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Meprobamate


General


Pronunciation

(me proe BA mate)


Indications


Use: Labeled Indications

Management of anxiety disorders


Contraindications


Hypersensitivity to meprobamate, related compounds (including carisoprodol), or any component of the formulation; acute intermittent porphyria


Dosing and Administration


Dosing: Adult

Anxiety: Oral: 1200-1600 mg/day in 3-4 divided doses, up to 2400 mg/day


Dosing: Pediatric

Anxiety: Oral: 6-12 years: 200-600 mg/day in 2-3 divided doses


Dosing: Renal Impairment

No dosage adjustment provided in manufacturer 's labeling; however, the following adjustments have been recommended (Aronoff, 2007): Adults:

CrCl 10-50 mL/minute: Administer every 9-12 hours.

CrCl <10 mL/minute: Administer every 12-18 hours.

Hemodialysis: No dosage adjustment necessary.

Peritoneal dialysis: Administer every 12-18 hours.

Continuous renal replacement therapy (CRRT): Administer every 9-12 hours.


Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer 's labeling; use with caution.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 200 mg, 400 mg


Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Yohimbine: May diminish the therapeutic effect of Antianxiety Agents. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification


Monitoring Parameters

Mental status


Adverse Reactions


Frequency not defined.

Cardiovascular: Abnormal electroencephalogram, cardiac arrhythmia, peripheral edema, palpitations, severe hypotension, syncope, tachycardia

Central nervous system: Ataxia, chills, dizziness, drowsiness, euphoria, headache, overstimulation, paradoxical excitation, paresthesia, slurred speech, vertigo

Dermatologic: Dermatitis, erythema multiforme, skin rash, Stevens-Johnson syndrome

Endocrine & metabolic: Exacerbation of porphyria

Gastrointestinal: Diarrhea, nausea, proctitis, stomatitis, vomiting

Genitourinary: Anuria, oliguria

Hematologic & oncologic: Agranulocytosis, aplastic anemia, bruise, eosinophilia, immune thrombocytopenia, leukopenia, petechia, purpura

Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction

Neuromuscular & skeletal: Weakness

Ophthalmic: Accommodation disturbance

Respiratory: Bronchospasm

Miscellaneous: Fever


Warnings/Precautions


Concerns related to adverse effects:

- Allergic reactions: May occur in patients with history of dermatological condition (usually by fourth dose).

- CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Disease-related concerns:

- Depression: Use with caution in patients with depression or suicidal tendencies.

- Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.

- Hepatic impairment: Use with caution in patients with hepatic impairment.

- Renal impairment: Use with caution in patients with renal impairment.

- Seizure disorder: Use with caution in patients with a history of seizure disorder.

Concurrent drug therapy issues:

- Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.

Other warnings/precautions:

- Abrupt discontinuation: May precipitate withdrawal.


Pregnancy Considerations

Meprobamate crosses the placenta and is found in cord blood in concentrations similar to those in the maternal plasma. Maternal use may be associated with congenital malformations; avoid use during pregnancy.


Actions


Pharmacology

Affects the thalamus and limbic system; also appears to inhibit multineuronal spinal reflexes


Metabolism

Hepatic


Excretion

Urine (8% to 20% as unchanged drug); feces (10% as metabolites)


Onset of Action

Sedation: ~1 hour


Half-Life Elimination

10 hours


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience headache, nausea, vomiting, diarrhea, fatigue, or anxiety. Have patient report immediately to prescriber signs of infection, enlarged lymph nodes, swelling of arms or legs, bruising, bleeding, urinary retention, change in amount of urine passed, difficulty breathing, severe loss of strength and energy, suicidal ideation, seizures, dysarthria, tachycardia, arrhythmia, behavioral changes, burning or numbness feeling, change in balance, vision changes, severe dizziness, passing out, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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