Voriconazole
**Voriconazole** is a broad-spectrum, second-generation triazole antifungal agent derived from fluconazole. It was developed to treat severe, refractory fungal infections. * **Broad Spectrum**: Highly effective against a variety of fungal organisms, particularly ***Aspergillus***, ***Blastomyces***, and ***Cryptococcus***, as well as *Candida*, *Histoplasma*, and *Fusarium* species. * **Clinical Use in Veterinary Medicine**: Currently, there is limited clinical experience in veterinary patients. It is extremely expensive, which limits its widespread use, though it is gaining interest for treating aspergillosis in pet birds due to their smaller size. * **Tissue Penetration**: It has excellent oral bioavailability in many species and readily crosses into the **central nervous system (CNS)**, tears, and synovial fluid, making it valuable for systemic and deep-seated infections. * **Feline Sensitivity**: Cats appear highly susceptible to severe adverse effects (neurologic and systemic). It should only be used in cats as an absolute last resort. * **Drug Interactions**: Like other azoles, it is a potent inhibitor of cytochrome P450 enzymes, leading to numerous significant drug interactions.
กลไกการออกฤทธิ์: Voriconazole exerts its fungistatic (and sometimes fungicidal against *Aspergillus*) effects by inhibiting fungal cell membrane synthesis. * **Primary Mechanism**: It inhibits the cytochrome P-450-dependent enzyme **14-alpha-sterol demethylase** (lanosterol 14-alpha-demethylase) → blocks the conversion of lanosterol to **ergosterol** → depletes ergosterol in the fungal cell wall → alters cell membrane fluidity and permeability, leading to fungal cell death. * **Secondary Mechanism**: Unlike fluconazole, voriconazole also inhibits **24-methylene dehydrolanosterol demethylation** in molds such as *Aspergillus*, which confers its enhanced activity against these specific fungi.
ขนาดยาตามชนิดสัตว์
- Orbital aspergillosis · 10 mg/kg PO once daily. · PO · q24h · Use with extreme caution; significant systemic and neurologic adverse reactions are common.
- Aspergillosis · 3 mg/kg PO q24h · PO · q24h · Higher doses (4-5 mg/kg) are probably necessary to treat infections with Fusarium spp.
- General / Pharmacokinetic study · 18 mg/kg PO q8h for 11 days · PO · q8h · 11 days · Studied in Hispaniolan Amazon parrots; further studies needed for long-term safety.
- Avian aspergillosis · 12.5 mg/kg PO twice daily for 60-90 days or by nebulization as a 1 mg/mL solution for 60 minutes once daily. · PO / Nebulization · q12h / q24h · 60-90 days
- Coccidioidomycosis · 4 mg/kg PO q12h. · PO · q12h
ขนาดยาเป็นข้อมูลอ้างอิงทางคลินิกสำหรับสัตวแพทย์ผู้มีใบอนุญาต โปรดตรวจสอบกับฉลากล่าสุดและผู้ป่วยแต่ละรายเสมอ
วิธีการให้ยา
ข้อห้ามใช้
- Hypersensitivity to voriconazole or other azole antifungals
- Concurrent use with barbiturates, carbamazepine, cisapride, pimozide, quinidine, rifampin, or rifabutin
- Caution in patients with hepatic dysfunction
- Caution in patients with proarrhythmic conditions
- Caution with the IV formulation in patients with decreased renal function (due to accumulation of the SBECD vehicle)
อาการไม่พึงประสงค์
- Dogs: Liver enlargement, significant increase in cytochrome P450 hepatic enzymes
- Cats: Azotemia, inappetence, lethargy, weight loss, cutaneous drug reactions, ataxia, hind limb paresis/paraplegia, visual signs (mydriasis, decreased PLR), arrhythmias, hypokalemia
- Humans: Visual disturbances (blurring, spots, wavy lines), rashes, GI effects (nausea, vomiting, diarrhea), hepatotoxicity, hypertension/hypotension, tachycardia, peripheral edema, hypokalemia, hypomagnesemia
- Rare (Humans): Eye hemorrhage, anemia, leukopenia, thrombocytopenia, pancytopenia, QT prolongation, nephrotoxicity
อันตรกิริยาระหว่างยา
- Antidiabetic agents (sulfonylureas) · May increase serum concentrations of these drugs and increase risk for hypoglycemia
- Barbiturates (phenobarbital) · Decreased voriconazole concentrations; concurrent use is contraindicated
- Benzodiazepines · May increase benzodiazepine concentrations
- Calcium-channel blockers (amlodipine, diltiazem, verapamil) · May increase serum concentrations; dosage adjustment may be required
- Carbamazepine · Decreased voriconazole concentrations; concurrent use is contraindicated
- Cisapride · Potential for serious cardiac arrhythmias; concurrent use is contraindicated
- Corticosteroids (prednisolone) · Potentially increased AUC for prednisolone
- Immunosuppressive agents (cyclosporine, tacrolimus) · Increased concentrations; decrease cyclosporine dosage by 50% and tacrolimus dosage by 33% when starting voriconazole
- Methadone · May increase plasma concentrations of R-methadone; monitor for toxicity
- Phenytoin · Can decrease voriconazole concentrations and voriconazole can increase phenytoin concentrations
- Pimozide · Potential for serious cardiac arrhythmias; concurrent use is contraindicated
- Proton-pump inhibitors (omeprazole) · May increase omeprazole (and potentially other PPIs) concentrations
การติดตาม
- Clinical efficacy (resolution of fungal infection)
- Liver function tests (baseline and periodic)
- Serum electrolytes (potassium, magnesium)
- Neurologic and visual signs (especially in cats)
การได้รับยาเกินขนาด
The minimum lethal dose in rats and mice is 300 mg/kg (4-7X maintenance dose). * **Clinical Signs**: Increased salivation, mydriasis, ataxia, depression, dyspnea, and seizures. In human pediatric patients, accidental 5X overdoses caused brief photophobia. * **Treatment**: No specific antidote is known. For very large oral overdoses, consider gut emptying (emesis/gastric lavage) followed by close observation and supportive treatment.
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