Adverse Drug Reaction Overview Most Frequent Adverse Reactions:
The most frequently reported adverse reactions with APO-BROMAZEPAM are related to CNS effects and include drowsiness, ataxia and dizziness. These phenomena occur predominantly when starting APO-BROMAZEPAM and usually disappear with repeated administration.
Serious and Important Adverse Reactions:
There have been reports of falls and fractures in benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly. Allergic reactions and a very few cases of anaphylaxis have been reported to occur with benzodiazepines.
Release of hostility and other paradoxical reactions such as irritability, excitability, restlessness, agitation, aggressiveness, delusion, anger, nightmares, hallucinations, psychosis, inappropriate behaviour and other adverse behavioural effects are known to occur with the use of benzodiazepines.
They are more likely to occur in children and elderly patients than in other patients. If these occur, use of APO-BROMAZEPAM should be discontinued. Anterograde amnesia may occur using therapeutic doses of benzodiazepines, the risk increasing with higher doses.
Effects of anterograde amnesia may be associated with inappropriate behaviour. Chronic use (even at therapeutic doses) may lead to the development of physical and psychological drug dependence: discontinuation of APO-BROMAZEPAM may result in withdrawal or rebound phenomena (see WARNINGS AND PRECAUTIONS).
Abuse of benzodiazepines is more common in poly-drug abusers. Post-Market Adverse Drug Reactions Other side effects which can occur, listed by body systems, include the following: Cardiovascular System: Cardiac failure including cardiac arrest; hypotension, palpitations, tachycardia.
Dependence/Withdrawal:
Development of physical dependence and withdrawal following discontinuation of therapy has been observed with benzodiazepines such as APO- BROMAZEPAM. Severe and life-threatening symptoms have been reported. (see SERIOUS WARNINGS AND PRECAUTIONS BOX, Addiction, Abuse and Misuse; WARNINGS AND PRECAUTIONS, Dependence/Tolerance).
Digestive System:
Dry mouth, nausea, non-specific gastrointestinal disturbances, vomiting.
Page 11 of 28 Hemic and Lymphatic System:
Decreased hemoglobin and hematocrit, increased and decreased WBC.
Injury, Poisoning and Procedural Complications:
There have been reports of falls and fractures in benzodiazepine users due to adverse reactions such as sedation, dizziness and ataxia. The risk is increased in those taking concomitant sedatives (including alcoholic beverages), the elderly and debilitated patients.
Metabolic and Nutritional Disorders:
Increased and decreased blood sugar levels, elevations of alkaline phosphatase, bilirubin, SGOT, SGPT.
Musculoskeletal System:
Muscle weakness, muscle spasm.
Nervous System:
Drowsiness, headache, dizziness, decreased alertness, ataxia, fatigue, seizures, confusional state, disorientation, emotional and mood disturbances, nervousness, anxiety, abnormal dreams, hyperactivity, depression, euphoria, changes in libido.
Respiratory Disorders:
Respiratory depression.
Skin and Subcutaneous Tissue Disorders Appendages:
Pruritus, rash.
Special Senses:
Diplopia, blurred vision.
Urogenital System:
Incontinence. DRUG INTERACTIONS Serious Drug Interactions Concomitant use of APO-BROMAZEPAM and opioids may result in profound sedation, respiratory depression, coma and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are not possible.
Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. (see WARNINGS AND PRECAUTIONS BOX, General, Risks from Concomitant use with Opioids) Drug-Drug Interactions Pharmacokinetic Drug-Drug Interaction (DDI) The specific enzymes involved in the metabolism of bromazepam have not been fully elucidated.
There is a possibility that compounds which inhibit key oxidative hepatic enzymes may enhance the activity of benzodiazepines. Co-administration of cimetidine, a multi-CYP inhibitor, and possibly propranolol may prolong the elimination half-life of bromazepam through a substantially reduced clearance (with cimetidine reduction by 50%).
9-time). Bromazepam at therapeutic doses does not change the pharmacokinetics of co- administered antipyrine, a substrate of several CYP enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C18, and CYP3A4). Furthermore, bromazepam did not induce major CYP450 isozymes in vitro at the level of mRNA; also it did not activate nuclear hormone receptors.
Therefore, bromazepam is unlikely to cause pharmacokinetic drug- drug interactions based on CYP450 induction. Pharmacodynamic Drug-Drug Interaction (DDI) CNS-acting drugs Enhanced side effects such as sedation and cardio-respiratory depression may also occur when APO-BROMAZEPAM is co-administered with any centrally acting depressants including alcohol, narcotics, narcotic analgesics, barbiturates, non-barbiturate hypnotics, antihistamines, phenothiazines, thioxanthenes, butyrophenones classes of antipsychotics, anxiolytics/ sedatives, anesthetics, monoamine oxidase inhibitors, tricyclic antidepressants and anticonvulsants (see WARNINGS AND PRECAUTIONS, Concomitant use of alcohol / CNS depressants, and OVERDOSAGE sections).
Because of the enhancement of side effects that might occur, patients should be advised against the simultaneous use of other CNS depressant drugs and should be cautioned not to take alcohol during the administration of APO-BROMAZEPAM.
Opioids Due to additive CNS depressant effect, the concomitant use of benzodiazepines, including APO-BROMAZEPAM, and opioids increases the risk of profound sedation, […]