NIVESTYM Solution for injection Ref.[10897] Active ingredients: Filgrastim

2.1 Dosage in Patients with Cancer Receiving Myelosuppressive Chemotherapy or Induction and/or Consolidation Chemotherapy for AML

The recommended starting dosage of NIVESTYM 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 NIVESTYM 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 NIVESTYM if the ANC increases beyond 10‚000/mm³ [see Warnings and Precautions (5.10)].

Administer NIVESTYM at least 24 hours after cytotoxic chemotherapy. Do not administer NIVESTYM within the 24-hour period prior to chemotherapy [see Warnings and Precautions (5.13)]. A transient increase in neutrophil count is typically seen 1 to 2 days after initiation of NIVESTYM therapy. Therefore, to ensure a sustained therapeutic response‚ administer NIVESTYM daily for up to 2 weeks or until the ANC has reached 10‚000/mm³ following the expected chemotherapy-induced neutrophil nadir. The duration of NIVESTYM 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 NIVESTYM 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 NIVESTYM 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 NIVESTYM against the neutrophil response (see Table 1).

Table 1. Recommended Dosage Adjustments During Neutrophil Recovery in Patients with Cancer Following BMT:

^* If ANC decreases to less than 1000/mm at any time during the 5 mcg/kg/day administration‚ increase NIVESTYM to 10 mcg/kg/day‚ and then follow the above steps.

2.3 Dosage in Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy

The recommended dosage of NIVESTYM for the mobilization of autologous peripheral blood progenitor cells (PBPC) is 10 mcg/kg/day given by subcutaneous injection. Administer NIVESTYM for at least 4 days before the first leukapheresis procedure and continue until the last leukapheresis. Although the optimal duration of NIVESTYM 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 [see Clinical Studies (14.4)]. Monitor neutrophil counts after 4 days of NIVESTYM‚ and discontinue NIVESTYM 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 NIVESTYM 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 NIVESTYM 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 NIVESTYM 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 Important Administration Instructions

Patient self-administration and administration by a caregiver may benefit from training by a healthcare professional. Training should aim to demonstrate to those patients and caregivers how to measure the dose using the prefilled syringe, and the focus should be on ensuring that a patient or caregiver can successfully perform all of the steps in the Instructions for Use of NIVESTYM prefilled syringe with BD UltraSafe Plus 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 NIVESTYM [see Instructions for Use].

NIVESTYM prefilled syringe with BD UltraSafe Plus 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 NIVESTYM less than 0.3 mL (180 mcg) for direct administration. 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. For direct administration of doses less than 0.3 mL (180 mcg) use NIVESTYM single-dose vial.

NIVESTYM is supplied in single-dose vials (for subcutaneous use or intravenous infusion) and single-dose prefilled syringes (for subcutaneous use) [see Dosage Forms and Strengths (3)]. Prior to use‚ remove the vial or prefilled syringe from the refrigerator and allow NIVESTYM to reach room temperature for a minimum of 30 minutes and a maximum of 24 hours. Discard any vial or prefilled syringe left at room temperature for greater than 24 hours. Visually inspect NIVESTYM for particulate matter and discoloration prior to administration (the solution is clear and colorless). Do not administer NIVESTYM if particulates or discoloration are observed.

Discard unused portion of NIVESTYM in vials or prefilled syringes; do not re-enter the vial. Do not save unused drug for later administration.

Subcutaneous Injection

Inject NIVESTYM subcutaneously in the outer area of upper arms, abdomen, thighs, or upper outer areas of the buttock. If patients or caregivers are to administer NIVESTYM, instruct them in appropriate injection technique and ask them to follow the subcutaneous injection procedures in the Instructions for Use for the vial or prefilled syringe [see Patient Counseling Information (17)].

Training by the healthcare provider should aim to demonstrate to those patients and caregivers how to measure the dose of NIVESTYM, 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. 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 NIVESTYM or whether the patient would benefit from a different NIVESTYM presentation. If a patient or caregiver experiences difficulty measuring the required dose, especially if it is other than the entire contents of the NIVESTYM prefilled syringe, use of the NIVESTYM vial may be considered.

If the patient or caregiver misses a dose of NIVESTYM, instruct them to contact their healthcare provider.

Administration Instructions for the Prefilled Syringe

The NIVESTYM syringe plunger stopper and needle cover are not made with natural rubber latex.

Administration Instructions for Dilution (Vial Only)

If required for intravenous administration‚ NIVESTYM (vial only) may be diluted in 5% Dextrose Injection, USP from a concentration of 300 mcg/mL to 5 mcg/mL (do not dilute to a final concentration less than 5 mcg/mL). NIVESTYM 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)‚ NIVESTYM is compatible with glass bottles‚ polyvinyl chloride (PVC) and polyolefin intravenous bags‚ and polypropylene syringes. Do not dilute with saline at any time because the product may precipitate.

Diluted NIVESTYM solution can be stored at room temperature 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.

The maximum tolerated dose of filgrastim products has not been determined. In filgrastim clinical trials of patients with cancer receiving myelosuppressive chemotherapy‚ WBC counts >100‚000/mm³ have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. Patients in the BMT studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day.

Store NIVESTYM in the refrigerator at 2° to 8°C (36° to 46°F) in the original carton to protect from light. Do not leave NIVESTYM in direct sunlight. Avoid freezing; if frozen, thaw in the refrigerator before administration. Discard NIVESTYM if frozen more than once. Avoid shaking. Transport via a pneumatic tube has not been studied.