Use Caution/Monitor.cobimetinibSerious - Use Alternative (1)zileuton will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).darunavirMonitor Closely (1)darunavir increases levels of zileuton by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .deferasiroxMonitor Closely (1)deferasirox will increase the level or effect of zileuton by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.difelikefalinMonitor Closely (1)difelikefalin and zileuton both increase sedation. Use Caution/Monitor.duloxetineSerious - Use Alternative (1)zileuton will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.eliglustatSerious - Use Alternative (1)zileuton increases levels of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Moderate CYP3A4 inhibitors are not recommended with eliglustat poor or intermediate metabolizers; reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive metabolizers .eltrombopagMonitor Closely (1)zileuton will increase the level or effect of eltrombopag by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.eluxadolineMonitor Closely (1)zileuton increases levels of eluxadoline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP1A2 inhibitors.fentanylSerious - Use Alternative (1)zileuton will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.fentanyl intranasalSerious - Use Alternative (1)zileuton will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.fentanyl transdermalSerious - Use Alternative (1)zileuton will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.fentanyl transmucosalSerious - Use Alternative (1)zileuton will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.fezolinetantContraindicated (1)zileuton will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitorsfinerenoneMonitor Closely (1)zileuton will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.flibanserinContraindicated (1)zileuton will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of flibanserin with moderate or strong CYP3A4 inhibitors is contraindicated. Severe hypotension or syncope can occur.fosamprenavirMonitor Closely (1)fosamprenavir increases levels of zileuton by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .frovatriptanMinor (1)zileuton will increase the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.imipramineMonitor Closely (1)zileuton will increase the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.indinavirMonitor Closely (1)indinavir increases levels of zileuton by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .irinotecan liposomalSerious - Use Alternative (1)zileuton will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.isavuconazonium sulfateMonitor Closely (1)zileuton will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.ivabradineSerious - Use Alternative (1)zileuton will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.lemborexantMonitor Closely (1)zileuton will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.letermovirMonitor Closely (1)letermovir increases levels of zileuton by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.lidocaineMonitor Closely (1)zileuton will increase the level or effect of lidocaine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.lomitapideMonitor Closely (1)zileuton increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.lonafarnibSerious - Use Alternative (1)zileuton will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.lopinavirMonitor Closely (1)lopinavir increases levels of zileuton by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity.mefloquineMonitor Closely (1)zileuton will increase the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.melatoninSerious - Use Alternative (1)zileuton will increase the level or effect of melatonin by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of melatonin with strong CYP1A2 inhibitorsmexiletineMonitor Closely (1)zileuton will increase the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.naloxegolSerious - Use Alternative (1)zileuton will increase the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministation of naloxegol with moderate CYP3A4 inhibitors is unavoidable, reduce naloxegol dose to 12.5 mg qDaynelfinavirMonitor Closely (1)nelfinavir increases levels of zileuton by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .olanzapineMonitor Closely (1)zileuton will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.olaparibSerious - Use Alternative (1)zileuton will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A inhibitors cannot be avoided, reduce olaparib dose to 200 mg (capsule) or 150 mg (tablet) PO BID. Do not substitute tablets with capsules.ondansetronMinor (1)zileuton will increase the level or effect of ondansetron by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown. No dosage adjustment is needed for ondansetron.palbociclibMonitor Closely (1)zileuton will increase the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.pentoxifyllineMonitor Closely (1)zileuton will increase the level or effect of pentoxifylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.pimozideSerious - Use Alternative (1)zileuton increases levels of pimozide by decreasing metabolism. Contraindicated. May prolong QTc interval.pirfenidoneSerious - Use Alternative (1)zileuton will increase the level or effect of pirfenidone by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Use of strong CYP1A2 inhibitors should be discontinued before initiating pirfenidone and avoided during treatment; if strong CYP1A2 inhibitors are the only drug of choice, dosage reductions are recommendedramelteonMonitor Closely (1)zileuton will increase the level or effect of ramelteon by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.rasagilineMonitor Closely (1)zileuton will increase the level or effect of rasagiline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Recommended dose of rasagiline is 0.5mg daily in combination with CYP1A2 inhibitors.riluzoleMinor (1)zileuton will increase the level or effect of riluzole by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.ritonavirMonitor Closely (1)ritonavir increases levels of zileuton by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .ropiniroleMonitor Closely (1)zileuton will increase the level or effect of ropinirole by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.sonidegibMonitor Closely (1)zileuton will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of sonidegib with moderate CYP3A4 inhibitors. If a moderate CYP3A inhibitor must be used, administer the moderate CYP3A inhibitor for <14 days and monitor closely for adverse reactions, particularly musculoskeletal adverse reactions.suvorexantMonitor Closely (1)zileuton will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorstazemetostatMonitor Closely (1)zileuton will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.terbinafineMonitor Closely (1)zileuton will increase the level or effect of terbinafine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.theophyllineMonitor Closely (1)zileuton will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.tinidazoleMonitor Closely (1)zileuton will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tizanidineSerious - Use Alternative (1)zileuton will increase the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.tofacitinibMonitor Closely (1)zileuton increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No specific dose adjustment recommended when tofacitinib coadministered with moderate CYP3A4 inhibitors; decrease tofacitinib dose if coadministered with both moderate CYP3A4 and potent CYP2C19 inhibitors .warfarinMonitor Closely (1)zileuton will increase the level or effect of warfarin by Other (see comment). Use Caution/Monitor. Warfarin's less potent R-enantiomer is metabolized in part by CYP3A4 (and also CYP1A2 and CYP2C19). Monitor INR more frequently if coadministered with inhibitors of these isoenzymes and adjust warfarin dose if needed. >10% Headache (24.6%) 1-10% Abdominal pain (5%) ALT elevation ≥3 times ULN (1.9-5%) Asthenia (3.8%) Dyspepsia (8.2%) Diarrhea (5%) Generalized pain (7.8%) Nausea (5.5%) Leukopenia (1-3%) Myalgia (7%) Weakness (4%) Sinusitis (7%) Pharyngolaryngeal pain (5%) < 1% Hepatitis Behavioral changes Jaundice Liver failure Suicidality Suicide Contraindications Hypersensitivity Liver disease, LFT's ≥3x ULN Cautions Not indicated for use in acute bronchospasm History of liver disease, heavy alcohol use Behavioral changes and sleep disorders reported Not recommended for patients <12 years due to risk of hepatotoxicity Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to asthma medications during pregnancy; for more information, contact the MothersToBaby Pregnancy Studies conducted by Organization of Teratology Information Specialists at 1- 877-311-8972 or visit http://mothertobaby.org/pregnancy-studies There are no adequate human data on use in pregnant women to inform a drug associated risk Animal data In animal studies, oral administration to pregnant rats and rabbits during organogenesis produced adverse developmental outcomes; structural abnormalities (cleft palate) were observed in rabbits at a dose similar to maximum recommended human daily oral dose (MRHD), alterations to growth (reduced fetal body weight and increased skeletal variations) were observed in rats at maternal plasma exposures 20 times greater than at MRHD; in a pre- and post-natal development study, oral administration to pregnant rats from organogenesis through weaning at maternal plasma exposures 20 times greater than MRHD resulted in reduced pup survival and body weights; the drug and/or its metabolites cross placental barrier of rats; therefore, drug may be transmitted from mother to developing fetus Lactation The drug and metabolites are excreted in rat milk; it is not known if zileuton is excreted in human milk, nor are there data on effects of drug on breastfed infant or effects on maternal milk production; because many drugs are excreted in human milk, and because of potential for tumorigenicity shown in animal studies, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for drug and any potential adverse effects on breastfed child from drug or from the underlying maternal conditionPregnancy 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.