Itraconazoleinteractions

Co-administration of a number of CYP3A4 substrates are contraindicated with itraconazole. Some examples of drugs for which plasma concentrations increase are: methadone, disopyramide, dofetilide, dronedarone, quinidine, isavuconazole, ergot alkaloids (such as dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergometrine (methylergonovine)), irinotecan, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ivabradine, ranolazine, eplerenone, cisapride, naloxegol, lomitapide, lovastatin, simvastatin, avanafil, ticagrelor, finerenone, voclosporin. In addition, co-administration with colchicine, fesoterodine, and solifenacin is contraindicated in subjects with varying degrees of renal or hepatic impairment, and co-administration with eliglustat is contraindicated in subjects that are poor or intermediate metabolizers of CYP2D6 and in subjects taking strong or moderate CYP2D6 inhibitors (see PRECAUTIONS: Drug Interactions Section for specific examples). This increase in drug concentrations caused by co-administration with itraconazole may increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs. For example, increased plasma concentrations of some of these drugs can lead to QT prolongation and ventricular tachyarrhythmias including occurrences of torsade de pointes, a potentially fatal arrhythmia. Some specific examples are listed in PRECAUTIONS: Drug Interactions. Co-administration with venetoclax is contraindicated in patients with CLL/SLL during the dose initiation and ramp-up phase of venetoclax due to the potential for an increased risk of tumor lysis syndrome. Itraconazole oral solution is contraindicated for patients who have shown hypersensitivity to itraconazole. There is limited information regarding cross-hypersensitivity between itraconazole and other azole antifungal agents. Caution should be used when prescribing itraconazole to patients with hypersensitivity to other azoles.

Drug Interactions: Effect of Itraconazole on Other Drugs Itraconazole and its major metabolite, hydroxy-itraconazole, are potent CYP3A4 inhibitors. Itraconazole is an inhibitor of the drug transporters P-glycoprotein and breast cancer resistance protein (BCRP). Consequently, itraconazole has the potential to interact with many concomitant drugs resulting in either increased or sometimes decreased concentrations of the concomitant drugs. Increased concentrations may increase the risk of adverse reactions associated with the concomitant drug which can be severe or life-threatening in some cases (e.g., QT prolongation, torsade de pointes, respiratory depression, hepatic adverse reactions, hypersensitivity reactions, myelosuppression, hypotension, seizures, angioedema, atrial fibrillation, bradycardia, priapism). Reduced concentrations of concomitant drugs may reduce their efficacy. The table below lists examples of drugs that may have their concentrations affected by itraconazole, but it is not a comprehensive list. Refer to the approved product labeling to become familiar with the interaction pathways, risk potential and specific actions to be taken with regards to each concomitant drug prior to initiating therapy with itraconazole. Although many of the clinical drug interactions in Table 1 below are based on information with a similar azole antifungal, ketoconazole, these interactions are expected to occur with itraconazole.

Table 1: Drug Interactions with Itraconazole that Affect Concomitant Drug Concentrations Examples of Concomitant Drugs Within Class Prevention or Management Drug Interactions with Itraconazole that Increase Concomitant Drug Concentrations and May Increase Risk of Adverse Reactions Associated with the Concomitant Drug Alpha Blockers Alfuzosin Silodosin Tamsulosin Not recommended during and 2 weeks after itraconazole treatment. Analgesics Methadone Contraindicated during and 2 weeks after itraconazole treatment. Fentanyl Not recommended during and 2 weeks after itraconazole treatment. Alfentanil Buprenorphine (IV and sublingual) Oxycodone a Sufentanil Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antiarrhythmics Disopyramide Dofetilide Dronedarone Quinidine a Contraindicated during and 2 weeks after itraconazole treatment. Digoxin a Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antibacterials Bedaquiline b Concomitant itraconazole not recommended for more than 2 weeks at any time during bedaquiline treatment. Rifabutin Not recommended 2 weeks before, during, and 2 weeks after itraconazole treatment. See also Table 2. Clarithromycin Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. See also Table 2. Trimetrexate Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Anticoagulants and Antiplatelets Ticagrelor Contraindicated during and 2 weeks after itraconazole treatment. Apixaban Rivaroxaban Vorapaxar Not recommended during and 2 weeks after itraconazole treatment. Cilostazol Dabigatran Warfarin Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Anticonvulsants Carbamazepine Not recommended 2 weeks before, during, and 2 weeks after itraconazole treatment. See also Table 2. Antidiabetic Drugs Repaglinide a Saxagliptin Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antihelminthics, Antifungals and Antiprotozoals Isavuconazonium Contraindicated during and 2 weeks after itraconazole treatment. Praziquantel Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Artemether-lumefantrine Quinine a Monitor for adverse reactions. Antimigraine Drugs Ergot alkaloids (e.g., dihydroergotamine, ergotamine) Contraindicated during and 2 weeks after itraconazole treatment. Eletriptan Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antineoplastics Irinotecan Contraindicated during and 2 weeks after itraconazole treatment. Venetoclax Contraindicated during the dose initiation and ramp-up phase in patients with CLL/SLL. Refer to the venetoclax prescribing information for dosing and safety monitoring instructions. Mobocertinib a Avoid use during and 2 weeks after itraconazole treatment. Axitinib Bosutinib Cabazitaxel Cabozantinib Ceritinib Cobimetinib a Crizotinib Dabrafenib Dasatinib Docetaxel Ibrutinib Lapatinib Nilotinib Olaparib a Pazopanib Sunitinib Trabectedin Trastuzumab-emtansine Vinca alkaloids Avoid use during and 2 weeks after itraconazole treatment. Entrectinib a Pemigatinib a Talazoparib a Refer to the entrectinib, pemigatinib and talazoparib prescribing information for dosing instructions if concomitant use cannot be avoided. Glasdegib Refer to the glasdegib prescribing information for safety monitoring if concomitant use cannot be avoided. Bortezomib Brentuximab- vedotin Busulfan Erlotinib Gefitinib a Idelalisib Imatinib Ixabepilone Nintedanib Panobinostat Ponatinib Ruxolitinib Sonidegib Tretinoin (oral) Vandetanib a Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

For idelalisib: see also Table 2. Antipsychotics, Anxiolytics and Hypnotics Alprazolam a Aripiprazole a Buspirone a Cariprazine Diazepam a Haloperidol a Midazolam (IV) a Quetiapine Ramelteon Risperidone a Suvorexant Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Zopiclone a Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Lurasidone Midazolam (oral) a Pimozide Triazolam a Contraindicated during and 2 weeks after itraconazole treatment. Antivirals Daclatasvir Indinavir a Maraviroc Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

For indinavir: see also Table 2. Cobicistat Elvitegravir (ritonavir-boosted) Ombitasvir/Paritaprevir/Ritonavir with or without Dasabuvir Ritonavir Saquinavir (unboosted) a Monitor for adverse reactions. Elbasvir/grazoprevir Glecaprevir/pibrentasvir Tenofovir disoproxil fumarate Not recommended during and 2 weeks after itraconazole treatment. Monitor for adverse reactions. Monitor for adverse reactions. Beta Blockers Nadolol a Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Calcium Channel Blockers Felodipine a Nisoldipine Contraindicated during and 2 weeks after itraconazole treatment. Diltiazem Other dihydropyridines Verapamil Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

For diltiazem: see also Table 2. Cardiac Myosin Inhibitor Mavacamten Refer to the mavacamten prescribing information for detailed guidance including dosing and safety monitoring. Cardiovascular Drugs, Miscellaneous Ivabradine Ranolazine Contraindicated during and 2 weeks after itraconazole treatment. Aliskiren a Riociguat Sildenafil (for pulmonary hypertension) Tadalafil (for pulmonary hypertension) Not recommended during and 2 weeks after itraconazole treatment. For sildenafil and tadalafil, see also Urologic Drugs below. Bosentan Guanfacine Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Contraceptives* Dienogest Ulipristal Monitor for adverse reactions. Diuretics Eplerenone Finerenone Contraindicated during and 2 weeks after itraconazole treatment. Gastrointestinal Drugs Cisapride Naloxegol Contraindicated during and 2 weeks after itraconazole treatment. Aprepitant Loperamide a Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Netupitant Monitor for adverse reactions. Immunosuppressants Voclosporin Contraindicated during and for 2 weeks after itraconazole treatment. Everolimus Sirolimus Temsirolimus (IV) Not recommended during and 2 weeks after itraconazole treatment. Budesonide (inhalation) a Budesonide (non- inhalation) Ciclesonide (inhalation) Cyclosporine (IV) a Cyclosporine (non- IV) Dexamethasone a Fluticasone (inhalation) a Fluticasone (nasal) Methylprednisolone a Tacrolimus (IV) a Tacrolimus (oral) Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Lipid-Lowering Drugs Lomitapide Lovastatin a Simvastatin a Contraindicated during and 2 weeks after itraconazole treatment. Atorvastatin a Monitor for drug adverse reactions. Concomitant drug dose reduction may be necessary. Respiratory Drugs Salmeterol Not recommended during and 2 weeks after itraconazole treatment. SSRIs, Tricyclics and Related Antidepressants Venlafaxine Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Urologic Drugs Avanafil Contraindicated during and 2 weeks after itraconazole treatment. Fesoterodine Patients with moderate to severe renal or hepatic impairment: Contraindicated during and 2 weeks after itraconazole treatment.

Other patients: Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Solifenacin Patients with severe renal or moderate to severe hepatic impairment: Contraindicated during and 2 weeks after itraconazole treatment.

Other patients: Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Darifenacin Vardenafil Not recommended during and 2 weeks after itraconazole treatment. Dutasteride Oxybutynin a Sildenafil (for erectile dysfunction) Tadalafil (for erectile dysfunction and benign prostatic hyperplasia) Tolterodine Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. For sildenafil and tadalafil, see also Cardiovascular Drugs above. Miscellaneous Drugs and Other Substances Colchicine Patients with renal or hepatic impairment: Contraindicated during and 2 weeks after itraconazole treatment.

Other patients: Not recommended during and 2 weeks after itraconazole treatment. Eliglustat CYP2D6 EMs c taking a strong or moderate CYP2D6 inhibitor, CYP2D6 IMs c, or CYP2D6 PMs c: Contraindicated during and 2 weeks after itraconazole treatment. CYP2D6 EMs c not taking a strong or moderate CYP2D6 inhibitor: Monitor for adverse reactions. Eliglustat dose reduction may be necessary. Lumacaftor/Ivacaftor Not recommended 2 weeks before, during, and 2 weeks after itraconazole treatment. Alitretinoin (oral) Cabergoline Cannabinoids Cinacalcet Galantamine Ivacaftor Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Valbenazine Concomitant drug dose reduction is necessary. Refer to the valbenazine prescribing information for dosing instructions. Vasopressin Receptor Antagonists Conivaptan Tolvaptan Not recommended during and 2 weeks after itraconazole treatment. Drug Interactions with Itraconazole that Decrease Concomitant Drug Concentrations and May Reduce Efficacy of the Concomitant Drug Antineoplastics Regorafenib Not recommended during and 2 weeks after itraconazole treatment. Gastrointestinal Drugs Saccharomyces boulardii Not recommended during and 2 weeks after itraconazole treatment. Nonsteroidal Anti-Inflammatory Drugs Meloxicam a Concomitant drug dose increase may be necessary. * CYP3A4 inhibitors (including itraconazole) may increase systemic contraceptive hormone concentrations. a Based on clinical drug interaction information with itraconazole. b Based on 400 mg bedaquiline once daily for 2 weeks. c EMs: extensive metabolizers;

IMs: intermediate metabolizers, PMs: poor metabolizers Effect of Other Drugs on Itraconazole Itraconazole is mainly metabolized through CYP3A4. Other substances that either share this metabolic pathway or modify CYP3A4 activity may influence the pharmacokinetics of itraconazole. Some concomitant drugs have the potential to interact with itraconazole resulting in either increased or sometimes decreased concentrations of itraconazole. Increased concentrations may increase the risk of adverse reactions associated with itraconazole. Decreased concentrations may reduce itraconazole efficacy. The table below lists examples of drugs that may affect itraconazole concentrations, but it is not a comprehensive list. Refer to the approved product labeling to become familiar with the interaction pathways, risk potential and specific actions to be taken with regards to each concomitant drug prior to initiating therapy with itraconazole. Although many of the clinical drug interactions in Table 2 below are based on information with a similar azole antifungal, ketoconazole, these interactions are expected to occur with itraconazole.

Table 2: Drug Interactions with Other Drugs that Affect Itraconazole Concentrations Examples of Concomitant Drugs Within Class Prevention or Management Drug Interactions with Other Drugs that Increase Itraconazole Concentrations and May Increase Risk of Adverse Reactions Associated with Itraconazole Antibacterials Ciprofloxacin a Erythromycin a Clarithromycin a Monitor for adverse reactions. Itraconazole dose reduction may be necessary. Antineoplastics Idelalisib Monitor for adverse reactions. Itraconazole dose reduction may be necessary. See also Table 1. Antivirals Cobicistat Darunavir (ritonavir-boosted) Elvitegravir (ritonavir-boosted) Fosamprenavir (ritonavir-boosted) Indinavir a Ombitasvir/Paritaprevir/Ritonavir with or without Dasabuvir Ritonavir Saquinavir Monitor for adverse reactions. Itraconazole dose reduction may be necessary. For Boceprevir, cobicistat, elvitegravir, indinavir, ombitasvir/paritaprevir/ritonavir with or without dasabuvir, ritonavir and saquinavir, see also Table 1. Calcium Channel Blockers Diltiazem Monitor for adverse reactions. Itraconazole dose reduction may be necessary. See also the table above. Drug Interactions with Other Drugs that Decrease Itraconazole Concentrations and May Reduce Efficacy of Itraconazole Antibacterials Isoniazid Rifampicin a Not recommended 2 weeks before and during itraconazole treatment. Rifabutin a Not recommended 2 weeks before, during, and 2 weeks after itraconazole treatment. See also Table 1. Anticonvulsants Phenobarbital Phenytoin a Not recommended 2 weeks before and during itraconazole treatment. Carbamazepine Not recommended 2 weeks before, during, and 2 weeks after itraconazole treatment. See also Table 1. Antivirals Efavirenz a Nevirapine a Not recommended 2 weeks before and during itraconazole treatment. Miscellaneous Drugs and Other Substances Lumacaftor/Ivacaftor Not recommended 2 weeks before, during, and 2 weeks after itraconazole treatment. a Based on clinical drug interaction information with itraconazole.