Sporotrichosis Medication

Cutaneous and lymphocutaneous sporotrichosis have historically been treated with saturated solution of potassium iodide (SSKI). Although relatively inexpensive, SSKI is poorly tolerated by many patients because of frequent adverse effects.

The orally available azole antifungals are the drugs of choice for cutaneous or lymphocutaneous sporotrichosis in developed nations. Ketoconazole has been used but is less effective than itraconazole or fluconazole; thus, ketoconazole is no longer indicated. Fluconazole is less effective than itraconazole.^[9] Itraconazole is the drug of choice for all types of sporotrichosis but CNS and disseminated sporotrichosis.^[10] Terbinafine has been demonstrated to be effective in the treatment of lymphocutaneous sporotrichosis, but no comparative data with itraconazole therapy exist.^[11]

The following is a summary of recent published guidelines for the medical management of sporotrichosis:^[12]

• Cutaneous and lymphocutaneous sporotrichosis: These are treated with oral itraconazole 200 mg/d until 2-4 weeks after all lesions have resolved, usually for a total of 3-6 months. Patients who do not respond should be given one of the following: (1) oral itraconazole 200 mg twice daily, (2) oral terbinafine 500 mg twice daily, or (3) SSKI initiated at a dose of 5 drops (initially using a standard eye dropper) thrice daily and increasing as tolerated to 40-50 drops thrice daily.
• Osteoarticular sporotrichosis: Oral itraconazole 200 mg twice daily for at least 12 months is recommended. An amphotericin preparation can be used for initial therapy with subsequent switch to oral itraconazole.
• Pulmonary sporotrichosis: For severe or life-threatening pulmonary sporotrichosis, initial therapy should be liposomal amphotericin B 3-5 mg/kg/d; if the patient has a favorable response, therapy can be changed to oral itraconazole 200 mg twice daily for a minimum of 12 months. For less-severe disease, therapy with oral itraconazole 200 mg twice daily for a minimum of 12 months is recommended.
• Meningeal sporotrichosis: Initial therapy should be liposomal amphotericin B 5 mg/kg/d. Upon clinical stabilization, therapy can be changed to oral itraconazole 200 mg twice daily for a minimum of 12 months. In patients with AIDS or other immunosuppressing conditions, life-long suppression with oral itraconazole 200 mg/d should be considered.
• Disseminated sporotrichosis: Initial therapy should be liposomal amphotericin B 5 mg/kg/d. Upon clinical stabilization, therapy can be changed to oral itraconazole 200 mg twice daily for a minimum of 12 months. In patients with AIDS or other immunosuppressing conditions, life-long suppression with oral itraconazole 200 mg/d should be considered.
• Sporotrichosis in pregnant women: Local hyperthermia can be used to treat cutaneous sporotrichosis that does not require urgent therapy. For sporotrichosis that must be treated during pregnancy, liposomal amphotericin B 3-5 mg/kg/d should be used. Azoles should be avoided.

Class Summary

These agents have a mechanism of action that may involve an alteration of RNA and DNA metabolism.

Itraconazole (Sporanox)

A DOC for many forms of sporotrichosis. A synthetic triazole antifungal agent that inhibits fungal cell growth by inhibiting the cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Amphotericin B, liposomal (AmBisome)

Novel lipid formulations of amphotericin B that deliver higher concentrations of the drug, with a theoretical increase in therapeutic potential and decreased nephrotoxicity. Produced from a strain of Streptomyces nodosus. Antifungal activity of amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at sites that contain ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large losses of ions and other molecules. A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity of amphotericin B mayreside in ability to cause auto-oxidation of cell membranes.

Fluconazole (Diflucan)

Comparative study demonstrates that fluconazole is less effective than itraconazole for treatment of sporotrichosis; nonetheless, may be useful in patients unable to tolerate itraconazole. A synthetic broad-spectrum bistriazole oral antifungal agent that is a highly selective inhibitor of fungal cytochrome P-450 and sterol C-14 alpha-demethylation.

Saturated solution of potassium iodide (SSKI)

Difficult for many patients to tolerate. This remains a useful treatment for cutaneous or lymphocutaneous sporotrichosis. Mechanism of action in sporotrichosis is unknown.

Terbinafine (Lamisil)

A fungicidal allylamine antifungal agent. An alternative agent for treatment of cutaneous or lymphocutaneous sporotrichosis unresponsive to itraconazole or if itraconazole cannot be tolerated. Blocks ergosterol synthesis by inhibiting squalene epoxidase. Effective against S schenckii and other fungi and fungal infections, including most dermatophytes, Aspergillus species, blastomycosis, histoplasmosis, and Scopulariopsis brevicaulis. Terbinafine is well absorbed PO and has a long half-life.

No elixir form is available; 250-mg tab is not scored and cannot be pulverized easily for use in children and is not palatable.