Phenobarbital (Luminal, numerous companies)
Phenobarbital was invented in 1912, and is perhaps the most used medicine worldwide because it can be given in a single daily dose and it costs much less than most prescription medications. Nevertheless, it is a sedating medication and produces a significant incidence of depression and cognitive problems. Epilepsy specialists usually consider it a second-line drug.
Phenobarbital has the advantage of being cheap, used with a single daily dose, safe, not requiring a lot of blood tests for checks of blood counts and liver function, and available in both oral and injectable forms. The injectable form can be given intravenously.
Disadvantages are several. First, the drug is sedative. It often impairs thinking and memory. Depression can be significant with barbiturates and an appreciable risk for suicide can emerge, particularly in a population that already is prone to depression. The half-life of phenobarbital is long, meaning that the medicine takes a long time to get into and out of the system. Without a loading dose the medication takes up to two weeks to come to steady state levels, and lingers a long time when the pills are stopped.
A typical dose of phenobarbital is 100 mg per day. The dose does not need to be split, although by long-standing and unnecessary practice it often is divided into 30 mg three times a day.
Summary Data for Phenobarbital
Pill sizes: 15, 16.2, 30, 32, 60, 65, 97, 100 mg - all little white pills (DO NOT mix up sizes!)
Liquid for oral: 15, 20, 30, 60, 65, 130 mg/5 ml.
Injectable: 30 mg/ml, 60 mg/ml, 130 mg/ml. The injection can be given intravenously, but it is irritating intramuscularly.
Typical adult dose: Start with 30-100 mg per day. Increase over a week to 60-200 mg/d (1-3.5 mg/kg). Because of the long half-life of phenobarbital, levels will build up slowly over weeks. To load in an emergency: 10-20 mg/kg intravenously.
Typical pediatric dose: 3-7 mg/kg/d.
Metabolism: metabolized by the liver (CYP 2C9), excreted in the urine.
Half-life: 2-5 days.
Plasma concentrations: 15-40 mcg/ml.
Pregnancy: Category D - known to cause birth defects in humans.
Drugs that raise PBB levels: valproate, felbamate.
Drugs that lower PBB levels: phenytoin (sometimes)
PBB increases effects of: acetaminophen, antidepressants, antipsychotics, antihistamines, benzodiazepines, opiates.
Decreases effects of other drugs: buproprion, buspirone, corticosteroids, Coumadin (interaction lowers INR, increases clotting), cyclosporine, doxyrubicin, lamotrigine, oral contraceptives, oxcarbazepine, phenytoin, protease inhibitors, quinidine, theophylline, thyroid hormone, topiramate, zonisamide.
Dangerous Side Effects
Severe depression, suicide, Stevens-Johnson rash, blood count suppression, liver injury, worsening of porphyria, addiction, birth defects; rare worsening of seizures with toxic doses.
Common Side Effects
Sleepiness, fatigue, cognitive impairment, depression, hyperactivity in children and elderly.
Other Side Effects
Sedation, depression, cognitive impairment, attention deficit, hyperactivity, behavior and personality changes, dizziness, sexual dysfunction, rash or itching, sensitivity to the sun, anemia, nausea, vomiting, connective tissue growth (frozen shoulder, hand contractions), bone weakening, neuropathy-numbness, inactivates birth control pills.