Filgastrim

Filgastrim
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];

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Overview

Filgastrim is a colony stimulating factor that is FDA approved for the treatment of severe neutropenia in patients with non‑myeloid malignancies receiving myelosuppressive anti‑cancer drugs associated with a clinically significant incidence of febrile neutropenia. Common adverse reactions include bone pain.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Dosage

• The recommended dose of GRANIX is 5 mcg/kg per day administered as a subcutaneous injection. Administer the first dose of GRANIX no earlier than 24 hours following myelosuppressive chemotherapy. Do not administer GRANIX within 24 hours prior to chemotherapy.
• Daily dosing with GRANIX should continue until the expected neutrophil nadir is passed and the neutrophil count has recovered to the normal range. Monitor complete blood count (CBC) prior to chemotherapy and twice per week until recovery.

General Considerations for Administration

• GRANIX may be administered by either a healthcare professional or by a patient or caregiver. Before a decision is made to allow GRANIX to be administered by a patient or caregiver, ensure that the patient is an appropriate candidate for self-administration or administration by a caregiver. Proper training on storage, preparation, and administration technique should be provided. If a patient or caregiver is not an appropriate candidate for any reason, then in such patients, GRANIX should be administered by a healthcare professional.
• Dispense only the pre-filled syringe without a safety needle guard device to patient or caregiver. Instruct patients and caregivers to follow the Instructions for Use provided with the GRANIX pre-filled syringe to properly administer an injection after training by a healthcare professional.
• Visually inspect parenteral drug products for particulate matter and discoloration prior to administration.
• Do not administer GRANIX if discoloration or particulates are observed.
• The prefilled syringe is for single use only. Discard unused portions.
• Recommended sites for subcutaneous GRANIX injections include the abdomen (except for the two-inch area around the navel), the front of the middle thighs, the upper outer areas of the buttocks, or the upper back portion of the upper arms. The injection site should be varied daily. GRANIX should not be injected into an area that is tender, red, bruised or hard, or that has scars or stretch marks.

Instructions for Use of the Safety Needle Guard Device by Healthcare Professionals

Hold the syringe assembly by the open sides of the device and remove the needle shield.

• Step Nº1:

• Step Nº2:

• Step Nº3:

• Step Nº4:

• Step Nº5:

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Filgastrim in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Filgastrim in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Filgastrim FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Filgastrim in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Filgastrim in pediatric patients.

Contraindications

None

Warnings

Splenic Rupture

• Splenic rupture, including fatal cases, can occur following administration of human granulocyte colony-stimulating factors. In patients who report upper abdominal or shoulder pain after receiving GRANIX, discontinue GRANIX and evaluate for an enlarged spleen or splenic rupture.

Acute Respiratory Distress Syndrome (ARDS)

• Acute respiratory distress syndrome (ARDS) can occur in patients receiving human granulocyte colony-stimulating factors. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving GRANIX, for ARDS. Discontinue GRANIX in patients with ARDS.

Allergic Reactions

• Serious allergic reactions including anaphylaxis can occur in patients receiving human granulocyte colony-stimulating factors. Reactions can occur on initial exposure. The administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine may reduce the severity of the reactions. Permanently discontinue GRANIX in patients with serious allergic reactions. Do not administer GRANIX to patients with a history of serious allergic reactions to filgrastim or pegfilgrastim.

Use in Patients with Sickle Cell Disease

• Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disease receiving human granulocyte colony-stimulating factors. Consider the potential risks and benefits prior to the administration of human granulocyte colony-stimulating factors in patients with sickle cell disease. Discontinue GRANIX in patients undergoing a sickle cell crisis.

Capillary Leak Syndrome

• Capillary leak syndrome (CLS) can occur in patients receiving human granulocyte colony-stimulating factors and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.

Potential for Tumor Growth Stimulatory Effects on Malignant Cells

• The granulocyte colony-stimulating factor (G‑CSF) receptor through which GRANIX acts has been found on tumor cell lines. The possibility that GRANIX acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded.

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

GRANIX clinical trials safety data are based upon the results of three randomized clinical trials in patients receiving myeloablative chemotherapy for breast cancer (N=348), lung cancer (N=240) and non-Hodgkin’s lymphoma (N=92). In the breast cancer study, 99% of patients were female, the median age was 50 years, and 86% of patients were Caucasian. In the lung cancer study, 80% of patients were male, the median age was 58 years, and 95% of patients were Caucasian. In the non-Hodgkin’s lymphoma study, 52% of patients were male, the median age was 55 years, and 88% of patients were Caucasian. In all three studies a placebo (Cycle 1 of the breast cancer study only) or a non-US-approved filgrastim product were used as controls. Both GRANIX and the non-US-approved filgrastim product were administered at 5 mcg/kg subcutaneously once daily beginning one day after chemotherapy for at least five days and continued to a maximum of 14 days or until an ANC of ≥10,000 x 106/L after nadir was reached.

Bone pain was the most frequent treatment-emergent adverse reaction that occurred in at least 1% or greater in patients treated with GRANIX at the recommended dose and was numerically two times more frequent than in the placebo group. Theoverall incidence of bone pain in Cycle 1 of treatment was 3.4% (3.4% GRANIX, 1.4% placebo, 7.5% non-US-approved filgrastim product).

Leukocytosis

• In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed in less than 1% patients with non-myeloid malignancies receiving GRANIX. No complications attributable to leukocytosis were reported in clinical studies.

Additional Adverse Reactions

• Other adverse reactions known to occur following administration of human granulocyte colony-stimulating factors include myalgia, headache, vomiting, Sweet’s syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitis and thrombocytopenia.

Postmarketing Experience

There is limited information regarding Filgastrim Postmarketing Experience in the drug label.

Drug Interactions

• No formal drug interaction studies between GRANIX and other drugs have been performed.
• Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution.
• Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C There are no adequate and well-controlled studies of GRANIX in pregnant women. In animal reproduction studies, treatment of pregnant rabbits with tbo-filgrastim resulted in increased spontaneous abortion and fetal malformations at systemic exposures substantially higher than the human exposure. GRANIX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Filgastrim in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Filgastrim during labor and delivery.

Nursing Mothers

It is not known whether tbo-filgrastim is secreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GRANIX is administered to a nursing woman. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates.

Pediatric Use

The safety and effectiveness of GRANIX in pediatric patients have not been established.

Geriatic Use

Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111 patients were 65 years of age and older. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients.

Gender

There is no FDA guidance on the use of Filgastrim with respect to specific gender populations.

Race

There is no FDA guidance on the use of Filgastrim with respect to specific racial populations.

Renal Impairment

The safety and efficacy of GRANIX have not been studied in patients with moderate or severe renal impairment. No dose adjustment is recommended for patients with mild renal impairment.

Hepatic Impairment

The safety and efficacy of GRANIX have not been studied in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Filgastrim in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Filgastrim in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Filgastrim Administration in the drug label.

Monitoring

There is limited information regarding Filgastrim Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Filgastrim and IV administrations.

Overdosage

• No case of overdose has been reported.

Pharmacology

There is limited information regarding Filgastrim Pharmacology in the drug label.

Mechanism of Action

• Tbo-filgrastim is a human granulocyte colony-stimulating factor (G-CSF) produced by recombinant DNA technology. Tbo-filgrastim binds to G-CSF receptors and stimulates proliferation of neutrophils. G-CSF is known to stimulate differentiation commitment and some end-cell functional activation, which increases neutrophil counts and activity.

Structure

There is limited information regarding Filgastrim Structure in the drug label.

Pharmacodynamics

• In the clinical trials of patients with cancer, the time to the ANCmax was between 3 to 5 days and returned to baseline by 21 days following completion of chemotherapy. In the healthy volunteer trials, doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16%-19% increase in the ANCmax and a 33%-36% increase in the area under the effect curve for ANC.

Cardiac Electrophysiology: At the maximum recommended intravenous dose of 5 μg/kg, tbo-filgrastim did not prolong the QT interval to any clinically relevant extent.

Pharmacokinetics

• In healthy subjects, the absolute bioavailability of 5 mcg/kg subcutaneous tbo-filgrastim was 33%. Increasing the dose of tbo-filgrastim from 5 to 10 mcg/kg in these healthy subjects resulted in an approximately 200% increase in both the maximum concentration (Cmax) and the area under the curve (AUC0-48h) of the drug.
• In the clinical trials of patients with cancer, the AUC and Cmax were greater and more variable compared to healthy volunteers receiving the same dose of tbo-filgrastim subcutaneously. The median time to maximum concentration was between 4 to 6 hours and the median elimination half-life was between 3.2 to 3.8 hours. Accumulation was not observed after repeated dosing.

Pharmacokinetics in Specific Populations

• Age: Not evaluated.
• Gender: No gender-related differences were observed.
• Renal Impairment: Mild renal impairment (creatinine clearance 60 - 89 mL/min) had no effect on tbo-filgrastim pharmacokinetics (N=11). The pharmacokinetic profile in patients with moderate and severe renal impairment has not been assessed.
• Hepatic Impairment: The pharmacokinetic profile in patients with hepatic impairment has not been assessed.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

• Carcinogenicity and genetic toxicology studies have not been conducted with tbo-filgrastim.
• A fertility study was not conducted with tbo-filgrastim. Toxicology studies of up to 26 weeks in rats or monkeys did not reveal findings in male or female reproductive organs that would suggest impairment of fertility.

Clinical Studies

• The efficacy of GRANIX was evaluated in a multinational, multicenter, randomized and controlled Phase 3 study in 348 chemotherapy-naive patients with high-risk stage II, stage III, or stage IV breast cancer receiving doxorubicin (60 mg/m2) and docetaxel (75 mg/m2) comparing GRANIX to placebo and a non-US-approved filgrastim product as controls. The median age of the patients was 50 years (range 25 to 75 years) with 99% female and 86% Caucasian.
• GRANIX, placebo, and the non-US-approved filgrastim product were administered at 5 mcg/kg subcutaneously once daily beginning one day after chemotherapy for at least five days and continued to a maximum of 14 days or until an ANC of ≥10,000 x 106/L after nadir was reached.
• GRANIX was superior to placebo in duration of severe neutropenia (DSN) with a statistically significant reduction in DSN (1.1 days vs. 3.8 days, p < 0.0001).

How Supplied

GRANIX 300 mcg/0.5 mL: Each prefilled syringe contains 300 mcg of tbo-filgrastim in 0.5 mL solution with a blue plunger in:

• Pack of 1 with a safety needle guard in blister: NDC 63459-910-11
• Packs of 10 with a safety needle guard in blisters: NDC 63459-910-15
• Pack of 1 without a safety needle guard (for patients and caregivers): NDC 63459-910-17
• Packs of 5 without a safety needle guard (for patients and caregivers): NDC 63459-910-36

GRANIX 480 mcg/0.8 mL: Each prefilled syringe contains 480 mcg of tbo-filgrastim in 0.8 mL solution with a clear plunger in:

• Pack of 1 with a safety needle guard in blister: NDC 63459-912-11
• Packs of 10 with a safety needle guard in blisters: NDC 63459-912-15
• Pack of 1 without a safety needle guard (for patients and caregivers): NDC 63459-912-17
• Packs of 5 without a safety needle guard (for patients and caregivers): NDC 63459-912-36

Storage

GRANIX syringes should be stored in a refrigerator at 36° to 46° F (2° to 8° C). Protect from light. Within its shelf life, the product may be removed from 36° to 46° F (2° to 8° C) storage for a single period of up to 5 days between 73° to 81° F (23° to 27° C). If not used within 5 days, the product may be returned to 36° to 46° F (2° to 8° C) up to the expiration date.

Images

Drug Images

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Patient Counseling Information

There is limited information regarding Filgastrim Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Filgastrim interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Filgastrim Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Filgastrim Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.