Treatment of invasive aspergillosis and mucormycosis.
A prodrug that is converted (rapidly hydrolyzed) to isavuconazole. Inhibits the synthesis of ergosterol, a key component of fungal cell walls.
Resolution of invasive fungal infections.Spectrum:
Active against Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucormycetes species including Rhizopus oryzae.
Absorption: Prodrug is rapidly converted to isavuconazole, the active component. 98% absorbed following oral administration. Similar conversion follows intravenous administration, resulting in complete bioavailability.
Distribution: Extensively distributed.
Protein Binding: >99%
Metabolism and Excretion: Extensively metabolized (mostly by CYP3A4 and CYPA5); inactive metabolites are mostly renally eliminated, <1% excreted unchanged in urine.
Half-life: 130 hr
TIME/ACTION PROFILE (blood levels)
|IV||unknown||end of infusion||unknown|
- Known hypersensitivity;
- Strong CYP3A4 inhibitors;
- Familial short QT syndrome;
- Strong CYP3A4 inducers;
- Lactation: Discontinue breast feeding.
Use Cautiously in:
- Severe hepatic impairment (use only if benefits outweigh risks, monitor carefully for adverse reactions);
- OB: Use during pregnancy only if maternal benefits outweigh risks to the fetus
- Pedi: Safe and effective use in children <18 yr has not been established.
Adverse Reactions/Side Effects
CNS: fatigue, insomnia, headache, anxiety, delerium
Resp: cough, dyspnea, respiratory failure
CV: peripheral edema, chest pain, hypotension
GI: constipation, diarrhea, ↑ liver enzymes, nausea, vomiting, ↓ appetite, dyspepsia
GU: renal failure
Derm: pruritus, rash
F and E: hypokalemia, hypomagnesemia
Local: injection site reactions
MS: back pain
Misc: infusion-related reactions
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- ↑ levels and risk of toxicity with strong inhibitors of CYP3A4, including ketoconazole or high-dose ritonavir ; concurrent use is contraindicated.
- Lopinavir/ritonavir significantly ↑ levels and risk of toxicity; concurrent use should be undertaken with caution.
- Isavuconazonium ↓ levels and effectiveness of lopinavir/ritonavir.
- Isavuconazonium ↑ levels and risk of toxicity with atorvastatin, cyclosporine, digoxin, midazolam, mycophenolate, sirolimus, tacrolimus ; undertake concurrent use with caution, monitoring drug effects and making adjustments if necessary.
- Strong inducers of CYP3A4 including long-acting barbiturates, carbamazepine, or rifampin ↓ levels and effectiveness; concurrent use is contraindicated.
- ↓ levels and effectiveness of bupropion ; bupropion dose may need to be ↑ but should not exceed maximum recommended dose.
St. John's wort ↓ blood levels and effectiveness; concurrent use is contraindicated.
186 mg isavuconazonium = 100 mg isavuconazole; doses expressed as isavuconazole.
PO IV (Adults ≥18 yr): Loading dose– 200 mg every 8 hr for six doses; maintenance dose– 200 mg once daily starting 12–24 hr after last loading dose.
186 mg isavuconazonium = 100 mg isavuconazole; strength expressed as isavuconazole
Capsules: 100 mg
Lyophilized powder for intravenous injection (requires reconstitution): 200 mg
- Obtain specimens for culture and sensitivity prior to therapy. First dose may be given before receiving results.
- Monitor for signs and symptoms of infusion-related reactions (hypotension, dyspnea, chills, dizziness, paresthesia, hypoesthesia) periodically during therapy. Discontinue infusion if symptoms occur.
- Monitor skin for hypersensitivity reactions during therapy.
Lab Test Considerations: Monitor liver function tests prior to and periodically during therapy. Discontinue therapy if clinical signs of liver disease occur.
- May cause hypokalemia and hypomagnesemia.
- Risk for infection (Indications)
- Oral and IV formulations are bioequivalent; may be used interchangeably. Loading dose is not needed when switching.
- PO Administer without regard to food. Swallow capsule whole; do not open, dissolve, crush or chew.
- Reconstitute by adding 5 mL sterile water to vial. Shake gently to dissolve powder completely. Solution should be clear and colorless; do not administer solutions that are discolored or contain particulate matter. Solution is stable for 1 hr at room temperature.
- Intermittent Infusion: Diluent: Remove 5 mL of reconstituted solution from vial and add to 250 mL 0.9% NaCl or D5W. Concentration: 1.5 mg isavuconazonium/mL. Diluted solution may show visible translucent to white particulates; removed with in-line filter. Roll bag to mix gently; avoid shaking. Solution is stable if infused at room temperature within 6 hrs; may refrigerate for up to 24 hrs; do not freeze. Flush line with 0.9% NaCl or D5W prior to and following infusion.
- Rate: Infuse over at least 1 hr to minimize infusion-related reactions. Infuse through a 0.2–1.2 micron in-line filter. Do not administer as a bolus injection.
- Y-Site Incompatibility: Do not infuse with other medication.
- Instruct patient to take isavuconazonium as directed. Do not stop taking isavuconazonium without consulting heath care professional. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
- Advise patient to notify health care professional promptly of signs and symptoms of liver disease (itchy skin, nausea, vomiting, yellowing of eyes, feeling very tired, flu-like symptoms), infusion-related reactions, or rash occur.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
- Advise female patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.
- Emphasize the importance of lab tests to monitor for side effects during therapy.
Resolution of signs and symptoms of invasive fungal infection.
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