DRUG INTERACTIONS-(summary)

 • 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 

Novel Drug Approvals for 2015

1.Name                        BALVERSA

2.Active ingredient-    Erdafitinib- (Apr 2015)

3. Indication-               Anti-cancer drug

Date of Approval  2/23/2015

HIGHLIGHTS OF PRESCRIBING INFORMATION-

 These highlights do not include all the information needed to use                          CRESEMBA safely and effectively.

See full prescribing information for CRESEMBA. CRESEMBA® (isavuconazonium sulfate) Capsules for oral administration For Injection for intravenous administration

Initial U.S. Approval: 2015

INDICATIONS AND USAGE-

 CRESEMBA is an azole antifungal indicated for use in the treatment of: • Invasive aspergillosis

 • Invasive mucormycosis

ADVERSE REACTIONS-

 Most frequent adverse reactions: nausea, vomiting, diarrhea, headache, elevated liver chemistry tests, hypokalemia, constipation, dyspnea, cough, peripheral edema, and back pain

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 

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 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.

Advise patients to inform their physician if they are taking other drugs or before 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.

Product of Portugal Marketed and Distributed by: Astellas Pharma US, Inc. Northbrook, IL 60062 Licensed from: Basilea Pharmaceutica International Ltd. Approved: March 2015 14D023-ISA

 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.

Risk Summary-                                                                                                                   Based on animal data, CRESEMBA is predicted to have the potential for increasing the risk of adverse developmental outcomes above background risk.

3 Nursing Mothers-                                                                                                Isavuconazole is excreted in the milk of lactating rats following intravenous administration. Mothers should not breast feed while taking CRESEMBA. 8.4 Pediatric Use The safety and efficacy of CRESEMBA in pediatric patients less than 18 years of age have not been established.

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.

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/1.73m2 .

No dose adjustment is needed in patients with mild, moderate, or severe renal impairment, including those patients with End Stage Renal Disease (ESRD)

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

CRESEMBA has not been studied in patients with severe hepatic impairment (ChildPugh 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