflect the Clinical Trials Experience section of the current Xyrem package insert.

The current Xyrem package insert can be found at: https://www.xyrem.com/prescribinginformation.pdf

Please delete the current section and update with the following sections of the package insert.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Xyrem was studied in three placebo-controlled clinical trials in 611 patients with narcolepsy (398 subjects treated with Xyrem, and 213 with placebo). Of the 398 Xyrem-treated patients with narcolepsy, 10.3% of patients discontinued because of adverse reactions compared with 2.8% of patients receiving placebo. The most common adverse reaction leading to discontinuation was nausea (2.8%). The majority of adverse reactions leading to discontinuation began during the first few weeks of treatment. The most common adverse reactions (incidence ≥5% and twice the rate seen with placebo) in Xyrem-treated patients were nausea, dizziness, vomiting, somnolence, enuresis,and tremor.

References

Jipeuxer83 (talk) 03:02, 23 February 2016 (UTC)Jipeuxer83

Request Edit: Broken Links in References

I am an employee of Synchrony Healthcare Communications, Inc. (Synchrony). Synchrony is an agent acting on behalf of Jazz Pharmaceuticals plc (Jazz), and my intent is to correct misinformation about Jazz products in a truthful and non-misleading manner. All of the edits that I request are made with the knowledge and approval of Jazz.

I suggest updating the Xyrem package insert link throughout the reference section of the sodium oxybate Wikipedia Article. There are repeated references to the package insert. The current link is no longer active due to updates made to the package insert. The current Xyrem package insert can be found at: https://www.xyrem.com/prescribinginformation.pdf

References numbered 13 and 15 both refer to the Xyrem package insert. The links within the references are either broken or link to a previous version of the PI. Please update and renumber references with the current link to the Xyrem package insert.

References

Jipeuxer83 (talk) 15:13, 16 March 2016 (UTC)Jipeuxer83

 Done. The external links are all currently working. Leschnei (talk) 15:23, 31 December 2016 (UTC)

Side effects

WP:MEDMOS "a long list of side effects is largely useless without some idea of which are common or serious."

For example, if I read in The Lancet that one of the adverse effects of steroid drugs is heart disease, that's a major serious adverse effect which doctors have to consider when treating, say, autoimmune diseases. But nonspecific adverse effects like nausea or dizziness aren't useful. If someone wants that information, they can look it up in the package insert.

I think that the package insert is not a WP:MEDRS, because it's a primary source, not a secondary source. I would only use it if it reinforced a secondary source. Copying from the package insert, or even published monographs in medical journals, would be WP:OR. It does belong as an external link, though. --Nbauman (talk) 22:27, 3 March 2017 (UTC)

Accuracy Updates

I am an employee of Jazz Pharmaceuticals plc (Jazz), and my intent is to correct misinformation related to Jazz products or related disease states in a truthful and non-misleading manner.

All proposed edits will be requested through the Talk Page function of the site, in accordance with FDA’s draft Guidance, “Internet/Social Media Platforms: Correcting Independent Third-Party Misinformation About Prescription Drugs and Medical Devices”. I will disclose my employment at Jazz with each requested edit made through the Talk page. All of the edits that I request are made with the knowledge and approval of Jazz.

To report any potential negative side effects for Jazz products, please contact Jazz Pharmaceuticals at 1-800-520-5568. You are also encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

I suggest making edits to the lead section, the side effects section and the History section in order to correct the information regarding the adverse affects, pregnancy considerations, and marketing of off-label use. --CPark 2017 (talk) 16:47, 13 April 2018 (UTC)

Lead Section Sodium oxybate (USAN) (brand names Xyrem, Alcover, Anetamin, Gamanest, Gioron, Somsanit), contracted from sodium γ-hydroxybutyrate, is a prescription medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy,and by the FDA, Health Canada and in some areas of the United Kingdom National Health Service for the treatment of cataplexy associated with narcolepsy. Sodium oxybate is the sodium salt of γ-hydroxybutyric acid (GHB). Xyrem is manufactured by Jazz Pharmaceuticals in the US and in Canada. (please remove Valeant Pharmaceuticals in Canada. Product MonographUnder the name Alcover, it is used in Italy for treatment of alcohol withdrawal and dependence.

--CPark 2017 (talk) 16:47, 13 April 2018 (UTC)

 Not done The whole article needed revising, and lead accordingly. When I am done updating the body I will revise the lead to better summarize the body per WP:LEAD, which I will do differently than what is suggested above. Jytdog (talk) 22:06, 14 April 2018 (UTC)

Side Effects On October 18, 2011, Jazz Pharmaceuticals, Inc. disclosed that it had received a Warning Letter from the FDA for specific violations during the FDA's inspection of the firm from April 27, 2011 through May 6, 2011. In the letter the FDA cited 2 specific violations: 1. Failure to develop adequate written procedures for the surveillance, receipt, evaluation, and reporting of postmarketing adverse drug experiences to FDA [21 C.F.R § 314.80(b)]. 2. Failure to submit adverse drug experience (ADE) reports that are both serious and unexpected to FDA within 15 calendar days of initial receipt of the information by the applicant [21 C.F.R. § 314.80(c)(1)(i)]. (please add the following text) The FDA subsequently sent a Close Out letter in Aug 2013 stating based on their evaluation of the firm’s corrective actions in response to the Warning Letter, the firm addressed the violations contained in the Warning Letter. FDA Closeout Letter

--CPark 2017 (talk) 16:47, 13 April 2018 (UTC)

 Done Jytdog (talk) 22:03, 14 April 2018 (UTC)

Adverse Effects Sodium oxybate is generally well tolerated by most patients. The most common side effects reported in clinical trials include nausea, dizziness, headache, vomiting, sleepiness, and bed-wetting, (please add tremor). Some patients treated with sodium oxybate have also experienced (please remove moderate to significant) weight loss. This may be due to the fact that sodium oxybate improves sleep architecture and increases the length of deep sleep stages, resulting in increased production of human growth hormone (HGH) and changes in energy metabolism. The weight loss could also be due to decreased (please remove daytime) appetite (Please remove experienced by many users and add the following text) a side effect reported from use of sodium oxybate) and the instructions to not eat for two hours before bedtime. Serious side effects, as listed on all prescriptions of sodium oxybate, can include hallucinations, agitation, (please remove severe mental confusion and replace with mental confusion), abnormal thinking, disrupted sleep, and depression.[http://pp.jazzpharma.com/pi/xyrem.en.USPI.pdf Prescribing --CPark 2017 (talk) 16:47, 13 April 2018 (UTC)

 Not done - i will revise this based on the labels. It has a black box warning and a REMS plan for pete's sake. Jytdog (talk) 22:05, 14 April 2018 (UTC)

Pregnancy Considerations (please delete text from "The U.S. Food and Drug Administration through of pregnancy". FDA Pregnancy Lactation Labeling Rule

Currently, there are no well-controlled studies in pregnant women. (please add following text) There is no adequate data on the developmental risk associated with the use of sodium oxybate in pregnant women.

Animal studies have shown adverse effects on the fetus. In one study, rats were given oral sodium oxybate throughout pregnancy and lactation. This resulted in increased stillbirths, decreased offspring survival after birth, and decreased body weight gain. In another study, pregnant rats and pregnant rabbits were given oral sodium oxybate during organogenesis. This resulted in no evidence of adverse effects on fetal development. As such, sodium oxybate should be used in pregnancy only if the benefit outweighs the risk for the fetus. (please add the following text). GHB is excreted in human milk after oral administration of sodium oxybate. There is insufficient information on the risk to a breastfed infant or milk production in nursing mothers.Prescribing Information --CPark 2017 (talk) 16:47, 13 April 2018 (UTC)

I will revise this too, according to the labels. We do not go into the level of detail you go into there. Jytdog (talk) 22:08, 14 April 2018 (UTC)

History Marketing of off-label use (please delete text from "In 2007, the makers of Xyrem through psychiatric disorders" and replace with the following text) In 2007, Jazz Pharmaceuticals agreed to pay more than $20 million in penalties and victim compensation to resolve criminal and civil investigations relating to illegal marketing practices of Orphan Medical, Inc., which Jazz had acquired in 2005. As part of the resolution, Orphan Medical, Inc. pleaded guilty to felony misbranding, including illegally promoting Xyrem for unapproved uses, including as a treatment for fatigue, insomnia, chronic pain and psychiatric disorders.

References

--CPark 2017 (talk) 16:47, 13 April 2018 (UTC)

Thanks for the ref. DoJ press releases describing settlements are very reliable. I have used that ref and generated content from it. Thanks again for that. Jytdog (talk) 21:58, 14 April 2018 (UTC)

status

i worked most of this over.

The history part is very interesting to me and I will work that over tomorrow. It needs to lay out the background of medical use in the 1960s and 70s for anesthesia etc, and what happened with that, then the history of mounting abuse/alarm in the 1990s as orphan was developing it and how that culimanted in the bifurcated classification in 2000. It is also fairly astounding to me that the FDA asked the company to develop this for narcolepsy. This FDA transcript has some interesting stuff about the history as well as clinical trial history. I also need to find refs on the history of deals that have been done. The drug is sold in the europe by UCB under the Xyrem name; there must be some deal that Orphan Medical or Jazz did, under which that is happening. more to come, in any case... Jytdog (talk) 02:08, 15 April 2018 (UTC)

U.S. Scheduling

The article states that sodium oxybate is a schedule III treated like a schedule I. However, the reference citation given returns a http not found error and the FDA monogram states that it is a schedule III and makes no mention of schedule I except in the context of GHB itself, which is a technically different substance that is not FDA approved. I have therefore inserted the dubious tag, until better references can be found. 98.178.191.34 (talk) 23:15, 9 May 2021 (UTC)

Proposed merge of Xywav into Sodium oxybate

This is a very similar drug to Xyrem. It is an oxybate salt, I don't see strong justification for two independent articles. We should have one on the salt with a section on its applications in the two drugs Xyrem and Xywav Polyamorph (talk) 13:37, 28 November 2021 (UTC)

"For information about its illicit use, see gamma-hydroxybutyric acid"

GHB is, although related, a totally independent chemical composition and therefore a different chemical altogether. Nearly alike is not the same as exactly alike. Therefore I do not see how the ABOUT box in the introduction is appropriate. I've therefore removed this sentence in the introduction. If you feel that my action is inappropriate, then feel free to give me a shout. BenBrownBoy (Aye?) 17:33, 20 September 2022 (UTC)

Merger proposal

The following discussion is closed. Please do not modify it. Subsequent comments should be made in a new section. A summary of the conclusions reached follows.

The result of this discussion was that the Sodium Oxybate (Xyrem) and Xywav wiki pages should not be merged. BenBrownBoy (Aye?) 13:27, 21 September 2022 (UTC)

---

The merger proposal was that Sodium Oxybate (Xyrem) and Xywav pages be merged.

• Though highly related, these two drugs are independent of each other and are backed by different compositional chemistry as well as other notable differences such as distribution of specific salt concentrations, salts, taste, and potentially interactions. 76.89.203.179 (talk) 17:54, 27 June 2022 (UTC)

I totally agree with you here. I don't think this proposal to merge needs to be kept open anymore. It's pretty much an open and shut case. I intend to propose that the said discussion be closed in the near future. BenBrownBoy (Aye?) 17:44, 20 September 2022 (UTC)

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

Information added for D&A Pharma

Hello, I've added a few items to the "medical use" and "statistics" sections that were sent to me by the D&A Pharma company. They seem legitimate to me (I've double-checked the sources) and I don't yet know whether I'll be paid for them, so if in doubt I'd rather announce it here. I'm open to any comments or suggestions. Thank you! Jul.H (talk) 09:12, 11 August 2023 (UTC)