Version May 2024
Procedural sedation: Note: Not routinely used in adults; other agents are preferred for procedural sedation (ASA 2018).
Oral: 500 mg to 1 g once; administer 30 minutes prior to surgery/procedure.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl >50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: Use is contraindicated.
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling.
Severe impairment: Use is contraindicated.
(For additional information see "Chloral hydrate (United States: Not available): Pediatric drug information")
Note: Commercially available product no longer available in the United States.
Sedation, mechanically ventilated patient: Limited data available: Infants, Children, and Adolescents: Oral: Initial: 8 to 25 mg/kg/dose every 6 to 8 hours; titrate to effect based on patient response up to 50 mg/kg/dose every 6 hours; maximum dose: 1,000 mg/dose (Parkinson 1997; manufacturer's labeling). Dosing based on randomized controlled trial of 44 patients (age range: 1 day to 15 years) that compared continuous infusion midazolam (n=20) to promethazine plus chloral hydrate (n=23) at a dose of 25 mg/kg/dose every 6 hours for sedation in ventilated patients. If sedation unsatisfactory, doses could be increased up to 50 mg/kg/dose every 6 hours. The total number of satisfactory sedation assessments was significantly higher in the chloral hydrate/promethazine group (61%) compared to the midazolam group (48%) (Parkinson 1997).
Sedation, procedural (eg, echocardiogram or EEG): Limited data available: Infants and Children (best results in children <3 years of age): Oral: 25 to 100 mg/kg/dose 10 to 30 minutes prior to procedure; maximum dose: 1,000 mg/dose; may repeat after 30 minutes with 25 to 50 mg/kg/dose if necessary. Maximum total dose: 100 mg/kg/procedure or 2,000 mg/procedure (Derakhshani 2022; Heistein 2006; Krauss 2006; Napoli 1996; Wheeler 2001). Note: Although dosing may be used in adolescent patients, use in these patients is not common; older children and adolescent patients may not require sedation for echocardiogram and other agents should be used for EEG.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. Use is contraindicated in patients with marked renal impairment.
Dialysis: Dialyzable.
There are no dosage adjustments provided in the manufacturer's labeling. Use is contraindicated in patients with marked hepatic impairment.
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Postmarketing:
Cardiovascular: Atrial arrhythmia, depression of myocardial contractility, hypotension, shortening of refractory periods, supraventricular tachycardia (infants and children) (Hirsch 1986), torsades de pointes, ventricular arrhythmia
Dermatologic: Allergic skin rash (including bullous dermatitis, eczema, erythema multiforme, erythema of skin, scarlatiniform rash, urticaria)
Endocrine & metabolic: Acute intermittent porphyria, ketonuria
Gastrointestinal: Diarrhea, flatulence, gastric irritation, intestinal obstruction (infants), nausea, unpleasant taste, vomiting
Hematologic & oncologic: Eosinophilia, leukopenia, nonthrombocytopenic purpura
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms (Yoo 2014)
Nervous system: Abnormal gait (staggering), ataxia, confusion, delirium, dizziness, drowsiness, drug dependence, excitement, hallucinations, hangover effect, malaise, nightmares, seizure (Muñoz 1997), somnambulism, vertigo
Ophthalmic: Allergic conjunctivitis, blepharoptosis, keratoconjunctivitis
Otic: Increased middle ear pressure (infants and children)
Respiratory: Airway obstruction (young children), laryngeal edema (children)
Miscellaneous: Drug tolerance, paradoxical reaction (Slatt 2009)
Hypersensitivity to chloral hydrate or any component of the formulation; marked hepatic or renal impairment
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).
Disease-related concerns:
• Cardiac disease: Avoid use in patients with severe cardiac disease; larger doses may precipitate arrhythmias and hypotension (Fazio 2013).
• Gastrointestinal disorders: Because of irritant properties, avoid use in patients with gastritis, esophagitis, or gastric/duodenal ulcer (Joffe 2017).
• Porphyria: Although manufacturer labeling suggests choral hydrate may precipitate attacks of acute intermittent porphyria and to use with caution, chloral hydrate is considered to be safe based on evidence and expert consensus (Porphyria Foundation) (Crimlisk 1997; Gorchein 1997; Jensen 1995; Porphyria Foundation 2023).
• Respiratory disease: Closely monitor patients with respiratory insufficiency.
Special populations:
• Children: Life-threatening respiratory obstruction and deaths have been reported with use in children; use with extreme caution.
• Older adult: Excessive sedation or other adverse effects may be more likely to occur in elderly patients; avoid use in older adults.
• 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.
Other warnings/precautions:
• Abuse/misuse/diversion: May be habit forming; long-term use or larger than therapeutic doses may result in tolerance and in physical and/or psychological dependance. Use with caution in patients with a history of substance abuse disorder, mentally depressed, or suicidal. Sudden withdrawal may result in hallucinations and symptoms similar to delirium tremens (sometimes fatal); taper chloral hydrate gradually.
Deaths and permanent neurologic injury from respiratory compromise have been reported in children sedated with chloral hydrate; respiratory obstruction may occur in children with tonsillar and adenoidal hypertrophy, obstructive sleep apnea, and Leigh encephalopathy, and in ASA class III children; depressed levels of consciousness may occur; chloral hydrate should not be administered for sedation by nonmedical personnel or in a nonsupervised medical environment; sedation with chloral hydrate requires careful patient monitoring (Coté 2000). Animal studies suggest that chloral hydrate may depress the genioglossus muscle and other airway-maintaining muscles in patients who are already at risk for life-threatening airway obstruction (eg, obstructive sleep apnea); alternative sedative agents should be considered for these patients (Hershenson 1984).
Not available in the US
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Generic: 500 mg [DSC]
Syrup, Oral:
Generic: 500 mg/5 mL (500 mL)
Oral: May dilute syrup in water or other oral liquid (eg, fruit juice, ginger ale) to minimize gastric irritation; administer 30 minutes prior to surgery/procedure.
Oral: Minimize unpleasant taste and gastric irritation by administering with water, infant formula, fruit juice, or ginger ale.
Note: Not approved in the United States.
Procedural sedation: Sedative/hypnotic for surgery and diagnostic procedures.
Note: The manufacturer labeling includes indications for short-term treatment of insomnia; however, chloral hydrate is no longer recommended to be used this way (Schutte-Rodin 2008).
The Institute for Safe Medication Practices (ISMP) includes this medication (for sedation of children) among its list of drugs which 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.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
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
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
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
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 at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
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
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Furosemide: May enhance the adverse/toxic effect of Chloral Hydrate. Risk X: Avoid combination
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
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
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
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
Melatonin: May enhance the sedative effect of Hypnotics (Nonbenzodiazepine). Risk C: 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 the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
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
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
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
Oxybate Salt Products: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Oxybate Salt Products. Risk X: Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
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
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. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Chloral Hydrate may increase the serum concentration of Vitamin K Antagonists. Risk C: 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. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Animal reproduction studies have not been conducted. Chloral hydrate crosses the placenta, and long-term use may lead to withdrawal symptoms in the neonate.
Chloral hydrate is excreted in breast milk; use by breast-feeding women may cause sedation in the infant.
Vital signs, O2 saturation/respiratory function, BP, level of sedation, resedation (may persist up to 24 hours) (Grissinger 2019).
Central nervous system depressant effects are due to its active metabolite trichloroethanol, mechanism unknown
Onset of action: 15 to 30 minutes (Krauss 2006)
Duration: 1 to 2 hours (Krauss 2006)
Absorption: Oral: Well absorbed
Protein binding: Trichloroethanol: 35% to 40%; trichloroacetic acid: ∼94% (may compete with bilirubin for albumin binding sites)
Metabolism: Rapidly metabolized in the liver by alcohol dehydrogenase to trichloroethanol (active metabolite); trichloroethanol undergoes glucuronidation in the liver; variable amounts hepatically and renally to trichloroacetic acid (inactive)
Half-life elimination:
Chloral hydrate (Mayer 1991):
Preterm infants (postmenstrual age [PMA] 31 to 37 weeks): 1.01 ± 0.97 hours
Term infants (PMA 38 to 42 weeks): 3.01 ± 5.81 hours
Children and Adolescents <14 years: 9.68 ± 7.73 hours
Active metabolite (trichloroethanol) (Mayers 1991):
Preterm infants (PMA 31 to 37 weeks): 39.82 ± 14.27 hours
Term infants (PMA 38 to 42 weeks): 27.8 ± 21.32 hours
Children and Adolescents <14 years: 9.67 ± 1.72 hours
Adults: 8 to 12 hours (Fuhrman 2011)
Trichloroacetic acid: Adults: 67 hours (Furhman 2011)
Excretion: Urine (as metabolites); feces (small amounts)
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