• Tranxene®

• Benzodiazepines
• Anxiolytics
• Sedatives
• Anti-Consultants

Tablets: 3.75 mg, 7,5 mg, 15 mg 

1. Pathological anxiety : short-term symptomatic relief

• Acute Panic Attack
• Limited Social phobia

2. psychoneurotic patients: short-term relief of tension(those with functional somatic complains)

3. seizure

4. Alcohol withdrawal: (adjunctive therapy)

Pharmacodynamics:

• Mechanism of action & Pharmacodynamics: Rapidly decarboxylated to form nordiazepam (N-desmethyldiazepam)

Pharmacokinetics:

• Absorption: Gastrointestinal tract
• Distribution: penetrates the brain rapidly, plasma concentration of nordiazepam in 5 days to 2 weeks. Peak serum level of 1-2 hours
• Metabolism: hepatic
• Excretion: urine, half-life: 48 hours

1. Adults:

• Initial: 15 to 60 mg/day. It is suitable to start with 15mg/day, then increase the dose to reach the desired goal. Properly, prescribe every night once daily (also can be divided into two doses).
• Maximum dose: 60 mg/day

•  Debilitated and Elderly Patients: Initial: 3.75 mg/day (preferably at night), then increase slowly and carefully to stabilize the patient.
• Acute alcoholic withdrawal: First 24 hours: 30-90mg in divided doses (depend on response and tolerance) Second 24 hours: the dosage should be reduced to not more than 60 mg in divided doses. Till 4^th day: reduce slowly, not more than 15-30mg, and then taper off rapidly to discontinue.

2. Pediatrics: It is not recommended

•  When relief of symptoms are observed, reduce to lowest dosage in which no symptoms return
• If the dosage exceeds 20mg/day in elderly, cardiovascular system should be monitored

• Sodium oxybate
• Idelalisib
• Ivacaftor
• Acetaminophen / propoxyphene
• Albuterol
• Alfentanil
• Alprazolam
• Amitriptyline
• Aspirin / Caffeine / Propoxyphene
• Buprenorphine
• Clozapine
• Fluoxetine / Olanzapine
• Antacids

Most common => drowsiness

Less common (in descending order):

• Dizziness
• Gastrointestinal complaints
• Nervousness
• Blurred vision
• Dry mouth
• Headache
• Mental confusion
• Insomnia,
• Transient skin rashes
• Fatigue
• Ataxia
• Genito-urinary complaints
• Irritability
• Diplopia
• Depression
• Slurred speech
• Hypotension and dysfunction liver and kidney tests

1. Hypersensitivity to this drug
2. Myasthenia gravis

• Pregnancy: Not recommended => great risk of malformations
• Lactation: Not Recommended in nursing mother

1. Concurrent use of antacids with clorazepate may reduce 12% of bioavailability of this drug

2. It is not recommended for use in:

• Anxiolytic to address everyday life stress
• Depressive neuroses
• Treatment of psychotic or severely depressed patients
• Psychotic reactions
• Patients less than 18 years of age

3. Use with caution in the setting of other CNS depressant drugs (e.g. benzodiazepines may be potentiated by barbiturates, narcotics, phenothiazines, monoamine oxidase inhibitors), because of its CNS depressant effect

4. Clorazepate increases the effect of alcohol and chlorpromazine.

5. Increasing sedation: Use with caution in patients who is working in dangerous occupations that need mental alertness. Avoid driving and using dangerous machineries while taking medication.

6. Long-term use=> do complete blood counts and liver function tests periodically(also renal precautions in patients with kidney disease)

7. Malformations has been published in the infant of a mother who had taken this drug during the first trimester of pregnancy.

8. Do NOT prescribe for patients prone to drug abuse.

9. Use with caution in those who have potential risk for psychological dependence=>

• withdrawal symptoms after abrupt discontinuation: insomnia, nervousness, irritability, muscle aches, diarrhea, tremor, and memory impairment
• Do not do abrupt discontinuation

10. Be administered with caution to patients with acute narrow-angle glaucoma.

11. Elderly and disabled patients or organic brain syndromeàbecause of their susceptibility to CNS depression, administer with low dose and increase gradually if needed.

12. Clorazepate overdose treatment=> Supportive therapy is recommended:

• Flumazenil ( Benzodiazepines antidotes) may induce seizures in patients with a history of seizures disorder or who are on tricyclic antidepressants.
• Over-dosage:
• • Clinical manifestations has wide ranges, from drowsiness to coma
  • Treatment: 1) Activated charcoal should be given to reduce absorption. 2) Do supportive treatments for any possible respiratory depression or hypotension
  • Flumazenil >>> 0.2 mg IV in 13-30 minutes >>> If no response after 30 minutes, add 0.3 mg in 30 seconds one minute later. Maximum total dose: 3 mg/hr (contact your regional Poison Control Centre for more information)

13. This drug may cause=> aggression, antegrade amnesia