Isavuconazonium

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

• CRESEMBA ® is an azole antifungal indicated for the treatment of: Invasive aspergillosis ( 1.1 ) and Invasive mucormycosis ( 1.2 ) as follows: • CRESEMBA for injection : adults and pediatric patients 1 year of age and older • CRESEMBA capsules : adults and pediatric patients 6 years of age and older who weigh 16 kilograms (kg) and greater 1.1 Invasive Aspergillosis CRESEMBA ® is indicated for the treatment of invasive aspergillosis as follows: CRESEMBA for injection : adults and pediatric patients 1 year of age and older [see Clinical Studies ( 14.1 ) and Clinical Pharmacology ( 12.4 )] CRESEMBA capsules : adults and pediatric patients 6 years of age and older who weigh 16 kilograms (kg) and greater [see Dosage and Administration ( 2.3 ) Clinical Studies ( 14.1 ) and Clinical Pharmacology ( 12.4 )] 1.2 Invasive Mucormycosis CRESEMBA is indicated for the treatment of invasive mucormycosis as follows: CRESEMBA for injection : adults and pediatric patients 1 year of age and older [see Clinical Studies ( 14.1 ) and Clinical Pharmacology ( 12.3 , 12.4 )] CRESEMBA capsules : adults and pediatric patients 6 years of age and older who weigh 16 kg and greater [see Dosage and Administration …

• • CRESEMBA is contraindicated in persons with known hypersensitivity to isavuconazole. • Coadministration of strong CYP3A4 inhibitors, such as ketoconazole or high-dose ritonavir (400 mg every 12 hours), with CRESEMBA is contraindicated because strong CYP3A4 inhibitors can significantly increase the plasma concentration of isavuconazole [see Drug Interactions ( 7 ) and Clinical Pharmacology ( 12.3 )] .contraindicated

Important Administration Instructions: • CRESEMBA for injection is intended for use in patients who are 1 year of age and older ( 2.1 , 2.3 ). • CRESEMBA for injection via nasogastric (NG) tube administration is intended for use by patients who are 6 years of age and older and weighing 16 kg and greater. ( 2.1 , 2.6 ). • CRESEMBA for injection must be administered through an in-line filter over a minimum of 1 hour. ( 2.1 , 2.5 ). • CRESEMBA capsules are intended for use in patients who are 6 years of age and older and weighing 16 kg and greater ( 2.1 , 2.3 ). • CRESEMBA capsules can be taken with or without food. ( 2.1 ). Recommended Dosage in Adult Patients ( 2.2 ): Recommended Dosage for CRESEMBA in Adult Patients ( 2.2 ) Dosage Form Loading Dose Maintenance Dose Start maintenance doses 12 to 24 hours after the last loading dose CRESEMBA for Injection, 372 mg/vial 372 mg of isavuconazonium sulfate per vial One reconstituted vial (372 mg) intravenously every 8 hours for 6 doses (48 hours) One reconstituted vial (372 mg) intravenously once daily CRESEMBA Capsules, 186 mg 186 mg of isavuconazonium sulfate per capsule Two 186 mg capsules (372 mg) orally every 8 hours for 6 doses (48 hours) Two 186 mg capsules (372 mg) orally once daily CRESEMBA Capsules, 74.5 mg 74.5 mg of isavuconazonium sulfate per capsule Five 74.5 mg capsules (372 mg) orally every 8 hours for 6 doses (48 hours) Five 74.5 mg capsules (372 mg) orally once daily Recommended Dosage in Pediatric Patients ( 2.3 ): • The maximum of any individual loading or daily maintenance dose to be administered to any pediat…

• Hepatic Adverse Drug Reactions: Serious hepatic reactions have been reported. Evaluate liver-related laboratory tests at the start and during the course of CRESEMBA therapy. ( 5.1 ) • Infusion-related reactions were reported during intravenous administration of CRESEMBA. Discontinue the infusion if these reactions occur. ( 5.2 ) • Hypersensitivity Reactions: Anaphylactic reactions, with fatal outcome, have been reported during treatment with CRESEMBA. Serious skin reactions, such as Stevens-Johnson syndrome, have been reported during treatment with other azole antifungal agents. Discontinue CRESEMBA if anaphylactic or serious skin reactions occur, and initiate supportive treatment as needed. ( 5.3 ) • Embryo-Fetal Toxicity: 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. ( 5.4 , 8.1 , 8.3 ) • Drug Interactions: Review patient’s concomitant medications. Several drugs may significantly alter isavuconazole concentrations. Isavuconazole may alter concentrations of several drugs. ( 5.5 , 7 , 12.3 ) • Drug Particulates: Intravenous formulation may form insoluble particulates following reconstitution. Administer CRESEMBA through an in-line filter. ( 2.4 , 5.6 ) 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 following are discussed in more detail in other sections of the labeling: • Hepatic Adverse Drug Reactions [see Warnings and Precautions ( 5.1 )] • Infusion-Related Reactions [see Warnings and Precautions ( 5.2 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )] • Embryo-Fetal Toxicity [see Warnings and Precautions ( 5.4 )] • Adult Patients: The most frequent adverse reactions in adult patients were nausea, vomiting, diarrhea, headache, elevated liver chemistry tests, hypokalemia, constipation, dyspnea, cough, peripheral edema, and back pain. ( 6.1 ) • Pediatric Patients: The most frequent adverse reactions in pediatric patients were diarrhea, abdominal pain, vomiting, elevated liver chemistry tests, rash, nausea, pruritus, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of CRESEMBA cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials Experience in Adult Patients A total of 403 adult patients were exposed to CRESEMBA in two clinical trials.

• Breastfeeding should be discontinued during treatment with CRESEMBA. ( 8.2 ) • Use in patients with severe hepatic impairment only when the benefits outweigh the risks; clinical monitoring for CRESEMBA‑related adverse reactions is recommended. ( 8.7 ) 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.

Metabolism

General Pharmacokinetics In healthy subjects, the pharmacokinetics of isavuconazole following oral administration of CRESEMBA capsules at isavuconazole equivalent doses up to 600 mg per day (6 capsules) are dose proportional ( Table 6 ). Based on a population pharmacokinetics analysis of healthy subjects and patients, the mean plasma half-life of isavuconazole was 130 hours and the mean volume of distribution (V ss ) was approximately 450 L following intravenous administration.

During clinical studies, total daily CRESEMBA doses higher than the recommended dose regimen were associated with an increased rate of adverse reactions. At supratherapeutic doses (three times the recommended maintenance dose) evaluated in a thorough QT study, there were proportionally more treatment-emergent adverse reactions than in the therapeutic dose group (maintenance dose) for the following: headache, dizziness, paresthesia, somnolence, disturbance in attention, dysgeusia, dry mouth, diarrhea, oral hypoesthesia, vomiting, hot flush, anxiety, restlessness, palpitations, tachycardia, photophobia and arthralgia. Adverse reactions leading to discontinuation of study drug occurred in 7 of 39 (17.9%) subjects in the supratherapeutic dose group. Isavuconazole is not removed by hemodialysis. There is no specific antidote for isavuconazole. Treatment should be supportive with appropriate monitoring.

• Mar 6, 2015NDANDA207501Astellas
• Mar 6, 2015NDANDA207500Astellas

1. 1Off Label Use98029%
2. 2Death3189.3%
3. 3Nausea1564.6%
4. 4Febrile Neutropenia1414.1%
5. 5Drug Ineffective1384.0%
6. 6Pyrexia1303.8%
7. 7Pneumonia1213.5%
8. 8Condition Aggravated1143.3%
9. 9Fatigue1063.1%
10. 10Diarrhoea972.8%
11. 11Dyspnoea942.7%
12. 12Drug Interaction932.7%
13. 13Vomiting862.5%
14. 14Product Use In Unapproved Indication802.3%
15. 15Acute Kidney Injury782.3%

The 10 most recently updated of 14 ClinicalTrials.gov registrations naming Isavuconazonium as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Cresemba® in Treating Chinese Patients With IFD Caused by Aspergillus Species or Other Filamentous Fungi
  Completed · Phase 4 · Interventional · 70 enrolled · Pfizer
  NCT05630976updated 2026-05-27
• Post Marketing Surveillance (PMS) Study of Cresemba in Korea.
  Completed · Observational · 94 enrolled · Pfizer
  NCT04744454updated 2026-04-13
• A Study to Understand How the Use of Paxlovid Affected the Healthcare Use in People With Pre-existing Conditions.
  Completed · Observational · 307 enrolled · Pfizer
  NCT04550936updated 2025-12-09
• Fungal Prophylaxis With Isavuconazole for Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant (HCT)
  Completed · Phase 2 · Interventional · 99 enrolled · Memorial Sloan Kettering Cancer Center
  NCT03149055updated 2025-05-16
• A Study to Evaluate Isavuconazonium Sulfate for the Treatment of Invasive Aspergillosis (IA) or Invasive Mucormycosis (IM) in Pediatric Participants
  Completed · Phase 2 · Interventional · 31 enrolled · Astellas Pharma Global Development, Inc.
  NCT03816176updated 2024-12-05
• A Study to Assess Isavuconazole Following a Single Dose of Isavuconazonium Sulfate Intravenous Solution Via Nasogastric (NG) Tube Compared to a Single Dose of Oral Capsules Under Fasting Conditions in Healthy Participants
  Completed · Phase 1 · Interventional · 17 enrolled · Astellas Pharma Global Development, Inc.
  NCT04096157updated 2024-11-20
• A Study of Intravenous and Oral Isavuconazonium Sulfate in Pediatric Patients
  Completed · Phase 1 · Interventional · 49 enrolled · Astellas Pharma Global Development, Inc.
  NCT03241550updated 2024-11-19
• Registry of Patients Treated With Systemic Mold-Active Triazoles
  Completed · Observational · 2,015 enrolled · Astellas Pharma Global Development, Inc.
  NCT03066011updated 2024-10-21
• Isavuconazole for the Prevention of COVID-19-associated Pulmonary Aspergillosis
  Terminated · Phase 3 · Interventional · 8 enrolled · Jeffrey Jenks, MD, MPH
  NCT04707703updated 2022-11-25
• Pharmacokinetics of Isavuconazole in Patients in the Intensive Care Unit
  Completed · Observational · 20 enrolled · Radboud University Medical Center
  NCT04777058updated 2022-10-26

Frequently asked questions

How does Isavuconazonium work?

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

What is Isavuconazonium used for?

According to FDA labeling, Isavuconazonium carries indications including: CRESEMBA ® is an azole antifungal indicated for the treatment of: Invasive aspergillosis ( 1.1 ) and Invasive mucormycosis ( 1.2 ) as follows: • CRESEMBA for injection : adults and pediatric patients 1 year of age and older • CRESEMBA capsules : adults and pediatric patients 6 years of age and older who weigh 16 kilograms (kg) and greater 1.1 Invasive Aspergillosis CRESEMBA ® is indicated for the treatment of invasive aspergillosis as follows: CRESEMBA for injection : adults and pediatric patients 1 year of age and older [see Clinical Studies ( 14.1 ) and Clinical Pharmacology ( 12.4 )] CRESEMBA capsules : adults and pediatric patients 6 years of age and older who weigh 16 kilograms (kg) and greater [see Dosage and Administration ( 2.3 ) Clinical Studies ( 14.1 ) and Clinical Pharmacology ( 12.4 )] 1.2 Invasive Mucormycosis CRESEMBA is indicated for the treatment of invasive mucormycosis as follows: CRESEMBA for injection : adults and pediatric patients 1 year of age and older [see Clinical Studies ( 14.1 ) and Clinical Pharmacology ( 12.3 , 12.4 )] CRESEMBA capsules : adults and pediatric patients 6 years of age and older who weigh 16 kg and greater [see Dosage and Administration …. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What are the brand names for Isavuconazonium?

Isavuconazonium is marketed under brand names including Cresemba.

What are the contraindications for Isavuconazonium?

Isavuconazonium labeling lists contraindications including: • CRESEMBA is contraindicated in persons with known hypersensitivity to isavuconazole. • Coadministration of strong CYP3A4 inhibitors, such as ketoconazole or high-dose ritonavir (400 mg every 12 hours), with CRESEMBA is contraindicated because strong CYP3A4 inhibitors can significantly increase the plasma concentration of isavuconazole [see Drug Interactions ( 7 ) and Clinical Pharmacology ( 12.3 )] .. Always consult the full prescribing information and a clinician.