LYMPHOSEEK Kit for radiopharmaceutical preparation Ref.[10981] Active ingredients: Technetium ⁹⁹ᵐTc tilmanocept

This medicinal product is restricted to hospital use only.

The medicinal product should only be administered by trained healthcare professionals with technical expertise in performing and interpreting sentinel lymph node mapping procedures.

Posology

The recommended dose is 50 micrograms tilmanocept radiolabelled with technetium Tc 99m at 18.5 MBq for same day surgery or 74 MBq for next day surgery. The dose of 50 micrograms should not be adjusted for body weight differences. The total injection amount should not exceed 50 micrograms tilmanocept, with a total maximum radioactivity of 74 MBq per dose.

The recommended minimum time for imaging is 15 minutes post injection. Intraoperative lymphatic mapping may begin as early as 15 minutes post injection.

Patients scheduled for surgery on the day of injection will receive 18.5 MBq technetium Tc 99m radiolabelled product. Administration should occur within 15 hours of the scheduled time of the surgery and intraoperative detection.

Patients scheduled for surgery on the day after injection will receive 74 MBq technetium Tc 99m radiolabelled product. Administration should occur within 30 hours of the scheduled time of the surgery and intraoperative detection.

Special populations

Hepatic or renal impairment

Careful consideration of the activity to be administered in these patients is required since an increased radiation exposure is possible. The radiation dose to the patient would not exceed 2.28 mSv even if none of a 74 MBq dose were eliminated.

Extensive dose-range and adjustment studies with the medicinal product in normal and special populations have not been performed. The pharmacokinetics of technetium Tc 99m tilmanocept in patients with renal or hepatic impairment have not been characterised (see section 5.2).

Elderly population

Elderly patients aged 65 or older (32%) were evaluated in clinical studies; no safety issues were identified. No dose adjustment is recommended based on age.

Paediatric population

The safety and efficacy of Lymphoseek in children and adolescents below the age of 18 years has not yet been established. No data are available.

Method of administration

This medicinal product must be radiolabelled before administration to the patient. The radiolabelled product is a clear, colourless solution with no visible particles.

Following radiolabelling, administration can be by either intradermal, subcutaneous, intratumoural, or peritumoural injection.

For melanoma, administration is intradermal in single or multiple divided injections.

For breast cancer, administration is intradermal, subareolar (single or multiple divided injections) or peritumoural (multiple divided injections).

For squamous cell carcinoma of the oral cavity, administration is peritumoural (multiple divided injections).

Each 50 microgram vial contains an additional overfill to ensure that 50 micrograms of tilmanocept can be delivered. However, it is required that the vial be prepared as instructed and a 50 microgram aliquot be used for a single patient dose.

Individual injection volumes should not exceed 0.5 mL or be less than 0.1 mL. Total injection volume should be no greater than 1.0 mL and no less than 0.1 mL. Dilution of the product in volumes greater than 1.0 mL could affect the in vivo disposition of Lymphoseek.

For instructions for preparation and control of the radiochemical purity of the radiopharmaceutical, see section 12.

For patient preparation, see section 4.4.

The total injection amount should not exceed 50 micrograms tilmanocept, with a total maximum radioactivity of 74 MBq per dose. Chronic or acute overdose is unlikely to occur given the total injection amount.

No clinical consequences were observed at dose levels of 3.7 times the recommended dose of Lymphoseek in humans, or at 390 times the anticipated human exposure of tilmanocept in animals.

In the event of administration of a radiation overdose with tilmanocept the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by frequent micturition or by forced diuresis and frequent bladder voiding.

Unopened vial: 18 months.

After radiolabelling: 6 hours. Do not store above 25°C. Store using appropriate radiation shielding.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

Do not store above 25°C.

Store the vial in the outer carton in order to protect from light.

For storage conditions after radiolabelling of the medicinal product, see section 6.3.

Storage of radiopharmaceuticals should be in accordance with national regulation on radioactive materials.

8 mL type I glass vial with a butyl rubber stopper sealed with a flip-off seal. Each vial contains 50 micrograms tilmanocept.

Pack-size of 1 and 5 vials.

General warning

Radiopharmaceuticals should be received, used, and administered only by authorised persons in designated clinical settings. Their receipt, storage, use, transfer, and disposal are subject to the regulations and/or appropriate licenses of the competent official organisation.

Radiopharmaceuticals should be prepared in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken.

Contents of the vial are intended only for use in the preparation and radiolabelling of Lymphoseek and are not to be administered directly to the patient without first undergoing the preparative procedure. Each 50 microgram vial contains an additional overfill to ensure that 50 micrograms of tilmanocept can be delivered. However, it is required that the vial be prepared as instructed and a 50 microgram aliquot be used for a single patient dose; any remaining material should be discarded after reconstitution and use, see section 12.

For instructions on reconstitution and radiolabelling of the medicinal product before administration, see section 12. The radiolabelled product is a clear, colourless solution with no visible particles.

If at any time in the preparation of this medicinal product the integrity of this vial is compromised it should not be used.

Administration procedures should be carried out in a way to minimise risk of contamination of the medicinal product and irradiation of the operators. Adequate shielding is mandatory.

The content of the kit before extemporary preparation is not radioactive. However, after sodium pertechnetate (^99mTc) is added, adequate shielding of the final preparation must be maintained.

The administration of radiopharmaceuticals creates risks for other persons from external radiation or contamination from spill of urine, vomiting, etc. Radiation protection precautions in accordance with national regulations must therefore be taken.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.