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phenobarbital; PB; PHB (Luminal, Barbita, Solfoton)

Tradenames: Luminal, Barbita, Solfoton. DEA-controlled substance: class 4. Indications: 1) seizures: a) partial seizures b) focal seizures c) prevention of febrile seizures in infants & young children 2) 3rd line agent for management of status epilepticus 3) prevention & treatment of neonatal hyperbilirubinemia 4) lowering bilirubin in chronic cholestasis Contraindications: - generalized tonic-clonic seizures - may exacerbate generalized seizures [7] Dosage: 1) load 15-20 mg/kg up to 300-800 mg IV @ 25-50 mg/min 2) maintenance: 60 mg PO BID/TID 3) Children: 3-6 mg/kg/day Tabs: 15, 16, 30, 60 100 mg. Elixir: 15 & 20 mg/5 mL (120 mL). Injection: 65 mg/mL (1 mL), 130 mg/mL (1 mL) injectable form also works given rectally [6] * dosage adjustment for liver failure [7] Dosage adjustment in renal failure: - none - supplemental dose after dialysis uncertain [7] Pharmacokinetics: 1) well absorbed after oral administration 2) onset of action: a) within 5 minutes of IV administration b) 20-60 minutes after oral dosage 3) duration of action 4-10 hours 4) 1/2life is 53-140 hours, increased with cirrhosis 5) steady state in 21 days 6) metabolized by the liver 7) eliminated as active & inactive drug in the urine 8) alkalinization of the urine increases excretion 9) therapeutic level for seizures is 15-35 mg/L Adverse effects: 1) common (> 10%) - dizziness, lightheadedness, drowsiness, somnolence, hangover effect, pain at site of injection 2) less common (1-10%) - confusion, depression, unusual excitement, nervousness, constipation, faintness, headache, nausea/vomiting, insomnia, nightmares 3) uncommon (< 1%) - agranulocytosis, thrombocytopenia, megaloblastic anemia - thrombophlebitis - rash, exfoliative dermatitis, Stevens-Johnson syndrome - hallucinations - hypotension - respiratory depression - heptotoxicity [7] 4) other [3,7] a) neurologic: - sedation - ataxia - confusion - dizziness - impotence - depression - impaired reaction time - hyperkinetic activity - barbiturate withdrawal syndrome b) arrhythmias c) connective tissue disorders d) hepatic dysfunction e) osteoporosis f) hypothermia 5) overdose [8] - nystagmus - ataxia - hypotension - stupor, coma - respiratory depression Drug interactions: 1) phenobarbital metabolism decreased & serum levels increased by: valproic acid, phenytoin, methylphenidate, chloramphenicol, propoxyphene 2) enhances metabolism of other drugs via induction of cyt P450 1A2, cyt P450 2B6, cyt P450 2C9 & cyt P450 3A4 3) increases effects of alcohol, benzodiazepines, CNS depressants, valproic acid 4) decreases effects of digoxin, doxycycline, anti-fungal agents, tricyclic antidepressants, theophylline, warfarin, oral contraceptives, beta blockers, phenothiazines, cyclosporine, corticosteroids, ethosuximide, quinidine, haloperidol, chloramphenicol 5) disulfiram inhibits metabolism of phenobarbital Laboratory: 1) specimen: a) serum, plasma (heparin, EDTA) b) stable at room temperature for several hours c) stable for 1 year at -20 degrees C 2) methods: GLC, HPLC, EIA, FPIA, FIA 3) labs with Loincs - phenobarbital in specimen - phenobarbital in hair - phenobarbital in body fluid - phenobarbital in saliva - phenobarbital in gastric fluid - phenobarbital in stool - phenobarbital in meconium - phenobarbital in milk - phenobarbital in serum/plasma/blood - phenobarbital in blood - phenobarbital in serum/plasma - phenobarbital in urine - phenobarbital in vitreous fluid Mechanism of action: 1) interferes with impulse transmission from the thalamus to the cerebral cortex 2) thought to increase inhibitory effects of GABA by increasing permeability of chloride Management: - failure to control symptoms: - use another anticonvulsant indicated for partial seizures

Interactions

drug interactions drug adverse effects of anticonvulsants monitor with anticonvulsants

Related

cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2) cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10) cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4) phenobarbital in serum/plasma

General

anticonvulsant barbiturate

Properties

MISC-INFO: elimination route LIVER KIDNEY 1/2life 50-140 HOURS 40-70 HOURS therapeutic-range 10-50 UG/ML protein-binding 45-50% elimination by hemodialysis + hemoperfusion + peritoneal dialysis +/- pregnancy-category D safety in lactation ?

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 700
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  6. Prescriber's Letter 13(10): 2006 Alternative or 'Off-label' Routes of Drug Administration Detail-Document#: 221012 (subscription needed) http://www.prescribersletter.com
  7. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17. American College of Physicians, Philadelphia 2009, 2012, 2015
  8. Henry's Clinical Diagnosis & Management by Laboratory Methods, 21st edition, McPherson RA & Pincus MR (es), W.B. Saunders Co., Philadelphia, PA. 2007, pg 311

Component-of

atropine/belladonna/hyoscyamine/phenobarbital/scopolamine (Donnatal) atropine/hyoscyamine/phenobarbital/scopolamine belladonna alkaloid/caffeine/ergotamine/phenobarbital belladonna alkaloid/ergotamine/phenobarbital belladonna/ergotamine/phenobarbital (Bellergal-S, Spastrin) carbamazepine/lamotrigine/phenobarbital/phenytoin/primidone/valproic acid dyphylline/ephedrine/guaifenesin/phenobarbital ephedrine/phenobarbital/potassium iodide/theophylline hyoscyamine/phenobarbital/scopolamine

Databases & Figures

PUBCHEM correlations Pharmacologic Inhibitors of Apoptosis