1.1 Invasive Aspergillosis

CRESEMBA® is an azole antifungal indicated for patients 18 years of age and older for the treatment of invasive aspergillosis [see Clinical Studies (14.1) and Clinical Pharmacology (12.4)].

1.2 Invasive Mucormycosis

CRESEMBA is an azole antifungal indicated for patients 18 years of age and older for the treatment of invasive mucormycosis [see Clinical Studies (14.2) and Clinical Pharmacology (12.4)].

1.3 Usage

Specimens for fungal culture and other relevant laboratory studies (including histopathology) to isolate and identify causative organism(s) should be obtained prior to initiating antifungal therapy. Therapy may be instituted before the results of the cultures and other laboratory studies are known. However, once these results become available, antifungal therapy should be adjusted accordingly.

2.1 Important Instructions for Intravenous Administration

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Intravenous formulation must be administered via an infusion set with an in-line filter (pore size 0.2 to 1.2 micron).

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Infuse the intravenous formulation over a minimum of 1 hour in 250 mL of a compatible diluent, to reduce the risk for infusion-related reactions. Do not administer as an intravenous bolus injection.

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Do not infuse CRESEMBA with other intravenous medications.

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Flush intravenous lines with 0.9% sodium chloride injection, USP or 5% dextrose injection, USP prior to and after infusion of CRESEMBA.

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After dilution of the intravenous formulation, avoid unnecessary vibration or vigorous shaking of the solution. Do not use a pneumatic transport system.

2.2 Dosage Regimen

CRESEMBA (isavuconazonium sulfate) is the prodrug of isavuconazole, an azole antifungal drug. Prescribe CRESEMBA as shown in Table 1 below.

Switching between the intravenous and oral formulations of CRESEMBA is acceptable as bioequivalence has been demonstrated. Loading dose is not required when switching between formulations.

With oral administration, swallow capsules whole. Do not chew, crush, dissolve, or open the capsules. CRESEMBA capsules can be taken with or without food.

2.3 Reconstitution Instructions for the Injection Formulation

Aseptic technique must be strictly observed in all handling since no preservative or bacteriostatic agent is present in CRESEMBA or in the materials specified for reconstitution. CRESEMBA is water soluble, preservative-free, sterile, and nonpyrogenic.

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Reconstitute one vial of CRESEMBA by adding 5 mL water for injection, USP to the vial.

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Gently shake to dissolve the powder completely.

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Visually inspect the reconstituted solution for particulate matter and discoloration. Reconstituted CRESEMBA should be clear and free of visible particulate.

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The reconstituted solution may be stored below 25°C for a maximum of 1 hour prior to preparation of the patient intravenous infusion solution [see Dosage and Administration (2.4)].

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For nasogastric tube administration, the reconstituted solution should be administered within 1 hour of reconstitution [see Dosage and Administration (2.5)].

2.4 Dilution and Preparation Instructions for the Intravenous Administration of the Injection Formulation

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Remove 5 mL of the reconstituted solution from the vial and add it to an infusion bag containing 250 mL (approximately 1.5 mg isavuconazonium sulfate per mL) of compatible diluent. The diluted solution may show visible translucent to white particulates of isavuconazole (which will be removed by in-line filtration).

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Use gentle mixing or roll bag to minimize the formation of particulates. Avoid unnecessary vibration or vigorous shaking of the solution.

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Apply in-line filter with a microporous membrane pore size of 0.2 to 1.2 micron and in-line filter reminder sticker to the infusion bag.

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Do not use a pneumatic transport system.

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The intravenous administration should be completed within 6 hours of dilution at room temperature. If this is not possible, immediately refrigerate (2°C to 8°C / 36°F to 46°F) the infusion solution after dilution and complete the infusion within 24 hours. Do not freeze the infusion solution.

2.5 Preparation Instructions for the Nasogastric Tube Administration of the Injection Formulation

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Utilizing aseptic technique, reconstitute one vial of CRESEMBA for injection (equivalent to 200 mg isavuconazole) with 5 mL of water for injection, USP [see Dosage and Administration (2.3)].

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Withdraw the entire contents (5 mL) of the vial using an appropriate syringe and needle. Discard the needle and cap the syringe.

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To administer, remove the cap from the syringe containing the reconstituted solution and connect the syringe to the nasogastric (NG) tube to deliver the dose. After administering the dose, administer three 5 mL rinses to the NG tube with water [see Clinical Pharmacology (12.3)].

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The reconstituted solution should be administered via nasogastric tube within 1 hour of reconstitution.

2.6 Compatibility for the Injection Formulation

CRESEMBA for injection should only be administered with the following diluents:

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0.9% sodium chloride injection, USP

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5% dextrose injection, USP

5.1 Hepatic Adverse Drug Reactions

Hepatic adverse drug reactions (e.g., elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin) have been reported in clinical trials. The elevations in liver-related laboratory tests were generally reversible and did not require discontinuation of CRESEMBA. Cases of more severe hepatic adverse drug reactions including hepatitis, cholestasis or hepatic failure including death have been reported in patients with serious underlying medical conditions (e.g., hematologic malignancy) during treatment with azole antifungal agents, including CRESEMBA.

Evaluate liver-related laboratory tests at the start and during the course of CRESEMBA therapy. Monitor patients who develop abnormal liver-related laboratory tests during CRESEMBA therapy for the development of more severe hepatic injury. Discontinue CRESEMBA if clinical signs and symptoms consistent with liver disease develop that may be attributable to CRESEMBA [see Adverse Reactions (6.1)].

5.2 Infusion-Related Reactions

Infusion-related reactions including hypotension, dyspnea, chills, dizziness, paresthesia, and hypoesthesia were reported during intravenous administration of CRESEMBA. Discontinue the infusion if these reactions occur [see Adverse Reactions (6.1)].

5.3 Hypersensitivity Reactions

Anaphylactic Reactions

Anaphylactic reactions, with fatal outcome, have been reported during treatment with CRESEMBA. Symptoms including dyspnea, hypotension, generalized erythema with flushing, and urticaria have been reported in such cases often soon after the initiation of treatment.

Severe Skin Reactions

Severe skin reactions, such as Stevens-Johnson syndrome, have been reported during treatment with other azole antifungal agents.

Discontinue CRESEMBA if a patient develops an anaphylactic or severe cutaneous adverse reaction and initiate supportive treatment as needed. There is no information regarding cross-sensitivity between CRESEMBA and other azole antifungal agents though cross-sensitivity between other triazole agents has been reported. When prescribing CRESEMBA to patients with hypersensitivity to other azoles, monitor for signs and symptoms of hypersensitivity reactions.

5.4 Embryo-Fetal Toxicity

Based on findings from animal reproduction studies, CRESEMBA may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus.

Perinatal mortality was significantly increased in the offspring of pregnant rats dosed orally with isavuconazonium sulfate at 90 mg/kg/day (less than half the maintenance human dose based on AUC comparisons) during pregnancy through the weaning period.

Isavuconazonium chloride administration was associated with dose-related increases in the incidences of rudimentary cervical ribs in rats and rabbits at 30 and 45 mg/kg, respectively, doses equivalent to about 0.2 and 0.1 of the human maintenance dose based on AUC comparisons. In rats, dose-related increases in the incidences of zygomatic arch fusion and supernumerary ribs/rudimentary supernumerary ribs were also noted at 30 mg/kg and above, equivalent to one fifth the maintenance human dose based on AUC comparisons [see Use in Specific Populations (8.1)].

Advise females of reproductive potential to use an effective method of contraception during treatment with CRESEMBA and for 28 days after the final dose [see Use in Specific Populations (8.3)].

5.5 Drug Interactions

Coadministration of CRESEMBA with strong CYP3A4 inhibitors such as ketoconazole or high-dose ritonavir and strong CYP3A4 inducers such as rifampin, carbamazepine, St. John’s wort, or long acting barbiturates is contraindicated [see Contraindications (4) and Drug Interactions (7)].

5.6 Drug Particulates

Following dilution, CRESEMBA intravenous formulation may form precipitate from the insoluble isavuconazole. Administer CRESEMBA through an in-line filter [see Dosage and Administration (2.4)].

6.1 Clinical Trial Experience

A total of 403 patients were exposed to CRESEMBA in two clinical trials. The most frequently reported adverse reactions among CRESEMBA-treated patients were nausea (26%), vomiting (25%), diarrhea (22%), headache (17%), elevated liver chemistry tests (16%), hypokalemia (14%), constipation (13%), dyspnea (12%), cough (12%), peripheral edema (11%), and back pain (10%). Serious adverse reactions occurred in 223/403 (55%) of patients and 56/403 (14%) of patients permanently discontinued treatment with CRESEMBA due to an adverse reaction in the two trials. The adverse reactions which most often led to permanent discontinuation of CRESEMBA therapy during the clinical trials were: confusional state (0.7%), acute renal failure (0.7%), increased blood bilirubin (0.5%), convulsion (0.5%), dyspnea (0.5%), epilepsy (0.5%), respiratory failure (0.5%), and vomiting (0.5%).

Patients in the clinical trials were immunocompromised with underlying conditions including hematological malignancy, neutropenia post-chemotherapy, graft-versus-host disease, and hematopoietic stem cell transplant. The patient population was 61% male, had a mean age of 51 years (range 17-92, including 85 patients aged greater than 65 years), and was 79% white and 3% black. One hundred forty-four (144) patients had a duration of CRESEMBA therapy of greater than 12 weeks, with 52 patients receiving CRESEMBA for over six months.

In Trial 1, a randomized, double-blind, active-controlled clinical trial for treatment of invasive aspergillosis, treatment-emergent adverse reactions occurred in 247/257 (96%), and 255/259 (99%) patients in the CRESEMBA and voriconazole treatment groups, respectively. Treatment-emergent adverse reactions resulting in permanent discontinuation were reported in 37 (14%) CRESEMBA-treated patients and 59 (23%) voriconazole-treated patients. Table 2 includes selected treatment-emergent adverse reactions which were reported at an incidence of ≥ 5% during CRESEMBA therapy in Trial 1.

In Trial 2, an open-label, non-comparative trial of CRESEMBA in patients with invasive aspergillosis and renal impairment or invasive mucormycosis, treatment-emergent adverse reactions occurred in 139/146 (95%) of patients in the CRESEMBA treatment group. Adverse reactions resulting in permanent discontinuation were reported in 19 (13%) CRESEMBA-treated patients. The frequencies and types of adverse reactions observed in CRESEMBA-treated patients were similar between Trial 1 and Trial 2.

The following adverse reactions occurred in less than 5% of all CRESEMBA-treated patients in Trial 1 or 2. The list does not include reactions presented in Table 2. This listing includes adverse reactions where a causal relationship to CRESEMBA cannot be ruled out or those which may help the physician in managing the risks to the patients.

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Blood and lymphatic system disorders: agranulocytosis, leukopenia, pancytopenia

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Cardiac disorders: atrial fibrillation, atrial flutter, bradycardia, reduced QT interval on electrocardiogram, palpitations, supraventricular extrasystoles, supraventricular tachycardia, ventricular extrasystoles, cardiac arrest

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Ear and labyrinth disorders: tinnitus, vertigo

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Eye disorders: optic neuropathy

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Gastrointestinal disorders: abdominal distension, gastritis, gingivitis, stomatitis

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General disorders and administration site conditions: catheter thrombosis, malaise, chills

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Hepatobiliary disorders: cholecystitis, cholelithiasis, hepatitis, hepatomegaly, hepatic failure

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Immune system disorders: hypersensitivity

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Injury, poisoning and procedural complications: fall

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Metabolism and nutrition disorders: hypoalbuminemia, hypoglycemia, hyponatremia

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Musculoskeletal and connective tissue disorders: myositis, bone pain, neck pain

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Nervous system disorders: convulsion, dysgeusia, encephalopathy, hypoesthesia, migraine, peripheral neuropathy, paresthesia, somnolence, stupor, syncope, tremor

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Psychiatric disorders: confusion, hallucination, depression

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Renal and urinary disorders: hematuria, proteinuria

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Respiratory, thoracic and mediastinal disorders: bronchospasm, tachypnea

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Skin and subcutaneous tissue disorders: alopecia, dermatitis, exfoliative dermatitis, erythema, petechiae, urticaria

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Vascular disorders: thrombophlebitis

Laboratory effects
In Trial 1, elevated liver transaminases (alanine aminotransferase or aspartate aminotransferase) greater than three times the upper limit of normal were reported at the end of study treatment in 4.4% of patients who received CRESEMBA. Elevations of liver transaminases greater than ten times the upper limit of normal developed in 1.2% of patients who received CRESEMBA.

6.2 Post-Marketing Experience

The following additional adverse reactions have been identified during post-approval use of CRESEMBA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Immune system disorders: anaphylactic reaction

8.1 Pregnancy

Risk Summary

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. In animal reproduction studies, perinatal mortality was increased in the offspring of pregnant rats dosed orally with isavuconazonium sulfate at approximately 0.5 times the clinical exposure during pregnancy through the weaning period. In animal studies when isavuconazonium chloride was administered by oral gavage to pregnant rats and rabbits during organogenesis at exposures corresponding to less than the human maintenance dose, increases in the incidences of multiple skeletal abnormalities, including rudimentary cervical ribs and fused zygomatic arches, were observed (see Data). Advise pregnant women of the potential risk to a fetus [see Warnings and Precautions (5.4)].

The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Isavuconazonium chloride administration during organogenesis (gestational days 6-17 in rats and gestational days 6-18 in rabbits) was associated with dose-related increases in the incidences of rudimentary cervical ribs in rats and rabbits at 30 and 45 mg/kg, respectively, equivalent to about 0.2 and 0.1 times of the clinical exposure based on AUC comparisons. In rats, dose-related increases in the incidences of zygomatic arch fusion and supernumerary ribs/rudimentary supernumerary ribs were also noted at 30 mg/kg and above, equivalent to 0.2 times the human AUC. Skeletal abnormalities have also been observed in embryo-fetal development studies of other azole antifungal agents.

Isavuconazonium sulfate increased perinatal mortality in the pups when orally administered to pregnant rats during pregnancy and lactation (gestational day 6 through postpartum day 20) at doses up to 90 mg/kg/day (approximately 0.5 times the clinical exposure based on AUC comparison). No effect on the duration of pregnancy or delivery was seen in the pups at this same dose.

8.2 Lactation

Risk Summary

There are no data on the presence of isavuconazole in human milk, the effects on the breastfed infant or the effects on milk production. Isavuconazole was present in the milk of lactating rats following intravenous administration. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Therefore, breastfeeding should be discontinued during treatment with CRESEMBA.

8.3 Females and Males of Reproductive Potential

Contraception

CRESEMBA may cause embryo-fetal harm when administered to pregnant women [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1)]. Advise female patients of reproductive potential to use effective contraception during treatment with CRESEMBA and for 28 days after the final dose.

8.4 Pediatric Use

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

8.5 Geriatric Use

Of the 547 patients who received CRESEMBA in the Phase 2 and 3 trials, 86 (16%) of patients were greater than 65 years of age and 20 (4%) were greater than 75 years of age. The pharmacokinetics of isavuconazole are comparable in young and elderly subjects (65 years of age and older) [see Clinical Pharmacology (12.3)]. No dose adjustment of CRESEMBA is needed in elderly patients.

8.6 Renal Impairment

Of the 403 patients who received CRESEMBA in the Phase 3 trials, 79 (20%) of patients had an estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2. No dose adjustment is needed in patients with mild, moderate, or severe renal impairment, including those patients with End-Stage Renal Disease (ESRD) [see Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

No dose adjustment is necessary in patients with mild or moderate hepatic impairment (Child-Pugh Class A and B) [see Clinical Pharmacology (12.3)]. CRESEMBA has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and should be used in these patients only when the benefits outweigh the risks. Clinical monitoring for CRESEMBA-related adverse reactions is recommended when treating patients with severe hepatic impairment [see Warnings and Precautions (5.1)].

12.1 Mechanism of Action

Isavuconazonium sulfate is the prodrug of isavuconazole, an azole antifungal [see Microbiology (12.4)].

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Microbiology

Mechanism of Action

Isavuconazonium sulfate is the prodrug of isavuconazole, an azole antifungal drug. Isavuconazole inhibits the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is responsible for the conversion of lanosterol to ergosterol. An accumulation of methylated sterol precursors and a depletion of ergosterol within the fungal cell membrane weakens the membrane structure and function. Mammalian cell demethylation is less sensitive to isavuconazole inhibition.

Resistance

There is a potential for development of resistance to isavuconazole.

The mechanism of resistance to isavuconazole, like other azole antifungals, is likely due to multiple mechanisms that include substitutions in the target gene CYP51. Changes in sterol profile and elevated efflux pump activity were observed; however, the clinical relevance of these findings is unclear.

In vitro and animal studies suggest cross-resistance between isavuconazole and other azoles. The relevance of cross-resistance to clinical outcome has not been fully characterized; however, patients failing prior azole therapy may require alternative antifungal therapy.

Antimicrobial Activity

Isavuconazole has activity against most strains of the following microorganisms, both in vitro and in clinical infections: Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucorales such as Rhizopus oryzae and Mucormycetes species [see Clinical Studies (14)].

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 2-year rat carcinogenicity study and a 2-year mouse carcinogenicity study, dose-related increases in hepatocellular adenomas and/or carcinomas were observed in male and female B6C3F1/Crl mice, and male, but not female Han Wistar rats at doses as low as 0.1 times the exposure seen in humans administered the maintenance dose. Hepatic hemangiomas were increased in female mice at 300 mg/kg, at an exposure similar to the maintenance dose. Hepatoblastoma were increased in male mice at 100 mg/kg, about 0.4 times the systemic exposures based on AUC comparisons.

Thyroid follicular cell adenomas were observed in male and female rats at doses as low as 60 mg/kg in male rats (about 0.2 times the human clinical maintenance dose). The relevance of the rat thyroid tumors to human carcinogenic risk remains unclear.

A significant increase in the incidence of skin fibromas was seen in male rats at 300 mg/kg, exposures 0.8 times the human exposure at the human clinical maintenance dose. Uterine adenocarcinomas were observed in female rats at 200 mg/kg, at systemic exposures similar to the human exposure at the human clinical maintenance dose.

No mutagenic or clastogenic effects were detected in the in vitro bacterial reverse mutation assay and the in vivo bone marrow micronucleus assay in rats.

Oral administration of isavuconazonium sulfate did not affect the fertility in male or female rats treated at doses up to 90 mg/kg/day (approximately 0.3 times the systemic exposure at the human clinical maintenance dose).

14.1 Treatment of Invasive Aspergillosis

Trial 1 was a randomized, double-blind, non-inferiority active controlled trial which evaluated the safety and efficacy of CRESEMBA versus voriconazole for primary treatment of invasive fungal disease caused by Aspergillus species or other filamentous fungi. Eligible patients had proven, probable, or possible invasive fungal infections per European Organisation for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria1. Patients were stratified by history of allogeneic bone marrow transplant, uncontrolled malignancy at baseline, and by geographic region. The mean age of patients was 51 years (range 17-87) and the majority were Caucasians (78%), male (60%), with fungal disease involving the lungs (95%). At least one Aspergillus species was identified in 30% of the subjects; A. fumigatus and A. flavus were the most common pathogens identified. There were few patients with other Aspergillus species:
A. niger, A. sydowii, A. terreus, and A. westerdijkiae. Baseline risk factors are presented in Table 7.

Patients randomized to receive CRESEMBA treatment were administered a loading dose intravenously of 372 mg of isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) every 8 hours for the first 48 hours. Beginning on Day 3, patients received intravenous or oral therapy of 372 mg of isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) once daily. Patients randomized to receive voriconazole treatment were administered voriconazole intravenously with a loading dose of 6 mg/kg every 12 hours for the first 24 hours followed by 4 mg/kg intravenously every 12 hours for the following 24 hours. Therapy could then be switched to an oral formulation of voriconazole at a dose of 200 mg every 12 hours. In this trial, the protocol-defined maximum treatment duration was 84 days. Mean treatment duration was 47 days for both treatment groups, of which 8 to 9 days was by an intravenous route of administration.

All-cause mortality through Day 42 in the overall population (ITT) was 18.6% in the CRESEMBA treatment group and 20.2% in the voriconazole treatment group for an adjusted treatment difference of -1.0% with 95% confidence interval of -8.0% to 5.9%. Similar results were seen in patients with proven or probable invasive aspergillosis confirmed by serology, culture or histology (see Table 8).

Overall success at End-of-Treatment (EOT) was assessed by a blinded, independent Data Review Committee (DRC) using pre-specified clinical, mycological, and radiological criteria. In the subgroup of patients with proven or probable invasive aspergillosis confirmed by serology, culture or histology, overall success at EOT was seen in 35% of CRESEMBA-treated patients compared to 38.9% of voriconazole-treated patients (see Table 9).

14.2 Treatment of Invasive Mucormycosis

Trial 2, an open-label, non-comparative trial, evaluated the safety and efficacy of a subset of patients with invasive mucormycosis. Thirty-seven (37) patients had proven or probable mucormycosis according to criteria based on those established by the European Organisation for Research and Treatment of Cancer/Mycoses Study Group1. Rhizopus oryzae and Mucormycetes were the most common pathogens identified. There were few patients with other Mucorales: Lichtheimia corymbifera, Mucor amphibiorum, Mucor circinelloides, Rhizomucor pusillus, Rhizopus azygosporus, and Rhizopus microsporus. The patients were white (68%), male (81%), and had a mean age of 49 years (range 22-79). Fifty-nine percent (59%) of patients had pulmonary disease involvement, half of whom also had other organ involvement. The most common non-pulmonary disease locations were sinus (43%), eye (19%), CNS (16%) and bone (14%). Baseline risk factors are presented in Table 10. The Independent Data Review Committee classified patients receiving CRESEMBA as primary therapy, or for invasive mold disease refractory to, or patients intolerant of other antifungal therapy.

Patients were treated with CRESEMBA intravenously or via oral administration at the recommended doses. Median treatment duration was 102 days for patients classified as primary, 33 days for refractory, and 85 days for intolerant [see Dosage and Administration (2.2)].

For patients with invasive mucormycosis, all-cause mortality through Day 42 and success in overall response at the End-of-Treatment as assessed by the Independent Data Review Committee is shown in Table 11. These results provide evidence that CRESEMBA is effective for the treatment of mucormycosis, in light of the natural history of untreated mucormycosis. However, the efficacy of CRESEMBA for the treatment of invasive mucormycosis has not been evaluated in concurrent, controlled clinical trials.

16.1 How Supplied

CRESEMBA Capsules
CRESEMBA (isavuconazonium sulfate) 74.5 mg capsules are supplied as opaque capsules and have a Swedish orange (reddish-brown) body imprinted with the Astellas logo in black ink and a Swedish orange cap imprinted with “557” in black ink. Each capsule contains 74.5 mg isavuconazonium sulfate (equivalent to 40 mg of isavuconazole) and is packaged as follows:

CRESEMBA (isavuconazonium sulfate) 186 mg capsules are supplied as opaque and elongated capsules and have a Swedish orange (reddish-brown) body imprinted with the Astellas logo in black ink and a white cap imprinted with “766” in black ink. Each capsule contains 186 mg isavuconazonium sulfate (equivalent to 100 mg of isavuconazole) and is packaged as follows:

CRESEMBA for Injection
CRESEMBA (isavuconazonium sulfate) for injection is supplied as white to yellow sterile lyophilized powder containing 372 mg isavuconazonium sulfate (equivalent to 200 mg isavuconazole) in a single-dose vial and is packaged as follows:

16.2 Storage and Handling

CRESEMBA Capsules

Store CRESEMBA capsules at 20°C to 25°C (68°F to 77°F) in the original packaging to protect from moisture. Excursions are permitted from 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature].

CRESEMBA for Injection

Store CRESEMBA for injection unreconstituted vials at 2°C to 8°C (36°F to 46°F) in a refrigerator. CRESEMBA for injection is a single-dose vial of unpreserved sterile lyophile.

Following reconstitution of the lyophile with water for injection USP, the reconstituted solution should be used immediately, or stored below 25°C for a maximum of 1 hour prior to preparation of the patient infusion solution [see Dosage and Administration (2.3)]. The prepared infusion solution should be kept for not more than 6 hours at room temperature [20°C to 25°C (68°F to 77°F)] or 24 hours at 2°C to 8°C (36°F to 46°F) prior to use [see Dosage and Administration (2.4)]. For nasogastric tube use, the reconstituted solution should be used within 1 hour of reconstitution [see Dosage and Administration (2.5)].