Silapo (Epoetin Zeta): Uses, Dosage & Side Effects
Biosimilar erythropoietin for the treatment of anemia
Quick Facts About Silapo
Key Takeaways About Silapo
- Biosimilar erythropoietin: Silapo contains epoetin zeta, a biosimilar of the reference medicine Eprex/Erypo. It works identically to endogenous erythropoietin by stimulating red blood cell production in the bone marrow.
- Three main indications: Approved for anemia in chronic kidney disease (dialysis and pre-dialysis), chemotherapy-induced anemia in adults with solid tumors, lymphoma, or myeloma, and reduction of allogeneic blood transfusions before major elective surgery.
- Target hemoglobin matters: Hemoglobin should be maintained between 10 and 12 g/dL. Exceeding 12 g/dL increases the risk of stroke, myocardial infarction, and venous thromboembolism.
- Iron supplementation is essential: Adequate iron stores (transferrin saturation >20%, ferritin >100 ng/mL) are required for Silapo to work. Most patients need concomitant oral or intravenous iron.
- Close monitoring required: Blood pressure, hemoglobin, iron status, and serum potassium should be checked regularly. Dose adjustments are based on the rate of hemoglobin rise, which should not exceed 2 g/dL per month.
What Is Silapo and What Is It Used For?
Quick Answer: Silapo is a biosimilar medicine containing epoetin zeta, a laboratory-produced version of the human hormone erythropoietin. It stimulates the bone marrow to produce more red blood cells and is used primarily to treat anemia in chronic kidney disease, chemotherapy-induced anemia, and to reduce blood transfusion requirements around major elective surgery.
Silapo belongs to a class of medicines known as erythropoiesis-stimulating agents (ESAs). Its active substance, epoetin zeta, is a 165-amino acid glycoprotein produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells. Epoetin zeta has the same amino acid sequence as naturally occurring human erythropoietin and binds to the same erythropoietin receptor on bone marrow progenitor cells, producing the same biological effect as the endogenous hormone.
Erythropoietin is essential for the body's ability to transport oxygen. Under normal conditions, specialized cells in the kidneys sense the amount of oxygen reaching the tissues. When oxygen delivery falls – for example, during bleeding, at high altitude, or when red blood cells are produced too slowly – these cells release erythropoietin into the bloodstream. The hormone then travels to the bone marrow, where it signals erythroid progenitor cells to multiply and mature into red blood cells (erythrocytes). In chronic kidney disease, this feedback loop is broken because the damaged kidneys can no longer produce enough erythropoietin, leading to progressive anemia. Silapo replaces the missing hormone and restores the body's capacity to make red blood cells.
Silapo was approved by the European Medicines Agency (EMA) in 2007 as a biosimilar of the reference medicine Eprex/Erypo (epoetin alfa). A biosimilar is a biological medicine that is highly similar to a previously authorized reference biological medicine. Extensive comparability studies – spanning analytical characterization, non-clinical pharmacology, pharmacokinetics, pharmacodynamics, and confirmatory clinical trials – have demonstrated that Silapo matches its reference medicine in quality, safety, and efficacy. Regulatory review for biosimilars is rigorous, and patients can expect comparable therapeutic outcomes to those of the originator product.
Silapo is manufactured by STADA Arzneimittel AG under a license originally developed by Norbitec (now part of Hospira/Pfizer). The same active substance, epoetin zeta, is also marketed under the brand name Retacrit. Both products are identical in terms of active ingredient and clinical effect, but are distributed through different commercial partners in the European Union.
Approved Indications
Silapo is authorized for the following indications according to the EMA Summary of Product Characteristics:
- Chronic kidney disease (CKD): Treatment of symptomatic anemia in adult patients on hemodialysis, adult patients on peritoneal dialysis, and adult patients with renal insufficiency not yet on dialysis (pre-dialysis). Silapo is also indicated for the treatment of symptomatic anemia in pediatric patients aged 1–18 years on hemodialysis.
- Chemotherapy-induced anemia: Treatment of anemia and reduction of transfusion requirements in adult patients receiving chemotherapy for non-myeloid malignancies – including solid tumors, malignant lymphoma, and multiple myeloma – who are at risk of transfusion based on their general condition (for example, cardiovascular status or pre-existing anemia at the start of chemotherapy).
- Autologous blood predonation: To increase the yield of autologous blood from patients in a predonation program before planned major elective surgery that is expected to require a large volume of blood. Use is limited to patients with moderate anemia (hemoglobin 10–13 g/dL) in whom blood-conservation procedures are insufficient.
- Reduction of allogeneic blood transfusions: To reduce exposure to allogeneic blood transfusions in adult patients without iron deficiency who are scheduled for major elective orthopedic surgery and are considered at high risk of transfusion complications. Expected perioperative blood loss should be in the range of 900–1,800 mL.
The choice of indication, route of administration, and dosing must always be made by a qualified healthcare professional who can evaluate the individual patient's clinical situation – including hemoglobin level, iron stores, blood pressure, cardiovascular risk profile, and overall health status. Self-medication with any erythropoietin-based product is inappropriate and can result in serious complications. Silapo is not used to treat anemia caused by iron, vitamin B12, or folate deficiency, which require correction of the underlying nutritional deficit.
What Should You Know Before Taking Silapo?
Quick Answer: Silapo should not be used if you have uncontrolled high blood pressure, have had pure red cell aplasia from any erythropoietin, or are hypersensitive to epoetin zeta or any excipient. Careful monitoring of blood pressure and hemoglobin is required, iron stores must be adequate, and special caution is needed in pregnancy, breastfeeding, and cardiovascular disease.
Contraindications
Silapo must not be used in the following situations:
- Uncontrolled hypertension: Patients with poorly controlled high blood pressure should not start Silapo. Blood pressure must be adequately controlled before the first dose and monitored closely throughout treatment.
- Hypersensitivity: Known hypersensitivity to epoetin zeta, to any other erythropoietin, or to any of the excipients is an absolute contraindication. Patients who have had severe allergic reactions to any erythropoietin product should not receive Silapo.
- Pure red cell aplasia (PRCA) after any erythropoietin treatment: Patients who have developed PRCA following previous treatment with any erythropoietin must not receive Silapo or any other erythropoietin. PRCA is a rare but serious condition in which neutralizing antibodies to erythropoietin essentially stop all red blood cell production.
- High risk of thromboembolic events in the surgical setting: In patients undergoing major elective surgery who cannot receive adequate antithrombotic prophylaxis for medical reasons, the risk of venous thromboembolism outweighs the benefit of reduced transfusion needs. These patients should not receive Silapo.
- Patients unable to receive antithrombotic prophylaxis: For the autologous predonation and surgery indications, Silapo is contraindicated in patients who cannot receive adequate antithrombotic prophylaxis due to medical reasons.
Targeting hemoglobin levels above 12 g/dL (7.5 mmol/L) with erythropoiesis-stimulating agents, including Silapo, has been associated with an increased risk of death, serious cardiovascular events (stroke, myocardial infarction, congestive heart failure), and thromboembolic events (deep vein thrombosis and pulmonary embolism). Always use the lowest dose sufficient to reduce the need for red blood cell transfusions.
Warnings and Precautions
Treatment with Silapo requires careful medical supervision. Before initiating therapy and throughout treatment, your healthcare provider will consider the following precautions:
- Blood pressure monitoring: Hypertension is one of the most common side effects of erythropoietin therapy. Blood pressure should be measured regularly and treated adequately. If blood pressure is difficult to control, the dose of Silapo may need to be reduced or treatment temporarily interrupted. In rare cases, hypertensive crisis with encephalopathy-like symptoms (severe headache, confusion, visual disturbance, seizures) may occur – this is a medical emergency.
- Hemoglobin monitoring: Hemoglobin should be measured every 1–2 weeks during dose adjustment and at least monthly during maintenance therapy. The rate of rise should not exceed 2 g/dL in 4 weeks in order to minimize the risk of hypertension and thromboembolic complications. Hemoglobin targets are individualized but generally 10–12 g/dL.
- Iron status: Iron deficiency is the single most common cause of poor response to erythropoietin. Transferrin saturation and serum ferritin should be assessed before starting treatment and monitored regularly afterwards. Iron supplementation (oral or intravenous) is recommended for patients with transferrin saturation below 20% or ferritin below 100 ng/mL.
- Thrombosis risk: There is an increased risk of thromboembolic vascular events during ESA therapy, particularly during the early phase when hemoglobin is rising. Patients with pre-existing cardiovascular disease, a history of thrombosis, active malignancy, or immobilization should be monitored closely.
- Seizure risk: Epoetin therapy has been associated with seizures, particularly in patients with chronic kidney disease. Caution should be used in patients with a history of epilepsy or other seizure disorders, and in the first 90 days of treatment.
- Hepatic impairment: The safety and efficacy of epoetin zeta have not been fully established in patients with hepatic dysfunction. Caution should be exercised in this population, with more frequent monitoring of hemoglobin and potential dose adjustment.
- Potassium levels: Mild increases in serum potassium have been observed during epoetin therapy, particularly in patients with chronic kidney disease. Potassium should be monitored, especially in patients taking other medications that raise potassium (ACE inhibitors, potassium-sparing diuretics).
- Tumor growth concern in cancer patients: Some studies have raised concerns that targeting hemoglobin above 12 g/dL in cancer patients may be associated with shorter overall survival and faster disease progression in certain tumor types. For this reason, ESAs in oncology are reserved for patients at risk of transfusion, and the lowest effective dose is used.
- Pure red cell aplasia (PRCA): PRCA caused by anti-erythropoietin neutralizing antibodies has been reported during subcutaneous treatment with erythropoietins in CKD patients. If a patient's hemoglobin falls unexpectedly despite continued treatment, PRCA should be excluded.
Pregnancy and Breastfeeding
Clinical data regarding the use of Silapo during pregnancy are limited. Animal studies with epoetin have shown reproductive toxicity at doses much higher than those used clinically. Because of the potential risks, Silapo should only be used during pregnancy if the expected benefit to the mother clearly outweighs the potential risk to the fetus. Pregnant patients with severe CKD anemia are sometimes treated to avoid the risks of blood transfusion.
It is not known whether epoetin zeta is excreted in human breast milk. A risk to the breastfed infant cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue Silapo treatment, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother. In most cases, decisions are guided by individual clinical circumstances.
Women of childbearing potential should discuss contraception with their healthcare provider before starting Silapo. If you are pregnant, think you may be pregnant, or are planning to become pregnant, inform your doctor before receiving this medicine.
How Does Silapo Interact with Other Drugs?
Quick Answer: Silapo may interact with cyclosporine (higher blood levels as hematocrit rises), heparin and other anticoagulants (dose may need adjustment during dialysis), ACE inhibitors and ARBs (may blunt response to EPO), and antihypertensive medications (blood pressure effects). Iron supplements are essential for an optimal response. Always inform your healthcare provider about every medicine, supplement, and herbal product you take.
Compared with small-molecule drugs, epoetin zeta has relatively few direct pharmacokinetic drug–drug interactions, because it is a protein that is cleared primarily by target-mediated mechanisms rather than by hepatic metabolism. However, several important pharmacodynamic and indirect interactions should be considered. The pharmacological effects of Silapo – raising hemoglobin and hematocrit – can influence the pharmacokinetics of other drugs, and some drugs can alter the response to ESA therapy.
| Interacting Drug | Type | Effect | Clinical Recommendation |
|---|---|---|---|
| Cyclosporine | Major | Rising hematocrit increases cyclosporine binding to red blood cells and may raise whole-blood levels | Monitor cyclosporine trough levels; anticipate dose adjustment during the first months of Silapo therapy |
| Heparin & anticoagulants | Moderate | Rising hematocrit may require increased heparin dose during hemodialysis; risk of clotting in dialysis lines | Adjust heparin dose based on hematocrit; monitor the dialysis circuit for clotting |
| ACE inhibitors & ARBs | Moderate | May blunt erythropoietin response, possibly by reducing endogenous EPO production or by affecting iron metabolism | Monitor hemoglobin response; higher Silapo doses may be required in some patients |
| Iron supplements | Beneficial (required) | Adequate iron stores are essential for an effective erythropoietin response; iron deficiency limits red blood cell production | Supplement iron (oral or IV) to maintain transferrin saturation >20% and ferritin >100 ng/mL |
| Antihypertensive medications | Moderate | Blood pressure may rise during EPO therapy, potentially counteracting antihypertensive effects | Monitor blood pressure frequently; intensify antihypertensive therapy as needed |
| Hormonal contraceptives & HRT | Moderate | May further increase the thromboembolic risk associated with ESA therapy | Assess overall thrombotic risk profile; consider non-hormonal alternatives when appropriate |
Major Interactions
Cyclosporine is the most clinically significant drug interaction with Silapo, especially in kidney transplant recipients and other patients on calcineurin-inhibitor therapy. Cyclosporine is extensively bound to red blood cells. As Silapo therapy raises hemoglobin and hematocrit, a larger fraction of circulating cyclosporine becomes sequestered within red cells, potentially altering whole-blood levels and tissue distribution. Cyclosporine trough levels should be monitored regularly during the first several months of Silapo therapy, and dose adjustments may be needed to maintain therapeutic concentrations without causing nephrotoxicity.
Erythropoietin therapy may also compound the risk of thromboembolic events in patients already at elevated risk due to estrogen-containing hormonal contraceptives, hormone replacement therapy, or other prothrombotic medications such as tamoxifen. Healthcare providers should assess the overall thrombotic risk profile before initiating Silapo in such patients, and antithrombotic prophylaxis should be considered when appropriate.
Minor Interactions
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have been reported to blunt the erythropoietin response in some patients. Proposed mechanisms include suppression of endogenous erythropoietin production, interference with iron metabolism, and effects on bone marrow progenitor cells. Patients on ACE inhibitors or ARBs who show a suboptimal response to Silapo may require dose escalation or evaluation for other causes of EPO hyporesponsiveness before the regimen is changed.
Other medications that may affect the response to Silapo include nonsteroidal anti-inflammatory drugs (NSAIDs), which can contribute to gastrointestinal blood loss and worsen anemia, and aluminum-containing phosphate binders, which may impair iron absorption and reduce the effectiveness of erythropoietin therapy. Certain chemotherapy regimens, particularly those containing platinum agents, can cause bone marrow suppression that offsets the expected response to Silapo.
It is important to note that epoetin zeta does not undergo significant cytochrome P450-mediated metabolism, so interactions mediated through enzyme induction or inhibition are generally not expected. Food and alcohol have no clinically relevant effect on the pharmacokinetics of Silapo.
What Is the Correct Dosage of Silapo?
Quick Answer: The dosage of Silapo is individualized based on indication, baseline hemoglobin, and response. For chronic kidney disease, typical starting doses are 50 IU/kg three times per week. Doses are adjusted to maintain hemoglobin between 10 and 12 g/dL, with a rate of rise no greater than 2 g/dL per month. Treatment must always be supervised by a qualified healthcare provider.
Silapo dosing is highly individualized and depends on the clinical indication, the patient's current hemoglobin level, the desired target, the rate of rise, and individual response to therapy. All dosing decisions should be made by a physician experienced in the management of anemia with erythropoiesis-stimulating agents. The guidance below summarizes typical dosing based on the EMA Summary of Product Characteristics and international clinical guidelines. The 10,000 IU/1.0 mL pre-filled syringe discussed here provides a convenient unit dose for many adults; other strengths are available for dose titration.
Adults with Chronic Kidney Disease
Hemodialysis Patients
Starting dose: 50 IU/kg three times per week, administered intravenously (typically at the end of dialysis through the venous line).
Dose adjustment: Increase or decrease by approximately 25 IU/kg three times per week if the hemoglobin change is outside target; the rate of rise should not exceed 2 g/dL per month. Adjust at 4-week intervals.
Maintenance dose: Typically 75–300 IU/kg per week, divided into 2–3 doses. Some patients may stabilize outside this range.
Target hemoglobin: 10–12 g/dL; do not exceed 12 g/dL.
Peritoneal Dialysis and Pre-dialysis Patients
Starting dose: 50 IU/kg three times per week, administered subcutaneously.
Dose adjustment: Increase by 25 IU/kg three times per week at 4-week intervals until the target hemoglobin is achieved. Reduce the dose by approximately 25% if hemoglobin rises above 12 g/dL or increases by more than 2 g/dL in 4 weeks.
Maintenance dose: Typically lower than in hemodialysis patients. Once- or twice-weekly subcutaneous administration may suffice due to the longer absorption half-life.
Children (1–18 years) on Hemodialysis
Pediatric Dosing
Starting dose: 50 IU/kg three times per week, administered intravenously.
Dose adjustment: The same principles as in adults apply. Doses are increased by approximately 25 IU/kg three times per week at 4-week intervals if the response is inadequate.
Maintenance dose: Typically 75–300 IU/kg per week. Children, especially those under 5 years, often require higher per-kilogram doses than adults.
Note: Pediatric dosing for pre-dialysis CKD has not been established in clinical trials and is generally individualized.
Adults with Chemotherapy-Induced Anemia
Chemotherapy-Induced Anemia
Starting dose: 150 IU/kg three times per week subcutaneously, or 450 IU/kg once weekly.
Dose escalation: If hemoglobin increases by less than 1 g/dL after 4 weeks, the dose may be increased to 300 IU/kg three times per week.
Discontinuation: If there is no adequate response after a further 4 weeks at the higher dose, treatment should be discontinued. Therapy should also be stopped approximately 4 weeks after the end of chemotherapy.
Target hemoglobin: The lowest hemoglobin concentration that avoids the need for blood transfusions; do not exceed 12 g/dL.
Surgical Indications
Reduction of Allogeneic Blood Transfusion
Dose: 600 IU/kg subcutaneously on days 21, 14, and 7 before surgery and on the day of surgery. Alternatively, 300 IU/kg daily for 10 days before surgery, on the day of surgery, and for 4 days afterwards.
Iron supplementation: All surgical patients should receive adequate iron supplementation throughout the treatment period, ideally started before the first dose of Silapo.
Thrombosis prevention: Adequate antithrombotic measures are mandatory in all surgical patients receiving an ESA. Patients who cannot receive prophylaxis should not be treated with Silapo.
Autologous Blood Predonation
Dose: 600 IU/kg intravenously twice weekly for 3 weeks before surgery, following each predonation session and on the day of surgery. Iron supplementation should be provided throughout.
Eligibility: Reserved for patients with moderate anemia (hemoglobin 10–13 g/dL) where the expected surgery will require a larger blood volume than blood-conservation procedures can provide alone.
Elderly Patients
No specific dose adjustment is required for elderly patients on the basis of age alone. However, elderly patients often have more comorbidities, including cardiovascular disease, and are more likely to receive concomitant medications. A lower starting dose, slower titration, and closer monitoring of blood pressure and hemoglobin are usually prudent. The target hemoglobin of 10–12 g/dL should not be exceeded.
Missed Dose
If you miss a scheduled dose of Silapo, contact your healthcare provider for instructions. Do not take a double dose to compensate for a missed one. The next dose should be administered as soon as possible according to your regular dosing schedule. If you are unsure what to do, seek advice from your doctor, pharmacist, or nurse. Consistent adherence is important for maintaining stable hemoglobin levels and achieving optimal treatment outcomes.
Overdose
The therapeutic margin of erythropoietin products is wide, and acute intoxication from a single overdose is unlikely. However, repeated overdosing can lead to polycythemia (excessively high red blood cell count), which significantly increases the risk of thromboembolic complications such as deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction. Severe hypertension may also develop. If polycythemia occurs, Silapo should be temporarily withheld and the patient should receive appropriate supportive care, which may include phlebotomy (therapeutic blood removal) to reduce the hematocrit. Monitoring of vital signs, blood pressure, and complete blood count is essential following a suspected overdose.
Silapo should only be used under the supervision of a healthcare professional experienced in managing anemia with erythropoiesis-stimulating agents. Self-injection at home is possible after adequate training, but dosage adjustments must always be made by your doctor based on regular blood test results. Before each injection, visually inspect the pre-filled syringe: the solution should be clear and colorless. Do not use if it appears cloudy, discolored, or contains visible particles.
What Are the Side Effects of Silapo?
Quick Answer: The most common side effects of Silapo include headache, hypertension (high blood pressure), flu-like symptoms, and injection-site reactions. More serious but less common side effects include thromboembolic events (blood clots), hypertensive crisis, stroke, and rare cases of pure red cell aplasia. Seek urgent medical attention for sudden chest pain, leg swelling, severe headache, or signs of allergic reaction.
Like all medicines, Silapo can cause side effects, although not everyone will experience them. The side-effect profile of erythropoietin therapy is well characterized through decades of clinical experience with the reference product and multiple biosimilars. Frequency and severity can vary depending on the underlying condition being treated, the dose used, the route of administration, and individual patient factors such as age, comorbidities, and concomitant medications.
The side-effect profile may differ between patient populations. Patients with chronic kidney disease on dialysis have a different risk profile from cancer patients receiving chemotherapy or surgical patients receiving short-term perioperative therapy. Your healthcare provider will discuss the risks that are most relevant to your individual situation before starting treatment.
Very Common (affects more than 1 in 10 people)
Reported in >10% of patients
- Headache, particularly at the start of treatment or after dose escalation
- Hypertension (high blood pressure) or worsening of existing hypertension
- Flu-like symptoms (fever, chills, myalgia, bone pain), especially with initial doses
- Upper respiratory tract infections (particularly in CKD patients)
- Nausea (particularly in cancer patients receiving chemotherapy)
Common (affects 1 in 10 to 1 in 100 people)
Reported in 1–10% of patients
- Arthralgia (joint pain)
- Injection-site reactions (pain, redness, or swelling at the injection site)
- Diarrhea
- Vomiting
- Pyrexia (fever)
- Cough
- Rash and skin irritation
- Thromboembolic events, including deep vein thrombosis
- Hypertensive crisis (sudden severe increase in blood pressure)
- Seizures (particularly in CKD patients)
Uncommon (affects 1 in 100 to 1 in 1,000 people)
Reported in 0.1–1% of patients
- Hyperkalemia (elevated blood potassium levels)
- Pulmonary embolism
- Myocardial infarction (heart attack)
- Cerebrovascular accident (stroke)
- Thrombosis of arteriovenous fistula in hemodialysis patients
- Hypersensitivity reactions (allergic reactions)
Rare (affects less than 1 in 1,000 people)
Reported in <0.1% of patients
- Pure red cell aplasia (PRCA) due to anti-erythropoietin antibodies – a medical emergency requiring permanent discontinuation
- Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis
- Anaphylactic reactions
- Angioedema
- Exacerbation of porphyria
- Sudden severe headache, confusion, visual disturbance, or seizures (may indicate hypertensive encephalopathy)
- Chest pain, shortness of breath, or sudden leg swelling (may indicate thromboembolism)
- Sudden weakness or numbness on one side of the body or difficulty speaking (may indicate stroke)
- Severe skin rash with blistering or peeling
- Signs of a severe allergic reaction: swelling of the face, lips, tongue, or throat; difficulty breathing; rapid heartbeat
Most side effects of Silapo are manageable with appropriate monitoring and dose adjustments. Risks can be minimized by adhering to recommended hemoglobin targets, monitoring and treating blood pressure, ensuring adequate iron supplementation, and reporting new symptoms promptly. Your healthcare provider will weigh the benefits of treatment against the potential risks for your individual clinical situation and will modify therapy as needed based on your response.
Patients and caregivers should also be aware of the signs of worsening anemia that might indicate an inadequate response to treatment or the development of PRCA: persistent fatigue, shortness of breath on exertion, pale skin, or a sudden drop in hemoglobin despite continued therapy. These symptoms should be discussed promptly with your care team.
How Should You Store Silapo?
Quick Answer: Store Silapo pre-filled syringes in a refrigerator at 2–8°C. Do not freeze. Keep the syringes in the outer carton to protect them from light. For convenience, Silapo may be removed from the refrigerator and stored at room temperature (up to 25°C) for a single period of up to 3 days; after this, unused syringes must be discarded.
Proper storage of Silapo is critical to maintaining its potency and safety. As a biological medicine containing a glycoprotein (epoetin zeta), it is sensitive to temperature extremes, light exposure, and mechanical agitation. Improper storage can lead to protein degradation, loss of clinical effect, or the formation of protein aggregates that may increase the risk of hypersensitivity reactions or PRCA.
- Refrigerate at 2–8°C (36–46°F): Keep pre-filled syringes in the refrigerator whenever they are not in use. Place them in the main body of the refrigerator rather than the door or next to the freezer compartment, where temperature fluctuations are more pronounced.
- Do not freeze: Freezing irreversibly damages the protein structure of epoetin zeta and renders the medicine ineffective. If a syringe has been accidentally frozen, it must not be used; dispose of it safely and obtain a replacement.
- Protect from light: Keep pre-filled syringes in their original outer carton until just before use. Light exposure can degrade the active substance over time.
- Do not shake: Avoid vigorous shaking, which can cause protein aggregation and denaturation. If a syringe has been dropped or handled roughly, check that the solution still appears clear and colorless before use.
- Temporary room-temperature storage: If needed (for example, when travelling), Silapo may be kept at room temperature (not above 25°C/77°F) for a single period of up to 3 days. Once removed from the refrigerator, the syringe should not be returned to refrigerated storage and must be used within the 3-day window or discarded.
- Keep out of the sight and reach of children: Store in a safe location inaccessible to children and pets.
- Check expiry date: Do not use Silapo after the expiry date shown on the label and outer carton. The expiry date refers to the last day of the indicated month.
- Visual inspection: Before every injection, visually inspect the solution. It should be clear and colorless. Do not use if it is cloudy, discolored, or contains visible particles.
Dispose of unused or expired Silapo according to your local regulations. Do not throw medicines away via household waste or wastewater. Ask your pharmacist how to dispose of medicines you no longer need – these measures help protect the environment. Used pre-filled syringes should always be placed in a sharps disposal container immediately after use; never attempt to recap needles, which increases the risk of accidental needle-stick injury.
What Does Silapo Contain?
Quick Answer: Each pre-filled syringe of Silapo 10,000 IU/1.0 mL contains 10,000 international units of epoetin zeta (approximately 83.4 micrograms) as the active substance. Inactive ingredients (excipients) include sodium dihydrogen phosphate dihydrate, disodium phosphate dihydrate, sodium chloride, calcium chloride dihydrate, polysorbate 20, glycine, leucine, isoleucine, threonine, glutamic acid, phenylalanine, and water for injections.
Active Ingredient
The active substance in Silapo is epoetin zeta, a 165-amino acid glycoprotein produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells. Epoetin zeta has the same amino acid sequence as naturally occurring human erythropoietin, including the glycosylation pattern that is essential for biological activity and for a prolonged circulating half-life. Epoetin zeta is indistinguishable from epoetin alfa in its clinical effect, and the "zeta" designation reflects the regulatory process used to name biosimilars during the early years of biosimilar legislation in Europe.
Each 10,000 IU/1.0 mL pre-filled syringe contains 10,000 international units (IU) of epoetin zeta, equivalent to approximately 83.4 micrograms of protein, in 1 mL of solution. Other strengths of Silapo are available (ranging from 1,000 IU to 40,000 IU per pre-filled syringe) to allow flexible dosing across indications and body weights.
Inactive Ingredients (Excipients)
The excipients in Silapo have been selected to maintain the stability and biological activity of epoetin zeta and to ensure that the solution is compatible with subcutaneous or intravenous administration:
- Sodium dihydrogen phosphate dihydrate: Buffer component that helps maintain the pH of the solution within an optimal range for protein stability and tissue compatibility.
- Disodium phosphate dihydrate: Buffer component that works together with sodium dihydrogen phosphate to stabilize pH.
- Sodium chloride: Adjusts tonicity (osmolarity) to match physiological conditions, helping to minimize injection-site discomfort.
- Calcium chloride dihydrate: Contributes to ionic strength and helps stabilize the protein conformation.
- Polysorbate 20: A non-ionic surfactant that helps stabilize the protein, prevents aggregation, and reduces adsorption to glass and plastic surfaces.
- Glycine, leucine, isoleucine, threonine, glutamic acid, phenylalanine: Free amino acids used as stabilizers that protect epoetin zeta from oxidation and deamidation during storage.
- Water for injections: The solvent used to dissolve all components into a clear, injectable solution.
Silapo does not contain human serum albumin as a stabilizer, in line with modern formulation practice for erythropoietins. The polysorbate 20 and amino-acid stabilizer system has been shown to maintain stability and efficacy comparable to albumin-containing formulations while avoiding the use of blood-derived products.
Silapo contains less than 1 mmol sodium (23 mg) per dose, meaning it is essentially sodium-free. This is relevant for patients on a sodium-restricted diet, particularly those with chronic kidney disease or heart failure.
Frequently Asked Questions About Silapo
Medical References & Sources
All medical information in this article is based on peer-reviewed scientific research and official product information from regulatory agencies. Sources include:
- European Medicines Agency (EMA). Silapo – Summary of Product Characteristics (SmPC) and European Public Assessment Report (EPAR). EMA/H/C/000760. Available at: EMA – Silapo
- KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney International Supplements. 2012;2(4):279–335. Updated 2024.
- Sorensen S, Rodstein F, Holtmann M, et al. Pharmacokinetic and pharmacodynamic equivalence of epoetin zeta and reference epoetin alfa. Current Medical Research and Opinion. 2008;24(2):415–422.
- World Health Organization. WHO Model List of Essential Medicines – 23rd Edition (2023). Geneva: WHO; 2023. Erythropoietin listed as essential for anemia management.
- European Society for Medical Oncology (ESMO). Clinical Practice Guidelines: Management of Anaemia and Iron Deficiency in Patients with Cancer. Annals of Oncology. 2018;29(Supplement 4):iv96–iv110.
- Weise M, Bielsky MC, De Smet K, et al. Biosimilars: what clinicians should know. Blood. 2012;120(26):5111–5117.
- Drüeke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. New England Journal of Medicine. 2006;355(20):2071–2084. (CREATE trial)
- Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. New England Journal of Medicine. 2006;355(20):2085–2098. (CHOIR trial)
- Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. New England Journal of Medicine. 2009;361(21):2019–2032. (TREAT trial)
- Bohlius J, Bohlke K, Castelli R, et al. Management of Cancer-Associated Anemia with Erythropoiesis-Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update. Journal of Clinical Oncology. 2019;37(15):1336–1351.
- British National Formulary (BNF). Epoetin zeta – monograph. National Institute for Health and Care Excellence. 2026 edition.
- U.S. Food and Drug Administration (FDA). Biosimilars: Information for healthcare professionals. Available at FDA.gov.
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