Grafalon (Concentrate) Instructions for Use

Marketing Authorization Holder

Neovii Biotech, GmbH (Germany)

ATC Code

L04AA04 (Antithymocyte immunoglobulin (rabbit))

Active Substance

Anti-T lymphocyte immunoglobulin for human use, animal (Ph.Eur.)

Dosage Form

Grafalon

Concentrate for solution for infusion 20 mg/1 ml: fl. 5 ml 1 or 10 pcs.

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion as a clear or slightly opalescent, colorless or slightly yellowish liquid.

Excipients: sodium dihydrogen phosphate dihydrate – 1.56 mg, phosphoric acid (85%) – 0.5-1.0×10^-4 ml, water for injections – up to 1 ml.

5 ml – type II glass vials (1) – cardboard boxes.
5 ml – type II glass vials (10) – cardboard boxes.

Clinical-Pharmacological Group

Antithymocyte immunoglobulin

Pharmacotherapeutic Group

Immunosuppressive agent – immunoglobulin

Pharmacological Action

Immunosuppressive agent. Isolated from the serum of rabbits immunized with human T-lymphocytes of the Jurkat cell line. It is a solution with a high titer of polyclonal anti-T-lymphocyte antibodies. It has immunosuppressive activity. It has a direct effect on T-cells, leading to a decrease in their number.

Pharmacokinetics

After intravenous administration, the bioavailability is 100%. It undergoes protein metabolism (does not form non-physiological metabolites). T_1/2 is 14 days (at a dose of 4 mg/kg for more than 7 days).

Indications

Suppression of the immune response during organ transplantation (in combination with other immunosuppressants – methylprednisolone, prednisone, azathioprine, cyclosporine); acute corticosteroid-resistant transplant rejection.

ICD codes

Dosage Regimen

Administer intravenously as an infusion. Do not administer by bolus injection.

Reconstitute the concentrate with sodium chloride 0.9% or dextrose 5% solution. The final concentration for infusion should be not less than 0.5 mg/ml.

Infuse the total daily dose over at least 4 hours into a high-flow central vein or through a peripheral vein with adequate blood flow.

For prophylaxis of rejection in organ transplantation, the recommended dose is 3-5 mg/kg/day for 3-9 days. Initiate therapy within 24 hours before or after transplantation.

For treatment of acute corticosteroid-resistant rejection, the recommended dose is 3-5 mg/kg/day for 7-14 days.

Adjust the dose based on platelet count and clinical tolerance. Premedicate with a corticosteroid, an antihistamine, and an antipyretic approximately 1 hour before infusion to mitigate infusion-related reactions.

Monitor the patient closely for anaphylactic reactions, especially during the first 30 minutes of the initial infusion and for the first 3 days of therapy.

Adverse Reactions

Possible: nausea, subfebrile body temperature, dizziness, thrombocytopenia or granulocytopenia (associated with immunosuppression, rarely require discontinuation of therapy).

Rarely: hyperthermia up to 40°C (104°F) and above, chills (disappear during the first days of treatment), anaphylactic reactions (fever, generalized skin rash (erythema), edema, difficulty breathing, stridor, and decreased blood pressure), on days 8-14 – serum sickness.

Contraindications

Hypersensitivity (including to rabbit proteins); severe thrombocytopenia (less than 50 thousand/µl); pregnancy; acute infectious diseases of viral, fungal, and bacterial origin, resistant to therapy.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy.

Immunoglobulins can pass into breast milk, therefore, should not be used during breastfeeding.

Special Precautions

The patient should be under close supervision of medical personnel during the first 30 minutes after drug administration and the first 3 days of treatment (to exclude the risk of anaphylactic shock and other allergic reactions). Medical offices should be equipped with the necessary equipment for anti-shock therapy.

The risk of anaphylactic shock is greatest during the first 3 days of treatment. If the allergic reaction is mild, the use of the drug can be continued if necessary under the cover of antihistamine therapy. In case of a severe reaction that poses a risk to the patient, the administration of the drug should be suspended and anti-shock therapy should be started. It has been established that systemic and local tolerance improves if corticosteroids and/or antihistamines are used before the injection.

With immunosuppression, the risk of developing bacterial, viral, and fungal infections increases, so it is advisable to carry out concomitant therapy (antibiotics, antiviral and antifungal drugs).

It should be borne in mind that previous or simultaneous immunosuppressive therapy may be the cause of negative skin allergy tests, despite the presence of hypersensitivity in the patient. In vitro testing revealed no mutagenic effect of the drug in three different tests with and without metabolic activation.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Combination with other immunosuppressive drugs (corticosteroids, azathioprine, cyclosporine) increases the risk of infection, thrombocytopenia, and anemia (patients require careful monitoring).

Vaccination with live attenuated viral vaccines is contraindicated during immunosuppressive therapy (other vaccines may lead to the development of an insufficient immune response).

Pharmaceutically incompatible with other drugs.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.