TRIAZOLAM 0.250mg. Tablets.

BOXED WARNING

As with other benzodiazepines, triazolam should be used with extreme caution in patients with pulmonary disease or conditions associated with compromised respiratory function such as sleep apnea, bronchitis, pneumonia, asthma, or chronic obstructive pulmonary disease (COPD). Additionally, avoid coadministration with other CNS depressants, especially opioids, unless no other alternatives are available as coadministration significantly increases the risk for respiratory depression, low blood pressure, and death. Triazolam should not be used in patients with preexisting respiratory depression, cases of shock, or coma because the drug can worsen respiratory and CNS depression. Triazolam should be used cautiously in patients who snore regularly, because partial airway obstruction may convert to obstructive sleep apnea with benzodiazepine administration.

DEA CLASS

Rx, schedule IV

DESCRIPTION

Short acting benzodiazepine; no active metabolites; anterograde amnesia reported more frequently with triazolam than with other hypnotic benzodiazepines; used for insomnia.

COMMON BRAND NAMES

Halcion

HOW SUPPLIED

Halcion/Triazolam Oral Tab: 0.125mg, 0.25mg

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

0.5 mg/day PO.

0.25 mg/day PO.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Specific guidelines are not available; however, an initial dosage of 0.125 mg PO at bedtime has been suggested for patients with hepatic impairment (e.g., cirrhosis).

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. No dosage adjustment is needed for patients on hemodialysis or CAPD.

ADMINISTRATION

A Med Guide that provides information about proper use and risks of sedative-hypnotics should be dispensed with each new prescription.

STORAGE

Halcion:
– Store at controlled room temperature (between 68 and 77 degrees F)

CONTRAINDICATIONS / PRECAUTIONS

Triazolam is contraindicated in any patient with a known triazolam or other benzodiazepine hypersensitivity or known allergies to any component of the formulation. Reactions including anaphylaxis or angioedema may become evident as early as the initial dose. Patients should be instructed on the appropriate action in the event of an allergic reaction. Treatment with triazolam should not be reinitiated in patients who experience angioedema after administration of the drug.

It is important to use the smallest effective dose of triazolam. Patients who present initially for treatment for sleep disturbances may have an underlying psychological and/or physiological disturbance and should be thoroughly evaluated prior to initiation of triazolam. The failure of the insomnia to remit or worsening of the insomnia after 7—10 days may indicate the presence of other primary disorders. Worsening of depression has been reported with benzodiazepine use. Although triazolam is occasionally beneficial for patients with major depression or psychosis, the drug should be administered cautiously, if at all, to patients with suicidal ideation. Triazolam should be used cautiously in patients with bipolar disorder because mania and hypomania have been reported in conjunction with the use of benzodiazepines in depressive disorders.

Triazolam can cause physical and psychological dependence, and should be used with extreme caution in patients with known, suspected, or a history of substance abuse. Generally, benzodiazepines should be prescribed for short periods (2—4 weeks) with continued re-evaluation of the need for treatment. Abrupt discontinuation of triazolam after prolonged use can cause seizures in susceptible patients. Abrupt discontinuation of benzodiazepine therapy has been reported to cause a withdrawal syndrome (see Adverse Effects), especially following high dose or prolonged benzodiazepine therapy. However, benzodiazepine dependence can occur with therapeutic doses administered for as few as 1—2 weeks and withdrawal symptoms may be seen following the discontinuance of therapy. Benzodiazepine withdrawal also can be more intense if the benzodiazepine involved possesses a relatively short duration of action such as triazolam. Patients with a history of a seizure disorder or who are taking other drugs that lower the seizure threshold (e.g., bupropion, TCAs, phenothiazines) should not be withdrawn abruptly from benzodiazepines due to the risk of precipitating a seizure; status epilepticus has also been reported. Benzodiazepines should be withdrawn cautiously and slowly, using a very gradual dosage-tapering schedule. During withdrawal, the greatest risk of seizure appears to be during the first 24 to 72 hours.

Worsening of daytime anxiety has been reported with the use of triazolam as few as 10 days after continuous use. In some patients this may be due to interdose withdrawal. If increased daytime anxiety is observed, it may be advisable to discontinue treatment gradually.

As with other benzodiazepines, triazolam should be used with extreme caution in patients with pulmonary disease or conditions associated with compromised respiratory function such as sleep apnea, bronchitis, pneumonia, asthma, or chronic obstructive pulmonary disease (COPD). Additionally, avoid coadministration with other CNS depressants, especially opioids, unless no other alternatives are available as coadministration significantly increases the risk for respiratory depression, low blood pressure, and death. Triazolam should not be used in patients with preexisting respiratory depression, cases of shock, or coma because the drug can worsen respiratory and CNS depression. Triazolam should be used cautiously in patients who snore regularly, because partial airway obstruction may convert to obstructive sleep apnea with benzodiazepine administration.

Patients should be cautioned against driving or operating machinery until they know how triazolam may affect them. Some patients may experience excessive sedation and impaired ability to perform tasks; however, this is usually less than that seen with intermediate- or long-acting benzodiazepines. Sedative-hypnotic medications have the potential to cause sleep-related behaviors such as sleep-driving, a state of driving after ingestion of a sedative-hypnotic while not fully awake and having no memory of the event. Other sleep-related behaviors may include making phone calls or eating while asleep. The exact incidences among various sedative products are unknown; however patients should be informed of the risks prior to receiving any medication from this class. Increased CNS effects may be seen with use of triazolam in patients with acute ethanol intoxication or psychosis. Patients with ethanol intoxication who have also consumed triazolam have an increased risk of respiratory depression and coma. Ethanol should be avoided during treatment with triazolam. Anterograde amnesia has been reported to occur more frequently with triazolam than with other benzodiazepines. Many reports of severe ‘traveler’s amnesia’ have occurred in patients traveling by plane, consuming alcohol with triazolam and/or taking the medication too late to allow the effects to wear off prior to arrival at their destination.

Triazolam should be used with extreme caution in patients with myasthenia gravis because the drug can exacerbate this condition.

The administration of triazolam can exacerbate acute intermittent porphyria, so the drug should be used with caution in patients with this condition.

Many benzodiazepines are contraindicated in patients with acute closed-angle glaucoma. However, the manufacturers of triazolam do not contraindicate its use in any type of glaucoma. The mechanistic rational for this contraindication has been questioned, as benzodiazepines do not have antimuscarinic activity and do not raise intraocular pressure. Benzodiazepines may be used in patients with open-angle glaucoma who are receiving appropriate therapy.

Triazolam is classified as FDA pregnancy risk category X and is contraindicated during pregnancy. Positive evidence of human fetal risk exists based on investigational, marketing, or human studies of various benzodiazepines. Inform females of childbearing potential of the potential risk to the fetus if she should become pregnant during triazolam therapy. Discontinue the drug prior to intended pregnancy. It should be anticipated that neonates may experience withdrawal symptoms and CNS/respiratory depression if the mother has been using benzodiazepines late in pregnancy. Neonatal flaccidity has been reported in an infant whose mother was using benzodiazepines. Triazolam has no established use in labor or obstetric delivery.

According to the manufacturer, the use of triazolam during breast-feeding is not recommended. Studies in humans have not been done; however, triazolam and its metabolites are secreted into the milk of lactating rats. The use of triazolam in women who are breast-feeding may result in potential side effects in the nursing infant, including somnolence and feeding difficulties. The American Academy of Pediatrics (AAP) classifies many benzodiazepines as drugs for which the effects on a nursing infant are unknown but may be of concern. For the treatment of insomnia, alternate medications for consideration during breast-feeding include zaleplon and zolpidem. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Triazolam should be administered cautiously to patients with severe hepatic disease because the elimination half-life of the drug can be prolonged, possibly resulting in toxicity. Patients with hepatic disease are more likely to experience adverse CNS reactions and should receive reduced initial dosages. Triazolam is significantly metabolized via the hepatic P450 microsomal isoenzyme CYP3A4. Concomitant administration of triazolam and potent inhibitors of CYP3A4 is contraindicated. Medications considered to be potent CYP3A4 inhibitors which should not be used concurrently with triazolam include systemically-administered azole antifungals, some antibiotics, and anti-retroviral protease inhibitors (See Drug Interactions). Other CYP3A4 inhibitors may also potentially cause triazolam toxicity (see Drug Interactions). This list is not inclusive of all CYP3A4 inhibitors.

Although specific dosage alterations of triazolam are not required in patients with renal impairment or renal failure, the manufacturer recommends to use caution in these patients.

Patients with late stage Parkinson’s disease may experience worsening of their psychosis or impaired cognition with administration of benzodiazepines, such as triazolam. Benzodiazepines may also cause incoordination or paradoxical reactions that may worsen symptoms of Parkinson’s disease.

Use triazolam with caution in the geriatric patient. The clearance and/or elimination of triazolam is reduced in the geriatric and/or debilitated patient compared to a younger patient, which may intensify or prolong adverse reactions. The impairment of cognitive and motor function may be more marked in the geriatric patient and a lower initial dosage is recommended together with close monitoring to decrease the possibility of development of oversedation, dizziness, or impaired coordination. Benzodiazepines have been associated with falls in the elderly. According to the Beers Criteria, benzodiazepines are considered potentially inappropriate medications (PIMs) for use in geriatric patients and avoidance is generally recommended, although some agents from this class may be appropriate for conditions such as rapid eye movement sleep disorders and end of life care. Older adults have an increased sensitivity to benzodiazepines. Triazolam is not generally a benzodiazepine of choice. In general, all benzodiazepines increase the risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents in older adults. The Panel recommends avoiding benzodiazepines in geriatric patients with the following disease states or symptoms due to the potential for exacerbation of the condition or increased risk of adverse effects: delirium (possible new-onset or worsening delirium), dementia (adverse CNS effects), and history of falls/fractures (ataxia, impaired psychomotor function, syncope, and additional falls). If a benzodiazepine must be used in a patient with a history of falls or fractures, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). When triazolam is used as a sedative, factors potentially causing insomnia should be evaluated before medication initiation (e.g., sleep environment, inadequate physical activity, provision of care disruptions, caffeine or medications, pain and discomfort, or other underlying conditions that cause insomnia). Initiation of sleep induction or maintenance medication should be preceded or accompanied by non-pharmacologic interventions and maximized treatment of underlying conditions (if applicable). All sleep medications should be used in accordance with approved product labeling. The use of sedating medications for individuals with diagnosed sleep apnea requires careful assessment, documented clinical rationale, and close monitoring. Exceptions to the OBRA provisions include: single dose sedative use for a dental or medical procedure or short-term sedative use during initiation of treatment for depression, pain, or other comorbid condition until symptoms improve or the underlying causative factor can be identified and/or effectively treated. It should be noted that benzodiazepines may increase the risk of confusion, sedation, and falls. OBRA provides dosing guidance for triazolam as a sedative; however, the guidelines state that triazolam is not a medication of choice for insomnia, particularly in older individuals. When a medication is used to induce sleep or treat a sleep disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity in accordance with OBRA guidelines.

The safe and effective use of triazolam in infants or children under 18 years old has not been established. Children are generally more sensitive to the CNS effects of the benzodiazepines. In general, the use of triazolam in children should be avoided.