Drug Interaction:
CYP3A4 inhibitors or inducers may alter the plasma concentrations
of isavuconazole
Appropriate therapeutic drug monitoring and dose adjustment of
immunosuppressants (i.e., tacrolimus, sirolimus, and cyclosporine)
may be necessary when co-administered 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
Indication:
CRESEMBA® (isavuconazonium sulfate) Capsules for oral administration
For Injection for intravenous administration
Initial U.S. Approval: 2015
Proprietary Name- CRESEMBA
Established Name- Isavuconazonium Sulfate
Applicant- Astella Pharma US INC.
Indication- For the treatment of Invasive Aspergillosis and Invasive
Mucormycosis
Approval Date- 3/6/2015
Approved by U.S.FDA on 30-06-2015 (Ref- FDA approved List- 2015)
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.8
Drug Name - Isavuconazonium Sulfate
Active Ingredient- Cresemba Capsule
Date of approval - 3/06/2015
FDA-approved use - To treat adults with invasive asperillous and
invasive mucormycosis, rare but serious infections
Approved by US FDA on 3/06/2015- (Ref- FDA approved List- 2015)
Adverse Reaction:
Most frequent adverse reactions: nausea, vomiting, diarrhea, headache,
elevated liver chemistry tests, hypokalemia, constipation, dyspnea, cough,
peripheral edema, and back pain
Contra-Indications:
CONTRAINDICATIONS
Hypersensitivity to CRESEMBA
Coadministration with strong CYP3A4 inhibitors, such as ketoconazole or
high-dose ritonavir
Coadministration with strong CYP3A4 inducers, such as rifampin,
carbamazepine, St. John’s wort, or long acting barbiturates
Use in patients with familial short QT syndrome
WARNINGS AND PRECAUTIONS
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 .
Infusion-related reactions were reported during intravenous administration of
CRESEMBA. Discontinue the infusion if these reactions occur
Hypersensitivity Reactions: 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 for exfoliative cutaneous reactions
Embryo-Fetal Toxicity: Do not administer to pregnant women unless the benefit
to the mother outweighs the risk to the fetus. Inform pregnant patients of
the hazard
Drug Interactions:
Review patient’s concomitant medications.
Several drugs may significantly alter isavuconazole concentrations.
Isavuconazole may alter concentrations of several drugs
Drug Particulates: Intravenous formulation may form insoluble particulates
following reconstitution. Administer CRESEMBA through an in-line filter
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
CRESEMBA is an azole antifungal indicated for use in the treatment of:
Invasive aspergillosis
Invasive mucormycosis .
DOSAGE AND ADMINISTRATION
CRESEMBA for injection must be administered through an in-line filter over
a minimum of 1 hour .
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 .
Capsules can be taken with or without food
DOSAGE FORMS AND STRENGTHS
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)
Patient Information:
PATIENT COUNSELING INFORMATION
Advise patients to read the FDA-approved patient labeling (Patient Information).
Advise patients that CRESEMBA can be taken with or without food.
Each capsule should be swallowed whole.
Do not chew, crush, dissolve, or open the capsules.
they begin taking other drugs as certain drugs can decrease or increase
the plasma concentrations of CRESEMBA.
CRESEMBA can decrease or increase the plasma concentrations of other drugs.
Advise patients to inform their physician if they are pregnant, plan to become
pregnant, or are nursing.
Marketed and Distributed by:
Astellas Pharma US, Inc.
Northbrook, IL 60062
Licensed from: Basilea Pharmaceutica International Ltd.
14D023-ISA
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLGY-
1.Mechanism of action
Isavuconazonium sulfate is a prodrug of isaconazole and is an anti-fungal
12.3 Pharmacokinetics
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
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 (Vss) was approximately 450 L
following intravenous administration
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category C
There are no adequate and well-controlled clinical studies of CRESEMBA in pregnant
women. CRESEMBA should be used during pregnancy only if the potential benefit
to the patient outweighs the risk to the fetus. Women who become pregnant during
CRESEMBA treatment are encouraged to contact their physician
2.Nursing Mothers
Isavuconazole is excreted in the milk of lactating rats following intravenous
administration. Mothers should not breast feed while taking CRESEMBA.
3. Pediatric Use
The safety and efficacy of CRESEMBA in pediatric patients less than 18 years
of age have not been established.
4. 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)
. No dose adjustment of CRESEMBA is needed in elderly patients
Manufacturer Details