Brotizolam [Discontinued in SA Market]

Registered South African indications: 

• Insomnia 

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other benzodiazepines
• Severe hepatic impairment
• Children  
• Myasthenia gravis
• Severe respiratory insufficiency
• Sleep apnoea syndrome

Cautions

• Pregnancy
• Breastfeeding 
• Mild to moderate hepatic impairment 
• Elderly
• Chronic respiratory insufficiency
• Prolonged use
• High doses
• Abrupt withdrawal
• Dependence
• Psychotic illness
• Monotherapy for depression or anxiety associated with depression
• History of alcohol or drug abuse
• Galactose intolerance
• May impair ability to drive and operate machinery 

Forms avail. in SA and covered in this monograph: tab 

Insomnia - severe

• Oral (tab): 0.25mg, dly at bedtime; Max: 0.25mg/24hrs

Patients should ensure that they will be able to have an uninterrupted sleep of 6-7 hours 

Should be taken on an empty stomach with some liquid or allowed to dissolve under the tongue 

Not established for use in children

Pregnancy

• Caution; not recommended
• Safety during pregnancy has not been established
• There is evidence that and its brotizolam and its metabolites cross the placenta
• At high maternally toxic doses, embryotoxic or embryolethal effects were observed

Breastfeeding 

• Caution; not recommended
• In animal studies, there is evidence that brotizolam and its metabolites cross the placenta and are excreted in the milk

Renal Impairment

• No dose adjustment recommended 

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended 
• Severe: Contraindicated

Elderly 

• Caution; dose adjustment recommended
  Recommended dose: Oral (tab): 0.125mg, dly at bedtime

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Nightmare
• Depression
• Altered mood
• Anxiety
• Dependence
• Emotional disorder
• Abnormal behaviour
• Agitation
• Libido disorder
• Confusional state
• Restlessness
• Somnolence
• Headache
• Dizziness
• Sedation
• Ataxia
• Anterograde amnesia
• Dementia
• Mental impairment
• Impaired psychomotor skills
• Depressed level of consciousness
• Withdrawal syndrome
• Paradoxical drug reaction
• Irritability
• Fatigue

Gastrointestinal Disorders

• Dry mouth

Hepatobiliary Disorders

• Jaundice
• Abnormal hepatic function test

Musculoskeletal Disorders

• Muscular weakness

Skin and Subcutaneous Tissue Disorders

• Skin reaction

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity 

Sensory Disorders

• Diplopia

• Central nervous system depressants
• CYP3A4 inducers 
• CYP3A4 inhibitors 

None routine. Specific cases may require

• Hepatic function

Brotizolam is a hetrazepine which binds specifically and with high affinity to benzodiazepine receptors in the central nervous system. Binding of gamma aminobutyric acid to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

Tablet 0.25mg

• Lendormin (Ingelheim) originator