UCSF Health Adult (18+ years) Azole Therapeutic Drug Monitoring Reference Document
Table of Contents
- Antifungal Drug Information and Monitoring Chart
- General Dosing Considerations
- When to Obtain an Additional Level
- How Often to Obtain Levels Once Therapeutic
- Considerations Prior to Dose Adjustment
- Voriconazole CYP2C19 polymorphisms
- Instructions for Dose Adjustment Based Upon Levels
- Azole Drug-Drug Interaction Table
Disclaimer: Practice guidelines are intended to assist with clinical decision-making for common situations but cannot replace personalized evaluation and management decisions based on individual patient factors. All patients should be carefully evaluated and treated for suspected focal infection if identified. Consult ID or ASP if you have clinical questions or questions about antifungal selection. Additionally, the information reflects the best available data at the time the guideline was prepared. The results of future studies may prompt revisions of these guidelines to reflect new data.
Antifungal Drug Information and Monitoring Chart
¥ ¥ = Conversion between formulations is NOT 1:1, please reach out to ASP/ID pharmacy when converting between the two formulations.
Drug |
Formulations |
Administration |
Therapeutic Drug Monitoring |
Adverse Reactions |
---|---|---|---|---|
Class Effect Hepatotoxicity |
||||
Fluconazole (IDMP)
|
IV
Enteral Suspension
Tablet |
Enteral formulations can be given with or without meal |
Not routinely recommended |
QT Prolongation |
Voriconazole (IDMP)
|
IV
Enteral Suspension
Tablet |
Food decreases absorption of enteral formulations
Must be taken 1 hr before or after meal |
Obtain trough after steady state (3-5 days) - Prophylaxis trough goal: 2-6 mcg/mL - Treatment trough goal: 2-6 mcg/mL
Serum levels > 4 mcg/L are associated with visual hallucinations/risk of neurotoxicity and may be associated with hepatotoxicity |
QT Prolongation Photosensitivity Visual Disturbances
Rare (<1%): Skeletal Fluorosis Dermatologic Complications |
Posaconazole (IDMP)
|
¥ ¥ Delayed Release Tablet
|
Increased bioavailability when taken with meal
May crush and give via a feeding tube if patient unable to swallow pills
If crushing is needed, crush tablet into a fine powder, dilute with 30 mL purified water, allow to dissolve for 10 min, administer, and flush tube with an additional 10 mL purified water. |
Obtain first trough after steady state (5-7 days) - 6 days for IV & delayed-release tablet - 7-10 days for the IR enteral suspension
- Prophylaxis trough goal: ≥ 0.7 mcg/mL - Treatment trough goal: ≥ 1.25 mcg/mL
|
QT Prolongation
Rare (<1%): Pseudohyperaldosteroinism |
IV (Restricted to ID/ASP) |
|
|||
¥ ¥ IR Suspension |
Not recommended due to unpredictable bioavailability - Administer with high-fat meals to improve bioavailability and avoid concomitant acid-suppression therapy |
|||
Isavuconazole (IDMP)
|
IV
Capsule |
Enteral formulations can be given with or without meals
Crushing instructions for capsule: - Open capsules and mix contents with saline or tube feed formulations for administration via enteral feeding tubes. Then administer 15 mL of water afterwards. |
TDM is generally not recommended unless concern for toxicity, therapeutic failure, or altered absorption; consult ID/ASP for further guidance if indicated
Obtain first trough after steady state (5-7 days) - Treatment trough goal: 2-5 mcg/mL
|
|
Itraconazole
|
¥ ¥ Solution
¥ ¥ Capsule (Sporanox)
¥ ¥ Capsule (Tolsura) |
It is necessary to take the capsule and solution with food and avoid acid-suppressing agents |
Obtain first trough after steady state (10-14 days)
NOTE: HPLC assay measures itraconazole and hydroxyitraconazole levels; both values should be added to evaluate true level
- Prophylaxis trough goal: > 0.5 mcg/mL - Treatment trough goal: >1-2 mcg/mL |
Heart Failure |
Flucytosine (IDMP)
|
Capsule |
Food can decrease rate of absorption |
TDM is generally not indicated unless under the guidance of ID/ASP
Obtain peak level after day 3 of therapy ~2 hours after administration - Treatment peak goal: 50-75 mcg/mL |
|
Red = Nonformulary Item
¥ ¥ = Conversion between formulations is NOT 1:1, please reach out to ASP/ID pharmacy when converting between the two formulations.
Note: Timing of labs and other additional information regarding drug levels are available in the lab manual here. Reference ranges may vary by lab and must be interpreted according to specific assays utilized.
General Dosing Considerations
- If patient has previous history of being on a triazole, please review medication history and prior levels to determine dosing before reinitiation
- If patient has past medical history involving hepatic impairment (cirrhosis, acute liver failure, etc.), consider initiating voriconazole at a reduced dose
- Voriconazole is extensively metabolized by liver and patients with hepatic impairment (cirrhosis, acute liver failure, etc.) are susceptible to overexposure and adverse reactions
When to Obtain an Additional Level
- Change in dose
- Change in body habitus (morbid obesity, etc.)
- Introduction or discontinuation of drugs with significant interactions
- Disease progression
- Toxicity concern
- Concern for non-adherence
How Often to Obtain Levels Once Therapeutic
- Once level is within goal, can check intermittently, deferring to primary clinical team judgement, unless patient undergoes change that qualifies them for an additional level (see above)
Considerations Prior to Dose Adjustment
- New drug-drug interactions
- Altered absorption (i.e. diarrhea, vomiting, tube feedings, etc.)
- Erratic administration/missed doses
- Incorrect trough draws (not at steady state, drawn after dose administered, etc.)
Voriconazole CYP2C19 polymorphisms (per PharmKGB)
- Poor metabolizer: consider use of alternate agent OR if unable to switch, use 50% of standard dose and monitor serum concentrations
- Normal, intermediate metabolizer: monitor serum concentrations
- Ultrarapid metabolizer: consider use of alternate agent OR if unable to switch, use 150% of standard dose and monitor serum concentrations
Instructions for Dose Adjustment Based Upon Levels
Voriconazole: Based upon Expert Opinion and Trial Data
Voriconazole Trough Level (mcg/mL) |
Intervention |
<0.1-1.9 |
Increase total daily dose by 100 mg Recheck trough level after steady state achieved (3-5 days)
|
2.0-6.0* |
No change |
6.1-7.9 WITHOUT symptoms of toxicity |
Consider decreasing total daily dose by 100 mg Recheck trough level after steady state achieved |
6.1-7.9 WITH symptoms of toxicity |
Hold 1-2 doses/until toxicity resolved, recheck trough, then restart at total daily dose 100 mg less when trough is no longer supratherapeutic Recheck trough level after steady state achieved
|
>8 |
Hold dose Recheck trough and restart at 50% dose reduction when trough is therapeutic Recheck trough level after steady state achieved |
* If patient is experiencing symptoms of toxicity, see row with symptoms of toxicity
Posaconazole (Prophylaxis) - Delayed Release Capsules: Based on Expert Opinion
Posaconazole Trough Level (mcg/mL) |
Intervention |
<0.7 |
Increase dose by 100 mg, recheck trough level after steady state achieved (5-7 days) |
0.7-4.9 |
No change |
>5 WITH symptoms of toxicity |
Decrease dose by 100 mg Consider holding 1-2 doses and rechecking trough after steady state achieved
|
Posaconazole (Treatment) - Delayed Release Capsules: Based on Expert Opinion
Posaconazole Trough Level (mcg/mL) |
Intervention |
<1.0 |
Increase dose by 100 mg, recheck trough level after steady state achieved (5-7 days) |
1.0-4.9 |
No change |
>5 WITH symptoms of toxicity |
Consider holding 1-2 doses and rechecking trough level after steady state achieved Decrease dose by 100 mg
|
Azole Drug-Drug Interaction Table:
This table highlights established DDIs but is not meant to be a comprehensive list. Be sure to run all patient medications for interactions. Please evaluate the significance of the interaction on a case-by-case basis weighing benefits and risks of therapy. Check the package insert for specific dosing instructions with interacting medications.
Interactions with increased azole concentration |
|||
Drug Class |
Examples |
Affected Azoles |
Management |
CYP2C9/2C19 inhibitors |
Fluvoxamine |
Voriconazole |
Consider modifying treatment to avoid combined use of CYP inhibitor with azole |
CYP3A inhibitors |
Ritonavir, Cobicistat, Clarithromycin |
Isavuconazole, itraconazole |
|
Interactions with decreased azole concentration |
|||
Drug Class |
Examples |
Affected Azoles |
Management |
CYP inducers |
Rifampin, carbamazepine, phenobarbital, phenytoin, St. John's wort |
Voriconazole, posaconazole, isavuconazole, or itraconazole |
Consider modifying treatment to avoid combined use of CYP3A inducer with azole
|
Interactions with increased concentration of co-administered drug |
|||
Drug Class |
Examples |
Affected Azoles |
Management |
CYP3A substrates |
Apixaban, cyclosporine, dronedarone, everolimus, lovastatin, methadone, rivaroxaban, simvastatin, sirolimus, tacrolimus, venetoclax, vincristine |
Fluconazole, posaconazole, voriconazole, itraconazole |
Increased Monitoring: Rivaroxaban Dose Adjustment: Immunosuppressive agents (mTOR, CNI); apixaban, methadone, venetoclax (see prescribing information for specific dose adjustments in combination with azole therapy) Change in Therapy: Lovastatin, simvastatin Change in Azole: Vincristine |
Last Updated: February 2024
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