Estazolam (Desmethylalprazolam), ProSom®, Eurodin®

• ProSom®

• Eurodin®

• Benzodiazepines
• Sedative-hypnotics

• Tablets: 1mg, 2mg

Insomnia: short-term treatment (no more than 7-10 days)

Pharmacodynamics:

• Mechanism of action: Decrease the activity of CNS by increase the inhibitory effect of neurotransmitter GABA on neurone

Pharmacokinetics:

• Absorption: gastrointestinal tract
• Distribution: 93% bound to protein in plasma
• Metabolism: hepatic (Metabolized by Cytochrome P450 3A)with 0.5-6 hours(mean: 2 hours) peak plasma time and 13.5 to 34.6(mean: 18 hours) hours half-life
• Excretion: urine (4% in feces)

Adults:

• Initial dose: start 1 mg/bedtime, if no responseàincrease to 2 mg
• Maximum dose: 2 mg/day
• Geriatric or Debilitated Patients: Smaller dose => 0.5 mg /bedtime

Pediatrics: It is not recommended under 18 years of age

Concomitant use with medications having Enzyme inhibitor effect (Cytochrome p450) Increase plasma concentration of Estazolam :

• Ketoconazole
• Itraconazole
• Erythromycin
• Nefazodone
• Fluvoxamine
• Cimetidine
• Diltiazem
• Isoniazid
• Macrolides

Concomitant use with medications having Enzyme inducer effect (Cytochrome p450) decrease plasma concentration of Estazolam :

• Carbamazepine
• Phenytoin
• Rifampin
• Barbiturates

More than 10% :

1. Somnolence
2. Headache
3. Hypokinesia
4. Dizziness
5. General weakness
6. ataxia

Less than 10% :

1. Anaphylaxis and angioedema
2. Respiratory depression(esp: in respiratory compromise patients)
3. Abnormal thoughts
4. Confusion
5. Seizure
6. Sleep disorder
7. Drug dependence

1. Known hypersensitivity to medication
2. Pregnancy(congenital malformations)
3. Simultaneous prescription of ketoconazole or Itraconazole

• Pregnancy: Category X
• Lactation: Not Recommended in nursing mother

1. plasma clearance is increased in smokers.

2. Taper slowly, if it is used for more than 6 weeks (prolong therapy)=>To avoid withdrawal symptoms

3. Use with caution in acute alcohol intoxication

4. In pregnancy => increase fetal morbidity and mortality

5. If insomnia worsen or new psychiatric symptoms appears, it should raise the suspicion of other underlying disease.

6. Daytime sleepiness and dizziness => Be cautious for sleep-related behaviors(driving)

7. Abnormal psychiatric problems are reported: combativeness, excitement, bizarre behavior, agitation, hallucinations, depersonalization, amnesia

8. Use with caution in depressed patients=> increase suicidal thoughts

9. Not use alcohol concomitantly

10. Avoid prescription with Ketoconazole, Itraconazole

11. Failure of treatment indicates possible underlying disease

12. Abuse: Caution in administering Oxazepam to individuals known to be addiction prone or those whose history suggests they may increase the dosage on their own initiative.

13. Dependence: The use of benzodiazepines may lead to dependence as defined by the presence of a withdrawal syndrome on discontinuation of the drug.

14. Tolerance: As defined by a need to increase the dose in order to achieve the same therapeutic effect seldom occurs in-patients receiving recommended doses under medical supervision >>> Caution for Tolerance to sedation may occur with benzodiazepines especially in those with drug seeking behaviour.

15.  Impaired Respiratory Function: Caution in the use of Estazolam is recommended in-patients with respiratory depression. In-patients with chronic obstructive pulmonary disease, benzodiazepines can cause increased arterial carbon dioxide tension and decreased arterial oxygen tension.

16. Avoid driving while taking Estazolam!

17. Avoid using dangerous machinery vehicles while taking Estazolam!

18. Caution in concomitant use with CNS-depressant medications! May cause synergistic effect => may increase sedation!

19. 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)