Isavuconazonium sulfate

What is Isavuconazonium sulfate?

Isavuconazonium sulfate (CRESEMBA) is an azole antifungal used to treat invasive aspergillosis and mucormycosis.

What are the uses of this medicine?

• This medicine is used to treat people 18 years of age and older with certain types of fungal infections in the blood or body called “aspergillosis,” and “mucormycosis” (zygomycosis).

How does this medicine work?

• The sulfate ester form of isavuconazonium, a prodrug of the triazole antifungal agent isavuconazole, with broad-spectrum antifungal activity.
• Upon administration, isavuconazonium sulfate is hydrolyzed by plasma esterases to yield the active moiety isavuconazole.
• Isavuconazole binds to and inhibits the fungal cytochrome P450 family enzyme lanosterol 14-alpha-demethylase (CYP51), which catalyzes the demethylation of lanosterol to yield ergosterol, an important component of the fungal cell membrane.
• Inhibition of CYP51 leads to a decrease in fungal ergosterol production and disrupts synthesis of the fungal cell membrane, which decreases membrane integrity, increases cell membrane permeability and promotes the loss of essential intracellular elements.
• This results in fungal cell lysis and death.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• known hypersensitivity to isavuconazole

are taking any of the following medicines:

• ketoconazole
• high-dose ritonavir
• rifampin
• carbamazepine
• St. John’s wort (herbal supplement)
• long-acting barbiturates

• a genetic problem that affects the electrical system of the heart (familial short QT syndrome)

What drug interactions can this medicine cause?

Appropriate therapeutic drug monitoring and dose adjustment of immunosuppressants (i.e., tacrolimus, sirolimus, and cyclosporine) may be necessary when coadministered with CRESEMBA. Drugs with a narrow therapeutic window that are P-gp substrates, such as digoxin, may require dose adjustment when administered concomitantly with CRESEMBA. CRESEMBA cannot be used with:

• ketoconazole
• high-dose ritonavir
• rifampin
• carbamazepine
• St. John’s wort (herbal supplement)
• long-acting barbiturates

Is this medicine FDA approved?

• It was approved for use in the United States in 2015.

How should this medicine be used?

• CRESEMBA for injection must be administered through an in-line filter over a minimum of 1 hour.

Recommended Dosage:

• Loading Dose: 372 mg isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) every 8 hours for 6 doses (48 hours) via oral (2 capsules) or intravenous administration (1 reconstituted vial).
• Maintenance Dose: 372 mg isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) once daily via oral (2 capsules) or intravenous administration (1 reconstituted vial) starting 12 to 24 hours after the last loading dose.

Administration

• Take CRESEMBA exactly as your healthcare provider tells you to take it.
• Do not stop taking CRESEMBA until your healthcare provider tells you to.
• If you take too much CRESEMBA, call your healthcare provider.
• CRESEMBA capsules can be taken with or without food.
• Swallow CRESEMBA capsules whole.
• Do not chew, crush, dissolve, or open the capsules.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As CRESEMBA capsules contain 186 mg of isavuconazonium sulfate (equivalent to 100 mg of isavuconazole).
• CRESEMBA for injection is supplied in a single-dose vial as a sterile lyophilized powder containing 372 mg of isavuconazonium sulfate (equivalent to 200 mg of isavuconazole).

This medicine is available in fallowing brand namesː

• CRESEMBA

What side effects can this medication cause?

The most common side effects of this medicine include:

• nausea
• vomiting
• diarrhea
• headache
• changes in the level of a liver enzyme in your blood
• low potassium
• constipation
• shortness of breath
• cough
• swelling of arms or legs
• back pain

CRESEMBA may cause serious side effects, including:

• liver problems
• infusion reactions
• severe allergic and skin reactions
• drug interactions with cyclosporine, sirolimus, or tacrolimus
• medicine interactions

What special precautions should I follow?

• Hepatic adverse drug reactions (e.g., elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin) have been reported in clinical trials. Evaluate liver-related laboratory tests at the start and during the course of CRESEMBA therapy.
• Infusion-related reactions were reported during intravenous administration of CRESEMBA. Discontinue the infusion if these reactions occur.
• Serious hypersensitivity and severe skin reactions, such as anaphylaxis or Stevens-Johnson syndrome, have been reported during treatment with other azole antifungal agents. Discontinue CRESEMBA if a patient develops a severe cutaneous adverse reaction.
• CRESEMBA may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use an effective method of contraception.
• Review patient’s concomitant medications. Several drugs may significantly alter isavuconazole concentrations. Isavuconazole may alter concentrations of several drugs.
• Following dilution, CRESEMBA intravenous formulation may form precipitate from the insoluble isavuconazole. Administer CRESEMBA through an in-line filter.

What to do in case of emergency/overdose?

• Symptoms of overdosage including headache, dizziness, paresthesia, somnolence, disturbance in attention, dysgeusia, dry mouth, diarrhea, oral hypoesthesia, vomiting, hot flush, anxiety, restlessness, palpitations, tachycardia, photophobia and arthralgia.

Management for overdosage:

• Isavuconazole is not removed by hemodialysis.
• There is no specific antidote for isavuconazole.
• Treatment should be supportive with appropriate monitoring.

Can this medicine be used in pregnancy?

• Based on findings from animal studies, CRESEMBA may cause fetal harm when administered to a pregnant woman.
• There are no available human data on the use of CRESEMBA in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Can this medicine be used in children?

• The safety and efficacy of CRESEMBA in pediatric patients less than 18 years of age have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: isavuconazonium sulfate.
• Inactive ingredients: magnesium citrate, microcrystalline cellulose, talc, colloidal silicon dioxide, stearic acid, hypromellose, red iron oxide, titanium dioxide, purified water, gellan gum, potassium acetate, disodium edetate, sodium laurylsulfate, shellac, propylene glycol, strong ammonia solution, potassium hydroxide, black iron oxide.

Who manufactures and distributes this medicine?

• Marketed and Distributed by:

Astellas Pharma US, Inc. Northbrook

What should I know about storage and disposal of this medication?

• Store CRESEMBA at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep CRESEMBA in the original package and protect it from moisture.
• Do not remove CRESEMBA from original packaging.
• Do not put CRESEMBA in pill boxes or pill organizers.
• Safely throw away medicine that is out of date or no longer needed.
• Keep CRESEMBA and all medicines out of the reach of children.

• Dailymed label info on Isavuconazonium sulfate
• FDA Isavuconazonium sulfate

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