Sodium oxybate (USAN; sodium ?-hydroxybutyrate; sodium oxybutyrate; brand names Xyrem, Alcover, Anetamin, Gamanest, Gioron, Somsanit) is a prescription medication used to treat two symptoms of narcolepsy: sudden muscle weakness and excessive daytime sleepiness.
Sodium oxybate is the sodium salt of ?-hydroxybutyric acid (GHB). Xyrem is manufactured by Jazz Pharmaceuticals in the US and Valeant Pharmaceuticals in Canada. Under the name Alcover, it is used in Italy for treatment of alcohol withdrawal & dependence.
Video Sodium oxybate
Medical use
Sodium oxybate is used to treat two symptoms of narcolepsy: sudden muscle weakness and excessive daytime sleepiness.
Because of the risks of the drug it is available in the US only through a risk evaluation and mitigation strategy (REMS) program mandated by the FDA. The program requires that providers who prescribe it are certified to do so, that it is only dispensed from a central pharmacy that is certified to do so, and people to whom it is prescribed must be enrolled in a program for the drug and must document that they are using the drug safely.
Pregnant women should not take it, and women should not become pregnant while taking it. It is excreted in breast milk and should not be used by breast feeding mothers.
Maps Sodium oxybate
Adverse effects
The US label for sodium oxybate has a black box warning because it is a central nervous system depressant and may cause respiratory depression, seizures, coma, or death, especially if used in combination with other CNS depressants, such as alcohol. Its use may cause dependence and there is a history of drug abuse of GHB, its active metabolite, including in date rape.
It causes dizziness, nausea, and headache in 10% to 20% of people who take it; nausea is more common in women than men.
Between 1% and 10% of people experience nasal congestion, runny nose, or sore throat, loss of appetite, distorted sense of taste, cataplexy, weakness, nervousness or anxiety, depressed mood, nightmares or abnormal dreams, sleep paralysis, sleepwalking, or other sleep disturbances including insomnia, sleepiness or sedation, falls, vertigo, tremor, balance disorder, cognitive issues including disturbance in attention, confusion or disorientation, numbed sense of touch, tingling, blurred vision, heart palpitations, high blood pressure, shortness of breath, snoring, vomiting, diarrhea, stomach pain, excessive sweating, rashes, joint pain, muscle pain, back pain, muscle spasms, bedwetting, urinary incontinence, and swelling of the limbs.
Overdose
Reports of overdose in the medical literature are generally from abuse, and often involve other drugs as well. Symptoms include vomiting, excessive sweating, agitation, coma, periods of stopped breathing, seizures, agitation, loss of psychomotor skills, and coma. Overdose can lead to death due to respiratory depression. People who overdosed may die from inhaling their own vomit. People may need to made to vomit, intubated, and put on a respirator.
Interactions
It should not be used with other drugs that are CNS depressants like alcohol or sedatives. Use with divalproex results in about a 25% increase in the availability of sodium oxybate.
Pharmacology
The mechanism of action of sodium oxybate is unknown. GHB is a normal metabolite of GABA that interacts with the GABAB receptor.
It is rapidly absorbed and is about 88% bioavailable; very little is bound to plasma protein. The average time to peak plasma concentration ranges from 0.5 to 1.25 hours. Very little of the drug is excreted; instead it is mostly metabolized through several steps into carbon dioxide and water.
Chemistry
Sodium oxybate is the sodium salt of gamma hydroxybutyrate (GHB). Its chemical name is sodium 4-hydroxybutyrate, the molecular formula is C4H7NaO3, and the molecular weight is 126.09 g/mole. It is very hydrophilic.
History
- In 1994, the OOPD petitioned a pharmaceutical company called Orphan Medical to investigate sodium oxybate as a potential treatment for narcolepsy.
- In 1996, Orphan Medical submitted an Investigational New Drug Application (IND) to the FDA and began Phase I, II, and III clinical trials to investigate the safety and efficacy of sodium oxybate.
- In 2000, Orphan Medical submitted a New Drug Application (NDA) to the FDA for sodium oxybate. Sodium oxybate was granted "Priority Review".
- In 2002, sodium oxybate received approval from the FDA for the treatment of cataplexy in patients with narcolepsy.
- In 2005, the Xyrem brand was acquired by Jazz Pharmaceuticals when they purchased Orphan Medical. Later that year, sodium oxybate was granted a second indication by the FDA for the treatment of EDS in patients with narcolepsy. Also that year sodium oxybate was approved for the treatment of cataplexy in patients with narcolepsy by Health Canada and for the same indication in adult patients by the European Medicines Agency for the European Union (EU) and the Swiss Agency for Therapeutic Products, Swissmedic.
In 2006, sodium oxybate received an expanded indication for narcolepsy with cataplexy in the EU.
The FDA sent Jazz an FDA warning letter about safety violations in September 2007.
In 2010 the FDA rejected Jazz' New Drug Application for use of sodium oxybate in fibromyalgia.
In October 2011, the FDA sent Jazz another FDA warning letter for failing to collect, evaluate, and promptly report adverse effects to the FDA after it started marketing the drug. It sent another letter in 2013 saying that the problems described in 2011 letter appeared to be resolved.
Marketing of off-label use
In July 2007 Jazz and their subsidiary Orphan Medical pleaded guilty to a criminal charge of felony misbranding in their marketing of sodium oxybate; they also settled a civil suit at the same time. The matter had been raised by a former sales representative who filed a qui tam case against the company under the False Claims Act. Sales representatives had made sales calls to doctors who did not treat people with narcolepsy and told them about potential uses for the drug including fatigue, insomnia, chronic pain, weight loss, depression, bipolar disorders, and movement disorders like Parkinson's Disease, and downplayed the risks described in the label's black box warning. A sales manager who had been involved in the illegal marketing scheme had previously pleaded guilty and a psychiatrist who promoted the drug had previously been charged. Jazz paid $20M in total and agreed to a corporate integrity agreement and to implement internal reforms.
Society and culture
Regulation
In the US, sodium oxybate is classified as a Schedule III controlled substance for medicinal use under the Controlled Substances Act, with illicit use subject to Schedule I penalties. Examples of other schedule III products in the US include Tylenol with codeine and testosterone. In Canada and the European Union (EU), it is classified as a Schedule III and a Schedule IV controlled substance, respectively. Sodium oxybate is the only treatment for narcolepsy approved by the World Anti-Doping Agency.
Cost
In the US, the cost (as of Q3 2015) of Xyrem is $5,468.09 per 180 mL bottle (500 mg/mL)(a 10 to 15-day supply) As of 2017 the cost of sodium oxybate in the UK was £540.00 to £1,080.00 for a thirty day supply, which at typical doses is £6,500 to £13,100 per year.
Jazz Pharmaceuticals raised the price of Xyrem 841% earning a total of $569 million in 2013 and representing more than 50% of Jazz Pharmaceutical's revenues. In 2007 it cost $2.04; by 2014 it cost $19.40 per 1-milliliter dose. Jazz offers copay assistance to help patients access the expensive drug. According to DRX, a drug-data report published by Bloomberg, Jazz Pharmaceuticals price increase on Xyrem topped the list of price hikes in 2014.
Historically, orphan drugs cost more than other drugs and have received special treatment since the enactment of the U.S. Orphan Drug Act of 1983. However, these steep price increases of orphan and other specialty drugs has come under scrutiny. The average cost of a specialty drug in the US was $65,000 annually in June 2013 (about $5,416 a month). The price of Xyrem in the US has inflated by an average of 40% annually since it became available as a prescription.
In European Union (EU) countries, the government either provides national health insurance (as in the UK and Italy) or strictly regulates quasi-private social insurance funds (as in Germany, France, and the Netherlands). These government agencies are the sole purchaser (or regulator) of medical goods and services and have the power to set prices. The cost of pharmaceuticals, including sodium oxybate, tends to be lower in these countries.
NHS England authorises and pays for sodium oxybate by means of individual funding requests on the basis of exceptional circumstances. The British Department of Health pays for the medication for 80 patients who are taking legal action over problems linked to the use of the swine flu vaccine Pandemrix at a cost of £12,000 a year. As of 2016 there were many areas in the UK where NHS did not pay for it. In May 2016 they were ordered by the High Court to provide funding to treat a teenager with severe narcolepsy. The judge criticised their "thoroughly bad decision" and "absurd" policy discriminating against the girl when hundreds of other NHS patients already receive the drug.
As of April 2018, there were 18 US patents listed in the FDA orange book for sodium oxybate.
References
Source of the article : Wikipedia
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