フルコナゾール
フルコナゾールは全身性の**トリアゾール系抗真菌薬**です。ケトコナゾールなどの古い第一世代アゾール系とは異なり、親水性が高く、**中枢神経系（CSF）**、**眼**、**尿路**への移行性に優れています。 > **臨床のポイント:** 吸収に胃酸を必要としないため、制酸薬を服用している患者でも経口バイオアベイラビリティが非常に安定しています。さらに、ケトコナゾールに比べて哺乳類のシトクロムP450酵素への親和性がはるかに低いため、哺乳類のステロイドホルモン合成への影響が最小限であり、一般的に副作用が少ないです。
作用機序: Fluconazole acts by inhibiting the fungal cytochrome P450-dependent enzyme **lanosterol 14-α-demethylase**. Lanosterol → (blocked by fluconazole) → **Ergosterol** This depletion of ergosterol disrupts the synthesis of the fungal cell membrane, increasing its permeability and causing leakage of essential cellular contents. It also impairs the uptake of purine and pyrimidine precursors. Fluconazole is primarily **fungistatic**.
動物種別の用量
- Nasal or dermal cryptococcosis · 5-10 mg/kg PO q12-24h, or 10 mg/kg PO q24h · PO · q12-24h · For most infections, 50 mg/cat PO once daily achieves adequate therapeutic levels
- CNS, intraocular, or multisystemic cryptococcosis · 50-100 mg/cat PO or IV q12h · PO/IV · q12h · Often treat neurologic ocular cryptococcosis for at least 12 weeks or 2 weeks after CSF exam shows resolution
- CNS, intraocular or multisystemic mycoses · 50 mg/cat PO once daily (q24h) · PO · q24h
- Cryptococcosis · 50 mg (total dose) PO twice daily · PO · q12h · 1 month beyond resolution of clinical signs
- Cryptococcosis · 50 mg (total dose) PO twice daily · PO · q12h · At least 2 months beyond resolution of clinical signs
- C. immitis infection or Candida bacteremia · Loading dose of 14 mg/kg followed by 5 mg/kg PO once daily · PO · q24h
- Fungal keratitis · 1 mg/kg PO q24h · PO · q24h · Anecdotal reports of successful treatment
- Candidiasis (cockatoos, parrots) · 20 mg/kg PO q24-48h or 10 mg/kg PO q24h · PO · q24-48h · Likely effective for C. albicans. C. galabrata and C. papasilosis may have higher MICs.
- Candidiasis (cockatiels) · 10 mg/kg fluconazole PO suspension and 100 mg/mL fluconazole treated drinking water · PO · Maintained plasma levels above the MIC for most strains of Candida albicans
- Alternate treatment of aspergillosis · 5-10 mg/kg PO once daily · PO · q24h · up to 6 weeks · With or after amphotericin B
- General (Rabbits) · 25-43 mg/kg slow IV q12h · IV · q12h
- Cryptococcosis, candidiasis, systemic mycoses, nasal aspergillosis · 2.5-5 mg/kg PO or IV q12-24h · PO/IV · q12-24h · 56-84 days · Often treat neurologic ocular cryptococcosis for at least 12 weeks or 2 weeks after CSF exam shows resolution
- Fungal meningitis · 5-8 mg/kg PO or IV q12h OR 8-12 mg/kg PO or IV once daily (q24h) · PO/IV · q12h or q24h · 56-84 days
- Urinary candidiasis · 5-10 mg/kg PO q24h · PO · q24h · 21-42 days
- Urinary Candida glabrata infection · 12 mg/kg PO once daily · PO · q24h · 21-42 days
- Cryptococcosis · 5 mg/kg PO once or twice daily · PO · q12h or q24h · At least 2 months beyond resolution of clinical signs
- Blastomycosis · 5 mg/kg PO q12h · PO · q12h · 60 days
- Cryptococcosis · 5-15 mg/kg PO q12-24h · PO · q12-24h · 6-10 months
- Treatment of Malassezia (may be safer than itraconazole or ketoconazole in dogs with hepatic disease) · 5 mg/kg PO once daily · PO · q24h
- Systemic treatment of Malassezia dermatitis · 5 mg/kg PO once daily · PO · q24h
- Recurrent Malassezia dermatitis · 5 mg/kg PO 3 times per week · PO · 3 times per week
- Systemic treatment of Malassezia dermatitis · 2-5 mg/kg PO once daily (q24h) · PO · q24h
- Nasal aspergillosis (alternative to itraconazole or terbinafine) · 2.5-5 mg/kg PO q12h · PO · q12h · 3-6 months · Cure rates up to 60%
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- Hypersensitivity to fluconazole or other azole antifungals
- Budgerigars (reportedly toxic)
- Pregnant animals
- Lactating animals
有害事象
- Inappetence
- Vomiting
- Diarrhea
- Hepatotoxicity (rare)
- Headache (humans)
- Increased liver enzymes (humans)
- Exfoliative skin disorders (humans)
- Thrombocytopenia (humans)
- Nausea
- Diarrhoea
- Hepatotoxicity
薬物相互作用
- Amphotericin B · May be antagonistic against Aspergillus or Candida; clinical importance unclear
- Buspirone · Plasma concentrations of buspirone may be elevated
- Cisapride · May increase cisapride levels and the possibility for toxicity
- Corticosteroids · May inhibit the metabolism of corticosteroids; potential for increased adverse effects
- Cyclophosphamide · May inhibit the metabolism of cyclophosphamide and its metabolites; potential for increased toxicity
- Cyclosporine · Increases cyclosporine levels; dosage of cyclosporine may need to be decreased by 29%-51%
- Diuretics, Thiazides · Increased fluconazole concentrations
- Fentanyl/Alfentanil · May increase fentanyl levels
- Midazolam · Increased midazolam levels and effects
- NSAIDs · May increase NSAID plasma levels; increased risk for adverse effects
- Quinidine · Increased risk for cardiotoxicity
- Rifampin · May decrease fluconazole efficacy; fluconazole may increase rifampin levels
- Theophylline/Aminophylline · Increased theophylline concentrations
モニタリング
- Clinical efficacy
- Liver function tests (occasional, with long-term therapy)
- Liver enzyme panel (ALT, AST, ALP, Bilirubin) prior to and during prolonged therapy
- Renal function (BUN, Creatinine)
- Resolution of clinical signs of fungal infection
- Therapeutic drug monitoring for concurrent medications like ciclosporin or theophylline
過量投与
There is limited information on acute toxicity in domestic animals. In rodents, massive overdoses (1-2 g/kg) caused respiratory depression, salivation, lacrimation, urinary incontinence, and cyanosis, leading to death within several days. **Treatment:** If a massive overdose occurs, consider gut emptying (emesis or gastric lavage) if recent, and provide supportive therapy as required. Fluconazole may be removed by hemodialysis or peritoneal dialysis.
VetSheet の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。