TOLSURA

General Pharmacokinetic Characteristics The steady-state pharmacokinetics of itraconazole following administration of a 130 mg twice daily dose regimen of TOLSURA (2 × 65 mg) was compared with a 200 mg twice daily dose regimen of itraconazole capsules (2 × 100 mg) immediately after a meal for 14.5 days in 16 healthy volunteers; the results from this study are presented in Table 6 below

Table 6Pharmacokinetics of Itraconazole Following Administration of TOLSURA and Itraconazole Capsules Given T...

Overview of the Clinical Studies Clinical studies in invasive mycoses listed in this section were conducted with itraconazole 100 mg capsules. Dosage for TOLSURA is different from that of other itraconazole formulations. TOLSURA is not interchangeable or substitutable with other itraconazole products [see Indications and Usage (1) , Dosage and Administration (2) and Clinical Pharmacology (12.3) ] 14.1 Blastomycosis Analyses were conducted on data from two open-label, non-concurrently controlled studies (N=73 combined) in patients with normal or abnormal immune status treated with the100 mg itr...

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....

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 increas...

Hepatotoxicity : Serious hepatotoxicity, including liver failure and death were reported with the use of itraconazole. Discontinue treatment if signs of liver dysfunction occur ( 5.2 ) Cardiac Dysrhythmias : Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using certain drugs that are metabolized by human CYP450 enzymes concomitantly with oral itraconazole and/or other CYP3A4 inhibitors. ( 4 , 5.3 , 5.5 ) Pseudoaldosteronism : Manifested by the onset or worseni...

7 DRUG INTERACTIONS 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 transpo...