Enwylma

Enwylma should be administered under the responsibility of a healthcare professional. 4). Patients treated with Enwylma should be given the package leaflet and the patient reminder card. Prevention of skeletal related events in adults with advanced malignancies involving bone The recommended dose is 120 mg administered as a single subcutaneous injection once every 4 weeks into the thigh, abdomen or upper arm.

3 Giant cell tumour of bone The recommended dose of Enwylma is 120 mg administered as a single subcutaneous injection once every 4 weeks into the thigh, abdomen or upper arm with additional 120 mg doses on days 8 and 15 of treatment of the first month of therapy.

Patients in the phase II study who underwent complete resection of giant cell tumour of bone did receive an additional 6 months of treatment following the surgery as per study protocol. Patients with giant cell tumour of bone should be evaluated at regular intervals to determine whether they continue to benefit from treatment.

In patients whose disease is controlled by denosumab, the effect of interruption or cessation of treatment has not been evaluated, however limited data in these patients does not indicate a rebound effect upon cessation of treatment.

2). 2). 2). Paediatric population The safety and efficacy of denosumab have not been established in paediatric patients (age < 18) other than skeletally mature adolescents (aged 12-17 years) with giant cell tumour of bone. 4). Treatment of skeletally mature adolescents with giant cell tumour of bone that is unresectable or where surgical resection is likely to result in severe morbidity: the posology is the same as in adults.

3). Method of administration For subcutaneous use. 7 mL vial should only be performed by a healthcare professional. 6.

Summary of the safety profile Overall safety profile is consistent in all approved indications for denosumab. Hypocalcaemia has very commonly been reported following denosumab administration, mostly within the first 2 weeks. 8 – description of selected adverse reactions).

The decreases in serum calcium were generally appropriately managed by calcium and vitamin D supplementation. The most common adverse reactions with denosumab are musculoskeletal pain. 8 – description of selected adverse reactions) have been commonly observed in patients taking denosumab.

Tabulated list of adverse reactions The following convention has been used for the classification of the adverse reactions based on incidence rates in four phase III, two phase II clinical studies and post-marketing experience (see table 1): very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and not known (cannot be estimated from the available data).

Within each frequency grouping and system organ class, adverse reactions are presented in order of decreasing seriousness. Table 1. Adverse reactions reported in patients with advanced malignancies involving bone, multiple myeloma, or with giant cell tumour of bone MedDRA system organ class Frequency category Adverse reactions Neoplasms benign, malignant and unspecified (including cysts and polyps) Common New primary malignancy1 Immune system disorders Rare Drug hypersensitivity1 Rare Anaphylactic reaction1 Metabolism and nutrition disorders Very common Hypocalcaemia1,2 Common Hypophosphataemia Uncommon Hypercalcaemia following treatment discontinuation in patients with giant cell tumour of bone3 Respiratory, thoracic and mediastinal disorders Very Common Dyspnoea Gastrointestinal disorders Very Common Diarrhoea Common Tooth extraction Skin and subcutaneous tissue disorders Common Hyperhidrosis Uncommon Lichenoid drug eruptions1 Musculoskeletal and connective tissue disorders Very common Musculoskeletal pain1 Common Osteonecrosis of the jaw1 Uncommon Atypical femoral fracture1 Not Known Osteonecrosis of the external auditory canal3,4 1 See section Description of selected adverse reactions.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. 2). Hypocalcaemia Pre-existing hypocalcaemia must be corrected prior to initiating therapy with denosumab.

Hypocalcaemia can occur at any time during therapy with denosumab. 8 for symptoms). Additional monitoring of calcium level should be considered during therapy in patients with risk factors for hypocalcaemia, or if otherwise indicated based on the clinical condition of the patient.

Patients should be encouraged to report symptoms indicative of hypocalcaemia. If hypocalcaemia occurs while receiving denosumab, additional calcium supplementation and additional monitoring may be necessary. 8), with most cases occurring in the first weeks of initiating therapy, but can occur later.

Renal impairment Patients with severe renal impairment (creatinine clearance < 30 mL/min) or receiving dialysis are at greater risk of developing hypocalcaemia. The risk of developing hypocalcaemia and accompanying elevations in parathyroid hormone increases with increasing degree of renal impairment.

Regular monitoring of calcium levels is especially important in these patients. 8). The start of treatment/new treatment course should be delayed in patients with unhealed open soft tissue lesions in the mouth. A dental examination with preventive dentistry and an individual benefit- risk assessment is recommended prior to treatment with denosumab.

The following risk factors should be considered when evaluating a patient’s risk of developing ONJ: • potency of the medicinal product that inhibits bone resorption (higher risk for highly potent compounds), route of administration (higher risk for parenteral administration) and cumulative dose of bone resorption therapy.

g. anaemia, coagulopathies, infection), smoking. • concomitant therapies: corticosteroids, chemotherapy, angiogenesis inhibitors, radiotherapy to head and neck. g. tooth extractions). All patients should be encouraged to maintain good oral hygiene, receive routine dental check-ups, and immediately report any oral symptoms such as dental mobility, pain or swelling, or non-healing of sores or discharge during treatment with denosumab.

1. 4). Unhealed lesions from dental or oral surgery. 4