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{{Drugbox|
{{DrugProjectFormSinglePage
|IUPAC_name = [2-(carbamoyloxymethyl)-2-methyl-pentyl] carbamate
|authorTag={{KS}}
| image=Meprobamate.svg
|genericName=meprobamate
| image2 = Meprobamate3d.png
|aOrAn=an
| width = 250
|drugClass=anti anxiety drug
| CAS_number=57-53-4
|indicationType=treatment
| ATC_prefix=N05
|indication=[[anxiety disorders]]
| ATC_suffix=BC01
|adverseReactions=[[nausea]],  [[vomiting]],  [[diarrhea]]. [[drowsiness]], [[ataxia]], [[dizziness]], [[slurred speech]], [[headache]], [[vertigo]], [[weakness]], [[paresthesias]]
| PubChem=4064
|blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
| DrugBank=APRD01095
|blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
| C = 9 | H = 18 | N = 2 | O = 4
 
| molecular_weight = 218.250 g/mol
* Content
| bioavailability= ?
 
<!--Adult Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Adult)-->
|fdaLIADAdult===Indications==
 
* Meprobamate tablets are indicated for the management of [[anxiety disorders]] or for the short-term relief of the symptoms of [[anxiety]]. [[Anxiety]] or tension associated with the stress of everyday life usually do not require treatment with an anxiolytic.
 
* The effectiveness of meprobamate tablets in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.
 
==Dosage==
 
* Meprobamate Tablets USP: The usual adult daily dosage is 1200mg to 1600 mg, in three or four divided doses; a daily dosage above 2400 mg is not recommended.
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
|fdaLIADPed===Indications==
 
* Meprobamate tablets are indicated for the management of [[anxiety disorders]] or for the short-term relief of the symptoms of [[anxiety]]. [[Anxiety]] or tension associated with the stress of everyday life usually do not require treatment with an anxiolytic.
 
* The effectiveness of meprobamate tablets in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.
 
==Dosing==
* The usual daily dosage for children ages six to twelve years is 200 mg to 600 mg, in two or three divided doses.
 
* Not recommended for children under age 6 (see Usage in Children).
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
|contraindications=* [[Acute intermittent porphyria]] as well as allergic or idiosyncratic reactions to meprobamate or related compounds such as carisoprodol, mebutamate, tybamate, or carbromal.
|warnings='''Drug Dependence'''
 
* Physical dependence, psychological dependence, and abuse have occurred. When chronic intoxication from prolonged use occurs, it usually involves ingestion of greater than recommended doses and is manifested by [[ataxia]], slurred speech, and [[vertigo]].
 
* Therefore, careful supervision of dose and amounts prescribed is advised, as well as avoidance of prolonged administration, especially for alcoholics and other patients with a known propensity for taking excessive quantities of drugs.
 
* Sudden withdrawal of the drug after prolonged and excessive use may precipitate recurrence of pre-existing symptoms such as [[anxiety]], [[anorexia]], insomnia, or withdrawal reactions such as [[vomiting]], [[ataxia]], tremors, muscle twitching, confusional states, hallucinosis, and rarely, convulsive [[seizures]]. Such [[seizures]] are more likely to occur in persons with central nervous system damage or pre-existent or latent convulsive disorders. Onset of withdrawal symptoms occurs usually within 12 to 48 hours after discontinuation of meprobamate; symptoms usually cease within the next 12 to 48 hours.
 
* When excessive dosage has continued for weeks or months, dosage should be reduced gradually over a period of one or two weeks rather than abruptly stopped. Alternatively, a long-acting barbiturate may be substituted, then gradually withdrawn.
 
'''Potentially Hazardous Tasks'''
 
* Patients should be warned that meprobamate may impair the mental and/or physical abilities required for performance of potentially hazardous tasks such as driving or operating machinery.
 
'''Additive Effects'''
 
* Since the effects of meprobamate and alcohol or meprobamate and other CNS depressants or psychotropic drugs may be additive, appropriate caution should be exercised with patients who take more than one of these agents simultaneously.
 
'''Usage in Pregnancy and Lactation'''
 
* An increased risk of congenital malformations associated with the use of minor tranquilizers (meprobamate, chlordiazepoxide and diazepam) during the first trimester of pregnancy has been suggested in several studies. Because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physician about the desirability of discontinuing the drug.
 
* Meprobamate passes the placental barrier. It is present both in umbilical cord blood at or near maternal plasma levels and in breast milk of lactating mothers at concentrations two to four times that of maternal plasma. When use of meprobamate is contemplated in breastfeeding patients, the drug's higher concentration in breast milk as compared to maternal plasma should be considered.
 
'''Usage in Children'''
 
* Meprobamate tablets should not be administered to children under age six, since there is a lack of documented evidence for safety and effectiveness in this age group.
 
==PRECAUTIONS==
 
* The lowest effective dose should be administered, particularly to elderly and/or debilitated patients, in order to preclude oversedation.
 
* The possibility of suicide attempts should be considered and the least amount of drug feasible should be dispensed at any one time.
 
* Meprobamate is metabolized in the liver and excreted by the kidney; to avoid its excess accumulation, caution should be exercised in administration to patients with compromised liver or kidney function.
 
* Meprobamate occasionally may precipitate [[seizures]] in epileptic patients.
|clinicalTrials='''Central Nervous System'''
 
* [[Drowsiness]],  [[ataxia]], [[dizziness]], slurred speech, [[headache]], [[vertigo]], weakness, [[paresthesias]], impairment of visual accommodation, euphoria, overstimulation, paradoxical excitement, fast EEG activity.
 
'''Gastrointestinal'''
 
* [[Nausea]], [[vomiting]], [[diarrhea]].
 
'''Cardiovascular'''
 
* [[Palpitation]], [[tachycardia]], various forms of [[arrhythmia]], transient ECG changes, [[syncope]]; also [[hypotensive]] crisis (including one fatal case).
 
'''Allergic or Idiosyncratic'''
 
* Allergic or idiosyncratic reactions are usually seen within the period of the first to fourth dose in patients having had no previous contact with the drug. Milder reactions are characterized by an [[itchy]], [[urticarial]], or erythematous maculopapular rash which may be generalized or confined to the groin. Other reactions have included [[leukopenia]], acute [[nonthrombocytopenic purpura]], [[petechiae]], [[ecchymoses]], eosinophilia, [[peripheral edema]], adenopathy, fever, fixed drug eruption with cross reaction to carisoprodol, and cross sensitivity between meprobamate/mebutamate and meprobamate/carbromal.
 
* More severe hypersensitivity reactions, rarely reported, include hyperpyrexia [[chills]], [[angioneurotic edema]], [[bronchospasm]], [[oliguria]] and [[anuria]]. Also, [[anaphylaxis]], [[erythema multiforme]], [[exfoliative dermatitis]], [[stomatitis]], [[proctitis]], [[Stevens-Johnson syndrome]] and [[bullous dermatitis]], including one fatal case of the latter following administration of meprobamate in combination with prednisolone.
 
* In case of allergic or idiosyncratic reactions to meprobamate, discontinue the drug and initiate appropriate symptomatic therapy, which may include epinephrine,antihistamines, and in severe cases, corticosteroids. In evaluating possible allergic reactions, also consider allergy to excipients.
 
'''Hematologic'''
 
* [[Agranulocytosis]] and  [[aplastic anemia]] have been reported. These cases rarely were fatal. Rare cases of [[thrombocytopenic Purpura]] have been reported.
'''Other'''
 
* Exacerbation of porphyric symptoms.
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
|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=* Clinical studies of meprobamate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
|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=* Oral
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
 
 
 
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
|overdose=* Suicidal attempts with meprobamate have resulted in drowsiness, lethargy, stupor, ataxia, coma, shock, vasomotor, and respiratory collapse. Some suicidal attempts have been fatal.
 
* The following data on meprobamate tablets have been reported in the literature and from other sources. These data are not expected to correlate with each case (considering factors such as individual susceptibility and length of time from ingestion to treatment), but represent the usual ranges reported.
 
'''Acute simple overdose'''  (meprobamate alone): Death has been reported with ingestion of as little as 12 g meprobamate and survival with as much as 40 g.
 
'''Blood Levels'''
 
* 0.5-2 mg% represents the usual blood level range of meprobamate after therapeutic doses. The level may occasionally be as high as 3 mg%.
 
* 3-10 mg% usually corresponds to findings of mild to moderate symptoms of overdosage, such as stupor or light coma.
 
* 10-20 mg% usually corresponds to deeper coma, requiring more intensive treatment. Some fatalities occur.
 
* At levels greater than 20 mg%, more fatalities than survivals can be expected.
 
'''Acute combined overdose''' (meprobamate with alcohol or other CNS depressants or psychotropic drugs): Since effects can be additive, a history of ingestion of a low dose of meprobamate plus any of these compounds (or of a relative low blood or tissue level) cannot be used as a prognostic indicator.
 
* In cases where excessive doses have been taken, sleep ensues rapidly and blood pressure, pulse, and respiratory rates are reduced to basal levels. Any drug remaining in the stomach should be removed and symptomatic therapy given. Should respiration or blood pressure become compromised, respiratory assistance, central nervous system stimulants, and pressor agents should be administered cautiously as indicated. Meprobamate is metabolized in the liver and excreted by the kidney. Diuresis, osmotic (mannitol) diuresis, peritoneal dialysis, and hemodialysis have been used successfully. Careful monitoring of urinary output is necessary and caution should be taken to avoid overhydration. Relapse and death, after initial recovery, have been attributed to incomplete gastric emptying and delayed absorption. Meprobamate can be measured in biological fluids by two methods: colorimetric (Hoffman, A.J. and Ludwig, B.J.: J Amer Pharm Assn 48: 740, 1959) and gas chromatographic (Douglas, J.F. et al: Anal Chem 39: 956, 1967).
|drugBox={{Drugbox2
| Watchedfields = changed
| verifiedrevid = 459508597
| IUPAC_name = [2-(carbamoyloxymethyl)-2-methyl-pentyl] carbamate
| image = Meprobamate2DCSD.png
| width = 230px
| image2 = Meprobamate3DanJ.gif
| width2 = 300px
 
<!--Clinical data-->
| tradename = Miltown
| Drugs.com = {{drugs.com|monograph|meprobamate}}
| MedlinePlus = a682077
| pregnancy_AU = C
| pregnancy_US = D
| legal_AU = S4
| legal_US = Schedule IV
| legal_Ca = Schedule IV
| routes_of_administration = Oral
 
<!--Pharmacokinetic data-->
| bioavailability = ?
| metabolism = [[Liver|Hepatic]]
| metabolism = [[Liver|Hepatic]]
| elimination_half-life= 10 hours
| elimination_half-life = 10 hours
| excretion = [[Kidney|Renal]]
| excretion = [[Kidney|Renal]]
| pregnancy_US = D
| legal_US = Schedule IV
| routes_of_administration= Oral
}}
'''Meprobamate''' (marketed under the brand names '''Miltown'''® by Wallace Laboratories, '''Equanil'''® by Wyeth, and '''Meprospan®''') is a [[carbamate]] derivative which is used as an [[anxiolytic]] drug. It was the best-selling minor tranquilizer for a time, but has largely been replaced by the [[benzodiazepine]]s.


==History==
<!--Identifiers-->
Meprobamate was first synthesized by Bernie Ludwig at Carter Products in May 1950. Wallace Laboratories bought the license and named it Miltown after the village [[Milltown, New Jersey|Milltown]] in [[New Jersey]]. Launched in 1955, it rapidly became a best seller and famous in the popular media as "Happy Pills".{{Fact|date=September 2007}}
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 57-53-4
| ATC_prefix = N05
| ATC_suffix = BC01
| PubChem = 4064
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00371
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3924
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9I7LNY769Q
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00376
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 979


A December [[1955]] study of 101 patients at the Mississippi State Hospital in Whitfield, Mississippi, found Meprobamate useful in the alleviation of ''mental symptoms''. 3% of the patients made a complete recovery, 29% were greatly improved, and 50% were somewhat better. 18%  realized little change. Self-destructive patients became cooperative and calmer, and experienced a resumption of logical thinking. In 50%
<!--Chemical data-->
of the cases relaxation brought about more favorable sleep habits. [[Hydrotherapy]] and all types of [[shock treatment]] were halted.<ref>''New Hope Arises On Cancer Serum'', New York Times, December 28, 1955, Page 21.</ref> Meprobamate was found to help in the treatment of alcoholics by [[1956]].<ref>''Alcohol Peril Found In Drugs'', [[New York Times]], April 1, 1956, Page 28.</ref>
| C=9 | H=18 | N=2 | O=4
Dr. Frank Berger, clinical director of Wallace Laboratories, described it as a relaxer of the [[central nervous system]], whereas other
| molecular_weight = 218.250 g/mol
[[tranquilizers]] suppressed it. A [[University of Michigan]] study found that Meprobamate affected driving skills. Patients reported being able to relax more even though they continued to feel tense. The disclosures came at a special scientific meeting at the Barbizon Plaza Hotel in [[New York City]]. [[Aldous Huxley]] addressed an evening session. He predicted the development of many
| smiles = O=C(OCC(COC(=O)N)(C)CCC)N
chemicals ''capable of changing the quality of human consciousness'', in the next few years.<ref>''Behavior Drugs Now Envisioned'', New York Times,
| InChI = 1/C9H18N2O4/c1-3-4-9(2,5-14-7(10)12)6-15-8(11)13/h3-6H2,1-2H3,(H2,10,12)(H2,11,13)
October 19, 1956, Page 29.</ref>
| InChIKey = NPPQSCRMBWNHMW-UHFFFAOYAM
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C9H18N2O4/c1-3-4-9(2,5-14-7(10)12)6-15-8(11)13/h3-6H2,1-2H3,(H2,10,12)(H2,11,13)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = NPPQSCRMBWNHMW-UHFFFAOYSA-N
| density = 1.229
| melting_point = 105
| melting_high = 106
| boiling_point = 200
| boiling_notes = to  210 °C (410 °F)
}}
|structure=Meprobamate is a white powder with a characteristic odor and a bitter taste. It is slightly soluble in water, freely soluble in acetone and alcohol, and sparingly soluble in ether. The structural formula of meprobamate is:


Miltown was sometimes referred to incorrectly as [[Chlorpromazine]]. One such instance of this was a review by author [[Frank Slaughter]] of the book, ''A Man Against Insanity'', by [[Paul de Kruif]].<ref>''Letters To The Editor: Drugs'', New York Times, April 7, 1957, Page 263.</ref>
[[File:Meprobamate structure.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
In January [[1960]] Carter Products, Inc., makers of Miltown and American Home Products Corporation, which marketed Equinal, were charged with having conspired to monopolize the market in mild tranquilizers. It was revealed that in [[1948]] the sale of Meprobamate earned $40,000,000 for the defendants. Of this amount American Home Products accounted for approximately 2/3 and Carter about 1/3. The U.S. Government sought an
order mandating that Carter make its Meprobamate patent available at no charge to any company desiring to use it.<ref>''Trust Suit Names 2 Drug Concerns'', New York Times, January 28, 1960, Page 1.</ref>


In April [[1965]] Meprobamate was removed from the list of tranquilizers when experts ruled that the drug was a [[sedative]] instead. U.S. Pharmacopoeia published the ruling. At the same time the [[Medical Letter]] disclosed that Meprobamate could be addictive ''at dosage levels not much above recommended.''<ref>''Miltown Off List Of Tranquilizers'', New York Times, April 22, 1965, Page 34.</ref> In December [[1967]] Meprobamate was placed under abuse control amendments to the [[Food, Drug and Cosmetic Act]]. Records on production and distribution were required to be kept. Limits were placed on prescription duration and refills.<ref>''Tranquilizer Is Put Under U.S. Curbs; Side-Effects Noted'', New York Times, December 6, 1967, Page 35.</ref>
Meprobamate Tablets USP 200 mg and 400 mg for oral administration contain the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, sodium starch glycolate and pregelatinised starch.
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
|howSupplied=* Meprobamate Tablets USP 200 mg are white to off white, round, biconvex, uncoated tablets debossed with “L125” on one side and break line on other side.


Production continued throughout the 1960s but by 1970 it was listed as a controlled substance after it was discovered to cause physical and psychological dependence.
:*NDC 23155-128-03  Bottle of 30


==Pharmacology==
:*NDC 23155-128-01  Bottle of 100
Although it was marketed as being safer, meprobamate has most of the pharmacological effects and dangers of the [[barbiturate]]s (though it is less sedating at effective doses). It is reported to have some anticonvulsant properties against absence seizures, but can exacerbate generalized tonic-clonic seizures.


Meprobamate's mechanism of action is not known. It has been shown in animal studies to have effects at multiple sites in the central nervous system, including the [[thalamus]] and [[limbic system]]. Meprobamate binds to [[GABA A receptor]]s which interrupt neuronal communication in the [[reticular formation]] and [[spinal cord]], causing sedation and altered perception of pain.
:*NDC 23155-128-10  Bottle of 1000


Related drugs include [[carisoprodol]] (a [[prodrug]] of meprobamate) and tybamate.
* Meprobamate Tablets USP 400 mg are white to off white, round, biconvex, uncoated tablets debossed with “L105” on one side and break line on other side.


==Indications==
:*NDC 23155-129-03  Bottle of 30
Meprobamate is used for treatment of anxiety disorders or for short-term relief of anxiety.


It has also been used [[off-label]] as a [[sedative]]. However, it is currently only licensed as an anxiolytic, and is not used as often as the benzodiazepines for this purpose.
:*NDC 23155-129-01  Bottle of 100


Meprobamate is available in 200mg and 400mg tablets for oral administration. Meprobamate is also a component of the combination drug [[Equagesic]] (discontinued in the UK in 2002) acting as a [[muscle relaxant]].
:*NDC 23155-129-10  Bottle of 1000


[[Image:Meprobamate DOJ.jpg|frame|right]]
* Dispense in well-closed container with child-resistant closure.
|storage=* Store at controlled room temperature, excursions permitted to 15°C-30°C (59°F-86°F).


==Overdose==
* Preserve in well closed container.
Symptoms of meprobamate overdose include: coma, drowsiness, loss of muscle control, severely impaired breathing, shock, sluggishness, and unresponsiveness. Death has been reported with ingestion of as little as 12g of meprobamate and survival with as much as 40g.  
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|brandNames=MEPROBAMATE
|drugShortage=
}}
{{PillImage
|fileName=No image.jpg
}}
{{LabelImage
|fileName=Meprobamate ingredients and appearance.png
}}
{{LabelImage
|fileName=Meprobamate fig01.jpg
}}
{{LabelImage
|fileName=Meprobamate fig.jpg
}}
<!--Pill Image-->


==Legal Issues==
Meprobamate is a [[Schedule IV]] drug under the [[Convention on Psychotropic Substances]].
Meprobamate may cause GI concretions in overdose; therefore, charcoal should be considered even after 4 hours or if levels are rising.


==Trivia==
{{Trivia|date=September 2007}}
Meprobamate was the first drug ever used to lower high blood pressure or [[hypertension]]; however, it was later replaced by better drugs like [[metoprolol]] which do not make the patient sleepy.


Outed CIA Russian spy Aldrich H. Ames was reported in the Feb. 27, 1994 edition of The Washington Post as saying that taking 400mg of Meprobamate was an effective method for 'cheating' a polygraph (lie detector) test.<ref>http://www.csicop.org/klassfiles/SUN-50.html</ref>
<!--Label Display Image-->


[[Maude]] Findlay, played by [[Bea Arthur]] in the 1970's sitcom ''Maude'' announced that she had taken two Miltown before giving a dinner party during an episode in the first season of the program.


==References==
<references/>
* Barondes, Samuel H. ''Better Than Prozac''. New York: Oxford University Press, 2003. ISBN 0-19-515130-5.
* ''A History of Psychiatry: From the Era of the Asylum to the Age of Prozac'' by Edward Shorte. John Wiley and Sons.
* [http://www.incb.org/pdf/e/list/green.pdf List of psychotropic substances under international control].
* [http://ctd.mdibl.org/voc.go?voc=chem&termUI=Meprobamate The Comparative Toxicogenomics Database: Meprobamate].
* [http://www.biam2.org/www/Sub2341.html BIAM: Meprobamate] (French).


==External links==
* [http://www.rxlist.com/cgi/generic2/meprobamate.htm RxList.com - Meprobamate]


{{Anxiolytics}}


<!--Category-->
[[Category:Sedatives]]
[[Category:Sedatives]]
[[Category:Hypnotics]]
[[Category:Hypnotics]]
[[Category:Muscle relaxants]]
[[Category:Muscle relaxants]]
[[Category:Anxiolytics]]
[[Category:Drug]]
 
[[de:Meprobamat]]
[[ru:Мепротан]]
[[sv:Meprobamat]]
{{WikiDoc Sources}}

Latest revision as of 19:35, 9 March 2015

Meprobamate
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Disclaimer

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Overview

Meprobamate is an anti anxiety drug that is FDA approved for the treatment of anxiety disorders. Common adverse reactions include nausea, vomiting, diarrhea. drowsiness, ataxia, dizziness, slurred speech, headache, vertigo, weakness, paresthesias.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

  • Meprobamate tablets are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually do not require treatment with an anxiolytic.
  • The effectiveness of meprobamate tablets in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.

Dosage

  • Meprobamate Tablets USP: The usual adult daily dosage is 1200mg to 1600 mg, in three or four divided doses; a daily dosage above 2400 mg is not recommended.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Meprobamate in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Meprobamate in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Indications

  • Meprobamate tablets are indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually do not require treatment with an anxiolytic.
  • The effectiveness of meprobamate tablets in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.

Dosing

  • The usual daily dosage for children ages six to twelve years is 200 mg to 600 mg, in two or three divided doses.
  • Not recommended for children under age 6 (see Usage in Children).

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Meprobamate in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Meprobamate in pediatric patients.

Contraindications

  • Acute intermittent porphyria as well as allergic or idiosyncratic reactions to meprobamate or related compounds such as carisoprodol, mebutamate, tybamate, or carbromal.

Warnings

Drug Dependence

  • Physical dependence, psychological dependence, and abuse have occurred. When chronic intoxication from prolonged use occurs, it usually involves ingestion of greater than recommended doses and is manifested by ataxia, slurred speech, and vertigo.
  • Therefore, careful supervision of dose and amounts prescribed is advised, as well as avoidance of prolonged administration, especially for alcoholics and other patients with a known propensity for taking excessive quantities of drugs.
  • Sudden withdrawal of the drug after prolonged and excessive use may precipitate recurrence of pre-existing symptoms such as anxiety, anorexia, insomnia, or withdrawal reactions such as vomiting, ataxia, tremors, muscle twitching, confusional states, hallucinosis, and rarely, convulsive seizures. Such seizures are more likely to occur in persons with central nervous system damage or pre-existent or latent convulsive disorders. Onset of withdrawal symptoms occurs usually within 12 to 48 hours after discontinuation of meprobamate; symptoms usually cease within the next 12 to 48 hours.
  • When excessive dosage has continued for weeks or months, dosage should be reduced gradually over a period of one or two weeks rather than abruptly stopped. Alternatively, a long-acting barbiturate may be substituted, then gradually withdrawn.

Potentially Hazardous Tasks

  • Patients should be warned that meprobamate may impair the mental and/or physical abilities required for performance of potentially hazardous tasks such as driving or operating machinery.

Additive Effects

  • Since the effects of meprobamate and alcohol or meprobamate and other CNS depressants or psychotropic drugs may be additive, appropriate caution should be exercised with patients who take more than one of these agents simultaneously.

Usage in Pregnancy and Lactation

  • An increased risk of congenital malformations associated with the use of minor tranquilizers (meprobamate, chlordiazepoxide and diazepam) during the first trimester of pregnancy has been suggested in several studies. Because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physician about the desirability of discontinuing the drug.
  • Meprobamate passes the placental barrier. It is present both in umbilical cord blood at or near maternal plasma levels and in breast milk of lactating mothers at concentrations two to four times that of maternal plasma. When use of meprobamate is contemplated in breastfeeding patients, the drug's higher concentration in breast milk as compared to maternal plasma should be considered.

Usage in Children

  • Meprobamate tablets should not be administered to children under age six, since there is a lack of documented evidence for safety and effectiveness in this age group.

PRECAUTIONS

  • The lowest effective dose should be administered, particularly to elderly and/or debilitated patients, in order to preclude oversedation.
  • The possibility of suicide attempts should be considered and the least amount of drug feasible should be dispensed at any one time.
  • Meprobamate is metabolized in the liver and excreted by the kidney; to avoid its excess accumulation, caution should be exercised in administration to patients with compromised liver or kidney function.
  • Meprobamate occasionally may precipitate seizures in epileptic patients.

Adverse Reactions

Clinical Trials Experience

Central Nervous System

Gastrointestinal

Cardiovascular

Allergic or Idiosyncratic

  • Allergic or idiosyncratic reactions are usually seen within the period of the first to fourth dose in patients having had no previous contact with the drug. Milder reactions are characterized by an itchy, urticarial, or erythematous maculopapular rash which may be generalized or confined to the groin. Other reactions have included leukopenia, acute nonthrombocytopenic purpura, petechiae, ecchymoses, eosinophilia, peripheral edema, adenopathy, fever, fixed drug eruption with cross reaction to carisoprodol, and cross sensitivity between meprobamate/mebutamate and meprobamate/carbromal.
  • In case of allergic or idiosyncratic reactions to meprobamate, discontinue the drug and initiate appropriate symptomatic therapy, which may include epinephrine,antihistamines, and in severe cases, corticosteroids. In evaluating possible allergic reactions, also consider allergy to excipients.

Hematologic

Other

  • Exacerbation of porphyric symptoms.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Meprobamate in the drug label.

Drug Interactions

There is limited information regarding Meprobamate Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Meprobamate in women who are pregnant.
Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Meprobamate in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Meprobamate during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Meprobamate with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Meprobamate with respect to pediatric patients.

Geriatic Use

  • Clinical studies of meprobamate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Gender

There is no FDA guidance on the use of Meprobamate with respect to specific gender populations.

Race

There is no FDA guidance on the use of Meprobamate with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Meprobamate in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Meprobamate in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Meprobamate in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Meprobamate in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral

Monitoring

There is limited information regarding Monitoring of Meprobamate in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Meprobamate in the drug label.

Overdosage

  • Suicidal attempts with meprobamate have resulted in drowsiness, lethargy, stupor, ataxia, coma, shock, vasomotor, and respiratory collapse. Some suicidal attempts have been fatal.
  • The following data on meprobamate tablets have been reported in the literature and from other sources. These data are not expected to correlate with each case (considering factors such as individual susceptibility and length of time from ingestion to treatment), but represent the usual ranges reported.

Acute simple overdose (meprobamate alone): Death has been reported with ingestion of as little as 12 g meprobamate and survival with as much as 40 g.

Blood Levels

  • 0.5-2 mg% represents the usual blood level range of meprobamate after therapeutic doses. The level may occasionally be as high as 3 mg%.
  • 3-10 mg% usually corresponds to findings of mild to moderate symptoms of overdosage, such as stupor or light coma.
  • 10-20 mg% usually corresponds to deeper coma, requiring more intensive treatment. Some fatalities occur.
  • At levels greater than 20 mg%, more fatalities than survivals can be expected.

Acute combined overdose (meprobamate with alcohol or other CNS depressants or psychotropic drugs): Since effects can be additive, a history of ingestion of a low dose of meprobamate plus any of these compounds (or of a relative low blood or tissue level) cannot be used as a prognostic indicator.

  • In cases where excessive doses have been taken, sleep ensues rapidly and blood pressure, pulse, and respiratory rates are reduced to basal levels. Any drug remaining in the stomach should be removed and symptomatic therapy given. Should respiration or blood pressure become compromised, respiratory assistance, central nervous system stimulants, and pressor agents should be administered cautiously as indicated. Meprobamate is metabolized in the liver and excreted by the kidney. Diuresis, osmotic (mannitol) diuresis, peritoneal dialysis, and hemodialysis have been used successfully. Careful monitoring of urinary output is necessary and caution should be taken to avoid overhydration. Relapse and death, after initial recovery, have been attributed to incomplete gastric emptying and delayed absorption. Meprobamate can be measured in biological fluids by two methods: colorimetric (Hoffman, A.J. and Ludwig, B.J.: J Amer Pharm Assn 48: 740, 1959) and gas chromatographic (Douglas, J.F. et al: Anal Chem 39: 956, 1967).

Pharmacology

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Meprobamate
Systematic (IUPAC) name
[2-(carbamoyloxymethyl)-2-methyl-pentyl] carbamate
Identifiers
CAS number 57-53-4
ATC code N05BC01
PubChem 4064
DrugBank DB00371
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 218.250 g/mol
SMILES eMolecules & PubChem
Physical data
Density 1.229 g/cm³
Melt. point 105–106 °C (221–223 °F)
Boiling point 200 °C (392 °F) to 210 °C (410 °F)
Pharmacokinetic data
Bioavailability ?
Metabolism Hepatic
Half life 10 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

C(AU) D(US)

Legal status

Prescription Only (S4)(AU) Schedule IV(US)

Routes Oral

Mechanism of Action

There is limited information regarding Meprobamate Mechanism of Action in the drug label.

Structure

Meprobamate is a white powder with a characteristic odor and a bitter taste. It is slightly soluble in water, freely soluble in acetone and alcohol, and sparingly soluble in ether. The structural formula of meprobamate is:

This image is provided by the National Library of Medicine.

Meprobamate Tablets USP 200 mg and 400 mg for oral administration contain the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, sodium starch glycolate and pregelatinised starch.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Meprobamate in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Meprobamate in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Meprobamate in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Meprobamate in the drug label.

How Supplied

  • Meprobamate Tablets USP 200 mg are white to off white, round, biconvex, uncoated tablets debossed with “L125” on one side and break line on other side.
  • NDC 23155-128-03 Bottle of 30
  • NDC 23155-128-01 Bottle of 100
  • NDC 23155-128-10 Bottle of 1000
  • Meprobamate Tablets USP 400 mg are white to off white, round, biconvex, uncoated tablets debossed with “L105” on one side and break line on other side.
  • NDC 23155-129-03 Bottle of 30
  • NDC 23155-129-01 Bottle of 100
  • NDC 23155-129-10 Bottle of 1000
  • Dispense in well-closed container with child-resistant closure.

Storage

  • Store at controlled room temperature, excursions permitted to 15°C-30°C (59°F-86°F).
  • Preserve in well closed container.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Meprobamate in the drug label.

Precautions with Alcohol

  • Alcohol-Meprobamate interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

MEPROBAMATE

Look-Alike Drug Names

There is limited information regarding Meprobamate Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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