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Important Drug Information Subject: Temporary importation of Doxorubicin Hydrochloride 50 mg Powder for Injection (50 mg/vial) to address drug shortage issue May 2016 Dear Health Care Provider, Due to the current critical shortage of Doxorubicin Hydrochloride for Injection, USP in the United States (U.S.) market, Hospira, Inc., a Pfizer company (Hospira), is coordinating with the U.S. Food and Drug Administration (FDA) to increase the availability of the drug. Hospira has initiated temporary importation of non-U.S. approved product, Doxorubicin Hydrochloride 50 mg Powder for Injection from Hospira Limited, United Kingdom (Hospira Limited): Lot DO21502A, expiration 12/2017. The Doxorubicin Hydrochloride 50 mg Powder for Injection from Hospira Limited is manufactured by Zydus Hospira Oncology Private Limited (ZHOPL) in Ahmedabad, India, at an FDA-inspected facility that is in compliance with current good manufacturing practice requirements. At this time, no other entity except Hospira Limited or their distributor Hospira is authorized by the FDA to import or distribute Doxorubicin Hydrochloride 50 mg Powder for Injection in the U.S. FDA has not approved Hospira Limited’s Doxorubicin Hydrochloride 50 mg Powder for Injection (50 mg/vial) product in the U.S. Effective immediately, and during this temporary period, Hospira will offer the following presentation of Doxorubicin Hydrochloride for Injection: Product Strength Size Marketing Authorization # Doxorubicin Hydrochloride PL 4515/0073 50 mg/vial Box of 1 vial 50 mg Powder for Injection (United Kingdom) The barcode used for Hospira Limited’s non-U.S. approved Doxorubicin Hydrochloride 50 mg Powder for Injection is an international pharmaceutical manufacturing code and may not be appropriately recognized by scanning systems used in the U.S. Institutions should confirm the barcode systems do not provide incorrect information when the product is scanned. Alternative procedures should be followed to assure that the correct drug product is being used and administered to individual patients. © 2016 Hospira, Inc., a Pfizer company, 275 North Field Drive, Lake Forest, IL 60045 PP-HSP-USA-0096 -April 2016 1 of 13 It is important to note that there are substantive differences in the format and content of the labeling between the U.S.-approved Doxorubicin Hydrochloride for Injection, USP and the Hospira Limited’s Doxorubicin Hydrochloride 50 mg Powder for Injection. The product comparison tables attached highlight the differences between the reference listed drug (RLD) Doxorubicin Hydrochloride for Injection, USP and Hospira Limited’s non-U.S. approved Doxorubicin Hydrochloride 50 mg Powder for Injection. This letter and the attachments are not intended as a complete description of the benefits and risks related to the use of Doxorubicin Hydrochloride 50 mg Powder for Injection. Please refer to the package insert for the FDA-approved Doxorubicin Hydrochloride for Injection, USP for full prescribing information. To place an order, or if you have any questions, customers can contact Hospira directly by calling Customer Care at 1-877-946-7747 (Monday – Friday, 7AM-6PM CDT). Hospira will make reasonable attempts to fill your orders. Hospira will be closely monitoring the distribution of Doxorubicin Hydrochloride 50 mg Powder for Injection to help manage supply. For clinical inquiries, please contact Hospira Medical Communications at 1-800-615-0187 (available 24 hours a day/7 days per week), or email at [email protected]. To report adverse events or quality problems associated with the use of this product, please call Hospira Global Complaint Management at 1-800-441-4100 (Monday – Friday, 8AM-5PM CDT), or email at [email protected]. Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax. Complete and submit the report Online: www.fda.gov/medwatch/report.htm. Regular Mail or Fax: Download form www.fda.gov/MedWatch/getforms.htm or call 1- 800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178 (1-800-332-0178). For Full U.S.-approved Prescribing Information for Doxorubicin Hydrochloride for Injection, including the BOXED WARNING, please visit: http://www.accessdata.fda.gov/spl/data/bb405a38-3e4e-49af-b30d-fb728f209022/bb405a38- 3e4e-49af-b30d-fb728f209022.xml For Full Prescribing Information for Hospira Limited’s product, please visit: http://www.pfizerinjectables.com/sites/default/files/doxorubicinSmPC-HospiraUK.pdf © 2016 Hospira, Inc., a Pfizer company, 275 North Field Drive, Lake Forest, IL 60045 PP-HSP-USA-0096 -April 2016 2 of 13 Product Vial and Carton Comparison Table Doxorubicin Hydrochloride for Injection, USP- Doxorubicin Hydrochloride 50 mg Powder for doxorubicin hydrochloride injection, powder, Injection – Hospira Limited Vial Label lyophilized, for solution – Reference Listed Drug (RLD) (Mylan Institutional LLC) Vial Label Not Available Doxorubicin Hydrochloride for Injection, USP- Doxorubicin Hydrochloride 50 mg Powder for doxorubicin hydrochloride injection, powder, Injection – Hospira Limited Carton Label lyophilized, for solution – Reference Listed Drug (RLD) (Mylan Institutional LLC) Carton Label © 2016 Hospira, Inc., a Pfizer company, 275 North Field Drive, Lake Forest, IL 60045 PP-HSP-USA-0096 -April 2016 4 of 13 Product Label Comparison Table Doxorubicin Hydrochloride for Injection, USP - Doxorubicin Hydrochloride 50 mg Powder for doxorubicin hydrochloride injection, powder, Injection – Hospira Limited lyophilized, for solution – Reference Listed Drug (RLD) (Mylan Institutional, LLC) BOXED WARNING WARNING: CARDIOMYOPATHY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS and SEVERE MYELOSUPPRESSION Cardiomyopathy: Myocardial damage, including acute left ventricular failure can occur with doxorubicin hydrochloride. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 1% to 20% for cumulative doses ranging from 300 mg/m2 to 500 mg/m2 when doxorubicin hydrochloride is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess LVEF before and regularly during and after treatment with doxorubicin hydrochloride [see Warnings and Precautions (5.1)]. Secondary Malignancies : Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including doxorubicin hydrochloride [see Warnings and Precautions (5.2)]. Extravasation and Tissue Necrosis : Extravasation of doxorubicin hydrochloride can result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate the drug and apply ice to the affected area [see Warnings and Precautions (5.3)]. Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions , hospitalization, and death may occur [see Warnings and Precautions (5.4)]. Indications and contraindications Doxorubicin hydrochloride, USP is an anthracycline Therapeutic indications topoisomerase II inhibitor indicated: Doxorubicin has been used successfully in the treatment as a component of multiagent adjuvant of neoplastic conditions such as acute leukaemia, soft chemotherapy for treatment of women with axillary tissue and osteogenic sarcomas, breast carcinoma, lymph node involvement following resection of lymphomas, bronchogenic (lung) carcinoma. It has also primary breast cancer. been used in the treatment of paediatric malignancy. for the treatment of: acute lymphoblastic leukemia, Doxorubicin is frequently used in combination acute myeloblastic leukemia, Hodgkin lymphoma, chemotherapy regimen involving other cytotoxic drugs. Non-Hodgkin lymphoma, metastatic breast cancer, Doxorubicin can be used in the treatment of metastatic Wilms' tumor, metastatic non-metastatic transitional cell carcinoma, carcinoma in neuroblastoma,, metastatic soft tissue sarcoma, situ and papillary tumours of the bladder, by intravesical metastatic bone sarcomas, metastatic ovarian administration. carcinoma, metastatic transitional cell bladder carcinoma, metastatic thyroid carcinoma, metastatic © 2016 Hospira, Inc., a Pfizer company, 275 North Field Drive, Lake Forest, IL 60045 PP-HSP-USA-0096 -April 2016 5 of 13 Product Label Comparison Table gastric carcinoma, metastatic bronchogenic carcinoma. Contraindications Doxorubicin hydrochloride is contraindicated in Hypersensitivity to doxorubicin or any of the excipients. patients with: Severe myocardial insufficiency [see Warnings and Dosage should not be repeated in cases of bone marrow Precautions (5.1)] depression or buccal ulceration or buccal burning Recent (occurring within the past 4-6 weeks) sensation, which can precede ulceration. myocardial infarction [see Warnings and Precautions (5.1)] Severe persistent drug-induced myelosuppression [see Warnings and Precautions (5.4)] Severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin level greater than 5 mg/dL) [see Warnings and Precautions (5.5)] Severe hypersensitivity reaction to doxorubicin hydrochloride including anaphylaxis [see Adverse Reactions (6.2)] Dosage and Administration Recommended Dose Intravenous administration Adjuvant Breast Cancer When used as a single agent, the recommended dosage 2 The recommended dose of doxorubicin
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