phenobarbital; PB; PHB (Luminal, Barbita, Solfoton)
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Introduction
Tradenames: Luminal, Barbita, Solfoton. DEA-controlled substance: class 4.
Indications
- seizures:
- partial seizures
- focal seizures
- prevention of febrile seizures in infants & young children
- 3rd line agent for management of status epilepticus
- prevention & treatment of neonatal hyperbilirubinemia
- lowering bilirubin in chronic cholestasis
Contraindications
- generalized tonic-clonic seizures
- may exacerbate generalized seizures[7]
Dosage
- load 15-20 mg/kg up to 300-800 mg IV @ 25-50 mg/min
- maintenance: 60 mg PO BID/TID
- 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
Pharmacokinetics
- well absorbed after oral administration
- onset of action:
- within 5 minutes of IV administration
- 20-60 minutes after oral dosage
- duration of action 4-10 hours
- 1/2life is 53-140 hours, increased with cirrhosis
- steady state in 21 days
- metabolized by the liver
- eliminated as active & inactive drug in the urine
- alkalinization of the urine increases excretion
- therapeutic level for seizures is 15-35 mg/L
elimination via liver
elimination via kidney
1/2life = 50-140 hours adult
1/2life = 40-70 hours child
protein binding = 45-50 %
elimination by hemodialysis = +
elimination by hemoperfusion = +
elimination by peritoneal dialysis = +/-
Adverse effects
- common (> 10%)
- dizziness, lightheadedness, drowsiness, somnolence, hangover effect, pain at site of injection
- less common (1-10%)
- confusion, depression, unusual excitement, nervousness, constipation, faintness, headache, nausea/vomiting, insomnia, nightmares
- uncommon (< 1%)
- other[3][7]
- neurologic:
- sedation
- ataxia
- confusion
- dizziness
- impotence
- depression
- impaired reaction time
- hyperkinetic activity
- barbiturate withdrawal syndrome
- arrhythmias
- connective tissue disorders
- hepatic dysfunction
- osteoporosis
- hypothermia
- neurologic:
- overdose[8]
Drug interactions
- phenobarbital metabolism decreased & serum levels increased by: valproic acid, phenytoin, methylphenidate, chloramphenicol, propoxyphene
- enhances metabolism of other drugs via induction of cyt P450 1A2, cyt P450 2B6, cyt P450 2C9 & cyt P450 3A4
- increases effects of alcohol, benzodiazepines, CNS depressants, valproic acid
- decreases effects of digoxin, doxycycline, anti-fungal agents, tricyclic antidepressants, theophylline, warfarin, oral contraceptives, beta blockers, phenothiazines, cyclosporine, corticosteroids, ethosuximide, quinidine, haloperidol, chloramphenicol
- disulfiram inhibits metabolism of phenobarbital
- drug interaction(s) anticonvulsants with anti-bacterial agents
- drug interaction(s) anticonvulsants with statins
- drug interaction(s) of beta-adrenergic receptor antagonists with barbiturates
Laboratory
- specimen:
- serum, plasma (heparin, EDTA)
- stable at room temperature for several hours
- stable for 1 year at -20 degrees C
- methods: GLC, HPLC, EIA, FPIA, FIA
- labs with Loincs
Mechanism of action
- interferes with impulse transmission from the thalamus to the cerebral cortex
- thought to increase inhibitory effects of GABA by increasing permeability of chloride
Management
- failure to control symptoms:
- use another anticonvulsant indicated for partial seizures
More general terms
Additional terms
- 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
Component of
- atropine/hyoscyamine/phenobarbital/scopolamine
- ephedrine/phenobarbital/potassium iodide/theophylline
- dyphylline/ephedrine/guaifenesin/phenobarbital
- carbamazepine/lamotrigine/phenobarbital/phenytoin/primidone/valproic acid
- belladonna alkaloid/ergotamine/phenobarbital
- belladonna alkaloid/caffeine/ergotamine/phenobarbital
- hyoscyamine/phenobarbital/scopolamine
- belladonna/ergotamine/phenobarbital (Bellergal-S, Spastrin)
- atropine/belladonna/hyoscyamine/phenobarbital/scopolamine (Donnatal)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 700
- ↑ 3.0 3.1 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ 6.0 6.1 Prescriber's Letter 13(10): 2006 Alternative or 'Off-label' Routes of Drug Administration Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=221012&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17. American College of Physicians, Philadelphia 2009, 2012, 2015
- ↑ 8.0 8.1 Henry's Clinical Diagnosis & Management by Laboratory Methods, 21st edition, McPherson RA & Pincus MR (es), W.B. Saunders Co., Philadelphia, PA. 2007, pg 311