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Neupogen

Pronunciation

Generic Name: Filgrastim
Class: Hematopoietic Agents
Chemical Name: 121181-53-1
CAS Number: 121181-53-1

Introduction

Biosynthetic (recombinant DNA origin) hematopoietic agents that principally affect the proliferation and differentiation of neutrophils within the bone marrow1 3 4 12 76 78 79 80 81 82 113 145 and possibly other sites (e.g., spleen).23 42 105 113 Exert same pharmacologic effects as endogenous granulocyte colony-stimulating factor (G-CSF).1 3 4 12 76 78 79 80 81 82 113 Filgrastim and tbo-filgrastim are structurally and pharmacologically similar and contain a related drug substance.1 145 151 155 Tbo-filgrastim was licensed by FDA through a biologics license application (BLA), not as a biosimilar to filgrastim;155 at the time of tbo-filgrastim's submission for approval, FDA had not finalized a process for approving biosimilars.151 153 154 155

Uses for Neupogen

Chemotherapy-induced Neutropenia (Filgrastim or Tbo-filgrastim)

Management of chemotherapy-induced neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive antineoplastic therapies associated with a clinically important risk of febrile neutropenia; in clinical studies, filgrastim reduced risk of infectious complications (as manifested by febrile neutropenia) and tbo-filgrastim reduced duration of severe neutropenia.1 5 6 7 8 9 10 26 32 36 65 77 102 145 152

Efficacy not established in patients receiving antineoplastic therapy associated with delayed myelosuppression (e.g., nitrosourea derivatives) or in those receiving mitomycin or myelosuppressive doses of antimetabolites (e.g., cytarabine, fluorouracil).1 110 113

Filgrastim has been used in conjunction with empiric anti-infective therapy for the treatment of chemotherapy-induced febrile neutropenia.129

Autologous and Allogeneic Bone Marrow Transplantation (Filgrastim)

Reduction of the duration of neutropenia and neutropenia-related clinical sequelae (e.g., febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT);1 4 12 16 24 32 33 102 125 126 designated an orphan drug by FDA for the treatment of neutropenia associated with BMT.135

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Peripheral Blood Progenitor Cell Transplantation (Filgrastim)

Mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis;1 72 77 designated an orphan drug by FDA for mobilization of peripheral blood progenitor cells (PBPC) for collection in patients who will receive myeloablative or myelosuppressive chemotherapy.135

Also used for acceleration of myeloid engraftment following autologous PBPC transplantation.1 72 77

Severe Chronic Neutropenias (Filgrastim)

Reduction of the incidence and duration of sequelae of neutropenia (e.g., fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia,1 4 13 20 32 46 73 104 cyclic neutropenia,1 12 15 104 or acquired idiopathic neutropenia;1 4 12 30 62 designated an orphan drug by FDA for treatment of severe chronic neutropenia (ANC <500/m3).135

Initiate therapy in patients with severe chronic neutropenia only after a diagnosis of congenital, cyclic, or idiopathic neutropenia has been confirmed and other diseases associated with neutropenia have been excluded.1

Myelodysplastic Syndromes and Aplastic Anemia (Filgrastim)

Has been used to increase leukocyte counts in adults with myelodysplastic syndrome (MDS)12 28 29 32 35 37 55 57 61 75 77 classified as refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), or refractory anemia with excess blasts in transformation (RAEB-T);4 28 29 37 57 61 however, it is unclear whether filgrastim will alter (either increase or decrease) the rate of progression to acute myeloid leukemia or alter the usually fatal outcome of the disease.4 35 37 77 Safety and efficacy for this use not established;1 use generally should be limited to experts in such therapy.110 113

Has been used with some success to increase leukocyte counts in a limited number of children 1–17 years of age with moderate to severe aplastic anemia.4 12 18 40 Use generally should be limited to experts in such therapy.110 113

Leukemia (Filgrastim)

Reduction of the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in adults with acute myeloid leukemia (AML).1 136 137 138

Use of filgrastim in patients with acute leukemia has been controversial, since results of in vitro studies indicate that certain leukemic cell lines have receptors for G-CSF and that the survival, proliferation, and differentiation of the cells are supported by CSFs.4 11 19 23 42 50 63 77 Some experts state that use of filgrastim in the treatment of myeloid leukemia should be considered investigational and undertaken with caution.11 42 77 110 113

Neutropenia Associated with HIV Infection and Antiretroviral Therapy (Filgrastim)

Treatment to correct or minimize HIV-associated neutropenia and/or drug-induced neutropenia.4 25 26 27 31 38 52 54 59 77 130 131 132

Treatment, alone or in conjunction with epoetin alfa, to ameliorate the hematologic toxicity (severe anemia and/or granulocytopenia) associated with zidovudine therapy in adults with AIDS or AIDS-related complex (ARC).4 25 59 77

Designated an orphan drug by FDA for the treatment of HIV-infected patients who, in addition, are afflicted with cytomegalovirus retinitis and are being treated with ganciclovir.135

Neupogen Dosage and Administration

Administration

Depending on use, administer filgrastim by IV infusion1 4 6 8 10 11 12 13 14 15 18 19 20 24 29 36 65 87 91 92 110 or by sub-Q injection1 2 4 7 9 10 11 12 13 15 17 20 28 35 37 48 58 61 76 92 102 110 or infusion.1 9 11 12 16 72 110 Sub-Q injection is most convenient for self-administration4 7 11 13 15 17 35 48 76 102 and especially useful for prolonged maintenance therapy.4 6 13 15 17 28 48 102

Administer tbo-filgrastim sub-Q.145

Do not administer filgrastim within 24 hours before or after myelosuppressive chemotherapy.1

First dose of tbo-filgrastim should be administered ≥24 hours after myelosuppressive chemotherapy; do not administer drug within 24 hours before such chemotherapy.145 Do not administer first dose of tbo-filgrastim within 24 hours before myelosuppressive chemotherapy.145

When used in patients undergoing myeloablative chemotherapy followed by BMT, administer first dose of filgrastim ≥24 hours after cytotoxic therapy and ≥24 hours after BMT.1 125 126

Do not shake injections.1 145

Vials and prefilled syringes are for single use only.1 145 Discard any unused portion.1 145

Filgrastim may be self-administered; tbo-filgrastim should be administered by a healthcare professional.1 2 145 (See Advice to Patients.)

For solution and drug compatibility information, see Compatibility under Stability.

IV Administration

Dilution

If required, may dilute filgrastim with 5% dextrose injection.1 If diluted to a concentration of 5–15 mcg/mL, add albumin human to the infusion solution to a final concentration of 2 mg/mL (0.2%) to minimize adsorption of the drug to drug delivery system components.1 69 110 Do not dilute to a final concentration of <5 mcg/mL.1 Do not dilute with 0.9% sodium chloride injection since precipitation may occur.1 156

Rate of Administration

If filgrastim is administered by IV infusion in patients with chemotherapy-induced neutropenia, may administer as a brief IV infusion (e.g., over 15–30 minutes)1 8 15 18 19 24 29 36 65 76 87 110 113 or by continuous IV infusion.1 5 6

If filgrastim is administered by IV infusion in patients undergoing BMT, manufacturer recommends an infusion duration of 4 or 24 hours.1 126

Sub-Q Administration

Recommended sites for sub-Q injection include upper back portion of upper arms, abdomen (except for 2-inch area around navel), front of middle thighs, or upper outer areas of the buttocks.2 145 Rotate injection sites daily; avoid any area that is tender, red, bruised, hard, or has stretch marks or scars.2 145

Dilution

If required, may dilute filgrastim with 5% dextrose injection for sub-Q infusion.1 If diluted to a concentration of 5–15 mcg/mL, add albumin human to the infusion solution to a final concentration of 2 mg/mL (0.2%) to minimize adsorption of the drug to drug delivery system components.1 69 110 Do not dilute to a final concentration of <5 mcg/mL.1 Do not dilute with 0.9% sodium chloride injection since precipitation may occur.1 156

Dosage

Pediatric Patients

Chemotherapy-induced Neutropenia (Filgrastim)
IV or Sub-Q

Individualize dosage depending on type and dosage of myelosuppressive chemotherapy.1 4 48 77 Initially, 5 mcg/kg daily, administered by sub-Q injection, brief (15–30 minutes) IV infusion, or continuous IV or sub-Q infusion.1 4 5 6 8 9 19 36 77 If response inadequate after 5–7 days, may increase dosage in increments of 5 mcg/kg with each chemotherapy cycle, according to the duration and severity of the ANC nadir.1 4 110

Continue treatment for up to 2 weeks or until ANC reaches 10,000/mm3 following the expected chemotherapy-induced ANC nadir.1 4 113 110

Discontinue if ANC increases to >10,000/mm3 following expected chemotherapy-induced neutrophil nadir; such ANC levels may not result in additional clinical benefit and may increase potential for complications from excessive leukocytosis.1

Congenital, Cyclic, and Idiopathic Neutropenias (Filgrastim)
Congenital Neutropenia
Sub-Q

Initially, 6 mcg/kg twice daily; individualize dosage according to clinical course and neutrophil count.1 13 20 133

Cyclic or Idiopathic Neutropenia
Sub-Q

Initially, 5 mcg/kg once daily; individualize dosage according to clinical course and neutrophil count.1 4 15 133

Neutropenia Associated with HIV Infection and Antiretroviral Therapy (Filgrastim)
Sub-Q

Adolescents: 5–10 mcg/kg once daily for 2–4 weeks.131

Adults

Chemotherapy-induced Neutropenia (Filgrastim)
IV or Sub-Q

Individualize dosage depending on type and dosage of myelosuppressive chemotherapy.1 4 48 77 Initially, 5 mcg/kg daily, administered by sub-Q injection, brief (15–30 minutes) IV infusion, or continuous IV or sub-Q infusion.1 4 5 6 8 9 19 36 77 Administer ≥24 hours after cytotoxic chemotherapy.1 If response inadequate after 5–7 days, may increase dosage in increments of 5 mcg/kg with each chemotherapy cycle, according to the duration and severity of the ANC nadir.1 4 110

Continue treatment for up to 2 weeks until ANC reaches 10,000/mm3 following the expected chemotherapy-induced ANC nadir.1 4 113 110

Discontinue if ANC increases to >10,000/mm3 following expected chemotherapy-induced neutrophil nadir; such ANC levels may not result in additional clinical benefit and may increase potential complications from excessive leukocytosis.1

Chemotherapy-induced Neutropenia (Tbo-filgrastim)
Sub-Q

5 mcg/kg daily.145 Administer first dose ≥24 hours after myelosuppressive chemotherapy.145 Continue treatment until expected chemotherapy-induced neutrophil nadir has passed and ANC has recovered to within normal range.145

Bone Marrow Transplantation (Filgrastim)
IV or Sub-Q

Initially, 10 mcg/kg daily,1 127 administered by IV infusion over 4 or 24 hours or by continuous sub-Q infusion over 24 hours.1 Administer first dose ≥24 hours after cytotoxic chemotherapy and ≥24 hours after BMT.1 125 126 Reduce dosage to 5 mcg/kg daily when ANC is >1000/mm3 for 3 consecutive days.1 127 Discontinue filgrastim if ANC remains >1000/mm3 for an additional 3 consecutive days.1 If ANC is <1000/mm3 following discontinuance of filgrastim, reinitiate therapy at 5 mcg/kg daily.1 If ANC is <1000/mm3 at any time when the 5-mcg/kg daily dosage is being used, increase dosage to 10 mcg/kg daily and repeat preceding steps.1

Peripheral Blood Progenitor Cell Transplantation (Filgrastim)
Mobilization of Hematopoietic Progenitor Cells
Sub-Q

10 mcg/kg once daily, administered by sub-Q injection or continuous sub-Q infusion.1 Manufacturer recommends that filgrastim be administered at least 4 days prior to first leukapheresis and continued until the last leukapheresis is performed.1 Optimum duration of therapy not established; in clinical trials, filgrastim was administered for 6–7 days with leukapheresis on days 5, 6, and 7.1

Monitor neutrophil counts after 4 days; modify dosage if leukocyte count increases to >100,000/mm3.1

Administration Following Reinfusion of PBPC Collection
Sub-Q

5–24 mcg/kg daily until a sustainable ANC (≥500/mm3) is attained.1

Congenital, Cyclic, and Idiopathic Neutropenias (Filgrastim)
Congenital Neutropenia
Sub-Q

Initially, 6 mcg/kg twice daily; individualize dosage according to clinical course and neutrophil count.1 13 20 133

Cyclic or Idiopathic Neutropenia
Sub-Q

Initially, 5 mcg/kg once daily; individualize dosage according to clinical course and neutrophil count.1 4 15 133

Myelodysplastic Syndromes andAplastic Anemia (Filgrastim)
Myelodysplastic Syndromes
IV

Dosages of 50–400 mcg/m2 administered once daily over 30 minutes have been used.28 29 35 37 61

Sub-Q

Dosages of 0.3–10 mcg/kg administered once daily have been used.28 29 35 37 61

Neutropenia Associated with HIV Infection and Antiretroviral Therapy (Filgrastim)
Sub-Q

5–10 mcg/kg once daily for 2–4 weeks.131

Cautions for Neupogen

Contraindications

  • Filgrastim: Known hypersensitivity to filgrastim, any ingredient in the formulation, or proteins derived from Escherichia coli.1

  • Tbo-filgrastim: Manufacturer states none known.145

Warnings/Precautions

Warnings

Splenic Rupture

Splenic rupture (including fatalities) reported following administration of filgrastim.1 144 Although no cases in clinical trials with tbo-filgrastim, consider possible risk.153

Evaluate patients experiencing left upper abdominal and/or shoulder tip pain for splenomegaly or splenic rupture.1 145 Manufacturer of tbo-filgrastim states to discontinue drug if such symptoms occur.145

Respiratory Effects

Acute respiratory distress syndrome (ARDS) reported in patients receiving filgrastim.1 145 Although no cases to date with tbo-filgrastim, consider possible risk.153

If fever, lung infiltrates, or respiratory distress develops, evaluate patient for the presence of ARDS.1 If ARDS occurs, provide appropriate treatment; discontinue or withhold filgrastim until ARDS has resolved, and discontinue tbo-filgrastim.1 145

Sickle Cell Disease

Severe, sometimes fatal, sickle cell crisis reported in patients with sickle cell disease receiving filgrastim.1 Although no cases to date with tbo-filgrastim, consider possible risk.145 153

Prior to administering filgrastim or tbo-filgrastim in patients with sickle cell disease, consider potential risks versus benefits of therapy.1 145 Only clinicians qualified in the management of sickle cell disease should prescribe filgrastim to such patients.1 Discontinue tbo-filgrastim if sickle cell crisis occurs.145

Severe Chronic Neutropenia

Initiate filgrastim therapy in patients with severe chronic neutropenia only after a diagnosis of congenital, cyclic, or idiopathic neutropenia has been confirmed and other diseases associated with neutropenia have been excluded; safety and efficacy in the treatment of neutropenia caused by other hematopoietic disorders (e.g., MDS) not established.1

Cytogenetic abnormalities, MDS, and AML reported during filgrastim therapy in patients with severe chronic neutropenia.1 The risk of developing MDS or AML appears to be limited to patients with congenital neutropenia.1 The effect of filgrastim on the development of abnormal cytogenetics and the effect of continued use of the drug in patients with abnormal cytogenetics or MDS are unknown.1

Carefully consider risks and benefits of continuing filgrastim therapy if abnormal cytogenetics or myelodysplasia develops in patients with severe chronic neutropenia.1

Sensitivity Reactions

Hypersensitivity Reactions

Risk of serious allergic reactions, including anaphylaxis, with filgrastim or tbo-filgrastim.1 145 154 Do not use in patients with known hypersensitivity to filgrastim or related drug products (e.g., pegfilgrastim).1 145 (See Contraindications under Cautions.)

If a serious allergic reaction occurs, discontinue therapy; manufacturer of tbo-filgrastim states to permanently discontinue the drug.2 145 May administer antihistamines, corticosteroids, bronchodilators, and/or epinephrine to reduce allergic-type symptoms.1 145 154

Latex Sensitivity

Some packaging components (i.e., needle cover) of prefilled syringes of filgrastim contain natural latex proteins in the form of dry natural rubber.1 Some individuals may be hypersensitive to natural latex proteins; rarely, hypersensitivity reactions to natural latex proteins have been fatal.146 147 148

General Precautions

Chemotherapy and Radiation Therapy

Filgrastim therapy may allow use of higher cumulative chemotherapy dosages; possible increased risk of thrombocytopenia, anemia, and nonhematologic adverse effects associated with the chemotherapy regimen.1 6 8 43 64 102

Safety and efficacy of concomitant radiation therapy or cytotoxic chemotherapy not established.1 Do not administer filgrastim concomitantly with radiation therapy.1 Do not administer filgrastim or tbo-filgrastim during the 24 hours before or after administration of cytotoxic chemotherapy.1 145 (See Interactions.)

Effect on Malignant Cells

The possibility that filgrastim or tbo-filgrastim could act as a growth factor for any tumor type, particularly myeloid malignancies, has not been excluded.1 3 11 42 49 64 76 77 145 Safety of filgrastim in patients with chronic myeloid leukemia (CML) or MDS not established.1 Tbo-filgrastim not FDA-labeled for use in patients with myeloid malignancies or myelodysplasia.145

When filgrastim is used for mobilization of hematopoietic progenitor cells, possible release of tumor cells from the marrow and subsequent collection in the leukapheresis product;1 effect of reinfusion of tumor cells not well studied and limited data available to date are inconclusive.1

Excessive Leukocytosis

Marked leukocytosis (leukocyte counts ≥100,000/mm3) reported occasionally with filgrastim and tbo-filgrastim therapy.1 23 145 Manufacturer of filgrastim recommends that leukocyte counts be monitored to avoid potential complications of excessive leukocytosis.1 95 (See Laboratory Monitoring under Cautions.)

Premature Discontinuance

Transient increase in neutrophil count generally occurs 1–2 days following initiation of filgrastim in patients receiving myelosuppressive chemotherapy.1 For a sustained response, continue therapy in such patients until post-nadir ANC reaches 10,000/mm3.1 4 113 110 Premature discontinuance prior to recovery from the expected chemotherapy-induced ANC nadir generally not recommended.1

Immunogenicity

Potential risk of immunogenicity.1 145 154 Available data suggest that a small proportion of patients receiving filgrastim develop binding antibodies; however, nature and specificity of these antibodies not adequately studied.1 Although not observed to date, possibility exists that an antibody directed against filgrastim could cross-react with endogenous G-CSF, resulting in immune-mediated neutropenia.1

Binding or neutralizing antibodies to tbo-filgrastim not detected in principal efficacy study; however, further study needed to determine immunogenicity potential of the drug.152

Dermatologic Effects

Cutaneous vasculitis reported rarely with filgrastim therapy,1 4 11 12 20 62 principally in patients with severe chronic neutropenia receiving long-term therapy.1 Symptoms generally develop simultaneously with an increase in ANC and abate when ANC is decreased; many patients are able to continue filgrastim at reduced dosage.1

Laboratory Monitoring

Perform CBC and platelet counts prior to initiation of chemotherapy and routinely (twice weekly) during filgrastim or tbo-filgrastim therapy for chemotherapy-induced neutropenia.1 102 113 145

Perform CBC and platelet counts at least 3 times weekly in patients receiving filgrastim following BMT.1

Monitor neutrophil counts after 4 days of filgrastim therapy for mobilization of PBPC.1

In patients with severe chronic neutropenia, perform CBC with differential and platelet counts prior to filgrastim therapy, twice weekly during the initial 4 weeks of therapy, and during the first 2 weeks following any dosage adjustment; once patient is clinically stable, may perform hematologic monitoring once monthly during the first year of treatment, then at least quarterly thereafter.1 Annual bone marrow and cytogenetic evaluations advised in patients with congenital neutropenia.1

Specific Populations

Pregnancy

Category C.1 145

Lactation

Not known whether filgrastim or tbo-filgrastim is distributed into milk; caution advised.1 95 145

Pediatric Use

Safety and efficacy of filgrastim not established in neonates or patients with autoimmune neutropenia of infancy.1

Cytogenetic abnormalities and transformation to MDS and AML have occurred during filgrastim therapy in pediatric patients with congenital types of neutropenia (Kostmann’s syndrome, congenital agranulocytosis, Schwachman-Diamond syndrome).1 The relationship between these events and filgrastim is unknown.1

Adverse effects reported in children with cancer receiving filgrastim are similar to those reported in adults.1 Alterations in growth and development, sexual maturation, or endocrine function not reported.1 Possible subclinical splenomegaly.1

Safety and efficacy of tbo-filgrastim not established in pediatric patients <18 years of age.145

Geriatric Use

Safety and efficacy profiles similar to those in younger adults receiving filgrastim or tbo-filgrastim following myelosuppressive chemotherapy.1 145 Clinical studies for other filgrastim indications (e.g., BMT, PBPC mobilization, severe chronic neutropenia) did not include sufficient number of individuals ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1

Hepatic Impairment

Pharmacokinetic profile of tbo-filgrastim not evaluated in patients with hepatic impairment.145

Renal Impairment

No effect of mild renal impairment (Clcr 60–89 mL/minute) on pharmacokinetics of tbo-filgrastim; not evaluated in patients with moderate or severe renal impairment.145

Common Adverse Effects

Filgrastim: Medullary bone pain, nausea, vomiting.1 4 7 10 11 12 14 15 24 87 102

Tbo-filgrastim: Bone pain.145 153 154

Interactions for Neupogen

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Antineoplastic agents

Sensitivity of rapidly dividing cells to cytotoxic chemotherapy may be increased1

Safety and efficacy of concomitant administration not established;1 do not administer filgrastim or tbo-filgrastim within 24 hours of administration of an antineoplastic agent1 145

Bone imaging

Increased hematopoietic activity of the bone marrow may cause transient positive bone-imaging changes1 145

Consider possibility of such interference when interpreting results of bone-imaging tests1 145

Lithium

Possible increased myeloproliferative effects1 145

Use with caution1 145

Neupogen Pharmacokinetics

Absorption

Bioavailability

Filgrastim: Rapidly absorbed following sub-Q injection,2 9 11 12 92 95 with peak serum concentrations generally attained within 4–5 hours.2 4 9 11 12 92 95

Tbo-filgrastim: Median time to peak plasma concentrations approximately 4–6 hours following sub-Q dose.145 Absolute bioavailability following sub-Q injection is approximately 33%.145

Distribution

Extent

Filgrastim is rapidly distributed in animals, appearing in highest concentrations in bone marrow, adrenal glands, kidney, and liver.95

Not known whether filgrastim distributes into CSF or milk or crosses the placenta in humans.2 Not known whether tbo-filgrastim distributes into human milk.145

Elimination

Metabolism

Not known whether filgrastim is metabolized.2 12 66 76 92 95

Elimination Route

Elimination route of filgrastim is not known.2 12 66 76 92 95 Level of circulating neutrophils may affect filgrastim clearance, with clearance increasing as neutrophil counts increase.12 92

Half-life

Filgrastim: About 3.5 hours.1

Tbo-filgrastim: About 3.2–3.8 hours (median) in patients with cancer receiving chemotherapy; approximately 8.9 hours in healthy individuals.145 153

Stability

Storage

Parenteral

Filgrastim: 2–8°C.1 May be allowed to reach room temperature for up to 24 hours before use.1

Tbo-filgrastim: 2–8°C; protect from light.145 May be removed from refrigerator storage for a single period of up to 5 days and kept at 23–27°C; if not used, may return to refrigerator until expiration date.145 Stable when exposed to temperatures of -1 to -5°C for up to 72 hours and -15 to -25°C for up to 24 hours.145

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

The following compatibility information applies to filgrastim.

Solution Compatibility

Incompatible

Sodium chloride 0.9%1 2 69 110

Compatible

Dextrose 5%1

Drug Compatibility
Y-Site Compatibility156

Compatible

Acyclovir sodium

Allopurinol sodium

Amikacin sulfate

Aminophylline

Ampicillin sodium

Ampicillin sodium–sulbactam sodium

Aztreonam

Bleomycin sulfate

Bumetanide

Buprenorphine HCl

Butorphanol tartrate

Calcium gluconate

Carboplatin

Carmustine

Cefazolin sodium

Cefotetan disodium

Ceftazidime

Chlorpromazine HCl

Cisplatin

Co-trimoxazole

Cyclophosphamide

Cytarabine

Dacarbazine

Daunorubicin HCl

Dexamethasone sodium phosphate

Diphenhydramine HCl

Doxorubicin HCl

Doxycycline hyclate

Droperidol

Enalaprilat

Famotidine

Floxuridine

Fluconazole

Fludarabine phosphate

Gallium nitrate

Ganciclovir sodium

Granisetron HCl

Haloperidol lactate

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Idarubicin HCl

Ifosfamide

Leucovorin calcium

Lorazepam

Mechlorethamine HCl

Melphalan HCl

Meperidine HCl

Mesna

Methotrexate sodium

Metoclopramide HCl

Mitoxantrone HCl

Morphine sulfate

Nalbuphine HCl

Ondansetron HCl

Potassium chloride

Promethazine HCl

Ranitidine HCl

Sodium bicarbonate

Streptozocin

Ticarcillin disodium–clavulanate potassium

Tobramycin sulfate

Vancomycin HCl

Vinblastine sulfate

Vincristine sulfate

Vinorelbine tartrate

Zidovudine

Incompatible

Amphotericin B

Cefotaxime sodium

Cefoxitin sodium

Ceftaroline fosamil

Ceftriaxone sodium

Cefuroxime sodium

Clindamycin phosphate

Dactinomycin

Etoposide

Fluorouracil

Furosemide

Heparin sodium

Mannitol

Methylprednisolone sodium succinate

Metronidazole

Mitomycin

Prochlorperazine edisylate

Thiotepa

Variable

Gentamicin sulfate

Imipenem–cilastatin sodium

Actions

  • Influences leukopoiesis;1 4 12 23 32 76 78 84 85 86 87 88 89 90 103 145 affects the proliferation and differentiation of neutrophils within the bone marrow1 3 4 12 76 78 79 80 81 82 113 145 and possibly other sites (e.g., spleen).23 42 105 113

  • Binds directly to G-CSF receptors on neutrophil progenitor target cell surfaces.1 32 42 50 60 87 93 94 145 Stimulates neutrophil proliferation, thereby increasing neutrophil counts and activity.10 12 76 86 145

  • Increases and sustains the ANC throughout administration; however, an initial transient decline in ANC has been observed with each dose of filgrastim.2 4 9 11 12 23 76 86 87

  • Filgrastim also may increase lymphocyte and monocyte counts;1 4 11 12 26 32 76 87 89 however, does not affect eosinophil or basophil counts4 11 12 87 89 nor consistently affect hemoglobin levels or hematocrit;4 11 12 transient dose-dependent decrease in platelet count may occur.4 10 11 35 59 61 87

  • Filgrastim reduces duration and severity of neutropenia in patients with chemotherapy-induced neutropenia;1 11 36 ANC nadir occurs sooner and there is accelerated recovery of neutrophil counts.1 Tbo-filgrastim has been shown to reduce duration of severe neutropenia in patients with chemotherapy-induced neutropenia.145

Advice to Patients

  • Importance of advising patients about the possibility of bone pain, which can usually be relieved by the use of analgesics such as acetaminophen or NSAIAs.2 145

  • Risk of splenomegaly or splenic rupture; importance of immediately informing clinician if abdominal pain, left upper quadrant pain, or left shoulder pain occurs.2 145

  • Risk of ARDS; importance of immediately informing clinician if shortness of breath, difficulty breathing, or rapid breathing occurs.2 145

  • Importance of discussing potential risks (e.g., sickle cell crisis, death) and benefits of therapy for patients with sickle cell disease.2 145

  • Importance of immediately informing clinician if signs and symptoms of infection (e.g., fever, chills, rash, sore throat, diarrhea, redness, swelling, pain around a cut or sore) occur.2 145

  • If filgrastim is to be self-administered, importance of providing the patient with instruction on proper dosage and administration of the drug, including aseptic technique and safe disposal of needles, syringes, and unused drug.1 2

  • Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.1 2 145 Importance of advising women not to become pregnant while receiving tbo-filgrastim; advise of potential for fetal harm if pregnancy occurs.145

    Encourage women who become pregnant during filgrastim therapy to enroll in the manufacturer's pregnancy surveillance program at 1-800-77-AMGEN (1-800-772-6436).2

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., sickle cell disease).1 2 145

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Filgrastim (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV or subcutaneous use

300 mcg/mL (300 mcg and 480 mcg)

Neupogen (available in single-dose vials)

Amgen

600 mcg/mL (300 mcg and 480 mcg)

Neupogen (available in prefilled syringes with an UltraSafe needle guard)

Amgen

Tbo-filgrastim (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

600 mcg/mL (300 mcg and 480 mcg)

Granix (available in prefilled syringes with or without UltraSafe needle guard)

Teva

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Neupogen 300MCG/0.5ML Solution (AMGEN): 1/$298.00 or 3/$1,482.95

Neupogen 300MCG/ML Solution (AMGEN): 1/$275.99 or 3/$802.99

Neupogen 480MCG/0.8ML Solution (AMGEN): 1/$514.98 or 3/$2,007.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 31, 2014. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Amgen. Neupogen (filgrastim) prescribing information. Thousand Oaks, CA; 2013 Sep.

2. Amgen. Neupogen (filgrastim) information for patients and caregivers. Thousand Oaks, CA; 2013 Sep.

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