Drug reference

Voriconazole

Triazole antifungal agent (broad-spectrum) · Antifungal

Also known as Vfend, Voriconazole IV, Voriconazole oral

START

Baseline LFTs, renal function (CrCl for IV vs oral decision), ECG (QTc). TDM recommended (target trough 1-5.5 mcg/mL). Review ALL medications for CYP2C19/CYP3A4 interactions. Counsel on visual disturbances (transient, reversible, avoid driving at night).

TYPICAL MAX

300mg PO BID (600mg/day). Hepatic impairment requires 50% dose reduction after loading. Visual and hepatic toxicities are dose-related.

STOP IF

ALT/AST >5x ULN, severe rash (SJS/TEN), QTc >500ms, anaphylaxis, severe visual disturbances persisting, signs of periostitis with long-term use.

WATCH

TDM at day 5 (trough 1-5.5 mcg/mL). LFTs at least weekly during first month. Visual symptoms are common (~30%)—usually transient and reversible, but counsel patients. Photosensitivity—strict sun protection. CYP2C19 poor metabolizers have ~4x higher levels—may need dose reduction. IV formulation contraindicated in CrCl <50 due to vehicle accumulation.

CDSCO approvedSchedule HATC J02AC03

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 30min · Onset ~30 min
PEAK: 1.5h · Tmax 1-2 hours
t½: 6h · t½ ~6 hours (nonlinear)
DURATION: 12h · 12 hours (BID)

EXCRETION

Renal as metabolites (~80%)

route + CYP

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Contraindicated in pregnancy—teratogenic in animals (cleft palate, skeletal defects). Effective contraception required during and for 1 month after treatment.

FDA category + note

Top interactionssee all 12 →

CilostazoleContraindicatedTextbookKDT 7e · p555
Cyp450 InducersContraindicatedDatabaseKimi deep-research + Cla
AbemaciclibSevereDatabaseDDInter
AcalabrutinibSevereDatabaseDDInter

Available in India

77 branded formulations. Look up specific brands in the Drugs workspace.

Mechanism

Inhibits fungal cytochrome P450-dependent enzyme lanosterol 14α-demethylase, blocking conversion of lanosterol to ergosterol (essential fungal cell membrane component). Disrupts cell membrane synthesis, causing cell death. Broad spectrum including Aspergillus, Candida (including fluconazole-resistant), Fusarium, Scedosporium.

Indications

Invasive aspergillosis (first-line)Candidemia in non-neutropenic patientsEsophageal candidiasisSerious fungal infections due to Scedosporium apiospermum and Fusarium speciesInvasive candidiasis (fluconazole-refractory)Prophylaxis of fungal infections in HSCT recipients

Dosing

Adult: IV: 6mg/kg q12h x 2 doses (loading), then 4mg/kg q12h. Oral: 400mg q12h x 2 doses (loading), then 200mg q12h. Increase to 300mg q12h if inadequate response and tolerated. Take 1 hour before or after meals.
Pediatric: ≥2 years: 9mg/kg q12h IV loading x 1 dose, then 8mg/kg q12h IV; OR 9mg/kg PO q12h (max 350mg). <15kg: higher mg/kg dosing needed due to nonlinear pharmacokinetics.
Renal adjustment: CrCl <50: avoid IV (sulfobutylether-beta-cyclodextrin accumulates); use oral formulation if possible. Oral: no adjustment.
Hepatic adjustment: Mild-moderate (Child-Pugh A/B): standard loading, then HALVE maintenance dose (2mg/kg IV or 100mg PO q12h). Severe: avoid unless benefit outweighs risk.
Geriatric: No specific adjustment; monitor drug levels and liver function closely.
Max dose: 600mg/day (oral)

Pharmacokinetics

Onset

Antifungal effect within days; clinical improvement 3-7 days

Peak effect

Tmax 1-2 hours (oral); steady-state in ~5 days without loading; 1 day with loading

Duration

12 hours (BID dosing)

Half-life

~6 hours (dose-dependent nonlinear pharmacokinetics)

Bioavailability

~96% (oral; reduced 22% with high-fat meal)

Protein binding

~58%

Metabolism

Extensive hepatic via CYP2C19 (major), CYP2C9, CYP3A4; many drug interactions

Excretion

~80% renal (metabolites); <2% unchanged in urine

Contraindications

Hypersensitivity to voriconazole or azoles
Concomitant CYP3A4 substrates (terfenadine, astemizole, cisapride, pimozide, quinidine—QT prolongation risk)
Concomitant sirolimus (contraindicated)
Concomitant high-dose ritonavir (400mg BID)
Concomitant efavirenz (600mg daily)
Concomitant St. John's wort
Concomitant carbamazepine
Concomitant long-acting barbiturates
Pregnancy (teratogenic)
Galactose intolerance (tablets contain lactose)

Side effects

Common

Visual disturbances (photopsia, altered color vision, blurred vision—~30%, reversible)Hepatotoxicity (elevated LFTs—~15-20%)Skin rash (~6%)Nausea and vomitingHeadacheFeverPeripheral edemaHallucinations (visual, auditory)Photosensitivity

Serious

Severe hepatotoxicity (hepatic failure, rare)
Severe cutaneous reactions (SJS/TEN, erythema multiforme)
QT prolongation / torsades de pointes
Cardiac arrhythmias
Periostitis / fluorosis (long-term use)
Transient visual disturbances (may affect driving)
Anaphylaxis
Pancreatitis (rare)

Pregnancy & lactation

Pregnancy

Contraindicated in pregnancy—teratogenic in animals (cleft palate, skeletal defects). Effective contraception required during and for 1 month after treatment.

Lactation

Excreted in breast milk; avoid during breastfeeding.

Drug interactions

Cilostazole

Contraindicated

Textbook

Increased plasma levels and toxicity of cilostazole.

Should not be administered along with inhibitors of CYP3A4.

Source: KDT 7e · p555

Cyp450 Inducers

Contraindicated

Database

Markedly reduces voriconazole levels; rifampicin reduces voriconazole Cmax by ~93%.

Absolutely contraindicated. Use alternative antifungal if these drugs are essential.

Source: Kimi deep-research + Cla

Abemaciclib

Severe

Database