Antifungal Medications

There are 2 formulations of amphotericin B:

• Deoxycholate (standard)

• Lipid-based

The standard formulation,

Many patients have chills, fever, nausea, vomiting, anorexia, headache, and, occasionally, hypotension during and for several hours after an infusion. Amphotericin Bhydrocortisone

Several lipid vehicles

• Amphotericin B lipid complex

• Liposomal amphotericin B

Lipid formulations are preferred over conventional amphotericin B because they cause fewer infusion-related symptoms and less nephrotoxicity.

The main adverse effects of amphotericin B are

• Nephrotoxicity (most common)

• Hypokalemia

• Hypomagnesemia

• Bone marrow suppression

Renal impairment is the major toxic risk of amphotericin B

Amphotericin B is unique among nephrotoxic antimicrobials because it is not eliminated appreciably via the kidneys and does not accumulate as renal failure worsens. Nevertheless, dosages should be lowered or a lipid formulation should be used instead if serum creatinine rises to > 2.0 to 2.5 mg/dL (> 177 to 221 micromol/L) or BUN rises to > 50 mg/dL (> 18 millimole/L). Acute nephrotoxicity can be reduced by aggressive IV hydration with saline before amphotericin B infusion; at least 1 L of normal saline should be given before amphotericin B infusion.

Mild to moderate renal function abnormalities induced by amphotericin B usually resolve gradually after therapy is completed. Permanent damage occurs primarily after prolonged treatment; after > 4 g total dose, approximately 75% of patients have persistent renal insufficiency.

Amphotericin B also may blunt the erythropoietin response and cause anemia. Hepatotoxicity or other untoward effects are unusual.

> 24 hours, allowing single daily doses. It has high penetration into cerebrospinal fluid (CSF) (≥ 70% of serum levels) and has been especially useful in treating cryptococcal meningitis and coccidioidal meningitis. It is also one of the first-line drugs for treatment of candidemia in nonneutropenic patients.

Candida glabrata infection and coccidioidal meningitis. Daily doses of ≥ 1000 mg have been given and have acceptable toxicity. Of note, Pichia kudriavzevii (Candida krusei) is inherently resistant to fluconazole.

Adverse effects that occur most commonly with fluconazole are gastrointestinal (GI) discomfort and rash. More severe toxicity is unusual, but the following have occurred: hepatic necrosis, Stevens-Johnson syndrome, anaphylaxis, alopecia, and, when taken for long periods of time during the first trimester of pregnancy, congenital fetal anomalies.

Drug interactions occur less often with fluconazole than with other azoles. However, fluconazolefluconazole blood levels.

sporotrichosis as well as for mild or moderately severe histoplasmosis, blastomycosis, and paracoccidioidomycosis. It is also effective for chronic pulmonary aspergillosis, coccidioidomycosis, and certain types of chromoblastomycosis. Despite poor CSF penetration, itraconazole can be used to treat some types of fungal meningitis, but it is not the drug of choice. Because of its high lipid solubility and protein binding, itraconazole blood levels tend to be low, but tissue levels are typically high. Drug levels are negligible in urine and CSF. Use of itraconazole

Adverse effects of itraconazole with doses of up to 400 mg/day most commonly are GI, but a few men have reported erectile dysfunction, and higher doses may cause hypokalemia, hypertension, and peripheral edema. Other reported adverse effects include allergic rash, hepatitis, and hallucinations. A U.S. Food and Drug Administration boxed warning for heart failure has been issued.

Drug and food interactions can be significant. When the capsule form is used, acidic drinks (eg, cola, acidic fruit juices) or foods (especially high-fat foods) improve absorption of itraconazole

itraconazoleItraconazoleitraconazole.

A new formulation of itraconazole (SUBA-itraconazole, for SUper BioAvailable) has improved bioavailability without the need for an acidic environment in the stomach. SUBA-itraconazole is taken with food and can be used to treat histoplasmosis, blastomycosis, and aspergillosis. Its dosage is different from other forms of itraconazole.

This broad-spectrum triazole is available as a tablet and an IV formulation. It is considered the treatment of choice for Aspergillus infections (aspergillosisScedosporium apiospermum and Fusarium infections. Additionally, this medication is effective in candidal esophagitis and invasive candidiasis, although it is not usually considered a first-line treatment; it has activity against a broader spectrum of Candida

Adverse effects that must be monitored for include hepatotoxicity, visual disturbances (common), hallucinations, and dermatologic reactions (eg, photosensitivity). Voriconazole can prolong the QT interval.

Drug interactions are numerous, notably with certain immunosuppressants used after organ transplantation.

Cladophialophora species). It is effective against many of the species that cause mucormycosis. Posaconazole can also be used as antifungal prophylaxis in patients with neutropenia with hematologic malignancies and in bone marrow transplant recipients.

Adverse effects of posaconazole, as for other triazoles, include a prolonged QT interval and hepatitis.

Drug interactions

aspergillosis and mucormycosis. It is available as an IV formulation as well as an oral capsule. No drug level monitoring is required.

Adverse effects of isavuconazonium include GI upset and hepatitis; the QT interval may decrease.

Drug interactions occur with many medications.

is an oral, novel azole antifungal that is used for the treatment of recurrent vulvovaginal candidiasis.

Adverse effects of oteseconazole include headache and nausea.

Drug interactions