isavuconazonium

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/Excretion: Extensively metabolized (mostly by CYP3A4 and CYP3A5); inactive metabolites are mostly renally eliminated, <1% excreted unchanged in urine.

Half-life: 130 hr.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Known hypersensitivity
Strong CYP3A4 inhibitors
Familial short QT syndrome
Strong CYP3A4 inducers
OB: Pregnancy (may cause fetal harm)
Lactation: Lactation.

Use Cautiously in:

Severe hepatic impairment (use only if benefits outweigh risks, monitor carefully for adverse reactions)
Rep: Women of reproductive potential
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema, chest pain, hypotension.

Derm: pruritus, rash.

F and E: hypokalemia, hypomagnesemia.

GI: constipation, diarrhea, ↑liver enzymes, nausea, vomiting, ↓ appetite, dyspepsia.

GU: renal failure.

Local: injection site reactions.

MS: back pain.

Neuro: fatigue, insomnia, headache, anxiety, delirium.

Resp: cough, dyspnea, respiratory failure.

Misc: infusion-related reactions.

Interactions ⬆ ⬇

Drug-Drug:

↑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.

Drug-Natural Products:

St. John's wort↓ blood levels and effectiveness; concurrent use is contraindicated.

Route/Dosage ⬆ ⬇

PO, IV (Adults 18 yr): Loading dose — 372 mg isavuconazonium (equivalent to 200 mg isavuconazole) every 8 hr for six doses; Maintenance dose — 372 mg isavuconazonium (equivalent to 200 mg isavuconazole) once daily starting 12–24 hr after last loading dose.

Implementation ⬆ ⬇

Oral and IV formulations are bioequivalent; may be used interchangeably. Loading dose is not needed when switching.
PO: Administer without regard to food. DNC: Swallow capsule whole; do not open, dissolve, crush or chew.
- To administer via NG tube, reconstitute one vial isavuconazonium for injection (equivalent to 200 mg isavuconazonium) with 5 mL of water for injection. Withdraw the entire contents (5 mL) of vial using a syringe and needle. Discard the needle and cap the syringe. To administer, remove cap from syringe containing the reconstituted solution and connect the syringe to NG tube to deliver dose. After administering, administer three 5 mL rinses to NG tube with water. Administer reconstituted solution via NG tube within 1 hr of reconstitution

IV Administration:

Reconstitution: 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:
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 Compatibility:
- amikacin
- amiodarone
- anidulafungin
- aztreonam
- calcium chloride
- calcium gluconate
- caspofungin
- ceftozolane/tazobactam
- ciprofloxacin
- cisatracurium
- daptomycin
- dexamethasone
- dexmedetomidine
- digoxin
- diltiazem
- diphenhydramine
- dobutamine
- dopamine
- doxycycline
- epinephrine
- eptifibatide
- esmolol
- famotidine
- fentanyl
- gentamicin
- hydrocortisone
- hydromorphone
- imipenem/cilastatin
- insulin, regular
- labetalol
- levofloxacin
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- meperidine
- mesna
- metoclopramide
- midazolam
- milrinone
- morphine
- mycophenolate
- naloxone
- nicardipine
- nitroglycerin
- nitroprusside
- norepinephrine
- octreotide
- ondansetron
- pantoprazole
- phenylephrine
- plazomicin
- potassium chloride
- rocuronium
- tacrolimus
- tigecycline
- tobramycin
- vancomycin
- vasopressin
- vecuronium
Y-Site Incompatibility:
- albumin, human
- amphotericin B deoxycholate
- amphotericin B lipid complex
- amphotericin B liposome
- ampicillin/sulbactam
- cefazolin
- cefepime
- ceftaroline
- ceftazidime
- ceftriaxone
- cefuroxime
- cyclosporine
- ertapenem
- esomeprazole
- filgrastim
- fosphenytoin
- furosemide
- heparin
- meropenem
- meropenem/vaborbactam
- methyprednisolone
- micafungin
- phenytoin
- potassium phosphates
- propofol
- sodium bicarbonate
- sodium phosphates
- tedizolid

US Brand Names ⬆ ⬇

Classifications ⬆ ⬇

Therapeutic Classification: antifungals

Pharmacologic Classification: azoles

Availability ⬆ ⬇

Capsules: 186 mg isavuconazonium (equivalent to 100 mg isavuconazole);
Lyophilized powder for injection: 372 mg isavuconazonium (equivalent to 200 mg isavuconzole)/vial;

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	2 hr	unknown
IV	unknown	end of infusion	unknown

Assessment ⬆ ⬇

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.

Pot. Nursing Diagnoses ⬆ ⬇

Risk for infection (Indications).

Patient/Family Teaching ⬆ ⬇

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.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 28 days after final dose and to avoid breastfeeding during therapy. Advise patient to notify health care professional if pregnancy is planned or suspected.
Emphasize the importance of lab tests to monitor for side effects during therapy.

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Pronunciation ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇