Grafalon

What Is Grafalon and What Is It Used For?

Quick answer: Grafalon is a selective immunosuppressant containing polyclonal anti-human T-lymphocyte antibodies obtained from rabbits. It is used to prevent and treat organ rejection after kidney transplantation and to prevent graft-versus-host disease before stem cell (bone marrow) transplantation.

Grafalon belongs to a class of medicines known as immunosuppressants. These medications work by dampening the activity of the immune system, which is essential in the context of organ and cell transplantation. Without immunosuppressive therapy, the recipient’s immune system would recognise the transplanted organ or cells as foreign and mount an attack against them, leading to rejection or, in the case of stem cell transplantation, graft-versus-host disease.

The active substance in Grafalon is a purified immunoglobulin G (IgG) preparation obtained by immunising rabbits with the Jurkat human T-cell line. The resulting polyclonal antibodies have specificity for a wide range of surface antigens expressed on human T-lymphocytes. When administered intravenously, these antibodies bind to circulating and tissue-resident T-cells, leading to their depletion through complement-dependent cytolysis and antibody-dependent cell-mediated cytotoxicity (ADCC). This profound T-cell depletion forms the basis of Grafalon’s therapeutic efficacy.

Kidney Transplantation

In the context of kidney transplantation, Grafalon is used both as induction therapy (given at the time of transplantation to prevent acute rejection) and as rescue therapy (given to treat acute rejection episodes that have not responded to standard corticosteroid treatment). Acute cellular rejection remains a significant barrier to long-term graft survival, occurring in approximately 10–20% of kidney transplant recipients in the first year despite modern immunosuppressive regimens. Anti-thymocyte globulin (ATG) preparations, including Grafalon, have been a cornerstone of transplant immunosuppression for decades and are recommended by international guidelines such as those published by KDIGO.

Clinical studies have demonstrated that ATG induction therapy reduces the incidence of acute rejection episodes, particularly in patients at high immunological risk, such as those with high levels of pre-formed donor-specific antibodies, previous transplant failures, or significant HLA mismatches. Grafalon enables a delayed introduction of calcineurin inhibitors (such as tacrolimus or cyclosporine), which can be beneficial for protecting kidney function in the early post-transplant period.

Stem Cell Transplantation

In allogeneic haematopoietic stem cell transplantation (also known as bone marrow transplantation), Grafalon is used as part of the conditioning regimen administered before the transplant. The primary purpose in this setting is to deplete the recipient’s T-lymphocytes, thereby reducing the risk of graft-versus-host disease (GvHD) — a common and potentially life-threatening complication in which the donor’s immune cells attack the recipient’s tissues.

GvHD can be acute (occurring within the first 100 days after transplantation) or chronic (developing later), and it affects the skin, liver, gastrointestinal tract, and other organs. According to the EBMT and other international guidelines, ATG-based GvHD prophylaxis is particularly recommended when using unrelated or mismatched donors, where the risk of GvHD is significantly higher. Randomised controlled trials have shown that the inclusion of ATG in the conditioning regimen reduces the incidence of both acute and chronic GvHD without adversely affecting overall survival or relapse rates in many patient populations.

Grafalon is always used in combination with other immunosuppressive medications as part of a comprehensive immunosuppressive regimen tailored to the individual patient’s clinical situation and risk profile.

What Should You Know Before Taking Grafalon?

Quick answer: Grafalon must not be used if you have active uncontrolled infections, severe bleeding disorders, known allergy to rabbit proteins, or malignancies (unless undergoing stem cell transplantation). Always inform your doctor about all existing medical conditions and medications before treatment.

Contraindications

You must not receive Grafalon under the following circumstances:

• Hypersensitivity to the active substance (anti-human T-lymphocyte immunoglobulin from rabbit) or to any of the excipients. Patients with a known allergy to rabbit proteins are at particular risk of severe allergic reactions.
• Active infections that are not adequately controlled by current treatment. Because Grafalon profoundly suppresses the immune system, administering it during an uncontrolled infection could lead to overwhelming sepsis or rapid progression of the infection.
• Severe bleeding disorders (coagulopathies), as Grafalon can further impair blood clotting by reducing platelet counts.
• Active malignancy, unless the patient is undergoing stem cell transplantation as part of their cancer treatment. The immunosuppressive effects of Grafalon could promote tumour growth or progression in patients with existing cancers.

Warnings and Precautions

Before receiving Grafalon, it is essential to inform your doctor if any of the following apply to you:

• Previous allergic reactions to immunosuppressive medicines or to proteins derived from rabbits. Prior sensitisation increases the risk of anaphylaxis or severe infusion reactions.
• Liver disease, as hepatic impairment may affect the metabolism and clearance of the immunoglobulin, and Grafalon has been associated with veno-occlusive liver disease in rare cases.
• Heart problems, because infusion-related reactions can cause haemodynamic instability, including hypotension or hypertension and tachycardia, which may be poorly tolerated in patients with pre-existing cardiac conditions.

Pregnancy and Breastfeeding

The safety of Grafalon during pregnancy has not been fully established in clinical studies. If you are pregnant or suspect you may be pregnant, inform your doctor before receiving Grafalon. Your doctor will carefully evaluate the potential risks and benefits of treatment in your specific clinical situation. In general, immunosuppressive therapy during pregnancy requires close collaboration between the transplant team, obstetrician, and neonatologist.

Grafalon may pass into breast milk. If treatment with Grafalon is considered medically necessary while you are breastfeeding, your doctor will discuss the potential risks and benefits, and you may be advised to discontinue breastfeeding during and for an appropriate period after treatment.

Manufacturing and Safety Information

The production of Grafalon involves the use of human-derived materials, specifically human red blood cells used in the manufacturing process. Stringent safety measures are applied to minimise the risk of transmitting infectious agents to patients. These measures include careful screening and selection of blood donors to exclude those at risk of carrying infections, testing of all donated blood for viruses and other pathogens, and incorporation of manufacturing steps designed to inactivate or remove viruses.

The measures implemented for Grafalon are considered effective against enveloped viruses such as HIV, hepatitis B virus, and hepatitis C virus, as well as non-enveloped viruses such as hepatitis A virus and parvovirus B19. However, as with all biological medicinal products derived from human materials, the risk of transmitting infectious agents can never be completely eliminated. This includes unknown or emerging viruses and other pathogens.

How Does Grafalon Interact with Other Drugs?

Quick answer: Grafalon is always used alongside other immunosuppressive medications. Combining it with additional immunosuppressants increases the risk of infections and blood count abnormalities. Live vaccines must be avoided during treatment, and non-live vaccines may have reduced effectiveness.

Because Grafalon is exclusively used in hospital settings as part of a broader immunosuppressive regimen, drug interactions are carefully managed by the transplant medical team. However, understanding these interactions is important for comprehensive patient care and for informing patients about the medications they receive.

Major Interactions

The most clinically significant interactions involve other medications that also suppress the immune system. Grafalon is routinely combined with immunosuppressive agents such as corticosteroids (e.g., methylprednisolone, prednisolone), calcineurin inhibitors (e.g., tacrolimus, cyclosporine), and antimetabolites (e.g., mycophenolate mofetil, azathioprine). While these combinations are intentional and form the standard of care, the additive immunosuppressive effect significantly increases the risk of:

• Opportunistic infections (bacterial, viral, fungal, and parasitic)
• Reactivation of latent infections (e.g., cytomegalovirus, Epstein-Barr virus, tuberculosis)
• Severe cytopenias (abnormally low blood cell counts)
• Post-transplant lymphoproliferative disorder (PTLD), a form of cancer associated with intense immunosuppression

Vaccines

Live vaccines (such as measles, mumps, rubella, oral polio, yellow fever, and varicella vaccines) are strictly contraindicated during treatment with Grafalon and for a prolonged period after treatment, as the profoundly suppressed immune system may not be able to prevent the live vaccine organisms from causing disease. Non-live (inactivated) vaccines may be administered, but their effectiveness is likely to be significantly reduced because the depleted immune system may not generate an adequate antibody response. Your medical team will advise on the appropriate timing for any vaccinations.

Always inform your medical team about all medications you are taking, including over-the-counter medicines, herbal supplements, and vitamins. Some herbal products (such as echinacea or St John’s wort) may interact with immunosuppressive therapy and should generally be avoided.

What Is the Correct Dosage of Grafalon?

Quick answer: Grafalon dosage is calculated based on body weight and varies by indication. For kidney transplant rejection, the typical dose is 3–5 mg/kg/day for 5–14 days. For stem cell transplant conditioning, the typical dose is 20 mg/kg/day, starting 1–3 days before transplantation. It is always administered as an intravenous infusion in a hospital.

Grafalon is prescribed and administered exclusively by physicians with expertise in immunosuppressive therapy and transplant medicine. The dosage is individualised based on the patient’s body weight, clinical indication, immunological risk profile, and response to treatment. Grafalon is never self-administered; it is given as an intravenous infusion (IV drip) after dilution with sodium chloride solution.

Adults

Children and Adolescents

Available clinical data suggest that children and adolescents do not require a different dosage regimen compared with adults. Doses are calculated on a per-kilogram body weight basis, using the same dosing ranges as for adults. The transplant team will carefully determine the appropriate dose for each paediatric patient based on their specific clinical circumstances, body weight, and overall treatment plan.

Overdose

In the event of an overdose, the infusion of Grafalon will be stopped immediately and any concomitant immunosuppressive therapy will be adjusted accordingly. Because an overdose leads to excessive suppression of the immune system, the patient may receive prophylactic antimicrobial medications to prevent infections. Close monitoring of blood counts (particularly white blood cells, platelets, and red blood cells) is essential, as profound cytopenias may develop. Supportive care will be provided as clinically indicated.

What Are the Side Effects of Grafalon?

Quick answer: Very common side effects (affecting more than 1 in 10 patients) include fever, chills, headache, tremor, nausea, vomiting, diarrhoea, breathing difficulties, flushing, increased infections, and anaemia. Allergic reactions occur in 1–10% of patients and can rarely progress to anaphylactic shock. Always report any unusual symptoms immediately.

Like all medicines, Grafalon can cause side effects, although not everybody gets them. The side effects of Grafalon are largely related to its mechanism of action — the profound suppression of the immune system and the infusion of foreign (rabbit-derived) proteins into the body. Many of the acute side effects occur during or shortly after the infusion and are related to cytokine release as T-lymphocytes are destroyed. Your medical team is trained to manage these reactions and will monitor you closely throughout treatment.

Side Effects in Children and Adolescents

Based on available clinical data, the side effect profile of Grafalon in children and adolescents is generally comparable to that observed in adults. The same categories of adverse reactions — infusion-related reactions, cytopenias, infections, and allergic responses — are expected. Paediatric patients are monitored with the same vigilance as adult patients, with particular attention to growth and development during prolonged immunosuppressive therapy.

Reporting Side Effects

If you experience any side effects, including those not described in this information, please inform your doctor or nurse. You can also report suspected side effects directly to your national medicines regulatory authority. Reporting side effects helps to provide more information on the safety of medicines and can contribute to improved patient care.

How Should You Store Grafalon?

Quick answer: Grafalon must be stored in a refrigerator (2–8°C), protected from light, and kept in its original outer carton. It must not be used if the solution appears cloudy. Storage and handling are managed by hospital pharmacy staff.

Grafalon is a hospital-administered medication, and its storage is managed by the hospital pharmacy and nursing staff. However, understanding the storage requirements provides useful context about the drug’s stability and handling:

• Temperature: Store in a refrigerator at 2°C to 8°C. Do not freeze.
• Light protection: Keep the unopened vials in the outer carton to protect from light, as the immunoglobulin solution is light-sensitive.
• Visual inspection: Grafalon must not be used if the solution is cloudy. The solution should appear clear to slightly opalescent and colourless to slightly yellow.
• Shelf life: Do not use after the expiry date printed on the label. The expiry date refers to the last day of that month.
• Single use: Vials are intended for single use only and must not be punctured multiple times.
• Preparation: The withdrawal and preparation of the infusion solution must not be performed using siliconised syringes.
• Disposal: Any unused medicine or waste material is disposed of by the hospital pharmacy in accordance with local regulations.

Keep all medicines out of the sight and reach of children. Your doctor or pharmacist will take responsibility for the correct storage and disposal of any unused Grafalon.

What Does Grafalon Contain?

Quick answer: The active ingredient is anti-human T-lymphocyte immunoglobulin from rabbit at a concentration of 20 mg/ml. Other ingredients include sodium dihydrogen phosphate dihydrate, phosphoric acid, and water for injections. It is available in 5 ml (100 mg) and 10 ml (200 mg) glass vials.

Active Substance

The active substance in Grafalon is anti-human T-lymphocyte immunoglobulin from rabbit, present at a concentration of 20 mg per millilitre. This is a polyclonal immunoglobulin G (IgG) preparation produced by immunising rabbits with the Jurkat human T-cell line and subsequently purifying the resulting antibodies. The polyclonal nature of the preparation means it contains antibodies directed against multiple different surface antigens on human T-lymphocytes, which contributes to its potent immunosuppressive activity.

Excipients (Inactive Ingredients)

• Sodium dihydrogen phosphate dihydrate — acts as a buffering agent to maintain the solution at the appropriate pH
• Phosphoric acid (85%) — pH adjustment agent
• Water for injections — solvent

Packaging and Appearance

Grafalon is supplied as a clear to slightly opalescent, colourless to slightly yellow solution in glass vials. Two vial sizes are available:

• 5 ml vial containing 100 mg of Grafalon
• 10 ml vial containing 200 mg of Grafalon

Grafalon is packaged in cartons containing either 1 vial or 10 vials. Not all pack sizes may be marketed in all countries.

Manufacturer

Grafalon is manufactured by Neovii Biotech GmbH, Am Haag 6+7, 82166 Gräfelfing, Germany. Neovii Biotech specialises in biopharmaceutical products for transplant medicine and oncology.