Leitlinien & Arzneimittelsicherheit

HOS-100740 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most common side effects with denosumab (seen in more than one patient in ten) are musculoskeletal pain and pain in the extremity. Uncommon cases of cellulitis, rare cases of hypocalcaemia, hypersensitivity, osteonecrosis of the jaw and atypical femoral fractures (see sections 4.4 and 4.8 - description of selected adverse reactions) have been observed in patients taking denosumab. Tabulated list of adverse reactions The data in table 1 below describe adverse reactions reported from phase II and III clinical trials in patients with osteoporosis and breast or prostate cancer patients receiving hormone ablation; and/or spontaneous reporting. The following convention has been used for the classification of the adverse reactions (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 osteoporosis and breast or prostate cancer patients receiving hormone ablation MedDRA system organ class Frequency category Adverse reactions Infections and infestations Common Urinary tract infection Common Upper respiratory tract infection Uncommon Diverticulitis1 Uncommon Cellulitis1 Uncommon Ear infection Immune system disorders Rare Drug hypersensitivity1 Rare Anaphylactic reaction1 Metabolism and nutrition Rare Hypocalcaemia1 disorders Nervous system disorders Common Sciatica Gastrointestinal disorders Common Constipation Common Abdominal discomfort Skin and subcutaneous tissue Common Rash disorders Common Eczema

Auszug; vollständigen Abschnitt im Original lesen.

HOS-100736 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Hypocalcaemia (see section 4.4).

HOS-100735 · has-indication-information · PDF-Seite 2

Treatment of osteoporosis in postmenopausal women and in men at increased risk of fractures. In postmenopausal women denosumab significantly reduces the risk of vertebral, non-vertebral and hip fractures. Treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures (see section 5.1). In men with prostate cancer receiving hormone ablation, denosumab significantly reduces the risk of vertebral fractures. Treatment of bone loss associated with long-term systemic glucocorticoid therapy in adult patients at increased risk of fracture (see section 5.1).

HOS-100738 · has-interaction-information · PDF-Seite 5

In an interaction study, denosumab did not affect the pharmacokinetics of midazolam, which is metabolised by cytochrome P450 3A4 (CYP3A4). This indicates that denosumab should not alter the pharmacokinetics of medicinal products metabolised by CYP3A4. There are no clinical data on the co-administration of denosumab and hormone replacement therapy (oestrogen), however the potential for a pharmacodynamic interaction is considered to be low. In postmenopausal women with osteoporosis the pharmacokinetics and pharmacodynamics of denosumab were not altered by previous alendronate therapy, based on data from a transition study (alendronate to denosumab).

HOS-100739 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no or limited amount of data from the use of denosumab in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Denosumab is not recommended for use in pregnant women and women of child-bearing potential not using contraception. Women should be advised not to become pregnant during and for at least 5 months after treatment with denosumab. Any effects of denosumab are likely to be greater during the second and third trimesters of pregnancy since monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester. Breast-feeding It is unknown whether denosumab is excreted in human milk. In genetically engineered mice in which RANKL has been turned off by gene removal (a “knockout mouse”), studies suggest absence of RANKL (the target of denosumab see section 5.1) during pregnancy may interfere with maturation of the mammary gland leading to impaired lactation post-partum (see section 5.3). A decision on whether to abstain from breast-feeding or to abstain from therapy with denosumab should be made, taking into account the benefit of breast-feeding to the newborn/infant and the benefit of denosumab therapy to the woman. Fertility No data are available on the effect of denosumab on human fertility. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

HOS-100737 · has-warning-information · PDF-Seite 3

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. Calcium and vitamin D supplementation Adequate intake of calcium and vitamin D is important in all patients. Precautions for use Hypocalcaemia It is important to identify patients at risk for hypocalcaemia. Hypocalcaemia must be corrected by adequate intake of calcium and vitamin D before initiating therapy. Clinical monitoring of calcium levels is recommended before each dose and, in patients predisposed to hypocalcaemia within two weeks after the initial dose. If any patient presents with suspected symptoms of hypocalcaemia during treatment (see section 4.8 for symptoms) calcium levels should be measured. Patients should be encouraged to report symptoms indicative of hypocalcaemia. In the post-marketing setting, severe symptomatic hypocalcaemia (resulting in hospitalisation, life- threatening events, and fatal cases ) has been reported. While most cases occurred in the first few weeks of initiating therapy, it has also occurred later. Concomitant glucocorticoid treatment is an additional risk factor for hypocalcaemia. Renal impairment Patients with severe renal impairment (creatinine clearance < 30 mL/min) or receiving dialysis are at greater risk of developing hypocalcaemia. The risks of developing hypocalcaemia and accompanying parathyroid hormone elevations increase with increasing degree of renal impairment. Severe and fatal cases have been reported. Adequate intake of calcium, vitamin D and regular monitoring of calcium is especially important in these patients, see above. Skin infections Patients receiving denosumab may develop skin infections (predominantly cellulitis) leading to hospitalisation (see section 4.8). Patients should be advised to seek prompt medical attention if they develop signs or symptoms of cellulitis. Osteonecrosis of the jaw (ONJ) ONJ has been reported rarely in patients receiving denosumab for osteoporosis (see section 4.8). 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 in patients with concomitant risk factors. The following risk factors should be considered when evaluating a patient’s risk of developing ONJ: • potency of the m

Auszug; vollständigen Abschnitt im Original lesen.