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Equagesic (Meprobamate / Aspirin) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interactions

Angiotensin Converting Enzyme (ACE) Inhibitors: The hyponatremic and hypotensive effects of ACE inhibitors may be diminished by the concomitant administration of aspirin due to its indirect effect on the reninangiotensin conversion pathway.

Acetazolamide: Concurrent use of aspirin and acetazolamide can lead to high serum concentrations of acetazolamide (and toxicity) due to competition at the renal tubule for secretion.

Alcohol, General Anesthetics, Narcotic Analgesics, Sedative Hypnotics, Tranquilizers such as Chlordiazepoxide, or Other CNS Depressants: The effects of these substances may be enhanced, causing increased CNS depression.

Anticoagulant Therapy (Heparin and Warfarin): Patients on anticoagulation therapy are at increased risk for bleeding because of drug-drug interactions and the effect on platelets. Aspirin can displace warfarin from protein binding sites, leading to prolongation of both the prothrombin time and the bleeding time. Aspirin can increase the anticoagulant activity of heparin, increasing bleeding risk.

Anticonvulsants: Salicylates can displace protein-bound phenytoin and valproic acid, leading to a decrease in the total concentration of phenytoin and an increase in serum valproic acid levels.

Beta Blockers: The hypotensive effects of beta blockers may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.

Corticosteroids: In patients receiving concomitant corticosteroids and chronic use of medications containing aspirin, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Diuretics: The effectiveness of diuretics in patients with underlying renal or cardiovascular disease may be diminished by the concomitant administration of aspirin due to inhibition of renal prostaglandins, leading to decreased renal blood flow and salt and fluid retention.

6-Mercaptopurine and Methotrexate: Bone marrow toxicity and blood dyscrasia may result from displacing these drugs from secondary binding sites, and in the case of methotrexate, also reducing its excretion.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): The concurrent use of aspirin with other NSAIDs should be avoided because this may increase bleeding or lead to decreased renal function.

Oral Hypoglycemics: Moderate doses of aspirin may increase the effectiveness of oral hypoglycemic drugs, leading to hypoglycemia.

Uricosuric Agents (Probenicid and Sulfinpyrazone): Salicylates antagonize the uricosuric action, reducing their effectiveness in the treatment of gout. Aspirin competes with these agents for protein binding sites.

Overdosage

Treatment of overdose with Equagesic is essentially symptomatic and supportive. In cases where excessive doses of Equagesic 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. After emesis and/or lavage, activated charcoal may reduce absorption of both aspirin and meprobamate. 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. Salicylate toxicity may result from acute ingestion (overdose) or chronic intoxication. Signs and symptoms include abdominal pain, acid-base disturbances with development of metabolic acidosis, convulsions, delirium, hyperpnea, hyperthermia, hypoprothrombinemia, restlessness, Tinnitus (ringing in the ears), and vomiting. The early signs of salicylic overdose (salicylism), including tinnitus, occur at plasma concentrations approaching 200 μg/mL. Plasma concentrations of aspirin above 300 μg/mL are clearly toxic. Severe toxic effects are associated with levels above 400 μg/mL. A single lethal dose of aspirin in adults is not known with certainty but death may be expected at 30 g. For real or suspected overdose, a Poison Control Center should be contacted immediately. Careful medical management is essential. In acute aspirin overdose, severe acid-base and electrolyte disturbances may occur and are complicated by hyperthermia and dehydration. Respiratory alkalosis occurs early while hyperventilation is present, but is quickly followed by metabolic acidosis. Treatment of aspirin overdose consists primarily of supporting vital functions, increasing salicylate elimination, and correcting the acid-base disturbance. Gastric emptying and/or lavage is recommended as soon as possible after ingestion, even if the patient has vomited spontaneously. After lavage and/or emesis administration of activated charcoal, as a slurry, is beneficial, if less than 3 hours have passed since ingestion. Charcoal adsorption should not be employed prior to emesis and lavage.

Severity of aspirin intoxication is determined by measuring the blood salicylate level. Acid-base status should be closely followed with serial blood gas and serum pH measurements. Fluid and electrolyte balance should also be maintained. In severe cases, hyperthermia and hypovolemia are the immediate threats to life. Children should be sponged with tepid water. Replacement fluid should be administered intravenously and augmented with correction of acidosis. Plasma electrolytes and pH should be monitored to promote alkaline diuresis of salicylate if renal function is normal. Infusion of glucose may be required to control hypoglycemia.

Hemodialysis and peritoneal dialysis can be performed to reduce the body drug content. In patients with renal insufficiency or in cases of life-threatening intoxication, dialysis is usually required. Exchange transfusion may be indicated in infants and young children. Suicidal attempts with meprobamate have resulted in ataxia, coma, drowsiness, lethargy, shock, stupor, and respiratory and vasomotor 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 mg percent represents the usual blood-level range of meprobamate after therapeutic doses. 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 CNS 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.

Drug Abuse and 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 anorexia, anxiety, or insomnia, or withdrawal reactions, such as ataxia, confusional states, hallucinosis, muscle twitching, tremors, vomiting, 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 long-acting barbiturate may be substituted, then gradually withdrawn.

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