Inductos

HOS-216110 · has-adverse-reaction-information · PDF-Seite 8

Summary of the safety profile The most common adverse reactions for InductOs in lumbar interbody fusion surgery were radiculopathic events, and in acute tibia fracture surgery it was localised infection. The most severe adverse reaction is localised oedema in cervical spine surgery. The incidence of adverse reactions with InductOs was not affected by gender, age or race. Tabulated list of adverse reactions Over 1700 patients have received InductOs in clinical studies. In the long-bone fracture studies, over 500 patients received InductOs. In lumbar interbody fusion studies, over 600 patients received InductOs. The remaining patients participated in studies using InductOs for indications not currently approved in the EU. These data are supplemented with information from use of InductOs in the general population. The frequency of adverse reactions in patients exposed to treatment with InductOs is presented in the table below. Frequencies are defined as very common (≥1/10) or common (≥1/100 to <1/10). No reactions are observed with the frequency uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) or very rare (<1/10,000). The frequencies of adverse reactions identified during post-marketing use of InductOs are not known as these reactions were reported from a population of uncertain size. 8 System organ class Frequencies Very common Common Unknown General disorders Device dislocation1* and administration Fluid collection2* site conditions Musculoskeletal and Heterotopic Osteolysis* connective tissue ossification1, 3* Resorption bone disorders increased* Nervous system Radiculopathic events1, 4 disorders Infections and Localised infection5* infestations 1 Observed during use in lumbar interbody fusion 2 Fluid collection includes localised oedema, pseudocyst and implant site effusion. 3 Heterotopic ossification includes exostosis, extraskeletal ossification, postoperative heterotopic calcification, bone formation increased and implant site calcification. 4 Radiculopathic events includes radiculitis, lumbar radiculopathy, radicular pa

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HOS-216106 · has-contraindication-information · PDF-Seite 5

InductOs is contraindicated for patients with: • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 • Skeletal immaturity • Any active malignancy or patient undergoing treatment for a malignancy • An active infection at the operative site • Persistent compartment syndrome or neurovascular residua of compartment syndrome • Pathological fractures such as those observed in (but not limited to) Paget’s disease or in metastatic bone

HOS-216105 · has-indication-information · PDF-Seite 2

InductOs is indicated for single-level lumbar interbody spine fusion as a substitute for autogenous bone graft in adults with degenerative disc disease who have had at least 6 months of non-operative treatment for this condition. InductOs is indicated for the treatment of acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation. See section 5.1.

HOS-216108 · has-interaction-information · PDF-Seite 7

No interaction studies have been performed. As dibotermin alfa is a protein and has not been identified in the general circulation, it is an unlikely candidate for pharmacokinetic drug-drug interactions. In acute tibia fracture clinical trials, more InductOs patients receiving concomitant NSAIDs for 14 consecutive days experienced mild or moderate adverse events related to wound healing (e.g., wound drainage) than InductOs patients not taking NSAIDs. Although patient outcome was not affected, an interaction between NSAIDs and InductOs cannot be excluded. Information from clinical studies in acute tibia fractures indicated that the use of InductOs in patients receiving glucocorticoids was not associated with any apparent adverse reactions. In non-clinical studies, concurrent administration of glucocorticoids depressed bone repair (measured as a % change from control), but the effects of InductOs were not altered. In an in vitro study, dibotermin alfa was shown to bind to fibrin-based haemostatic agents or sealants. The use of these products in close proximity to InductOs is not recommended as this may lead to bone formation at the site of implant of the fibrin-based haemostatic agent or sealant (see section 4.2).

HOS-216109 · has-pregnancy-information · PDF-Seite 7

7 Pregnancy There are no or limited amount of data from the use of dibotermin alfa in pregnant women. Animal studies have shown reproductive toxicity (see section 5.3). Due to the unknown risks to the foetus associated with the potential development of neutralising antibodies to dibotermin alfa, InductOs is not recommended during pregnancy and in women of childbearing potential not using contraception (see section 4.4). Breast-feeding There is no information on the excretion of dibotermin alfa/metabolites in human milk. Considering the type of product, systemic exposure of the suckling infant is not expected, however a risk to the newborn/infant cannot be excluded. A decision must be made whether to discontinue breast-feeding or to abstain from InductOs therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. Fertility No impact on fertility was detected in non-clinical studies. No clinical data are available; potential risk for human is unknown.

HOS-216107 · has-warning-information · PDF-Seite 5

Failure to follow the product preparation instructions in section 6.6 and the method of administration in section 4.2 may compromise the safety and efficacy of InductOs. Cervical spine surgery The safety and efficacy of InductOs in cervical spine surgery have not been established, and InductOs should not be used in this condition. Localised oedema associated with the use of InductOs has been reported in patients undergoing cervical spine surgery. The oedema was delayed in onset and usually occurred in the first week post-operation. In some cases, the oedema was severe enough to result in airway compromise. Malignancy InductOs should not be used in patients with history or clinical suspicion of malignancy at the site of application (see section 4.3). Heterotopic ossification Use of InductOs may cause heterotopic ossification at the site of implantation and/or the surrounding tissues, which may result in complications. Bone resorption increased InductOs can cause initial resorption of surrounding trabecular bone as evidenced by radiolucency. Therefore, in the absence of clinical data, the product should not be used for direct applications to trabecular bone where transient bone resorption may create a risk of bone fragility (see section 4.8). Fluid collections Formation of a fluid collection (pseudocyst, localised oedema, implant site effusion), sometimes encapsulated and in some cases resulting in nerve compression and pain, has been reported associated with the use of InductOs. Clinical intervention (aspiration and/or surgical removal) may be required if symptoms persist (see section 4.8). Immune response 5 Both dibotermin alfa and bovine Type I collagen have been found to elicit immune responses in patients. Anti-dibotermin alfa antibodies: In spine fusion studies, 1.3% of patients receiving InductOs developed antibodies to dibotermin alfa versus 0.8% of patients receiving autogenous bone graft. In long-bone fracture studies, 6.3% of patients receiving dibotermin alfa with bovine Type I collagen matrix developed antibodies to dibotermin alfa versus 1.3% in the control group. All patients who were tested for neutralizing antibodies to bone morphogenetic protein-2 were negative. Anti-bovine Type I collagen antibodies: In spine fusion studies, 13.5% of patients receiving InductOs developed antibodies to bovine Type I collagen versus 14.3% of patients receiving autogenous bone graft. In long-bone

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