Histoplasmosis

To assess for resolution of disease, all patients with histoplasmosis infection should be periodically monitored in an outpatient setting. Patients with chronic pulmonary histoplasmosis should be monitored with pulmonary function tests for disease progression or resolution. Patients with progressive disseminated histoplasmosis and severe acute progressive histoplasmosis or severe chronic pulmonary histoplasmosis may require inpatient intensive care monitoring.

Azole antifungals are hepatotoxic. Therefore, liver enzymes should be checked before initiation of therapy; at weeks 1, 2, and 4 after initiating treatment; and every 3 months thereafter until end of therapy. Itraconazole levels should be therapeutically monitored at least 2 weeks after initiation of therapy and randomly throughout the treatment period, to ensure therapeutic concentrations (≥1 microgram/mL) are maintained.

Azole antifungals have a number of potential drug-drug interactions, which should be reviewed prior to administration. Azoles are metabolised primarily through the CYP3A4 enzyme and have interactions with other drugs that are also metabolised by this pathway. Co-administration of drugs that induce CYP3A4 can lead to decreased levels of the azole and should be avoided before and during therapy if possible. In contrast, drugs that inhibit CYP3A4 can increase azole concentrations and should also be used with caution. If co-administration of either of these drugs is deemed necessary, azole drug levels should be monitored carefully with dosage adjustment as necessary. Azoles inhibit CYP3A4 and can elevate plasma concentrations of drugs that are metabolised by this pathway leading to adverse effects, including drugs that prolong the QT interval leading to fatal arrhythmias.

Itraconazole can have negative inotropic activity and patients should be monitored for new onset of cardiac failure while receiving therapy. The drug should be used with caution in patients with heart failure or reduced ejection fraction. If worsening heart failure develops while on itraconazole, another azole may be tried.

Up to 10% to 15% of patients experience relapse despite treatment, which is an indication for long-term maintenance therapy with itraconazole.[24]Dismukes WE, Bradsher RW Jr, Cloud GC, et al. Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group. Am J Med. 1992 Nov;93(5):489-97. http://www.ncbi.nlm.nih.gov/pubmed/1332471?tool=bestpractice.com Due to high rates of relapse, patients should be closely monitored for at least 1 year after treatment is discontinued. Urine Histoplasma capsulatum antigen levels should be taken monthly to monitor response to therapy and followed for 12 months to detect disease relapse.