Primidone

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Dosage 4 Pharmacokinetics 5 Monitor 6 Adverse-effects 7 Drug-interactions 8 Laboratory 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Introduction

• Tradename: Primaclone, Mysoline.

Indications

• prophylactic management of tonic-clonic seizures & complex partial seizures (not absence seizures)
• used alone or in combination with other anticonvulsants
• treatment of essential tremor

Dosage

• start 100-125 mg PO QHS
• increase over 10 days to 250 mg TID/ QID

• day 1-3: 100-125 mg QHS
• day 4-6: 100-125 mg BID
• day 7-9: 100-125 mg TID
• day 10: maintenance dose

• max dose 2 g/day
• children:
• > 8 years: 125-200 mg PO TID
• < 8 years: 250 mg PO TID
• avoid abrubt discontinuation; may precipitate seizures

• Tabs: 50 & 250 mg
• Liquid: 250 mg/5 mL .

Pharmacokinetics

• 60-80% absorbed from the GI tract
• protein binding 0-20%
• metabolized to:

• phenobarbital ( PHB)
• phenylethylmalonamide ( PEMA)

• approximately 40% of drug excreted unchanged into urine
• elimination 1/2life

• t1/2 (primidone): 8 hours (10-21 hours [4])
• t1/2 ( PEMA): 24-48 hours
• t1/2 ( PHB): 90 hours
  

• elimination via liver
• elimination via kidney
• 1/2life = 4-12 hours
• protein binding = 0-20 %
• elimination by hemodialysis = +

Monitor

• serum ALT or serum AST & CBC within 180 days [8]
  
• monitor with anticonvulsants

Adverse-effects

• (same as phenobarbital)

• common (> 10%)

• drowsiness, sedation, vertigo, ataxia, headache

• less common (1-10%)

• anorexia, nausea/vomiting, impotence

• uncommon (< 1%)

• megaloblastic anemia, maculopapular skin rash, behavioral change, leukopenia, malignant lymphoma-like syndrome, systemic lupus-like syndrome, diplopia, nystagmus

• neurologic:

• sedation, ataxia, confusion, dizziness & vertigo, impotence, depression, drowsiness, lethargy, may occasionally cause hyperexcitability in children
  
• drug adverse effects of anticonvulsants

Drug-interactions

• level increased by valproic acid & phenytoin
• carbamazepine in combination increases carbamazepine levels & diminishes primidone levels
• succinimides decrease primidone levels
• barbiturates induce cyt P450 1A2, 2C9 & 3A4

• may diminish levels of drugs metabolized by cyt P450 1A2, 2C9 & 3A4

• codaministration of isoniazid may increase primodone t1/2
• codaministration of acetazolamide may decrease absorption
  
• drug interaction(s) of beta-adrenergic receptor antagonists with barbiturates

Laboratory

• specimen:

• serum, plasma ( heparin, EDTA)
• stable at room temperature for 1 year at -20 degrees C

• methods: HPLC, GLC, EIA, FPIA

Mechanism-of-action

• related to barbiturates
• activation of inhibitory effect of GABA receptors by enhancing permeability of neurons to chloride

More General Terms

• barbiturate
• anticonvulsant

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; PB; PHB (Luminal, Barbita, Solfoton)
• primidone in serum/plasma

Internet Database

PubChem: 4909
PubChem: 589869

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. The Pharmacological Basis of Therapeutics, 8th ed. Gilman et al, eds. Permagon Press/McGraw Hill pg 446
4. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
5. Kaiser Permanente Northern California Regional Drug Formulary, 1998
6. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
7. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: [1] (subscription needed) [2]
8. Anvita Health guideline :id 1686

primidone; desoxyphenobarbital (Primaclone, Mysoline)