antifungal drugs Flashcards
name the triazoles
fluconazole
itra
posa
vori
which triazole has good penetration into CSF to treat fungal meningitis
fluconazole
why is fluconazole used to treat candiduria
largely excreted unchanged in the urine
itraconazole is active against a wide range of…
dermatophytes
which capsules need acid environment in stomach for optimal absorption
itraconazole
which drug has been associated with liver damage and should be avoided or used with caution in patients with liver disease? and which one would. you use instead
Itraconazole has been associated with liver damage and should be avoided or used with caution in patients with liver disease; fluconazole is less frequently associated with hepatotoxicity.
name the imidazoles
clotrimazole, econazole nitrate, ketoconazole, and tioconazole, miconazole
3 indications for imidazoles
local treatment of vaginal candidiasis and for dermatophyte infections. Miconazole can be used locally for oral infections; it is also effective in intestinal infections
name the polyene antifungals
amphotericin B and nystatin
are the polyenes (amph, nystatin) absorbed when given by mouth
no
which drug is highly protein bound and penetrates poorly into body fluids and tissues
amph B (polyene antifungal)
when conventional forms of amph B are CI because of toxicity (esp nephrotixicty) or when response is inadeqaute, what can you give instead
liposomal amph B
name the echinocandins
anidulafungin, caspofungin and micafungin.
activity of the echinocandins
They are only active against Aspergillus spp. and Candida spp.; however, anidulafungin and micafungin are not used for the treatment of aspergillosis
are echinocandins effective against CNS fungal infections
no
Flucytosine is used with amphotericin B in a synergistic combination. what side effect can occur, esp in HIV +ve pt
bone marrow depression
this limits its use
weekly blood counts needed with prolonged therapy
resistance to this drug can develop during therapy so you must do sensitivity testing before and during treatment
flucytosine
for this drug, when given parenterally, toxicity is common so close supervision necessary and close observation required for at least 30 minutes after test dose
amphotericin B
to avoid potential toxicity with amph B what must you do when given parenterally
close supervision necessary and close observation required for at least 30 minutes after test dose
why is test dose advisable for amph B
Anaphylaxis can occur with any intravenous amphotericin B product and a test dose is advisable before the first infusion in a new course; the patient should be carefully observed for at least 30 minutes after the test dose.
somebody has previously experienced infusion-related reactions but continued treatment with amph B is essential. what should you do
Manufacturer advises prophylactic antipyretics or hydrocortisone can be used in patients who have previously experienced infusion-related reactions (in whom continued treatment with amphotericin B is essential).
what to do if hepatic function abnormal with amph B
discontinue
monitoring for amph B
Hepatic and renal function tests, blood counts, and plasma electrolyte (including plasma-potassium and magnesium concentration) monitoring required.
amph B is …toxic
nephro
(reduced with liposomal)
what electrolyte disturbance can amph B cause
hypokalaemia
potentially increases risk of TDP when given with other drugs e.g. amiodarone, antipsychotics, theophylline, apomorphine, clomipramine, citalopram, fluconazole, flucytosine, hydroxychloroquine, hydroxyzine, quinine etc
clotrimazole conception and contraception
Cream and pessaries may damage latex condoms and diaphragms.
use of clotrimazole in pregnancy with vaginal use
With vaginal use:
Pregnant women need a longer duration of treatment, usually about 7 days, to clear the infection. Oral antifungal treatment should be avoided during pregnancy.
fluconazole dose for vaginal candidiasis
150mg for one dose
triazole (fluconazole, itraconazole etc) main interactions
hypokalaemia (increased TDP risk): theophylline, antifungals, diuretics, CCs,
QT interval prolongation: antipsychotics, amiodarone, apomorphine, citalopram, clomipramine, domperidone, quinine, hyroxyzine, methadone
hepatotoxicity
interaction of fluconazole with this antiplatelet
Fluconazole is predicted to decrease the efficacy of Clopidogrel. Manufacturer advises avoid.
fluconazole monitoring
Monitor liver function with high doses or extended courses—discontinue if signs or symptoms of hepatic disease (risk of hepatic necrosis).
The CHMP has recommended that the marketing authorisation for oral ……. to treat fungal infections should be suspended. The CHMP concluded that the risk of hepatotoxicity associated with oral ….. is greater than the benefit in treating fungal infections
ketoconazole
ketoconazole is only used orally for
Cushing’s syndrome
the use of carbonated drinks, such as cola, improves ….. bioavailability.
ketoconazole
miconazole fungal skin infections dose
Apply twice daily continuing for 10 days after lesions have healed.
miconazole oral candidiasis dose
2.5 mL 4 times a day treatment should be continued for at least 7 days after lesions have healed or symptoms have cleared, to be administered after meals, retain near oral lesions before swallowing (dental prostheses and orthodontic appliances should be removed at night and brushed with gel).
miconazole interactions
vit K antagonists - increases AC effect, avoid unless closely monitoring INR, monitor for signs of bleeding
carbamazepine, phenytoin, fosphenytoin - increased risk toxicity, monitor and adjust dose
avoid simvastatin, increased exposure
ciclosprin, tacrolimus, sildenafil, disopyramide - increases conc. monitor and adjust dose
avoid this statin + miconazole
avoid simvastatin, increased exposure of simvastatin
discontinue terbinafine if the following 2 occur
With oral use; discontinue treatment if liver toxicity develops (including jaundice, cholestasis and hepatitis).
With oral use; discontinue treatment in progressive skin rash (including Stevens-Johnson syndrome and toxic epidermal necrolysis).
terbinafine age otc
over 16 years
terbinafine increases exposure to…
TCAs (clomi, imi, lofep, nort etc) - moniotr for toxicity and adjust dose
SSRIs
atomoxetine - markedly increasex exposure, adjust dose
terbinafine interaction with this antipsychotic
Terbinafine is predicted to increase the exposure to Clozapine. Manufacturer advises use with caution and adjust dose.
terbinafine and tamoxifen
Terbinafine is predicted to decrease the efficacy of Tamoxifen. Manufacturer advises avoid.
terbinafine and tramadol, codeine
Terbinafine is predicted to decrease the efficacy
nystatin dose oral candidiasis
100 000 units 4 times a day usually for 7 days, and continued for 48 hours after lesions have resolved.
ketoconazole interactions (imidazole)
DOACS - it increases their exposure, avoid apixaban
Statins - increases exposure - avoid or adjust dose and monitor for rhabdomyolosis
CCs - increases exposure, avoid or monitor adverse effects
Alfentanil, buprenorphine, buspirone - increases exposure, monitor and adjust dose
ketoconazole and colcichine
Ketoconazole is predicted to increase the exposure to Colchicine. Manufacturer advises avoid potent CYP3A4 inhibitors or adjust Colchicine dose. (Reduce dose by 75% to one quarter of usual dose)
ketoconazole and digoxin
Ketoconazole is predicted to markedly increase the concentration of Digoxin. Manufacturer advises monitor Digoxin concentration.
ketoconazole and dronedarnoe
Ketoconazole very markedly increases the exposure to Dronedarone. Manufacturer advises avoid.
ketoconazole and eplerenone
Ketoconazole is predicted to markedly increase the exposure to Eplerenone. Manufacturer advises avoid.
ketoconazole and simvastatin
Ketoconazole is predicted to increase the exposure to Simvastatin. Manufacturer advises avoid.
monitoring pt parameters for systemic terbinafine
Monitor hepatic function before treatment and then periodically after 4–6 weeks of treatment—discontinue if abnormalities in liver function tests.
griseofulvin oral use - contraception and conception
Effective contraception required during and for at least 1 month after administration to women (important: effectiveness of oral contraceptives may be reduced, additional contraceptive precautions e.g. barrier method, required).
Men should avoid fathering a child during and for at least 6 months after administration
If a pt is on a triazole e.g. fluconazole and they get a rash what should they do
If rash occurs, discontinue treatment (or monitor closely if infection invasive or systemic); severe cutaneous reactions are more likely in patients with AIDS.
Which antifungal has been associated with heart failure
Itraconazole
At risk pt:
- higher doses
- longer courses
- cardiac disease
- chronic lung disease
- CCB treatment
Manufacturer advises avoid in patients with ventricular dysfunction, such as history of congestive heart failure, unless the infection is serious.
itraconazole conception and contraception
Ensure effective contraception during treatment and until the next menstrual period following end of treatment.
itraconazole monitoring
Monitor liver function if treatment continues for longer than one month, if receiving other hepatotoxic drugs, or if history of hepatotoxicity with other drugs.
Which antifungal has the uncommon but important SE of phototoxicity
Phototoxicity occurs uncommonly with VORICONAZOLE
If phototoxicity occurs, consider treatment discontinuation; if treatment is continued, monitor for pre-malignant skin lesions and squamous cell carcinoma, and discontinue treatment if they occur.
Which antifungal has this label
Protect your skin from sunlight—even on a bright but cloudy day. Do not use sunbeds
voriconazole
Which antifungals may have risk of SJS and TEN
The azole antifungals (fluconazole, itraconazole, voriconazole, and posaconazole) and terbinafine are particularly associated with SJS and TEN.
