Equagesic

Equagesic (meprobamate and aspirin) ® (meprobamate with aspirin) Tablets, 200 mg meprobamate and 325 mg aspirin, are available as follows:

NDC 0008-0091, pink and yellow, double-layer, round, scored tablet marked "WYETH" and "91", in bottles of 100 tablets.

Store at room temperature, approx. 25^o C (77^o F). Keep tightly closed. Protect from light. Dispense in light-resistant, tight container.

As an adjunct in the short-term treatment of pain accompanied by tension and/or anxiety in patients with musculoskeletal disease. Clinical trials have demonstrated that in these situations relief of pain is somewhat greater than with aspirin alone. The effectiveness of Equagesic (meprobamate and aspirin) 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

The usual dosage of Equagesic (meprobamate and aspirin) is one or two tablets, each tablet containing meprobamate, 200 mg, and aspirin, 325 mg, orally 3 to 4 times daily as needed for the relief of pain when tension or anxiety is present. Equagesic (meprobamate and aspirin) is not recommended for patients 12 years of age and under.

ASPIRIN Allergic or idiosyncratic reactions to aspirin or related compounds.

MEPROBAMATE Acute intermittent porphyria and allergic or idiosyncratic reactions to meprobamate or related compounds, such as carisoprodol, mebutamate, or carbromal.

WARNINGS

ASPIRIN

Salicylates should be used with extreme caution in patients with peptic ulcer, asthma, coagulation abnormalities, hypoprothrombinemia, vitamin K deficiency, or in those on anticoagulant therapy.

In rare instances, the use of aspirin in persons allergic to salicylates may result in life-threatening allergic episodes.

MEPROBAMATE

Drug Dependence

Physical dependence, psychological dependence, and abuse have occurred. Chronic intoxication from prolonged ingestion of, usually, greater-than-recommended doses 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 preexisting 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 preexistent 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- hour period. When excessive dosage has continued for weeks or months, dosage should be reduced gradually over a period of 1 to 2 weeks rather than abruptly stopped. Alternatively, a short- acting barbiturate may be substituted, then gradually withdrawn.

Potentially Hazardous Tasks

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

Additive Effects

Since CNS- suppressant effects of meprobamate and alcohol or meprobamate and other 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, chiordiazepoxide, 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 physicians 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 concentrations in breast milk as compared to maternal plasma levels should be considered.

USAGE IN CHILDREN

Preparations containing aspirin should be kept out of the reach of children. Equagesic (meprobamate and aspirin) is not recommended for patients 12 years of age and under.

PRECAUTIONS

ASPIRIN

Salicylates antagonize the uricosuric activity of probenecid and sulfinpyrazone. Salicylates are reported to enhance the hypoglycemic effect of the sulfonylurea antidiabetic drugs.

MEPROBAMATE

The lowest effective dose should be administered, particularly to elderly and/or debilitated patients, in order to preclude oversedation.

Meprobamate is metabolized in the liver and excreted by the kidney: to avoid its excess accumulation, caution should be exercised in the administration to patients with compromised liver or kidney function. Meprobamate occasionally may precipitate seizures in epileptic patients.

The drug should be prescribed cautiously and in small quantities to patients with suicidal tendencies.

SIDE EFFECTS

ASPIRIN

Aspirin may cause epigastric discomfort, nausea, and vomiting. Hypersensitivity reactions, including urticaria, angioneurotic edema, purpura, asthma, and anaphylaxis, may rarely occur. Patients receiving large doses of salicylates may develop tinnitus.

MEPROBAMATE

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, hypotensive crisis.

Allergic or Idiosyncratic

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, exfoliative dermatitis, stomatitis, and proctitis. Stevens-Johnson syndrome and bullous dermatitis have occurred.

Hematologic (see also Allergic or Idiosyncratic section above)

Agranulocytosis, aplastic anemia have been reported, although n o causal relationship has been established, and thrombocytopenic purpura.

Other

Exacerbation of porphyric symptoms.

DRUG INTERACTIONS

No information provided.

ASPIRIN

Aspirin may cause epigastric discomfort, nausea, and vomiting. Hypersensitivity reactions, including urticaria, angioneurotic edema, purpura, asthma, and anaphylaxis, may rarely occur. Patients receiving large doses of salicylates may develop tinnitus.

MEPROBAMATE

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, hypotensive crisis.

Allergic or Idiosyncratic

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, exfoliative dermatitis, stomatitis, and proctitis. Stevens-Johnson syndrome and bullous dermatitis have occurred.

Hematologic (see also Allergic or Idiosyncratic section above)

Agranulocytosis, aplastic anemia have been reported, although n o causal relationship has been established, and thrombocytopenic purpura.

Other

Exacerbation of porphyric symptoms.

Treatment of overdose with Equagesic (meprobamate and aspirin) is essentially symptomatic and supportive. Any drug remaining in the stomach should be removed. Induction of vomiting or gastric lavage may be indicated.

Activated charcoal may reduce absorption of both aspirin and meprobamate.

Overdosage with aspirin produces the usual symptoms and signs of salicylate intoxication. Observation and treatment should include management of hyperthermia, specific parenteral electrolyte therapy for ketoacidosis and dehydration, watching for evidence of hemorrhagic manifestations due to hypoprothrombinemia which, if it occurs, usually requires whole-blood transfusions.

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 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 grams meprobamate and survival with as much as 40 grams.

BLOOD LEVELS

0.5 to 2.0 mg percent represents the usual blood-level range of meprobamate after therapeutic doses. The level may occasionally be as high as 3.0 mg percent.

3 to 10 mg percent usually corresponds to findings of mild-to-moderate symptoms of overdosage, such as stupor or light coma.

10 to 20 mg percent usually corresponds to deeper coma, requiring more intensive treatment Some fatalities occur.

At levels greater than 20 mg percent, more fatalities than survivals can be expected.

Acute combined overdose (meprobamate with other psychotropic drugs or alcohol): Since effects can be additive, a history of ingestion of a low dose of meprobamate plus any of these compounds (or of a relatively 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 treatment given. Should respiration or blood pressure become compromised, respiratory assistance, central-nervous-system stimulants, and pressor agents should be administered cautiously as indicated. Diuresis, osmotic (mannitol) diuresis, peritoneal dialysis, and hemodialysis have been used successfully in removing both aspirin and meprobamate. Alkalinization of the urine increases the excretion of salicylates. 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.