Tenkasi (Previously Orbactiv)

Posology Adults 1 200 mg administered as a single dose by intravenous infusion over 3 hours. Paediatric patients aged 3 months to < 18 years 15 mg/kg administered as a single dose by intravenous infusion over 3 hours (maximum 1 200 mg).

6 for further details. 2). Renal impairment No dose adjustment is needed in patients with mild or moderate renal impairment. Very limited data are available in patients with severe renal impairment. 2), however caution should be exercised when prescribing oritavancin in patients with severe renal impairment.

Oritavancin is not removed from blood by haemodialysis procedures. 2). The pharmacokinetics of oritavancin in patients with severe hepatic impairment (Child-Pugh Class C) has not been evaluated, however based on pharmacokinetic parameters, severe hepatic impairment is not expected to have an impact on oritavancin exposure.

Therefore, no dose adjustment is required, even if caution should be exercised when prescribing oritavancin to patients with severe hepatic impairment (Child-Pugh Class C). Paediatric population The safety and efficacy of oritavancin in paediatric patients < 3 months of age have not yet been established.

Method of administration Intravenous use. There are two oritavancin medicinal products (Tenkasi 400 mg and Tenkasi 1 200 mg) that: • Are supplied in different dose strengths of oritavancin. • Have different recommended duration of infusion.

• Have different preparation instructions, including differences in reconstitution, dilution, and compatible diluents. 6). Each of the three 400 mg vials should first be reconstituted with 40 mL of sterile water for injection (WFI). 6).

Only D5W should be used for dilution. 2) Refer to Tenkasi 1 200 mg for relevant information on the other oritavancin medicinal product. 4

Summary of the safety profile The most commonly reported adverse reactions (≥5%) were: nausea, hypersensitivity reactions, infusion site reactions, and headache. 1%). 3%). Female patients had a higher reporting rate for adverse reactions than male patients.

Tabulated list of adverse reactions Adverse reactions for oritavancin from the pooled Phase 3 ABSSSI clinical trials with single-dose oritavancin are listed by system organ class in the following table. Frequencies are defined as: 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); not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 4) ** Infusion site reactions includes: infusion site phlebitis, infusion site erythema, extravasation, induration, pruritus, rash, oedema peripheral.

Paediatric population The safety assessment in paediatric patients is based on data from one trial in which 38 patients aged from 3 months to 18 years with suspected or confirmed Gram-positive bacterial infection received Tenkasi. Overall, the safety profile in these 38 patients was similar to that observed in the adult population.

4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Hypersensitivity reactions Serious hypersensitivity reactions, including anaphylactic reactions and anaphylactic shock have been reported with the use of oritavancin. If an acute hypersensitivity reaction occurs during oritavancin infusion, oritavancin should be discontinued immediately and appropriate supportive care should be instituted.

No data are available on cross-reactivity between oritavancin and other glycopeptides, including vancomycin. g. vancomycin, telavancin). Due to the possibility of cross-hypersensitivity, there should be careful monitoring of patients with any history of glycopeptide hypersensitivity during and after the infusion.

Infusion related reactions Oritavancin is given via intravenous infusion over 3 hours, to minimise the risk of infusion-related reactions. Intravenous infusions of oritavancin can cause reactions such as flushing of the upper body, urticaria, pruritus and/or rash.

Infusion-associated reactions characterised by chest pain, chest discomfort, chills, tremor, back pain, neck pain, dyspnoea, hypoxia, abdominal pain, and fever have been observed with the use of oritavancin, including after the administration of more than one dose of oritavancin during a single course of therapy.

8). 1). In mixed infections where Gram-negative and/or certain types of anaerobic bacteria are suspected, oritavancin should be co- administered with appropriate antibacterial agent(s). Concomitant use of warfarin Oritavancin has been shown to artificially prolong prothrombin time (PT) and international normalised ratio (INR) for up to 12 hours, making the monitoring of the anticoagulation effect of warfarin unreliable up to 12 hours after an oritavancin dose.

5). Oritavancin concentrations that are found in the blood of patients following administration of a single dose have been shown to artificially prolong: • aPTT for up to 120 hours, • PT and INR for up to 12 hours, • Activated Clotting Time (ACT) for up to 24 hours, • Silica Clot Time (SCT) for up to 18 hours, and • Dilute Russell’s Viper Venom Test (DRVVT) for up to 72 hours.

1. 5).