Clorazepate Dipotassium
Name: Clorazepate Dipotassium
Interactions for Clorazepate Dipotassium
Specific Drugs
| Drug | Interaction | Comments |
|---|---|---|
| Antacids | Possible decrease in rate and extent of conversion of clorazepate to desmethyldiazepam;b however, manufacturer states that usual antacid dosages do not substantially alter clorazepate bioavailabilityc | |
| Cimetidine | Decreased plasma clearance and increased plasma half-lives and concentrations of the benzodiazepine | Clinical importance not well established; consider possible need for clorazepate dosage reduction |
| CNS depressants (e.g., alcohol, anticonvulsants, antidepressants, barbiturates, hypnotics, opiates, phenothiazines) | Additive CNS depressionb c | Use with caution to avoid overdosageb c |
| Disulfiram | Possible inhibition of clorazepate metabolism | Use with caution; consider possible need for clorazepate dosage reduction |
| HIV protease inhibitors (e.g., amprenavir, fosamprenavir, ritonavir, saquinavir) | Possible increased benzodiazepine concentrations | Clinical importance not established; consider possible need for clorazepate dosage reduction |
Clorazepate Dipotassium Pharmacokinetics
Absorption
Bioavailability
Rapidly decarboxylated in the GI tract and absorbed as desmethyldiazepam (nordiazepam).b c Rate of decarboxylation decreases as gastric pH increases.b
Distribution
Extent
Benzodiazepines are widely distributed into body tissues and cross the blood-brain barrier.b
Desmethyldiazepam is distributed into milk.c
Benzodiazepines and their metabolites generally cross the placenta.b
Plasma Protein Binding
Desmethyldiazepam: 97–98%.b c
Elimination
Metabolism
Rapidly decarboxylated in the GI tract to form desmethyldiazepam;b c further metabolized in the liver via hydroxylation and subsequent conjugation with glucuronic acid.b c g g Major active metabolites are desmethyldiazepam and oxazepam.b
Elimination Route
Excreted principally in urine.b c
Half-life
Metabolites: Desmethyldiazepam: 40–50 hours (range: 30–200 hours).b c Oxazepam: 3–21 hours.b
Special Populations
In geriatric patients and patients with liver disease, half-life of desmethyldiazepam may be prolonged.b
Benzodiazepines are not appreciably removed by hemodialysis.b