Drug class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
VA class: CN309
Chemical name: 2-Methyl-2-propyl-1,3-propanediol dicarbamate
CAS number: 57-53-4

Introduction

Anxiolytic agent.

Uses for Meprobamate

Anxiety

Management of anxiety disorders or short-term relief of symptoms of anxiety.

Efficacy for long-term use (i.e., >4 months) has not been evaluated.

Adjunct therapy when anxiety complicates psychosis or treatment of alcohol dependence; however, consider additive CNS depressant effects of meprobamate and alcohol.

Anxiety or tension associated with stress of everyday life usually does not require treatment with an anxiolytic.

Sedation

Has been used preoperatively to relieve anxiety and provide sedation^{† [off-label]}.

Effective in promoting sleep^{† [off-label]} in the anxious, tense patient.

No evidence that drug has an advantage over other sedatives (e.g., barbiturates) in relieving anxiety and tension.

Seizures

Not effective as an anticonvulsant in the management of seizure disorders^{† [off-label]}; may precipitate seizures. (See Seizures under Cautions.)

Pain with Tension/Anxiety

Meprobamate in fixed combination with aspirin used as adjunct in the short-term (≤10 days) therapy of pain accompanied by tension and/or anxiety in patients with musculoskeletal disease.

The combination has been shown to be more effective than aspirin alone.

Meprobamate Dosage and Administration

Administration

Administer orally.

Avoid prolonged administration; may induce psychologic or physical dependence.

If discontinuing meprobamate after chronic therapy, withdraw slowly to avoid the possibility of precipitating withdrawal symptoms.

Dosage

Individualize dosage and administer the smallest effective dosage (especially in geriatric or debilitated patients) to avoid oversedation.

Periodically reassess need for continued therapy.

Pediatric Patients

Anxiety

Oral

Children 6–12 years of age: 100–200 mg 2 or 3 times (200–600 mg) daily.

Children >12 years of age: 1.2–1.6 g daily in 3 or 4 divided doses.

Sedation† [off-label]

Oral

Children 6–12 years of age: 100–200 mg 2 or 3 times (200–600 mg) daily. Alternatively, 25 mg/kg daily or 700 mg/m² daily in 2 or 3 divided doses.

Children >12 years of age: Usual hypnotic dose: 800 mg.

Preoperative Anxiety/Sedation† [off-label]

Oral

Children 6–12 years of age: 200 mg.

Children >12 years of age: 400 mg.

Pain and Anxiety

Fixed-combination Meprobamate/Aspirin

Oral

Children >12 years of age: 200 or 400 mg (1 or 2 tablets) 3 or 4 times daily as needed for up to 10 days.

Adults

Anxiety

Oral

1.2–1.6 g daily in 3 or 4 divided doses.

Sedation†

Oral

Usual hypnotic dose: 800 mg.

Preoperative Anxiety/Sedation†

Oral

400 mg.

Pain and Anxiety

Fixed-combination Meprobamate/Aspirin

Oral

200 or 400 mg (1 or 2 tablets) 3 to 4 times daily as needed for up to 10 days.

Prescribing Limits

Pediatric Patients

Oral

Children >12 years of age: Maximum 2.4 g daily.

Adults

Oral

Maximum 2.4 g daily.

Special Populations

Geriatric or Debilitated Patients

Select dosage with caution, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Use the smallest effective dosage to avoid oversedation.

Cautions for Meprobamate

Contraindications

• History of porphyria.

• Allergic or idiosyncratic reactions to meprobamate or related compounds (e.g., carisoprodol, carbromal, mebutamate, tybamate).

Warnings/Precautions

Warnings

Abuse Potential

Tolerance, psychologic and physical dependence, and abuse may occur following prolonged use of high doses. Dependence may be manifested by drowsiness, ataxia, slurred speech, and vertigo.

Use with caution, especially in those with a history of drug or alcohol dependence or abuse.

Do not prescribe large quantities in those with suicidal tendencies or in those who might abuse the drug.

Withdrawal Effects

Abrupt cessation of therapy in physically dependent patients may produce severe withdrawal symptoms within 12–48 hours, including anxiety, anorexia, insomnia, vomiting, ataxia, tremors, muscle twitching, confusion, hallucinations, and seizures (clinically indistinguishable from generalized tonic-clonic [grand mal] seizures). Seizures are most likely to occur in patients ingesting large amounts of the drug or patients who have CNS damage or a history of seizure disorders.

Fatalities have occurred following abrupt withdrawal.

Symptoms usually cease within 12–48 hours after they appear.

When discontinuing meprobamate if excessive dosage has been administered for weeks or months, gradually reduce the dosage over 1 to 2 weeks. Alternatively, substitute a long-acting barbiturate, then gradually withdraw.

CNS Effects

May impair mental and/or physical activities needed to perform potentially hazardous activities such as driving or operating machinery.

Fetal/Neonatal Morbidity and Mortality

Increased risk of fetal harm during the first trimester of pregnancy.

Avoid use in pregnant women.

If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.

Sensitivity Reactions

Hypersensitivity Reactions

Mild to severe allergic or idiosyncratic reactions may occur, particularly in those with a history of dermatologic or allergic conditions. In meprobamate-naive patients, these reactions usually are evident by the fourth dose of the drug.

Mild reactions are characterized by pruritus, urticaria, and/or erythematous maculopapular rash which may be generalized or confined to the groin area.

Other idiosyncratic reactions include leukopenia, acute nonthrombocytopenic purpura, petechiae, ecchymoses, eosinophilia, adenopathy, peripheral edema, fever, and fixed drug eruptions with a cross-reaction to carisoprodol and cross sensitivity with mebutamate and carbromal.

Rarely, severe hypersensitivity reactions manifested as hyperpyrexia, chills, angioedema, bronchospasm, anaphylaxis, stomatitis, proctitis, oliguria, or anuria may occur. Exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, and bullous dermatitis also occurred. Bullous dermatitis resulting in death occurred in one patient following administration of meprobamate in combination with prednisolone.

Discontinue meprobamate if allergic or idiosyncratic reactions occur, and administer appropriate symptomatic therapy (e.g., epinephrine, antihistamines, corticosteroids).

General Precautions

Use of Fixed Combination with Aspirin

When used in fixed combination with aspirin, consider the cautions, precautions, and contraindications associated with aspirin.

Seizures

Risk of seizures; use with caution, if at all, in patients with a history of seizures. (See Withdrawal Effects under Cautions.)

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into human milk.

Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy of conventional tablets in children <6 years of age have not been established.

Safety and efficacy of the fixed combination tablets containing meprobamate and aspirin in children <12 years of age have not been established.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.

No substantial differences in safety and efficacy relative to younger adults.

Hepatic Impairment

Use with caution in patients with impaired hepatic function.

Renal Impairment

Use with caution in patients with impaired renal function.

Common Adverse Effects

Anorexia, nausea, vomiting, diarrhea, palpitations, tachycardia, arrhythmias, transient ECG changes, syncope, hypotension (e.g., hypotensive crisis), drowsiness, ataxia, slurred speech, headache, vertigo, weakness, paresthesias, impairment of visual accommodation, euphoria, overstimulation, paradoxical excitement, fast EEG activity, exacerbation of porphyric symptoms, agranulocytosis, aplastic anemia.

Drug Interactions

Specific Drugs

Meprobamate Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration, with peak plasma concentration usually attained within 1–3 hours.

Onset

Onset of sedative effects is <1 hour following oral administration.

Plasma Concentrations

Plasma concentrations between 100–200 mcg/mL associated with deep coma and are potentially lethal; fatalities frequently occur when plasma concentrations >200 mcg/mL.

Distribution

Extent

Distributed throughout the body.

Distributed into milk in lactating women, at concentrations 2 to 4 times that of maternal plasma.

Crosses placenta and is present in umbilical cord blood at or near maternal plasma concentrations.

Plasma Protein Binding

About 20% in vitro.

Elimination

Metabolism

Rapidly metabolized in the liver to inactive metabolites.

Elimination Route

Excreted in urine (10–12%) as unchanged drug within 24 hours; remainder is excreted in urine as metabolites.

Half-life

10–11 hours (may range from 6–16 hours).

Stability

Storage

Oral

Tablets

Tight, child-resistant containers at 15–30°C.

Fixed-Combination Tablets with Aspirin

Tight, light-resistant containers at 20–25°C. Protect from moisture.

Actions

• CNS depressant actions similar to those of barbiturates.

  Mechanism of action is not known. Apparently acts at multiple sites in the CNS including the hypothalamus, thalamus, limbic system, and spinal cord, but not the medulla, the reticular activating system, or in the autonomic nervous system.

  Although there is some evidence that meprobamate relaxes skeletal muscle tension, the skeletal muscle relaxant effects probably are caused by its sedative effect.

Advice to Patients

• Potential for meprobamate to impair mental alertness or physical coordination; use caution when driving or operating machinery.

• Importance of immediately informing clinician if sore throat, fever, easy bruising, or unusual bleeding occurs; may be an indication of hematologic toxicity.

• Importance of not abruptly discontinuing therapy; consult clinician about discontinuing use.

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of informing patients of other precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Meprobamate and preparations containing the drug combined with aspirin are subject to control under the Federal Controlled Substances Act of 1970 as schedule IV (C-IV) drugs.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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