Infectious Diseases II
Agent
Antiretroviral
Interactions
Sildenafil
Protease inhibitors; delavirdine
Increase in sildenafil concentration
Anticoagulants:
Warfarin
Apixaban
Rivaroxaban
Delavirdine, efavirenz
Protease inhibitor/cobicistat, protease
inhibitor/ritonavir
Protease inhibitor/cobicistat, protease
inhibitor/ritonavir
Increase in warfarin concentration
Increases in apixaban concentrations: Do
not administer in patients who require 2.5
mg BID; in patients requiring 10 mg or 5
mg twice daily, reduce apixaban by 50%
Increases in rivaroxaban expected: Do
not coadminister
Mechanism of action: Binds to ergosterol in the fungal cell membrane, which alters the membrane
permeability, leading to ion leakage and fungal cell death
Candida spp. (except for C. lusitaniae), Blastomycetes, coccidioidomycosis, Cryptococcus,
Paracoccidioides, histoplasmosis, aspergillosis, mucormycosis
Wide spectrum of activity allows its clinical use in many different systemic fungal infections.
Dose
Conventional amphotericin: 0.5–1.0 mg/kg/day
Lipid amphotericin: 3–5 mg/kg/day (higher doses have not been associated with improved
outcomes)
Adverse effects
Renal toxicity
Decrease in glomerular filtration rate, which is associated with cumulative doses greater than
4–5 g
ii.
Clinical manifestation
| (a) | Renal tubular acidosis |
|---|---|
| (b) | Oliguria |
| (c) | Azotemia |
| (d) | Potassium, magnesium, phosphate wasting |
iii.
Prevention
| (a) | Avoid concomitant nephrotoxins. |
|---|---|
| (b) | Avoid dehydration. |
| (c) | Salt loading: 500 mL of normal saline before and after infusion of amphotericin |
Infusion-related reactions
Mediated by cytokine release and prostaglandin synthesis
ii.
Presentation: Fever, chills, nausea, vomiting, flushing, rigors
iii.
Prevention
| (a) | Premedications – Administered 30–60 minutes before infusion |
|---|---|
| (1) | Hydrocortisone 25–50 mg intravenously/orally |
(continued)