Leukoscan, INN-Sulesomab
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authorised ANNEX I longer SUMMARY OF PRODUCT CHARACTERISTICS no product Medicinal 1 1. NAME OF THE MEDICINAL PRODUCT LeukoScan 0.31 mg, powder for solution for injection 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Kit for the preparation of 99mTc-labelled LeukoScan. Each 3 ml vial contains 0.31 mg sulesomab (IMMU-MN3 murine Fab′-SH antigranulocyte monoclonal antibody fragments) for the preparation of 99mTc labelled LeukoScan. The kit does not include the radioisotope. Excipients: Sucrose (37.8 mg) For a full list of excipients, see section 6.1. authorised 3. PHARMACEUTICAL FORM Powder for solution for injection. 4. CLINICAL PARTICULARS longer 4.1 Therapeutic indications This medicinal product is for diagnostic use only. no LeukoScan is indicated for diagnostic imaging for determining the location and extent of infection/inflammation in bone in patients with suspected osteomyelitis, including patients with diabetic foot ulcers. LeukoScan has not been employed to diagnose osteomyelitis in patients with sickle cell anaemia. 4.2 Posology and methodproduct of administration The radiolabelled solution should be administered as an intravenous injection. After injection, any remaining portion of the reconstituted solution should be discarded. LeukoScan is not recommended for use in children. Formal studies have not been performed in patients with renal or hepatic impairment. However, due to the low dose of protein administered and the short half-life of 99mTc, dosage adjustment is probably not necessary in such patients. Medicinal Radiopharmaceutical agents should be used only by qualified personnel with appropriate government authorisation for the use and manipulation of radionuclides. 2 This radiopharmaceutical may be received, used and administered only by authorised persons in designated clinical settings. Its receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licenses of local competent official organisations. Immediately prior to use, contents of the vial are reconstituted in the unlabeled form to prepare LeukoScan [99mTc]. The unreconstituted contents of the vial before radiolabelling are not to be directly administered to patients. For instructions for preparation see section 6.6. For readministration see section 4.4. 4.3 Contraindications Patients with known allergies or hypersensitivity to mouse proteins. Pregnancy. authorised 4.4 Special warnings and special precautions for use Safety and diagnostic accuracy in persons under 21 years of age have not been established. Administration of LeukoScan to young subjects should only be performed after consideration of the possible risks and benefits to the individual subject. Recommended imaging protocol longer Immunoscintigraphy should be performed one to eight hours after injection. There was essentially no difference in the detection ofno the presence or absence of osteomyelitis between the 1-2 hour timepoint and the 5-8 hour timepoint after injection. This suggests that imaging can be accomplished anytime between one and eight hours after injection (at the convenience of the nuclear medicine department and the patient). Planar imaging in all views necessary to adequately visualise the affected area at 1-8 h post-injection with at least 500 k counts or ten minutes per view should be made. Image acquisition in analogue and/or digital word-mode and at least a 128 x 128 matrix is recommended. product Single photon emission computed tomography (SPECT) imaging can also be conducted and may aid in differentiating osteomyelitis from soft tissue infections. SPECT acquisition parameters recommended are: 60 projections in a 360o step-and-shoot technique, 30 seconds per view in at least a 64 x 64 matrix. Data processing by filtered backprojection and reconstruction in three planes (transaxial, coronal, and sagittal) is recommended. Interpretation of the images When a bone scan is positive and imaging with LeukoScan is negative, infection is unlikely. MedicinalWhen a bone scan is negative, imaging with LeukoScan may rarely show a positive response and this may indicate early osteomyelitis. 3 Hypersensitivity Anaphylactic and other hypersensitivity reactions are possible whenever mouse protein materials are administered to patients. Appropriate cardiopulmonary resuscitation facilities and trained personnel should be available for immediate use in the event of an adverse reaction. Human Anti-mouse Antibody (HAMA) In clinical trials involving over 350 patients, no induction of human anti-mouse antibody (HAMA) to antibody fragments has been observed nor has there been any elevation of HAMA levels in patients with pre-existing HAMA. Patients who have previously received murine monoclonal antibody products are more likely to have HAMA. In subjects with HAMA, there may be a greater chance of hypersensitivity reactions and diminished efficacy in imaging. Readministration authorised There are, as yet, limited data on safety following repeated use. Readministration should only be considered in patients whose sera are negative for human anti-mouse antibody (HAMA) elevation in the fragment assay. The overall radiation dose received by the patient over time should also be taken into account. HAMA titers should be determined before repeated administration of LeukoScan. longer Paroxysmal nocturnal hemoglobinuria LeukoScan is not expected to bind to leukocytes in patients with paroxysmal nocturnal hemoglobinuria. no 4.5 Interactions with other medicinal products and other forms of interaction Formal drug interaction studies have not been performed, but no drug interactions have been described to date, including patients receiving antibiotics. 4.6 Pregnancy and lactation Women of childbearing potentialproduct When it is necessary to administer radioactive medicinal products to women of childbearing potential, information should always be sought about pregnancy. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. Where uncertainty exists, it is important that radiation exposure should be the minimum consistent with achieving the desired clinical information. Alternative techniques which do not involve ionising radiation should be considered. Pregnancy MedicinalLeukoScan is contraindicated in pregnancy. Radionuclide procedures carried out on pregnant women also involve radiation doses to the foetus. LeukoScan is contraindicated in pregnancy. Administration of 750 MBq LeukoScan will give an estimated absorbed dose of 4.1 mGy to an embryo or fetus at an early stage. 4 Lactation Before administering a radioactive medicinal product to a mother who is breast feeding, consideration should be given as to whether the investigation could be reasonably delayed until the mother has ceased breast feeding and as to whether the most appropriate choice of radiopharmaceutical has been made, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breast feeding should be interrupted and the expressed feeds discarded. It is usual to advise that breast feeding can be restarted when the level in the milk will not result in a radiation dose to the child greater than 1 mSv. Due to the short six-hour, half-life of 99mTc, a dose of less than 1 mSv in mother’s milk can be expected 24 hours after the administration of LeukoScan [99mTc]. 4.7 Effects on ability to drive and use machines No studies on the effects on the ability to drive and use machines have been performed. 4.8 Undesirable effects The following minor, self-limiting, rare adverse events were reported in the clinicalauthorised trials and considered at least possibly related to LeukoScan: eosinophilia (3); and facial rash (1). None of these were considered serious, and all resolved without sequelae. Post-marketing experience currently comprises greater than 70,000 vials sold, with two reports of self- limiting allergic reactions. 1. Statistically significant reductions in white blood cell (WBC) count were observed in the controlled longer 3 3 studies at 24 hours post-injection, from a mean value of 8.9 to a mean value of 8.0 (× 10 /mm ), but remained within the normal range, and returned to their pre-injection values by the time of the next measurement at 10 days. By contrast, in non-infected subjects, transient increases in WBC count were seen 24 hours after LeukoScan administration.no The eosinophil count increased from 2.7% pre- injection to 2.9% at 24 hours post-injection, and to 3.9% at 10 days, with the magnitude of both increases being statistically significant. The magnitude of these increases were assessed by the investigators to be of no clinical consequence on an individual patient basis. It is unknown whether the changes in WBC or eosinophil counts observed, although of no clinical significance, are due to a transient effect on WBC function. If so, no inferences concerning the underlying mechanism(s) responsible may be derived from the clinical laboratory results. However, in vitro granulocyte functionproduct tests did not show significant changes when the sulesomab was added. In vitro, a positive binding to lymphocytes up to 2-6% has been shown. The effect on lymphocyte function has not been determined. 2. HAMA: No induction of human anti-mouse antibody (HAMA) reactive with fragment was observed in any patient administered LeukoScan. 3. For each patient, exposure to ionising radiation must be justifiable on the basis of likely benefit. MedicinalThe activity administered must be such that the resulting radiation dose is as