Disorders: Peripheral neuropathy, paresthesia, hypoesthesia, tremorEye Disorders: Visual disturbances, including blurred vision and diplopiaEar and Labyrinth Disorders: Transientor permanent hearing lossRespiratory, Thoracic and Mediastinal Disorders: Pulmonary edema, dyspneaGastrointestinal Disorders: Pancreatitis, dysgeusiaHepatobiliary Disorders: Serious hepatotoxicity (including some cases of fatal acuteliver failure), hepatitisSkin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome,acute generalized exanthematous pustulosis, erythema
multiforme, exfoliative dermatitis, leukocytoclastic vasculitis,alopecia, photosensitivity, urticariaMusculoskeletal and Connective Tissue Disorders: Arthralgia
Renal and Urinary Disorders: Urinary incontinence, pollakiuriaReproductive System and Breast Disorders: Erectile dysfunctionGeneral Disorders and Administration Site
Conditions:
Peripheral edema
Investigations: Blood creatine phosphokinase increased
7 DRUG INTERACTIONS
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 concomitantdrugs. Increased concentrations may increase the risk of adverse reactions associated with theconcomitant 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 examplesof drugs that may have their concentrations affected by itraconazole, but is not a comprehensivelist. 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 toinitiating therapy with itraconazole.
Although many of the clinical drug interactions in Table 4 are based on information with asimilar azole antifungal, ketoconazole, these interactions are expected to occur with itraconazole.
Table 4: Drug Interactions with TOLSURA that Affect Concomitant DrugConcentrations
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)
Oxycodonea
Sufentanil
Monitor for adverse reactions. Concomitant drug dose
reduction may be necessary.
Antiarrhythmics
Disopyramide
Dofetilide
Dronedarone
Quinidinea
Contraindicated during and 2 weeks after TOLSURA
treatment.
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