Pill Identifier App

Paraldehyde (Systemic)


VA CLASSIFICATION
Primary: CN400

Note: Controlled substance classification—

Note: Controlled substance classification


U.S.—Schedule IV
Commonly used brand name(s): Paral.

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



Category:


Anticonvulsant—

Indications

Accepted

Convulsions (treatment) or
Status epilepticus (treatment)—Parenteral paraldehyde may be indicated in the emergency treatment of status epilepticus and of convulsions induced by tetanus or eclampsia, when other agents are not effective {04} {05}. Oral paraldehyde may be used in the management of convulsions induced by tetanus when other agents are not effective.

Unaccepted
Paraldehyde has been used as a sedative-hypnotic; however, it generally has been replaced by safer and/or more effective agents for the following indications


Insomnia


Sedation


Delirium tremens and other psychiatric states characterized by excitement, to quiet the patient and produce sleep (generally replaced by benzodiazepines such as chlordiazepoxide and diazepam) {05}


Convulsions caused by convulsant drug toxicity {09}


Parenterally for intractable pain not responsive to other types of therapy (e.g., in an occasional patient with acute coronary thrombosis who fails to obtain relief from repeated injections of morphine sulfate)


Intramuscularly to induce artificial sleep and thereby to facilitate electroencephalographic study, especially in children {05}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    132.16

Mechanism of action/Effect:

The precise mechanism of action of paraldehyde is unknown. It may depress many levels of the central nervous system (CNS) including the ascending reticular activating system to produce imbalances between facilitatory and inhibitory mechanisms.

Absorption:

Rapidly absorbed from the gastrointestinal tract and from intramuscular injection sites {03} {05}.

Biotransformation:

Hepatic. Approximately 70 to 90% of a dose of paraldehyde is metabolized {05}.

Half-life:

Biological—3.4 to 9.8 hours {03} {05}.

Onset of action:

Hypnotic—Within 15 minutes {05}.

Time to peak serum concentration

Oral—30 to 60 minutes {05}.

Rectal—About 2.5 hours {05}.

Duration of action:

Hypnotic—About 8 to 12 hours {05}.

Elimination:
    Unmetabolized paraldehyde (11 to 28%) is excreted via exhalation. Trace amounts are excreted in the urine {05}.


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Paraldehyde crosses the placenta {03} {05}. Studies have not been done in humans {03} {05}.

Studies have not been done in animals {03} {05}.

FDA Pregnancy Category C {03} {05}.

Labor—

Use of paraldehyde during labor may cause respiratory depression in the neonate {05}.

Breast-feeding

Problems in humans have not been documented {05}.

Pediatrics

Appropriate studies on the relationship of age to the effects of paraldehyde have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date.


Geriatrics


No information is available on the relationship of age to the effects of paraldehyde in geriatric patients.

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 paraldehyde; caution is recommended and dosage of one or both agents should be reduced {05})


» Disulfiram    (concurrent use with paraldehyde is not recommended because disulfiram may decrease the metabolism of paraldehyde by inhibition of acetaldehyde dehydrogenase, resulting in increased blood concentrations of paraldehyde and acetaldehyde {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 diagnostic test results
Metyrapone test    (paraldehyde may interfere with the assay for urine 17-ketosteroids or 17-ketogenic steroids)


Phentolamine test    (paraldehyde 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 17-hydroxycorticosteroid determinations    (may be interfered with when a modification of the Reddy, Jenkins, and Thorn procedure is used)


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    (predisposition of patient to habituation and dependence)


» Bronchopulmonary disease    (paraldehyde excreted via lungs {05})


» Hepatic function impairment    (paraldehyde metabolized in liver; patients may be more susceptible to effects of paraldehyde {05})


Sensitivity to paraldehyde
With oral use {05}:
Gastroenteritis or
» Peptic ulcer    (condition may be exacerbated)


With rectal use {05}:
Colitis    (condition may be exacerbated)




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 more frequent
    
Effects on pulmonary capillaries (coughing)—with intravenous administration only{05}
    
skin rash{05}

Incidence less frequent
    
Thrombophlebitis (redness, swelling, or pain at injection site){05}

With prolonged use
    
Hepatitis (yellow eyes or skin){05}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Drowsiness
    
unpleasant breath odor
    
nausea or vomiting —with oral use
    
stomach pain —with oral use

Incidence less frequent
    
Clumsiness or unsteadiness
    
dizziness
    
``hangover'' effect



Those indicating possible withdrawal and the need for medical attention if they occur after medication is discontinued
    
Convulsions
    
hallucinations
    
increased sweating
    
muscle cramps
    
nausea or vomiting
    
stomach cramps
    
trembling




Overdose
For specific information on the agents used in the management of paraldehyde overdose, see:
   • Mineral Oil in Laxatives (Local) monograph; and/or
   • Sodium Bicarbonate (Systemic) 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:
    
Cloudy urine{05}
    
decreased urination{05}
    
fast and deep breathing{05}
    
metabolic acidosis{05} (confusion; muscle tremors; continuing or severe nausea or vomiting; nervousness; restlessness; irritability; severe stomach cramps)
    
shortness of breath or slow or troubled breathing{05}
    
slow heartbeat{05}
    
weakness, severe{05}


Treatment of overdose
Recommended treatment for paraldehyde overdose includes the following {05}:


To decrease absorption:
For oral overdose, performing gastric lavage (provided an endotracheal tube with cuff inflated is in place to prevent aspiration of vomitus), followed by administering a demulcent (e.g., mineral oil) to relieve gastric irritation.

For rectal overdose, performing rectal lavage.



Specific treatment:
Correcting metabolic acidosis, if necessary, by intravenous administration of sodium bicarbonate or sodium lactate.



Supportive care:
Re-establishing adequate respiratory exchange by maintaining an adequate airway, controlling respiration, and administering oxygen.

Maintaining body temperature.

Supporting circulation.

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



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

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

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

Pregnancy—Paraldehyde crosses placenta

Labor—Use of paraldehyde during labor may cause respiratory depression in neonate
Other medications, especially alcohol or other CNS depression–producing medications or disulfiram
Other medical problems, especially bronchopulmonary disease, hepatic function impairment, or peptic ulcer (with oral use only)

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

» Not using medication if it is brownish in color or has a strong vinegar-like odor

Avoiding contact with eyes, skin, and clothing

Keeping away from heat, open flame, and sparks

» Not using plastic containers for administration of this medication

» Proper dosing
Missed dose: If on scheduled dosing regimen—Taking right away if remembered within an hour or so; not taking if remembered later; not doubling doses

» Proper storage

For oral use
» Taking liquid diluted in milk or iced fruit juice to mask odor and taste and to minimize gastric irritation

For rectal use
Proper administration: Paraldehyde may need diluting before using

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

Caution if any laboratory tests required; possible interference with metyrapone or phentolamine test results

» Suspected overdose: Getting emergency help at once

» Caution if drowsiness occurs


Side/adverse effects
Signs of potential side effects, especially effects on pulmonary capillaries (with intravenous use only), skin rash, thrombophlebitis (with injection only), and, with prolonged use, hepatitis

Strong unpleasant breath odor may be alarming to patient although medically insignificant


General Dosing Information
Do not use plastic containers or plastic syringes or tubing for administration since paraldehyde is incompatible with many plastics.

Prolonged use of larger than usual therapeutic doses may result in tolerance and psychic or physical dependence.

Following prolonged administration, paraldehyde should be withdrawn gradually in order to avoid the possibility of precipitating withdrawal symptoms.

For oral use only
When paraldehyde is administered orally, it should be well diluted in milk or iced fruit juice to mask the odor and taste and to minimize gastric irritation {05}.

For parenteral use only
Intramuscular injection is the preferred route of administration. The paraldehyde injection should be administered deeply into the gluteus maximus muscle, care being taken to avoid nerve trunks because paraldehyde may cause nerve injury and paralysis. No more than 5 mL should be administered at each injection site. {05}

Paraldehyde should not be administered subcutaneously because it is irritating to tissue {05}.

Intravenous administration is not recommended except in emergencies, since it may produce circulatory collapse or pulmonary edema {05}.

If administered intravenously, paraldehyde should be diluted with several volumes of 0.9% sodium chloride injection and injected slowly at a rate not to exceed 1 mL per minute.

For rectal use only
For rectal administration, paraldehyde should be diluted with 1 or 2 parts of olive oil, cottonseed oil, or 0.9% sodium chloride solution to prevent rectal irritation {05}.


Oral/Rectal Dosage Forms

PARALDEHYDE USP

Usual adult dose
Anticonvulsant
Oral, up to 12 mL (diluted to a 10% solution) via gastric tube every four hours as needed {07}.

Rectal, 10 to 20 mL {07}.


Usual pediatric dose
Anticonvulsant
Oral, 0.3 mL per kg of body weight or 12 mL per square meter of body surface {06}.

Rectal, 0.3 mL per kg of body weight or 12 mL per square meter of body surface {06}.


Size(s) usually available:
U.S.—


30 mL (Rx) [Paral][Generic]

Canada—
Not commercially available.

Note: In Canada, the sterile paraldehyde dosage form can be used whenever oral or rectal paraldehyde is prescribed.


Packaging and storage:
Store below 25 °C (77 °F), in a tight, light-resistant container holding not more than 30 mL. Paraldehyde solidifies at approximately 12 °C (54 °F) and must be liquefied before use. Keep paraldehyde away from heat, open flame, or sparks. Store in glass containers since paraldehyde is incompatible with many plastics.

Preparation of dosage form:
For rectal administration, dilute paraldehyde with 1 or 2 parts of olive oil, cottonseed oil, or 0.9% sodium chloride solution {05}.

Stability:
When exposed to light and air, paraldehyde decomposes to form acetaldehyde, which is oxidized to acetic acid. If liquid turns brownish in color and has a sharp penetrating odor of acetic acid, it should not be used. The unused contents of any container that has been opened for more than 24 hours should be discarded. {05}

Incompatibilities:
Paraldehyde is incompatible with most plastics; therefore, plastic containers should not be used for administration of the medication {03} {05}.

Auxiliary labeling:
   • Avoid alcoholic beverages.
   • May cause drowsiness.
   • Discard any unused liquid if container has been opened for more than 24 hours.

Note: Controlled substance in the U.S.




Parenteral Dosage Forms

PARALDEHYDE STERILE USP

Usual adult dose
Anticonvulsant
Intramuscular, 5 to 10 mL {05} {07}.

Intravenous infusion, 5 mL diluted with at least 100 mL of 0.9% sodium chloride injection and administered slowly at a rate not exceeding 1 mL per minute {03} {05}.


Usual pediatric dose
Anticonvulsant
Intramuscular, 0.15 mL per kg of body weight or 6 mL per square meter of body surface {05} {07} {08}.

Intravenous, 0.1 to 0.15 mL per kg of body weight diluted with 0.9% sodium chloride injection and administered slowly {07} {08}.


Size(s) usually available:
U.S.—
Not commercially available.

Canada—


5 mL (Rx)[Generic]

Packaging and storage:
Store below 25 °C (77 °F), in a light-resistant container. Paraldehyde solidifies at approximately 12 °C (54 °F) and must be liquefied before use. Keep paraldehyde away from heat, open flame, and sparks.

Preparation of dosage form:
For intravenous administration, paraldehyde should be diluted with several volumes of 0.9% sodium chloride injection.

Stability:
When exposed to light and air, paraldehyde decomposes to form acetaldehyde, which is oxidized to acetic acid. If injection turns brownish in color and has a sharp penetrating odor of acetic acid, it should not be used. Any unused portion of the injection should be discarded.

Incompatibilities:
Paraldehyde is incompatible with most plastics; therefore, a glass syringe should be used for administration of the medication {03}.

Auxiliary labeling:
   • For single dose only. Discard unused portion.



Revised: 03/19/1993



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

  1. USAN 1986.
  1. USP/NF 1985.
  1. Facts & Comparisons: 12/83, 2/85, 10/85.
  1. AMA-DE 6th ed, p 193.
  1. Facts & Comparisons, 12/86: 270, 285f.
  1. Ped Dosage Handbk, 1980: 209.
  1. American Hospital Formulary Service 1988: 1269.
  1. Ped Drug Therapy, pp 614-5.
  1. Clinical Toxicology/Substance Abuse Advisory Panel Meeting, 5/18/91.
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