Strong Cyp3a4 Inducers
Contraindicated
Database
Markedly reduced exposure
Contraindicated per label
Source: Kimi deep-research + Cla
Drug reference
Isavuconazole
Triazole antifungal (prodrug isavuconazonium) · Antifungal
START
200 mg q8h ×6 doses (load), then 200 mg once daily
TYPICAL MAX
Equivalent of 200 mg isavuconazole once daily (maintenance)
STOP IF
Significant hepatotoxicity or severe hypersensitivity
WATCH
LFTs, potassium, ECG (short QT); CYP3A4 interactions
CDSCO approvedSchedule HATC J02AC05
KDIGO 2024 + manufacturer label
- ONSET
- 1h · absorption
- PEAK
- 2.5h · Tmax
- t½
- 5.4d · t½
- DURATION
- 1d · once-daily
EXCRETION
Faecal metabolites; <1% renal unchanged
route + CYP
INTERACTIONS
3 major
incl. contraindicated
PREGNANCY
Avoid unless benefit outweighs risk (animal embryotoxicity).
FDA category + note
Top interactionssee all 10 →
- Strong Cyp3a4 InducersContraindicatedDatabaseKimi deep-research + Cla
- Strong Cyp3a4 InhibitorsContraindicatedDatabaseKimi deep-research + Cla
- TacrolimusSevereDatabaseKimi deep-research + Cla
Mechanism
Inhibits fungal CYP51 (lanosterol 14-alpha-demethylase), blocking ergosterol synthesis and disrupting the fungal cell membrane; broad activity including Aspergillus and Mucorales.
Indications
Invasive aspergillosisInvasive mucormycosis
Dosing
- Adult
- Loading: 372 mg isavuconazonium (≈200 mg isavuconazole) IV/PO every 8 h for 6 doses, then 372 mg once daily starting 12–24 h after last loading dose.
- Pediatric
- Not established (adult/specialist use).
- Renal adjustment
- No adjustment (no IV cyclodextrin accumulation concern unlike voriconazole).
- Hepatic adjustment
- Mild–moderate: no adjustment; severe: not studied — use caution.
- Geriatric
- No dose adjustment.
- Max dose
- 372 mg isavuconazonium once daily (maintenance)
Pharmacokinetics
Onset
Antifungal effect over days
Peak effect
~2–3 h (Tmax)
Duration
~24 h (once-daily)
Half-life
~130 h (long)
Bioavailability
~98% (oral)
Protein binding
>99%
Metabolism
Hepatic CYP3A4/3A5 then UGT
Excretion
Faecal (~46%) and renal metabolites; <1% unchanged renal
Contraindications
- Familial short-QT syndrome (isavuconazole shortens QT)
- Coadministration with strong CYP3A4 inhibitors/inducers
- Hypersensitivity
Side effects
Common
Nausea/vomitingDiarrhoeaHeadacheHypokalaemiaElevated liver enzymesPeripheral oedema
Serious
- Hepatotoxicity
- Infusion-related reactions
- Severe hypersensitivity
- QT shortening (paradoxical vs other azoles)
Pregnancy & lactation
Pregnancy
Avoid unless benefit outweighs risk (animal embryotoxicity).
Lactation
Avoid breastfeeding (limited data).
Drug interactions
Strong Cyp3a4 Inhibitors
Contraindicated
Database
Markedly increased isavuconazole exposure
Contraindicated per label
Source: Kimi deep-research + Cla
Tacrolimus
Severe
Database
CYP3A4 inhibition by isavuconazole
Monitor levels; reduce dose
Source: Kimi deep-research + Cla
Ketoconazole
Moderate
Textbook
A 5-fold increase in isavuconazole AUC.
Monitor for increased isavuconazole adverse effects and consider dose adjustment or alternative agents.
Source: G&G 14e · p1202
Midazolam
Moderate
Textbook
Increased midazolam AUC.
Monitor for increased sedative effects of midazolam and adjust dose as necessary.
Source: G&G 14e · p1202
P450 Related Drugs
Moderate
Textbook
Fewer drug interactions compared to voriconazole.
Source: Harrison 22e · p1692
Rifampin
Moderate
Textbook
Substantial reductions in isavuconazole AUC, potentially leading to reduced efficacy.
Monitor for reduced isavuconazole efficacy and consider dose adjustment or alternative agents.
Source: G&G 14e · p1202
Sirolimus
Moderate
Textbook
Increased sirolimus AUC.
Monitor sirolimus levels closely and adjust dose as necessary to avoid toxicity.
Source: G&G 14e · p1202
Digoxin
Moderate
Database
P-gp inhibition
Monitor digoxin
Source: Kimi deep-research + Cla
Qt Shortening Drugs
Moderate
Database
Additive QT shortening
Avoid in familial short-QT syndrome
Source: Kimi deep-research + Cla
Related guidelines
Ask House about Isavuconazole
Continue into a citation-backed clinical answer with the drug context already attached.
Sources: Goodman & Gilman 14e, Harrison 22e, Katzung, BNF·Verified: 2026-05-20 · House clinical team·Cockpit curated: 2026-05-20