Filgrastim-sndzdosage

Patients with cancer receiving myelosuppressive chemotherapy or induction and/or consolidation chemotherapy for AML o Recommended starting dose is 5 mcg/kg/day subcutaneous injection, short intravenous infusion (15 to 30 minutes), or continuous intravenous infusion. See Full Prescribing Information for recommended dosage adjustments and timing of administration

Patients with cancer undergoing bone marrow transplantation o 10 mcg/kg/day given as an intravenous infusion no longer than 24 hours. See Full Prescribing Information for recommended dosage adjustments and timing of administration.

Patients undergoing autologous peripheral blood progenitor cell collection and therapy o 10 mcg/kg/day subcutaneous injection o Administer for at least 4 days before first leukapheresis procedure and continue until last leukapheresis

Patients with congenital neutropenia o Recommended starting dose is 6 mcg/kg subcutaneous injection twice daily

Patients with cyclic or idiopathic neutropenia o Recommended starting dose is 5 mcg/kg subcutaneous injection daily

Patients acutely exposed to myelosuppressive doses of radiation o 10 mcg/kg/day subcutaneous injection

Direct administration of less than 0.3 mL (180 mcg) using ZARXIO prefilled syringe is not recommended due to potential for dosing errors

2.1 Dosage in

Patients with Cancer Receiving Myelosuppressive Chemotherapy or Induction and/or Consolidation Chemotherapy for AML The recommended starting dosage of ZARXIO is 5 mcg/kg/day‚ administered as a single daily injection by subcutaneous injection‚ by short intravenous infusion (15 to 30 minutes)‚ or by continuous intravenous infusion. Obtain a complete blood count (CBC) and platelet count before instituting ZARXIO therapy and monitor twice weekly during therapy. Consider dose escalation in increments of 5 mcg/kg for each chemotherapy cycle‚ according to the duration and severity of the absolute neutrophil count (ANC) nadir. Recommend stopping ZARXIO if the ANC increases beyond 10‚000/mm 3. Administer ZARXIO at least 24 hours after cytotoxic chemotherapy. Do not administer ZARXIO within the 24-hour period prior to chemotherapy. A transient increase in neutrophil count is typically seen 1 to 2 days after initiation of ZARXIO therapy. Therefore, to ensure a sustained therapeutic response‚ administer ZARXIO daily for up to 2 weeks or until the ANC has reached 10‚000/mm 3 following the expected chemotherapy-induced neutrophil nadir. The duration of ZARXIO therapy needed to attenuate chemotherapy-induced neutropenia may be dependent on the myelosuppressive potential of the chemotherapy regimen employed.

2.2 Dosage in

Patients with Cancer Undergoing Bone Marrow Transplantation The recommended dosage of ZARXIO following bone marrow transplantation (BMT) is 10 mcg/kg/day given as an intravenous infusion no longer than 24 hours. Administer the first dose of ZARXIO at least 24 hours after cytotoxic chemotherapy and at least 24 hours after bone marrow infusion. Monitor CBCs and platelet counts frequently following marrow transplantation. During the period of neutrophil recovery‚ titrate the daily dosage of ZARXIO against the neutrophil response (see Table 1). Table 1. Recommended Dosage Adjustments During Neutrophil Recovery in Patients with Cancer Following BMT Absolute Neutrophil Count ZARXIO Dosage Adjustment When ANC greater than 1,000/mm 3 for 3 consecutive days Reduce to 5 mcg/kg/day If ANC decreases to less than 1,000/mm 3 at any time during the 5 mcg/kg/day administration‚ increase ZARXIO to 10 mcg/kg/day‚ and then follow the above steps. Then, if ANC remains greater than 1,000/mm 3 for 3 more consecutive days Discontinue ZARXIO Then, if ANC decreases to less than 1,000/mm 3 Resume at 5 mcg/kg/day

2.3 Dosage in

Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy The recommended dosage of ZARXIO for the mobilization of autologous peripheral blood progenitor cells (PBPC) is 10 mcg/kg/day given by subcutaneous injection. Administer ZARXIO for at least 4 days before the first leukapheresis procedure and continue until the last leukapheresis. Although the optimal duration of ZARXIO administration and leukapheresis schedule have not been established‚ administration of filgrastim for 6 to 7 days with leukaphereses on days 5‚ 6‚ and 7 was found to be safe and effective. Monitor neutrophil counts after 4 days of ZARXIO‚ and discontinue ZARXIO if the white blood cell (WBC) count rises to greater than 100‚000/mm 3.

2.4 Dosage in

Patients with Severe Chronic Neutropenia Prior to starting ZARXIO in patients with suspected chronic neutropenia, confirm the diagnosis of severe chronic neutropenia (SCN) by evaluating serial CBCs with differential and platelet counts‚ and evaluating bone marrow morphology and karyotype. The use of ZARXIO prior to confirmation of a correct diagnosis of SCN may impair diagnostic efforts and may thus impair or delay evaluation and treatment of an underlying condition‚ other than SCN‚ causing the neutropenia. The recommended starting dosage in patients with Congenital Neutropenia is 6 mcg/kg as a twice daily subcutaneous injection and the recommended starting dosage in patients with Idiopathic or Cyclic Neutropenia is 5 mcg/kg as a single daily subcutaneous injection. Dosage Adjustments in Patients with Severe Chronic Neutropenia Chronic daily administration is required to maintain clinical benefit. Individualize the dosage based on the patient’s clinical course as well as ANC. In the SCN postmarketing surveillance study, the reported median daily doses of filgrastim were: 6 mcg/kg (congenital neutropenia), 2.1 mcg/kg (cyclic neutropenia), and 1.2 mcg/kg (idiopathic neutropenia). In rare instances, patients with congenital neutropenia have required doses of filgrastim greater than or equal to 100 mcg/kg/day. Monitor CBCs for Dosage Adjustments During the initial 4 weeks of ZARXIO therapy and during the 2 weeks following any dosage adjustment‚ monitor CBCs with differential and platelet counts. Once a patient is clinically stable‚ monitor CBCs with differential and platelet counts monthly during the first year of treatment. Thereafter, if the patient is clinically stable, less frequent routine monitoring is recommended.

2.5 Dosage in

Patients Acutely Exposed to Myelosuppressive Doses of Radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) The recommended dosage of ZARXIO is 10 mcg/kg as a single daily subcutaneous injection for patients exposed to myelosuppressive doses of radiation. Administer ZARXIO as soon as possible after suspected or confirmed exposure to radiation doses greater than 2 gray (Gy). Estimate a patient’s absorbed radiation dose (i.e., level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics. Obtain a baseline CBC and then serial CBCs approximately every third day until the ANC remains greater than 1,000/mm 3 for 3 consecutive CBCs. Do not delay administration of ZARXIO if a CBC is not readily available. Continue administration of ZARXIO until the ANC remains greater than 1,000/mm 3 for 3 consecutive CBCs or exceeds 10,000/mm 3 after a radiation-induced nadir.

2.6 Important

Administration Instructions ZARXIO (for subcutaneous use or intravenous use) is supplied in single-dose vials and in single-dose prefilled syringes. Administration Instructions for Subcutaneous Injection Inject ZARXIO subcutaneously in the outer area of upper arms, abdomen, thighs, or upper outer areas of the buttock. If patients or caregivers are to administer ZARXIO, instruct them in appropriate injection technique and ask them to follow the subcutaneous injection procedures in the Instructions for Use for prefilled syringe with BD UltraSafe Passive ® Needle Guard or for the vial. If the patient or caregiver misses a dose of ZARXIO, instruct them to contact their healthcare provider. Patients who will self-administer and caregivers who will administer to the patient may benefit from training by a healthcare professional. Training should aim to demonstrate to those patients and caregivers how to measure the dose of ZARXIO, and the focus should be on ensuring that a patient or caregiver can successfully perform all of the steps in the Instructions for Use for the vial or prefilled syringe with BD UltraSafe Passive ® Needle Guard. If a patient or caregiver is not able to demonstrate that they can measure the dose and administer the product successfully, you should consider whether the patient is an appropriate candidate for self-administration of ZARXIO prefilled syringe or whether the patient would benefit from the ZARXIO vial presentation. If a patient or caregiver experiences difficulty measuring the required dose, especially if it is other than the entire content of the ZARXIO prefilled syringe, use of the ZARXIO vial may be considered. Instructions for the Prefilled Syringe ZARXIO prefilled syringe with BD UltraSafe Passive ® Needle Guard is not designed to allow for direct administration of doses of less than 0.3 mL (180 mcg). The spring-mechanism of the needle guard apparatus affixed to the prefilled syringe interferes with the visibility of the graduation markings on the syringe barrel corresponding to 0.1 mL and 0.2 mL. The visibility of these markings is necessary to accurately measure doses of ZARXIO less than 0.3 mL (180 mcg) for direct administration to patients. Thus, the direct administration to patients requiring doses of less than 0.3 mL (180 mcg) is not recommended due to the potential for dosing errors. If less than 0.3 mL is needed the ZARXIO single-dose vial should be used. The prefilled syringe with safety guard is not made with natural rubber latex. Prior to use‚ remove the prefilled syringe from the refrigerator and allow ZARXIO to reach room temperature [between 20°C to 25°C (68°F to 77°F)] for a minimum of 30 minutes. If not used immediately, the prefilled syringe may be stored at room temperature for up to 8 days. Discard any prefilled syringe left at room temperature for greater than 8 days. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit (the solution is clear and colorless to slightly yellowish). Do not administer ZARXIO if particulates or discoloration are observed. Discard unused portion of ZARXIO in prefilled syringes. Do not save unused drug for later administration. Instructions for the Single-dose vial Prior to use‚ remove the vial from the refrigerator and allow ZARXIO to reach room temperature for a minimum of 30 minutes. If not used immediately, the vial may be stored at room temperature for up to 8 days. Discard any vial left at room temperature for greater than 8 days. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit (the solution is clear and colorless to slightly yellowish). Do not administer ZARXIO if particulates or discoloration are observed. The vial stopper is not made with natural rubber latex. Discard the unused portion of ZARXIO in single-dose vial and do not re-enter the vial. Do not save unused drug for later administration. Administration Instructions for Dilution If required for intravenous administration, ZARXIO may be diluted in 5% Dextrose Injection, USP to concentrations between 5 mcg/mL and 15 mcg/mL. ZARXIO diluted to concentrations from 5 mcg/mL to 15 mcg/mL should be protected from adsorption to plastic materials by the addition of Albumin (Human) to a final concentration of 2 mg/mL. When diluted in 5% Dextrose Injection, USP or 5% Dextrose plus Albumin (Human)‚ ZARXIO is compatible with glass, polyvinylchloride, polyolefin, and polypropylene. Do not dilute with Sodium Chloride Injection at any time because the product may precipitate. Diluted ZARXIO solution from ZARXIO prefilled syringe can be stored at room temperature [between 20℃ to 25℃ (68℉ to 77℉)] for up to 24 hours. This 24‑hour time period includes the time during room temperature storage of the infusion solution and the duration of the infusion. Diluted ZARXIO solution from ZARXIO vial can be stored refrigerated [2°C to 8°C (36°F to 46°F)] for up to 24 hours or at room temperature [between 20℃ to 25℃ (68℉ to 77℉)] for up to 4 hours, including the time during room temperature storage of the infusion solution and the duration of the infusion.