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Chloral Hydrate

Pronunciation

Pronunciation

(KLOR al HYE drate)

Index Terms

  • Chloral
  • Hydrated Chloral
  • Trichloroacetaldehyde Monohydrate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Somnote: 500 mg [DSC]

Syrup, Oral:

Generic: 500 mg/5 mL (5 mL [DSC], 473 mL [DSC])

Brand Names: U.S.

  • Somnote [DSC]

Pharmacologic Category

  • Hypnotic, Miscellaneous

Pharmacology

Central nervous system depressant effects are due to its active metabolite trichloroethanol, mechanism unknown

Absorption

Oral: Well absorbed

Metabolism

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)

Excretion

Urine (as metabolites); feces (small amounts)

Onset of Action

10-20 minutes; Maximum effect (time to sleep): 0.5-1 hour

Duration of Action

4-8 hours

Half-Life Elimination

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

Protein Binding

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

Contraindications

Hypersensitivity to chloral hydrate or any component of the formulation; marked hepatic or renal impairment

Dosing: Adult

Sedation, anxiety: Oral: 250 mg 3 times daily

Hypnotic: Oral: 500-1000 mg 15-30 minutes before bedtime or 30 minutes prior to procedure, not to exceed 2000 mg per 24 hours

Dosing: Geriatric

Hypnotic: Oral: Usual dose: 250 mg 15-30 minutes before bedtime

Dosing: Pediatric

Hypnotic: Oral: 50 mg/kg/day in 1 or more divided doses; maximum single dose: 1000 mg

Sedation or anxiety: Oral: 25 mg/kg/day in 1 or more divided doses; maximum single dose: 500 mg

Procedural sedation: Oral: 25-50 mg/kg/dose, 30 minutes prior to procedure; may repeat in 30 minutes using half the dose

Dosing: Renal Impairment

Contraindicated in patients with marked renal impairment.

Dialysis: Dialyzable (50% to 100%)

Dosing: Hepatic Impairment

Contraindicated in patients with marked hepatic impairment.

Administration

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).

Storage

Store syrup and capsules at controlled room temperature. Store syrup in a light-resistant, airtight container; protect from freezing.

Drug Interactions

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

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

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. Monitor therapy

Dimethindene: May enhance the CNS depressant effect of CNS Depressants. 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

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

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

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification

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

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Test Interactions

May interfere with copper sulfate tests for glycosuria or with fluorometric urine catecholamine and urinary 17-hydroxycorticosteroid tests.

Adverse Reactions

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

Warnings/Precautions

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.

• 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.

Special populations:

• 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.

Other warnings/precautions:

• 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.

Monitoring Parameters

Vital signs, O2 saturation and blood pressure with doses used for conscious sedation

Pregnancy Considerations

Animal reproduction studies have not been conducted. Chloral hydrate crosses the placenta, and long-term use may lead to withdrawal symptoms in the neonate.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, fatigue next day, nausea, vomiting, or diarrhea. Have patient report immediately to prescriber urinary retention; change in amount of urine passed; severe abdominal pain; change in balance; confusion; or driving, eating, or having intercourse and not being fully awake or remember (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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