Clonazepam

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

Introduction

• Tradename: Klonopin. DEA-controlled substance: class 4.

Indications

• absence ( petit mal) seizures
• atypical absence seizures ( Lennox-Gastaut)
• akinetic seizures
• myoclonic seizures
• neuralgia
• acute manic episodes
• restless legs syndrome
• multifocal tic disorder
• muscle spasms
• panic disorder
• rapid eye movement behavioral disorder

Dosage

• epilepsy

• start 0.5 mg PO TID
• max 20 mg/day.

• panic/ neuralgia/ muscle spasms:

• 0.5 mg BID
• usual dose 1-3 mg QD

• Tabs: 0.5, 1, 2 mg.

Pharmacokinetics

• well absorbed after oral administration
• onset of action 20-60 minutes
• duration of action 12 hours
• metabolized extensively by liver;

• metabolite 7-amino-clonazepam is active, but NOT an efficient anticonvulsant

• 1/2life 35 hours [5]
  

• elimination via liver
• elimination via kidney
• 1/2life = 20-60 hours
• protein binding = 86 %

Adverse-effects

• common (> 10%)

• drowsiness, fatigue, impaired coordination, ataxia, light- headedness, memory impairment, insomnia, dysarthria, anxiety, decreased libido, depression, headache, dry mouth, constipation, diarrhea, decreased salivation, nausea/vomiting, tachycardia, chest pain, blurred vision, sweating, rash, increased or decreased appetite

• less common (1-10%)

• confusion, nervousness, syncope, dizziness, akathisia, increased salivation, hypotension, rigidity, tremor, dermatitis, nasal congestion, weight gain or weight loss, hyperventilation, tinnitus, muscle cramps

• uncommon (< 1%)

• menstrual irregularities, blood dyscrasias, reflex slowing, drug dependence

• other [5]

• hallucinations, GERD, withdrawal, dependence
  
• drug adverse effects of sedatives
• drug adverse effects of anticonvulsants
• drug adverse effects of benzodiazepines

Drug-interactions

• may precipitate absence status if given with valproic acid
• disulfiram, nefazodone, fluoxetine, fluvoxamine, cimetidine, estrogens, erythromycin & grapefruit juice increase serum levels of clonazepam
• clonazepam may increase effects of CNS depressants
• phenytoin, phenobarbital, carbamazepine & rifampin increase metabolism of clonazepam
• flumazenil antagonizes effects of benzodiazepines
  
• drug interaction(s) of antipsycotics with benzodiazepines
• drug interaction(s) of antidepressants with benzodiazepines
• drug interaction(s) of beta-adrenergic receptor antagonists with benzodiazepines
• drug interaction(s) of beta-adrenergic receptor antagonists with benzodiazepines

Laboratory

• specimen:

• serum, plasma ( heparin, EDTA)
• collect at trough concentration
• stable at -20 degrees C

• methods: HPLC, GLC, RIA
• interferences:

• chlordiazepoxide may interfere with analysis by GLC

Mechanism-of-action

• potentiates inhibitory activity of GABA in the motor cortex
• increases neuronal membrane permeability to chloride

More General Terms

• benzodiazepine
• anticonvulsant

Internet Database

PubChem: 2802

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 701.
3. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 555
4. Clinical Guide to Laboratory Tests, 3rd edition, NW Tietz ed, WB Saunders, Philadelphia, 1995
5. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
6. Kaiser Permanente Northern California Regional Drug Formulary, 1998

clonazepam (Klonopin)