Posology : מינונים

2. Dosage and Administration
For insomnia:
Adults and children over 12 years: 10 ml daily, in certain cases a higher dosage may be required - up to 20 ml daily.
Children 6-12 years: 5-10 ml daily.
Children 1-5 years: 2.5-5 ml daily.
Infants up to 1 year: 1-2.5 ml daily.
As a sedative:
Adults and children over 12 years: 5 ml twice daily.
Children 6-12 years: 5 ml daily.
Children 1-5 years: 2.5 ml daily.
Infants up to 1 year: 1 ml daily.
3. Clinical Results
(1) Clinical Data Package
None
(2) Clinical Effects
Clinical results judging by sleeping effects were 84.3% (321/381).
(3) Clinical Pharmacological Test
No applicable data
(4) Exploratory Test
No applicable data
(5) Verification Test
1) Randomized Parallel Dosage Response Study
No applicable data
2) Comparative Test
The following results were obtained comparing chloral hydrate (22mg/kg) and triclofos sodium (33mg/kg) in 71 children aged 4 to 14 years old who require sedation during EEG. EEG was used for the sleep start monitor.


Triclofos Sodium syrup (37 subjects)          Chloral hydrate (34 subjects) 
Dosage*              Average 1 g (480 mg to 1960 mg)          Average: 680 mg (300mg to 1,510mg) Sleep introduction time              37.3 ± 12.1 minutes                       36.6 ± 14.4 minutes Ineffective cases                       6 cases                                   4 cases Taste       Aversion                    2 cases (5%)                              9 cases (27%) Good                     14 cases (33%)                            11 cases (32%) Very good                   21 cases (51%)                            14 cases (41%) Adverse reactions              16 types in 9 people (24%)                16 types in 9 people (26%) *: Dosage is expressed in the amount of the active ingredient.
Triclofos Sodium Syrup active ingredient: Triclofos sodium
Chloral hydrate active ingredient
3) Safety Test
No applicable data
4) Testing by patient/condition
No applicable data
(6) Therapeutic Use
1) Treatment outcome study and research of specific uses (special survey)/Clinical studies after manufacturing and sales (post-marketing clinical results) No applicable uses
2) Approval conditions of details for execution or overview of the executed testing
None
Pharmacology Matters


1. Pharmacologically-related Chemical Compound or Compound Group
Chloral hydrate
2. Pharmacological Action
(1) Site and mechanism of action
Site of action:                 Reticular of brainstem
Mechanism of action:            Inside the body, it becomes the metabolite trichloroethanol, in the same way chloral hydrate does, and exhibits sedation and hypnotic activity. There is less gastrointestinal irritation than with chloral hydrate.
(2) Study results that support drug efficacy
See Treatment Matters I-2. Pharmacological Action (3) Onset time/duration of action (3) Onset time/duration of action
Onset time of action
Within 60 minutes
Fell asleep within 30 minutes of administration: 381/1075 cases (35.4%) within 45 minutes:                       818/1075 cases (76.1%) within 60 minutes:                       1011/1075 cases (94.0%)

Duration of action:
Action lasted 2 to 3 hours in the highest amount of cases
Out of 295 pediatric cases, sleep duration was 2 to 3 hours in 41.7% (123), 5 to 6 hours in 14.2% (42) and at least 2 hours in 68.8% (203) of cases.
Out of 143 adult cases, sleep duration was at least 2 hours in 62.9% (90) of cases.


Pharmacokinetic Matters

1. Change in Blood Concentration and Method of Measurement
(1) Blood concentration effective in treatment
No applicable data
(2) Time to reach peak blood concentration
About 1 hour
(3) Blood concentration confirmed in clinical trials
Blood concentration of trichloroethanol when a 22.5 mg/kg dose was administered orally to a healthy adult (n=7) reached a peak of 8.2 ± 0.6μg/mL one hour after administration, with a half-life (T1/2β) of 8.2 hours. 4)



(4) Toxicity Zone
No applicable data
(5) Effects of diet and concomitant drugs
No applicable data
(6) Pharmacokinetic variability factors found by population analysis No applicable data


2. Pharmacokinetic Parameters
(1) Analysis method
No applicable data
(2) Absorption rate constant
No applicable data
(3) Bioavailability
No applicable data
(4) Elimination rate constant
No applicable data
(5) Clearance
No applicable data
(6) Distribution volume
No applicable data
(7) Blood plasma protein coupling
35%
3. Absorption
Absorption site: Stomach

4. Distribution
(1) Permeability of blood-brain barrier
High (permeates)
(2) Permeability of blood-placental barrier
High (permeates)
(3) Transferability to breastmilk
No applicable data
(4) Transferability to cerebrospinal fluid
No applicable data
(5) Penetrability to other tissue
No applicable data

5. Metabolism
(1) Metabolic site and metabolic pathway
Trichloroethanol is metabolized by trichloro acetic acid in red blood cells, liver and other tissue.5) Biological half-life is 4 to 12 hours.
(2) Molecular species of enzymes involved in metabolism (CYP450, etc.) No applicable data
(3) Initial permeation effects and ratio, if any
No applicable data
(4) Metabolite action and ratio, if any
No applicable data
(5) Kinetic parameters of metabolites
No applicable data

6. Excretion
(1) Excretion site and route
There are excretions in the urine and excretions in bile in the form of trichloroethanol, glucuronic acid conjugate and trichloro acetic acid.
(2) Excretion rate
At 24 hours after administration, 17 to 40% is excreted in the urine comprising 4.6% (0.5 to 19%) of the dosage (15mg/kg) as an unaltered substance, combined with glucuronic acid conjugate.
(3) Excretion speed
Trichloro acetic acid excretion is slower with 10% or less during the first two hours, 25% or less during the next 6 hours and reaching 38% at 24 hours (excretion is slow and there are still traces in the blood even three days after administration).

7. Transporter Information
No applicable data
8. Extraction Ratio by Dialysis, etc.
No applicable data

Safety Matters (precautions in use)

1. Warnings and Reasons
None