the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)rifabutin decreases levels of diazepam by increasing metabolism. Minor/Significance Unknown.rifampinSerious - Use Alternative (1)rifampin will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.Minor (1)rifampin will decrease the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.rifapentineMonitor Closely (1)rifapentine will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.risperidoneMonitor Closely (1)diazepam and risperidone both increase sedation. Use Caution/Monitor.ritonavirMonitor Closely (1)ritonavir increases levels of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available.rocuroniumMinor (1)diazepam decreases effects of rocuronium by pharmacodynamic antagonism. Minor/Significance Unknown.rufinamideMonitor Closely (1)rufinamide will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ruxolitinibMinor (1)diazepam will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ruxolitinib topicalMinor (1)diazepam will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.sageMinor (2)diazepam and sage both increase sedation. Minor/Significance Unknown. sage decreases effects of diazepam by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction; some species of sage may cause convulsions.saquinavirMonitor Closely (1)saquinavir increases levels of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available.scullcapMonitor Closely (1)diazepam and scullcap both increase sedation. Use Caution/Monitor.secobarbitalMonitor Closely (2)secobarbital will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. secobarbital and diazepam both increase sedation. Use Caution/Monitor.selinexorSerious - Use Alternative (1)selinexor, diazepam. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.serdexmethylphenidate/dexmethylphenidateMinor (1)serdexmethylphenidate/dexmethylphenidate increases effects of diazepam by decreasing metabolism. Minor/Significance Unknown.sevelamerMonitor Closely (1)sevelamer decreases levels of diazepam by increasing elimination. Use Caution/Monitor.sevofluraneMonitor Closely (1)sevoflurane and diazepam both increase sedation. Use Caution/Monitor.shepherd's purseMonitor Closely (1)diazepam and shepherd's purse both increase sedation. Use Caution/Monitor.sodium oxybateSerious - Use Alternative (1)diazepam, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.sofosbuvir/velpatasvirMonitor Closely (1)sofosbuvir/velpatasvir increases levels of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.sparsentanMonitor Closely (1)sparsentan will decrease the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates. St John's WortSerious - Use Alternative (1)St John's Wort will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.stiripentolMonitor Closely (3)stiripentol, diazepam. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence. stiripentol, diazepam. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment. stiripentol will decrease the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of CYP2C19 substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.succinylcholineMinor (1)diazepam decreases effects of succinylcholine by pharmacodynamic antagonism. Minor/Significance Unknown.sufentanilMonitor Closely (1)diazepam and sufentanil both increase sedation. Use Caution/Monitor.sufentanil SLSerious - Use Alternative (1)sufentanil SL, diazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.suvorexantMonitor Closely (1)suvorexant and diazepam both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarytapentadolMonitor Closely (1)diazepam and tapentadol both increase sedation. Use Caution/Monitor.tazemetostatMonitor Closely (2)tazemetostat will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. diazepam will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (2)tecovirimat will increase the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with sensitive substrates of these enzymes. tecovirimat will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.teduglutideMonitor Closely (1)teduglutide increases levels of diazepam by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.temazepamMonitor Closely (1)diazepam and temazepam both increase sedation. Use Caution/Monitor.thioridazineMonitor Closely (1)diazepam and thioridazine both increase sedation. Use Caution/Monitor.thiothixeneMonitor Closely (1)diazepam and thiothixene both increase sedation. Use Caution/Monitor.tinidazoleMonitor Closely (1)diazepam will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tipranavirSerious - Use Alternative (1)tipranavir will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.topiramateMonitor Closely (2)topiramate will decrease the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. diazepam and topiramate both increase sedation. Modify Therapy/Monitor Closely.tramadolMonitor Closely (1)diazepam and tramadol both increase sedation. Use Caution/Monitor.trazodoneMonitor Closely (1)diazepam and trazodone both increase sedation. Use Caution/Monitor.triazolamMonitor Closely (1)diazepam and triazolam both increase sedation. Use Caution/Monitor.triclabendazoleMonitor Closely (1)triclabendazole will increase the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. If plasma concentrations of the CYP2C19 substrates are elevated during triclabendazole, recheck plasma concentration of the CYP2C19 substrates after discontinuation of triclabendazole. triclofosMonitor Closely (1)diazepam and triclofos both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (1)diazepam and trifluoperazine both increase sedation. Use Caution/Monitor.trimipramineMonitor Closely (1)diazepam and trimipramine both increase sedation. Use Caution/Monitor.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of diazepam 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.valerianSerious - Use Alternative (1)valerian and diazepam both increase sedation. Avoid or Use Alternate Drug.vecuroniumMinor (1)diazepam decreases effects of vecuronium by pharmacodynamic antagonism. Minor/Significance Unknown.verapamilMonitor Closely (1)verapamil will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.vinpocetineMinor (1)diazepam 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 diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)voriconazole will increase the level or effect of diazepam by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of diazepam 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)diazepam increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.zafirlukastMonitor Closely (1)zafirlukast will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ziconotideMonitor Closely (1)diazepam and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (1)diazepam and ziprasidone both increase sedation. Use Caution/Monitor.zolpidemMinor (1)zolpidem, diazepam. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.zotepineMonitor Closely (2)diazepam increases levels of zotepine by decreasing metabolism. Use Caution/Monitor. diazepam and zotepine both increase sedation. Use Caution/Monitor. 1-10% Ataxia (3%) Somnolence (>1%) Rectal gel Diarrhea (4%) Rash (3%) Incoordination (3%) Euphoria (3%) Dizziness (3%) Asthma (2%l) Intranasal Nasal discomfort (6%) Nasal congestion (3%) Epistaxis (3%) Dysgeusia (2%) Frequency Not Defined Hypotension Fatigue Muscle weakness Respiratory depression Urinary retention Depression Incontinence Blurred vision Dysarthria Headache Skin rash Changes in salivation Drowsiness Venous thrombosis Confusion Hypoactivity Slurred speech Syncope Tremor Vertigo Constipation Nausea Changes in libido Bradycardia Cardiovascular collapse Diplopia Nystagmus Urticaria Paradoxical reactions, including acute hyperexcited states, anxiety, hallucinations, increased muscle spasticity, insomnia, rage, sleep disturbances and stimulation Peroral endoscopic procedures: Coughing, depressed respiration, dyspnea, hyperventilation, laryngospasm, and pain in throat or chest Serious Neutropenia Jaundice Local effects: Pain, swelling, thrombophlebitis, carpal tunnel syndrome, tissue necrosis Phlebitis if too rapid IV push Oral Central nervous system: Confusion, depression, dysarthria, headache, slurred speech, tremor, vertigo Gastrointestinal system: Constipation, nausea, gastrointestinal disturbances Special senses: Blurred vision, diplopia, dizziness Cardiovascular system: Hypotension Psychiatric and paradoxical reactions: Stimulation, restlessness, acute hyperexcited states, anxiety, agitation, aggressiveness, irritability, rage, hallucinations, psychoses, delusions, increased muscle spasticity, insomnia, sleep disturbances, and nightmares. Inappropriate behavior and other adverse behavioral effects have been reported when using benzodiazepines. Urogenital system: Incontinence, changes in libido, urinary retention Skin and appendages: Skin reactions Laboratories: Elevated transaminases and alkaline phosphatase Other: Changes in salivation, including dry mouth, hypersalivation Antegrade amnesia may occur using therapeutic dosages, the risk increasing at higher dosages; amnestic effects may be associated with inappropriate behavior Minor changes in EEG patterns, usually low-voltage fast activity, have been observed in patients during and after diazepam therapy and are of no known significance Because of isolated reports of neutropenia and jaundice, periodic blood counts and liver function tests are advisable during long-term therapy Postmarketing Reports Injury, poisoning, and procedural complications: Falls and fractures in benzodiazepine users; risk is increased in those taking concomitant sedatives (including alcohol), and in the elderly 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 diazepam is used with opioids and that such drugs should not be used concomitantly unless supervised by a health care provider Prescribers are strongly advised to take all reasonable steps to ensure that caregivers fully understand their role and obligations vis a vis the administration of diazepam rectal gel to individuals in their care 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 On September 2020, FDA addressed serious risks of benzodiazepine addiction, abuse, and misuse, which can lead to overdose and death 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 Physical dependence can occur when taken steadily for several days to weeks, even as prescribed 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 Assess each patient’s risk prior to prescribing and monitor regularly for the development of these conditions Contraindications Documented hypersensitivity Acute narrow-angle glaucoma and open-angle glaucoma unless patients receiving appropriate therapy Cautions Efficacy and safety of parenteral diazepam has not been established in neonate (30 days or less of age); prolonged central nervous system depression has been observed in neonates, apparently due to inability to biotransform diazepam into inactive metabolites; benzyl alcohol has been reported to be associated with a fatal gasping syndrome in premature infants Not recommended for chronic, daily use as an anticonvulsant because of potential for development of tolerance to diazepam; chronic daily use of diazepam may increase frequency and/or severity of tonic-clonic seizures, requiring an increase in dosage of standard anticonvulsant medication; in