'''Phenobarbital''' ([[International Nonproprietary Name|INN]]) or '''phenobarbitone''' (former [[British Approved Name|BAN]]) is a [[barbiturate]], first marketed as '''[[Luminal]]''' by [[Bayer|Farbwerke Fr. Bayer and Co]]. It is the most widely used [[anticonvulsant]] worldwide and the oldest still in use. It also has [[sedative]] and [[hypnotic]] properties but, as with other barbiturates, has been superseded by the [[benzodiazepine]]s for these indications. The [[World Health Organization]] recommends its use as first-line for partial and generalized tonic–clonic [[seizure]]s in [[developing country|developing countries]]. It is a ''core'' medicine in the [[WHO Model List of Essential Medicines]], which is a list of minimum medical needs for a basic health care system.<ref name="essentialWHO">{{cite web
}}</ref> In more affluent countries, it is no longer recommended as a first or second-line choice anticonvulsant for most seizure types,<ref name="NICEguidelines2004">{{cite web
though it is still commonly used to treat [[neonatal]] seizures.<ref name="BNFc4.8.1">{{cite book
* Dosing Information
| title =[[British National Formulary for Children]]
| chapter = 4.8.1 Control of epilepsy
:* Dosage
| pages = 255-6
| author = [[British Medical Association]], [[Royal Pharmaceutical Society of Great Britain]], [[Royal College of Paediatrics and Child Health]] and Neonatal and Paediatric Pharmacists Group
=====Condition2=====
| date = 2006
| id = ISBN 0-85369-676-4
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
}}</ref>
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
<!--Off-Label Use and Dosage (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport======Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Contraindications-->
|contraindications=* Condition1
<!--Warnings-->
|warnings=* Description
====Precautions====
* Description
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Drug Interactions-->
|drugInteractions=* Drug
:* Description
<!--Use in Specific Populations-->
|useInPregnancyFDA=* '''Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
|useInHepaticImpair=There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
<!--Administration and Monitoring-->
|administration=* Oral
* Intravenous
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
* Description
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
==History==
<!--Overdosage-->
The first barbiturate drug, [[barbital]], was synthesized in 1902 by German chemists [[Emil Fischer]] and [[Joseph von Mering]] at Bayer. By 1904 several related drugs, including phenobarbital, had been synthesized by Fischer. Phenobarbital was brought to market in 1912 by the drug company Bayer using the brand Luminal. It remained a commonly prescribed sedative and hypnotic until the introduction of benzodiazepines in the 1950s.<ref name="Sneader2005">{{cite book
|overdose====Acute Overdose===
| last = Sneader
| first = Walter
| title = Drug Discovery
| accessdate = 2006-09-06
| date = 2005-06-23
| publisher = John Wiley and Sons
| id = ISBN 0-471-89979-8
| pages = 369
}}</ref>
Phenobarbital's soporific, sedative and hypnotic properties were well known in 1912, but nobody knew it was also an effective anticonvulsant. The young doctor [[Alfred Hauptmann]] gave it to his epilepsy patients as a tranquiliser and discovered that their epileptic attacks were susceptible to the drug. Hauptmann performed a careful study of his patients over an extended period. Most of these patients were using the only effective drug then available, [[potassium bromide|bromide]], which had terrible side effects and limited efficacy. On phenobarbital, their epilepsy was much improved: the worse patients suffered fewer and lighter seizures and some patients became seizure free. In addition, they improved physically and mentally as bromides were removed from their regime. Patients who had been institutionalised due to the severity of their epilepsy were able to leave and, in some cases, resume employment. Hauptman dismissed concerns that its effectiveness in stalling epileptic attacks could lead to patients suffering a build-up that needed to be "discharged". As he expected, withdrawal of the drug lead to an increase in seizure frequency – it was not a cure. The drug was quickly adopted as the first widely effective anticonvulsant, though [[World War I]] delayed its introduction in the U.S.<ref name="Scott1993">{{cite book
====Signs and Symptoms====
| last = Scott,
| first = Donald F
| title = The History of Epileptic Therapy
| accessdate = 2006-09-06
| date = [[1993-02-15]]
| publisher = Taylor & Francis
| id = ISBN 1-85070-391-4
| pages = 59-65
}}</ref>
Phenobarbital was used to treat [[neonatal jaundice]] by increasing liver metabolism and thus lowering [[bilirubin]] levels. In the 1950s, [[phototherapy]] was discovered, and became the standard treatment.<ref name="Pepling2005">{{cite journal
In 1940, Winthrop Chemical produced [[sulfathiazole]] tablets that were contaminated with phenobarbital. This occurred because both tablets were produced side-by-side and equipment could be interchanged. Each antibacterial tablet contained more than twice the required dose of phenobarbital necessary to induce sleep. Hundreds of patients died or were injured as a result. A U.S. [[Food and Drug Administration]] investigation was highly critical of Winthrop and the scandal lead to the introduction of [[Good Manufacturing Practice]] for drugs.<ref name="Pepling2005"/>
====Management====
The drug itself through predated FDA approval processes and has failed to be formally cleared for use in subsequent years. Guidance was issued in June 2006 of plans to enforce US approval for unapproved drugs.<ref>{{cite web| author=Michelle Meadows |title=The FDA Takes Action Against Unapproved Drugs |url=http://www.fda.gov/fdac/features/2007/107_drug.html |date=January-February 2007 |publisher=FDA Consumer magazine |accessdate=2007-09-27}}</ref>
* Description
Phenobarbital was used for over 25 years as [[prophylaxis]] in the treatment of [[febrile seizure]]s.<ref name="Scott1993Febrile">{{cite book
===Chronic Overdose===
| author = John M. Pellock, W. Edwin Dodson, Blaise F. D. Bourgeois
| title = Pediatric Epilepsy
| accessdate = 2006-09-06
| date = [[2001-01-01]]
| publisher = Demos Medical Publishing
| id = ISBN 1-888799-30-7
| pages = 169
}}</ref> Although an effective treatment in preventing recurrent febrile seizures, it had no positive effect on patient outcome or risk of developing epilepsy. The treatment of simple febrile seizures with anticonvulsant prophylaxis is no longer recommended.<ref name="Baumann2005">{{cite web
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
Phenobarbital is indicated in the treatment of all types of seizures except [[absence seizure]]s.<ref name="NICEguidelines2004"/><ref name="BNF51">[[British National Formulary]] 51</ref> Phenobarbital is no less effective at seizure control than more modern drugs such as [[phenytoin]] and [[carbamazepine]]. It is, however, significantly less well tolerated.<ref name="Taylor">{{cite journal
| author = Taylor S, Tudur Smith C, Williamson PR, Marson AG
| title = Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalized onset tonic-clonic seizures.
The first line drugs for treatment of [[status epilepticus]] are fast acting benzodiazepines such as [[diazepam]] or [[lorazepam]]. If these fail then [[phenytoin]] may be used, with phenobarbital being an alternative in the U.S. but used only third line in the UK.<ref name="BNFc4.8.2">{{cite book
<!--Pharmacology-->
| title =[[British National Formulary for Children]]
| chapter = 4.8.2 Drugs used in status epilepticus
| pages = 269
| author = [[British Medical Association]], [[Royal Pharmaceutical Society of Great Britain]], [[Royal College of Paediatrics and Child Health]] and Neonatal and Paediatric Pharmacists Group
| date = 2006
| id = ISBN 0-85369-676-4
}}</ref>
Failing that, the only treatment is [[anaesthesia]] in [[intensive care]].<ref name="BNF51"/><ref name="Kalvaiainen2005">{{cite journal
| author = Kälviäinen R, Eriksson K, Parviainen I
| title = Refractory generalised convulsive status epilepticus : a guide to treatment.
| journal = CNS Drugs
| volume = 19
| issue = 9
| pages = 759-68
| year = 2005
| id = PMID 16142991
}}</ref>
Phenobarbital is the first line choice for the treatment of [[neonatal]] seizures.<ref name="BNFc4.8.1"/><ref name="Scott1993Neonatal">{{cite book
<!--Drug box 2-->
| author = John M. Pellock, W. Edwin Dodson, Blaise F. D. Bourgeois
}}</ref> Concerns that neonatal seizures in themselves could be harmful make most physicians treat them aggressively. There is, however, no reliable evidence to support this approach.<ref name="Booth2004">{{cite journal
| author = Booth D, Evans DJ
| title = Anticonvulsants for neonates with seizures
| journal = Cochrane Database of Systematic Reviews
Sedation and hypnosis are the principal side effects of phenobarbital. [[Central nervous system]] effects like dizziness, [[nystagmus]] and [[ataxia]] are also common. In elderly patients, it may cause excitement and confusion while in children, it may result in paradoxical hyperactivity.
|structure=*
==Contraindications==
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
[[Acute intermittent porphyria]], oversensitivity for barbiturates, prior dependence on barbiturates, severe respiratory insufficiency and hyperkinesia in children.
==Overdose==
<!--Pharmacodynamics-->
{{Infobox_Disease |
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
Name = Poisoning by barbiturates |
ICD10 = {{ICD10|T|42|3|t|36}} |
eMedicineSubj = med |
eMedicineTopic = 207 |
}}
Phenobarbital causes a "depression" of the body's systems, mainly the [[central nervous system|central]] and [[peripheral nervous system]]s; thus, the main characteristic of phenobarbital overdose is a "slowing" of bodily functions, including decreased [[consciousness]] (even [[coma]]), [[bradycardia]], [[bradypnea]], [[hypothermia]], and [[hypotension]] (in massive overdoses). Overdose may also lead to [[pulmonary edema]] and [[acute renal failure]] as a result of [[Shock (medical)|shock]].
The [[electroencephalogram]] of a person with phenobarbital overdose may show a marked decrease in electrical activity, to the point of mimicking [[brain death]]. This is due to profound depression of the central nervous system, and is usually reversible.<ref name="Habal">{{cite web
<!--Pharmacokinetics-->
| url = http://www.emedicine.com/MED/topic207.htm
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
| title = Barbiturate Toxicity
| accessdate = 2006-09-14
| author = Rania Habal
| date = [[2006-01-27]]
| work = eMedicine
| publisher = WebMD
}}</ref>
Treatment of phenobarbital overdose is supportive, and consists mainly in the maintenance of [[airway]] patency (through [[endotracheal intubation]] and [[mechanical ventilation]]), correction of bradycardia and hypotension (with [[intravenous therapy|intravenous fluid]]s and [[vasopressor]]s, if necessary) and removal of as much drug as possible from the body. Depending on how much time has elapsed since ingestion of the drug, this may be accomplished through [[gastric lavage]] (stomach pumping) or use of [[activated charcoal]]. [[Hemodialysis]] is effective in removing phenobarbital from the body, and may reduce its half-life by up to 90%.<ref name="Habal"/> There is no specific antidote for barbiturate poisoning.
<!--Nonclinical Toxicology-->
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
==Pharmacokinetics==
<!--Clinical Studies-->
Phenobarbital has an oral [[bioavailability]] of approximately 90%. Peak plasma concentrations are reached 8 to 12 hours after oral administration. It is one of the longest-acting barbiturates available – it remains in the body for a very long time (half-life of 2 to 7 days) and has very low [[Plasma protein binding|protein binding]] (20 to 45%). Phenobarbital is metabolized by the liver, mainly through [[hydroxylation]] and [[glucuronidation]], and induces most [[isozyme]]s of the [[cytochrome P450 oxidase|cytochrome P450 system]]. Cytochrome P450 2B6 System is more specifically induced by Phenobarbital. It is excreted primarily by the [[kidney]]s.
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
==Veterinary uses==
<!--How Supplied-->
Phenobarbital is one of the initial drugs of choice to treat [[epilepsy]] in [[dog]]s, and is the initial drug of choice to treat epilepsy in cats.<ref name = Dewey>
|howSupplied=*
{{cite book
| author = Thomas, WB
| title = Seizures and narcolepsy. ''In: Dewey, Curtis W. (ed.)'' A Practical Guide to Canine and Feline Neurology | publisher = Iowa State Press
| location = Ames, Iowa
| year = 2003
| id = ISBN 0-8138-1249-6}}</ref>
It may also be used to treat seizures in [[horse]]s when [[benzodiazepine]] treatment has failed or is contraindicated.<ref name = MVM>
<!--Patient Counseling Information-->
{{cite book
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
|editor= Kahn, Cynthia M., Line, Scott, Aiello, Susan E. (ed.)
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Black Box Warning
ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Overview
Phenobarbital (injection) is a {{{drugClass}}} that is FDA approved for the {{{indicationType}}} of {{{indication}}}. There is a Black Box Warning for this drug as shown here. Common adverse reactions include .
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Condition1
Dosing Information
Dosage
Condition2
Dosing Information
Dosage
Condition3
Dosing Information
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Condition4
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Off-Label Use and Dosage (Adult)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Phenobarbital (injection) in adult patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Phenobarbital (injection) in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding FDA-Labeled Use of Phenobarbital (injection) in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
Condition1
Developed by:
Class of Recommendation:
Strength of Evidence:
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Guideline-Supported Use of Phenobarbital (injection) in pediatric patients.
Non–Guideline-Supported Use
Condition1
Dosing Information
Dosage
Condition2
There is limited information regarding Off-Label Non–Guideline-Supported Use of Phenobarbital (injection) in pediatric patients.
Contraindications
Condition1
Warnings
ConditionName:
See full prescribing information for complete Boxed Warning.
ConditionName:
Content
Description
Precautions
Description
Adverse Reactions
Clinical Trials Experience
There is limited information regarding Clinical Trial Experience of Phenobarbital (injection) in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Phenobarbital (injection) in the drug label.
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