Sodium oxybate, sold under the brand name Xyrem among others, is a
medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
used to treat two symptoms of
narcolepsy
Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...
:
sudden muscle weakness and
excessive daytime sleepiness
Excessive daytime sleepiness (EDS) is characterized by persistent sleepiness and often a general lack of energy, even during the day after apparently adequate or even prolonged nighttime sleep. EDS can be considered as a broad condition encompass ...
.
It is used sometimes in France and Italy as an
anesthetic
An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
given intravenously;
it is also used in Italy to treat alcohol addiction and alcohol withdrawal syndrome.
[Index page]
/ref>
Sodium oxybate is the sodium salt of γ-hydroxybutyric acid
''gamma''-Hydroxybutyric acid (or γ-hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid) is a naturally occurring neurotransmitter and a depressant drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. ...
(GHB). The clinical trials for narcolepsy were conducted just as abuse of GHB as a club drug
Club drugs, also called rave drugs or party drugs, are a loosely defined category of recreational drugs which are associated with discothèques in the 1970s and nightclubs, dance clubs, electronic dance music (EDM) parties, and raves in the 198 ...
and date rape drug
A date rape drug is any drug that incapacitates another person and renders that person vulnerable to sexual assault, including rape. The substances are associated with date rape because of reported incidents of their use in the context of two pe ...
became a matter of public concern; in 2000 GHB was made a Schedule I controlled substance, while sodium oxybate, when used under an FDA NDA
NDA may stand for:
Military
* National Defence Academy (India), a military academy in India
* National Defence Act, legislation for organizing and funding Canada's military
* National Defense Academy of Japan, a military academy in Japan
* Nig ...
or IND
Ind or IND may refer to:
General
* Independent (politician), a politician not affiliated to any political party
* Independent station, used within television program listings and the television industry for a station that is not affiliated with ...
application, was classified as a Schedule III controlled substance for medicinal use under the Controlled Substances Act
The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...
, with illicit use subject to Schedule I penalties.
Sodium oxybate was approved for use by the US Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) to treat symptoms of narcolepsy in 2002, with a strict risk evaluation and mitigation strategy Risk Evaluation and Mitigation Strategies (REMS) is a program of the US Food and Drug Administration for the monitoring of medications with a high potential for serious adverse effects. REMS applies only to specific prescription drugs, but can apply ...
(REMS) program mandated by the FDA. The US label for sodium oxybate also has a black box warning
In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because
the U.S. Food and Drug Administration specifies that it i ...
because it is a central nervous system depressant
A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the l ...
and may cause respiratory depression
Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia ...
, seizures, coma, or death, especially if used in combination with other central nervous system depressants, such as alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
and its use may cause dependence. In Canada
Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
and the European Union
The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...
it was classified as a Schedule III and a Schedule IV controlled substance, respectively.
It was approved for treating symptoms of narcolepsy in the European Union in 2005.[
Orphan Medical had developed it and was acquired by ]Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (a merger of Jazz Pharmaceuticals, Inc. and Azur Pharma plc) is a biopharmaceutical company based in Ireland. It was founded in 2003. One of the company's considerable products is the United States Food and Drug Adminis ...
in 2005. The drug is marketed in Europe by UCB. Jazz raised the price of the drug dramatically after it acquired Orphan, and paid a $20M fine for off-label marketing
Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although m ...
of the drug in 2007.
Medical use
Clinical use of sodium oxybate was introduced in Europe in 1964, as anesthetic
An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
given intravenously but it was not widely used since it sometimes caused seizures; as of 2006, it was still authorized for this use in France and Italy but not widely used.[
The major use of sodium oxybate is in treating two of the symptoms of ]narcolepsy
Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...
– cataplexy
Cataplexy is a sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically triggered by emotions such as laughing, crying, or terror. Cataplexy affects approximately 70% of people who have narcolepsy, and is ...
(sudden muscle weakness) and excessive daytime sleepiness
Excessive daytime sleepiness (EDS) is characterized by persistent sleepiness and often a general lack of energy, even during the day after apparently adequate or even prolonged nighttime sleep. EDS can be considered as a broad condition encompass ...
. Reviews of sodium oxybate concluded that it is well tolerated and associated with "significant reductions in cataplexy and daytime sleepiness," and that its effectiveness "in treating major, clinically relevant narcolepsy symptoms and sleep architecture abnormalities" has been established. However, because of the risks of abuse associated with this medication, it is available in the US only through a REMS program mandated by the FDA. The program requires that providers who prescribe it are certified to do so, that it is dispensed only 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.
In more recent times, investigations of its use in dealing with alcohol withdrawal syndrome
Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. M ...
have begun. These started in Italy, where its use in treating alcohol addiction was also explored; the evidence for these uses is weak[ but growing and it has also been approved for use in Austria.] There is insufficient evidence to make a definitive comparison with clomethiazole
Clomethiazole (also called chlormethiazole or Heminevrin) is a sedative and hypnotic originally developed by Hoffmann-La Roche in the 1930s. The drug is used in treating and preventing symptoms of acute alcohol withdrawal.
It is structurally r ...
or benzodiazepine
Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...
-based treatment approaches, though some data suggest it may be "better than naltrexone
Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found t ...
and disulfiram
Disulfiram is a medication used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by inhibiting the enzyme acetaldehyde dehydrogenase, causing many of the effects of ...
regarding abstinence maintenance and prevention of craving in the medium term i.e. 3-12 months." In a 2014 review, Gillian Keating described sodium oxybate as a "useful option for the treatment of alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence." However, a 2018 review recognised the evidence for its efficacy but noted safety concerns and concluded that "studies are still limited and investigations including a larger number of patients are needed."
Multiple trials have shown sodium oxybate to be effective in treating important symptoms of fibromyalgia such as pain and poor sleep structure however in 2010 the FDA voted unanimously against with commenters citing potential for abuse as a street drug. As of 2022 there remain few effective drugs approved to treat fibromyalgia.
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.[
]
Adverse effects
The US label for sodium oxybate has a black box warning
In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because
the U.S. Food and Drug Administration specifies that it i ...
because it is a central nervous system depressant
A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the l ...
(CNS depressant) and for its potential for abuse
Abuse is the improper usage or treatment of a thing, often to unfairly or improperly gain benefit. Abuse can come in many forms, such as: physical or verbal maltreatment, injury, assault, violation, rape, unjust practices, crimes, or other t ...
. Other potential adverse side effects include respiratory depression
Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia ...
, seizures, coma, and death, especially when it is taken in combination with other CNS depressants such as alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
. Cases of severe dependence and cravings have been reported with excessive and illicit use of this medication. GHB
''gamma''-Hydroxybutyric acid (or γ-hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid) is a naturally occurring neurotransmitter and a depressant drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. ...
, the protonated (acidic) form of this salt
Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantitie ...
, has been used to commit drug-facilitated sexual assault
Drug-facilitated sexual assault (DFSA) is a sexual assault (rape or otherwise) carried out on a person after the person has become intoxicated due to being under the influence of any mind-altering substances, such as having consumed alcohol or b ...
and date rape
Date rape is a form of acquaintance rape and dating violence. The two phrases are often used interchangeably, but date rape specifically refers to a rape in which there has been some sort of romantic or potentially sexual relationship between ...
, though the illicit form of GHB typically has different characteristics from pharmaceutical-grade sodium oxybate.
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 medical literature are generally from abuse, and often involve other drugs as well. Symptoms include vomiting, excessive sweating, periods of stopped breathing, seizures, agitation, loss of psychomotor skills, and coma. Overdose can lead to death due to respiratory depression. People who overdose may die from asphyxiation resulting from choking on vomit and/or aspiration. People that have overdosed or suspected of overdosing may need to be made to vomit, be intubated, or/and put on a ventilator.[
]
Interactions
It should not be used with other drugs that are CNS depressants like alcohol or sedatives. Use with divalproex
Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in thos ...
results in about a 25% increase in the availability of sodium oxybate.
Pharmacology
The mechanism of action
In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...
of sodium oxybate is unknown.[ ]GHB
''gamma''-Hydroxybutyric acid (or γ-hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid) is a naturally occurring neurotransmitter and a depressant drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. ...
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
Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantitie ...
of γ-hydroxybutyric acid
''gamma''-Hydroxybutyric acid (or γ-hydroxybutyric acid (GHB), also known as 4-hydroxybutanoic acid) is a naturally occurring neurotransmitter and a depressant drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. ...
(GHB). Its systematic chemical name is sodium 4-hydroxybutanoate, though synonyms like sodium γ-hydroxybutyrate are commonly used. Its condensed structural formula
The structural formula of a chemical compound is a graphic representation of the molecular structure (determined by structural chemistry methods), showing how the atoms are possibly arranged in the real three-dimensional space. The chemical bondi ...
is (molecular formula
In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, ...
: ) and its molar mass
In chemistry, the molar mass of a chemical compound is defined as the mass of a sample of that compound divided by the amount of substance which is the number of moles in that sample, measured in moles. The molar mass is a bulk, not molecular, p ...
is 126.09 g mol−1. It is highly hydrophilic. Treating the salt with acid allows the carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
form of the compound, which is GHB, to be recovered.
History
Alexander Zaytsev worked on this chemical family and published work on it in 1874. The first extended research into GHB and its use in humans was conducted in the early 1960s by Dr. Henri Laborit
Henri Laborit (21 November 1914 – 18 May 1995) was a French surgeon, neurobiologist, writer and philosopher. In 1952, Laborit was instrumental in the development of the drug chlorpromazine, published his findings, and convinced three psychiatri ...
to use in studying the neurotransmitter GABA.[ It was studied in a range of uses including obstetric surgery and during childbirth and as an anxiolytic; there were anecdotal reports of it having antidepressant and aphrodisiac effects as well.][ It was also studied as an intravenous ]anesthetic
An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
agent and was marketed for that purpose starting in 1964 in Europe but it was not widely adopted as it caused seizures; as of 2006 that use was still authorized in France and Italy but not widely used.[ GHB was also studied to treat alcohol addiction][ and for use in ]narcolepsy
Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...
from the 1960s onwards.[
In May 1990 GHB was introduced as a ]dietary supplement
A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
and was marketed to bodybuilders, for help with weight control and as a sleep aid, and as a "replacement" for L-tryptophan, which was removed from the market in November 1989 when batches of it were found to cause eosinophilia-myalgia syndrome. By November of that year 57 cases of illness caused by the GHB supplements had been reported to the Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...
, with people having taken up to three teaspoons of GHB; there were no deaths but nine people needed care in an intensive care unit
220px, Intensive care unit
An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensiv ...
. The FDA issued a warning in November 1990 that sale of GHB was illegal.[ GHB continued to be manufactured and sold illegally and it and analogs were adopted as a ]club drug
Club drugs, also called rave drugs or party drugs, are a loosely defined category of recreational drugs which are associated with discothèques in the 1970s and nightclubs, dance clubs, electronic dance music (EDM) parties, and raves in the 198 ...
and came to be used as a date rape drug
A date rape drug is any drug that incapacitates another person and renders that person vulnerable to sexual assault, including rape. The substances are associated with date rape because of reported incidents of their use in the context of two pe ...
. The DEA made seizures and the FDA reissued warnings several times throughout the 1990s.
At the same time, research on the use of GHB in the form of sodium oxybate had formalized, as a company called Orphan Medical Inc. had filed an Investigational New Drug application and was running clinical trials with the intention of gaining regulatory approval for use to treat narcolepsy.[ In 1996 Orphan contracted with ]Lonza Group
Lonza Group is a Swiss multinational manufacturing company for the pharmaceutical, biotechnology and nutrition sectors, headquartered in Basel, with major facilities in Europe, North America and South Asia. Lonza was established under that name in ...
, a contract manufacturer
A contract manufacturer (CM) is a manufacturer that contracts with a firm for components or products (in which case it is a turnkey supplier). It is a form of outsourcing. A contract manufacturer performing packaging operations is called copacker ...
for supply of the drug.
In 2000 the Hillory J. Farias and Samantha Reid Date-Rape Prevention Act of 2000 was signed into law in the US, which put GHB on Schedule I of the Controlled Substances Act
The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...
, but sodium oxybate, when used under an IND or NDA from the US FDA, was considered a Schedule III substance but with Schedule I trafficking penalties.
It was approved by the FDA in 2002 under the trade name Xyrem with a strict risk control strategy to prevent drug diversion
Drug diversion is a medical and legal concept involving the transfer of any legally prescribed controlled substance from the individual for whom it was prescribed to another person for any illicit use. The definition varies slightly among different ...
and control the risk of abuse by people to whom it was prescribed.
Orphan Medical licensed the right to market the drug in Europe to Celltech in 2003. In 2004 Celltech was acquired by UCB and in 2005 Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (a merger of Jazz Pharmaceuticals, Inc. and Azur Pharma plc) is a biopharmaceutical company based in Ireland. It was founded in 2003. One of the company's considerable products is the United States Food and Drug Adminis ...
acquired Orphan Medical.
In January 2007 Valeant announced that Jazz had licensed rights to market Xyrem in Canada to Valeant.
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
In common law, a writ of ''qui tam'' is a writ through which private individuals who assist a prosecution can receive for themselves all or part of the damages or financial penalties recovered by the government as a result of the prosecution. Its ...
case against the company under the False Claims Act
The False Claims Act (FCA), also called the "Lincoln Law", is an American federal law that imposes liability on persons and companies (typically federal contractors) who defraud governmental programs. It is the federal government's primary litigat ...
. Sales representatives were said to have made sales calls to doctors who did not treat people with narcolepsy and also told them about potential off label uses for the drug including fatigue, insomnia, chronic pain, weight loss, depression, bipolar disorders, and movement disorders like Parkinson's Disease. The disgruntled ex employee also accused sales representatives of downplaying (not denying) the risks described in the label's black box warning. An unassuming sales manager who had been suspected of being involved in the said illegal marketing scheme pleaded guilty, but was later acquitted under appeal. A well-known psychiatrist who believed in and promoted the benefits of Xyrem was arrested. After a five-year federal court battle fought by a public defender, the charges against the doctor were reduced to a single misdemeanor and a twenty-five dollar fine. Jazz paid $20M in total and agreed to a corporate integrity agreement A corporate integrity agreement (CIA) is a document outlining the obligations that a company involved in health care in the United States makes with a federal government agency or a state government as part of a civil settlement. On the federal lev ...
and to implement internal reforms.[
The FDA sent Jazz an ]FDA warning letter An FDA warning letter is an official message from the United States Food and Drug Administration (FDA) to a manufacturer or other organization that has violated some rule in a federally regulated activity.
The FDA defines an FDA warning letter as: ...
about safety violations in September 2007.
In 2010 the FDA rejected Jazz' New Drug Application for use of sodium oxybate in fibromyalgia
Fibromyalgia (FM) is a medical condition defined by the presence of chronic widespread pain, fatigue, waking unrefreshed, cognitive symptoms, lower abdominal pain or cramps, and depression. Other symptoms include insomnia and a general hyp ...
.
In October 2011, the FDA sent Jazz another FDA warning letter An FDA warning letter is an official message from the United States Food and Drug Administration (FDA) to a manufacturer or other organization that has violated some rule in a federally regulated activity.
The FDA defines an FDA warning letter as: ...
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 the 2011 letter appeared to be resolved.
In January 2017 the FDA approved the first generic sodium oxybate product for narcolepsy symptoms, which is also subject to the same REMS program conditions as the original. By April 2017 seven companies had filed Abbreviated New Drug Application
An Abbreviated New Drug Application (ANDA) is an application for a U.S. generic drug approval for an existing licensed medication or approved drug.
The ANDA is submitted to Food and Drug Administration, FDA's Center for Drug Evaluation and Resea ...
s (ANDAs) with the FDA to market generic versions of Xyrem and Jazz had filed patent infringement cases against them. Hikma Pharmaceuticals
Hikma Pharmaceuticals plc is a British multinational pharmaceutical company with headquarters in London, UK that manufactures non-branded generic and in-licensed pharmaceutical products. It was founded by Samih Darwazah in Amman, Jordan in 197 ...
had been the first company to file an ANDA and Jazz settled with them in April 2017; under the agreement Hikma could begin selling an authorized generic Authorized generics are prescription drugs produced by brand pharmaceutical companies and marketed under a private label, at generic prices. Authorized generics compete with generic products in that they are identical to their brand counterpart in b ...
in 2023 under Jazz' REMS, and would have five years of exclusivity, however, those conditions could change if Jazz' patents were invalidated.
In 2017, Jazz and Valeant terminated the agreement under which Valeant marketed Xyrem in Canada.
Society and culture
Regulation
In the US, GHB is a Schedule I controlled substance, while sodium oxybate, when used under an FDA NDA
NDA may stand for:
Military
* National Defence Academy (India), a military academy in India
* National Defence Act, legislation for organizing and funding Canada's military
* National Defense Academy of Japan, a military academy in Japan
* Nig ...
or IND
Ind or IND may refer to:
General
* Independent (politician), a politician not affiliated to any political party
* Independent station, used within television program listings and the television industry for a station that is not affiliated with ...
application, is classified as a Schedule III controlled substance for medicinal use under the Controlled Substances Act
The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...
, with illicit use subject to Schedule I penalties.[
In ]Canada
Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
and the European Union
The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...
(EU), as of 2009 it was classified as a Schedule III and a Schedule IV controlled substance, respectively.
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
Jazz Pharmaceuticals plc (a merger of Jazz Pharmaceuticals, Inc. and Azur Pharma plc) is a biopharmaceutical company based in Ireland. It was founded in 2003. One of the company's considerable products is the United States Food and Drug Adminis ...
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
An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases.
The assignment of ...
cost more than other drugs and have received special treatment since the enactment of the US Orphan Drug Act of 1983
The Orphan Drug Act of 1983 is a law passed in the United States to facilitate development of orphan drugs—drugs for rare diseases such as Huntington's disease, myoclonus, ALS, Tourette syndrome and muscular dystrophy which affect small numbers ...
. However, these steep price increases of orphan and other specialty drugs
Specialty drugs or specialty pharmaceuticals are a recent designation of pharmaceuticals that are classified as high-cost, high complexity and/or high touch. Specialty drugs are often biologics—"drugs derived from living cells" that are injectab ...
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
The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...
(EU) countries, the government either provides national health insurance (as in the UK and Italy
Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical re ...
) or strictly regulates quasi-private social insurance funds (as in Germany
Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...
, France
France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...
, and the Netherlands
)
, anthem = ( en, "William of Nassau")
, image_map =
, map_caption =
, subdivision_type = Sovereign state
, subdivision_name = Kingdom of the Netherlands
, established_title = Before independence
, established_date = Spanish Netherl ...
). 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
NHS England, officially the NHS Commissioning Board, is an executive non-departmental public body of the Department of Health and Social Care. It oversees the budget, planning, delivery and day-to-day operation of the commissioning side of the ...
authorises and pays for sodium oxybate by means of individual funding requests on the basis of exceptional circumstances. The British Department of Health
A health department or health ministry is a part of government which focuses on issues related to the general health of the citizenry. Subnational entities, such as states, counties and cities, often also operate a health department of their ow ...
pays for the medication for 80 patients who are taking legal action over problems linked to the use of the swine flu vaccine Pandemrix
Pandemrix is an influenza vaccine for influenza pandemics, such as the 2009 flu pandemic. The vaccine was developed by GlaxoSmithKline (GSK) and patented in September 2006.
The vaccine was one of the H1N1 vaccines approved for use by the Europea ...
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.
Names
Sodium oxybate is the common name for the chemical; it has no international nonproprietary name (INN).
As of April 2018 sodium oxybarate was sold under the following brands: Alcover (Italy), Gamma-OH (France), Natrii oxybutyras Kalceks (Latvia), Somsanit (Germany), Xyrem (many countries by Jazz and UCB).
Research
Sodium oxybate needs to be given during the night; as of 2017 research was ongoing to create formulations that would last through the night.
Jazz has been developing JZP-386, a deuterated
Isotopic labeling (or isotopic labelling) is a technique used to track the passage of an isotope (an atom with a detectable variation in neutron count) through a reaction, metabolic pathway, or cell. The reactant is 'labeled' by replacing specific ...
analog of sodium oxybate. The company presented Phase I results in 2015, stating that deuterium-related effects made it necessary to do further formulation work as part of the drug's development.
References
External links
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{{Portal bar , Medicine
Gamma-Hydroxybutyric acid
GHB receptor agonists
GABAB receptor agonists
Orphan drugs
Treatment of sleep disorders
Narcolepsy
Organic sodium salts
Histone deacetylase inhibitors