Triazolam (Page 3 of 6)

5.10 Neonatal Sedation and Withdrawal Syndrome

Use of triazolam during the later stages of pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate. Observe newborns for signs of sedation and neonatal withdrawal syndrome and manage accordingly [ see Use in Specific Populations (8.1) ] .

5.11 Compromised Respiratory Function

In patients with compromised respiratory function, respiratory depression and apnea have been reported. Closely monitor patients with compromised respiratory function. If signs and symptoms of respiratory depression or apnea occur, consider discontinuation.

6 ADVERSE REACTIONS

The following serious adverse reactions are discussed in greater detail in other sections:

  • Risks from Concomitant Use with Opioids [see Warnings and Precautions (5.1)]
  • Abuse, Misuse, and Addiction [see Warnings and Precautions (5.2)]
  • Dependence and Withdrawal Reactions [see Warnings and Precautions (5.3)]
  • Persistent or Worsening Insomnia [see Warnings and Precautions (5.4)]
  • “Sleep-driving” and Other Complex Behaviors [see Warnings and Precautions (5.5)]
  • Central Nervous System Manifestations [see Warnings and Precautions (5.6)]
  • Effects on Driving and Operating Heavy Machinery [see Warnings and Precautions (5.7)]
  • Patients with Depression [see Warnings and Precautions (5.9)]
  • 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 triazolam.

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.

Table 1: Common Adverse Drug Reactions in 1% or More of Triazolam-Treated Subjects (and Greater than Placebo) Reported in Placebo-Controlled Clinical Trials
Event Triazolam
(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 Table 1, 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 triazolam. 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 complication s : 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

7 DRUG INTERACTIONS

7.1 Drugs Having Clinically Important Interactions With Triazolam

Table 2 includes clinically significant drug interactions with triazolam [see Clinical Pharmacology (12.3)] .

Table 2: Clinically Important Drug Interactions with Triazolam
Opioids
Clinical implication The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists.
Prevention or managemen t Limit dosage and duration of concomitant use of triazolam and opioids, and monitor patients closely for respiratory depression and sedation [see Warnings and Precautions (5.1)].
CNS Depressants
Clinical implication Triazolam produces additive CNS depressant effects when co-administered with other CNS depressants.
Prevention or management Limit dosage and duration of triazolam during concomitant use with CNS depressants.
Strong Inhibitors of CYP 3A
Clinical implication Concomitant use of triazolam with strong CYP3A inhibitors has a profound effect on the clearance of triazolam, resulting in increased concentrations of triazolam and increased risk of adverse reactions [see Clinical Pharmacology (12.3)].
Prevention or management Do not administer triazolam with a strong CYP3A4 inhibitor [see Contraindications (4), Warnings and Precautions (5.8)].
Moderate and Weak Inhibitors of CYP 3A
Clinical implication Concomitant use of triazolam with moderate or weak inhibitors of CYP3A inhibitors may increase the concentrations of triazolam, resulting in increased risk of adverse reactions [see Clinical Pharmacology (12.3)] .
Prevention or management Use with caution and consider appropriate dose reduction of triazolam when coadministered with moderate and weak CYP3A inhibitors [see Warnings and Precautions (5.8)] .
Strong Inducers of CYP 3A
Clinical implication Coadministration of triazolam with strong inducers of CYP3A4 can significantly decrease the plasma concentration of triazolam and may decrease effiectiveness of triazolam.
Prevention or management Caution is recommended during coadministration of triazolam with strong inducers of CYP3A4.
Interactions Based on Experience with Other Benzodiazepines or in vitro Studies with Triazolam
Clinical implication Available data from clinical studies of benzodiazepines other than triazolam, from in vitro studies with triazolam, or from in vitro studies with benzodiazepines other than triazolam suggest a possible drug interaction with triazolam [see Clinical Pharmacology (12.3)].
Prevention or management Caution is recommended during coadministration of triazolam tablets with any of these drugs. [see Warnings and Precautions (5.8)] .

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