Itraconazole: uses, dosing, side effects & brands

The following clinically significant adverse reactions are described elsewhere in the labeling: Congestive Heart Failure [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Cardiac Dysrhythmias [see Warnings and Precautions (5.3) ] Pseudoaldosteronism [see Warnings and Precautions (5.4) ] Peripheral Neuropathy [see Warnings and Precautions (5.6) ] Hearing Loss [see Warnings and Precautions (5.7) ] Hypersensitivity Reactions [see Warnings and Precautions (5.8) ] Most common adverse reactions (incidence ≥ 1%) are nausea, rash, vomiting, edema, headache, diarrhea, fatigue, fever, pruritus, hypertension, abnormal hepatic function, abdominal pain, dizziness, hypokalemia, anorexia, malaise, decreased libido, somnolence, albuminuria, impotence ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions in the Treatment of Systemic Fungal Infections Safety data with itraconazole capsules were derived from 602 patients treated for systemic fungal disease…

Co-administration with certain drugs that either affect metabolism of itraconazole or whose metabolism is affected by itraconazole. ( 4.1 ) Hypersensitivity to itraconazole ( 4.2 ) 4.1 Drug Interactions Co-administration of certain drugs that are metabolized by human CYP3A4 substrates are contraindicated with TOLSURA because plasma concentrations of such drugs are increased, which may also increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs [see Warnings and Precaution (5.5) and Drug Interactions (7.1) ] . Co-administration with colchicine, fesoterodine and solifenacin is contraindicated in subjects with varying degrees of renal or hepatic impairment. 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 Drug Interactions (7.1) ] . Increased plasma concentrations of some of these drugs due to co-administration of TOLSURA can lead to QT prolongation and ventricular tachyarrhythmias including occurrences of torsade de pointes , a potentially fatal arrhythmia [ see Drug Interactions (7.1) ] . 4.2 Hypersensitivity TOLSURA is contraindicated in patients with known hypersensitivity to itraconazole. There is limited information regarding cross-hypersensitivity between itraconazole and other azole antifungal agents [see Warnings and Precautions (5.8) ] .

Itraconazole is mainly metabolized through CYP3A4. Other drugs that either share this metabolic pathway or modify CYP3A4 activity may influence the pharmacokinetics of itraconazole. ( 4 , 5 , 7.1 , 7.2 ) 7.1 Effect of TOLSURA 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. Table 4 lists examples of drugs that may have their concentrations affected by itraconazole, but 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 4 are based on information with a similar azole antifungal, ketoconazole, these interactions are expected to occur with itraconazole. Table 4: Drug Interactions with TOLSURA that Affect Concomitant Drug Concentrations Concomitant Drug Within Class Prevention or Management Drug Interactions with TOLSURA 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 TOLSURA treatment. Analgesics Methadone Contraindicated during and 2 weeks after TOLSURA treatment. Fentanyl Not recommended during and 2 weeks after TOLSURA treatment. Alfentanil Buprenorphine (IV and sublingual) Oxycodone Based on clinical drug interaction information with itraconazole. Sufentanil Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antiarrhythmics Disopyramide Dofetilide Dronedarone Quinidine Contraindicated during and 2 weeks after TOLSURA treatment. Digoxin Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antibacterials Bedaquiline Based on 400 mg Bedaquiline once daily for 2 weeks. Concomitant TOLSURA not recommended for more than 2 weeks at any time during bedaquiline treatment. Rifabutin Not recommended 2 weeks before, during, and 2 weeks after TOLSURA treatment. See also Table 5 . Clarithromycin Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. See also Table 5 . Trimetrexate Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Anticoagulants and Antiplatelets Ticagrelor Contraindicated during and 2 weeks after TOLSURA treatment. Apixaban Rivaroxaban Vorapaxar Not recommended during and 2 weeks after TOLSURA 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 TOLSURA treatment. See also Table 5 . Antidiabetic Drugs Repaglinide Saxagliptin Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Antihelminthics, Antifungals and Antiprotozoals Isavuconazonium Contraindicated during and 2 weeks after TOLSURA treatment. Praziquantel Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Artemether-lumefantrine Quinine Monitor for adverse reactions. Antimigraine Drugs Ergot alkaloids (e.g., dihydroergotamine, ergotamine) Contraindicated during and 2 weeks after TOLSURA treatment. Eletriptan Monitor for adverse reactions. Concomitant drug dose reduction may be necessary Antineoplastics Irinotecan Contraindicated during and 2 weeks after TOLSURA treatment. Axitinib Bosutinib Cabazitaxel Cabozantinib Ceritinib Cobimetinib Crizotinib Dabrafenib Dasatinib Docetaxel Ibrutinib Lapatinib Nilotinib Olaparib Pazopanib Sunitinib Trabectedin Trastuzumab-­emtansine Vinca alkaloids Not recommended during and 2 weeks after TOLSURA treatment. Bortezomib Brentuximab-vedotin Busulfan Erlotinib Gefitinib Idelalisib Imatinib Ixabepilone Nintedanib Panobinostat Ponatinib Ruxolitinib Sonidegib Vandetanib Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. For Idelalisib, see also Table 5 . Antipsychotics, Anxiolytics and Hypnotics Alprazolam Aripiprazole Buspirone Diazepam Haloperidol Midazolam (IV) Quetiapine Ramelteon Risperidone Suvorexant Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Zopiclone Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Lurasidone Midazolam (oral) Pimozide Triazolam Contraindicated during and 2 weeks after TOLSURA treatment. Antivirals Simeprevir Not recommended during and 2 weeks after TOLSURA treatment. Daclatasvir Indinavir Maraviroc Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. For indinavir, see also Table 5 . Cobicistat Elvitegravir (ritonavir-boosted) Ritonavir Saquinavir (unboosted) Monitor for adverse reactions. See also Table 5 . Tenofovir disoproxil fumarate Monitor for adverse reactions. Beta Blockers Nadolol Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Calcium Channel Blockers Felodipine Nisoldipine Contraindicated during and 2 weeks after TOLSURA treatment. Diltiazem Other dihydropyridines Verapamil Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. For diltiazem, see also Table 5 . Cardiovascular Drugs, Miscellaneous Ivabradine Ranolazine Contraindicated during and 2 weeks after TOLSURA treatment. Aliskiren Riociguat Sildenafil (for pulmonary hypertension) Tadalafil (for pulmonary hypertension) Not recommended during and 2 weeks after TOLSURA 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 Contraindicated during and 2 weeks after TOLSURA treatment. Gastrointestinal Drugs Naloxegol Contraindicated during and 2 weeks after TOLSURA treatment. Aprepitant Loperamide Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Netupitant Monitor for adverse reactions. Immunosuppressants Everolimus Sirolimus Temsirolimus (IV) Not recommended during and 2 weeks after TOLSURA treatment. Budesonide (inhalation) Budesonide (noninhalation) Ciclesonide (inhalation) Cyclosporine (IV) Cyclosporine (non-IV) Dexamethasone Fluticasone (inhalation) Fluticasone (nasal) Methylprednisolone Tacrolimus (IV) Tacrolimus (oral) Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Lipid-Lowering Drugs Lomitapide Lovastatin Simvastatin Contraindicated during and 2 weeks after TOLSURA treatment. Atorvastatin Monitor for drug adverse reactions. Concomitant drug dose reduction may be necessary . Respiratory Drugs Salmeterol Not recommended during and 2 weeks after TOLSURA 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 TOLSURA treatment. Fesoterodine Patients with moderate to severe renal or hepatic impairment : Contraindicated during and 2 weeks after TOLSURA 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 TOLSURA treatment. Other patients : Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Darifenacin Vardenafil Not recommended during and 2 weeks after TOLSURA treatment. Dutasteride Oxybutynin 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 TOLSURA treatment. Other patients : Not recommended during and 2 weeks after TOLSURA treatment. Eliglustat CYP2D6 EMs EMs: extensive metabolizers; IMs: intermediate metabolizers, PMs: poor metabolizers. taking a strong or moderate CYP2D6 inhibitor, CYP2D6 IMs , or CYP2D6 PMs : Contraindicated during and 2 weeks after TOLSURA treatment. CYP2D6 EMs 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 TOLSURA treatment. Alitretinoin (oral) Cabergoline Cannabinoids Cinacalcet Ivacaftor Monitor for adverse reactions. Concomitant drug dose reduction may be necessary. Vasopressin Receptor Antagonists Conivaptan Tolvaptan Not recommended during and 2 weeks after TOLSURA treatment. Drug Interactions with TOLSURA that Decrease Concomitant Drug Concentrations and May Reduce Efficacy of the Concomitant Drug Antineoplastics Regorafenib Not recommended during and 2 weeks after TOLSURA treatment. Gastrointestinal Drugs Saccharomyces boulardii Not recommended during and 2 weeks after TOLSURA treatment. Nonsteroidal Anti-Inflammatory Drugs Meloxicam Concomitant drug dose increase may be necessary. 7.2 Effect of Other Drugs on TOLSURA 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 TOLSURA resulting in either increased or sometimes decreased concentrations of TOLSURA. Increased concentrations may increase the risk of adverse reactions associated with TOLSURA. Decreased concentrations may reduce TOLSURA efficacy. Table 4 lists examples of drugs that may affect itraconazole concentrations, but 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 TOLSURA. Although many of the clinical drug interactions in Table 5 are based on information with a similar azole antifungal, ketoconazole, these interactions are expected to occur with TOLSURA. Table 5: Drug Interactions with Other Drugs that Affect TOLSURA Concentrations Concomitant Drug Within Class Prevention or Management Drug Interactions with Other Drugs that Increase TOLSURA Concentrations and May Increase Risk of Adverse Reactions Associated with TOLSURA Antibacterials Ciprofloxacin Based on clinical drug interaction information with itraconazole. Erythromycin Clarithromycin Monitor for adverse reactions. TOLSURA dose reduction may be necessary. Antineoplastics Idelalisib Monitor for adverse reactions. TOLSURA dose reduction may be necessary. See also Table 4 . Antivirals Cobicistat Darunavir (ritonavir-boosted) Elvitegravir (ritonavir-boosted) Fosamprenavir (ritonavir-boosted) Indinavir Ritonavir Saquinavir Monitor for adverse reactions. TOLSURA dose reduction may be necessary. For, cobicistat, elvitegravir, indinavir, ritonavir, and saquinavir, see also Table 4 . Calcium Channel Blockers Diltiazem Monitor for adverse reactions. TOLSURA dose reduction may be necessary. See also Table 4 . Gastrointestinal Drugs Drugs that reduce gastric acidity e.g. acid neutralizing medicines such as aluminum hydroxide, or acid secretion suppressors such as H 2 - receptor antagonists and proton pump inhibitors (e.g., omeprazole). Co-administration of these drugs, including omeprazole, with TOLSURA increases the systemic exposure to itraconazole. Monitor for adverse reactions. TOLSURA dose reduction may be necessary [see Clinical Pharmacology (12.3) ]. Drug Interactions with Other Drugs that Decrease TOLSURA Concentrations and May Reduce Efficacy of TOLSURA Antibacterials Isoniazid Rifampicin Not recommended 2 weeks before and during TOLSURA treatment. Rifabutin Not recommended 2 weeks before, during, and 2 weeks after TOLSURA treatment. See also Table 4 . Anticonvulsants Phenobarbital Phenytoin Not recommended 2 weeks before and during TOLSURA treatment. Carbamazepine Not recommended 2 weeks before, during, and 2 weeks after TOLSURA treatment. See also Table 4 . Antivirals Efavirenz Nevirapine Not recommended 2 weeks before and during TOLSURA treatment. Miscellaneous Drugs and Other Substances Lumacaftor/Ivacaftor Not recommended 2 weeks before, during, and 2 weeks after TOLSURA treatment.