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Systemic and Topical Antifungals

Disclaimer - Please see package insert for additional information and possible updates. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.   Read the disclaimer
Topicals Link to UPDATED IV Section
Amphoterecin-B Ampho B lipid (Albecet ®):
anidulafungin - Eraxis ™ caspofungin - Cancidas ®
Clotrimazole (Mycelex ®): fluconazole (Diflucan ®)
flucytosine (Ancobon ®): Griseofulvin:
Itraconazole (Sporanox ®): ketoconazole (Nizoral ®):
Micafungin - Mycamine ®: nystatin (Mycostatin ®)
Posaconazole - Noxafil® terbinafine (Lamisil ®): 
voriconazole (Vfend ®): --

Amphoterecin-B: top of page

DOSAGE AND ADMINISTRATION
Test dose: (optional): 1 mg/20-50 ml D5W over 10-30 minutes. Monitor temp, pulse, RR and BP q30min x 4 hours. Do not give premeds with test dose. 

Maintenance dose: Initially give 0.25-0.3 mg/kg/day. Increase as tolerated by an equivalent amount once daily. Usual daily dose: 0.5-1 mg/kg/day or up to 1.5 mg/kg every other day. For life-threatening infection may give full dose the first day (usually 0.6-0.7 mg/kg IBW on Day # 1). 

Premedication: Prevention of fever/chills: Tylenol 650mg PO/PR + Benadryl 25-50mg PO/IVP 60min prior to maintenance infusion. May also add: Hydrocortisone 25-50mg IV/IM +/- Demerol 50mg IV.

Renal dosing: <10/ q24-36h. During therapy if the BUN increases above 40 mg/dl or the serum creatinine exceeds 2.5-3 mg/dl, Hold Ampho B until renal function improves, then restart at a reduced dose or change to every other day dosing until Serum creatinine/BUN improve. 


Bladder irrigation: Add 30-50mg Ampho B to 1000ml (or less) sterile H2O administered intermittently or continuously for 2 to 14 days. (Note: use of D5W for Bladder irrigations is not recommended because of the possibility of enhancing microbial and fungal growth in the bladder).

Ampho B lipid (Albecet ®): top of page

DOSAGE AND ADMINISTRATION

Premedication: For patients who experience infusion-related immediate reactions, premedicate with the following drugs 30-60 minutes prior to drug administration: A nonsteroidal anti-inflammatory agent +/- diphenhydramine or acetaminophen with diphenhydramine or hydrocortisone 50-100 mg. If the patient experiences rigors during the infusion, meperidine may be administered.

Usual dosage: I.V.: 2.5 to 5 mg/kg/day as a single infusion

anidulafungin - Eraxis ™: top of page

MOA: Anidulafungin is a semi-synthetic echinocandin with antifungal activity. Anidulafungin inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This results in inhibition of the formation of 1,3-β-D-glucan, an essential component of the fungal cell wall.  Indications: use in the treatment of the following fungal infections: Candidemia and other forms of Candida infections (intra-abdominal abscess, and peritonitis). ERAXIS has not been studied in endocarditis, osteomyelitis, and meningitis due to Candida, and has not been studied in sufficient numbers of neutropenic patients to determine efficacy in this group.

Dosage
The recommended dose is a single 200 mg loading dose of ERAXIS on Day 1, followed by 100 mg daily dose thereafter. Duration of treatment should be based on the patient’s clinical response. In general, antifungal therapy should continue for at least 14 days after the last positive culture. Esophageal candidiasis: The recommended dose is a single 100 mg loading dose of ERAXIS on Day 1, followed by 50 mg daily dose thereafter. Patients should be treated for a minimum of 14 days and for at least 7 days following resolution of symptoms. 

Preparation: must be reconstituted with the companion diluent (20% (w/w) Dehydrated Alcohol in Water for Injection) and subsequently diluted with only D5W or 0.9% NS.  Aseptically reconstitute each 50 mg vial with 15 mL of the companion diluent to provide a conc of 3.33 mg/mL. The reconstituted solution must be further diluted and administered within 24 hours. 
Dilution and Infusion:
  The rate of infusion should not exceed 1.1 mg/minute. 



Supplied:  50mg vial (powder for reconstitution) + 15 ml diluent.
Storage/stability:  Reconstituted vials & final solution: 24 hours at room temp.  Do not Freeze.

caspofungin - Cancidas ®: top of page

DOSING: ADULTS — Note: Duration of caspofungin treatment should be determined by patient status and clinical response. Empiric therapy should be given until neutropenia resolves. In patients with positive cultures, treatment should continue until 14 days after last positive culture. In neutropenic patients, treatment should be given at least 7 days after both signs and symptoms of infection and neutropenia resolve.

Empiric therapy: Initial dose: 70 mg on day 1; subsequent dosing: 50 mg/day; may increase up to 70 mg/day if tolerated, but clinical response is inadequate.

Invasive Aspergillus, candidiasis: I.V.: Initial dose: 70 mg on day 1; subsequent dosing: 50 mg/day

Esophageal candidiasis: I.V.: 50 mg/day; Note: The majority of patients studied for this indication also had oropharyngeal involvement.

Dosage adjustment with concomitant use of an enzyme inducer: Patients receiving rifampin: 70 mg caspofungin daily.
Patients receiving carbamazepine, dexamethasone, efavirenz, nevirapine, or phenytoin (and possibly other enzyme inducers) may require an increased daily dose of caspofungin (70 mg/day).

MOA: Inhibits synthesis of B(1,3)-D-glucan, an essential component of the cell wall of susceptible fungi. Highest activity in regions of active cell growth. Mammalian cells do not require B(1,3)-D-glucan, limiting potential toxicity.

USE — Treatment of invasive Aspergillus infections in patients who are refractory or intolerant of other therapy; treatment of candidemia and other Candida infections (intra-abdominal abscesses, esophageal, peritonitis, pleural space); empirical treatment for presumed fungal infections in febrile neutropenic patient

Clotrimazole (Mycelex ®): top of page

DOSAGE AND ADMINISTRATION

Oral troches 5 times per day x 14 days.

fluconazole (Diflucan ®): top of page

Candidiasis: Candidemia, primary therapy, non-neutropenic: 400-800 mg/day for 14 days after last positive blood culture and resolution of signs/symptoms.  Alternate therapy: 800 mg/day with amphotericin B for 4-7 days followed by 800 mg/day for 14 days after last positive blood culture and resolution of signs/symptoms.  Candidemia, secondary, neutropenic: 6-12 mg/kg/day for 14 days after last positive blood culture and resolution of signs/symptoms.  Chronic, disseminated: 6 mg/kg/day for 3-6 months.
Oropharyngeal (long-term suppression): 200 mg/day; chronic therapy is recommended in immunocompromised patients with history of oropharyngeal candidiasis (OPC).  Osteomyelitis: 6 mg/kg/day for 6-12 months.  Esophageal: 200 mg on day 1, then 100-200 mg/day for 2-3 weeks after clinical improvement.   Prophylaxis in bone marrow transplant: 400 mg/day; begin 3 days before onset of neutropenia and continue for 7 days after neutrophils >1000 cells/mm3.  Urinary: 200 mg/day for 1-2 weeks.

Coccidiomycosis: 400 mg/day; doses of 800-1000 mg/day have been used for meningeal disease; usual duration of therapy ranges from 3-6 months for primary uncomplicated infections and up to 1 year for pulmonary (chronic and diffuse) infection.   Endocarditis, prosthetic valve, early: 6-12 mg/kg/day for 6 weeks after valve replacement.
Endophthalmitis: 6-12 mg/kg/day or 400-800 mg/day for 6-12 weeks after surgical intervention. Note:C. krusei and C. galbrata infection acquired exogenously should be treated with voriconazole.
Meningitis, cryptococcal: 400-800 mg/day for 10-12 weeks or with flucytosine 100-150 mg/day for 6 weeks; maintenance: 200-400 mg/day.  Pneumonia, cryptococcal (mild-to-moderate): 200-400 mg/day for 6-12 months (life-long in HIV-positive patients)
Vaginal candidiasis: 150 mg x 1. 
Systemic candidiasis: 400 mg orally or IV once daily.   Esophageal candidiasis: 100-200 mg orally once daily (up to 400mg/day).  
Cryptococcal meningitis: 400mg orally x 1, followed by 200mg  once a day x 10-12 weeks  (Suppression: 50-200mg orally once daily). 
Onychomycosis: 200-300mg once a week or 100-200mg orally every other day  (further studies needed).  
Coccidioides immitis. Therapy with oral fluconazole is currently preferred. The dosage used in reported clinical trials was 400 mg/day. Some physicians begin therapy with 800 or 1000 mg/day of fluconazole. Alternative: (meningitis) 800mg qd for life. 

Renal Dosing: Loading dose:  [CRCL >50] No changes.  [CRCL <50]: Multiple dose regimens only: Give 50% of usual dose q24h. Some sources recommend for CRCL <20: 50% of usual dose q48h.   Hemo: Give usual dose after each hemodialysis session.

MECHANISM OF ACTION — Interferes with cytochrome P450 activity, decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting cell membrane formation.

PHARMACODYNAMICS / KINETICS:  Distribution: Widely throughout body with good penetration into CSF, eye, peritoneal fluid, sputum, skin, and urine
  Relative diffusion blood into CSF: Adequate with or without inflammation (exceeds usual MICs).  CSF:blood level ratio: Normal meninges: 70% to 80%; Inflamed meninges: >70% to 80%.

 

flucytosine (Ancobon ®): top of page

Dosing (Adults): Usual: 12.5 to 37.5 mg/kg q6h.   

Endocarditis:  25 to 37.5 mg/kg  orally every 6 hours (with amphotericin B) for at least 6 weeks after valve replacement.

Meningoencephalitis, cryptococcal
Induction:  25 mg/kg/dose orally (with amphotericin B) every 6 hours for 2 weeks; if clinical improvement, may discontinue both amphotericin and flucytosine and follow with an extended course of fluconazole (400 mg/day); alternatively, may continue flucytosine for 6-10 weeks (with amphotericin B) without conversion to fluconazole treatment.

Renal Dosing:  
[CRCL >40] No change.  
[20-40]: 12.5-37.5 mg/kg q12h.  
[10-20]: 12.5-37.5 mg/kg q24h. 
[<10]: 12.5-37.5 mg/kg q24-48h. 

Hemo: Give usual dose (12.5 – 37.5mg/kg) after each dialysis. Some sources recommend giving 25-50 mg/kg after each dialysis. Administration guidelines: Administer around-the-clock to promote less variation in peak and trough serum levels. To avoid nausea and vomiting, administer a few capsules at a time over 15 minutes until full dose is taken.

Supplied: Capsule: Ancobon®: 250 mg, 500 mg

Griseofulvin: top of page

DOSAGE AND ADMINISTRATION

Microsize: Adults: 500mg orally once daily will give a satisfactory response in most patients with tinea corporis, tinea cruris, and tinea capitis. For those fungus infections more difficult to eradicate such as tinea pedis and tinea unguium, a daily dose of 1.0 g is recommended. 
 [Supplied: Grifulvin V: 250 mg or 500 mg of griseofulvin microsize tablets.]


Ultramicrosize:  Adults:  375 mg (as a single dose or in divided doses) will give a satisfactory response in most patients with tinea corporis, tinea crurirs, and tinea capitis. For those fungal infections more difficult to eradicate, such as tinea pedis and tinea unguium, a divided dose of 750 mg is recommended.  
[Supplied:  Gris-PEG® (griseofulvin ultramicrosize)  125, 250mg tabs]

Itraconazole (Sporanox ®): top of page

Systemic mycosis: 200mg orally once daily with food (up to maximum of 400mg/day if unsatisfactory clinical response with lower dose).  Doses >200mg are given in 2 divided doses. 

Onychomycosis: 200mg orally twice daily for 1 week each month for  2 months (fingernails);   x 3-4 months (toenails).   

Oropharyngeal candidiasis: 200mg (20ml)-oral solution-swish vigorously then swallow once daily x 1-2 weeks. 

Esophageal candidiasis: 100mg (10ml) oral solution--swish and swallow once daily x 3 weeks. May increase to 200mg/day. 

Life-threatening infections: Loading dose: 200mg orally 3 times daily should be given for the first 3 days of therapy, then 200-400mg/day.

ketoconazole (Nizoral ®): top of page

Recommended starting dose: 200mg once daily. In very serious infections or if clinical responsiveness is insufficient within the expected time, the dose of Nizoral Tablets may be increased to 400 mg (two tablets) once daily.

Micafungin - Mycamine ®: top of page

MOA: Concentration-dependent inhibition of 1,3-beta-D-glucan synthase resulting in reduced formation of 1,3-beta-D-glucan, an essential polysaccharide comprising 30% to 60% of Candida cell walls (absent in mammalian cells); decreased glucan content leads to osmotic instability and cellular lysis

Dosing (Adults): 
Do not mix or co-infuse Mycamine with other medications. Mycamine has been shown to precipitate when mixed directly with a number of other commonly used medications.

Mycamine Dosage
Indication

Recommended Reconstituted Dose Once Daily

 Treatment of Candidemia, Acute Disseminated Candidiasis, Candida Peritonitis and Abscesses*  100 mg
Treatment of Esophageal Candidiasis† 150 mg
Prophylaxis of Candida Infections in HSCT Recipients‡ 50 mg
*In patients treated successfully for candidemia and other Candida infections, the mean duration of treatment was 15 days (range 10-47 days).

† In patients treated successfully for esophageal candidiasis, the mean duration of treatment was 15 days (range 10-30 days).

‡ In hematopoietic stem cell transplant (HSCT) recipients who experienced success of prophylactic therapy, the mean duration of prophylaxis was 19 days (range 6-51 days).

A loading dose is not required. Typically, 85% of the steady-state concentration is achieved after three daily Mycamine doses.

No dosing adjustments are required based on race, gender, or in patients with severe renal dysfunction or mild-to-moderate hepatic insufficiency. The effect of severe hepatic impairment on micafungin pharmacokinetics has not been studied.

No dose adjustment for Mycamine is required with concomitant use of mycophenolate mofetil, cyclosporine, tacrolimus, prednisolone, sirolimus, nifedipine, fluconazole, voriconazole, itraconazole, amphotericin B, ritonavir, or rifampin. 

Supplied:  Injection - 50 mg (powder for reconstitution).

nystatin (Mycostatin ®) top of page

DOSAGE AND ADMINISTRATION
Thrush: 4 to 6 ml orally (swish/swallow)  4 times a day.

Posaconazole - Noxafil®: top of page

DOSAGE AND ADMINISTRATION
Dosing (Adults):
Aspergillus and Candida prophylaxis in high-risk immunocompromised patients: Oral: 200 mg 3 times/day

Treatment of oropharyngeal candidiasis: Oral: Initial: 100 mg twice daily for 1 day; maintenance: 100 mg once daily for 13 days.

Treatment of refractory oropharyngeal candidiasis: Oral: 400 mg twice daily

Treatment of refractory invasive fungal infections (unlabeled use): Oral: 800 mg/day in divided doses

Renal Dosing:  No adjustment necessary; use caution in severe renal impairment and monitor for breakthrough fungal infections. Variability in posaconazole exposure observed with Clcr<20 mL/minute.

Supplied
Suspension, oral: Noxafil®: 40 mg/mL (123 mL)

terbinafine (Lamisil ®):  top of page

DOSAGE AND ADMINISTRATION
Superficial mycoses (tinea corporus, cruris, pedis, capitis; cutaneous candidiasis): 250 mg orally once daily. 

Onychomycosis:
(fingernails) 250mg orally once daily x 6 weeks or pulse dosing: 500mg orally once daily for 1st week of month x 2 months.
(Toenails): 250mg orally once daily x 12 weeks  or  pulse dosing: 500mg once daily for 1st week of month x 4 months. 

Systemic mycosis: 250-500mg orally once daily.

voriconazole (Vfend ®): top of page

DOSAGE AND ADMINISTRATION
Dosing (Adults): 
Invasive aspergillosis and other serious fungal infections
-  6 mg/kg IV q12h x 2 doses, then 4 mg/kg q12h.   
Candidemia and other deep tissue Candida infections: Initial: Loading dose 6 mg/kg IV every 12 hours for 2 doses; followed by maintenance dose of 3-4 mg/kg every 12 hours.

---------------------
(Oral): Conversion to oral dosing:  
Patients <40 kg: 100 mg every 12 hours; increase to 150 mg every 12 hours in patients who fail to respond adequately. 
Patients geq 40 kg: 200 mg every 12 hours; increase to 300 mg every 12 hours in patients who fail to respond adequately. 
Esophageal candidiasis: Oral:  Patients <40 kg: 100 mg every 12 hours.  
Patients geq 40 kg: 200 mg every 12 hours.  
Note: Treatment should continue for a minimum of 14 days, and for at least 7 days following resolution of symptoms.
---------------------

Dosage adjustment in patients unable to tolerate treatment: 
IV: Dose may be reduced to 3 mg/kg every 12 hours.  
Oral: Dose may be reduced in 50 mg increments to a minimum dosage of 200 mg every 12 hours in patients weighing geq 40 kg (100 mg every 12 hours in patients <40 kg). 

Renal Dosing: Oral: no adjustments necessary. 
[CRCL <50 ml/min]: IV voriconazole should be avoided, unless the benefit justifies the risk. Accumulation of the intravenous vehicle may occur.

Supplied: Tablet: 50 mg, 200 mg. Oral suspension: 200 mg/5 mL (70 mL). 200 mg (Inj - powder for reconstitution). 

®: top of page

 

Topical Antifungals: top of page

butenafine 
(Mentax ®)
Apply cream once or twice daily. [cream 1%]
ciclopirox 
(Loprox ®): 
Apply cream or lotion twice daily  [cream/lotion 1%]
clotrimazole (Lotrimin ®): Apply twice daily.   Supplied:  [1% cream /solution /lotion]
enconazole (Spectazole ®):  Tinea: apply once daily. Candida: apply twice daily.   Supplied:[1% cream]
ketoconazole
(Nizoril ®) 
Tinea/candida: apply once a day  Supplied: [2% cream]. Seborrheic dermatitis: apply shampoo/cream  once or twice daily. Dandruff: shampoo 2 times per week.
Miconazole: Tinea/candida: apply twice a day.  Supplied:  [2% cream/powder/spray]
naftifine 
(Naftin ®): 
Tinea: apply once daily (cream) or  twice a day- (gel)
nystatin: candidiasis: apply 2 to 3 times daily.   Supplied: [cream / powder/ ointment]
oxiconazole (Oxistat ®):  Tinea: apply once or twice daily.   Supplied: [cream/lotion 1%]
terbinafine 
(Lamisil ®):
Tinea: apply once or twice daily.   Supplied: [cream 1%]
tolnaftate 
(Tinactin ®):
 Apply twice a day.  Supplied:  [1% cream /powder/ gel /solution]

Disclaimer top of page icon

Listed dosages are for - Adult patients ONLY. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. GlobalRPH does not directly or indirectly practice medicine or provide medical services and therefore assumes no liability whatsoever of any kind for the information and data accessed through the Service or for any diagnosis or treatment made in reliance thereon.

David F. McAuley, Pharm.D., R.Ph.  GlobalRPh Inc.
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