Bromazepan: common spelling variant of bromazepam

Bromazepan is a frequent spelling variant of the active substance bromazepam. The correct name is bromazepam (ending am, like all benzodiazepines). The mix-up with bromazepan arises from typing errors or wrong transcription. Pharmacologically the same substance is meant, a classic benzodiazepine anxiolytic of medium duration.

Bromazepam has been on the market since 1974 under the brand name Lexotanil and many generics. The substance is mainly used for short-term treatment of anxiety, tension and agitation. Because of the dependence potential, treatment duration is usually limited to 4 to 8 weeks.

Mechanism of action

Like all benzodiazepines, bromazepam binds to the benzodiazepine binding site of the GABA A receptor, a ligand-gated chloride channel. Binding allosterically enhances the effect of GABA, the most important inhibitory neurotransmitter in the CNS. The opening probability of the chloride channel rises, the neuron is hyperpolarised and its excitability decreases.

This GABAergic enhancement produces the typical effects:

• Anxiolysis through inhibition of limbic structures
• Sedation via cortical and thalamic pathways
• Muscle relaxation at the spinal level
• Anticonvulsant action
• Anterograde amnesia

Bromazepam has a half-life of 10 to 20 hours, a medium duration of action and few active metabolites. Compared with diazepam, accumulation is limited.

Indications

• Acute and chronic states of tension, agitation and anxiety: short-term in psychologically stressful situations, before procedures and in crises
• Sleep disorders with an anxiety component: when anxiety dominates the sleep disturbance
• Vegetative accompanying symptoms of cardiovascular, gastrointestinal and respiratory disease: with psychogenic components
• Premedication: off-label before diagnostic or surgical procedures

Bromazepam is not suitable as monotherapy for depression or chronic anxiety disorder. In generalised anxiety disorder, SSRIs, SNRIs, pregabalin or buspirone are first choice; benzodiazepines remain reserve.

Dosing and administration

Outpatient setting: 1.5 to 3 mg three times daily, in mild cases also 3 mg in the evening as a single dose. Maximum outpatient dose: 12 mg per day.

Inpatient: up to 24 mg per day in selected cases under close monitoring.

Older patients and impaired hepatic function: initially half dose, slow build-up due to increased sensitivity and reduced metabolism.

Treatment duration including taper should not exceed 4 to 8 weeks. Longer use only on strict indication and after individual benefit-risk assessment.

Tapering: after several weeks of therapy a slow taper, often over weeks, is necessary to avoid withdrawal symptoms.

Side effects

Common: tiredness, drowsiness, dizziness, headache, concentration and reaction problems, muscle weakness, anterograde amnesia.

Uncommon: slurred speech, double vision, nausea, dry mouth, hypotension, rash.

Rare: paradoxical reactions with restlessness, agitation, aggression, nightmares, especially in older patients and children; respiratory depression, especially with other CNS depressants.

Important risks:

• Tolerance: attenuation of effect can occur within weeks
• Dependence: psychological and physical, possible after just 4 to 6 weeks of regular use
• Withdrawal symptoms on stopping: increased anxiety, insomnia, tremor, sweating, muscle pain, in severe cases seizures and delirium
• Fall risk in older patients: markedly increased through sedation and muscle relaxation
• Dementia risk: observational studies suggest a link between long-term benzodiazepine use and cognitive decline

Interactions

• Other CNS depressants (alcohol, opioids, antipsychotics, sedating antihistamines): additive sedation, respiratory depression; combination with opioids is the classic risk constellation for respiratory arrest
• Strong CYP3A4 inhibitors (ketoconazole, itraconazole, HIV protease inhibitors, erythromycin): raised levels, intensified sedation
• Strong CYP3A4 inducers (rifampicin, carbamazepine, St John's wort): reduced levels, loss of efficacy
• Cimetidine, omeprazole: moderate level increase
• Levodopa: attenuated antiparkinson effect

Special considerations

Pregnancy: not recommended, especially in the first trimester. In late pregnancy risk of floppy infant syndrome with hypotonia, feeding difficulty and respiratory depression in the newborn, plus withdrawal syndromes.

Breastfeeding: passes into milk, therefore not recommended.

Children and adolescents: not recommended, paradoxical reactions more frequent.

Older patients: increased sensitivity, fall and fracture risk, cognitive impairment. The PRISCUS list classifies benzodiazepines as potentially inappropriate.

Substance use history: in patients with alcohol or drug dependence, use should be avoided where possible due to high misuse potential.

Close monitoring: in impaired respiratory function, sleep apnoea, myasthenia gravis, acute glaucoma.

Driving: particularly at the start of treatment, with dose increases or in combination with alcohol, fitness to drive is not given.

Related substances

• Buspirone, non-dependence-causing anxiolytic
• Zolpidem, short-acting hypnotic
• Pregabalin, alternative anxiolytic
• Paroxetin as an SSRI for generalised anxiety disorder

Frequently asked questions

Sources

• BfArM Federal Institute for Drugs and Medical Devices
• EMA European Medicines Agency
• AWMF guideline anxiety disorders
• Gelbe Liste bromazepam monograph