Diflucan
Diflucan (fluconazole)
Generic Name
Diflucan (fluconazole)
Mechanism
Diflucan inhibits lanosterol 14‑α‑demethylase, a cytochrome P450–dependent enzyme (CYP51) responsible for converting lanosterol to ergosterol, a key component of fungal cell membranes.
• ↓ Ergosterol ➜ ↑ membrane permeability
• Accumulation of toxic methylated sterols and lipids disrupts cell wall integrity
• Results in cell death or inhibited proliferation
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Pharmacokinetics
| Parameter | Detail |
| Absorption | Rapid, >90 % oral bioavailability; peak serum 30–90 min (IV) |
| Distribution | Volume 100 L; high plasma protein binding (~30 %) |
| Metabolism | Hepatic, via CYP2C19, CYP3A4, and CYP2C9; glucuronide conjugation |
| Elimination | Renal (≈30 % unchanged) and hepatic; elimination half‑life 30–50 h (prolonged in hepatic impairment) |
| Drug–Drug Interactions | Inhibits/induced by many CYP3A4 inducers/inhibitors; caution with warfarin, anticonvulsants, and drugs with narrow therapeutic indices |
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Indications
- Oropharyngeal, esophageal, and vaginal candidiasis
- Candidemia and invasive candidiasis (in combination with other antifungals)
- Histoplasmosis (mucosal, pulmonary, disseminated)
- Cryptococcosis (including cryptococcal meningitis)
- Prophylaxis in AIDS patients, transplant recipients, and neutropenic patients
- Prophylaxis against invasive aspergillosis in patients on long‑term steroids
- Topical gel for vulvovaginal candidiasis
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Contraindications
- Hypersensitivity to fluconazole or sulfonamides
- Severe hepatic dysfunction (AST/ALT > 5× ULN)
- Pregnancy: category C; use only if benefits outweigh risks
- Breastfeeding: excreted in milk; avoid unless necessary
- Drug interactions: avoid concomitant use with medications causing QT prolongation or severe CYP450 interactions unless monitored closely
Dosing
| Condition | Adult Dose (mg) | Duration | Route | Notes |
| *Candida* (oropharyngeal/vaginal)* | 150–200 (single) | 1–2 d | Oral | 30 mg/kg/dose ≤ 140 kg |
| *Candida* (esophageal, invasive) | 150 mg i.v./po | 10–14 d | Oral or IV | 200 mg/day for severe disease |
| *Histoplasma* | 400 (loading) → 200 mg daily | 6–12 mo | PO | |
| *Cryptococcus* (meningitis) | 800 mg loading → 200 mg daily | 12–24 w | PO | |
| Prophylaxis | 400 mg q4w (IV) or 200 mg daily | 6‑12 mo | PO/IV | |
| Topical gel | 10 % (10 mg/g) | 5 d | Topical |
*Adjust for renal/hepatic impairment and weight.
• Start with IV for severe invasive infections; transition to oral when stable.
• For pediatric patients: 6 mg/kg PO daily (max 200 mg).
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Adverse Effects
| Adverse Effect | Frequency | Severity | Management |
| Nausea, vomiting | 5–10 % | Mild | Anti‑emetics |
| Headache | 2–5 % | Mild | Acetaminophen |
| Rash, pruritus | 1–3 % | Mild | Cetirizine, discontinue if severe |
| Elevated liver enzymes | <1 % | Moderate | LFT monitoring; dose reduction/discontinue |
| QTc prolongation | Rare | Severe | ECG monitoring, discontinue if significant |
| Severe allergic reactions | <0.1 % | Severe | Immediate cessation, epinephrine |
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Monitoring
- Baseline & periodic LFTs (AST, ALT, bilirubin) – every 2–4 weeks for >4 weeks therapy.
- Renal function – CrCl, BUN at baseline and periodically.
- Serum electrolytes – for QTc monitoring, especially with other QT‑extending drugs.
- Drug interactions – review patient meds for CYP3A4, CYP2C19 inhibitors/inducers.
- Platelets, ANC – in neutropenic patients or those receiving concurrent chemotherapy.
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Clinical Pearls
* High‑Yield Fact: Fluconazole’s high oral bioavailability (~95‑100 %) makes it ideal for outpatient therapy, eliminating the need for IV pumps in most cases.
* Renal Dosing: Fluconazole is *not* renally cleared in a dose‑adjusting manner; however, patients with CrCl < 30 mL/min should be monitored closely for accumulation.
* CYP2C19 Polymorphisms: Patients who are poor metabolizers may have higher plasma levels; consider LFT monitoring.
* Drug‑Drug Interaction “Pitfall”: Combining fluconazole with nifedipine can precipitate hypotension due to decreased metabolism of nifedipine.
* Topical vs. Systemic: For vaginal candidiasis, a single 150 mg PO dose can replace a 5‑day topical schedule, improving compliance.
* “Take Home” for Residents: Always double‑check renal function before dosing in a patient who has recently received antibiotics that may inhibit CYP2C19 (e.g., erythromycin).
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• Bottom line: Diflucan (fluconazole) is a versatile, orally bioavailable antifungal with a broad spectrum against *Candida* spp., *Histoplasma*, and *Cryptococcus*. Its favorable PK profile, minimal drug interactions, and ease of use make it a cornerstone treatment and prophylaxis agent in modern antifungal therapeutics.