Drug information of Chlormezanone

Chlormezanone

Drug group:

A non-benzodiazepine that is used in the management of anxiety. It has been suggested for use in the treatment of muscle spasm.

Mechanism of effect

Chlormezanone binds to central benzodiazepine receptors which interact allosterically with GABA receptors. This potentiates the effects of the inhibitory neurotransmitter GABA, increasing the inhibition of the ascending reticular activating system and blocking the cortical and limbic arousal that occurs following stimulation of the reticular pathways.

Pharmacodynamic

Chlormezanone is a non-benzodiazepine muscle relaxant. It was discontinued worldwide in 1996 by its manufacturer due to confirmed serious and rare cutaneous reactions (toxic epidermal necrolysis).

Pharmacokinetics

Onset and Duration
 Onset
 Initial Response
 Anxiety, oral: 15 to 30 minutes
 Duration
 Single Dose
 Anxiety, oral: 6 hours
Drug Concentration Levels
A) Therapeutic Drug Concentration
1) Not established, but were suggested to be in the 10 to 14 mcg/ml range
B) Time to Peak Concentration
1) Oral: 1 to 2 hours
a) Time to peak concentration is delayed in the elderly (mean time to peak: 3.1 hours versus 1.3 hours)
C) Area Under the Curve
1) 273 mcg/mL/h
a) Area under the curve has been reported to be 217 mcg/mL/h in elderly patients
ADME
Absorption
A) Bioavailability
1) Absorption was delayed (mean time to peak 3.1 vs 1.3 hours) but not reduced (mean peak levels 4.7 vs 4.9 mcg/mL; mean area under the curve 273 vs 217 mcg/mL/h) in 8 elderly patients compared with 5 healthy young subjects
Distribution
A) Distribution Sites
1) Protein Binding
a) 48%
2) OTHER DISTRIBUTION SITES
a) Tissue
1) Equally distributed between blood and tissue binding sites
Metabolism
A) Metabolism Sites and Kinetics
1) Stomach
a) Nonenzymatically hydrolyzed in the stomach
2) Liver
a) Hepatically metabolized by hydrolysis, oxidation, and conjugation to non-glucuronide conjugates
B) Metabolites
1) 4-chlorohippuric acid (major metabolite), 4-chloro-benzoyl-N-methylamide, 4-chlorobenzoic acid, N-methylimino-4-chlorobenzaldehyde, 4-chlorobenzaldehyde and "hydrolyzed" CHLORMEZANONE
Excretion
A) Kidney
1) Renal Clearance (rate)
a) 0.58 mL/min
2) Renal Excretion (%)
a) 40%
Elimination Half-life
A) Parent Compound
1) ELIMINATION HALF-LIFE
a) 19 to 24 hours
1) This half-life is thought to actually be the half-life of the hydrolyzed major metabolite since virtually no unchanged drug is detectable in serum
2) The mean elimination half-life in 8 elderly patients was 54 hours compared with 38 hours in 5 healthy young subjects
2) The mean elimination half-life in 8 elderly patients was 54 hours compared with 38 hours in 5 healthy young subjects

Drug indications

Chlormezanone (marketed under the brandname Trancopal or Fenaprim) is a drug used as an anxiolytic and a muscle relaxant
.

Dosage

Normal Dosage
    Oral route
        1) IMPORTANT NOTE
        a) As of November, 1996, Sanofi Winthrop manufacturers worldwide have voluntarily instituted a recall of all products which contain chlormezanone (Trancopal(R), Trancopal(R) compositum, Muskel Trancopal(R), Muskel Trancopal(R) compositum, Muskel Trancopal(R) cum codeino), due to toxic epidermal necrolytic reactions
        2) The usual adult dosage of chlormezanone for ANXIETY is 200 milligrams orally 3 or 4 times daily; in some patients, 100 milligrams may suffice
        3) The usually reported dosage of chlormezanone for treatment of INSOMNIA is 200 to 400 milligrams orally at bedtime with 400 milligrams being preferred by most patients
        4) Chlormezanone 400 milligrams given with acetaminophen and metoclopramide has been used in the treatment of acute MIGRAINE attack
        5) Chlormezanone has been used in doses of 200 to 400 milligrams 3 or 4 times daily for the relief of pain and MUSCLE SPASM

Drug contraindications

Hypersensitivity to CHLORMEZANONE

Side effects

   Hypotension
Drug-induced rash
Skin finding
Toxic epidermal necrolysis
    Acute intermittent porphyria
Disorder of taste
Gastrointestinal tract finding
    Disorder of taste
      NAUSEA and DRY MOUTH
Cholestatic jaundice syndrome
Hepatitis
 Tremor and MUSCLE WEAKNESS
 DROWSINESS, DIZZINESS, DEPRESSION, WEAKNESS, EXCITEMENT, TREMOR, CONFUSION, and HEADACHE

Pregnancy level

Available evidence is inconclusive or is inadequate for determining fetal risk when used in pregnant women or women of childbearing potential. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during pregnancy.

Breast feeding warning

Available evidence and/or expert consensus is inconclusive or is inadequate for determining infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment against potential risks before prescribing this drug during breastfeeding.

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