Cresemba

Common name: isavuconazonium sulfate

Trade name: Cresemba

Full names: isavuconazonium capsules, isavuconazonium sulfate, Cresemba

Indications:

CRESEMBA is indicated for the treatment of adults

Invasive aspergillosis

Mucormycosis in patients who are not suitable for amphotericin B.

Dosage:

Dose

Early targeted therapy (preemptive or diagnostic-driven therapy) may be given pending confirmation of the disease by specific diagnostic tests. However, once these results are obtained, antifungal treatment should be adjusted accordingly.

Loading dose

The recommended loading dose is two capsules (equivalent to 200 mg isavuconazole) taken every 8 hours for the first 48 hours.

Maintenance dose

The recommended maintenance dose is two capsules (equivalent to 200 mg isavuconazole) once daily, starting 12 to 24 hours after the last loading dose.

Duration of treatment should be determined by clinical response.

For long-term treatment beyond 6 months, the benefit-risk balance should be carefully considered.

Switch to intravenous infusion

CRESEMBA is also available as a concentrated powder containing 200 mg of isavuconazole as an infusion solution.

Based on high oral bioavailability (98%), switching between intravenous and oral administration is appropriate when clinically indicated.

Geriatric

No dose adjustment is required in elderly patients; however, clinical experience with elderly patients is limited.

Renal Impairment

No dose adjustment is required in patients with renal insufficiency, including patients with end-stage renal disease.

Hepatic Impairment

No dose adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh Class A and B).

Isavuconazole has not been studied in patients with severe hepatic impairment (Child-Pugh class C). Use in these patients is not recommended unless the potential benefits are considered to outweigh the risks.

Pediatric Population

The safety and effectiveness of CRESEMBA in children under 18 years of age have not been established. No data available.

Dosage

CRESEMBA capsules can be taken with or without food.

CRESEMBA capsules should be swallowed whole. Do not chew, crush, dissolve or open capsules.

Specifications:

100 mg

Contraindications:

Hypersensitivity to the active substance or any of the listed excipients.

Coadministered with ketoconazole.

Coadminister with high-dose ritonavir (>200 mg every 12 hours).

Coadministration with strong CYP3A4/5 inducers such as rifampicin, rifabutin, carbamazepine, long-acting barbiturates (e.g., phenobarbital), phenytoin, and St. John's wort or with moderate CYP3A4/5 inducers such as efavirenz, nafcillin, and etravirine.

Patients with familial short QT syndrome.

Precautions:

Hepatic adverse drug reactions: Serious liver reactions have been reported. Evaluate liver-related laboratory tests at the beginning and during the course of CRESEMBA treatment.

Infusion-related reactions have been reported during intravenous administration of CRESEMBA. If these reactions occur, terminate the infusion.

Hypersensitivity Reactions: Severe hypersensitivity and severe skin reactions, such as anaphylaxis or Stevens Johnson syndrome, have been reported during treatment with other azole antifungals. Discontinue CRESEMBA for exfoliative skin reactions.

Embryo-fetal toxicity: Do not give to pregnant women unless the maternal benefit outweighs the risk to the fetus. Inform pregnant patients of the hazards.

Drug Interactions: Review patients' concomitant medications. Several drugs may significantly alter isavuconazole concentrations. Isavuconazole may alter the concentrations of several drugs.

Drug particles: Insoluble particles may form after reconstitution of intravenous preparations. Administer CRESEMBA through an in-line filter.

Storage:

Do not store above 30°C.

Mechanism of action:

Isavuconazole is the active moiety formed after oral or intravenous injection of isavuconazole sulfate.

Isavuconazole exhibits fungicidal effects by blocking the synthesis of ergosterol, a key component of fungal cell membranes, by inhibiting the cytochrome P-450-dependent enzyme lanosterol 14-alpha-demethylase, which is responsible for converting lanosterol to ergosterol. This results in the accumulation of methylated sterol precursors and depletion of ergosterol within the cell membrane, thereby weakening the structure and function of the fungal cell membrane.

Safety and Efficacy:

Intratracheal infection of neutropenic mice with Rhizopus delemar or Mucor circinelloides. The researchers treated mice with isavuconazole, L-AMB in combination or alone for 8 hours after infection and continued until day 4, and placebo mice received vehicle control. Tissue fungal burden in mice surviving to day 21 and day 4 served as primary and secondary endpoints, respectively.

For infected mice, compared with L-AMB and placebo, isavuconazole and L-AMB prolonged the median survival time of mice and increased the survival rate of mice. The overall survival rate of mice using the two drugs alone was 50%, while the placebo was only 5%, while the overall survival rate of mice treated with the two drugs in combination was 80%! And compared with the placebo, the fungal burden in any organ was reduced by 2.0-3.5% when the two drugs were used in combination. log, while a single drug reduced 1.0-2.0 log.

The conclusion is that isavuconazole combined with L-AMB is more effective in treating mucormycosis than monotherapy. From the experimental data obtained in this study, it can be seen that isavuconazole combined with L-AMB therapy may become the best new therapy for the treatment of mucormycosis.