(KLOR al HYE drate)
- Hydrated Chloral
- Trichloroacetaldehyde Monohydrate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Somnote: 500 mg [DSC]
Generic: 500 mg/5 mL (5 mL [DSC], 473 mL [DSC])
Brand Names: U.S.
- Somnote [DSC]
- Hypnotic, Miscellaneous
Central nervous system depressant effects are due to its active metabolite trichloroethanol, mechanism unknown
Oral: Well absorbed
Rapidly hepatic metabolized by alcohol dehydrogenase to trichloroethanol (active metabolite); trichloroethanol undergoes glucuronidation in the liver; variable amounts hepatically and renally to trichloroacetic acid (inactive)
Urine (as metabolites); feces (small amounts)
Onset of Action
10-20 minutes; Maximum effect (time to sleep): 0.5-1 hour
Duration of Action
Chloral hydrate: Infants: 1 hour
Active metabolite (trichloroethanol):
Neonates: Range: 8.5-66 hours
Half-life decreases with increasing postmenstrual age (PMA):
Preterm infants (PMA 31-37 weeks): Mean half-life: 40 hours
Term infants (PMA 38-42 weeks): Mean half-life: 28 hours
Older children (PMA 57-708 weeks): Mean half-life: 10 hours
Adults: 8-10 hours
Trichloroacetic acid: Adults: 67.2 hours
Trichloroethanol: 35% to 40%; trichloroacetic acid: ∼94% (may compete with bilirubin for albumin binding sites)
Use: Labeled Indications
Note: Not approved in the US
Pain control: Adjunct to opiates and analgesics for postoperative pain control
Sedation: Short-term sedative and hypnotic (<2 weeks); sedative/hypnotic for diagnostic procedures; sedative prior to EEG evaluations
Withdrawal: Monotherapy or concomitant with paraldehyde for prevention of alcohol withdrawal symptoms and/or to suppress syndrome once it develops; reduction of anxiety associated with withdrawal of opiates or barbiturates
Hypersensitivity to chloral hydrate or any component of the formulation; marked hepatic or renal impairment
Hypnotic: 50 mg/kg/day in 1 or more divided doses; maximum single dose: 1000 mg
Sedation or anxiety: 25 mg/kg/day in 1 or more divided doses; maximum single dose: 500 mg
Procedural sedation: 25-50 mg/kg/dose 30 minutes prior to procedure; may repeat in 30 minutes using half the dose
Sedation, anxiety: 250 mg 3 times daily
Hypnotic: 500-1000 mg 15-30 minutes before bedtime or 30 minutes prior to procedure, not to exceed 2000 mg per 24 hours
Elderly: Oral: Hypnotic: Usual dose: 250 mg 15-30 minutes before bedtime
Dosage adjustment/comments in renal impairment: Contraindicated in patients with marked renal impairment.
Dosage adjustment/comments in hepatic impairment: Contraindicated in patients with marked hepatic impairment.
May dilute syrup in water or other oral liquid (eg, fruit juice or ginger ale) to minimize gastric irritation. Administer capsules after meals (when used as sedative).
Store syrup and capsules at controlled room temperature. Store syrup in a light-resistant, airtight container; protect from freezing.
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
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. Exceptions: Levocabastine (Nasal). 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
Flumazenil: May diminish the sedative effect of Hypnotics (Nonbenzodiazepine). Monitor therapy
Furosemide: May enhance the adverse/toxic effect of Chloral Hydrate. Avoid combination
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. 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
Mifepristone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification
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
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. 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
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
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: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Sodium Oxybate. Avoid combination
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
Vitamin K Antagonists (eg, warfarin): Chloral Hydrate may increase the serum concentration of Vitamin K Antagonists. 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
May interfere with copper sulfate tests for glycosuria or with fluorometric urine catecholamine and urinary 17-hydroxycorticosteroid tests.
Frequency not defined.
Cardiovascular: Atrial arrhythmia, depression of myocardial contractility, hypotension, shortening of refractory periods, torsades de pointes, ventricular arrhythmia
Central nervous system: Abnormal gait, ataxia, confusion, delirium, dizziness, drowsiness, drug dependence (physical and psychological; with prolonged use or large doses), hallucinations, hangover effect, malaise, nightmares, paradoxical excitation, somnambulism, vertigo
Dermatologic: Skin rash (including erythema, eczematoid dermatitis, urticaria, scarlatiniform exanthems)
Endocrine & metabolic: Acute porphyria, ketonuria
Gastrointestinal: Diarrhea, flatulence, gastric irritation, nausea, vomiting
Hematologic & oncologic: Acute porphyria, eosinophilia, leukopenia
Ophthalmic: Allergic conjunctivitis, blepharoptosis, keratoconjunctivitis
Otic: Increased middle ear pressure (infants and children)
Respiratory: Airway obstruction (young children), laryngeal edema (children)
Miscellaneous: Drug tolerance
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 that require mental alertness (eg, operating machinery or driving).
• Cardiac disease: Avoid use in patients with severe cardiac disease; larger doses may precipitate arrhythmias and hypotension.
• Gastrointestinal disorders: Because of irritant properties, avoid use in patients with gastritis, esophagitis, or gastric/duodenal ulcer.
• Porphyria: Use with caution in patients with porphyria.
• Respiratory disease: Closely monitor patients with respiratory insufficiency.
Concurrent drug therapy issues:
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
• Children: Life-threatening respiratory obstruction and deaths have been reported with use in children; use with extreme caution.
• Elderly: Excessive sedation or other adverse effects may be more likely to occur in elderly patients; dose reduction may be necessary.
• Neonates: Use with caution in neonates; prolonged use in neonates is associated with direct hyperbilirubinemia (active metabolite [TCE] competes with bilirubin for glucuronide conjugation in the liver).
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.
• Abuse/Misuse: Health care provider should be alert to problems of abuse and misuse. Patients should be assessed for risk of abuse or addiction prior to therapy and all patients should be monitored for signs of abuse or misuse.
• Duration of therapy: Tolerance to hypnotic effect develops, therefore, not recommended for use >2 weeks.
• Withdrawal: Abrupt discontinuance may lead to withdrawal symptoms.
Vital signs, O2 saturation and blood pressure with doses used for conscious sedation
Animal reproduction studies have not been conducted. Chloral hydrate crosses the placenta, and long-term use may lead to withdrawal symptoms in the neonate.
More about chloral hydrate
- Other brands: Somnote