Antifungals & Antivirals Flashcards
What are classified as fungi infections?
- yeasts
- mold
- dimorphic species
What are common yeasts that cause infections?
- Candida albicans
- Candida tropicalis
- Candida parapsilosis
- Candida glabrata
- Candida krusei
- Cryptococcus neoformans
What are common molds that cause infections?
- Aspergillus species
- Zygomycetes (Mucor and Rhizopus species; mucormycosis)
What are common dimorphic fungi that cause infections?
- Histoplasma capsulatum
- Blastomyces dermatitidis
- Coccidioides immitis
What fungi infections does Amphotericin B treat?
- Cryptococcus neoforms and most candida species (yeast)
- Aspergillus and Zygomycetes (molds)
- Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides immitis (dimorphic fungi)
Which formulation of Amphotericin B (deoxycholate or lipid formulations) is associated with less toxicity?
lipid formulations
What are boxed warnings with Amphotericin B?
- med errors with deoxycholate vs. lipid formulations have resulted in cardiopulmonary arrest and death
- Conventional amphotericin B (deoxycholate) dose should not exceed 1.5 mg/kg/day
What are SEs with Amphotericin B?
- infusion-related reactions: fever, chills, headache, malaise, rigors, hypo/hypertension, thrombophlebitis, N/V
- hypokalemia
- hypomagnesemia
- nephrotoxicity
- anemia
What SEs are specific to AmBisome?
severe back/chest pain with the first dose
What are the monitoring parameters for Amphotericin B?
- renal function
- LFTs
- electrolytes (K and Mg)
- CBC
What is the MOA of Amphotericin B?
binds to ergosterol, altering membrane permeability and causing cell death
What must Amphotericin B be diluted with for injection?
D5W
What must be done to administer lipid Amphotericin B formulations?
Lipid formulations must be filtered during preparation
What must be done to administer conventional Amphotericin B deoxycholate injection?
requires pre-medication 30-60 minutes prior to infusion to reduce infusion-related reactions
What medications are used to prevent infusion-related reactions with Amphotericin B deoxycholate?
- Acetaminophen/ NSAIDs
- diphenhydramineand/or hydrocortisone
- NS boluses to decrease the risk of nephrotoxicity
- meperidine to decrease the duration of rigors
What dosage forms of Amphotericin B are available?
injection; conventional and lipid formulations are yellow-orange in color
Amphotericin B Lipid Complex
Abeicet
Liposomal Amphotericin B
AmBisome
What drugs interact with Amphotericin B?
- additive risk of nephrotoxicity with nephrotoxic agents (aminoglycosides, cisplatin, polymixins, cyclosporine, loop diuretics, NSAIDs, radiocontrast dye, tacrolimus, vancomycin)
- increases the risk of digoxin toxicity due to hypokalemia
- caution with any agent that decreases potassium or magnesium
What is the MOA of flucytosine?
penetrates fungal cells and is converted to fluorouracil, which competes with uracil and interferes with fungal RNA and protein synthesis
Why should flucytosine not be used alone?
resistance has developed
What is flucytosine used in combination with to treat
invasive cryptococcal and candida infections?
Amphotericin B
What are boxed warnings with flucytosine?
use extreme caution in patients with renal dysfunction; monitor hematologic, renal, and hepatic status
What are SEs with flucytosine?
- dose-related myelosuppression (anemia, neutropenia, thrombocytopenia)
- increased BUN/SCr
- liver injury
- increased bilirubin
- many CNS effects
- hypoglycemia
- aplastic anemia (bone marrow stops making RBCs)
- hypokalemia
When does flucytosine require renal dosage adjustment?
CrCl ≤40
What is the normal dosing of flucytosine?
50-150 mg/kg/day PO divided Q6H
Flucytosine, 5-FC
Ancoban
What is the MOA of -azole antifungals?
decrease ergosterol synthesis and cell membrane formation
Which strains of Candida are resistant to fluconazole?
- C. glabrata
- C. krusei
What are the common uses for itraconazole?
- dimorphic fungi (Blastomycoses and Histoplasma)
- nail bed infections (onychomycosis)
What is the DOC for Aspergillus?
Voriconazole
What are SEs with all azole antifungals?
- Heaptotoxicity; elevated LFTs
- QT prolongation
Which azole antifungal requires renal dosage adjustment?
fluconazole
What are boxed warnings for Itraconazole?
- Can cause or worsen HF
- Do Not use to treat onychomycosis in patients with ventricular dysfunction or hx of HF
- can cause increased concentrations of drugs and can lead to QT prolongation and ventricular arrhythmias, including Torsades de Pointes
What are boxed warnings for ketoconazole?
- Hepatotoxicity; which has lead to liver transplant/ death
- QT prolongation
- Only use PO tabs when other antifungal therapy is unavailable or not tolerated and benefits outweigh risks (hepatotoxicity, drug interactions)
What are the warnings with fluconazole?
- exfoliative skin reactions
- NOT recommended in pregnancy
What are SEs with fluconazole, itraconazole, and ketoconazole?
- elevated LFTs
- QT prolongation
- headache
- N/V
- abdominal pain
- rash/pruritus
- dizziness
What are SEs with ketoconazole shampoo?
- hair loss/growth
- altered hair texture
Why is fluconazole the only azole that needs renal dose adjustment?
all other azoles are cleared hepatically (therefore, LFTs)
Which azole antifungals penetrate the CNS to treat fungal meningitis?
- Fluconazole
- Voriconazole
What is dosing for fluconazole?
50-800mg PO/IV QD
What is the dosing and duration of fluconazole for vaginal candidiasis?
150 mg PO x 1
What is the dosing of fluconazole for those with impaired renal function?
CrCl≤ 50mL/min: decrease the dose by 50%
Fluconazole
Diflucan
What dosage forms are available for fluconazole?
- tablet
- suspension
- injection (IV)
Itraconazole
Sporanox
Tolsura
What is the dosing for itraconazole?
200mg PO QD/BID
How is Tolsura dosed?
130mg PO QD/BID
What are the counseling points for itraconazole solution?
- solution should be taken on an empty stomach
- solution and capsule dosage forms are NOT interchangeable
What are the counseling points for itraconazole capsules?
- take with food
- not absorbed as well as solution and is not interchangable
How is itraconazole dosed for renal impairment?
limited data on use; use caution
What dosage forms are ketoconazole available in?
- tablet
- cream
- foam
- gel
- shampoo
What ketoconazole product is available OTC?
Nizoral A-D shampoo for dandruff
What is dosing for PO ketoconazole?
200-400mg PO daily
How is ketoconazole dosed for renal imapirment?
No adjustment
Voriconazole
Vfend
Vfend IV
What are CI to using voriconazole?
co-administration with barbituates (long-acting), carbamazepine, efavirenz (≥400mg/day), ergot alkaloids, pimozide, quinidine, rifabutin, rifampin, ritonavir (≥800mg/day), sirolimus, St. John’s wort
What are the warnings with Voriconazole?
- hepatotoxicity
- phototoxicity
- visual disturbances (optic neuritis and papilledema)
- QT prolongation (correct K, Ca, and Mg before initiating)
- nephrotoxicity
- avoid in pregnancy
- infusion-related reactions
- serious skin reactions (SJS/TENS)
- skeletal adverse effects (fluorosis, periostitis)
- pancreatitis
What are SEs with voriconazole?
- visual changes (~20% blurred vision, photophobia, altered color and visual acuity)
- elevated LFTs
- elevated SCr
- CNS toxicity (hallucinations, headache, dizziness)
- photosensitivity
- hypo/hyperkalemia
What should be monitored while taking voriconazole?
- LFTs
- renal function
- visual function (when used >28 days)
- trough concentrations (toxicity more likely when trough >5 mcg/mL)
What are the dosage forms for voriconazole?
- tablet
- suspension
- injection
What are the counseling points for PO voriconazole?
- take on an empty stomach, at least 1 hour before or after a meal
- hold tube feed for 1 hour before and 1 hour after doses
- use caution when driving at night due to vision changes
- avoid direct sunlight
- shake suspension for 10 seconds before use; DO NOT refrigerate
What are important considerations when dosing voriconazole?
- reduce maintenance dose by 50% for mild-mod hepatic impairment
- only use in severe hepatic impairment if benefit >risk
- PO preferred in renal impairment
What are important considerations when dosing IV voriconazole?
- CrCl <50: SBECD accumulates in renal impairment; PO preferred
- Monitor SCr when IV vorconazole used and switch to oral when possible
- therapeutic through =1-5 mcg/mL
How is voriconazole dosed IV?
Loading dose: 6mg/kg IV Q12H x 2 doses
Maintenance dose: 4mg/kg IV Q12H
How is voriconazole dosed PO?
200mg PO Q12H
Posaconazole
Noxafil
What are the dosage forms for Posaconazole?
- DR tablet
- suspension
- injection
How is posaconazole suspension dosed?
- 200mg TID or 400 mg BID given with a full meal (during or within 20 minutes following a meal)
- PPIs and cimetidine decrease abs of sus, D/C to avoid treatment failure
How are posaconazole tablets dosed?
300mg PO BID on day 1 then 300mg QD with food (100-400mg/day divided in 1-3 doses)
How is posaconazole IV dosed?
300mg BID on day 1 then 300mg QD
How is posaconazole IV dosed for renal impairment?
oral treatment is preferred because SBECD can accumulate and worsen renal function
What are CIs to using posaconazole?
Co-administration with sirolimus, ergot alkaloids, pimozide, quinidine, atorvastatin, lovastatin, and simvastatin
What are the warnings with posaconazole?
- QT prolongation (correct K, Ca, and Mg prior to initiating treatment)
- prescribing and dispensing errors; suspension and tablet are NOT interchangeable and dosing regimens differ (tablet better absorbed)
- neurotoxicity when used wth vincristine due to increased vincristine levels (seizures, SIADH, paralytic ileus)
What are SEs with posaconazole?
- N/V/D
- fever
- headache
- elevated LFTs
- rash
- hypokalemia
- low Mg
- cough
What is monitored on posaconazole?
- LFTs
- renal function
- electrolytes
- CBC
Isavuconazonium sulfate (prodrug of isavuconazole)
Cresemba
What are the dosage forms of isavuconazonium sulfate?
- capsules
- injection
What is the dosing for Isavuconazonium sulfate?
372mg Q8H x 6 doses, then 372mg QD IV/PO
What are dosing considerations for renal/hepatic impairment when using Isavuconazonium sulfate?
- use caution with severe hepatic impairment
- no adjustment for renal dysfunction
What are counseling points for Isavuconazonium sulfate capsules?
swallow whole; do NOT crush or open
What are the CIs to using Isavuconazonium sulfate?
- use with strong CYP3A4 inhibitors/inducers
- familial short QT syndrome (causes QT shortening)
What are the warnings with Isavuconazonium sulfate?
- hepatotoxicity
- infusion-related reactions (hypotension, dyspnea, chills, dizziness, tingling and numbness)
- hypersensitivity reactions (anaphylaxis, SJS/TENS)
- teratogenic
- drug interactions
- particulates (undissolved IV drug)
What are SEs with Isavuconazonium sulfate?
- N/V/D
- headache
- injection site reactions
- peripheral edema
- low K
- elevated LFTs
What should be monitored with Isavuconazonium sulfate?
- LFTs
- electrolytes
What are counseling points for Isavuconazonium sulfate administration?
- IV formulation requires a 0.2-1.2 micron filter during administration
- capsules must be protected from moisture; original container has desicant
What CYP enzyme is affected by azoles causing drug interactions?
azoles are mod-strong CYP3A4 inhibitors
Which CYP enzyme does fluconazole and voriconazole inhibit, increasing the effects of warfarin?
CYP2C9; monitor increased INR and s/s of bleeding
Which azoles require an acidic gut for absorption?
- Sporanox brand itraconazole capsules
- ketoconazole
What are counseling points for PO Sporanox brand itraconazole capsules and ketoconazole?
- separate antacids 2 hours before and after doses
- avoid PPis and H2RAs
- if PPI/H2RA must be used while on ketoconazole take with an acidic beverage (non-diet cola) to provide an acidic environment for absorption
What drugs do azoles interact with causing safety concerns?
- can increase concentrations of apixaban and rivaroxaban; monitor s/s of bleeding
- Other QT prolonging drugs: antiarrhythmic, quinolones, macrolides, antidepressants, antpsychotics, 5HT3 antagonists
What are major drug interactions with vorconazole?
- exhibits 1st order then 0 order (non-linear) kinetics; dangerously increased concentrations when given with CYP2C19, 2C9, or 3A4 inhibitors
- boxed warning
What is the MOA of echinocandins?
inhibits synthesis of beta 1,3-D-glucan an essential component of the fungal cell wall
Which fungi do echinocandins cover?
- most candida, including azole-resistant C.glabrata and C.krusei
- alternative combination regimen to treat aspergillus
What are warnings with echinocandins?
- anaphylaxis
- histamine-mediated symptoms (rash, pruritus, facial swelling, flushing, hypotension) have occurred
What dosage forms are echinocandins available in?
IV injection only
What are SEs with echinocandins?
- elevated LFTs
- headache
- hyper/hypokalemia
- low Mg
- fever
- N/V/D
- anemia
- increased SCr
- rash
What SEs are specific to capsofungin?
severe skin reactions, including SJS/TENS
What should be monitored when taking echinocandins?
LFTs
How often are echinocandins dosed (except rezafungin)?
once daily