Tieman - Antifungal Agents

Question 1

Risk factors for invasive candidiasis

Answer 1

-Prolonged stay in ICU
-Central venous catheters
-Prolonged therapy with broad spectrum antibacterial agents
-Receipt of parenteral nutrition
-Recent surgery
-Hemodialysis
-Diabetes

Question 2

What is aspergillus?

Answer 2

-Mold that is found in soil
-Primarily causes disease in immunocompromised hosts
-Pulmonary system is most common infection (can occur anywhere though)
-Definitive diagnosis requires positive culture from a sterile site
-Very difficult infection to treat

Question 3

Which fungi are seen in Indiana?

Answer 3

-Histoplasma capsulatum
-Blastomyces species

Question 4

Where do cryptococcus infections typically occur?

Answer 4

CNS and respiratory tract

Question 5

What fungi infections is amphotericin first line?

Answer 5

-Used as first line for SYSTEMIC INVASIVE fungal infections
-Cryptococcus
-Blastomyces
-Histoplasma
-Mucor

Question 6

What is the dose for deoxycholate amphotericin?

Answer 6

-0.5-1 mg/kg/day

Question 7

How long should deoxycholate amphotericin be infused for?

Answer 7

-Traditionally infused over 4-6 hours
-Data suggests that there are fewer adverse effects when infused over 24 hours

Question 8

Liposomal amphotericin dose

Answer 8

3-5 mg/kg daily

Question 9

Lipid complex amphotericin dose

Answer 9

5mg/kg daily

Question 10

Amphotericin adverse effects

Answer 10

-Infusion related reactions (pretreat with acetaminophen and antihistamines)
-Dose-dependent nephrotoxicity
-Hypokalemia
-Hypomagnesemia

Question 11

How is flucytosine administered?

Answer 11

Always orally

Question 12

What is the main use of flucytosine?

Answer 12

Combo therapy with amphotericin for cryptococcal meningitis

Question 13

How is flucytosine excreted?

Answer 13

Through the urine

Question 14

Flucytosine adverse effects

Answer 14

-GI effects (take with food)
-Bone marrow suppression

Question 15

What should be monitored in patients on flucytosine?

Answer 15

-CBC
-Platelets
-SCr
-BUN

Question 16

Can fluconazole be taken orally?

Answer 16

Yes with no food restrictions

Question 17

Can fluconazole be used for CSF infections?

Answer 17

Yes it has decent CSF concentration

Question 18

How is fluconazole excreted?

Answer 18

-Unchanged in the urine
-Reduce dose in renal insufficiency

Question 19

How do you dose fluconazole?

Answer 19

Using TOTAL body weight

Question 20

Which CYPs does fluconazole interact with?

Answer 20

-Potent CYP2C9 inhibitor
-Moderate CYP3A4 inhibitor

Question 21

What is fluconazole used to treat?

Answer 21

-Invasive candidiasis
-Noninvasive candidiasis
-Prophylaxis in BMT
-Cryptococcal meningitis as step-down therapy

Question 22

Fluconazole invasive candidiasis dosing

Answer 22

-C. albicans: 800 mg (12 mg/kg) loading dose, then 400 mg (6 mg/kg) daily
-C. glabrata: 800 mg daily (loading dose 1200-1600 mg) - dependent on susceptibility

Question 23

Fluconazole cryptococcal meningitis dosing

Answer 23

-Consolidation therapy: 800 mg daily for 10-12 weeks after CSF negative
-Maintenance therapy: 400 mg daily for at least 1 year

Question 24

Fluconazole adverse effects

Answer 24

-Headache
-Nausea
-Anorexia
-QTc prolongation
-Elevation of hepatic transaminases
-Adrenal insufficiency

Question 25

What fungi is fluconazole first line treatment for?

Answer 25

-Candida albicans -Candida parapsilosis -Candida tropicalis -Candida lusitaniae -Cocidoides

Question 26

What predominantly metabolizes itraconazole?

Answer 26

CYP3A4

Question 27

What is the active metabolite of itraconazole?

Answer 27

Hydroxyitraconazole

Question 28

How is itraconazole cleared?

Answer 28

Clearance decreases with higher doses due to saturable hepatic metabolism

Question 29

Can itraconazole treat CSF infections?

Answer 29

No

Question 30

Can itraconazole be taken orally?

Answer 30

-Yes but absorption is dependent on gastric acidity -Better when taken with meal or acidic cola beverage -Oral solution is absorbed well and not affected by gastric acidity

Question 31

What is itraconazole used to treat?

Answer 31

-Histoplasmosis -Blastomycosis

Question 32

Itraconazole dose for histoplasmosis

Answer 32

200 mg PO TID for three days, then 200 mg PO BID

Question 33

Itraconazole adverse effects

Answer 33

-Hepatotoxicity -Congestive heart failure (boxed warning) -QTc prolongation

Question 34

How can you reduce side effects of itraconazole?

Answer 34

-Make sure trough concentrations are between 1.5 and 3 -Concentration over 1.5 associated with efficacy -Concentration over 3 associated with adverse effects

Question 35

Can posaconazole be taken orally?

Answer 35

-Yes but it is affected by gastric pH so avoid taking with PPIs -Delayed release tablets not affected by gastric pH

Question 36

When must posaconazole IV be discontinued?

Answer 36

When CrCl is below 50

Question 37

Posaconazole adverse effects

Answer 37

-Nausea/vomiting -Abdominal pain -Diarrhea -QTc prolongation -AST/ALT/bilirubin increased -Hypokalemia -Rash -Pseudo-aldosteronism

Question 38

Posaconazole spectrum of activity

Answer 38

Not first-line for any infection but very broad spectrum

Question 39

How is voriconazole metabolized?

Answer 39

Significantly metabolized by CYP2C19, 2C9, 3A4

Question 40

How is voriconazole excreted?

Answer 40

-Mostly by the liver -No dosage adjustment needed for oral therapy

Question 41

When should voriconazole IV be avoided?

Answer 41

If CrCl is less than 50

Question 42

Can voriconazole be taken orally?

Answer 42

Yes it is not affected by gastric pH

Question 43

What infection is voriconazole used for?

Answer 43

Invasive aspergillosis

Question 44

Voriconazole dose for invasive aspergillosis

Answer 44

-Loading dose: 6 mg/kg IV q12h for first 24 hr -Maintenance dose: 4 mg/kg IV q12h or 200 mg PO q12h

Question 45

Voriconazole adverse effects

Answer 45

-Visual disturbances -Elevated liver function tests -CNS -Peripheral neuropathy -QTc prolongation -Phototoxic skin reactions -Diffuse, painful periostitis

Question 46

Voriconazole spectrum of activity

Answer 46

-Very broad -First line for aspergillus

Question 47

Isavuconazole adverse effects

Answer 47

-NVD -Headache -Hepatic -Infusion related reactions -Hypokalemia -Hypersensitivity -Does NOT cause QT prolongation (use in patients with prolonged QTc)

Question 48

What is voriconazole contraindicated in?

Answer 48

-CYP3A4 inducers and inhibitors -Patients with familial short QT syndrome

Question 49

Echinocandin spectrum of activity

Answer 49

-C. glabrata -C. Krusei -C. lusitaniae -C. auris -May add micafungin to voriconazole in severe aspergillus infections

Question 50

Caspofungin adverse effects

Answer 50

-Histamine mediated symptoms -Fever -Phlebitis at infusion site -NV -Headache -Increased liver transaminases -Hypokalemia

Question 51

Can micafungin be given orally?

Answer 51

No, must be IV

Question 52

How is micafungin excreted?

Answer 52

-Metabolized by the liver, no dosage adjustment needed in renal dysfunction -Do not use for urine infections

Question 53

Micafungin drug interactions

Answer 53

Not metabolized by CYP450 pathways

Question 54

Micafungin adverse effects

Answer 54

-Hyperbilirubinemia -Nausea -Diarrhea -Eosinophilia -Rash, pruritus, uticarial

Question 55

In what patients is ibrexafungerp contraindicated in?

Answer 55

Pregnant patients, use effective contraception during and for 4 days after treatment