pentobarbital

Pentobarbital is a sedative/hypnotic medication used for sedation (pre-anesthesia) before surgery, for a short term to treat insomnia, and for emergency control of certain types of seizures.

Pentobarbital belongs to a class of medications known as barbiturates which work by depressing the central nervous system (CNS). Pentobarbital is also used off-label to medically induce coma and control intracranial pressure in patients with severe brain injury.

Pentobarbital sedates by enhancing the activity of gamma-aminobutyric acid (GABA), the major inhibitory chemical (neurotransmitter) in the brain. Pentobarbital binds to GABA-A receptors, protein particles on nerve cells (neurons) that respond to GABA and send inhibitory signals. in addition, pentobarbital also inhibits the activity of glutamate, the primary stimulatory neurotransmitter in the brain.

At low doses, pentobarbital produces sedation, drowsiness, and hypnosis. At higher doses, it is anticonvulsive, depresses respiration, and reduces intracranial pressure by reducing blood flow to the brain and slowing down brain metabolism. Uses of pentobarbital include the following:

FDA approved:

• Sedative for short-term (under 2 weeks) treatment of insomnia or as pre-anesthesia prior to surgical procedures
• Emergency control of seizure episodes including:
  • Status epilepticus, a state of prolonged seizure
  • Meningitis
  • Cholera
  • Tetanus
  • Eclampsia, a complication in pregnancy
  • Toxic reactions to strychnine or local anesthetics

Off-label:

• Barbiturate coma to control elevated intracranial pressure in severe brain injury 

• Do not use pentobarbital in patients with hypersensitivity to barbiturates or any of the components in pentobarbital.
• Do not use pentobarbital in patients with:
  • Severe respiratory disease
  • Porphyria, a group of inherited disorders that cause buildup of porphyrin in the body, which can affect multiple organs.
• Pentobarbital causes CNS depression and can impair physical and mental abilities. Caution patients and caregivers appropriately.
• Use with caution in patients with respiratory disease. Intubation may be required before treatment for seizures or traumatic brain injury.
• Use with caution in patients with:
  • Impaired kidney or liver function
  • Depression or suicidal tendencies
  • History of drug abuse
• Use with caution in elderly or debilitated patients.
• Use with caution in pregnant women and children below 3 years of age. Pentobarbital can affect fetal and young children’s brain development.
• Use with caution in patients with acute or chronic pain, pentobarbital can induce paradoxical excitation and mask important symptoms.
• Rapid IV administration may cause respiratory depression, apnea, laryngospasm, or hypotension, exercise caution.
• Abrupt withdrawal of antiseizure medications may increase seizure frequency, withdraw pentobarbital gradually.
• Some dosage forms may contain propylene glycol, large amounts of which are potentially toxic.

Common side effects of pentobarbital include:

• Slow heart rate (bradycardia)
• Low blood pressure (hypotension)
• Fainting (syncope)
• Nausea
• Vomiting
• Constipation
• Pause in breathing (apnea), especially with rapid IV administration
• Slow and shallow breathing (hypoventilation)
• Respiratory depression
• Injection site reaction
• Fever
• Low red blood cell count with abnormally large red cells (megaloblastic anemia)
• Liver toxicity (hepatotoxicity)
• Skin rash
• Skin peeling with inflammation (exfoliative dermatitis)
• Hypersensitivity reaction
• Swelling under the skin and mucous membrane (angioedema)
• Excessive movements and muscle spasms (hyperkinesia)
• Voice box spasm (laryngospasm)
• Headache
• Dizziness
• Drowsiness
• Hallucination
• Insomnia
• Nightmares
• Impaired coordination, balance and speech (ataxia)
• Central nervous system stimulation
• Abnormality in thinking
• Agitation
• Anxiety
• Confusion
• Depression
• Nervousness
• Psychiatric disturbance

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable Solution: Schedule II

• 50 mg/mL

Adult:

Hypnotic

• Initial: 100 mg intravenous (IV) OR 150-200 mg intramuscular (IM)
• May give small increments of the drug after at least 1 minute to reach full effect
• Not to exceed 500 mg

Barbiturate Coma

• Load: 10-15 mg/kg IV over 30 minutes; follow by 5 mg/kg IV every 1 hour for 3 doses  
• Maintenance: 1 mg/kg/hour IV; may increase to 2-4 mg/kg/hour

Dosing Modifications:

Renal Failure

• Use lower dose

Hepatic Failure

• Use lower dose

Other Indications and Uses

• Acute convulsive episodes

Geriatric:

• Not recommended; use a lower dose if use becomes necessary

Pediatric:

Hypnotic

• 2-6 mg/kg IM once; not to exceed 100 mg  

Pre-procedure Sedation

• 2-6 mg/kg IM, OR  
• 1-3 mg/kg IV
• Not to exceed 100 mg IM

• Barbiturates including pentobarbital are addictive and have been historically misused and abused illegally as street drugs. Pentobarbital abuse can lead to tolerance, dependence, and overdose, and cause withdrawal symptoms such as tremors, difficulty sleeping, and agitation upon discontinuation.
• Pentobarbital depresses the central nervous system and overdose can result in airway compromise, cardiovascular collapse, coma, and death.
• There is no antidote for pentobarbital and overdose treatment is symptomatic and supportive. Treatment may require intubation and respiratory support, maintenance of blood pressure with medication and fluids, and maintenance of body temperature.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of pentobarbital include:
  • cariprazine
  • cobimetinib
  • dienogest/estradiol valerate
  • doravirine
  • elbasvir/grazoprevir
  • elvitegravir/cobicistat/emtricitabine/tenofovir DF
  • fostemsavir
  • isavuconazonium sulfate
  • lonafarnib
  • lorlatinib
  • lumacaftor/ivacaftor
  • lumefantrine
  • lurasidone
  • mavacamten
  • naloxegol
  • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
  • panobinostat
  • praziquantel
  • regorafenib
  • roflumilast
• vandetanib
• Pentobarbital has serious interactions with at least 127 different drugs.
• Pentobarbital has moderate interactions with at least 354 different drugs.
• Pentobarbital has mild interactions with at least 116 different drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or healthcare provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• Pentobarbital can cause fetal harm, avoid use in pregnant women except in life-threatening emergencies.
• Use in third semester can cause withdrawal symptoms in the newborn, including irritability and seizures.
• Use of sedative doses during labor does not impair uterine activity, however, full anesthetic dose can decrease the force and frequency of uterine contractions.
• Use of pentobarbital during labor can cause respiratory depression in the newborn. Resuscitation equipment should be ready, especially for premature infants.
• Pentobarbital is excreted in breast milk, use with caution in nursing mothers.

• Pentobarbital injection is a Schedule II controlled substance, diversion of Schedule II products is subject to criminal penalty.
• Pentobarbital is an injection meant for use in clinical settings by healthcare professionals. Diversion and misuse are illegal.
• Pentobarbital can cause drowsiness and impair mental and physical abilities. Avoid hazardous activities such as driving and operating heavy machinery.
• Abuse of pentobarbital can cause dependence and addiction and lead to overdose. In case of overdose immediately seek medical help or contact Poison Control.