MEPACT (Mifamurtide)
Immunostimulant for adjuvant treatment of osteosarcoma (bone cancer)
Quick facts about MEPACT
Key takeaways about MEPACT
- Immune system booster: MEPACT activates monocytes and macrophages to target and destroy residual osteosarcoma cells after surgery
- Used with chemotherapy: Always given as adjuvant treatment alongside standard multi-agent chemotherapy for non-metastatic, resectable osteosarcoma
- 36-week treatment course: Twice weekly for the first 12 weeks, then once weekly for 24 more weeks, totalling approximately 48 infusions
- Common initial side effects: Chills, fever, and fatigue are expected, especially during the first infusion, and are usually mild and manageable
- Key contraindications: Must not be used with ciclosporin, other calcineurin inhibitors, or high-dose NSAIDs as these can interfere with its immune-stimulating mechanism
What Is MEPACT and What Is It Used For?
MEPACT (mifamurtide) is an immunostimulant medicine used for the treatment of osteosarcoma (bone cancer) in patients aged 2 to 30. It is given after surgical removal of the tumour and together with chemotherapy to help the immune system destroy any remaining cancer cells and reduce the risk of recurrence.
MEPACT contains the active substance mifamurtide, which is a synthetic analogue of muramyl dipeptide (MDP), a naturally occurring component of certain bacterial cell walls. By mimicking this bacterial component, mifamurtide triggers an innate immune response that helps the body recognise and attack residual tumour cells that may remain after surgery.
Osteosarcoma is the most common primary malignant bone tumour in children and adolescents, typically affecting the long bones around the knee. Standard treatment involves surgical resection of the tumour combined with multi-agent chemotherapy. Despite advances in surgical techniques and chemotherapy regimens, approximately 30-40% of patients with localised osteosarcoma experience disease recurrence. MEPACT was developed to address this unmet need by adding an immunotherapy component to the standard treatment approach.
The European Medicines Agency (EMA) granted MEPACT marketing authorisation in 2009 for use in combination with post-operative multi-agent chemotherapy in patients with newly diagnosed, high-grade, resectable, non-metastatic osteosarcoma after macroscopically complete surgical resection. Clinical trial data demonstrated that adding MEPACT to chemotherapy improved overall survival compared to chemotherapy alone.
How does MEPACT work?
Mifamurtide works by activating the innate immune system, specifically targeting monocytes and macrophages. When administered intravenously as a liposomal formulation, mifamurtide binds to the NOD2 (nucleotide-binding oligomerization domain 2) receptor on monocytes and macrophages. This activation triggers the production of several pro-inflammatory cytokines, including tumour necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-12 (IL-12).
These activated immune cells develop tumoricidal activity, meaning they can directly recognise and kill osteosarcoma cells. The liposomal formulation of mifamurtide is particularly important because it ensures targeted delivery to monocytes and macrophages while prolonging the duration of immune cell activation. This approach represents a form of non-specific immunotherapy that harnesses the body's own immune defences against cancer.
MEPACT is not a standalone cancer treatment. It must always be used as part of a comprehensive treatment plan that includes surgery and multi-agent chemotherapy. The medicine is intended to complement, not replace, standard osteosarcoma treatment protocols.
What Should You Know Before Taking MEPACT?
Before receiving MEPACT, inform your doctor about all medical conditions, especially cardiovascular problems, asthma, autoimmune diseases, or previous allergic reactions to medicines. MEPACT must not be used with ciclosporin, other calcineurin inhibitors, or high-dose NSAIDs.
MEPACT is a powerful immunostimulant that activates the immune system in significant ways. Because of this mechanism of action, it is essential that your healthcare team has a complete understanding of your medical history, current medications, and overall health status before treatment begins. Careful patient selection and monitoring help ensure the safest possible treatment outcome.
Contraindications
You must not receive MEPACT if you:
- Are allergic to mifamurtide or any of the other ingredients in MEPACT (POPC, OOPS)
- Are taking medicines containing ciclosporin or other calcineurin inhibitors (e.g., tacrolimus), which are used to prevent organ rejection after transplantation or to treat autoimmune conditions such as psoriasis
- Are taking high doses of non-steroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid (aspirin), ibuprofen, or diclofenac
Calcineurin inhibitors and high-dose NSAIDs can interfere with the immune-stimulating mechanism of MEPACT, potentially rendering the treatment ineffective. It is therefore critical that these medications are not used concurrently with MEPACT therapy.
Warnings and Precautions
Tell your doctor before receiving MEPACT if you have or have had any of the following conditions:
- Cardiovascular problems: Blood clots (thrombosis), bleeding, or inflammation of the veins (vasculitis). You will need closer monitoring during treatment, and MEPACT may need to be postponed or discontinued if symptoms worsen.
- Asthma or other respiratory disorders: Discuss with your doctor whether you should take asthma medications when receiving MEPACT, as the immune activation can potentially exacerbate respiratory symptoms.
- Inflammatory or autoimmune disease: If you have been treated with corticosteroids or other immunosuppressive medicines, inform your doctor as these may affect how MEPACT works.
- Previous allergic reactions to medicines: Symptoms such as skin rash, breathing difficulties, or high blood pressure from other medicines should be reported, as MEPACT may cause similar reactions.
- Gastrointestinal problems: Nausea, vomiting, and loss of appetite may be worsened when MEPACT is used alongside chemotherapy.
If you experience chills, shaking, or feel warm during or after MEPACT infusion, measure your body temperature. A low white blood cell count (neutropenia) combined with fever may indicate a serious infection. Contact your healthcare team immediately if fever or chills persist for more than 8 hours after your MEPACT dose.
Pregnancy and Breastfeeding
MEPACT has not been studied in pregnant women. Due to the lack of safety data, MEPACT should not be used during pregnancy or by women of childbearing potential who are not using effective contraception. If you are receiving MEPACT treatment, you must use a reliable form of birth control throughout the entire treatment course.
It is unknown whether mifamurtide passes into breast milk. If you are breastfeeding or planning to breastfeed, discuss this with your doctor before starting treatment. The potential risk to the nursing infant must be weighed against the therapeutic benefit of the medicine to the mother.
If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before receiving MEPACT. Your healthcare team will help you evaluate the risks and benefits in your specific situation.
Driving and Operating Machinery
Some very common or common side effects of MEPACT treatment, including dizziness, vertigo, fatigue, and blurred vision, may impair your ability to drive or operate machinery safely. Avoid these activities if you experience any of these symptoms until they have resolved completely.
Sodium Content
MEPACT contains less than 1 mmol sodium (23 mg) per dose unit, meaning it is essentially sodium-free. This is relevant for patients on sodium-restricted diets.
How Does MEPACT Interact with Other Drugs?
MEPACT must not be used with ciclosporin, tacrolimus, or other calcineurin inhibitors. High-dose NSAIDs are also contraindicated. Regular corticosteroid use should be avoided. Doxorubicin administration should be separated from MEPACT when used in the same chemotherapy regimen.
Drug interactions are particularly important to understand with MEPACT because its therapeutic effect depends entirely on activating the immune system. Any medication that suppresses or modulates immune function can potentially reduce MEPACT's effectiveness or create unexpected adverse effects. Always inform your doctor about all medications you are taking, including prescription medicines, over-the-counter drugs, and herbal supplements.
Major Interactions
The following medications must not be used with MEPACT due to significant interaction potential:
| Drug/Class | Examples | Interaction Type | Recommendation |
|---|---|---|---|
| Calcineurin inhibitors | Ciclosporin, tacrolimus | Block immune activation pathway; may eliminate MEPACT efficacy | Contraindicated – do not use together |
| High-dose NSAIDs | Aspirin (high dose), ibuprofen, diclofenac | Inhibit prostaglandin-mediated immune signalling | Contraindicated at high doses |
Moderate Interactions
| Drug/Class | Examples | Interaction Type | Recommendation |
|---|---|---|---|
| Corticosteroids | Prednisolone, dexamethasone | Suppress immune response; may reduce MEPACT effectiveness | Avoid regular use during MEPACT treatment |
| Doxorubicin | Doxorubicin (Adriamycin) | Potential pharmacological interaction when co-administered | Separate administration timing when used in same chemotherapy regimen |
| Other immunosuppressants | Methotrexate, azathioprine, mycophenolate | May blunt immune activation from MEPACT | Discuss with specialist; close monitoring required |
Low-dose NSAIDs used for mild pain relief or fever management may be acceptable in some situations, but this should always be discussed with your treating physician. The distinction between high-dose and low-dose NSAIDs is clinically important, and your doctor will advise on appropriate analgesic options during MEPACT treatment.
What Is the Correct Dosage of MEPACT?
The recommended dose of MEPACT is 2 mg mifamurtide per m² body surface area. It is given twice weekly (with at least 3 days between doses) for the first 12 weeks, then once weekly for an additional 24 weeks, totalling 36 weeks (9 months) of treatment.
MEPACT must only be administered under the supervision of a specialist physician experienced in the treatment of osteosarcoma. The dosing is individualised based on body surface area (BSA), which is calculated using the patient's height and weight. The treatment follows a specific schedule designed to provide sustained immune system activation over the course of therapy.
Standard Dosing Schedule
Children, Adolescents, and Young Adults (2–30 years)
Dose: 2 mg/m² body surface area per infusion
Weeks 1–12 (Induction): Twice weekly, with at least 3 days between doses
Weeks 13–36 (Maintenance): Once weekly
Total treatment duration: 36 weeks (approximately 9 months)
Route: Intravenous infusion over approximately 1 hour
The treatment schedule for MEPACT can be adjusted to fit your chemotherapy schedule. If your chemotherapy is delayed, it is not necessary to interrupt the MEPACT schedule. However, you should complete the full 36-week course of MEPACT without unnecessary interruption to achieve maximum therapeutic benefit.
Dose Volume Calculation
Each reconstituted vial contains 0.08 mg mifamurtide per mL. The volume to be drawn up is calculated as follows:
Volume (mL) = 12.5 × calculated dose (mg)
| Dose | Volume to Draw Up |
|---|---|
| 1.0 mg | 12.5 mL |
| 2.0 mg | 25 mL |
| 3.0 mg | 37.5 mL |
| 4.0 mg | 50 mL |
Children Under 2 Years
MEPACT should not be given to children under 2 years of age. There is insufficient data on the safety and efficacy of mifamurtide in this age group to support its use.
Administration
The freeze-dried powder must be reconstituted, filtered using the supplied filter, and further diluted before use. MEPACT is then given as an intravenous infusion (drip) directly into a vein over approximately 1 hour. The infusion is performed by a doctor or nurse who will monitor you throughout the procedure. Hospitalisation is not required for MEPACT administration; it can be given in an outpatient setting.
Missed Dose
If you miss a scheduled MEPACT infusion, contact your healthcare team as soon as possible to arrange a replacement appointment. Do not attempt to make up for a missed dose by receiving extra infusions. Your doctor will advise on the best way to continue your treatment schedule.
Overdose
In the event of an overdose, you may experience more severe side effects including high fever, severe chills, extreme fatigue, nausea, vomiting, headache, and significant changes in blood pressure (either very high or very low). If you suspect an overdose, contact your doctor or the nearest hospital emergency department immediately. Treatment is symptomatic and supportive.
You should not discontinue MEPACT treatment before the full 36-week schedule is completed without first consulting your doctor. Completing the entire course is important for achieving optimal therapeutic outcomes. If you have concerns about continuing treatment, discuss them with your healthcare team.
What Are the Side Effects of MEPACT?
The most common side effects of MEPACT are chills, fever, and fatigue, which occur in the majority of patients, particularly during the first infusion. Other very common side effects include nausea, vomiting, headache, rapid heartbeat, and muscle or joint pain. These are generally mild to moderate and manageable with supportive care.
Like all medicines, MEPACT can cause side effects, although not everyone experiences them. The side effect profile of MEPACT is largely related to its mechanism of action as an immune system activator. When monocytes and macrophages are activated, they release pro-inflammatory cytokines that cause many of the observed side effects. Understanding this helps explain why symptoms like fever and chills are expected responses to the treatment.
Most patients experience chills, fever, and fatigue, particularly during the first MEPACT infusion. These side effects are typically mild to moderate in severity and transient in nature. They can usually be managed by your doctor, for example with paracetamol (acetaminophen) for fever. When MEPACT is used concurrently with chemotherapy, gastrointestinal side effects such as nausea, vomiting, and loss of appetite may be more pronounced.
- You have persistent fever or chills lasting more than 8 hours after your MEPACT dose, as this may indicate an infection
- You develop a skin rash or have difficulty breathing (wheezing)
- You experience severe or worsening gastrointestinal problems
Very Common Side Effects
- Fever, chills, shivering, and shaking
- Weakness, fatigue, and general malaise
- Nausea and/or vomiting
- Diarrhoea or constipation
- Headache or dizziness
- Rapid heartbeat (tachycardia)
- High blood pressure or low blood pressure
- Loss of appetite
- Excessive sweating
- Pain (general, muscle, joint, back, chest, abdominal, arm, or leg pain)
- Cough, breathing difficulties, or rapid breathing
- Low body temperature (hypothermia)
- Low red blood cell count (anaemia)
Common Side Effects
- Bluish discolouration of skin or gums (cyanosis) due to low oxygen
- Noticeable increase in heart rate or pounding heartbeat
- Swelling in arms, legs, or other areas (oedema)
- Chest discomfort
- Stomach upset, reduced appetite, or weight loss
- Redness, swelling, infection, or local reaction at the injection site
- Skin rash, redness, skin inflammation, itching, dry skin, pallor, or temporary flushing
- Inflammation of skin, tendons, muscles, or similar supporting tissues
- Inflammation of a vein (phlebitis)
- Upper abdominal or chest wall pain, bloating, indigestion, or liver pain
- Other pain: neck, shoulder, groin, bone, or throat pain; post-operative pain
- Muscle cramps or stiffness
- Feeling cold
- Drowsiness or sleepiness
- Burning, tingling, or decreased sensation; paraesthesia without stimulation
- Involuntary tremor
- Dehydration
- Low potassium levels (hypokalaemia)
- Mucous membrane inflammation (mucositis)
- Nasal congestion or inflammation of nose, throat, or sinuses
- Upper respiratory tract infections (e.g., common cold) or urinary tract infections
- General infection or herpes simplex virus infection
- Productive cough, wheezing, laboured breathing, or worsening shortness of breath
- Coughing up blood (haemoptysis) or nosebleed (epistaxis)
- Fluid in the pleural space (pleural effusion)
- Blood in urine (haematuria), difficulty or pain during urination, or frequent urination
- Difficulty sleeping (insomnia), depression, anxiety, or confusion
- Vertigo (sensation of spinning)
- Tinnitus (ringing in the ears)
- Blurred vision
- Hair loss (alopecia)
- Severe, painful menstruation
- Hearing loss
- Low white blood cell count (leucopenia) with or without fever; low platelet count (thrombocytopenia)
The side effects listed above are based on clinical trial data and post-marketing surveillance. If you experience any side effects not listed here, or if any side effects become serious, tell your doctor, pharmacist, or nurse. You can also report side effects directly through your national adverse drug reaction reporting system.
How Should You Store MEPACT?
Unopened MEPACT vials must be stored in a refrigerator at 2–8°C. Do not freeze. Keep the vial in the outer carton to protect from light. Once reconstituted with sodium chloride solution, the suspension should be stored at room temperature (20–25°C) and used within 6 hours.
Proper storage of MEPACT is essential to ensure the medicine remains effective and safe for use. As a biological product, mifamurtide is sensitive to temperature and light, and improper storage can compromise the integrity of the liposomal formulation.
Unopened Vials
- Store in a refrigerator at 2°C to 8°C
- Do not freeze – freezing can damage the liposomal structure
- Keep the vial in the outer carton to protect from light
- Check the expiry date on the vial label and carton before use
Reconstituted Suspension
- After reconstitution with 0.9% sodium chloride solution, store at room temperature (approximately 20–25°C)
- Use within 6 hours of reconstitution
- Do not use if there are visible signs of deterioration
Keep this medicine out of the sight and reach of children. Do not use MEPACT after the expiry date stated on the label and carton. The expiry date refers to the last day of the stated month. Medicines should not be disposed of via wastewater or household waste; consult your pharmacist for proper disposal methods to protect the environment.
What Does MEPACT Contain?
MEPACT contains 4 mg of mifamurtide per vial as the active ingredient. The excipients include two phospholipids (POPC and OOPS) that form the liposomal delivery system. When reconstituted, each millilitre contains 0.08 mg mifamurtide.
Active Ingredient
Each vial contains 4 mg of mifamurtide. After reconstitution with 50 mL of 0.9% sodium chloride solution, each mL of the suspension contains 0.08 mg mifamurtide.
Inactive Ingredients (Excipients)
- POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) – a phospholipid that forms the liposomal carrier
- OOPS (1,2-dioleoyl-sn-glycero-3-phospho-L-serine monosodium salt) – a phospholipid that aids in liposome formation and macrophage targeting
The liposomal formulation is a critical component of MEPACT's design. By encapsulating mifamurtide within liposomes composed of these two phospholipids, the medicine achieves targeted delivery to monocytes and macrophages, which naturally phagocytose (engulf) liposomal particles. This improves both the efficacy and safety profile of the drug compared to free mifamurtide.
Appearance and Packaging
MEPACT is a white to off-white homogeneous cake or powder for concentrate for dispersion for infusion. Each carton contains one 50 mL glass vial with a grey butyl stopper, aluminium seal and plastic cap, plus one sterile MEPACT filter supplied in a blister pack. The filter is essential for the reconstitution process and must be used when preparing the medicine for infusion.
Frequently Asked Questions About MEPACT
MEPACT (mifamurtide) is used to treat osteosarcoma (bone cancer) in children, adolescents, and young adults aged 2 to 30. It is given after surgical removal of the tumour and alongside chemotherapy to help the immune system destroy any remaining cancer cells and reduce the risk of cancer recurrence. MEPACT works by activating monocytes and macrophages, which are types of white blood cells that can recognise and kill tumour cells.
MEPACT is given as an intravenous infusion (drip) over approximately 1 hour. The freeze-dried powder is first reconstituted with sodium chloride solution, filtered, and then further diluted before infusion. It is administered by a healthcare professional who monitors the patient throughout the procedure. Treatment consists of twice-weekly infusions for the first 12 weeks, followed by once-weekly infusions for 24 additional weeks, totalling 36 weeks of treatment.
The most common side effects include chills, fever, fatigue, nausea, vomiting, headache, rapid heartbeat, high or low blood pressure, loss of appetite, sweating, and muscle or joint pain. These are most noticeable during the first infusion and tend to become less severe with subsequent doses. Your doctor can prescribe medications such as paracetamol (acetaminophen) to manage fever and other infusion-related symptoms.
MEPACT has not been studied in pregnant women and should not be used during pregnancy. Women of childbearing potential must use effective contraception during treatment. It is also unknown whether mifamurtide passes into breast milk, so breastfeeding should be discussed with your doctor. If you become pregnant during treatment, inform your doctor immediately so that appropriate decisions can be made about continuing therapy.
No, hospitalisation is not required for MEPACT administration. The infusion can be given in an outpatient setting. Each infusion takes approximately 1 hour, during which you will be monitored by a doctor or nurse. However, for your first few infusions, your healthcare team may want to observe you for a longer period to monitor for any adverse reactions, particularly chills and fever.
If you miss a scheduled MEPACT infusion, contact your healthcare team as soon as possible to arrange a replacement appointment. Do not try to make up for a missed dose by doubling up on infusions. Your doctor will advise on how to best continue your treatment schedule. Completing the full 36-week course is important for optimal results, so try to attend all scheduled appointments.
References
This article is based on the following peer-reviewed sources and international medical guidelines:
- European Medicines Agency (EMA). MEPACT Summary of Product Characteristics (SmPC). Last updated 2025. Available at: ema.europa.eu
- Meyers PA, Schwartz CL, Krailo MD, et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival – a report from the Children’s Oncology Group. Journal of Clinical Oncology. 2008;26(4):633-638.
- Chou AJ, Kleinerman ES, Krailo MD, et al. Addition of muramyl tripeptide to chemotherapy for patients with newly diagnosed metastatic osteosarcoma: a report from the Children’s Oncology Group. Cancer. 2009;115(22):5339-5348.
- European Society for Medical Oncology (ESMO). Bone sarcomas: ESMO-PaedCan-EURACAN Clinical Practice Guidelines. Annals of Oncology. 2021;32(12):1520-1536.
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Bone Cancer. Version 2.2025.
- World Health Organization (WHO). WHO Model List of Essential Medicines for Children. 9th edition, 2023.
- Kleinerman ES, Jia SF, Griffin J, et al. Phase II study of liposomal muramyl tripeptide in osteosarcoma: the cytokine cascade and monocyte activation following administration. Journal of Clinical Oncology. 1992;10(8):1310-1316.
- Ando K, Mori K, Corradini N, Redini F, Heymann D. Mifamurtide for the treatment of nonmetastatic osteosarcoma. Expert Opinion on Pharmacotherapy. 2011;12(2):285-292.
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