The P-I-E-N-O Parkinsn's List Drug Database
meprobamate / EquanilTM , MeprospanTM , MiltownTM
ANTIANXIETY:
Sedative
Description: Meprobamate is an oral anxiolytic. It was first approved as an anxiolytic in 1955 and is indicated for the treatment of anxiety disorders or for the short-term symptomatic treatment of anxiety; however, it also is widely used for its sedative-hypnotic properties. Clinical studies evaluating its effectiveness for prolonged therapy (>4 months) have not been conducted. It is similar in structure to carisoprodol and carbromal. Felbamate (see separate monograph), a new anticonvulsant, is also chemically related to meprobamate. Meprobamate has many properties similar to those of the benzodiazepines. Meprobamate was approved by the FDA in April 1955. It is classified as a schedule IV controlled substance.
Mechanism of Action: Meprobamate's exact mechanism of action is unknown. Meprobamate appears to exert CNS-depressive action at several sites in the CNS including the spinal cord, limbic system, hypothalamus, and thalamus. Skeletal muscle relaxation is believed to occur secondary to the sedative effect and is of negligible clinical significance. Very high doses can cause respiratory depression and vasomotor depression. In addition, hypnotic doses of meprobamate have been shown to significantly suppress rapid eye movement (REM) or the dreaming stage of sleep.
Pharmacokinetics: Meprobamate is administered orally and is readily absorbed from the GI tract. Peak plasma concentrations are achieved in 1-3 hours, with the onset of sedation occurring within 1 hour. The drug is distributed throughout the body. Meprobamate crosses the placenta in concentrations similar to maternal plasma concentrations. It also is distributed into breast milk in amounts 2-4 times that of maternal plasma concentrations (see Contraindications). Meprobamate is metabolized in the liver to inactive metabolites consisting of 2hydroxymeprobamate and glucosyluronide and glucuronide conjugates. This drug is an inducer of hepatic enzymes. The plasma half-life is 10-11 hours. Renal elimination of unchanged meprobamate is approximately 10-12% of a dose within 24 hours, with the remainder occurring as metabolites. Due to the sedation produced by meprobamate, dosage-interval adjustments in the presence of renal insufficiency are recommended (see Dosage).
CONTRAINDICATIONS/PRECAUTIONS: Meprobamate is contraindicated in patients with a known carbamate hypersensitivity, which includes the following compounds: felbamate, carisoprodol, carbromal, tybamate, and mebutamate. Some formulations of this drug contain tartrazine dye and should be avoided in patients who experience a severe reaction including bronchial asthma, anaphylaxis, or other lifethreatening symptoms. Symptoms of tartrazine dye hypersensitivity are frequently observed in patients with a hypersensitivity to aspirin. Milder reactions to these compounds may not be contraindications to therapy with meprobamate.
Meprobamate is contraindicated in patients with acute intermittent porphyria because this condition can be exacerbated by therapy with this agent.
Meprobamate can cause physical or psychological drug dependence. This dependence is of considerable significance in patients with a known history of substance abuse, including alcohol, and in patients prone to addiction or those with suicidal ideation. Careful monitoring of these patient populations is warranted, but meprobamate should be avoided, if possible.
Prolonged and excessive dosages can precipitate a withdrawal syndrome upon abrupt discontinuation of meprobamate. This syndrome is characterized by anxiety, nausea, vomiting, tremors, ataxia, hallucinations, muscle twitches, and confusion. Convulsions also have been reported, and patients with a history of seizures are at an increased risk for developing this complication. Tapering the dose over 2-4 weeks is recommended following long-term use.
Meprobamate should be used with extreme caution in patients with epilepsy or other seizure disorders because seizures can be precipitated by withdrawal of this agent.
Meprobamate is metabolized in the liver and is excreted renally; therefore, caution should be used in patients with hepatic disease or renal impairment (see Dosage) to avoid drug accumulation.
Meprobamate is classified as pregnancy category D. The use of meprobamate during pregnancy has been associated with congenital anomolies. This is of particular significance during the first 6 weeks of pregnancy. It is recommended that meprobamate be avoided during pregnancy, if possible. Meprobamate is distributed into breast milk in concentrations 2-4 times that of maternal plasma concentrations. This drug should be used during breast-feeding only if clearly needed due to potential adverse effects in the nursing infant such as excessive sedation.
DRUG INTERACTIONS: The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including ethanol, tricyclic antidepressants, antipsychotics, anticonvulsants, and MAOIs. In addition, chronic ethanol ingestion has been shown to increase the metabolism of meprobamate, producing variable responses to this agent.
ADVERSE REACTIONS: Frequently reported CNS adverse reactions during therapy with meprobamate include drowsiness and ataxia. Dizziness, dysarthria, headache, vertigo, weakness, and paresthesias occur less commonly. Paradoxical CNS stimulation has been reported, which results in fast EEG activity. Rebound REM sleep can occur following discontinuation of therapy due to suppression of REM sleep.
Cardiovascular effects during therapy with meprobamate include palpitations, sinus tachycardia, transient ECG changes, and hypotension. More severe reactions include cardiac arrhythmias, and hypotensive crisis (which included one fatality).
Allergic or idiosyncratic reactions can occur in patients previously untreated with meprobamate. Patients with a history of allergy or hypersensitivity are more susceptible and reactions are generally apparent by the fourth or fifth dose. These reactions are generally mild and include urticaria, or an erythematous maculopapular rash. The rash may be confined to the groin area or be more generalized. Other reactions can include acute nonthrombocytopenic purpura, leukopenia, petechiae, ecchymosis, eosinophilia, peripheral edema, adenopathy, fever, and fixed drug eruption, with cross-reaction to carisoprodol. More serious hypersensitivity reactions are rare. However, the following reactions have been reported: hyperpyrexia, chills, angioneurotic edema, bronchospasm, oliguria, and anuria. Also, anaphylaxis, erythema multiforme, exfoliative dermatitis, stomatitis, proctitis, Stevens-Johnson syndrome, and bullous dermatitis. If any allergic or idiosyncratic reaction develops, meprobamate therapy should be withdrawn and appropriate symptomatic therapy instigated.
Therapy with meprobamate produces severe hematological reactions in fewer than 1% of patients. Agranulocytosis, aplastic anemia, and thrombocytopenic purpura also have been reported; these cases rarely had a fatal outcome.
Anorexia, nausea/vomiting, and diarrhea are frequently reported gastrointestinal effects during therapy with meprobamate.
Patients can develop physical or psychological dependence while on meprobamate. After prolonged use, symptoms of ataxia, dysarthria, and vertigo may develop. Sudden withdrawal of meprobamate can produce withdrawal symptoms including vomiting, ataxia, tremors, muscle twitching, confusion, hallucinations, and occasionally seizures. Pre-existing symptoms such as anxiety, anorexia, or insomnia may also emerge. Withdrawal symptoms occur within 12 -48 hours of discontinuation of therapy. After prolonged use of meprobamate, dosage should be gradually reduced over a period of one to two weeks to minimize withdrawal symptoms.
PATIENT INFORMATION:
What do meprobamate tablets or extended-release capsules do?
Meprobamate (EquanilTM , MeprospanTM , MiltownTM ) has a sedative action that can cause relaxation and help reduce tension or anxiety. It can help give short-term relief for anxiety caused by lifes events. Meprobamate is sometimes used as a sedative before surgery or dental procedures. Federal law prohibits the transfer of meprobamate to any person other than the patient for whom it was prescribed. Generic meprobamate tablets are available, but not generic extended-release capsules.
What should my doctor, dentist, or pharmacist know before I take meprobamate?
They need to know if you have any of these conditions:
How should I take this medicine?
Take meprobamate by mouth. Follow the directions on the prescription label. Swallow the tablets or capsules with a drink of water. Swallow the capsules whole; do not crush or chew. Take your doses at regular intervals. Do not take your medicine more often than directed. Tablets or capsules may be taken with food or milk to reduce stomach upset.
Special precautions for use in children:
The 600 mg tablets and sustained-release preparations are not for children of any age. Other tablets are not for children under 6 years old.
What if I miss a dose?
If you miss a dose, take it if you remember within 1 hour. If you remember after more than 1 hour, skip the missed dose and resume your schedule at the next dose. Do not take double or extra doses.
What other medicines can interact with meprobamate?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking meprobamate?
Serious side effects with meprobamate include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with meprobamate include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take meprobamate?
Visit your doctor for regular checks on your progress. If you have been taking meprobamate regularly for a few weeks and suddenly stop taking it, you may get unpleasant withdrawal symptoms. Your doctor may want to gradually reduce the dose. Do not stop taking except on your doctor's advice.
After taking meprobamate you may get a residual hangover effect that leaves you drowsy or dizzy. Until you know how meprobamate affects you, do not drive, use machinery, or do anything that needs mental alertness. To reduce dizzy or fainting spells, do not sit or stand up quickly, especially if you are an older patient. Alcohol can increase possible unpleasant effects. Avoid alcoholic drinks.
If you are going to have any medical tests, tell your doctor that you are taking meprobamate.
While you are taking meprobamate, do not take any medicines for hay fever, allergies, or pain without asking your doctor or pharmacist for advice.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Keep container tightly closed. Throw away any unused medicine after the expiration date.
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