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8.1 Adverse Reaction Overview
The adverse reaction most frequently reported was drowsiness.
Reported adverse reactions (by system) are:
Body as a Whole
Angioedema, asthenia, muscle weakness, anaphylactic reactions, change in weight, drug withdrawal syndrome, hypersensitivity reactions, hyponatremia, hypothermia, SIADH;
Cardiovascular
Hypotension, lowering in blood pressure;
Digestive
Nausea, constipation, change in appetite, increase in bilirubin, jaundice, increase in liver transaminases, increase in alkaline phosphatase;
Hematological/Lymphatic
Agranulocytosis, pancytopenia, thrombocytopenia;
Nervous System and Special Senses (benzodiazepine effects on the CNS are dose dependent, with more severe CNS depression with higher doses)
Anterograde amnesia, drowsiness, fatigue, sedation, ataxia, confusion, depression, unmasking of depression, dizziness, change in libido, impotence, decreased orgasm, extrapyramidal symptoms, tremor, vertigo, visual disturbances (including diplopia, and blurred vision), dysarthria/slurred speech, headache, convulsions/seizures, amnesia, disinhibition, euphoria, coma, suicidal ideation/attempt, impaired attention/concentration, balance disorder, paradoxical reactions (including anxiety, agitation, excitation, hostility, aggression, rage, sleep disturbances/insomnia, sexual arousal, hallucinations), psychomotor agitation, drug abuse, drug dependence;
Respiratory
Respiratory depression, apnea, worsening of sleep apnea (the extent of respiratory depression with benzodiazepines is dose dependent - more severe depression at higher doses), worsening of obstructive pulmonary disease, and ear, nose and throat disturbances;
Skin
Allergic skin reactions, alopecia.
There is evidence that tolerance develops to the sedative effects of benzodiazepines.
Release of hostility and other paradoxical effects such as irritability and excitability, are known to occur with the use of benzodiazepines. Paradoxical reactions may be more likely to occur in children or the elderly. Should paradoxical reactions occur, use of the drug should be discontinued. In addition, hypotension, mental confusion, slurred speech, over sedation and abnormal liver and kidney function tests and hematocrit values have been reported with these drugs.
8.5 Post-Market Adverse Reactions
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), geriatric and debilitated patients.
Dependence/Withdrawal
Development of physical dependence and withdrawal following discontinuation of therapy has been observed with benzodiazepines such as ATIVAN. Severe and life-threatening symptoms have been reported. (see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX, Addiction, Abuse and Misuse; 7 WARNINGS AND PRECAUTIONS, Dependence/Tolerance)
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