inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.sunitinibSerious - Use Alternative (1)sunitinib and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.suvorexantMonitor Closely (1)suvorexant and buprenorphine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarytacrolimusSerious - Use Alternative (1)tacrolimus and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.tapentadolMonitor Closely (1)buprenorphine and tapentadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine, tapentadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.telavancinSerious - Use Alternative (1)buprenorphine and telavancin both increase QTc interval. Avoid or Use Alternate Drug.temazepamMonitor Closely (1)temazepam and buprenorphine both increase sedation. Use Caution/Monitor.tetrabenazineSerious - Use Alternative (1)buprenorphine and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.thioridazineContraindicated (1)buprenorphine and thioridazine both increase QTc interval. Contraindicated.Monitor Closely (1)buprenorphine and thioridazine both increase sedation. Use Caution/Monitor.thiothixeneMonitor Closely (1)buprenorphine and thiothixene both increase sedation. Use Caution/Monitor.tipranavirMonitor Closely (1)tipranavir will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.topiramateMonitor Closely (1)buprenorphine and topiramate both increase sedation. Modify Therapy/Monitor Closely.toremifeneSerious - Use Alternative (1)buprenorphine and toremifene both increase QTc interval. Avoid or Use Alternate Drug.tramadolMonitor Closely (1)buprenorphine and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)tramadol, buprenorphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent. buprenorphine, tramadol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.tranylcypromineSerious - Use Alternative (1)tranylcypromine increases toxicity of buprenorphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.trazodoneMonitor Closely (1)buprenorphine and trazodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.triazolamMonitor Closely (1)triazolam and buprenorphine both increase sedation. Use Caution/Monitor.triclabendazoleSerious - Use Alternative (1)buprenorphine and triclabendazole both increase QTc interval. Avoid or Use Alternate Drug.triclofosMonitor Closely (1)triclofos and buprenorphine both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (2)buprenorphine and trifluoperazine both increase sedation. Use Caution/Monitor. buprenorphine and trifluoperazine both decrease QTc interval. Use Caution/Monitor.trimipramineMonitor Closely (1)buprenorphine and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.triprolidineMonitor Closely (1)triprolidine and buprenorphine both increase sedation. Use Caution/Monitor.triptorelinSerious - Use Alternative (1)buprenorphine and triptorelin both increase QTc interval. Avoid or Use Alternate Drug.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of buprenorphine 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.valbenazineMonitor Closely (1)valbenazine and buprenorphine both increase QTc interval. Use Caution/Monitor.valerianSerious - Use Alternative (1)valerian and buprenorphine both increase sedation. Avoid or Use Alternate Drug.vandetanibSerious - Use Alternative (1)buprenorphine and vandetanib both increase QTc interval. Avoid or Use Alternate Drug.vardenafilSerious - Use Alternative (1)buprenorphine and vardenafil both increase QTc interval. Avoid or Use Alternate Drug.vemurafenibSerious - Use Alternative (1)buprenorphine and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.venlafaxineSerious - Use Alternative (1)buprenorphine and venlafaxine both decrease QTc interval. Avoid or Use Alternate Drug.voclosporinSerious - Use Alternative (1)buprenorphine and voclosporin both increase QTc interval. Avoid or Use Alternate Drug.voriconazoleSerious - Use Alternative (2)voriconazole will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. buprenorphine and voriconazole both increase QTc interval. Avoid or Use Alternate Drug.vorinostatSerious - Use Alternative (2)vorinostat and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug. buprenorphine and vorinostat both increase QTc interval. Avoid or Use Alternate Drug.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of buprenorphine 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)buprenorphine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziconotideMonitor Closely (1)buprenorphine and ziconotide both increase sedation. Use Caution/Monitor.Minor (1)ziconotide, buprenorphine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.ziprasidoneMonitor Closely (1)buprenorphine and ziprasidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.zotepineMonitor Closely (1)buprenorphine and zotepine both increase sedation. Use Caution/Monitor. >10% Headache (28-36.4%) Withdrawal syndrome (24-25.2%) Insomnia (14-23%) Pain (22.4%) Nausea (7-15%) Hyperhidrosis (14%) Asthenia (6.5-14%) Constipation (5-12.1%) Abdominal pain (11.2%) 1-10% Diarrhea (10%) Vasodilation or peripheral edema (9.3%) Chills (6-7.5%) Vomiting (4-7.5%) Postmarketing Reports Adrenal insufficiency Anaphylaxis Serotonin syndrome Hepatotoxicity Glossodynia Glossitis Oral mucosal erythema Oral hypoesthesia Stomatitis Contraindications Hypersensitivity Cautions Significant respiratory depression may occur with therapeutic doses Use with caution in hypothyroidism, preexisting respiratory compromise, obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve and kyphoscoliosis, myxedema, adrenocortical insufficiency, alcohol intoxication, alcohol withdrawal syndrome, coma, severe renal impairment, geriatric or debilitated patients, delirium tremens, toxic psychoses, kyphoscoliosis, prostatic hypertrophy, urethral stricture, comatose patients, central nervous system (CNS) depression, biliary tract dysfunction, severe hepatic impairment, head injury, intracranial lesions, and intracranial hypertension or conditions in which intracranial pressure (ICP) may be increased Use caution with concurrent use of other CNS depressants Respiratory sedation is dose-dependent; usual doses may depress respiration to same degree as 10 mg of parenteral morphine Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper Use caution in patients with history of ileus or bowel obstruction May cause orthostatic hypotension; use caution in patients with hypovolemia, cardiovascular disease, or drugs that may worsen hypertension Effects in CNS depression may impair ability to perform tasks that require mental alertness Life-threatening neonatal syndrome may occur in newborns following maternal exposure to opioids; treat according to protocols developed by neonatology experts; prescribers should discuss with patients importance and benefits of management of opioid addiction throughout pregnancy Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; unknown whether effects on fertility are reversible Use caution when switching between formulations; certain sublingual film strengths may have greater bioavailability compared to the same strength of sublingual tablet; monitor for overdosing or underdosing when switching formulations Buprenorphine may precipitate acute narcotic withdrawal in opioid-dependent patients upon rapid discontinuation or rapid taper; taper dose gradually when discontinuing therapy Because it contains naloxone, drug is highly likely to produce marked and intense withdrawal signs and symptoms if misused parenterally by individual dependent on full opioid agonists such as heroin, morphine, or methadone May obscure diagnosis or clinical course of patients with acute abdominal conditions Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency Advise pregnant women receiving opioid addiction treatment with sublingual film of risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available Due to risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose Drug can be abused in a manner similar to other opioids; consider this when prescribing or dispensing buprenorphine in situations when clinician is concerned about increased risk of misuse, abuse, or diversion QTc prolongation Thorough QT studies with buprenorphine products have demonstrated QT prolongation less than or equal to 15 msec; this QTc prolongation effect does not appear to be mediated by hERG channels; based on these two findings, buprenorphine is unlikely to be pro-arrhythmic when used alone in patients without risk factors; the risk of combining buprenorphine with other QT-prolonging agents is not known Consider these observations in clinical decisions when prescribing this medication to patients with risk factors such as hypokalemia, bradycardia, recent conversion from atrial fibrillation, congestive heart failure, digitalis therapy, baseline QT prolongation, subclinical long-QT syndrome, or severe hypomagnesemia Increased risk of dental problems On January 12, 2022, FDA warned of potential dental problems associated with transmucosal buprenorphine-containing products (eg, buccal, sublingual) Cases of dental caries, some severe (eg, tooth fracture, tooth loss), reported following use of transmucosal buprenorphine-containing products; reported events include cavities, tooth decay, dental abscesses/infection, rampant caries, tooth erosion, fillings falling out, and, in some cases, total tooth loss Treatment for these events included tooth extraction, root canal, dental surgery, as well as other restorative procedures (eg, fillings, crowns, implants, dentures); multiple cases were reported in individuals without any prior history of dental problems Despite these risks, buprenorphine is an important treatment option for opioid use disorder and pain, and the benefits of these medicines clearly outweigh the risks Review patient’s health before initiating with transmucosal buprenorphine Refer patients to dental care services and encourage them to have regular dental checkups while receiving therapy; educate patients to seek dental care and strategies to maintain or improve oral health while being treated with transmucosal buprenorphine-containing products Strategies include, but are not limited to, gently rinsing teeth and gums with water and then swallowing after completely dissolved in oral mucosa; advise patients to wait for at least one hour after taking drug before brushing teeth Counsel patients regarding potential for dental problems and importance of taking extra steps after the medicine has completely dissolved, including gently rinsing teeth and gums with water and then swallow; advise to wait at least 1 hour before brushing their teeth Dentists treating patients taking transmucosal buprenorphine should perform a baseline dental evaluation and caries risk assessment, establish a dental caries preventive plan, and encourage regular dental checkups Coadministration with benzodiazepines Life-threating respiratory depression and death may occur; many, but not all, postmarketing reports regarding coma and death involved misuses by self-injection or were associated with concomitant use of benzodiazepines or other CNS depressants, including alcohol; warn patients of potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment Concomitant use of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose and death; medication-assisted treatment of opioid use disorder, however, should not be categorically denied to patients taking these drugs; prohibiting or creating barriers to treatment can pose an even greater risk of morbidity and mortality due to the opioid use disorder alone If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response; follow patients closely for signs and symptoms of respiratory depression and sedation Develop strategies to manage use of prescribed or illicit benzodiazepines or other CNS depressants at initiation of buprenorphine treatment, or if it emerges as a concern during treatment; adjustments to induction procedures and additional monitoring may be required; there is no evidence to support dose limitations or arbitrary caps of buprenorphine as a strategy to address benzodiazepine use in buprenorphine-treated patients; however, if a patient is sedated at the time of buprenorphine dosing, delay or omit the buprenorphine dose if appropriate Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use. In some cases, monitoring in a higher level of care for taper