durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.tapentadolMonitor Closely (1)triazolam and tapentadol both increase sedation. Use Caution/Monitor.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.teclistamabMonitor Closely (1)teclistamab will increase the level or effect of triazolam by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed. tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.telotristat ethylMonitor Closely (1)telotristat ethyl will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.temazepamMonitor Closely (1)temazepam and triazolam both increase sedation. Use Caution/Monitor.terbutalineMonitor Closely (1)triazolam increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.thioridazineMonitor Closely (1)triazolam and thioridazine both increase sedation. Use Caution/Monitor.thiothixeneMonitor Closely (1)triazolam and thiothixene both increase sedation. Use Caution/Monitor.tipranavirContraindicated (1)tipranavir will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Serious - Use Alternative (1)tipranavir increases levels of triazolam by decreasing metabolism. Contraindicated.topiramateMonitor Closely (2)topiramate will decrease the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. triazolam and topiramate both increase sedation. Modify Therapy/Monitor Closely.tramadolMonitor Closely (1)triazolam and tramadol both increase sedation. Use Caution/Monitor.trazodoneMonitor Closely (1)triazolam and trazodone both increase sedation. Use Caution/Monitor.triclofosMonitor Closely (1)triazolam and triclofos both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (1)triazolam and trifluoperazine both increase sedation. Use Caution/Monitor.trimipramineMonitor Closely (1)triazolam and trimipramine both increase sedation. Use Caution/Monitor.triprolidineMonitor Closely (1)triprolidine and triazolam both increase sedation. Use Caution/Monitor.trofinetideMonitor Closely (1)trofinetide will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.turmericMonitor Closely (1)turmeric will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.valerianSerious - Use Alternative (1)valerian and triazolam both increase sedation. Avoid or Use Alternate Drug.verapamilMonitor Closely (1)verapamil will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.vinpocetineMinor (1)triazolam increases effects of vinpocetine by unspecified interaction mechanism. Minor/Significance Unknown. Desirable interaction enhanced memory improvement (based on preliminary trial).voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.xylometazolineMonitor Closely (1)triazolam increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)triazolam increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.zafirlukastMonitor Closely (1)zafirlukast will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ziconotideMonitor Closely (1)triazolam and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (1)triazolam and ziprasidone both increase sedation. Use Caution/Monitor.zolpidemMinor (1)zolpidem, triazolam. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.zotepineMonitor Closely (1)triazolam and zotepine both increase sedation. Use Caution/Monitor. >10% Drowsiness (14%) 1-10% Headache (5-10%) Dizziness (5-10%) Nervousness (5-10%) Ataxia (4-5%) Lightheadedness (4-5%) N/V (4-5%) <1% Anterogade amnesia Paradoxical reactions Travelers amnesia-especially if combined with EtOH Confusion Cramps Fatigue Memory impairment Depression Visual disturbance Xerostomia Anterograde amnesia Dreaming/nightmares Confusion Black Box Warnings Risks from concomitant use with opioids Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate Limit dosages and durations to the minimum required Follow patients for signs and symptoms of respiratory depression and sedation Inform patients and caregivers that potentially fatal additive effects may occur if drug is used with opioids and that such drugs should not be used concomitantly unless supervised by a health care provider Prescribers should advise caregivers that they expect to be informed immediately if a patient develops any new findings which are not typical of the patient’s characteristic seizure episode Addiction, abuse, and misuse In September 2020, FDA addressed serious risks of benzodiazepine addiction, abuse, and misuse, which can lead to overdose and death Physical dependence can occur when taken steadily for several days to weeks, even as prescribed Stopping abruptly or reducing dosage too quickly can result in withdrawal reactions, including seizures, which can be life-threatening Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes; before prescribing and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction Assess each patient’s risk prior to prescribing and monitor regularly for the development of these conditions Risks of dependence and withdrawal increase with longer treatment duration and higher daily dose; although injection is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction may precipitate acute withdrawal reactions, including seizures, which can be life-threatening; use gradual taper when discontinuing therapy to reduce withdrawal reactions risk Contraindications Documented hypersensitivity Acute alcohol intoxication Myasthenia gravis (allowable in limited circumstances) Narrow angle glaucoma (questionable) Severe respiratory depression Depressed neuroses, psychotic reactions IV use in shock, coma, depressed respiration, patients who recently received other respiratory depressants Medications that significantly impair oxidative metabolism mediated by cytochrome P450 3A (CYP 3A) including ketoconazole, itraconazole, nefazodone, and several HIV protease inhibitors Caution Use caution in COPD, sleep apnea, renal/hepatic disease, open-angle glaucoma (questionable), impaired gag reflex, depression, suicide ideation Benzodiazepines may worsen depression; take appropriate precautions (e.g., limiting total prescription size and increased monitoring for suicidal ideation) in patients with depression Anterograde amnesia may occur Hypersensitivity reactions reported Sleep related activities (sleep driving, sleep-cooking, sleep-eating etc) may occur Hyperactive aggressive behavior may occur May impair ability to perform hazardous tasks Failure of insomnia to remit after 7 - 10 days of treatment may indicate presence of primary psychiatric and/or medical illness that should be evaluated Increase in daytime anxiety may occur; consider therapy discontinuation if this occurs Use caution and consider appropriate dose reduction when used concomitantly with weak or moderate CYP450 3A inhibitors Therapy can cause drowsiness and a decreased level of consciousness; patients, particularly the elderly, are at higher risk of falls Use of Halcion during 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 neonates; observe newborns for signs of sedation and neonatal withdrawal syndrome and manage accordingly Benzodiazepines expose users to risks of abuse, misuse, and addiction, which can lead to overdose or death; abuse and misuse of benzodiazepines often (but not always) involve use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death Use of drug, particularly in patients at elevated risk of abuse, necessitates counseling about risks and proper use of drug along with monitoring for signs and symptoms of abuse, misuse, and addiction; do not exceed recommended dosing frequency Avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (eg, opioid analgesics, stimulants); advise patients on proper disposal of unused drug; if a substance use disorder is suspected, evaluate patient and institute (or refer them for) early treatment, as appropriate For patients treated more frequently than recommended, use a gradual taper to discontinue therapy (a patient-specific plan should be used to taper the dose), to reduce risk of withdrawal reactions Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months Withdrawal effects Withdrawal phenomena results in increased wakefulness during last third of the night, and appearance of increased signs of daytime anxiety or nervousness Withdrawal effects can occur after discontinuing these drugs following use for only a week or two, but may be more common and more severe after longer periods of continuous use A phenomena known as ‘rebound insomnia’ may occur after stopping therapy, on the first few nights after drug is stopped, insomnia is actually worse than before the sleeping pill was given Other withdrawal phenomena following abrupt stopping of benzodiazepine sleeping pills range from mild unpleasant feelings to a major withdrawal syndrome which may include abdominal and muscle cramps, vomiting, sweating, tremor, and convulsions Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to drug during pregnancy; healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Other Psychiatric Medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications/ Infants born to mothers using benzodiazepines during later stages of pregnancy reported to experience symptoms of sedation and neonatal withdrawal At this time, there is no clear evidence that triazolam exposure in early pregnancy can cause major birth defects Benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates; monitor neonates exposed to therapy during pregnancy and labor for signs of sedation, respiratory depression, withdrawal, and feeding problems and manage accordingly Animal data Oral administration to male and female rats before mating, and continuing during gestation and lactation did not result in embryotoxicity at doses up to approximately 100 times the MRHD based on mg/m2 body surface area, but did cause an increase in number of stillbirths and postnatal pup mortalities at doses greater than or equal to approximately 40 times the MRHD based mg/m2 body surface area Lactation There are no data on presence of drug in human milk or effects on milk production; there are reports of central nervous system depression (sedation, respiratory depression), withdrawal symptoms, and feeding problems in infants who are breastfed by mothers taking benzodiazepines The drug and its metabolites are present in the milk of lactating rats; when a drug is present in animal milk, it is likely that the drug will be present in human milk; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from drug or from underlying maternal condition Infants exposed to drug through breast milk should be monitored for sedation, respiratory depression, withdrawal symptoms, and feeding problems; a lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 28 hours (approximately 5 elimination half-lives) after therapy administration in order to minimize drug exposure to a breast fed infantPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Depresses all levels of CNS (eg, limbic and reticular formation), possibly