Azole - Antifungal Class

Question 1

(T/F) - Azoles have become mainstay of antifungal therapy

Answer 1

TRUE

Question 2

What is the MOA of azoles?

Answer 2

Inhibits fungal cytochrome P450, decreasing ergosterol production

Question 3

Itraconazole has a good spectrum in which fungi organisms?

Answer 3

• C. albicans
• C. lusitaniae
• C. tropicalis
• C. parapsilosis
• Cryptococcus neoformans
• Aspergillus spp
• Many dimorphic fungi

Question 4

What AEs can occur in itraconazole?

Answer 4

• Hepatotoxicity
• QTc prolongation
• Negative inotrope

Question 5

Itraconazole is contraindicated in what?

Answer 5

Heart failure patients

Question 6

Itraconazole strongly inhibits what?

Answer 6

CYP3A4

Question 7

What are the popular itraconazole formulations?

Answer 7

• Capsules

- Solution

Question 8

Which itraconazole formulation has a lower bioavailability?

Answer 8

Capsules

Question 9

Which itraconazole formulation is less preferred for systemic fungal infections?

Answer 9

Capsules

Question 10

Which itraconazole formulation should be taken with a full meal?

Answer 10

Capsules

Question 11

Which itraconazole formulation should be taken on an empty stomach?

Answer 11

Solution

Question 12

If someone wants to lower the absorption levels of itraconazole, how can it be lowered?

Answer 12

With PPIs; or take itraconazole with a soda

Question 13

What is the drug of choice for itraconazole?

Answer 13

Histoplasmosis; a dimorphic infection

Question 14

Fluconazole has a good spectrum in which fungi organisms?

Answer 14

• C. albicans
• C. tropicalis
• C. parapsilosis
• C. lusitaniae
• Cryptococcal neoformans
• Coccidioides immitis

Question 15

What AEs can occur with fluconazole?

Answer 15

• Rash
• Hepatotoxicity
• QTc prolongation

Question 16

Fluconazole strongly inhibits what?

Answer 16

• CYP2C19

- CYP2C9

Question 17

Fluconazole moderately inhibits what?

Answer 17

CYP3A4

Question 18

(T/F) - Fluconazole has a high bioavailability, regardless of formulation

Answer 18

TRUE

Question 19

(T/F) - Fluconazole needs to adjust doses in renal insufficient patients

Answer 19

TRUE

Question 20

(T/F) - Fluconazole has a strong activity against C. krusei and C. glabrata

Answer 20

FALSE - poor activity against those fungi organisms

Question 21

If fluconazole will be used for C. krusei or C. glabrata, what should be done before giving fluconazole and at what dose should fluconazole be given?

Answer 21

Check susceptibilities; 800 mg/day

Question 22

What is the drug of choice for fluconazole?

Answer 22

Susceptible fungal infections

Question 23

Voriconazole has a good spectrum in which fungi organisms?

Answer 23

• C. albicans
• C. tropicalis
• C. parapsilosis
• C. lusitaniae
• C. krusei
• Aspergillus spp
• Many other moulds

Question 24

What AEs can occur with voriconazole?

Answer 24

• Hepatotoxicity
• Rash
• QTc prolongation
• Visual and auditory hallucinations
• Visual effects
• Photosensitivity

Question 25

What kind of visual effects can occur with voriconazole?

Answer 25

- Wavy lines | - Flashing

Question 26

Voriconazole moderately inhibits what?

Answer 26

- CYP2C9 | - CYP3A4

Question 27

(T/F) - The IV formulation of voriconazole can be nephrotoxic

Answer 27

TRUE - it contains a cyclodextrin vehicle which can accumulate in renal dysfunction patients

Question 28

Voriconazole IV is contraindicated in what?

Answer 28

CrCl < 50 mL/min

Question 29

Can another formulation of voriconazole be used for renal dysfunction patients?

Answer 29

Oral formulations

Question 30

Voriconazole is not useful for what treatment?

Answer 30

Candiduria

Question 31

Voriconazole is eliminated where?

Answer 31

Hepatically

Question 32

What is the drug of choice for voriconazole?

Answer 32

Invasive aspergillus

Question 33

Posaconazole has a good spectrum in which fungi organisms?

Answer 33

- C. albicans - C. parapsilosis - C. tropicalis - C. lusitaniae - C. krusei - Aspergillus spp - Many moulds - Dimorphic fungi - Mucorales (Zygomycetes spp)

Question 34

What AEs can occur with Posaconazole?

Answer 34

- Hepatotoxicity - Rash - Possible QTc prolongation - GI disturbances

Question 35

Posaconazole is a strong inhibitor of what?

Answer 35

CYP3A4

Question 36

What are the formulation of Posaconazole in the market?

Answer 36

- Oral delayed release tablets - Oral suspension - IV injection

Question 37

Which formulations are not interchangeable with posaconazole?

Answer 37

Oral delayed release tablets and oral suspension

Question 38

Which formulations need to be taken with a meal with posaconazole?

Answer 38

Oral formulations

Question 39

What is the indicated choice for PO tabs, suspension and IV posaconazole formulations?

Answer 39

- Prophylaxis of candida | - Aspergillus in high-risk patients

Question 40

What is the indicated choice for PO suspension of posaconazole formulation?

Answer 40

- Oropharyngeal candidiasis | - Resistance of fluconazole and/or itraconazole

Question 41

Isavuconazole has a good spectrum in which fungal organisms?

Answer 41

- Candida spp - Aspergillus spp - Mucorales (zygomycetes spp) - Other moulds - Dimorphic fungi

Question 42

What AEs can occur with isavuconazole?

Answer 42

- Hepatotoxicity

Question 43

Isavuconazole is a substrate from what?

Answer 43

CYP3A4

Question 44

Isavuconazole is an inhibitor of what?

Answer 44

- CYP4A4 - P-gp - Organic cation transporter 2

Question 45

What are the formulations available with isavuconazole?

Answer 45

- Capsules | - IV

Question 46

(T/F) - Isavuconazole capsules need to be taken with food

Answer 46

FALSE - can be taken with or without food

Question 47

(T/F) - Isavuconazole is supplied as a prodrug

Answer 47

TRUE

Question 48

(T/F) - Isavuconazole is a narrow spectrum drug

Answer 48

FALSE - broad spectrum

Question 49

(T/F) - Isavuconazole has a very long t 1/2

Answer 49

TRUE

Question 50

Does the loading dose of isavuconazole need extensive dosing?

Answer 50

Yes; q8h for 48h then 24h

Question 51

What is the drug of choice for isavuconazole?

Answer 51

Invasive mold infections