Butalbital: Difference between revisions

{{Short description|Barbiturate drug used for headaches}}

| verifiedrevid = 459987133

| IUPAC_name = 5-(2-Methylpropyl)-5-(2-propenyl)-2,4,6(1''H'',3''H'',5''H'')-pyrimidinetrione

| image = Butalbital structure.svg

| width = 150

| image2 = Butalbital ball-and-stick.png

| width2 = 180

| pregnancy_US = C

| legal_BR = B1

| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>

| legal_CA = Schedule IV

| legal_DE = Anlage II

| legal_UK = Class B

| legal_UN = P III

| routes_of_administration = [[Oral administration|By mouth]]

| metabolism = [[Liver]] mainly [[CYP3A4]]

| elimination_half-life = 35 hours <ref>{{cite web|url=https://www.drugs.com/pro/butalbital-and-acetaminophen.html|title=Butalbital and Acetaminophen - FDA prescribing information, side effects and uses|website=drugs.com|url-status=live|archive-url=https://web.archive.org/web/20180121184658/https://www.drugs.com/pro/butalbital-and-acetaminophen.html|archive-date=2018-01-21}}</ref>

| excretion = [[Kidney]]

| IUPHAR_ligand = 7138

| CAS_number_Ref = {{cascite|correct|??}}

| C=11 | H=16 | N=2 | O=3

'''Butalbital''' is a [[barbiturate]] with an intermediate duration of action. Butalbital is often combined with other medications, such as [[paracetamol|paracetamol (acetaminophen)]] (as [[Butalbital/acetaminophen]]) or aspirin, for the treatment of [[pain]] and [[headache]]. The various formulations combined with [[codeine]] are [[Food and Drug Administration|FDA]]-approved for the treatment of [[tension headache]]s. Butalbital has the same chemical formula as [[talbutal]] but a different structure—one that presents as 5-allyl-5-isobutylbarbituric acid.<ref>DE Patent 526854</ref>

==Preparations==

*[[Butalbital/acetaminophen]], Butalbital and [[acetaminophen]] ([[paracetamol]]), (trade names: Axocet, Bucet, Bupap, Cephadyn, Dolgic, Phrenilin, Forte, Sedapap)

*Butalbital, paracetamol (acetaminophen), and [[caffeine]] (trade names: [[Fioricet]], Esgic, Esgic-Plus, Orbivan, Fiormor, Fiortal, Fortabs, Laniroif)

*Butalbital, paracetamol (acetaminophen), caffeine, and [[codeine phosphate]] (trade name: Fioricet#3 with Codeine)

*Butalbital, aspirin, caffeine (trade name: Fiorinal)

*Butalbital, aspirin, caffeine, and codeine phosphate (trade name: Fiorinal#3 with Codeine)

*[[Ergotamine]] tartrate, caffeine, butalbital, [[Atropa belladonna|belladonna]] alkaloids (trade name: Cafergot-PB)

==Contraindications==

There are specific treatments which are appropriate for targeting [[migraine]]s and headaches.<ref name="AANfive">{{Citation |author1 = American Academy of Neurology |author1-link = American Academy of Neurology |date = February 2013 |title = Five Things Physicians and Patients Should Question |publisher = American Academy of Neurology |work = [[Choosing Wisely]]: an initiative of the [[ABIM Foundation]] |url = http://www.choosingwisely.org/doctor-patient-lists/american-academy-of-neurology/ |access-date = August 1, 2013 |url-status = live |archive-url = https://web.archive.org/web/20130901115555/http://www.choosingwisely.org/doctor-patient-lists/american-academy-of-neurology/ |archive-date = September 1, 2013 }}, which cites

* {{cite journal | vauthors = Silberstein SD | title = Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology | journal = Neurology | volume = 55 | issue = 6 | pages = 754–62 | date = September 2000 | pmid = 10993991 | doi = 10.1212/WNL.55.6.754 | doi-access = free }}

* {{cite journal | vauthors = Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A, Sándor PS | title = EFNS guideline on the drug treatment of migraine--revised report of an EFNS task force | journal = European Journal of Neurology | volume = 16 | issue = 9 | pages = 968–81 | date = September 2009 | pmid = 19708964 | doi = 10.1111/j.1468-1331.2009.02748.x | author8 = European Federation of Neurological Societies | s2cid = 9204782 | doi-access = free }}

*{{Citation |author=Institute for Clinical Systems Improvement |year=2011 |title=Headache, Diagnosis and Treatment of |publisher=Institute for Clinical Systems Improvement |url=https://www.icsi.org/guidelines__more/catalog_guidelines_and_more/catalog_guidelines/catalog_neurological_guidelines/headache/ |url-status=dead |archive-url=https://web.archive.org/web/20131029201313/https://www.icsi.org/guidelines__more/catalog_guidelines_and_more/catalog_guidelines/catalog_neurological_guidelines/headache/ |archive-date=2013-10-29 |access-date=2013-10-24 }}</ref> Butalbital is not recommended as a first-line treatment because it impairs alertness, brings risk of dependence and addiction, and increases the risk that episodic headaches will become chronic.<ref name="AHSfive">{{Citation |author1 = American Headache Society |author1-link = American Academy of Dermatology |date = September 2013 |title = Five Things Physicians and Patients Should Question |publisher = [[American Headache Society]] |work = [[Choosing Wisely]]: an initiative of the [[ABIM Foundation]] |url = http://www.choosingwisely.org/doctor-patient-lists/american-headache-society/ |access-date = 10 December 2013 |url-status = dead |archive-url = https://web.archive.org/web/20131203001051/http://www.choosingwisely.org/doctor-patient-lists/american-headache-society/ |archive-date = 3 December 2013 }}, which cites

* {{cite journal | vauthors = Bigal ME, Lipton RB | title = Excessive opioid use and the development of chronic migraine | journal = Pain | volume = 142 | issue = 3 | pages = 179–82 | date = April 2009 | pmid = 19232469 | doi = 10.1016/j.pain.2009.01.013 | s2cid = 27949021 }}

* {{cite journal | vauthors = Bigal ME, Serrano D, Buse D, Scher A, Stewart WF, Lipton RB | title = Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study | journal = Headache | volume = 48 | issue = 8 | pages = 1157–68 | date = September 2008 | pmid = 18808500 | doi = 10.1111/j.1526-4610.2008.01217.x | s2cid = 17358333 | doi-access = free }}

* {{cite journal | vauthors = Scher AI, Stewart WF, Ricci JA, Lipton RB | title = Factors associated with the onset and remission of chronic daily headache in a population-based study | journal = Pain | volume = 106 | issue = 1–2 | pages = 81–9 | date = November 2003 | pmid = 14581114 | doi = 10.1016/S0304-3959(03)00293-8 | s2cid = 29000302 | url = https://zenodo.org/record/1260009 }}

* {{cite journal | vauthors = Katsarava Z, Schneeweiss S, Kurth T, Kroener U, Fritsche G, Eikermann A, Diener HC, Limmroth V | display-authors = 6 | title = Incidence and predictors for chronicity of headache in patients with episodic migraine | journal = Neurology | volume = 62 | issue = 5 | pages = 788–90 | date = March 2004 | pmid = 15007133 | doi = 10.1212/01.WNL.0000113747.18760.D2 | s2cid = 20759425 }}</ref> When other treatments are unavailable or ineffective, butalbital may be appropriate if the patient can be monitored to prevent the development of chronic headache.<ref name="AHSfive"/>

Side effects for any psychoactive drug are difficult to predict, though butalbital is usually well tolerated. Commonly reported side effects for butalbital, some of which tend to subside with continued use, include:

*[[Hypoventilation|Respiratory depression]] (impaired breathing)

Rare side-effects include [[Stevens–Johnson syndrome]], an adverse reaction to barbiturates, and [[anaphylaxis]].

The risk and severity of all side effects is greatly increased when butalbital (or butalbital-containing medications) are combined with other sedatives (ex. [[ethanol]], [[opiates]], [[benzodiazepines]], [[antihistamines]]). In particular, butalbital, especially when combined with other sedatives (e.g. opioids), can cause life-threatening respiratory depression and death. Inhibitors of the hepatic enzyme CYP3A4 may also increase the risk, severity, and duration of side effects, many drugs inhibit this enzyme as do some foods such as [[grapefruit]] and the [[blood orange]]. Taking butalbital-based medications with some other drugs may also increase the side effects of the other medication.

==Dangers and risks==

Butalbital can cause [[substance dependence|dependence]] or [[addiction]]. Mixing with [[alcohol (drug)|alcohol]], benzodiazepines, and other CNS-depressants increases the risk of intoxication, increases respiratory depression, and increases liver toxicity when in combination with paracetamol (acetaminophen). Use of butalbital and alcohol, benzodiazepines, and other CNS-depressants can contribute to coma, and in extreme cases, fatality.

== References ==

{{reflist}}

== External links ==

* [https://cancerweb.ncl.ac.uk/cgi-bin/omd?query=butalbital&action=Search+OMD Butalbital] {{Webarchive|url=https://web.archive.org/web/20081014233125/http://cancerweb.ncl.ac.uk/cgi-bin/omd?query=butalbital&action=Search+OMD |date=2008-10-14 }}, Online Medical Dictionary

* [https://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202102.html Butalbital and Acetaminophen (Systemic)] ([https://web.archive.org/web/20061230122834/http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202102.html archive]), MedicinePlus Drug Information

* [https://www.deadiversion.usdoj.gov/schedules/listby_sched/sched3.htm Controlled Substances in Schedule III], ([https://web.archive.org/web/20070202220447/http://www.deadiversion.usdoj.gov/schedules/listby_sched/sched3.htm archive]), U.S. Drug Enforcement Administration

{{GABAAR PAMs}}

[[Category:Allyl compounds]]

[[Category:CYP3A4 inducers]]

[[Category:Isobutyl compounds]]