6 ADVERSE REACTIONS
The following serious adverse reactions are discussed in greater detail in other sections:
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- Risks from Concomitant Use with Opioids [see Warnings and Precautions (5.1)]
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- Abuse, Misuse, and Addiction [see Warnings and Precautions (5.2)]
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- Dependence and Withdrawal Reactions [see Warnings and Precautions (5.3)]
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- Persistent or Worsening Insomnia [see Warnings and Precautions (5.4)]
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- "Sleep-driving" and Other Complex Behaviors [see Warnings and Precautions (5.5)]
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- Central Nervous System Manifestations [see Warnings and Precautions (5.6)]
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- Effects on Driving and Operating Heavy Machinery [see Warnings and Precautions (5.7)]
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- Patients with Depression [see Warnings and Precautions (5.9)]
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- Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions (5.10)]
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- Compromised Respiratory Function [see Warnings and Precautions (5.11)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The incidences cited below are estimates of clinical reactions among 1003 subjects who participated in the short term (duration of 1 to 42 days) placebo-controlled clinical trials of Halcion.
Adverse reactions leading to discontinuation in two multi-dose placebo controlled clinical trials include coordination disorders, drowsiness, grogginess, somnolence, depression, restlessness, dizziness, lightheadedness, headache, nausea, visual disturbance, nervousness, abdominal distress, bladder trouble, aching limbs, backache, and blepharitis.
| Event | Halcion (N=1003) % Patients Reporting | Placebo (N=997) % Patients Reporting |
|---|---|---|
Central Nervous System | ||
Drowsiness | 14.0 | 6.4 |
Headache | 9.7 | 8.4 |
Dizziness | 7.8 | 3.1 |
Nervousness | 5.2 | 4.5 |
Light-headedness | 4.9 | 0.9 |
Coordination disorders/ataxia | 4.6 | 0.8 |
Gastrointestinal | ||
Nausea/vomiting | 4.6 | 3.7 |
In addition to the common reactions enumerated above in Table1, the following adverse reactions have been reported at an incidence of 0.9% to 0.5%: euphoria, tachycardia, tiredness, confusional states/memory impairment, cramps/pain, depression, and visual disturbances.
Adverse reactions reported at an incidence less than 0.5% include: constipation, taste alterations, diarrhea, dry mouth, dermatitis/allergy, dreaming/nightmares, insomnia, paresthesia, tinnitus, dysesthesia, weakness, congestion, and death from hepatic failure in a patient also receiving diuretic drugs.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of Halcion. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
General disorders and administration site conditions: Paradoxical drug reaction, chest pain and fatigue
Gastrointestinal disorders: Tongue discomfort, glossitis, stomatitis
Hepatobiliary disorders: Jaundice
Injury, poisoning and procedural complications: Fall
Metabolism and nutrition disorders: Anorexia
Nervous system disorders: Anterograde amnesia, altered state of consciousness, dystonia, sedation, syncope, dysarthria and muscle spasticity
Psychiatric disorders: Confusional state (disorientation, derealisation, depersonalization), mania, agitation, restlessness, irritability, sleep disorder and libido disorder, hallucination, delusion, aggression, somnambulism, and abnormal behavior
Renal and urinary disorders: Urinary retention and urinary incontinence
Reproductive system and breast disorders: Menstruation irregular
Skin and subcutaneous tissue disorders: Pruritis