TRIAZOLAM

1 Dosing Considerations  TRIAZOLAM should always be prescribed at the lowest effective dose for the shortest duration possible. TRIAZOLAM (triazolam) Page 6 of 31  Treatment with triazolam should usually not exceed 7-10 consecutive days.

Use for more than 2-3 consecutive weeks requires complete reevaluation of the patient.  TRIAZOLAM can produce withdrawal signs and symptoms or rebound phenomena following abrupt discontinuation or rapid dose reduction. See 3 SERIOUS WARNINGS AND PRECAUTIONS BOX, Withdrawal; 7 WARNINGS AND PRECAUTIONS, Dependence/Tolerance.

Abrupt discontinuation should be avoided and treatment - even if only of short duration - should be terminated by gradually tapering the dosage schedule under close monitoring.  Tapering should be tailored to the specific patient. Special attention should be given to patients with a history of seizure.

See 3 SERIOUS WARNINGS AND PRECAUTIONS BOX, Withdrawal; 7 WARNINGS AND PRECAUTIONS, Error! Reference source not found..  If a patient experiences withdrawal signs and symptoms, consider postponing the taper or raising the benzodiazepine to the previous dosage prior to proceeding with a gradual taper.

 Geriatric patients in particular may be more sensitive to benzodiazepines. See 7 WARNINGS AND PRECAUTIONS, Falls and fractures.  Long-term use of TRIAZOLAM should be avoided in elderly patients. Enhanced monitoring is recommended. 125 mg; for many patients this dose immediately before retiring should be sufficient.

25 mg should not be exceeded. 5 mg should be used only for exceptional patients who do not respond adequately to a trial of the lower dose since the risk of several adverse reactions increases with the size of the dose administered.

125 mg before retiring. 25 mg dose should be used only for exceptional patients who do not respond to a trial of the lower dose. Caution and consideration of dose reduction are recommended during coadministration of CYP 3A inhibitors with triazolam.

4 Drug-Drug Interactions. Health Canada has not authorized an indication for pediatric use. 5 Missed Dose If the patient misses a dose, inform the patient to skip the missed dose and take the next dose at the regular dosing schedule.

, sedation (morning drowsiness, somnolence), dizziness, nervousness/irritability and impaired coordination. The most serious adverse reactions which may occur include memory impairment, abnormal thinking/behavior, confusion, anxiety, and depression.

See 7 WARNINGS AND PRECAUTIONS. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real- world use. The incidence of adverse reactions among patients receiving triazolam or placebo is listed in the TRIAZOLAM (triazolam) Page 12 of 31 table.

The figures cannot be used to predict precisely the incidence of untoward events in the course of usual medical practice where patient characteristics and other factors often differ from those in clinical trials. Comparison of the cited figures, however, can provide the prescriber with some basis for estimating the relative contributions of drug and nondrug factors to the untoward event incidence rate in the population studied.

5%) The adverse reaction profile of triazolam observed in controlled clinical trials illustrates the dose- dependency of most of the adverse reactions. At present, the higher dose range is not recommended. See 4 DOSAGE AND ADMINISTRATION.

3 TRIAZOLAM (triazolam) Page 13 of 31 The adverse reactions reported in the table were observed in controlled clinical trials conducted by The Upjohn Company. 5%) adverse reactions include: Cardiac disorders: syncope, dyspnea Ear and labyrinth disorders: hearing impairment, tinnitus Eye disorders: eye irritation/redness Gastrointestinal disorders: constipation, flatulence, oral irritation General disorders and administration site conditions: edema, chest pain, hot/cold flashes, malaise Investigations: Elevated levels of SGOT, bilirubin and alkaline phosphatase have also been noted.

2 Geriatrics Long-term use of TRIAZOLAM should be avoided in elderly patients. Enhanced monitoring is recommended. 1 Dosing considerations. 2 CONTRAINDICATIONS  TRIAZOLAM is contraindicated in patients with known hypersensitivity to this drug, other benzodiazepines, or to any ingredient in the formulation, including any non-medical ingredient, or component of the container.

For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.  Triazolam is contraindicated in patients who in the past manifested paradoxical reactions to alcohol and/or sedative medications, and in subjects with a history of substance or alcohol abuse.

 Triazolam is contraindicated in pregnant women. Benzodiazepines may cause fetal damage when administered during pregnancy. During the first trimester of pregnancy, several studies have suggested an increased risk of congenital malformations associated with the use of benzodiazepines.

During the last weeks of pregnancy, ingestion of therapeutic doses of a benzodiazepine hypnotic has resulted in neonatal CNS depression due to transplacental distribution. If triazolam is prescribed to women of child-bearing potential, the patient should be warned of the potential risk to a fetus and advised to consult her physician regarding the discontinuation of the drug is she intends to become pregnant.

 Triazolam is contraindicated in patients who have myasthenia gravis or a history of uncorrected narrow-angle glaucoma. 4 Drug-Drug Interactions). TRIAZOLAM (triazolam) Page 5 of 31 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions Addiction, Abuse and Misuse The use of benzodiazepines, including TRIAZOLAM, can lead to abuse, misuse, addiction, physical dependence and withdrawal reactions.

Abuse and misuse can result in overdose or death, especially when benzodiazepines are combined with other medicines, such as opioids, alcohol or illicit drugs.  Assess each patient’s risk prior to prescribing TRIAZOLAM  Monitor all patients regularly for the development of these behaviours or conditions.

 TRIAZOLAM is contraindicated in patients with known hypersensitivity to this drug, other benzodiazepines, or to any ingredient in the formulation, including any non-medical ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

 Triazolam is contraindicated in patients who in the past manifested paradoxical reactions to alcohol and/or sedative medications, and in subjects with a history of substance or alcohol abuse.  Triazolam is contraindicated in pregnant women.

Benzodiazepines may cause fetal damage when administered during pregnancy. During the first trimester of pregnancy, several studies have suggested an increased risk of congenital malformations associated with the use of benzodiazepines.

During the last weeks of pregnancy, ingestion of therapeutic doses of a benzodiazepine hypnotic has resulted in neonatal CNS depression due to transplacental distribution. If triazolam is prescribed to women of child-bearing potential, the patient should be warned of the potential risk to a fetus and advised to consult her physician regarding the discontinuation of the drug is she intends to become pregnant.

 Triazolam is contraindicated in patients who have myasthenia gravis or a history of uncorrected narrow-angle glaucoma. 4 Drug-Drug Interactions). TRIAZOLAM (triazolam) Page 5 of 31