BUTABARBITAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BUTABARBITAL (BUTABARBITAL).
Butabarbital is a barbiturate that acts as a central nervous system depressant. It enhances the activity of GABA, an inhibitory neurotransmitter, by binding to the GABA-A receptor and prolonging the opening of chloride ion channels, leading to neuronal hyperpolarization and reduced excitability.
| Metabolism | Hepatic metabolism via cytochrome P450 enzymes (primarily CYP2C9 and CYP3A4); undergoes hydroxylation and glucuronidation; active metabolites include hydroxybutabarbital. |
| Excretion | Primarily renal, with approximately 60-80% of the dose eliminated as metabolites (mostly hydroxylated and conjugated) and less than 5% as unchanged drug. Minor biliary/fecal excretion occurs (<10%). |
| Half-life | Terminal elimination half-life is 30-50 hours in adults, which may be prolonged in elderly or patients with hepatic impairment, leading to accumulation with repeated dosing. |
| Protein binding | Approximately 20-25% bound to plasma proteins, predominantly albumin. |
| Volume of Distribution | Approximately 1.0 L/kg, indicating distribution throughout total body water and extensive tissue binding. |
| Bioavailability | Oral bioavailability is nearly 100% (50-70% reported in some texts, but butabarbital is completely absorbed; first-pass metabolism is minimal). |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5-10 minutes. Onset depends on lipophilicity and rate of absorption. |
| Duration of Action | Duration of hypnotic effect is 6-8 hours after a single oral dose, but residual CNS depression may persist longer due to slow elimination. Repeated doses can cause accumulation. |
50-100 mg orally or intramuscularly 3-4 times daily; maximum 400 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: reduce dose by 25%; GFR <10 mL/min: reduce dose by 50%. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: avoid use. |
| Pediatric use | Children 2-6 years: 25-50 mg orally 3-4 times daily; children 6-12 years: 50-100 mg orally 3-4 times daily; maximum 200 mg/day. |
| Geriatric use | Initiate at 25-50 mg orally 3 times daily; increase cautiously to avoid excessive sedation and falls, maximum 200 mg/day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BUTABARBITAL (BUTABARBITAL).
| Breastfeeding | Butabarbital is excreted into breast milk in low concentrations. The milk-to-plasma ratio (M/P) is approximately 0.4–0.6. With therapeutic doses, infant serum levels are usually low; however, chronic high maternal doses may cause sedation or withdrawal in the nursing infant. Caution is recommended; alternate agents may be preferred if infant sedation occurs. |
| Teratogenic Risk | First trimester: Associated with increased risk of major congenital malformations, specifically oral clefts (relative risk ~2.0). Second/third trimester: Chronic use may lead to fetal dependence and withdrawal syndrome; neonatal respiratory depression if used near term; increased risk of neurobehavioral effects. Barbiturates cross the placenta rapidly. |
■ FDA Black Box Warning
Butabarbital has no FDA boxed warning.
| Serious Effects |
Hypersensitivity to barbiturates; porphyria (can exacerbate); severe respiratory insufficiency; history of addiction to sedative-hypnotics; acute or chronic pain (may cause paradoxical excitement); pregnancy (especially third trimester) and lactation.
| Precautions | Risk of dependence, tolerance, and withdrawal symptoms upon discontinuation; respiratory depression, especially with high doses or in patients with respiratory compromise; CNS depression may impair ability to drive or operate machinery; concomitant use with other CNS depressants (e.g., alcohol, opioids) increases risk of profound sedation and respiratory depression; geriatric patients may be more sensitive to effects; use with caution in patients with hepatic or renal impairment. |
| Food/Dietary | Grapefruit juice may decrease metabolism of butabarbital; avoid concurrent consumption. Alcohol increases CNS depression and should be avoided. No specific food restrictions otherwise. |
Loading safety data…
| Fetal Monitoring | Maternal monitoring: Assess sedation, respiratory rate, and signs of dependence/withdrawal. Fetal monitoring: Regular prenatal ultrasound for growth and anatomy; near delivery, monitor fetal heart rate patterns. Neonatal monitoring: Watch for withdrawal symptoms (hyperactivity, tremors, poor feeding) and respiratory depression. |
| Fertility Effects | Barbiturates may induce hepatic microsomal enzymes, potentially affecting hormonal contraception effectiveness (enzyme-inducing activity). No direct evidence of impaired male or female fertility in humans; however, chronic high doses may disrupt menstrual cyclicity due to hormonal alterations. |
| Clinical Pearls | Butabarbital is a short-acting barbiturate with rapid onset. It is primarily used for sedation and insomnia but has high abuse potential. Avoid use in patients with porphyria, severe hepatic impairment, or respiratory insufficiency. Abrupt discontinuation after prolonged use may precipitate withdrawal including seizures. Barbiturates induce CYP3A4 and other hepatic enzymes, reducing efficacy of oral contraceptives, warfarin, and corticosteroids. Use with caution in elderly due to increased risk of falls and cognitive impairment. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not stop taking suddenly as withdrawal reactions such as anxiety, tremors, or seizures can occur. · May cause drowsiness or dizziness; do not drive or operate machinery until you know how this medicine affects you. · Avoid alcohol and other central nervous system depressants (e.g., benzodiazepines, opioids) as they increase risk of severe sedation and respiratory depression. · Use effective contraception while taking this medication as it may reduce hormonal contraceptive effectiveness. · Store in a secure place away from children and others, as it can cause dependence and is habit-forming. |