Meprobamate

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.

`Miltown'-200 contains 200 mg meprobamate per tablet. Other ingredients: acacia, carnauba wax, corn starch, gelatin, magnesium carbonate, magnesium stearate, methylcellulose shellac, sugar, talc, titanium dioxide, white wax and other ingredients.

`Miltown'-400 contains 400 mg meprobamate per tablet. Other ingredients: corn starch, magnesium stearate, methylcellulose.

CLINICAL PHARMACOLOGY

Meprobamate is a carbamate derivative which has been shown in animal studies to have effects at multiple sites in the central nervous system, including the thalamus and limbic system.

INDICATIONS

`Miltown' (meprobamate) is 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 `Miltown' 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 AND ADMINISTRATION

`Miltown'-200 and 400:

The usual adult daily dosage is 1200 mg to 1600 mg, in three or four divided doses; a daily dosage above 2400 mg is not recommended. The usual daily dosage for children ages six to twelve is 200 mg to 600 mg, in two or three divided doses.

Not recommended for children under age 6 (see Usage in Children ).

  HOW SUPPLIED

`Miltown'-200: 200 mg white, sugar-coated tablets coded 37-1101 and Wallace; available in bottles of 100 (NDC 0037-1101-01).

`Miltown'-400: 400 mg white, scored tablets coded 37-1001 and Wallace; available in bottles of 100 (NDC 0037-1001-01), and 1000 (NDC 0037-1001-02).

Storage: Store at controlled room temperature 20°-25°C (68°-77°F). Dispense in a tight container.

WALLACE LABORATORIES
Division of CARTER-WALLACE, INC.
Cranbury, New Jersey 08512

SIDE EFFECTS

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

Palpitations, tachycardia, various forms of arrhythmia, transient ECG changes, syncope; also, hypotensive crises (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

(See also Allergic or Idiosyncratic .) 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.

DRUG INTERACTIONS

No Information Provided.

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, or 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 this drug may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a motor vehicle 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 breast-feeding patients, the drug's higher concentration in breast milk as compared to maternal plasma levels should be considered.

Usage in Children

`Miltown'-200 and `Miltown'-400 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.

Geriatric Use

Clinical studies of Miltown 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.