Chemical formula: C₁₅H₁₀BrClN₄S Molecular mass: 393.689 g/mol PubChem compound: 2451
Insufficient data are available on brotizolam to assess its safety during pregnancy. Consequently, the use of brotizolam is not recommended during pregnancy.
If the product is prescribed to a woman of childbearing potential, she should be warned to contact her physician regarding discontinuance of the product if she intends to become or suspects that she is pregnant.
If, although not recommended, brotizolam has been administered during the late phase of pregnancy, or during labour, effects on the neonate, such as hypothermia, hypotonia and moderate respiratory depression (Floppy Infant Syndrome), can be expected, due to the pharmacological action of the product.
Moreover, infants born to mothers who took benzodiazepines chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.
Insufficient data are available on brotizolam to assess its safety during lactation. Consequently, the use of brotizolam is not recommended during lactation.
Since benzodiazepines are found in the breast milk, brotizolam is not recommended for use in breast-feeding mothers.
No clinical data on fertility are available for brotizolam. Preclinical studies performed with brotizolam showed no adverse effects on fertility.
No studies on the effect on the ability to drive and use machines have been performed. However, patients should be advised that they may experience undesirable effects such as sedation, amnesia and impaired psychomotor skills during treatment. Psychomotor impairment may increase the risk of fall and road traffic accident. Concurrent use of alcohol and/or CNS-depressant drugs will potentiate this impairment. If sleep is of insufficient duration, the likelihood of impaired alertness is increased.
Therefore, caution should be recommended when driving a car or operating a machinery. If patients experience any of these events, they should avoid potentially hazardous tasks such as driving or operating machinery.
Most undesirable effects that have been observed so far, relate to the product’s pharmacological action. These phenomena are predominantly at the start of therapy and usually disappear with continued administration. The risk of drug dependence (e.g. rebound effect, altered mood, anxiety and restlessness) increases with the duration of therapy with brotizolam, which should not exceed two weeks.
For determination of the frequencies of side effects pooled data from studies, in which altogether 2,603 adult healthy volunteer and patients have been treated with brotizolam over 1 day to 26 weeks, have been brought up. The following listed frequencies refer to 1,259 healthy volunteers and patients, receiving brotizolam in the recommended dose of 0.25 mg.
Frequency according MedDRA-convention:
Very common (≥1/10)
Common (≥1/100, <1/10)
Uncommon (≥1/1,000, <1/100)
Rare (≥1/10,000, <1/1,000)
Very rare (<1/10,000),
Not known (cannot be estimated from the available data)
Uncommon: Nightmare, Drug Dependence, Depression, Mood altered, Anxiety, Drug dependence, Emotional disorder, Abnormal behaviour, Agitation, Libido disorder
Rare: Confusional state, Restlessness
Common: Somnolence, Headache
Uncommon: Dizziness, Sedation, Ataxia, Anterograde amnesia, Dementia*#, Mental impairment*#, Psychomotor skills impaired*#
Rare: Depressed level of consciousness
Uncommon: Diplopia
Common: gastrointestinal disturbance
Uncommon: Dry mouth
Uncommon: Liver disorder, Jaundice
Uncommon: Skin reactions
Uncommon: Muscle-weakness
Uncommon: Drug withdrawal syndrome, Paradoxical drug reaction, Rebound effect, Irritability, Fatigue
Uncommon: Liver function test abnormal
Road traffic accident*#, Fall*#
* These undesirable effects were not observed among the 1259 subjects exposed to 0.25 mg brotizolam in clinical trials. They have the frequency category “Uncommon” which is the worst value of the ADR point estimate. The corresponding frequency of 0.24% of these undesirable effects is a result of 3 divided by 1259 subjects, which is the rule to be applied for undesirable effects not observed in clinical trials, according to the EC SmPC Guideline 2009.
# Class effect of benzodiazepines
Use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena). Psychic dependence may occur. Abuse of benzodiazepines has been reported.
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