Chapter 24. Infectious Diseases III: Antifungals & Antivirals

What are examples of yeasts?

Candida species

Cryptococcus neoformans

What are examples of molds?

Aspergillus

Zygomycetes

What are examples of Dimorphic fungi?

Histoplasma

Blastomyces

Coccidiodes

Murcomycosis is the term used to describe a fungi that causes invasive diseases. Which type of fungi is this?

Zygomyces

Which species of candida is the most susceptible to drug treatment?

Candid albicans

What is the mechanism of action of amphotericin B?

Binds to ergosterol and alters cell membrane permeability and causes cell death

What types of fungi does amphotericin B cover?

Yeasts: most candida and cryptococus neoformans

Molds: aspergillus and zygomyces

Dimorphic: histoplasma, blastomyces, coccidiodes

What is amphotericin B lipid formulation?

A complex of active medication and associated with fewer toxicities (decreased infusion reactions, decreased nephrotoxicity)

What are BBWs of amphotericin B?

Errors with lipid-based forms [AmBisome (liposomal amphotericin B) and Abelcet (amphotericin B lipid COMPLEX) and conventional amphotericin B deoxycholate

Resulted in cardiopulmonary arrest and death

Conventional amphotericin B deoxycholate should not exceed 1.5 mg/kg/day

What are side effects of amphotericin B?

Infusion-related:
Fever
Chills
Headache
Rigors
Changes in BP
Thrombophlebitis

Decreased Mg
Decreased K
Nephrotoxicity
Anemia

What should amphotericin B be diluted with?

Dilute with D5W only

Lipid formulations must be filtered

What is an important note before administering amphotericin B deoxycholate?

Requires premedication 30-60 minutes prior to reduce infusion-related reactions:

Acetaminophen or NSAIDs

Diphenhydramine and/or HC

NS bolus to decrease risk of nephrotoxicity

+/- meperidine to decrease duration of severe rigors

A pharmacist received an order for amphotericin B and notices that it is yellow-orange in color. What should the next step be?

a. Discard the vial
b. Use the vial

b. Use the vial

What should be avoided while taking amphotericin B?

Other nephrotoxic agents:
Aminoglycosides
Cisplatin
Polymyxins
Cyclosporine / Tacrolimus
NSAIDs
Loop diuretics
Radiocontrast dye
Vancomycin

Since amphotericin B can decrease K and Mg, what should be avoided while taking this medication?

Digoxin
(Can increase the risk of digoxin toxicity due to hypokalemia)

Use caution with any agent that can decrease K or MG. Replacement should be considered

What is the mechanism of action of flucytosine?

Penetrates fungal cell and is converted to fluorouracil
(competes with uracil to disrupt fungal RNA and protein synthesis)

Should should always be taken with flucytosine?

Amphotericin B

What does flucytosine treat?

Invasive cryptococcal (meningitis) or Candida infections

What is a BBW of flucytosine?

Caution in those with renal dysfunction

Monitor renal and hepatis status

Dose-related myelosuppression (anemia, neutropenia, thrombocytopenia)

What is the mechanism of action of azole antifungals?

Decrease ergosterol synthesis and cell membrane formation

Azole antifungals are potent CYP 3A4 ______

a. Inhibitor
b. Inducer

a. Inhibitor

(Increases other drug's concentration)

Which two candida species is fluconazole not effective against?

C. glabrata
C. Krusei

What is the primary indication for itraconazole use?

Dimorphic fungi (blastomyces, histoplasma) and nail bed infections

What fungi does voriconazole cover?

Aspergillus

What are warnings with azole antifungals as a class effect?

Increases LFTs

QT prolongation (except isavuconazonium)

Many DDIs (3A4 inhibitor)

Which azole antifungal does not require renal dose adjustments?

Fluconazole

Which azole antifungal causes hepatotoxicity?

Ketoconazole

Which azole antifungal can cause heart failure?

Itraconazole

Which azole antifungal can cause visual changes and photosensitivity?

Voriconazole

What is the IV:PO conversion for all antifungals?

1:1

Which azole antifungal should be avoided in pregnancy?

Fluconazole

Which azole antifungals are renally cleared?

All except fluconazole

hich azole antifungals can penetrate the CNS?

Fluconazole

Voriconazole

(AKA these can be used to treat meningitis and should not be used in pregnancy)

A patient's CrCl is < 50 mL/min and they were prescribed Vfend IV, what should the pharmacist do?

a. Fill the prescription
b. Contact the prescriber and switch to PO
c. Change to a different medication

b. Contact the prescriber and switch to PO

PO is preferred when CrCl < 50 mL/min

What are warnings with voriconazole?

Hepatotoxicity (increased LFTs)
Visual disturbances
Optic neuritis (visual disturbances)
Phototoxicity
QT prolongation
Nephrotoxicity (increased SCr)
CNS toxicity (hallucinations)

A patient is newly prescribed Vfend, what is an important counseling note to tell the patient?

Take on an empty stomach at least an hour before or after a meal

Caution while driving at night (visual disturbances)

Avoid direct sunlight

Which antifungals Inhibit CYP 3A4 and 2C9?

Fluconazole

Voriconazole

What needs to be monitored with fluconazole and voriconazole?

INR

Can increase warfarin levels

Azole antifungals as a whole should be monitored when a patient is taking what other medications?

Apixaban
Rivaroxaban
(Can increase bleeding risk)

Other QT prolongating agents
(Antiarrhythmics, quinolones, macrolides, antidepressants(TCAs, SSRIs, mirtazapine, trazodone, venlafaxine) antipsychotics, 5-HT antagonist)

Posaconazole concentration can be decreased by what agents?

PPIs
Cimetidine

Which azole antifungals require an acidic gut?

Itraconazole (Sporanox brand capsule)

Ketoconazole

(PPIs will decrease concentration)

What is the mechanism of action of echinocandins?

Inhibit synthesis of (1,3) D-glucan
(Essential component of fungal cell wall)

What are echinocandins effective against?

Most candida species (including krusei and glabarata; which azoles do not cover)

What dosage form does echinocandins come in?

Injections only

What is the generic name for Cancidas?

Caspofungin

What is the brand name for micfungin?

Mycamine

What are the indications for micafungin?

Candidemia

Esophageal candidiasis

What are the doses for micafungin?

Candidemia = 100 mg IV QD

Esophageal candidiasis = 150 mg IV only

What are warnings with echinocandins?

What are warnings with echinocandins?

Histamine-mediated symptoms (rash, pruritis, facial swelling, flushing, hypotension)

Which echinocandins require light protection?

Micafungin

What are the indications for nystatin?

Oral candidiasis

Intestinal infections

What is griseofulvin indicated for?

Fungal infections of the skin, hair, and nails

What are important counseling notes for griseofulvin?

CI in pregnancy and severe liver disease

Can cause photosensitivity, increase LFTs

Take with a fatty meal or food/milk

What are warnings with terbinafine PO?

Hepatotoxicity (increase LFTs)
SJS/TENS
SLE
TTP
Loss of taste/smell

What is the indication for miconazole buccal tablet?

Oropharyngeal candidiasis

Griseofulvin has a drug interaction with what medication?

Can increase the metabolism of hormonal contraceptives (estrogen and progestin), leading to contraceptive failure

What is the preferred regimen for candida albicans for oropharyngeal infection (thrush)?

Mild: topical antifungals (clotrimazole, miconazole)

Moderate-severe or HIV positive = fluconazole

Alternative = nystatin

What is the preferred regimen for candida albicans for esophageal infection?

Fluconazole

Alternative = Echinocandin

What is the preferred regimen for candida krusei and glabarata?

Echinocandin

Alternative = Amphotericin B or high-dose fluconazole

What is the preferred regimen for aspergillus?

Voriconazole

Alternative = Amphotericin B or isavuconazonium

What is the preferred regimen for cryptococcus neoformans (meningitis)?

Amphotericin B + flucytosine (5-FC)

Alternative = high-dose fluconazole + 5-FC

What is the preferred regimen for dermatophytes (nail bed infection)?

Terbinafine or itraconazole

Alternative = fluconazole

Which types of influenza infect humans?

Influenza A & B

The flu vaccine is recommended for patients at least what age?

6 months

What drugs are neuraminidase inhibitors?

Oseltamivir
Zanamivir
Peramivir

What is the mechanism of action of neuraminidase inhibitors?

Inhibit the enzyme which enables release of new viral particles

When should neuraminidase inhibitors be started?

Within 48 hours of illness

Which medication is a single-dose regimen for the treatment of post-exposure prevention of flu?

Baloxavir (Xofluza)

Patients must be at least what age to use tamiflu?

12 years

What is the treatment regimen for oseltamivir for the flu?

75 mg PO BID x5 days

What are warnings with tamiflu?

Neuropsychiatric events
SJS/TEN

Headache, N/V

How long can tamiflu suspension be stored?

Room temp = 10 days
Fridge = 17 days

What is the treatment regimen for zanamivir?

10 mg (two inhalations) BID x5
Age > 7 YO

What is the prophylaxis regimen for zanamivir?

10 mg (two inhalations) QD x10 (household setting) or 28 days (outbreak)

What is the treatment regimen for baloxavir (Xofluza)?

Ages > 5 YO

>80kg = 60 mg PO once
20-80kg = 40 mg PO once
<20kg = 2 mg/kg/dose

What are the different types of Herpes viruses?

HSV-1, HSV-2
VZV (varicella zoster virus)
CMV (cytomegalovirus)
EBV (epstein-barr virus)

Which Herpes virus is more common in oropharyngeal disease?

HSV-1

Which Herpes virus is more common in genital disease?

HSV-2

What are drug treatments for HSV and VZV?

Acyclovir
Valacyclovir
Famiciclovir

What is the generic name for Zovirax?

Acyclovir

What are warnings with acyclovir, valacyclovir, famiciclovir?

Renal impairment in elderly
Nephrotoxicity
TTP

Can increase seizures

How should acyclovir be dosed?

Using IBW (including obese patients)

Decrease dose in renal impairment

What is a prodrome?

Symptoms appear before lesions appear (cold sores)

What are treatments for cold sores?

Docosanol (Abreva) OTC
Apply 5x daily until healed

Acyclovir (Zovirax) Cream
Apply 5x daily x4 days

What are treatment options for an initial episode systemic herpes labialis?

(More effective than topical)
Acyclovir 200 mg 5x daily or 400 mg TID

Valacyclovir 1 gram BID

Famciclovir 250 mg TID or 500 mg BID

How long should initial systemic treatment for herpes labia be?

5-7 days

What are treatment options for an recurrent episodes systemic herpes labialis?

Acyclovir 400 mg TID x 5-10 days

Valacyclovir 2 grams BID x1 day

Famciclovir 1.5 gram x1 dose

What are treatment options for chronic suppression of systemic herpes labialis?

Acyclovir 400 mg BID

Valacyclovir 500 mg or 1 gram QD

Genital warts is caused by which virus?

HSV-2

What can HSV commonly lead to?

Viral encephalitis

How is viral encephalitis treated?

IV acyclovir 10 mg/kg/dose Q8H x 14-21 days

What are treatment options for shingles?

Lidocaine patch
Pregabalin / gabapentin
Duloxetine
TCAs
NSAIDs
Opioids

What are treatment options for shingles?

Lidocaine patch
Pregabalin / gabapentin
Duloxetine
TCAs
NSAIDs
Opioids

Who are eligible for the singles vaccine?

Adults > 50 YO
Adults > 19 YO who are immunocompromised

What are treatment options for shingles?

Acyclovir (Zovirax) 800 mg PO 5x daily x7-10days

Valacyclovir (valtrex) 1g PO TID x7 days

Famciclovir 500 mg PO TID x7 days

What is CMV (cytomegalovirus)?

A ds-DNA virus in the HHV-5 family

Occurs in severely immunocompromised (AIDS/transplant recipients)

What can CMV cause?

Retinitis
Colitis
Esophagitis

What are the drugs of choice for CMV?

Ganciclovir
Valganciclovir

What drugs are reserved for refractory CMV?

Foscarnet
Cidofovir

What are BBWs with ganciclovir and valganciclovir?

Myelosuppression

Carcinogenic
Teratogenic
Inhibition of spermatogenesis