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Oral Antifungal Drugs Indications

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					                                                                              The University of Chicago
                                     PEDIATRIC EMERGENCY DEPARTMENT CLINICAL GUIDELINE:


Oral Antifungal Drugs & Indications
                  Griseofulvin       Ketoconazole       Fluconazole       Itraconazole       Terbinafine
                  (ultramicrosize)   (Nizoral)          (Diflucan)        (Sporanox)         (Lamisil)
Tinea capitis     15 mg/kg/day 4-    NR                 50 mg qd 3        3-5 mg/kg/day      125 mg qd (3-6
                  12 weeks                              weeks             4-6 weeks          mg/kg/day) 4
                  20-25mg/kg/day                        6mg/kg/day x 4    4-5mg/kg/day       weeks
                  x 8 weeks                             wks                                  <20kg 62.5mg
                                                                                             qd
                                                                                             20-40kg 125mg
                                                                                             qd
                                                                                             >40kg 250mg qd
                                                                                             some say best
                                                                                             dose may be
                                                                                             about
                                                                                             4.5mg/kg/day x
                                                                                             6-8wks
Onychomycosis     500-1000 qd 6 to   NR                 150 mg once a     200 mg qd          250 mg qd
Tx only           18 months                             week 9 months     fingernails 6      Fingernails 6
recommended       not really                            I don’t know      weeks Toenails     weeks Toenails
when culture      recommended                           anyone who uses   12 weeks Pulse     12 weeks
proven;                                                 this              dosing 200 mg      <20kg 62.5mg
discontinue                                                               bid – 1 week on,   qd
when culture                                                              3 weeks off,       20-40kg 125mg
negative                                                                  Toenails 3-4       qd
                                                                          months,            >40kg 250mg qd
                                                                          Fingernails 2-3    at least 6 wks for
                                                                          months             fingers, 12 wks
                                                                                             for toes
Tinea pedis       500 mg/qd –        NR                 150 mg once a     400 mg qd 4        250 mg qd 6
Systemic          adult 5-7                             week 3-4 weeks    weeks              weeks
generally not     mg/kg/day –
recommended       child 6-12 weeks
Tinea             Not effective      400 mg single      400 mg single     200 mg qd 5 or 7   Studies ongoing
versicolor                           dose or 200        dose              days
                                     g/day 5-10 days    300mg q wk x 2-
                                     I prefer 400mg     3 wks
                                     single dose, rpt
                                     in 1 wk
Vaginal           Not effective      200-400 mg qd 5    150 mg single     200 mg tid one     Studies ongoing
candidiasis                          days               dose              day or 200 mg
                                                                          qd 3 days

* Adapted from Clinical Dermatology, Habif, 1996, p 388-9.




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Oral Antifungal Drugs & Indications
                  Griseofulvin        Ketoconazole       Fluconazole            Itraconazole       Terbinafine
                  (ultramicrosize)    (Nizoral)          (Diflucan)             (Sporanox)         (Lamisil)
Dosage forms      125, 250, 333       200 mg tablet      50, 100, 200 mg        100 mg capsule     250mg
                  mg                  taken with         tablets – water        – food enhances
                  ultramicronized     breakfast with     soluble, well          absorption
                  tablet - 125        an acidic fruit    absorbed
                  mg/5 ml food        juice
                  enhances
                  absorption
Fungicidal        NO                  NO                 NO                     NO                 YES
Persistent in     2 weeks             2 days                      ---           I week             4 to 6 weeks
plasma after
Rx
Persistent in     1 to 2 weeks        Unknown            3 months               6 to 9 months      4 to 6 weeks
skin and nails
after Rx
Laboratory        Rx 6 weeks          Baseline CBC,      Baseline CBC, LFT;     Baseline CBC,      CBC, repeat
monitoring        complete blood      LFT; repeat        repeat each month      LFT; repeat each   each month
                  count (CBC)         each month                                month
                  liver function
                  test (LFT)
Adverse           8% to 15%           13%                7%                     7%                 5%
reactions
Safety Profile    Multiple            Fulminant          Les hepatotoxicity     Less               Few side
                  uncommon side       hepatotoxicity     than ketoconazole      hepatotoxicity     effects; minor
                  effects             in 1/10,000                               than               GI disturbances
                                                                                ketoconazole
Adverse           Abdominal Pain,     Abdominal          Abdominal pain,        Nausea and         Nausea and
reactions         erythema,           pain, nausea       nausea and             vomiting,          vomiting,
                  multiforme,         and vomiting,      vomiting, headache,    abdominal pain,    abdominal
                  headache, mixed     dizziness,         rash                   hypokalemia,       pain, dizziness,
                  drugs reactions,    fever,                                    increased          headache,
                  nausea and          headache,                                 aminotransferase   pruritus, rash,
                  vomiting,           pruritus,                                 activity,          taste loss
                  photosensitivity,   inhibition of                             dizziness,
                  urticaria           testicular and                            headache,
                                      adrenal                                   pruritus, rash,
                                      steroidogenesis                           sleepiness
Potential drug    Alcohol,            Alcohol,           Coumarin,              Astemizole,        H2 antagonists,
interactions      barbiturates,       antacids,          cyclosporine,          carbamazepine,     rifampin,
                  coumarin, oral      astemizole,        hydrochlorothiazids,   coumarin,          cyclosporine
                  contraceptives,     coumarin,          isoniazid, oral        cyclosporine,
                  warfarin            cyclosporine,      contraceptives,        digoxin,
                                      erythromycin,      phenytoin, rifampin,   erythromycin,
                                      H2 antagonists,    sulfonylureas,         H2 antagonists,
                                      isoniazid,         valproic acid          isoniazid,
                                      phenytoin,                                Phenobarbital,
                                      rifampin,                                 phenytoin,
                                      sulfonylureas,                            rifampin,
                                      terfenadine                               sulfonylureas,
                                                                                terfenadine
Cost to           $90 / 100 pills     $232 / 100 pills   $173 / 30 pills        $139 / 30 pills    Available in
pharmacist/pill                                          (100mg)                                   1995 or 1996 in
                                                                                                   the US
* Adapted from Clinical Dermatology, Habif, 1996, p 388-9.

				
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