Brand names: AquachloralSuprettes, Somnote
Drug class: Anxiolytics, Sedatives, and Hypnotics; Miscellaneous
VA class: CN309
CAS number: 302-17-0

Introduction

Sedative and hypnotic.^{100 101 103 106}

Uses for Chloral Hydrate

Hypnotic

Short term treatment of insomnia for <2 weeks; effective for inducing and maintaining sleep.^{100 101 103}

Sedation

Used for routine sedation.^{100 101 106}

Used preoperatively to relieve anxiety and to provide sedation^{100 101} without depressed respiration or cough reflex.¹⁰³

Also used to produce sleep prior to non-painful procedures (e.g., EEG, diagnostic imaging)^{104 105} to relieve anxiety and to provide sedation.^{100 101 103}

Has been used for conscious sedation† to relieve anxiety in young pediatric patients (usually <3 years of age) during procedures (e.g., diagnostic imaging).^{104 105 106}

Used often in geriatric and pediatric patients, because many clinicians suggest that the drug is associated with paradoxical excitement less frequently than barbiturates; however, no well controlled studies confirmed this clinical impression.^{100 101}

Postoperative Analgesia

Adjunct to opiates and analgesics for control of postoperative pain.¹⁰³

Withdrawal

Reduction of anxiety associated with withdrawal of opiates or barbiturates.^{100 101 103}

Used alone or in conjunction with paraldehyde for prevention of alcohol withdrawal symptoms and/or suppression of the syndrome once it develops.^{100 101}

Related/similar drugs

Quviviq, trazodone, hydroxyzine, lorazepam, promethazine, zolpidem, diphenhydramine

Chloral Hydrate Dosage and Administration

Administration

Administer orally^{100 101} or rectally.¹⁰³

Withdraw chloral hydrate slowly after chronic administration to avoid possibility of precipitating withdrawal symptoms.^{101 c} (See Withdrawal under Warnings and Precautions.)

Oral Administration

Administer capsules with a full glass of water or liquid after meals;¹⁰¹ dilute oral solution in 1/2 a glass of water or other liquid (e.g., fruit juice, ginger ale).^{100 101}

Rectal Administration

Moisten finger and suppository with water before inserting suppository.¹⁰³

Suppositories have been dissolved in cottonseed or olive oil and administered as a retention enema.^c

Dosage

Pediatric Patients

Hypnotic

Oral

50 mg/kg or 1.5 g/m² up to a maximum single dose of 1 g.^{100 101}

Rectal

18 mg/kg (325 mg/18 kg) once daily before bedtime.¹⁰³

Sedation

Routine Sedation

Oral

8 mg/kg or 250 mg/m² 3 times daily, up to a maximum of 500 mg 3 times daily.^{100 101}

Some experts recommend a dosage of 25–50 mg/kg per 24 hours, (given in 3 or 4 doses; every 8 or 6 hours, respectively), up to 500 mg per dose.¹⁰⁶

Rectal

9 mg/kg (325 mg/36 kg), do not exceed 1 dose in 24 hours.¹⁰³

Some experts recommend a dosage of 25–50 mg/kg per 24 hours, (given in 3 or 4 doses; every 8 or 6 hours, respectively), up to 500 mg per dose.¹⁰⁶

Preoperative Sedation

Oral

8 mg/kg or 250 mg/m² 3 times daily, up to a maximum of 500 mg 3 times daily.^{100 101}

Rectal

9 mg/kg (325 mg/36 kg); do not exceed 1 dose in 24 hours.¹⁰³

Procedural Sedation

Oral

20–25 mg/kg before procedure.^{100 101}

Some experts recommend a 25- to 100-mg/kg dose before procedure; do not exceed a 1-g dose in infants or a 2-g dose in children.^{105 106}

Rectal

Some experts recommend a 25- to 100-mg/kg dose before procedure; do not exceed a 1-g dose in infants or a 2-g dose in children.¹⁰⁶

Conscious Sedation†

Oral

Neonates: have been given 25–100 mg/kg once.¹⁰⁴

Pediatric patients <3 years of age (excluding neonates): were given a dose of 25–100 mg/kg and a second dose of 25–50 mg/kg may be administered after 30 minutes; maximum total dosage has been 2 g or 100 mg/kg (whichever was lower).^{104 105}

Rectal

Some experts recommend a 25- to 100-mg/kg dose before procedure; do not exceed a 1-g dose in infants or a 2-g dose in children.¹⁰⁶

Adults

Hypnotic

Oral

0.5–1 g 15–30 minutes prior to bedtime.^{100 101}

Some experts recommend a 0.5- to 1-g dose; do not exceed 2 g in 24 hours.¹⁰⁶

Rectal

0.65–1.3 g 30 minutes prior to bedtime.¹⁰³

Some experts recommend a 0.5- to 1-g dose; do not exceed 2 g in 24 hours.¹⁰⁶

Sedation

Routine Sedation

Oral

250 mg 3 times daily after meals.^{100 101}

Rectal

325–650 mg 3 times daily, up to a maximum total daily dosage of 1950 mg.¹⁰³

Some experts recommend 250 mg 3 times daily.¹⁰⁶

Preoperative Sedation

Oral

0.5–1 g 30 minutes prior surgery.^c

Alcohol Withdrawal

Oral

0.5–1 g every 6 hours as needed, up to a maximum single dose or daily dosage of 2 g.^{100 101}

Prescribing Limits

Pediatric Patients

Hypnotic

Oral

Maximum 1 g daily (as a single dose).^{100 101}

Sedation

Oral

For routine sedation, maximum 500 mg 3 times daily.^{100 101 c}

For procedural sedation, maximum 1-g dose in infants or a 2-g dose in children.¹⁰⁶

For conscious sedation, maximum total dosage in children <3 years of age (excluding neonates) is 2 g or 100 mg/kg (whichever is lower).^{104 105}

Rectal

For routine or preoperative sedation, maximum of one 9-mg/kg (325-mg/36 kg) dose daily.¹⁰³

Adults

Oral

Maximum 2 g daily.^{100 101 c}

Rectal

Maximum 1950 mg daily.¹⁰³

Special Populations

No special population recommendations at this time.^{100 101 c 103} (See Contraindications under Cautions.)

Cautions for Chloral Hydrate

Contraindications

• Marked hepatic impairment.^{100 101 c 103}

• Marked renal impairment. ^{100 101 c 103}

• Known hypersensitivity or idiosyncratic reaction to chloral hydrate.^{100 101 c 103}

Warnings/Precautions

Warnings

Carcinogenicity

Although the manufacturer of Aquachloral suppositories warns about potential carcinogenicity of the drug, some experts state that the assumption that chloral hydrate is a reactive metabolite of trichloroethylene (an industrial solvent) responsible for the carcinogenicity of trichloroethylene is questionable.¹⁰⁸ There is evidence that the carcinogenicity of trichloroethylene is due to a reactive intermediate epoxide metabolite rather than to chloral hydrate.¹⁰⁸

Abuse Potential

Although uncommon, tolerance and psychologic dependence may occur following prolonged administration of the drug; use with caution in patients with a history of drug abuse.^{100 101 c 103}

Symptoms of dependence are similar to those of chronic alcoholism^{100 101 c 103} (drowsiness, lethargy, hangover, slurring of speech, incoordination, tremulousness, and nystagmus).^c

Withdrawal

Sudden withdrawal may cause delirium tremens (sometimes fatal) and hallucinations; following chronic use, withdraw slowly.^{100 101 c 103}

Sensitivity Reactions

Hypersensitivity Reactions

Scarlatiniform or erythematous rash, urticaria, angioedema, purpura, eczema, bullous lesions, skin eruptions, and erythema multiforme reported, sometimes accompanied by fever.^{100 101 103}

Tartrazine Sensitivity

Aquachloral 325 mg rectal suppositories contain tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in susceptible individuals.¹⁰³ Incidence of tartrazine sensitivity is low, but it frequently occurs in patients who are sensitive to aspirin.¹⁰³

General Precautions

CNS Effects

Use with caution in mentally depressed patients or those having suicidal tendencies.^{100 101 c 103}

Rarely, somnambulistic reaction characterized by disorientation and incoherence reported.^{100 101 103}

GI Effects

Avoid oral administration in patients with esophagitis, gastritis, or gastric or duodenal ulcers.^{100 101 c}

Gastritis may develop following prolonged oral administration; minimize irritation by diluting oral syrup or administering other oral dosage forms with liquids.^{100 101 c} (See Administration under Dosage and Administration.)

Cardiac Effects

Prolonged administration of therapeutic doses was not associated with adverse cardiac effects.^{100 101 103}

Do not use high doses in patients with severe cardiac disease.^{100 101 103}

Renal Effects

Following prolonged administration, parenchymatous renal damage reported.^{100 101}

Porphyria

Attacks of acute intermittent porphyria reported; use caution in susceptible patients.¹⁰¹

Adequate Monitoring

Procedural sedation using chloral hydrate in pediatric patients should be performed only under the supervision of qualified clinicians experienced in cardiorespiratory complications.^{104 105 107}

Specific Populations

Pregnancy

Category C.^{100 101 c 103}

Lactation

Distributed into milk.¹⁰³ Use with caution in nursing women.^{100 101 c 103}

Pediatric Use

Used orally and rectally in pediatric patients for sedation and hypnosis.^{100 101 c 103 104 105 106 108}

Geriatric Use

Geriatric patients may tolerate chloral hydrate even when intolerant to barbiturates.¹⁰³

Common Adverse Effects

Nausea,^{100 101 c 103} vomiting, ^{100 101 c 103} diarrhea, ^{100 101 c 103} ataxia, ^{100 101 c 103} dizziness.^{100 101 c 103}

Interactions for Chloral Hydrate

Specific Drugs

Chloral Hydrate Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral or rectal administration.^c

Onset

Following oral administration of 0.5–1 g, sedation occurs within 30–60 minutes.^{c 105}

Following rectal administration, sedation occurs within 60 minutes.¹⁰³

Duration

Following oral administration of 0.5–1 g : 4–8 hours.^{c 105}

Distribution

Extent

Distributed into CSF, umbilical cord blood, fetal blood, amniotic fluid, and milk.^{100 101 c}

Elimination

Metabolism

Metabolized to trichloroethanol (active metabolite), principally in the liver and erythrocytes, by alcohol dehydrogenase and other enzymes.^c Small, but variable amounts of chloral hydrate metabolized to trichloroacetic acid (inactive metabolite) in liver and kidneys.^c

Elimination Route

Active and inactive metabolites are slowly and variably excreted in the kidneys.^c Trichloroethanol glucuronide (urochloralic acid), an inactive metabolite, may be secreted into the bile and excreted in feces.^c

Eliminated by dialysis.¹⁰³

Half-life

8–11 hours.^c

Stability

Storage

Oral

Capsules

25°C (may be exposed to 15–30°C).¹⁰¹

Solution

Tight, light resistant containers at 20–25°C; protect from freezing.¹⁰⁰

Rectal

Suppositories

15–30°C; do not refrigerate.^{c 103}

Actions

• Mechanism of action not fully elucidated; CNS depressant effect believed to result primarily from active metabolite trichloroethanol.^{c 103}

• CNS depressant effects similar to paraldehyde and barbiturates.^c

• Hypnotic doses produce mild cerebral depression and quiet, deep sleep.^c

• Higher doses may lead to general anesthesia and concurrent depression of respiratory and vasomotor centers; death may result from respiratory failure.^c

• Sedative or hypnotic doses have little anticonvulsant activity.^c

• Has little analgesic activity and may produce excitement or delirium in the presence of pain.^c

Advice to Patients

• Administer capsules with a full glass of water or liquid¹⁰¹ and oral solution with half glass of liquid (i.e., water, fruit juice, or ginger ale).¹⁰⁰ (See Administration under Dosage and Administration)

• Advise patients not to take CNS depressant drugs or alcohol concomitantly with chloral hydrate.^{100 101 103}

• Risk of dizziness or fatigue; potential for drug to impair mental alertness or physical coordination; use caution when driving or operating machinery until effects on the individual are known.^{100 101 c 103}

• Importance of informing clinicians of hypersensitivity to aspirin.¹⁰³ (See Tartrazine Sensitivity under Warnings and Precautions.)

• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses.^{100 101 c 103}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; breast-feeding may result in sedation of the infant.^{c 103}

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Chloral hydrate is subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.^c

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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