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clonazepam (Klonopin)
Tradename: Klonopin. DEA-controlled substance: class 4.
Indications:
1) absence (petit mal) seizures
2) atypical absence seizures (Lennox-Gastaut)
3) akinetic seizures
4) myoclonic seizures
5) neuralgia
6) acute manic episodes
- panic attacks
7) restless legs syndrome
8) multifocal tic disorder
9) muscle spasms
10) panic disorder
11) rapid eye movement sleep behavioral disorder
12) akasthisia [7]
13) essential tremor [7]
Dosage:
1) epilepsy
a) start 0.5 mg PO TID
b) max 20 mg/day.
2) panic/neuralgia/muscle spasms:
a) 0.5 mg BID
b) usual dose 1-3 mg QD
Tabs: 0.5, 1, 2 mg.
Pharmacokinetics:
1) well absorbed after oral administration
2) onset of action 20-60 minutes
3) duration of action 12 hours
4) metabolized extensively by liver;
-> metabolite 7-aminoclonazepam is active, but NOT an efficient anticonvulsant
5) 1/2life 35 hours [5]
Adverse effects:
1) 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
2) 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
3) uncommon (< 1%)
- menstrual irregularities, blood dyscrasias, reflex slowing, drug dependence
4) other [5]
- hallucinations, GERD, withdrawal, dependence
Drug interactions:
1) may precipitate absence status if given with valproic acid
2) disulfiram, nefazodone, fluoxetine, fluvoxamine, cimetidine, estrogens, erythromycin & grapefruit juice increase serum levels of clonazepam
3) clonazepam may increase effects of CNS depressants
4) phenytoin, phenobarbital, carbamazepine & rifampin increase metabolism of clonazepam
5) flumazenil antagonizes effects of benzodiazepines
Laboratory:
1) specimen:
a) serum, plasma (heparin, EDTA)
b) collect at trough concentration
c) stable at -20 degrees C
2) methods: HPLC, GLC, RIA
3) labs with loincs
- clonazepam in blood
- clonazepam in gastric fluid
- clonazepam in meconium
- clonazepam in saliva
- clonazepam in serum/plasma
- clonazepam in tissue
- clonazepam in urine
3) interferences:
- chlordiazepoxide may interfere with analysis by GLC
Mechanism of action:
1) potentiates inhibitory activity of GABA in the motor cortex
2) increases neuronal membrane permeability to chloride
Interactions
drug interactions
drug adverse effects (more general classes)
monitor with anticonvulsants
General
anticonvulsant
benzodiazepine
Properties
MISC-INFO: elimination route LIVER
KIDNEY
1/2life 20-60 HOURS
therapeutic-range 15-60 NG/ML
toxic-range >80 NG/ML
protein-binding 86%
pregnancy-category D
safety in lactation ?
Database Correlations
PUBCHEM cid=2802
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 701.
- Manual of Medical Therapeutics, 28th ed, Ewald &
McKenzie (eds), Little, Brown & Co, Boston, 1995,
pg 555
- Clinical Guide to Laboratory Tests, 3rd edition, NW Tietz
ed, WB Saunders, Philadelphia, 1995
- 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
- Deprecated Reference