7.1) and Adverse Reactions (6.2)]
5.2 Hepatotoxicity
Itraconazole has been associated with cases of serious hepatotoxicity, including liver failure anddeath. Some of these cases had neither pre-existing liver disease nor a serious underlyingmedical condition, and some of these cases developed within the first week of treatment. Ifclinical signs or symptoms develop that are consistent with liver disease, discontinue treatmentand perform testing for liver disease. Continued TOLSURA use or reinstitution of treatment withTOLSURA is strongly discouraged unless there is a serious or life-threatening situation wherethe expected benefit exceeds the risk [see Adverse Reactions (6.1)].
5.3 Cardiac Dysrhythmias
Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using drugssuch as, pimozide, methadone, or quinidine concomitantly with oral itraconazole and/or otherCYP3A4 inhibitors. Concomitant administration of these drugs with TOLSURA iscontraindicated [see Boxed Warning, Contraindications (4) and Drug Interactions (7)].
5.4 Drug Interaction Potential
Itraconazole has a potential for clinically important drug interactions [see Drug Interactions (7.1,7.2)]. Co-administration of specific drugs with TOLSURA may result in changes in the efficacyof itraconazole and/or the co-administered drug, life-threatening effects and/or sudden death.
[see Boxed Warning, Contraindications (4.1) and Drug Interactions (7.1, 7.2)].
5.5 Peripheral Neuropathy
Cases of peripheral neuropathy have been reported in patients on long-term therapy withitraconazole. Monitor for and promptly eva luate neurologic symptoms. If neuropathy attributableto TOLSURA occurs, discontinue treatment.
5.6 Hearing Loss
Reversible or permanent hearing loss has been reported in patients receiving treatment withitraconazole. Several of these reports included concurrent administration of quinidine which is contraindicated [see Boxed Warning, Contraindications (4.2) and Drug Interactions (7)]. Thehearing loss usually resolves when treatment is stopped but can persist in some patients.
5.7 Hypersensitivity Reactions
TOLSURA is contraindicated in patients with a known hypersensitivity to itraconazole [seeContraindications (4.2)]. Hypersensitivity reactions have been reported with the use ofitraconazole [see Adverse Reactions (6.2)]. Due to the limited information regarding crosshypersensitivitybetween itraconazole and other azole antifungal drugs, careful enquiry aboutprevious hypersensitivity to other azole antifungal drugs should be made when prescribingTOLSURA. If hypersensitivity reactions to TOLSURA occurs, discontinue the drug and instituteappropriate therapy.
6 ADVERSE REACTIONS
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)]
• Peripheral Neuropathy [see Warnings and Precautions (5.5)]
• Hearing Loss [see Warnings and Precautions (5.6)]
• Hypersensitivity Reactions [see Warnings and Precautions (5.7)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug c |
