Caspofungin Acetate and Ruxolitinib Phosphate

• Generic Name: caspofungin
• Dosage Forms: n.a.
• Other Brand Names: Cancidas

Treatment of invasive aspergillosis in adults, adolescents, and children ≥3 months of age whose disease is refractory to, or who are intolerant of, other antifungals. Has not been evaluated for initial therapy of invasive aspergillosis.

IDSA and other clinicians consider IV voriconazole the drug of choice for primary treatment of invasive aspergillosis in adult and pediatric patients, including HIV-infected patients; IV amphotericin B or isavuconazonium (prodrug of isavuconazole) usually recommended as alternatives for primary treatment.

For salvage therapy in patients refractory to or intolerant of primary antifungal therapy, IDSA recommends IV amphotericin B, an IV echinocandin (caspofungin, micafungin), oral or IV posaconazole, or itraconazole oral suspension. IDSA states that echinocandins (either alone or in conjunction with other antifungals) may be effective for salvage therapy of invasive aspergillosis; however, routine use of echinocandin monotherapy not recommended for primary treatment of invasive aspergillosis.

Candidemia and Other Invasive Candida Infections

Treatment of candidemia and certain other invasive Candida infections (intra-abdominal abscess, peritonitis, pleural space infections) in adults, adolescents, and children ≥3 months of age. A drug of choice.

Has been effective in C. albicans, C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis infections, principally in nonneutropenic patients.

Manufacturer states safety and efficacy not established for treatment of endocarditis, osteomyelitis, or meningitis caused by Candida.

For treatment of candidemia in nonneutropenic patients or for empiric treatment of suspected invasive candidiasis in nonneutropenic patients in intensive care units (ICUs), IDSA recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) for initial therapy; IV or oral fluconazole is an acceptable alternative for initial therapy in selected patients, including those who are not critically ill and unlikely to have infections caused by fluconazole-resistant Candida. IV amphotericin B recommended if echinocandin- and azole-resistant Candida suspected and is an alternative when echinocandins and fluconazole have been ineffective or cannot be used. Consider transition from the echinocandin to fluconazole (usually within 5–7 days) in clinically stable patients if strain susceptible to fluconazole (e.g., C. albicans) and initial treatment resulted in negative repeat blood cultures.

For treatment of candidemia in neutropenic patients, IDSA recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) or, alternatively, IV amphotericin B for initial therapy. Fluconazole is an alternative in those who are not critically ill and have had no prior exposure to azole antifungals; also can be used for step-down therapy in clinically stable patients who have fluconazole-susceptible isolates and documented bloodstream clearance. Voriconazole can be used as an alternative for initial therapy when broader antifungal coverage is required and also can be used as step-down therapy during neutropenia in clinically stable patients who have voriconazole-susceptible isolates and documented bloodstream clearance. An echinocandin, amphotericin B, or voriconazole recommended for infections known to be caused by C. krusei.

For treatment of osteoarticular infections (e.g., osteomyelitis, septic arthritis) caused by Candida, IDSA recommends initial treatment with fluconazole or an IV echinocandin (anidulafungin, caspofungin, micafungin) and follow-up treatment with fluconazole. If septic arthritis involves a prosthetic device that cannot be removed, long-term suppressive or maintenance therapy (secondary prophylaxis) with fluconazole recommended if isolate is susceptible.

For treatment of endocarditis (native or prosthetic valve) or implantable cardiac device infections caused by Candida, IDSA recommends initial treatment with IV amphotericin B (with or without flucytosine) or an IV echinocandin (anidulafungin, caspofungin, micafungin) and follow-up treatment with fluconazole. If isolate is susceptible, long-term suppressive or maintenance therapy (secondary prophylaxis) with fluconazole recommended to prevent recurrence in those with native valve endocarditis who cannot undergo valve replacement and in those with prosthetic valve endocarditis.

Esophageal Candidiasis

Treatment of esophageal candidiasis in adults, adolescents, and children ≥3 months of age. A drug of choice.

Esophageal candidiasis requires treatment with a systemic antifungal (not a topical antifungal).

IDSA recommends oral fluconazole as the preferred drug of choice for the treatment of esophageal candidiasis; if oral therapy not tolerated, IV fluconazole or an IV echinocandin (anidulafungin, caspofungin, micafungin) recommended. For fluconazole-refractory infections, IDSA recommends itraconazole oral solution or IV or oral voriconazole; alternatives are an IV echinocandin (anidulafungin, caspofungin, micafungin) or IV amphotericin B. IDSA states oral posaconazole (oral suspension or delayed-release tablets) is another possible alternative for treatment of fluconazole-refractory esophageal candidiasis.

For treatment of esophageal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend IV or oral fluconazole or itraconazole oral solution. Alternatives include oral or IV voriconazole, an IV echinocandin (anidulafungin, caspofungin, micafungin), or IV amphotericin B. For refractory esophageal candidiasis, including fluconazole-refractory infections, in HIV-infected adults and adolescents, itraconazole oral solution or posaconazole oral suspension is recommended; alternatives are IV amphotericin B, an IV echinocandin (anidulafungin, caspofungin, micafungin), or oral or IV voriconazole.

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence not usually recommended in patients adequately treated for esophageal candidiasis (including HIV-infected individuals), patients with frequent or severe recurrences of esophageal candidiasis may benefit from secondary prophylaxis with oral fluconazole or posaconazole oral suspension; however, consider potential for development of azole resistance.

Oropharyngeal Candidiasis

Treatment of oropharyngeal candidiasis. Considered an alternative, not a drug of choice.

For mild oropharyngeal candidiasis, IDSA recommends topical treatment with clotrimazole lozenges or miconazole buccal tablets; nystatin (oral suspension or tablets) is an alternative. For moderate to severe oropharyngeal candidiasis, IDSA recommends oral fluconazole. For fluconazole-refractory oropharyngeal candidiasis, IDSA recommends itraconazole oral solution or posaconazole oral suspension; oral voriconazole or amphotericin B oral suspension (not commercially available in the US) recommended as alternatives. Other alternatives for refractory oropharyngeal candidiasis are IV echinocandins (anidulafungin, caspofungin, micafungin) or IV amphotericin B.

For treatment of oropharyngeal candidiasis in HIV-infected adults and adolescents, CDC, NIH, and IDSA recommend oral fluconazole as the preferred drug of choice for initial episodes; if topical therapy used (e.g., mild to moderate episodes), drugs of choice are clotrimazole lozenges or miconazole buccal tablets. Alternatives for systemic treatment are itraconazole oral solution or posaconazole oral suspension; nystatin oral suspension is an alternative for topical treatment. For fluconazole-refractory infections in HIV-infected adults and adolescents, posaconazole oral suspension is preferred; itraconazole oral solution is an alternative.

Although routine long-term suppressive or maintenance therapy (secondary prophylaxis) to prevent relapse or recurrence not usually recommended in patients adequately treated for oropharyngeal candidiasis (including HIV-infected individuals), patients with frequent or severe recurrences of oropharyngeal candidiasis may benefit from secondary prophylaxis with oral fluconazole; however, consider potential for development of azole resistance.

Candida auris Infections

Treatment of infections caused by C. auris, an emerging pathogen associated with potentially fatal candidemia or other invasive infections.

First identified in 2009, C. auris has now been reported as the cause of serious invasive infections (including fatalities) in multiple countries worldwide (e.g., Japan, South Korea, India, Kuwait, South Africa, Pakistan, United Kingdom, Venezuela, Colombia, US). As of May 2017, a total of 77 clinical cases of C. auris had been reported to CDC from 7 different states. May be difficult to identify using standard in vitro methods. Large percentage of C. auris clinical isolates are resistant to fluconazole; multidrug-resistant isolates with reduced susceptibility or resistance to all 3 major classes of antifungal agents (azoles, polyenes, echinocandins) reported.

CDC issued interim recommendations regarding laboratory diagnosis, treatment, and infection control measures for suspected or known C. auris infections. Based on limited data available to date, CDC recommends an IV echinocandin (anidulafungin, caspofungin, micafungin) for initial treatment of invasive C. auris infections (e.g., bloodstream or intra-abdominal infections) in adults. CDC states a switch to IV amphotericin B (lipid formulation) could be considered if patient is clinically unresponsive to the echinocandin or if fungemia persists >5 days. Consultation with an infectious disease specialist highly recommended.

CDC recommends that infection control measures be observed for all patients with cultures yielding C. auris, including those with positive cultures only from noninvasive body sites.

Empiric Therapy in Febrile Neutropenic Patients

Empiric therapy of presumed fungal infections in febrile, neutropenic adults, adolescents, and children ≥3 months of age.

• Generic Name: ruxolitinib
• Dosage Forms: n.a.
• Other Brand Names: Jakafi

Treatment of intermediate- or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis (designated an orphan drug by FDA for this use).