ID3 pt 1: Antifungals

Question 1

Fungal classifications (and species in each)

Answer 1

Yeasts, molds, or dimorphic

Yeasts: candida, cryptococcus neoformans

Molds: Aspergillus, zygomycetes (mucor, rhizopus)

Dimorphic: histoplasma, blastomyces dermatidis, coccidioides

Question 2

When do fungi typically cause serious infections

Answer 2

Weakened immune system, compromised by drugs/diseases

Question 3

Most susceptible of the candida species

Answer 3

C albicans

Question 4

Candida species more difficult to treat

Answer 4

C glabrata, C krusei

Due to resistance of certain azole drugs

Question 5

Amphotericin B products are used as initial treatment for many invasive infections, including…

Answer 5

Cryptococcal meningitis
Histoplasmosis
Mucormycosis

Question 6

Difference between lipid formulation amp B and regular amp B

Answer 6

Less infusion reactions, less nephrotoxicity w lipid formulation

Conventional requires pre-medications to reduce infusion related reactions (30-60 mins prior to infusion):
APAP or NSAID
diphenhydramine and/or hydrocortisone
meperidine to reduce duration of severe rigors
NS boluses to decrease risk of nephrotoxicity

Also dose differs: conventional is 0.1-1.5 mg/kg/day, lipid formulations are 3-6 mg/kg/day (depends on formulation)

Question 7

Amp B side effects, boxed warnings, brands/dose forms

Answer 7

Side effects: infusion related (fever, chills, headache, malaise, rigors)
Other: Low K, low mag, nephrotoxicity (pre-treat w NS)

Boxed warnings: verify product name and dosage (conventional is 0.1-1.5 mg/kg/day, lipid formulations 3-6 mg/kg/day)

Amp B deoxycholate = conventional
Ambisome = liposomal amp B
Abelcet = amp B lipid complex

All injections

Question 8

Flucytosine place in therapy

Answer 8

Used in combination with amp B for treatment of invasive cryptocococal or candida infections

Do not use alone due to risk of resistance

Question 9

Flucytosine dosing, side effects, notes

Answer 9

50-150 mg/kg/day divided q6h PO
CrCL < 40 mL/min - adjust dose

Dose-related myelosuppression
Increased SCr, BUN, hepatitis

Avoid as monotherapy due to rapid resistance

Question 10

How do azole antifungals work and why is this important

Answer 10

Inhibitors of fungal CYP450 systems, so they interact with human CYP450 enzymes and cause drug interactions

Question 11

Azole antifungals notes (p 439, 6 things)

Answer 11

All can cause abnormal LFTs

Only fluconazole requires a renal dose adjustment (all others hepatically cleared)

Fluconazole has a narrow spectrum (Candida albicans, Candida tropicalis)

Voriconazole = Drug of choice for aspergillus, monitor for visual changes/phototoxicity

Posaconazole and isavuconazonium active against aspergillus, zygomycetes

Posaconazole - tablet dose different from suspension dose due to differences in bioavailability

Question 12

Ketoconazole brand, boxed warnings, side effects, notes

Answer 12

Nizoral, Ketodan, Extina, Xolegel
(All brand names are topicals)

Boxed warnings: hepatoxocitiy, use oral tablets ONLY when other effective antifungal therapy is unavailable or not tolerated

Side effects: QT prolongation, increased LFTs

Itraconazole and ketoconazole have pH dependent absorption (increased pH causes dec absorption, so dose antacids 2 hours from dose)
(Note: don’t give ketoconazole PO usually soo)

Question 13

Fluconazole brand, dose, side effects, notes

Answer 13

Diflucan
50-800 mg PO/IV daily. CrCL < 50 mL/min decrease dose by 50%

Side effects: QT prolongation, increased LFTs

“Safety issue” - pregnancy, but ok to use x 1 dose for vaginal candidiasis

Question 14

Itraconazole brand, boxed warnings, side effects, notes

Answer 14

Sporanox
200-400 mg PO daily-BID
capsules and oral solutions NOT interchangeable
Solution take WITHOUT food, capsule and tablet take WITH food

Itraconazole = contraindicated in pts with ventricular dysfunction, history of HF (QT prolongation)

Side effects: LFTs, QT prolongation

Itraconazole and ketoconazole have pH dependent absorption (increased pH causes dec absorption, so dose antacids 2 hours from dose)

Question 15

Voriconazole brand, coverage, warnings, side effects, monitoring

Answer 15

Vfend
Requires loading doses x 2 then maintenance dose
Therapeutic levels 1-5 mcg/mL
Covers pretty much everything except zygomycetes (mucor, rhizopus)
Drug of choice for aspergillosis
Warnings: liver damage, visual disturbances, embryofetal toxicity, QT prolongation (correct K, Ca, and Mg before starting), phototoxicity

Side effects: visual changes (~20%)
Increased LFTs, SCr, CNS toxicity, hallucinations

Monitoring: LFTs, renal function, electrolytes, visual function (for therapy > 28 days)

Notes: caution driving at night (visual changes), avoid direct sunlight (phototoxicity), suspension - shake for 10 secs before each use and DO NOT refrigerate

Concentrations can increase dangerously when given with drugs that inhibit voriconazoles metabolism or with small dose increases (first order followed by zero order kinetics)

Question 16

Posaconazole brand, coverage, warnings, side effects

Answer 16

Noxafil
Dose: give with food
Warnings: QT prolongation, correct K Ca and Mg before starting
Suspension and tablet dose not interchangeable (tablet better absorbed so only given daily)
Side effects: elevated LFTs, low K and low Mg

Covers everything

PPIs and cimetidine decrease absorption of posaconazole suspension, stop during therapy to avoid tx failure

Question 17

Isavuconazonium sulfate brand, warnings, concerns

Answer 17

Cresemba
IV - can have particulates (undissolved drug) so must be given with a 0.2-1.2 micron filter during administration
Similar spectrum to posaconazole (basically covers everything)

Question 18

Azole drug interactions

Answer 18

All = CYP3A4 inhibitors

Itraconazole and ketoconazole have pH dependent absorption (increased pH causes dec absorption, so dose antacids 2 hours from dose)

PPIs and cimetidine decrease absorption of posaconazole suspension, stop during therapy to avoid tx failure

Question 19

Echinocandins place in therapy

Answer 19

Covers almost everything, but usually used in combo when covering aspergillus
Well-tolerated, not associated with significant renal or hepatic toxicity
Expensive
IV only
Very few drug interactions

Question 20

Caspofungin brand, side effects, notes

Answer 20

Cancidas
Increased LFTs, hypotension, lot K, low Mg
All once daily, no renal dose adjustments needed

Question 21

Micafungin brand, side effects, notes

Answer 21

Mycamine
Increased LFTs, hypotension, lot K, low Mg
All once daily, no renal dose adjustments needed

Question 22

Thrush treatment

Answer 22

Nystatin suspension
Clotrimazole troche, lozenges

In HIV/moderate-severe infx (including esophageal candidiasis):
Flucoanzole, micafungin (systemic tx)

Question 23

Terbinafine brand, side effects

Answer 23

Lamisil

Headache, increased LFT’s

Question 24

Griseofulvin drug interactions

Answer 24

INDUCES some CYP enzymes (1A2, 2C9, 3A4)

May lead to contraceptive failure (underlined)

Question 25

Treatment recommendation: Candida albicans

Answer 25

Thrush:
Mild - topical clotrimazole, nystatin
HIV+ or mod/severe - fluconazole PO pref’d (underlined)

Esophageal infection:
Fluconazole or echinocandin (micofungin) (underlined)

Bloodstream or invasive:
Echinocandin, amp B, or fluconazole (alt)

Question 26

Treatment recommendation: Candida glabrata or candida krusei

Answer 26

Echinocandins (underlined)

Question 27

Treatment recommendation: Aspergillus

Answer 27

Voriconazole (pref’d), liposomal amp B, isavuconazonium (all underlined)

Question 28

Treatment recommendation: Dermatophytes

Answer 28

Nail bed infx: itraconazole, terbinafine, or fluconazole (underlined)