Ratiograstim (Filgrastim)

What Is Ratiograstim and What Is It Used For?

Ratiograstim belongs to a group of medicines called cytokines, more specifically a granulocyte colony-stimulating factor (G-CSF). G-CSF is a small protein that occurs naturally in the human body and regulates the production, maturation, and survival of neutrophils — the most abundant type of white blood cell and a critical component of the innate immune system. The filgrastim contained in Ratiograstim is manufactured using recombinant DNA technology in Escherichia coli bacteria. The resulting protein is a non-glycosylated, methionylated form of human G-CSF with a molecular weight of approximately 18.8 kDa. Clinically, it has an identical pharmacological profile to endogenous G-CSF and the reference medicine Neupogen.

A reduction in the number of circulating neutrophils, known as neutropenia, significantly weakens the body's ability to fight 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 infections. Febrile neutropenia — the combination of fever and severe neutropenia during or after chemotherapy — is one of the leading causes of hospital admission, treatment delay, and mortality in oncology. By accelerating the recovery of neutrophil counts, filgrastim reduces the incidence, severity, and duration of infections, limits the need for intravenous antibiotics, and helps maintain optimal chemotherapy dose intensity.

Ratiograstim is a biosimilar medicine, meaning it has been developed to be highly similar to an already authorized biological medicine (the reference product Neupogen, first approved in 1991). In 2008, Ratiograstim became one of the first biosimilar filgrastim products approved by the European Medicines Agency, alongside its parent brand Tevagrastim. Rigorous comparability studies, including physicochemical characterization, in vitro pharmacology, and clinical trials in patients with breast cancer and lung cancer, confirmed that Ratiograstim has equivalent quality, safety, and efficacy to the reference product. Today, numerous filgrastim biosimilars are widely used worldwide, providing affordable access to an essential supportive care medicine.

Mechanism of Action

Filgrastim exerts its effects by binding to specific G-CSF receptors (CD114) expressed on the surface of neutrophil progenitor cells in the bone marrow and on mature neutrophils. Receptor binding activates intracellular signaling cascades including the JAK2/STAT3, PI3K/AKT, and MAPK pathways. The downstream effect is an acceleration of neutrophil proliferation, maturation, and release from the bone marrow into the peripheral blood. In addition to increasing neutrophil numbers, filgrastim enhances the functional capacity of mature neutrophils, including chemotaxis, phagocytic activity, and oxidative burst — the three core mechanisms by which neutrophils kill invading pathogens.

Following a single subcutaneous dose, the serum concentration of filgrastim peaks within 4 to 6 hours, and the drug is eliminated with an effective half-life of approximately 3.5 hours. Daily subcutaneous administration over several days produces a rapid, dose-dependent rise in the absolute neutrophil count, which generally reaches its maximum within 3 to 5 days of starting treatment and returns toward baseline within a few days of stopping therapy. Clearance occurs primarily through receptor-mediated degradation in neutrophils themselves and through renal elimination.

Approved Indications

Ratiograstim is authorized for use in the following clinical situations:

• Chemotherapy-induced neutropenia: To reduce the duration of neutropenia and the incidence of febrile neutropenia in patients receiving cytotoxic chemotherapy for malignancies other than chronic myeloid leukemia and myelodysplastic syndromes. This is the most common indication for filgrastim worldwide.
• Bone marrow transplantation: To reduce the duration of neutropenia and the associated infection risk following myeloablative therapy and subsequent bone marrow or peripheral blood stem cell transplantation.
• Peripheral blood stem cell (PBSC) mobilization: In both patients and healthy donors, to mobilize hematopoietic stem cells from the bone marrow into the peripheral blood for collection by leukapheresis and subsequent autologous or allogeneic transplantation.
• Severe chronic neutropenia (SCN): Long-term treatment to raise neutrophil counts and reduce the incidence of infection-related events in adults and children with congenital, cyclic, or idiopathic neutropenia and a history of severe or recurrent infections (ANC persistently ≤ 0.5 × 10⁹/L).
• Advanced HIV infection with persistent neutropenia: To achieve and maintain a normal neutrophil count and reduce the risk of bacterial infections when other options are not considered appropriate.

In addition to its licensed indications, filgrastim is used in several specialized clinical contexts including the management of aplastic anemia, myelodysplastic syndromes where specific evidence supports its role, and radiation-induced myelosuppression. International guidelines from the American Society of Clinical Oncology (ASCO), the European Organisation for Research and Treatment of Cancer (EORTC), the National Comprehensive Cancer Network (NCCN), and the European Society for Medical Oncology (ESMO) recommend primary prophylactic use of G-CSFs when the overall risk of febrile neutropenia is approximately 20% or greater, or when individual patient risk factors elevate the risk above this threshold.

What Should You Know Before Taking Ratiograstim?

Contraindications

Ratiograstim must not be used in patients with known hypersensitivity (allergy) to filgrastim or to any of the excipients, which include glacial acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 80, and water for injections. If you have ever experienced an allergic reaction to any filgrastim-containing product — including the reference product Neupogen or any other filgrastim biosimilar — Ratiograstim is also contraindicated because of the potential for cross-reactivity. The needle shield of the pre-filled syringe contains dry natural rubber (a latex derivative), which may cause severe allergic reactions in latex-sensitive individuals.

Ratiograstim should also not be used to increase cytotoxic chemotherapy doses beyond established regimens, as doing so may increase toxicity without demonstrated survival benefit. The medicine is not intended for use in congenital neutropenia that is clearly associated with cytogenetic abnormalities predisposing to acute myeloid leukemia without careful specialist supervision.

Warnings and Precautions

Before starting treatment with Ratiograstim, inform your doctor or pharmacist if you have any of the following conditions. Filgrastim therapy requires close clinical and laboratory monitoring, and certain conditions may require dose adjustments or additional precautions:

• Sickle cell trait or sickle cell disease: Filgrastim has been reported to precipitate severe — and occasionally fatal — sickle cell crises. Your doctor will carefully weigh the benefits against the risks before prescribing filgrastim.
• Osteoporosis or low bone density: Long-term filgrastim therapy may be associated with further reductions in bone mineral density. Bone density monitoring may be recommended during extended treatment.
• Kidney disease: Although filgrastim is generally well tolerated, cases of glomerulonephritis have been reported. Urinalysis and kidney function tests may be performed during treatment.
• Known lung disease: Rare but serious pulmonary events, including acute respiratory distress syndrome (ARDS), have been described, especially in neutropenic patients with active pulmonary infection.
• Recent major surgery, trauma, or pulmonary infiltrates: Transient leukocytosis during filgrastim treatment could aggravate pre-existing inflammation in some settings.

If you respond poorly or stop responding to Ratiograstim, your doctor will investigate the underlying cause. Rarely, this may involve testing for neutralizing antibodies against filgrastim that can reduce the medicine's effectiveness over time. Immunogenicity to filgrastim is uncommon but has been described particularly with long-term administration.

Patients with severe chronic neutropenia (particularly congenital forms) have an inherent increased risk of developing blood cancers such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Long-term G-CSF therapy has been associated with cytogenetic abnormalities in some patients with congenital neutropenia, although a direct causal relationship has not been established. Your doctor will discuss this risk with you and recommend periodic monitoring, which may include bone marrow examinations and cytogenetic analysis.

If you are a healthy stem cell donor, you must be at least 16 years old (specific age limits depend on national guidelines and institutional protocols). Donors should be evaluated for contraindications to apheresis and carefully counseled about the typical mobilization-related symptoms (bone pain, headache) and the very rare but serious risk of splenic rupture. Post-donation follow-up is standard practice in most allogeneic donor programs.

Pregnancy and Breastfeeding

Ratiograstim has not been adequately studied in pregnant women and is therefore not recommended during pregnancy. Animal studies have shown some reproductive toxicity at high doses, and the potential risk to the human fetus is unknown. Inform your doctor before starting treatment if you are pregnant, think you may be pregnant, or are planning to have a baby. Women of childbearing potential should consider using effective contraception during treatment. If you become pregnant while receiving Ratiograstim, contact your treating physician without delay to discuss the benefits and risks of continuing therapy.

It is not known whether filgrastim passes into human breast milk. Because many proteins are excreted in breast milk and because of the potential for adverse effects in the nursing infant, breastfeeding should be discontinued during Ratiograstim therapy unless specifically advised otherwise by your doctor, who will weigh the benefits of breastfeeding against the potential risks.

Driving and Operating Machinery

Ratiograstim has not been studied for its effects on driving or using machines, and no significant impairment has been reported in clinical use. However, some patients may experience dizziness, fatigue, or weakness during treatment. If you experience any of these symptoms, you should avoid driving and operating machinery until they resolve.

Important Information About Excipients

How Does Ratiograstim Interact with Other Drugs?

As with any biological therapy, it is essential to inform your healthcare team about every medicine you are taking, have recently taken, or might take — including prescription drugs, over-the-counter products, herbal preparations, and nutritional supplements. Filgrastim interacts primarily with other myelotoxic or myelostimulatory agents, and timing of administration relative to cytotoxic chemotherapy is critical.

Major Interactions

The most clinically important interaction involves cytotoxic chemotherapy. Because filgrastim stimulates the proliferation of rapidly dividing myeloid precursors, those cells become more sensitive to the cytotoxic effects of chemotherapy drugs, particularly those acting on the S-phase of the cell cycle. Administering filgrastim too close to chemotherapy can worsen, rather than alleviate, myelosuppression. For this reason, filgrastim should not be given within 24 hours before or within 24 hours after the administration of cytotoxic chemotherapy.

The safety and efficacy of filgrastim given on the same day as cytotoxic chemotherapy has not been definitively established. Similarly, the safety of filgrastim in patients receiving high-dose chemotherapy combined with hematopoietic growth factors beyond the licensed indications should be assessed by specialist physicians with access to current protocols.

Minor Interactions

Ratiograstim is a protein product metabolized largely through receptor-mediated uptake and proteolytic degradation. It is not processed by the cytochrome P450 (CYP) enzyme system, and therefore the classic pharmacokinetic interactions that complicate small-molecule drug therapy are not expected. Filgrastim has not shown significant interactions with most commonly used supportive care medicines, including antiemetics (ondansetron, metoclopramide, aprepitant), proton-pump inhibitors, corticosteroids used as antiemetics, opioid analgesics, and antibiotics. Nevertheless, the medical team should review all concurrent therapy to ensure that the overall treatment plan is coordinated and safe.

Care should be exercised with medicines that may independently cause increases in white blood cell counts (such as corticosteroids, especially when used at high doses for extended periods), because the combined effect with filgrastim may produce leukocytosis that requires clinical monitoring. Non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are frequently co-administered with filgrastim to manage bone pain and do not show clinically significant interactions.

What Is the Correct Dosage of Ratiograstim?

Always use Ratiograstim exactly as your doctor has prescribed. The dose, route, and duration of treatment depend on your medical condition, your body weight, and how well your bone marrow responds to therapy. Your doctor will perform regular blood tests to monitor your absolute neutrophil count (ANC) and platelet count. These results guide when to stop treatment or whether to adjust the dose. Never change the dose or stop treatment without consulting your prescribing physician.

Adults

For most adult patients, Ratiograstim is administered as a once-daily subcutaneous injection. The standard starting dose for chemotherapy-induced neutropenia is 0.5 million units per kilogram of body weight per day (equivalent to 5 micrograms/kg/day). The first dose should be given no earlier than 24 hours after the last dose of cytotoxic chemotherapy and typically continues until the expected neutrophil nadir has passed and the ANC has recovered to within the normal range — usually a total treatment duration of up to 14 days. In bone marrow transplant recipients, a higher starting dose of 1.0 MU/kg/day (10 mcg/kg/day) is typically used, administered as a 30-minute or 24-hour intravenous infusion or a 24-hour subcutaneous continuous infusion.

For stem cell mobilization, the dose varies depending on whether filgrastim is used alone or in combination with mobilizing chemotherapy. When used as monotherapy for mobilization in patients or healthy donors, 1.0 MU/kg/day (10 mcg/kg/day) subcutaneously for 4 to 7 days is typical. When given after mobilizing chemotherapy in patients, 0.5 MU/kg/day (5 mcg/kg/day) starting the day after chemotherapy is common. The optimal timing of leukapheresis is guided by peripheral CD34+ cell counts, which correlate with stem cell yield.

Children

Ratiograstim may be used in children with chemotherapy-induced neutropenia, severe chronic neutropenia, or for stem cell mobilization. Paediatric dosing follows the same weight-based principles as adult dosing and is generally well tolerated. Safety and efficacy data in children are consistent with those observed in adult populations. Dose adjustments for very young children should be individualized by the pediatric oncology or hematology team, and injections should normally be administered by trained parents or caregivers after appropriate education. Infants and very small children may require reconstituted solutions or specialized preparations under the direction of the treating hospital pharmacy.

Elderly

No specific dose adjustments are routinely required for elderly patients. Clinical trials with filgrastim have included older adults, and efficacy and safety have generally been comparable to those observed in younger adults. However, older patients may have reduced physiological reserve, impaired renal or hepatic function, and more comorbidities, and may be more susceptible to certain adverse effects such as splenomegaly, bone pain, or capillary leak syndrome. Careful clinical monitoring is recommended. The dosing principles otherwise remain the same as for younger adults.

Renal or Hepatic Impairment

Studies of filgrastim in patients with severe renal impairment (including those on dialysis) or severe hepatic impairment have shown pharmacokinetic and pharmacodynamic profiles similar to those in patients with normal organ function. Consequently, no dose adjustment is required in renal or hepatic impairment. Clinical monitoring should nonetheless be intensified in such patients, and any signs of fluid retention, worsening kidney function, or significant liver enzyme abnormalities should be investigated promptly.

Missed Dose

If you forget to inject a dose or inject too little Ratiograstim, contact your doctor or nurse as soon as possible for advice. Do not take a double dose to make up for a missed one. Depending on when the missed dose was noticed and how far along in treatment you are, your doctor may advise resuming the normal daily schedule or adjusting the timing of the next injection. Missing more than one consecutive dose may reduce the effectiveness of the treatment and should always be discussed with the prescribing team.

Overdose

Do not increase the dose prescribed by your doctor. If you believe you have injected more Ratiograstim than recommended, or if a caregiver accidentally gives a higher dose, contact your doctor, emergency department, or local poison control center without delay. The effects of a filgrastim overdose are not fully characterized, but excessive doses would be expected to intensify the known pharmacological effects, including marked leukocytosis, significant bone pain, splenomegaly, and thrombocytopenia. There is no specific antidote; management is supportive and may include close monitoring of blood counts and discontinuation of therapy until values normalize.

Self-Injection Instructions

Patients, parents, or caregivers may be trained to administer subcutaneous injections at home. Self-injection should only be attempted after receiving proper training from a qualified healthcare professional (nurse, doctor, or pharmacist). When self-administering Ratiograstim, follow these steps carefully:

1. Remove the syringe from the refrigerator and allow it to reach room temperature naturally for approximately 30 minutes. Do not warm it using a microwave, hot water, or any direct heat source.
2. Wash your hands thoroughly with soap and water, and prepare a clean, well-lit workspace with good lighting.
3. Inspect the solution — it must be clear and colorless with no visible particles. Check the expiration date printed on the syringe and carton. Do not use if the product is expired, cloudy, discolored, or contains particles.
4. Choose an injection site: the upper thigh or the abdomen (avoiding a 5 cm area around the navel). Rotate sites daily to prevent local soreness, redness, or skin reactions.
5. Clean the site with an alcohol swab in a circular motion from the center outwards, and allow it to air-dry.
6. Remove the needle cap by pulling it straight off without touching the needle. If your doctor has prescribed a dose smaller than the full syringe, carefully adjust the plunger to the indicated mark.
7. Pinch the skin between your thumb and index finger and insert the needle at a 45 to 90 degree angle. Pull back gently on the plunger — if blood appears, withdraw the needle and choose a different site.
8. Inject slowly with steady pressure until the syringe is empty.
9. Remove the needle at the same angle it was inserted, apply gentle pressure with a clean cotton ball or gauze (do not rub), and dispose of the syringe immediately in an approved sharps container. Each syringe is for single use only.

What Are the Side Effects of Ratiograstim?

Like all medicines, Ratiograstim can cause side effects, although not everyone experiences them. The frequency and severity of side effects depends on the underlying condition being treated, the dose administered, the duration of therapy, and individual patient characteristics. Many of the side effects listed below (particularly anemia, thrombocytopenia, nausea, mucositis, and fatigue) are also commonly caused by the underlying disease or by concurrent chemotherapy, rather than by filgrastim itself. Your medical team will help interpret which effects are most likely attributable to Ratiograstim and which require specific intervention.

Side Effects by Frequency

A very common side effect specific to filgrastim is musculoskeletal pain, which manifests most often as deep bone pain in the sternum, pelvis, or long bones. This occurs because filgrastim stimulates increased cellular activity and expansion within the bone marrow cavity, producing mechanical pressure and the release of inflammatory mediators. The pain is typically mild to moderate, often begins 1 to 3 days after starting treatment, and can usually be managed with over-the-counter painkillers such as paracetamol (acetaminophen) or ibuprofen. Loratadine, an H1-antihistamine, has also shown modest benefit in some studies. If pain becomes severe or interferes with activities of daily living, contact your doctor, who may adjust the dose or prescribe stronger analgesia.

In patients undergoing allogeneic stem cell or bone marrow transplantation, graft-versus-host disease (GvHD) may occur — a reaction in which donor immune cells attack the recipient's tissues. GvHD can manifest as skin rash (especially on the palms and soles), mouth ulcers, liver inflammation, and involvement of the eyes, lungs, or intestinal tract. GvHD is typically managed by the transplant team using immunosuppressive medicines.

In healthy stem cell donors, transient leukocytosis (increased white blood cell counts) and thrombocytopenia (reduced platelets) are commonly observed during and immediately after filgrastim administration. These changes typically normalize within 1 to 2 weeks after the last dose. Donor blood counts should be monitored before apheresis begins and again shortly afterwards.

How Should You Store Ratiograstim?

Proper storage is essential to maintain the effectiveness and safety of Ratiograstim. As a recombinant protein biological product, filgrastim is sensitive to temperature extremes, light exposure, and mechanical agitation. Incorrect storage can cause the protein to aggregate or degrade, reducing its biological activity and potentially increasing the risk of immunogenic reactions. Follow these storage guidelines precisely:

• Refrigerate: Store in a refrigerator at 2 °C to 8 °C (36 °F to 46 °F). Keep the pre-filled syringe in its outer carton to protect from light.
• Do not freeze: Freezing can permanently damage the protein structure and render the medicine ineffective or unsafe. Brief accidental exposure to freezing temperatures for up to 24 hours is generally considered not to affect stability; however, if you suspect the product has been frozen, contact the pharmacy before using it. Do not use any syringe that shows signs of having been frozen (unusual appearance, ice crystals).
• Room temperature use: Within the shelf life, the pre-filled syringe may be removed from the refrigerator and stored at room temperature (not above 25 °C / 77 °F) for a single period of up to 3 days. If the product is not used within this time, it must be discarded and must not be returned to the refrigerator.
• Before injection: For a more comfortable injection, allow the pre-filled syringe to reach room temperature naturally for approximately 30 minutes before administration, or warm it gently by holding it in your hand for a few minutes. Do not warm it by any other method.
• Visual inspection: Always inspect the solution before use. It must be clear and colorless. Do not use the syringe if the solution appears cloudy, discolored, contains visible particles, or if the syringe shows any signs of damage (cracks, leaks).
• Expiration date: Check the expiration date printed on the label and carton. The expiry date 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 all medicines safely out of the reach and sight of children.

Do not replace the needle cap on used needles, as this increases the risk of accidental needle-stick injury. Dispose of used syringes in an approved sharps disposal container according to your local regulations and community pharmacy take-back programs. Do not dispose of medicines in household waste or flush them down toilets or drains. These measures protect the environment and prevent accidental exposure to others.

Dilution and Preparation (Healthcare Professionals)

When dilution is required for intravenous infusion, Ratiograstim may be diluted in 5% glucose (dextrose) solution only. It must not be diluted with sodium chloride (normal saline) solution, because this may cause precipitation and drug adsorption to glass and plastic infusion materials. Dilution to a final concentration below 0.2 MU (2 micrograms) per ml is not recommended. For final concentrations below 1.5 MU (15 micrograms) per ml, human serum albumin (HSA) must be added to a final concentration of 2 mg/ml to prevent adsorption of the drug. After dilution in 5% glucose, Ratiograstim is compatible with glass and various plastics including polyvinyl chloride (PVC), polyolefin, and polypropylene. The diluted solution is physically and chemically stable for up to 24 hours at 2–8 °C, but from a microbiological standpoint it should be used immediately unless dilution has occurred under controlled and validated aseptic conditions.

What Does Ratiograstim Contain?

Understanding the complete composition of Ratiograstim is important, particularly if you have known allergies or intolerances to any specific ingredient. Below is a full breakdown of both the active substance and the inactive excipients used in the formulation:

Active Substance

The active substance of Ratiograstim is filgrastim, a recombinant methionyl human granulocyte colony-stimulating factor (rhG-CSF). It is produced in Escherichia coli bacteria using recombinant DNA technology and is structurally and functionally analogous to endogenous human G-CSF, with the exception of an additional N-terminal methionine residue and the absence of glycosylation. Each pre-filled syringe contains either:

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

Note that 1 MU (million units) of filgrastim corresponds to 10 micrograms, based on the international standard for biological activity. This conversion is used consistently across all filgrastim products.

Other Ingredients (Excipients)

• Glacial acetic acid (pH adjustment)
• Sodium hydroxide (pH adjustment)
• Sorbitol (E420) — source of fructose; contraindicated in hereditary fructose intolerance
• Polysorbate 80 (non-ionic surfactant, prevents protein aggregation)
• Water for injections

Appearance and Packaging

Ratiograstim is a clear, colorless solution for injection or infusion supplied in pre-filled glass syringes. Each syringe is fitted with a stainless-steel needle and a needle shield containing dry natural rubber (a latex derivative). The syringes may be supplied with or without an automatic needle guard for added safety during administration and disposal. Ratiograstim is typically available in pack sizes of 1, 5, or 10 pre-filled syringes, although availability of specific pack sizes may vary between countries and over time.

The original marketing authorization holder of Ratiograstim is ratiopharm GmbH (Graf-Arco-Str. 3, 89079 Ulm, Germany), part of the Teva pharmaceutical group. Manufacturing is carried out under strict international quality standards according to EMA and national regulatory authority requirements.

References

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

1. European Medicines Agency (EMA). Ratiograstim: EPAR – Product Information. Updated 2025. Available at: EMA – Ratiograstim EPAR.
2. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2015;33(28):3199-3212. doi:10.1200/JCO.2015.62.3488
3. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Hematopoietic Growth Factors. Version 1.2025.
4. World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List (2023). Filgrastim is included as an essential medicine for chemotherapy-induced neutropenia.
5. Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47(1):8-32.
6. Gascon P, Tesch H, Verpoort K, et al. Clinical experience with Zarzio in Europe: what have we learned? Support Care Cancer. 2013;21(10):2925-2932.
7. Crawford J, Dale DC, Lyman GH. Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer. 2004;100(2):228-237.
8. Dale DC, Cottle TE, Fier CJ, et al. Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry. Am J Hematol. 2003;72(2):82-93.
9. Lyman GH, Dale DC, Culakova E, et al. The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials. Ann Oncol. 2013;24(10):2475-2484.
10. European Medicines Agency (EMA). Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. EMEA/CHMP/BMWP/42832/2005 Rev1. 2014.
11. British National Formulary (BNF). Filgrastim. National Institute for Health and Care Excellence (NICE). Available at: bnf.nice.org.uk.
12. del Giglio A, Eniu A, Ganea-Motan D, et al. XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy. BMC Cancer. 2008;8:332. (Key pivotal trial supporting Ratiograstim/Tevagrastim approval.)
13. Engert A, Griskevicius L, Zyuzgin Y, Lubenau H, del Giglio A. XM02, the first granulocyte colony-stimulating factor biosimilar, is safe and effective in reducing the duration of severe neutropenia and incidence of febrile neutropenia in patients with non-Hodgkin lymphoma receiving chemotherapy. Leuk Lymphoma. 2009;50(3):374-379.

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 all medical information is accurate, current, and evidence-based.

Last reviewed: January 29, 2026 | Next scheduled review: July 29, 2026