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

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

Administer RELEUKO at least 24 hours after cytotoxic chemotherapy. Do not administer RELEUKO 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 RELEUKO therapy. Therefore, to ensure a sustained therapeutic response‚ administer RELEUKO 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 RELEUKO therapy needed to attenuate chemotherapy-induced neutropenia may be dependent on the myelosuppressive potential of the chemotherapy regimen employed.

Dosage in Patients with Cancer Undergoing Bone Marrow Transplantation

The recommended dosage of RELEUKO 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 RELEUKO 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 RELEUKO against the neutrophil response (see Table 1).

a If ANC decreases to less than 1,000/mm3 at any time during the 5 mcg/kg/day administration‚ increase RELEUKO to 10 mcg/kg/day‚ and then follow the above steps.

Dosage in Patients with Severe Chronic Neutropenia

Prior to starting RELEUKO 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 RELEUKO 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 RELEUKO 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.

Important Administration Instructions

RELEUKO is supplied in single-dose vials and single-dose prefilled syringes [see Dosage Forms and Strengths (3)]. Prior to use‚ remove the vial or prefilled syringe from the refrigerator and allow RELEUKO 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. 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). Do not administer RELEUKO if particulates or discoloration are observed.

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

Subcutaneous Injection

Inject RELEUKO subcutaneously in the outer area of upper arms, abdomen, thighs, or upper outer areas of the buttock. If patients or caregivers are to administer RELEUKO, 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)].

Patient self-administration and administration by a caregiver may benefit from training by a healthcare professional. Training by the healthcare provider should aim to demonstrate to those patients and caregivers how to measure the dose of RELEUKO, and the focus should be on ensuring that a patient or caregiver can successfully perform all 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 RELEUKO or whether the patient would benefit from a different RELEUKO presentation.

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

Administration Instructions for the Prefilled Syringe

The RELUEKO 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 RELEUKO 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 of RELUEKO single-dose vial is recommended.

Administration Instructions for Dilution

If required for intravenous administration‚ RELEUKO 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). RELEUKO 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)‚ RELEUKO 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 RELEUKO solution can be stored at room temperature for up to 4 hours. This 4-hour time period includes the time during room temperature storage of the infusion solution and the duration of the infusion.