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Paul A. Pham Pharm.D. and John G. Bartlett M.D.
02-15-2010
- In vitro resistance to fluconazole remains uncommon (1% overall) among isolates of C. neoformans from 5 broad geographic regions including Africa. Has not increased over 15-year period.
- Treatment of cryptococcal meningitis with fluconazole (400 mg x1, followed by 200 mg daily x 6 months) is suboptimal.
- Induction treatment for cryptococcal meningitis with amphotericin B 0.7 mg/kg/day (+5FC) recommended for a minimum of14 days, followed by high dose fluconazole 400 mg x 8 weeks, then fluconazole 200 mg maintenance until immune reconstitution.
- Empiric treatment of esophageal candidiasis with fluconazole recommended in pts with recent onset of retrosternal pain or odynophagia, especially if accompanied by oral candidiasis.
- Limited drug interactions with ARVs, but fluconazole may increase amodiaquine (CYP2C8 substrate) and proguanil (CYP2C19) serum concentrations.
Zambia Information Author: Paul A. Pham, Pharm. D.
- Coccidioidomycosis (treatment); itraconazole preferred (for non-meningeal)
- Pityriasis versicolor
- Histoplasmosis (treatment of mild disease); itraconazole preferred
brand
name
| generic
| Mfg
| brand
forms
| cost*
|
| Diflucan | Fluconazole | Pfizer | PO
tablet
50 mg | $7.56 |
|
|
|
| PO
tablet
100 mg | $11.88 |
|
|
|
| PO
tablet
150 mg | $18.91 |
|
|
|
| PO
tablet
200 mg | $19.45 |
|
|
|
| IV
piggyback
200 mg | $36.09 |
|
|
|
| IV
piggyback
400 mg | $49.25 |
|
|
|
| PO
suspension
10 mg/ml; 40 mg/ml | $130.03 (40 mg/ml; 35 mL); $35.80 (10 mg/mL; 35 mL) |
*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP).
AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's
information, and the McKesson database.
^Dosage is indicated in mg unless otherwise noted.
-
Cryptococcal meningitis,induction phase: 1200 mg PO once-daily + flucytosine (5FC) 100 mg/kg/d x 6 wks (alternative regimen; amphotericin B or lipid amphotericinB plus 5FC a minimum of 2 wks preferred);
-
Cryptococcal meningitis, consolidation phase after a>2 wks of amphotericin + 5FC: 400 mg PO once-daily x 8 wks;
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Cryptococcal meningitis, maintenance phase: 200 mg PO once-daily (until CD4>100-200 x >6 mos and after >1 yr of antifungal therapy)
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Vaginal candidiasis: 150 mg PO x1. Multiple recurrences: fluconazole 150 mg PO q wk (topical azoles preferred)
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Esophageal candidiasis: 200 mg PO once-daily x 14-21 days (or IV up to 800 mg/d). Use chronic maintenance therapy (same dose) for recurrent esophagitis
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Oropharyngeal candidiasis (thrush): 100-200 mg PO once-daily x 7-14 days (topical therapy with clotrimazole preferred to avoid azole resistance)
- Coccidioidomycosis, meningitis: 400-800 mg IV or PO. Non-meningeal (diffuse pulmonary or disseminated): fluconazole 400-800 mg PO once-daily (amphotericin B preferred); maintenance: 400 mg PO once-daily (itraconazole equally effective).
- Histoplamosis: 800 mg daily (itraconazole preferred).
- For obese patients: 6mg/kg/d up to 1200 mg/d.
- Cryptococcemia or cryptococcal pneumonia: 6 mg/kg (400 mg) once daily x 6-12 months.
Usual
50% of dose.
25%-50% of dose; HD: 200mg post-HD
200mg post-HD
25-50% of dose daily
CVVH: 200-400 mg once daily. CVVHD: 400-800 mg once daily.
- GI intolerance w/ bloating, nausea, vomiting, pain,anorexia
- Reversible alopecia (with >400mg/d)
- Transaminase elevation
- Hepatitis (fatal hepatotoxicity in pts with serious underlying medical conditions; monitor LFTs)
- Dizziness
- Headache
- Hypokalemia
CYP2C8/9/19 and CYP3A4 inhibitor resulting in an increase in CYP2C8/9/19 and CYP3A4 substrate. No clinically significant drug-drug interactions with PIs.
| Drug | Effect of Interaction | Recommendations/Comments |
| Rifampin | May significantly decrease fluconazole serum concentrations. | Avoid co-administration. Consider rifabutin. |
| Zidovudine (AZT) | AZT AUC increased by 74%. | Monitor for AZT-associated toxicity. |
| Efavirenz (EFV) | No significant interaction | Usual dose |
| Nevirapine | NVP clearance decreased by 2-fold | Monitor LFTs closely with co-administration. |
| Etravirine | May increase ETR serum concentrations. | No data. Monitor for LFTs and rash with co-administration. |
| Maraviroc | May increase MVC serum concentrations | No data. Use standard dose. |
| Astemizole | May increase astemizole serum concentrations. | Contraindicated |
| Benzodiazepines (alprazolam, diazepam, midazolam, triazolam) | May increase benzodiazepine serum concentrations. | Use with caution. Benzodiazepine dose may need to be decreased. |
| Cisapride | May increase cisapride serum concentrations. | Contraindicated |
| Clopidogrel | May decrease the efficacy of clopidogrel | Avoid co-administration. |
| Cyclosporine | Cyclosporine concentrations may be significantly increased | Monitor cyclosporine concentrations closely.Cyclosporine dose may need to be decreased. |
| Fentanyl | Fentanyl serum concentrations may be significantly increased. | Use with caution. Fentanyl dose may need to be decreased. |
| Lovastatin | May increase lovastatin serum concentrations | Consider pravastatin or rosuvastatin |
| Oral hypoglycemics | Risk of hypoglycemia may may be increased | Monitor closely. |
| Phenytoin | Phenytoin AUC was increased by 88% | Monitor phenytoin concentrations closely with co-administration. |
| Raltegravir | Interaction unlikely | Use standard dose. |
| Rifabutin | No effect on fluconazole, but rifabutin serum concentrations increased by 80%. | Monitor for rifabutin-associated toxicity (i.e uveitis). Rifabutin dose may need to be decreased. |
| Simvastatin: | May increase simvastatin serum concentrations | Consider pravastatin or rosuvastatin |
| Sirolimus | Sirolimus concentrations may be significantly | Monitor sirolimus concentrations closely. Sirolimus dose may need to be significantly decreased. |
| Tacrolimus | Tacrolimus levels may be significantly (monitor tacrolimus levels closely) | Monitor tacrolimus concentrations closely. Tacrolimus dose may need to be significantly decreased. |
Terfenadine
| May increase terfenadine serum concentrations. | Contraindicated |
| Warfarin | INR may be significantly increased. | Monitor INR closely with co-administration. |
H. capsulatum, C. neoformans, C. immitis, C. albicans, C. glabrata (up to 30-40% azole-resistant), C. tropicalis (some azole-resistant), C. parapsilosis. Not C. lusitaniae.
Oral and parenteral azole with best oral bioavailability, independent of gastric pH. Use of fluconazole for treatment or suppression of thrush not recommended due to risk of azole-resistance; topical therapy (e.g. clotrimazole) preferred. However, if recurrences are frequent or mucocutaneous candidiasis is severe, oral fluconazole maintenance can be considered. Preferred drug for esophageal candidiasis. Fatal hepatotoxicity has been described. Fluconazole preferred over itraconazole for consolidation phase and maintenance of cryptococcal meningitis. Itraconazole has better in vitro activity against Coccidioides immitis, however due to better CNS penetration, fluconazole is recommended for meningitis.
- Perfect JR. Dismukes WE, Dromer F et al. ;
Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America ;
Clinical Infectious Diseases ;
2010 ; Vol.
50 ; pp.
291-322. ;
Rating:
Basis for recommendation
Comments:Fluconazole 1200 mg/day plus 5FC x 6 wks OR fluconazole 1200 mg/day monotherapy (up to 2000 mg/day) x 10-12 wks can be considered during induction/consolidation phase as an alternative regimen in patients unable to tolerate amphotericin.
- NIH, CDC, and HIVMA/IDSA ;
Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents ;
aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?MenuItem=Guidelines&Search=Off&GuidelineID=211&ClassID=4 ;
2008 (June 18). ; Vol.
Rating:
Basis for recommendation
Comments:Treatment guidelines recommend topical clotrimazole troches or nystatin suspension for the treatment of initial episodes of oropharyngeal candidiasis Secondary prophylaxis for recurrent oropharyngeal or vulvovaginal candidiasis is generally not recommended because of the potential for resistant candidiasis. However, if recurrences are frequent or mucocutaneous candidiasis is severe, oral fluconazole can be used for either oropharyngeal or vulvovaginal. In addition, it is prudent to institute secondary prophylaxis in pts with fluconazole-refractory oropharyngeal or esophageal candidiasis who have responded to echinocandins, voriconazole, or posaconazole therapy because of high relapse rate until ART produces immune reconstitution.
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