isavuconazonium

Contraindicated in:

Hypersensitivity
Strong CYP3A4 inhibitors
Familial short QT syndrome
Strong CYP3A4 inducers
OB: Pregnancy
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 <1 yr (IV) or <6 yr and <16 kg (PO).

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema, chest pain, hypotension.

Derm: pruritus, rash, STEVENS-JOHNSON SYNDROME (SJS).

F and E: hypokalemia, hypomagnesemia.

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

GU: renal failure.

Local: injection site reactions.

MS: back pain.

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

Resp: cough, dyspnea, respiratory failure.

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), infusion-related reactions.

Interactions ⬆ ⬇

Drug-Drug:

Strong CYP3A4 inhibitors, including ketoconazole or high-dose ritonavir, ↑ levels and risk of toxicity; concurrent use contraindicated.
Strong CYP3A4 inducers, including long-acting barbiturates, carbamazepine, or rifampin, may ↓ levels and effectiveness; concurrent use 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 of atorvastatin, cyclosporine, digoxin, midazolam, mycophenolate, sirolimus, and tacrolimus; undertake concurrent use with caution, monitoring drug effects and making adjustments if necessary.
↓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↓ levels and effectiveness; concurrent use contraindicated.

Availability ⬆ ⬇

Capsules: 74.5 mg isavuconazonium (equivalent to 40 mg isavuconazole); 186 mg isavuconazonium (equivalent to 100 mg isavuconazole);
Lyophilized powder for injection: 372 mg isavuconazonium (equivalent to 200 mg isavuconazole)/vial;

Route/Dosage ⬆ ⬇

PO, IV (Adults 18 yr): Loading dose: 372 mg isavuconazonium (PO as either two 186 mg capsules or five 74.5 mg capsules; equivalent to 200 mg isavuconazole) every 8 hr for six doses; Maintenance dose: 372 mg isavuconazonium (PO as either two 186 mg capsules or five 74.5 mg capsules; equivalent to 200 mg isavuconazole) once daily starting 12–24 hr after last loading dose.
IV (Children 3–<18 yr and 37 kg): 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.
IV (Children 3–<18 yr and <37 kg): Loading dose: 10 mg/kg isavuconazonium every 8 hr for six doses; Maintenance dose: 10 mg/kg isavuconazonium once daily starting 12–24 hr after last loading dose.
IV (Children 1–<3 yr and <18 kg): Loading dose: 15 mg/kg isavuconazonium every 8 hr for six doses; Maintenance dose: 15 mg/kg isavuconazonium once daily starting 12–24 hr after last loading dose.
PO (Children 6–<18 yr and 32 kg): Loading dose: 372 mg isavuconazonium (five 74.5 mg capsules; equivalent to 200 mg isavuconazole) every 8 hr for six doses; Maintenance dose: 372 mg isavuconazonium (five 74.5 mg capsules; equivalent to 200 mg isavuconazole) once daily starting 12–24 hr after last loading dose.
PO (Children 6–<18 yr and 25–<32 kg): Loading dose: 298 mg isavuconazonium (four 74.5 mg capsules; equivalent to 160 mg isavuconazole) every 8 hr for six doses; Maintenance dose: 298 mg isavuconazonium (four 74.5 mg capsules; equivalent to 160 mg isavuconazole) once daily starting 12–24 hr after last loading dose.
PO (Children 6–<18 yr and 18–<25 kg): Loading dose: 223.5 mg isavuconazonium (three 74.5 mg capsules; equivalent to 120 mg isavuconazole) every 8 hr for six doses; Maintenance dose: 223.5 mg isavuconazonium (three 74.5 mg capsules; equivalent to 120 mg isavuconazole) once daily starting 12–24 hr after last loading dose.
PO (Children 6–<18 yr and 16–<18 kg): Loading dose: 149 mg isavuconazonium (two 74.5 mg capsules; equivalent to 80 mg isavuconazole) every 8 hr for six doses; Maintenance dose: 149 mg isavuconazonium (two 74.5 mg capsules; equivalent to 80 mg isavuconazole) once daily starting 12–24 hr after last loading dose.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

A prodrug that is converted (rapidly hydrolyzed) to isavuconazole. Inhibits the synthesis of ergosterol, a key component of fungal cell walls.

Therapeutic Effects:

Resolution of invasive fungal infections.

Spectrum:

Active against Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucormycetes species, including Rhizopus oryzae.

Classifications ⬆ ⬇

Therapeutic Classification: antifungals

Pharmacologic Classification: azoles

Pharmacokinetics ⬆ ⬇

Absorption: Prodrug is rapidly converted to isavuconazole, the active component. 98% absorbed following oral administration. IV administration results in complete bioavailability.

Distribution: Extensively distributed.

Protein Binding: >99%.

Metabolism/Excretion: Extensively metabolized by liver by the CYP3A4 and CYP3A5 isoenzymes; inactive metabolites are mostly renally eliminated. <1% excreted unchanged in urine.

Half-life: 130 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

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

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of isavuconazonium to patient. Instruct patient to take isavuconazonium as directed. Do not stop taking isavuconazonium without consulting heath care professional. If missed dose, take as soon as remembered or resume regular dose if almost time; do not take extra dose. 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, dark urine, feeling very tired, stomach pain), infusion-related reactions (flu-like symptoms, dizziness, numb/tingling skin), or hypersensitivity reactions (blistering, peeling, red skin 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 therapy 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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Indications ⬇

Contraind./Precautions ⬆ ⬇