Tevagrastim (Filgrastim)

What Is Tevagrastim and What Is It Used For?

Tevagrastim belongs to a class of medicines called cytokines, specifically granulocyte colony-stimulating factors (G-CSFs). Colony-stimulating factors are proteins that occur naturally in the human body, where they regulate the production and activity of blood cells. The filgrastim in Tevagrastim is produced using recombinant DNA technology in Escherichia coli, a process that yields a non-glycosylated protein with the same amino acid sequence as the natural human G-CSF, with the addition of an N-terminal methionine residue required for bacterial expression. The product is therefore biotechnologically manufactured and is classified as a biological medicine.

A reduction in the number of circulating neutrophils, a condition called neutropenia, significantly impairs the body's ability to defend itself against bacterial and fungal infections. When the absolute neutrophil count (ANC) falls below 0.5 × 10⁹/L, the patient is considered severely neutropenic and is at high risk of life-threatening infection, particularly if the condition is accompanied by fever (febrile neutropenia). Filgrastim accelerates the recovery of neutrophil counts following bone marrow suppression, thereby reducing the incidence, severity, and duration of infection and related hospitalization.

Tevagrastim is a biosimilar medicine, which means it has been developed to be highly similar to an already authorized biological reference medicine (Neupogen, the originator filgrastim). The European Medicines Agency (EMA) approved Tevagrastim in 2008 after an extensive comparability exercise covering pharmaceutical quality, preclinical pharmacology and toxicology, and clinical pharmacokinetic, pharmacodynamic, efficacy, safety, and immunogenicity data. The EMA's biosimilar regulatory framework ensures that any differences between the biosimilar and the reference product have no clinically meaningful effect on safety or effectiveness.

Other approved filgrastim products include the originator Neupogen and several biosimilars such as Zarzio, Nivestim, Ratiograstim, Filgrastim Hexal, and Accofil. These products are considered clinically equivalent within their approved indications, and national and regional prescribing guidelines increasingly encourage interchangeability to reduce treatment costs and improve patient access.

Approved Indications

Tevagrastim is authorized by regulatory agencies for the following clinical situations:

• Chemotherapy-induced neutropenia: To reduce the duration and incidence of febrile neutropenia in patients receiving cytotoxic chemotherapy for established malignancies (with the exception of chronic myeloid leukemia and myelodysplastic syndromes). This is the most common indication, and meta-analyses have demonstrated that prophylactic G-CSF significantly reduces the rate of febrile neutropenia, hospitalization for infection, and infection-related mortality.
• Bone marrow transplantation: To reduce the duration of neutropenia and associated complications in patients undergoing myeloablative chemotherapy followed by bone marrow transplantation, who are at increased risk of prolonged severe neutropenia.
• Peripheral blood progenitor cell (PBPC) mobilization: To mobilize hematopoietic stem cells from the bone marrow into the peripheral blood, either alone or after myelosuppressive chemotherapy, so that the cells can be collected by apheresis for autologous or allogeneic transplantation. Tevagrastim is also used in healthy donors to mobilize stem cells for allogeneic transplantation.
• Severe chronic neutropenia (SCN): Long-term administration to increase neutrophil counts and reduce the incidence and duration of infection-related events in children and adults with severe congenital, cyclic, or idiopathic neutropenia with a history of severe or recurrent infections, after confirming that no other underlying cause is treatable.
• Advanced HIV infection with persistent neutropenia: To reduce the risk of bacterial infection when other management options are inadequate, by maintaining a normal neutrophil count.

Mechanism of Action

Filgrastim exerts its clinical effects by binding specifically to the G-CSF receptor (CD114) expressed on the surface of myeloid precursor cells and mature neutrophils. Receptor binding activates intracellular signaling cascades, including the JAK-STAT (Janus kinase / signal transducer and activator of transcription), PI3K-AKT, and RAS-MAPK pathways. These signaling events promote proliferation, differentiation, and survival of neutrophil progenitors, as well as enhanced functional activity of mature neutrophils. Mature neutrophils exposed to filgrastim display increased chemotaxis, phagocytosis, oxidative burst, and antibody-dependent cellular cytotoxicity, all of which contribute to improved antimicrobial defense.

Following a single subcutaneous dose, serum filgrastim concentrations peak between 2 and 8 hours, and the absolute neutrophil count begins to rise within 24 hours, often reaching two to three times baseline values within a few days of repeated dosing. The elimination of filgrastim follows both a saturable receptor-mediated pathway and non-saturable renal clearance, and the terminal half-life after subcutaneous administration is approximately 3 to 4 hours.

What Should You Know Before Taking Tevagrastim?

Contraindications

Tevagrastim must not be used in patients with known hypersensitivity to filgrastim or to any of the other ingredients listed in the formulation, including glacial acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 80, and water for injections. If you have previously experienced an allergic reaction to any filgrastim-containing product, regardless of brand, you should not use Tevagrastim. Cross-reactivity between filgrastim products, including the reference medicine and biosimilars, is expected given the identical active substance.

The needle shield of the pre-filled syringe may contain dry natural rubber (a latex derivative), which can cause severe allergic reactions in individuals with latex sensitivity. Patients with a known latex allergy should discuss alternative administration options with their healthcare provider.

Warnings and Precautions

Before starting treatment with Tevagrastim, tell your doctor if you have any of the following conditions:

• Sickle cell trait or sickle cell disease: Filgrastim can trigger a sickle cell crisis, which may be severe and life-threatening. If you have sickle cell anemia, your doctor will carefully weigh the potential benefits of filgrastim against the risk of precipitating a crisis, ensure adequate hydration, and monitor you closely during treatment.
• Osteoporosis or low bone density: Long-term filgrastim use has been associated with a decrease in bone mineral density. Your doctor may monitor bone density by DEXA scan during extended treatment courses and may recommend calcium and vitamin D supplementation or other bone-protective measures.
• Recent chemotherapy or radiotherapy: Filgrastim should not be administered in the 24-hour period before or after cytotoxic chemotherapy, and it has not been adequately studied in patients receiving concurrent radiotherapy.
• Pre-existing lung disease: Cases of pulmonary infiltrates, pneumonia, acute respiratory distress syndrome (ARDS), and diffuse alveolar hemorrhage have been reported in filgrastim-treated patients. Pre-existing respiratory conditions may increase this risk.
• Leukocytosis or a history of myeloproliferative disorders: Filgrastim can cause a marked rise in white blood cell count and should be used with caution in patients with a predisposition to myeloid malignancies.

Patients with severe chronic neutropenia may have an increased risk of developing blood cancers, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, it is not clear whether this risk is inherent to the underlying disease or is associated with long-term filgrastim treatment itself. Regular cytogenetic and morphological evaluation of the bone marrow is recommended during long-term therapy. If cytogenetic abnormalities suggestive of MDS develop, the risks and benefits of continued therapy should be carefully reconsidered.

A small proportion of patients may lose response to filgrastim during chronic treatment. In such cases, your doctor may investigate potential causes, including the development of neutralizing antibodies against filgrastim, evolution of the underlying disease, or other concurrent factors.

Healthy stem cell donors receiving filgrastim for allogeneic peripheral blood progenitor cell (PBPC) mobilization are typically between 16 and 60 years of age, and donation in donors outside this range should be considered only within established clinical trial protocols. Very rare but serious events, including splenic rupture and life-threatening anaphylactic reactions, have been reported in healthy donors, so donors are counseled and monitored closely before, during, and after mobilization.

Pregnancy and Breastfeeding

Tevagrastim has not been adequately studied in pregnant women, and animal reproductive studies have shown some evidence of reproductive toxicity, including embryonic loss in rabbits at high doses. Therefore, Tevagrastim is not recommended during pregnancy. If you are pregnant, think you may be pregnant, or are planning a pregnancy, tell your doctor before starting treatment, so that the benefits and risks can be weighed in the context of your specific clinical situation. If you become pregnant during treatment, contact your doctor immediately to discuss next steps.

It is not known whether filgrastim is excreted in human breast milk. Because many medicines are excreted in milk and because of the potential for adverse reactions in the breastfed infant, breastfeeding should be discontinued during Tevagrastim treatment unless your doctor explicitly advises otherwise.

Women of childbearing potential should discuss effective contraception with their doctor when starting Tevagrastim, particularly in the context of concurrent chemotherapy, which often has teratogenic potential in its own right.

Driving and Operating Machinery

Tevagrastim may have a minor influence on the ability to drive and to use machines. Dizziness, fatigue, and occasional headache have been reported, especially after the first few doses. If you experience symptoms that impair your alertness, you should not drive or operate heavy machinery until they resolve.

Important Information About Excipients

How Does Tevagrastim Interact with Other Drugs?

Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or might take, including prescription drugs, over-the-counter products, herbal remedies, and dietary supplements. Although filgrastim has few direct pharmacokinetic interactions, certain combinations require special attention because of pharmacodynamic effects on the bone marrow and neutrophil kinetics.

Major Interactions

The most clinically important interaction is with cytotoxic chemotherapy. Because filgrastim stimulates rapid proliferation of myeloid progenitors, these cells may become more sensitive to S-phase-specific cytotoxic agents. Filgrastim must not be administered within 24 hours before or 24 hours after cytotoxic chemotherapy. In practice, subcutaneous filgrastim is usually started 24 to 72 hours after the last dose of chemotherapy in a treatment cycle.

The safety and efficacy of Tevagrastim have not been established when given on the same day as 5-fluorouracil (5-FU)-based regimens or topotecan, both of which can prolong neutropenia. Clinicians typically schedule these agents separately from filgrastim administration to avoid compounding myelosuppression.

Minor and Theoretical Interactions

Lithium, used to treat bipolar disorder, independently increases the release of neutrophils from the bone marrow. When combined with filgrastim, white blood cell counts may rise more than expected. More frequent blood count monitoring is advised when the two are used together. Corticosteroids can similarly cause leukocytosis and demargination of neutrophils, adding to the pharmacodynamic effect of filgrastim, though this is rarely of clinical significance.

Co-administration of filgrastim and pegfilgrastim or other long-acting G-CSFs is not recommended, as there is no clinical benefit and it increases the risk of excessive leukocytosis, splenic enlargement, and bone pain.

What Is the Correct Dosage of Tevagrastim?

Always use Tevagrastim exactly as your doctor has prescribed. The dose and duration of treatment depend on the underlying condition, your body weight, other concurrent therapies, and how your neutrophil count responds. Your healthcare team will monitor your complete blood count (CBC) regularly to confirm response and to guide dose adjustments and timing of discontinuation.

Adults

For most adults, Tevagrastim is administered as a once-daily subcutaneous injection. In chemotherapy-induced neutropenia, the usual starting dose is 0.5 MU/kg/day (5 µg/kg/day), and the first dose is given at least 24 hours after the last cytotoxic chemotherapy dose. Treatment is continued until the absolute neutrophil count has recovered past its expected nadir and is back within the normal range. For bone marrow transplant recipients, a higher starting dose of 1.0 MU/kg/day is usually used, administered as a 30-minute or 24-hour intravenous infusion, with subsequent dose adjustment based on daily neutrophil counts.

Doses up to 10 µg/kg/day may be used for PBPC mobilization. When filgrastim is given alone for PBPC mobilization, apheresis is typically performed on days 5, 6, and 7 of administration. When it is given after myelosuppressive chemotherapy, apheresis is scheduled when the peripheral CD34+ cell count peaks, usually as neutrophils recover from the nadir.

Children

Filgrastim has been studied extensively in the pediatric population and is approved for use in children receiving chemotherapy or with severe chronic neutropenia. For children receiving cytotoxic chemotherapy, dosing is identical to that in adults on a per-kilogram basis. For severe chronic neutropenia, the starting dose depends on the subtype and is titrated based on neutrophil response. Safety and efficacy in children are considered comparable to those in adults.

Elderly

No specific dose adjustment is required in older patients. However, elderly individuals may have reduced renal or hepatic function, and may also be at greater risk of specific adverse effects such as splenomegaly or exacerbation of osteopenia. Careful clinical and laboratory monitoring is recommended, and dosing should be individualized based on response and tolerability.

Renal and Hepatic Impairment

No clinically significant differences in pharmacokinetics, pharmacodynamics, or safety have been observed in patients with mild to moderate renal or hepatic impairment. Data in severe impairment are limited, and routine dose adjustment is not recommended, but standard clinical monitoring applies.

Missed Dose

If you forget a dose, contact your doctor or pharmacist as soon as possible for advice. Do not inject a double dose to compensate for a missed dose. Your doctor will help you determine whether to resume the usual schedule or to adjust the timing of the next injection.

Overdose

The effects of filgrastim overdose have not been fully characterized. Higher than intended doses would be expected to amplify the known pharmacological effects, including a marked rise in leukocyte count, more pronounced bone pain, splenic enlargement, and potentially thrombocytopenia. If you believe you have administered too much Tevagrastim, contact your doctor or emergency services promptly. There is no specific antidote; management is supportive and includes blood count monitoring.

Self-Injection Technique

Patients and caregivers may be trained to administer Tevagrastim subcutaneously at home. Do not attempt self-injection without proper training from a healthcare professional. The following steps summarize standard technique:

1. Bring the syringe to room temperature by removing it from the refrigerator about 30 minutes before injection. Do not use a microwave or hot water to warm the product.
2. Wash your hands thoroughly with soap and water, and prepare a clean, well-lit work surface.
3. Inspect the solution: it should be clear and colorless, with no visible particles. Check the expiration date. Do not use an expired, cloudy, discolored, or particulate solution.
4. Choose an injection site — the front of the thigh or the abdomen, at least 5 cm from the navel. Rotate sites daily.
5. Clean the site with an alcohol swab and allow it to dry.
6. Remove the needle cap straight off. Do not twist.
7. Pinch the skin gently and insert the needle at a 45 to 90 degree angle.
8. Inject the solution slowly, pressing the plunger down with steady pressure until the syringe is empty.
9. Remove the needle and apply gentle pressure with a dry cotton ball if there is any bleeding. Do not rub the area.
10. Dispose of the used syringe in an approved sharps container. Do not recap or reuse.

What Are the Side Effects of Tevagrastim?

Like all medicines, Tevagrastim can cause side effects, although not everybody experiences them. The frequency and severity of adverse reactions depend on the underlying condition, the concomitant therapy (especially chemotherapy), the dose used, and individual patient factors. Many symptoms listed below — including anemia, thrombocytopenia, nausea, mucositis, and fatigue — may be related to the underlying disease or concurrent chemotherapy rather than to filgrastim itself, and distinguishing the cause often requires careful clinical judgment.

Side Effects by Frequency

Bone Pain: The Characteristic Filgrastim Side Effect

A very common and distinctive effect of filgrastim therapy is musculoskeletal pain, particularly in the long bones, lower back, pelvis, and sternum. This occurs because filgrastim stimulates a rapid expansion of the myeloid compartment within the bone marrow, which increases pressure on the periosteum and surrounding structures. The pain is usually mild to moderate, often worst on days 2 to 4 of treatment, and typically resolves within a few days of discontinuation. Most patients respond well to standard analgesics, such as paracetamol (acetaminophen) or ibuprofen. Stronger analgesia or dose adjustment is occasionally required, and it is important to report severe or persistent pain to your healthcare team.

Graft-versus-Host Disease (GvHD)

Patients who receive allogeneic stem cell transplants may develop graft-versus-host disease, in which donor immune cells attack the recipient's tissues. GvHD is classified as acute or chronic and can affect the skin (rash, especially on the palms and soles), the gastrointestinal tract (diarrhea, nausea, elevated bilirubin), the liver (cholestasis), and the eyes or lungs. GvHD is managed by the transplant team, usually with corticosteroids and other immunosuppressants, and its relationship to filgrastim is indirect: filgrastim facilitates engraftment but does not itself cause GvHD.

Effects in Healthy Stem Cell Donors

In healthy donors receiving filgrastim for peripheral blood stem cell mobilization, the most common effects are transient bone pain, headache, fatigue, and mild leukocytosis and thrombocytopenia. These effects resolve rapidly after completion of therapy. Very rare but serious events, including splenic rupture, severe allergic reactions, and pulmonary events, have been reported. Donors are carefully screened, counseled, and monitored before, during, and after mobilization.

How Should You Store Tevagrastim?

Correct storage of Tevagrastim is essential to maintain the medicine's effectiveness and safety. Because filgrastim is a recombinant protein, it is sensitive to temperature extremes, light, and mechanical agitation. Follow these storage and handling guidelines carefully:

• Refrigerate: Store in a refrigerator at 2 °C to 8 °C (36 °F to 46 °F). Keep the pre-filled syringe in the outer carton to protect from light.
• Do not freeze: Freezing can damage the tertiary structure of the protein and reduce efficacy. Accidental single exposure to freezing temperatures for less than 24 hours does not usually affect stability, but any product that has been frozen for longer, or frozen more than once, must be discarded.
• Room temperature use: Tevagrastim may be removed from the refrigerator and kept at room temperature (not above 25 °C / 77 °F) for a single period of up to 72 hours. After that period, any unused product must be discarded and must not be returned to the refrigerator.
• Bring to room temperature before use: For a more comfortable injection, let the pre-filled syringe sit at room temperature for about 30 minutes before administration. Do not use a microwave, hot water, or direct sunlight to warm the product.
• Visual inspection: Before use, check that the solution is clear and colorless. Do not use if the solution appears cloudy, discolored, or contains visible particles.
• Expiration date: The expiry date printed on the label refers to the last day of the indicated month. Do not use after the expiration date.
• Keep out of sight and reach of children: Store medicines safely, particularly when refrigerated at home.
• Disposal: Do not dispose of medicines in household waste or via wastewater. Return unused or expired medicines to your pharmacy or local take-back program, and always dispose of used syringes in an approved sharps container.

Do not replace the needle cap on a used needle, as this increases the risk of accidental needle-stick injury. Used syringes must be discarded in an approved sharps container immediately after use. Ask your pharmacist or nurse for local guidance on sharps disposal if you are unsure.

Dilution and Handling (Healthcare Professionals)

When intravenous administration is required, Tevagrastim may be diluted in 5% glucose (dextrose) solution only. It should not be diluted with sodium chloride 0.9% (normal saline), because filgrastim can adsorb to glass and some plastics under those conditions. Dilution to final concentrations below 0.2 MU (2 µg) per ml is not recommended. For concentrations between 0.2 and 1.5 MU/ml, human serum albumin (HSA) should be added to achieve a final albumin concentration of 2 mg/ml to prevent adsorption. After dilution in 5% glucose, Tevagrastim is chemically and physically stable for up to 24 hours at 2–8 °C; however, from a microbiological perspective, diluted solutions should be used as soon as possible after preparation, and not stored for more than 24 hours.

What Does Tevagrastim Contain?

Understanding the complete composition of Tevagrastim is important, particularly if you have known allergies or metabolic intolerances. Below is a breakdown of the active substance, excipients, and pharmaceutical form.

Active Substance

The active substance is filgrastim, a recombinant human granulocyte colony-stimulating factor (rhG-CSF) produced in Escherichia coli using recombinant DNA technology. Each pre-filled syringe contains one of the following strengths:

• 30 MU (300 micrograms) filgrastim in 0.5 ml solution, corresponding to a concentration of 60 MU/ml (0.6 mg/ml).
• 48 MU (480 micrograms) filgrastim in 0.8 ml solution, corresponding to a concentration of 60 MU/ml (0.6 mg/ml).

The unit "MU" stands for "million international units" and is a measure of biological potency used specifically for filgrastim. One microgram of filgrastim corresponds to approximately 0.1 MU (100,000 IU). The conversion is relevant because some prescribing guidelines use µg/kg while others use MU/kg to express the dose.

Other Ingredients (Excipients)

• Sodium hydroxide (for pH adjustment)
• Glacial acetic acid (for pH adjustment)
• Sorbitol (E420) — tonicity agent, 50 mg/ml; contraindicated in hereditary fructose intolerance
• Polysorbate 80 (surfactant and protein stabilizer)
• Water for injections (solvent)

Appearance and Packaging

Tevagrastim is a clear, colorless solution for injection or intravenous infusion. It is supplied in single-use pre-filled glass syringes with graduated markings that allow precise dose measurement. Tevagrastim is available in pack sizes of 1, 5, or 10 pre-filled syringes, with or without alcohol swabs or needle-stick safety devices, depending on the market and national approval. Not all pack sizes may be available in every country.

The marketing authorization for Tevagrastim is held by Teva GmbH, Ulm, Germany. Manufacturing is performed at European Medicines Agency-approved facilities. Tevagrastim received its initial EU marketing authorization in September 2008 and has since been marketed across the European Economic Area. Regulatory decisions, updated product information, and the latest SmPC are available from the European Medicines Agency.

References

This article is based on evidence from internationally recognized medical and regulatory sources. All information has been reviewed against current clinical guidelines and peer-reviewed research.

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Medical Editorial Team

This article was written and reviewed by the iMedic Medical Editorial Team, which includes board-certified physicians specializing in oncology, hematology, and clinical pharmacology. Our team follows international editorial standards and the GRADE evidence framework to ensure that all medical information is accurate, current, and evidence-based. We have no commercial ties to pharmaceutical manufacturers and disclose no conflicts of interest in relation to this content.

Last reviewed: January 2, 2026 | Next scheduled review: July 2, 2026