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primidone; desoxyphenobarbital (Primaclone, Mysoline)

Tradename: Primaclone, Mysoline. Indications: 1) prophylactic management of tonic-clonic seizures & complex partial seizures - not useful for absence seizures 2) used alone or in combination with other anticonvulsants 3) treatment of essential tremor Dosage: 1) start 100-125 mg PO QHS 2) increase over 10 days to 250 mg TID/QID a) day 1-3: 100-125 mg QHS b) day 4-6: 100-125 mg BID c) day 7-9: 100-125 mg TID d) day 10: maintenance dose 3) max dose 2 g/day 4) children: 1) > 8 years: 125-200 mg PO TID 2) < 8 years: 250 mg PO TID 5) avoid abrubt discontinuation; may precipitate seizures Tabs: 50 & 250 mg Liquid: 250 mg/5 mL . Pharmacokinetics: 1) 60-80% absorbed from the GI tract 2) protein binding 0-20% 3) metabolized to: a) phenobarbital (PHB) b) phenylethylmalonamide (PEMA) 4) approximately 40% of drug excreted unchanged into urine 5) elimination 1/2life a) t1/2 (primidone): 8 hours (10-21 hours [4]) b) t1/2 (PEMA): 24-48 hours c) t1/2 (PHB): 90 hours Monitor: - serum ALT or serum AST & CBC within 180 days [8] Adverse effects: (same as phenobarbital) 1) common (> 10%) - drowsiness, sedation, vertigo, ataxia, headache 2) less common (1-10%) - anorexia, nausea/vomiting, impotence 3) uncommon (< 1%) - megaloblastic anemia, maculopapular skin rash, behavioral change, leukopenia, malignant lymphoma-like syndrome, systemic lupus-like syndrome, diplopia, nystagmus 4) neurologic: - sedation, ataxia, confusion, dizziness & vertigo, impotence, depression, drowsiness, lethargy, may occasionally cause hyperexcitability in children Drug interactions: 1) level increased by valproic acid & phenytoin 2) carbamazepine in combination increases carbamazepine levels & diminishes primidone levels 3) succinimides decrease primidone levels 4) barbiturates induce cyt P450 1A2, 2C9 & 3A4 -> may diminish levels of drugs metabolized by cyt P450 1A2, 2C9 & 3A4 5) codaministration of isoniazid may increase primodone t1/2 6) codaministration of acetazolamide may decrease absorption Laboratory: 1) specimen: a) serum, plasma (heparin, EDTA) b) stable at room temperature for 1 year at -20 degrees C 2) methods: HPLC, GLC, EIA, FPIA 3) labs with Loincs - primidone in body fluid - primidone in gastric fluid - primidone in serum/plasma - primidone in urine Mechanism of action: 1) related to barbiturates 2) activation of inhibitory effect of GABA receptors by enhancing permeability of neurons to chloride

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

General

anticonvulsant barbiturate

Properties

MISC-INFO: elimination route LIVER KIDNEY 1/2life 4-12 HOURS therapeutic-range 5-12 UG/ML toxic-range >15 UG/ML protein-binding 0-20% elimination by hemodialysis + pregnancy-category D safety in lactation -

Database Correlations

PUBCHEM correlations

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#: 220233 (subscription needed) http://www.prescribersletter.com
  8. deprecated reference

Component-of

carbamazepine/lamotrigine/phenobarbital/phenytoin/primidone/valproic acid