Ethinamate (Systemic)


VA CLASSIFICATION
Primary: CN309

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Sedative-hypnotic—

Indications

Accepted

—Ethinamate has been used for the short-term treatment of insomnia {04} {05}; however, it generally has been replaced by other sedative-hypnotic agents.
—If ethinamate is used for the treatment of insomnia, prolonged administration is not recommended since ethinamate has not been shown to be effective for more than 7 days. {05} Also, if retreatment is necessary, intervals of 1 or more weeks should elapse between periods of treatment. {05}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    167.21

Mechanism of action/Effect:

Unknown. {04} {05}

Absorption:

Rapidly absorbed. {03} {04} {05}

Biotransformation:

Hepatic. {05}

Half-life:

2.5 hours. {05}

Onset of action:

20 to 30 minutes. {05}

Time to peak plasma concentration

Approximately 36 minutes following a single oral dose of 1 gram. {03} {04} {05}

Duration of action:

About 3 to 5 hours. {05}

Elimination:
    Renal. Approximately 36% of administered dose appears in urine within 24 hours. {03} {04} {05}


Precautions to Consider

Carcinogenicity

Long-term studies have not been done to determine the carcinogenic potential of ethinamate. {03} {04} {05}

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in either animals or humans (FDA Pregnancy Category C). {04} {05}

Breast-feeding

It is not known whether ethinamate is excreted in breast milk. However, problems in humans have not been documented. {04} {05}

Pediatrics

Appropriate studies have not been performed in children up to 15 years of age. {05} Safety and efficacy have not been established.


Geriatrics


Elderly patients may be more sensitive to the effects of ethinamate. Also, elderly patients are more likely to have age-related hepatic function impairment and renal function impairment, which may require reduction of dosage in patients receiving ethinamate.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Addictive medications, other, especially central nervous system (CNS) depressants with habituating potential    (prolonged concurrent use may increase the risk of habituation; caution is recommended)


» Alcohol or
» CNS depression–producing medications, other (See Appendix II )    (concurrent use may increase the CNS depressant effects of either these medications or ethinamate; caution is recommended and dosage of one or both agents should be reduced {04} {05})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Phentolamine test    (ethinamate may cause false-positive phentolamine test; it is recommended that all medications be withdrawn at least 24 hours, preferably 48 to 72 hours, prior to a phentolamine test)


Urinary steroid determinations    (ethinamate may cause falsely high 17-ketosteroid concentrations in the modified Zimmerman reaction and 17-hydroxycorticosteroid concentrations in the Porter-Silber test)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Alcoholism, active or in remission or
Drug abuse or dependence, history of{05}    (predisposition of patient to habituation or dependence)


Mental depression
Pain, uncontrolled
Sensitivity to ethinamate


Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Allergic reaction{04}{05} (skin rash)
    
paradoxical reaction (unusual excitement)—especially in children{04}{05}

Incidence rare
    
Thrombocytopenia{04}{05} (unusual bleeding or bruising)



Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
Indigestion{04}
    
nausea{04}
    
stomach pain{04}
    
vomiting{04}

Incidence rare
    
Drowsiness, daytime{04}



Those indicating possible withdrawal and the need for medical attention if they occur after medication is discontinued
    
Confusion{04}{05}
    
convulsions{04}{05}
    
hallucinations{04}{05}
    
restlessness, nervousness, or irritability{04}{05}
    
trembling{04}{05}
    
trouble in sleeping{04}{05}




Overdose
For specific information on the agents used in the management of ethinamate overdose, see:
   • Charcoal, Activated (Oral-Local) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)–not necessarily inclusive:
Acute
    
Shortness of breath or slow or troubled breathing{04}{05}
    
slow heartbeat{04}{05}
    
weakness, severe{04}{05}

Chronic
    
Confusion{04}
    
slurred speech{04}
    
staggering{04}


Treatment of overdose


To decrease absorption:
Administering activated charcoal to possibly decrease absorption of medication from gastrointestinal tract.

Peritoneal dialysis, hemodialysis, or charcoal hemoperfusion are effective in treating ethinamate overdosage; however, these procedures should be reserved for patients with life-threatening toxicity who do not respond to supportive measures or more conservative treatment.



Monitoring:
Monitoring and maintaining, within acceptable limits, patient's vital signs, blood gases, and serum electrolytes.



Supportive care:
Initiating (promptly) resuscitative measures; establishing airway and ensuring oxygenation and ventilation; protecting patient's airway when using gastric emptying or charcoal.

If patient is hypotensive, administering intravenous fluids or pharmacologic agents or elevating legs, if necessary.

Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.

{04}{05}

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Ethinamate (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to ethinamate





Use in the elderly—Elderly patients may be more sensitive to effects of ethinamate
Other medications, especially alcohol or other CNS depression–producing medications

Proper use of this medication
» Importance of not using more medication than the amount prescribed because of habit-forming potential

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress during prolonged therapy

Checking with physician before discontinuing medication after prolonged use; gradual dosage reduction may be necessary to avoid possibility of withdrawal symptoms

» Avoiding use of alcohol or other CNS depressants

» Suspected overdose: Getting emergency help at once

» Caution if daytime drowsiness occurs


Side/adverse effects
Signs of potential side effects, especially allergic reaction, paradoxical reaction, and thrombocytopenia

Side/adverse effects more likely to occur in elderly patients, who may be more sensitive to effects of ethinamate


General Dosing Information
Prolonged administration is not recommended since ethinamate has not been shown to be effective for a period of more than 7 days. {04} {05}

Prolonged use of larger than usual therapeutic doses may result in psychic or physical dependence. {04} {05}

If prolonged administration is necessary, ethinamate should be withdrawn gradually in order to avoid the possibility of precipitating withdrawal symptoms. {04} {05}

For treatment of dependence
Treatment of physical dependence consists of cautious and gradual withdrawal of ethinamate. Withdrawal may be accomplished by hospitalizing the patient, preferably, and reducing the addictive daily dose at a rate of 500 mg to 1 gram every 2 or 3 days. Psychiatric follow-up may be indicated. {04} {05}


Oral Dosage Forms

ETHINAMATE CAPSULES USP

Usual adult dose
Sedative-hypnotic—Oral, 500 mg to 1 gram twenty minutes before bedtime. {04} {05}

Note: Geriatric or debilitated patients may be more sensitive to the effects of the usual adult dose. The initial daily dose should not exceed 500 mg at bedtime. {04} {05}


Usual pediatric dose
Sedative-hypnotic—Children up to 15 years of age: Safety and efficacy have not been established. {04} {05}

Strength(s) usually available
U.S.—
Not commercially available.

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.



Revised: 10/16/2000



References
  1. USAN 1986.
  1. USP/NF 1985.
  1. Valmid package insert, Rev 5/85, Rec 5/86.
  1. PDR 1988, Valmid, p 912.
  1. Valmid package insert (Dista), Rev 4/28/88, Rec 1/89.
  1. F & C, 12/86, p 272b.
  1. Redbook 1989, p 718.
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