Version May 2024
Canadian labeling: Second- or third-line therapy: Note: Do not administer >5 mL per injection site.
Alcohol withdrawal: IM: 5 mL every 4-6 hours for 24 hours (maximum: 30 mL on day 1), followed by every 6 hours (maximum: 20 mL/day).
Hypnotic: IM: 10 mL.
Sedative: IM: 5 mL.
Seizure associated with status epilepticus, tetanus, or poisoning: IM: 5-10 mL.
No dosage adjustment provided in manufacturer's labeling.
Mild-to-moderate impairment: No dosage adjustment provided in manufacturer's labeling; however, undergoes extensive hepatic metabolism and should be used with extreme caution. Consider dose reductions.
Severe impairment: Use contraindicated.
Canadian labeling: Second- or third-line therapy: Note: Do not administer >5 mL per injection site.
Hypnotic: IM: 0.3 mL/kg/daily.
Sedative: IM: 0.15 mL/kg/daily.
Seizure associated with status epilepticus: IM: 0.1 to 0.15 mL/kg/dose every 4 to 8 hours.
There are no dosage adjustments provided in the manufacturer's labeling.
Mild-to-moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, undergoes extensive hepatic metabolism and should be used with extreme caution. Consider dose reductions.
Severe impairment: Use contraindicated.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined.
Central nervous system: Dizziness, drowsiness, drug dependence (psychological and physical dependence with prolonged use)
Dermatologic: Diaphoresis, skin rash
Endocrine & metabolic: Metabolic acidosis
Gastrointestinal: Halitosis
Genitourinary: Nephrosis
Hepatic: Toxic hepatitis
Local: Injection site reaction (exfoliation of skin, fat necrosis, muscle irritation, nerve damage [including permanent damage], sterile abscess), pain at injection site
Neuromuscular & skeletal: Muscle cramps, tremor
Hypersensitivity to paraldehyde or any component of the formulation; severe hepatic insufficiency; bronchopulmonary disease; pregnancy
Concerns related to adverse effects:
• 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).
• Hepatic effects: Toxic hepatitis has been reported following prolonged use.
• Metabolic acidosis: Has been reported following prolonged use.
• Renal effects: Nephrosis has been reported following prolonged use.
Disease-related concerns:
• Cardiovascular disease: Avoid or use with caution in patients with cardiovascular disease.
• 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 extreme caution and monitor closely for toxicity; large portions of the dose are metabolized via the liver; use is contraindicated in severe hepatic impairment.
• Respiratory disease: The lungs are responsible for a significant portion of elimination of unchanged paraldehyde. Avoid or use caution in patients with respiratory disease; use is contraindicated in patients with bronchopulmonary disease.
Concurrent drug therapy issues:
• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.
Other warnings/precautions:
• Administration: Per Canadian manufacturer's labeling, product is intended for IM administration only; avoid injecting IM near nerve trunks due to potential for severe and permanent nerve damage. IM administration is associated with severe pain and may also cause skin reactions (eg, sterile skin abscesses, skin sloughing), fat necrosis, and muscle irritation. Subcutaneous injections are not recommended; paraldehyde is a tissue irritant. In addition, do not inject intravenously due to potential for thrombophlebitis, pulmonary edema and hemorrhage, respiratory distress, cyanosis, hypotension and cardiac dilatation, and circulatory collapse.
• Appropriate use: Not appropriate as a first-line agent for any indication. Limited published information exists for paraldehyde use compared to more conventional agents with more published safety and efficacy data. If used as a hypnotic/sedative agent, therapy should be limited to short-term use.
• Decomposition: Paraldehyde decomposes when opened; prepare using only freshly opened vials. Use of partly decomposed paraldehyde is hazardous and may result in metabolic acidosis; use of decomposed paraldehyde has resulted in death from corrosive poisoning. If solution is a brownish color or smells of acetic acid, it should not be used.
• Irritant/solvent: Avoid contact with skin, eyes, and clothing. Since paraldehyde is a solvent, contact with plastic (eg, plastic syringes) or rubber should be avoided.
• Withdrawal: Use caution when withdrawing therapy after prolonged use in physically dependent patients; decrease slowly and monitor for withdrawal symptoms.
Not available in the US
Yes
IM: Administer by IM injection only; avoid injecting near nerve trunks (permanent nerve damage may occur). IM injection is associated with extreme pain and serious injection site reactions.
Do not administer intravenously (life-threatening effects may result) or SubQ.
Do not use any use plastic syringes or rubber for administration; glass syringes are recommended for administration.
Do not use if solution is brownish or has an odor of acetic acid. Use immediately after opening vial (paraldehyde decomposes to acetic acid causing toxicity).
IM:
Administer by IM injection only; not for IV (life-threatening effects may result) or SubQ (irritating to tissues) administration. Administer undiluted by deep IM injection into the buttocks; avoid injecting near nerve trunks (permanent nerve damage may occur). Do not administer more than 5 mL per injection site. Do not use if solution is brownish or has an odor of acetic acid. Use immediately after opening vial (paraldehyde decomposes to acetic acid causing toxicity).
Do not use any use plastic syringes or rubber for administration; glass syringes are recommended for administration.
Avoid contact with skin, eyes, and clothing.
Hazardous agent; use appropriate precautions for handling and disposal (EPA, U-listed).
Note: Not approved in the United States.
Alternative agent (only when conventional treatment is ineffective, inappropriate, or unavailable) in the treatment of convulsive seizure episodes associated with status epilepticus, tetanus, and convulsant drug toxicity. Historically, has also been used as a sedative/hypnotic, as an anxiolytic during withdrawal from opioids or barbiturates, and in the management of acute agitation or delirium due to alcohol withdrawal; however, these uses are not recommended due to the availability of safer and more efficacious agents.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Disulfiram: May increase the serum concentration of Paraldehyde. Risk X: Avoid combination
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Pregnancy should be excluded prior to initiating in females of childbearing potential.
Paraldehyde crosses the placenta; use in pregnancy is contraindicated. Use in obstetric anesthesia is not appropriate due to potential respiratory depression in neonates.
Due to the potential for serious adverse reactions in the nursing infant, breastfeeding is not recommended.
Paraldehyde, a cyclic trimer of acetaldehyde, has an unknown mechanism of action; causes CNS depression, including the ascending reticular activating system to provide sedation/hypnosis and antiseizure activity (at slightly lower doses than those required to produce hypnosis). It has no analgesic properties at sub-anesthetic doses and may cause excitement or delirium in the presence of pain.
Onset of sedation/hypnosis: IM: 5-15 minutes
Duration: 8 hours
Absorption: IM: Rapid
Distribution: Tissue distribution not extensively studied; diffuses into CSF with concentrations in CSF ~25% to 30% lower than that of serum concentrations
Metabolism: ~80% to 90% of the dose metabolized in the liver to acetaldehyde, then oxidized via aldehyde dehydrogenase to acetic acid, and further metabolized to carbon dioxide and water
Half-life elimination: Adults: ~3.5-9.5 hours (mean: 7.5 hours [in patients with normal hepatic function])
Time to peak: IM: Serum: 20-60 minutes; CSF: 30-60 minutes
Excretion: Significant portion excreted as unchanged drug in expired air via the lungs; trace amounts excreted in urine unchanged
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