Tenkasi 1 200 mg powder for concentrate for solution for infusion – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Tenkasi 1 200 mg powder for concentrate for solution for infusion

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains oritavancin diphosphate equivalent to 1 200 mg oritavancin.

After reconstitution, 1 ml of the solution contains 30 mg oritavancin.

After dilution, 1 ml of the solution for infusion contains 4.8 mg oritavancin.

Excipient with known effect

Each vial contains 2 400 mg of hydroxypropylbetadex.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for concentrate for solution for infusion (powder for concentrate).

White to off-white or pink powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Tenkasi is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults (see sections 4.4 and 5.1).

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

Posology

1 200 mg administered as a single dose by intravenous infusion over 1 hours.

Special populations

Elderly (≥ 65 years)

No dose adjustment is required for patients ≥ 65 years of age (see section 5.2).

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. Renal impairment had no clinically relevant effect on the exposure of oritavancin (see section 5.2), however caution should be exercised when prescribing oritavancin in patients with severe renal impairment. Oritavancin is not removed from blood by haemodialysis procedures. Hydroxypropyl-β-cyclodextrin (HPβCD) is almost exclusively eliminated through the kidneys via glomerular filtration; its pharmacokinetics in patients with severe renal impairment has not been evaluated.

Hepatic impairment

No dose adjustment is required for patients with mild to moderate hepatic impairment (Child-Pugh Class B) (see section 5.2). 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 children and adolescents (<18 years) have not yet been established. No data are available.

Method of administration

Intravenous use.

There are two oritavancin medicinal products (Tenkasi 1 200 mg and Tenkasi 400 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.

Carefully follow the recommended posology (see section 4.2) and the instructions on reconstitution and dilution for Tenkasi 1 200 mg before administration (see section 6.6).

The single 1 200 mg vial should first be reconstituted with 40 mL of sterile water for injections (WFI). The reconstituted solution should be withdrawn and added to a 250 mL glucose 5% (D5W) or sodium chloride 9 mg/mL (0.9%) solution for injection intravenous bag for an intravenous infusion over 1 hour (see sections 6.2 and 6.6).

Refer to Tenkasi 400 mg for relevant information on the other oritavancin medicinal product.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Use of intravenous unfractionated heparin sodium is contraindicated for 120 hours (5 days) after oritavancin administration because the activated partial thromboplastin time (aPTT) test results may remain falsely elevated for up to 120 hours after oritavancin administration (see sections 4.4 and 4.5).

4.4 Special warnings and precautions for use

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. Before using oritavancin it is important to inquire carefully about previous hypersensitivity reactions to glycopeptides (e.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 1 hour 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. If reactions do occur, stopping or slowing the infusion may result in cessation of these symptoms (see section 4.8).

Renal impairment

The solubiliser HPβCD is excreted in urine. Clearance of HPβCD may be reduced in patients with renal impairment. The clinical significance of this finding is unknown.

Need for additional antibacterial agents

Oritavancin is active against Gram-positive bacteria only (see section 5.1). 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.

Interference with assay for coagulation tests

Oritavancin has been shown to interfere with certain laboratory coagulation tests (see sections 4.3 and 4.5). 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.

These effects result from oritavancin binding to and preventing the action of the phospholipid reagents which activate coagulation in commonly used laboratory coagulation tests. For patients who require aPTT monitoring within 120 hours of oritavancin dosing, a non-phospholipid dependent coagulation test such as a Factor Xa (chromogenic) assay or an alternative anticoagulant not requiring aPTT monitoring may be considered.

The Chromogenic Factor Xa Assay, the Thrombin Time (TT) assay and the assays used for the diagnosis of Heparin Induced Thrombocytopenia (HIT) are not affected by oritavancin. In vitro, oritavancin 46.6 μg/mL did not affect an assay for activated protein C resistance (APCR), suggesting that there is a low likelihood that oritavancin will interfere with this test. However, APCR is a phospholipid-based test and it cannot be ruled out that higher concentrations of oritavancin that may occur during clinical use could interfere with this test.

No effect of oritavancin on the in vivo coagulation system was observed in nonclinical and clinical studies.

Clostridioides difficile-associated diarrhoea

Antibacterial-associated colitis and pseudomembranous colitis have been reported for oritavancin and may range in severity from mild to life threatening diarrhoea. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of oritavancin (see section 4.8). In such a circumstance, the use of supportive measures together with the administration of specific treatment for Clostridioides difficile should be considered.

Superinfection

The use of antibacterial medicinal products may increase the risk of overgrowth of non-susceptible micro-organisms. If superinfection occurs, appropriate measures should be taken.

Osteomyelitis

In Phase 3 ABSSSI clinical trials, more cases of osteomyelitis were reported in the oritavancin-treated arm than in the vancomycin-treated arm (see section 4.8). Patients should be monitored for signs and symptoms of osteomyelitis after administration of oritavancin. If osteomyelitis is suspected or diagnosed, appropriate alternative antibacterial therapy should be instituted.

Abscess

In the Phase 3 clinical trials, slightly more cases of newly emergent abscesses were reported in the oritavancin-treated arm than in the vancomycin-treated arm (4.6% vs 3.4%, respectively) (see section 4.8). If newly emergent abscesses occur, appropriate measures should be taken.

Limitations of the clinical data

In the two major trials in ABSSSI the types of infections treated were confined to cellulitis, abscesses and wound infections only. Other types of infections have not been studied. There is limited experience in clinical studies in patients with bacteraemia, peripheral vascular disease or neutropenia, in immunocompromised patients, in patients aged > 65 years, in patients with severe renal impairment and in infections due to Streptococcus pyogenes.

Excipients

This medicinal product contains 2 400 mg of hydroxypropylbetadex in each vial which is equivalent to 9.6 mg/ml.

4.5 Interaction with other medicinal products and other forms of interaction

Substances metabolised by cytochrome P450

A screening drug-drug interaction study was conducted in healthy volunteers (n=16) evaluating the concomitant administration of a single 1 200 mg dose of oritavancin with probe substrates for several CYP450 enzymes. Oritavancin was found to be a nonspecific, weak inhibitor (CYP2C9 and CYP2C19) or a weak inducer (CYP3A4 and CYP2D6) of several CYP isoforms.

Caution should be used when administering oritavancin concomitantly with medicinal products with a narrow therapeutic window that are predominantly metabolised by one of the affected CYP450 enzymes (e.g., warfarin), as co-administration may increase (e.g., for CYP2C9 substrates) or decrease (e.g., for CYP2D6 substrates) concentrations of the narrow therapeutic range medicinal product. Patients should be closely monitored for signs of toxicity or lack of efficacy if they have been given oritavancin while on a potentially affected compound (e.g. patients should be monitored for bleeding, if concomitantly receiving oritavancin and warfarin) (see section 4.4). A study to assess the drug-drug interaction effect of a single 1 200 mg dose of oritavancin on the pharmacokinetics of S-warfarin following a single dose was conducted in 36 healthy subjects. S-warfarin pharmacokinetics were evaluated following a single dose of warfarin 25 mg given alone, or administered at the start, 24 or 72 hours after a single 1 200 mg dose of oritavancin. The results showed no effect of oritavancin on S-warfarin AUC and C_max.

Drug-laboratory test interactions (see sections 4.3 and 4.4)

Oritavancin binds to and prevents the action of the phospholipid reagents which activate coagulation in commonly used laboratory coagulation tests. Oritavancin concentrations achieved in the blood after 1 200 mg doses may produce falsely elevated results from certain laboratory tests (see Table 1).

Table 1: Coagulation tests affected by oritavancin

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of oritavancin in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Tenkasiduring pregnancy unless the clinical condition of the woman requires treatment with oritavancin.

Breast-feeding

Available pharmacodynamic/toxicological data in animals have shown excretion of oritavancin in milk (for details see section 5.3). It is unknown whether oritavancin/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Tenkasi therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

Animal studies have revealed no evidence of impaired fertility due to oritavancin at the highest concentrations administered. However, there are no data on the effects of oritavancin on human fertility.

4.7 Effects on ability to drive and use machines

Tenkasi has a minor influence on the ability to drive and use machines. Dizziness may occur and this may have an effect on driving and use of machines (see section 4.8).

4.8 Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions (≥5%) were: nausea, hypersensitivity reactions, infusion site reactions, and headache. The most commonly reported serious adverse reaction was cellulitis (1.1%). The most common reported reasons for discontinuation were cellulitis (0.4%) and osteomyelitis (0.3%). 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.

Table 2: Frequency of adverse reactions by system organ class

*These reactions may be infusion-related (see section 4.4)

** Infusion site reactions includes: infusion site phlebitis, infusion site erythema, extravasation, induration, pruritus, rash, oedema peripheral.

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 Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

In the clinical programme of 3017 oritavancin-treated subjects, there was no incidence of accidental overdose of oritavancin.

Oritavancin is not removed from blood by haemodialysis procedures. In the event of overdose, supportive measures should be taken.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antibacterials for systemic use, glycopeptide antibacterials, ATC code: J01XA05

Mechanism of action

Oritavancin has three mechanisms of action: (i) inhibition of the transglycosylation (polymerisation) step of cell wall biosynthesis by binding to the stem peptide of peptidoglycan precursors; (ii) inhibition of the transpeptidation (crosslinking) step of cell wall biosynthesis by binding to the peptide bridging segments of the cell wall; and (iii) disruption of bacterial membrane integrity, leading to depolarisation, permeabilisation, and rapid cell death.

Resistance

Gram-negative organisms are intrinsically resistant to all glycopeptides, including oritavancin.

Resistance to oritavancin was observed in vitro in vancomycin-resistant isolates of Staphylococcus aureus. There is no known cross-resistance between oritavancin and non-glycopeptide classes of antibiotics.

Oritavancin exhibits reduced in vitro activity against certain Gram-positive organisms of the genera Lactobacillus, Leuconostoc and Pediococcus that are intrinsically resistant to glycopeptides.

Susceptibility testing break points

Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows:

Table 3: Susceptibility Interpretive Criteria for Oritavancin

S=Susceptible, R=Resistant

Pharmacokinetic/Pharmacodynamic (PK/PD) relationship The area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratio of oritavancin for the infecting organism has been shown to be the parameter that best correlates with efficacy.

Clinical efficacy against specific pathogens

Efficacy has been demonstrated in clinical studies against the following pathogens that were susceptible to oritavancin in vitro.

Gram-positive microorganisms:

• Staphylococcus aureus
• Streptococcus pyogenes
• Streptococcus agalactiae
• Streptococcus dysgalactiae
• Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus)

Antibacterial activity against other relevant pathogens

Clinical efficacy has not been established against the following pathogens although in vitro studies suggest that they would be susceptible to oritavancin in the absence of acquired mechanisms of resistance:

• Beta-haemolytic streptococci of Group G
• Clostridium perfringens
• Peptostreptococcus spp.

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with Tenkasi in one or more subsets of the paediatric population in the treatment of acute bacterial skin and skin structure infections (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

Oritavancin exhibits linear pharmacokinetics at a dose up to 1 200 mg.

The mean (±SD) pharmacokinetic parameters of oritavancin products (Tenkasi 400 mg powder for concentrate for solution for infusion and Tenkasi 1 200 mg powder for concentrate for solution for infusion) in patients with ABSSSI following a single 1 200 mg dose are presented in Table 4.

Table 4: Mean (±SD) Pharmacokinetic Parameters following a single 1 200 mg dose of Tenkasi 1 200 mg powder for concentrate for solution for infusion by intravenous infusion over 1 hour (N= 50) and Tenkasi 400 mg powder for concentrate for solution for infusion by intravenous infusion over 3 hours (N=50) in Patients with ABSSSI

C_max, Maximum plasma concentration; AUC_0-72, Area under the plasma concentration-time curve from time zero to 72 hours; SD, Standard deviation.

Note: for Tenkasi 400 mg, data refer to the administration of 3 vials x 400 mg

Distribution

Oritavancin is approximately 85% bound to human plasma proteins. Based on population PK analysis, the population mean total volume of distribution is estimated to be approximately 87.6 L, indicating oritavancin is extensively distributed into the tissues.

Exposures (AUC_0-24) of oritavancin in skin blister fluid were 20% of those in plasma after a single 800 mg dose in healthy subjects.

Biotransformation

No metabolites were observed in plasma or bile from oritavancin treated dogs and rats, respectively. Additionally, in vitro human liver microsome studies indicated that oritavancin is not metabolised.

Elimination

No mass balance study has been conducted in humans. In humans, less than 1% to 5% of the dose was recovered as parent active substance in faeces and urine respectively after 2 weeks of collection indicating that oritavancin is slowly excreted unchanged.

The mean terminal elimination plasma half-life of oritavancin is 245 hours (14.9% CV) based on population PK analysis of ABSSSI patients receiving a single 1 200 mg dose. The population mean total clearance is estimated at 0.445 L/h (27.2 % CV).

In a population PK analysis, a relationship between height and clearance was identified, where clearance increased with increasing height. Dose modification based on height is not necessary.

Special populations

Renal impairment

The pharmacokinetics of oritavancin were examined in the single dose Phase 3 ABSSSI studies in patients with normal renal function, CrCL ≥90 mL/min (n=213), mild renal impairment, CrCL 60-89 mL/min (n=59), moderate renal impairment, CrCL 30-59 mL/min (n=22), and severe renal impairment CrCL <30 mL/min (n=3). Population pharmacokinetic analysis indicated that renal impairment had no clinically relevant effect on the exposure of oritavancin. No dedicated studies in dialysis patients have been conducted. Dose adjustment of oritavancin is not needed in patients with mild or moderate renal impairment, whereas data on severe renal impairment are too limited to make dose adjustment recommendation.

The excipient hydroxypropylbetadex is excreted in urine. Clearance of hydroxypropylbetadex may be reduced in patients with renal impairment.

Hepatic impairment

The pharmacokinetics of oritavancin were evaluated in a study of subjects with moderate hepatic impairment (Child-Pugh Class B, n=20) and compared with healthy subjects (n=20) matched for gender, age and weight. There were no relevant changes in pharmacokinetics of oritavancin in subjects with moderate hepatic impairment.

Dose adjustment of oritavancin is not needed in patients with mild and moderate hepatic impairment. The pharmacokinetics of oritavancin in patients with severe hepatic impairment have not been studied.

Effects of age, weight, gender and race

Population PK analysis from the single dose Phase 3 ABSSSI studies in patients indicated that gender, age, weight, or race had no clinically relevant effect on the exposure of oritavancin. No dose adjustment is warranted in these subpopulations.

5.3 Preclinical safety data

The primary adverse effect of oritavancin administration to rats and dogs was a dose related accumulation of eosinophilic granules in tissue macrophages including hepatocytes, renal cortical epithelial cells, adrenal cells and macrophages of the reticulo endothelial system. The appearance of the eosinophilic granules did not occur following single dose administration and did not significantly affect innate macrophage function in vitro at intracellular levels anticipated from a single 1 200 mg dose.

Moderate, dose-related increases in liver enzymes (alanine transaminase and aspartate transaminase) were observed in rats and dogs and were shown to be reversible upon cessation of treatment. Biochemistry changes associated with kidney function including decreases in urine-specific gravity and pH and slight increases in blood urea nitrogen and sporadic increases in creatinine were present in both rat and dog after treatment of two weeks. Reversible minimal tubular vacuolar degeneration was also observed in the kidneys of rats, due to a well known effect of hydroxypropylbetadex in the formulation. Extramedullary haematopoiesis in the spleen was observed in rats. This histopathological finding correlated with an enlargement and an increase in the weight of the spleen. The exposure in rats at the no observed adverse effect level (NOAEL) was less to only slightly higher than the human exposure based on the AUC.

Histamine-like infusion reactions following immediately or shortly after dosing with oritavancin occurred in both rats and dogs. These reactions were associated with mortality at lower doses in male than in female rats in single dose studies; however, the same gender-related differences were not observed in other species. Studies in neonatal rats and dogs for 30 days showed the same tissue effects as those seen in adult animals including sensitivity to the oritavancin-mediated histamine-like infusion reactions. Mortality was observed in neonatal rats at slightly lower dosage levels than in adults.

A standard battery of in vitro and in vivo tests on the genotoxic potential did not reveal any clinically relevant findings. Lifetime studies in animals have not been conducted to evaluate the carcinogenic potential of oritavancin.

When administered intravenously at doses up to 30 mg/kg, oritavancin did not affect the fertility or reproductive performance of male and female rats. Studies in pregnant rats and rabbits do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. There was no evidence of transplacental transfer of oritavancin in pregnant rats. The exposure in rats at the NOAEL was less to only slightly higher than the human exposure based on the AUC.

Following a single intravenous infusion in lactating rats, radio-labelled ^[14C]oritavancin was excreted in milk and absorbed by nursing pups.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Hydroxypropylbetadex

Mannitol

Phosphoric acid (for pH-adjustment)

Sodium hydroxide (for pH-adjustment)

6.2 Incompatibilities

Medicinal products formulated at a basic or neutral pH may be incompatible with oritavancin (see section 6.6).

This medicinal product must not be mixed with other medicinal products or solutions except those listed in section 6.6.

6.3 Shelf life

4 years

After reconstitution

The reconstituted solution should be further diluted in glucose 50 mg/ml (5%) or sodium chloride 9 mg/mL (0.9%) intravenous infusion bag immediately.

After dilution

The diluted solution should be used immediately.

From a microbiological point of view, the product should be used immediately. If not used immediately storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 4 hours at 25 °C and 12 hours at 2 °C -8 °C following dilution in a glucose 5% or sodium chloride 0.9% intravenous infusion bag.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions. For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Single-use 50 ml Type 1 glass vials with rubber stoppers and aluminium flip off cap.

1 individual vial is packaged in a carton.

6.6 Special precautions for disposal and other handling

For single use only. Tenkasi should be prepared under aseptic techniques.

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.

Carefully follow the recommended instructions for each medicinal product.

Tenkasi 1 200 mg vial needs to be reconstituted and diluted to prepare a single once-only 1 200 mg IV dose. The powder must be reconstituted with sterile water for injection and the resulting concentrate must be diluted in a glucose 5% or sodium chloride 0.9% intravenous infusion bag prior to use. Both the reconstituted solution and the diluted solution for infusion should be clear, colourless to pink solution. Parenteral medicinal products should be inspected visually for particulate matter after reconstitution.

Reconstitution:

• 40 mL of sterile water for injections (WFI) should be added using a sterile syringe to reconstitute thevial to provide a 30 mg/mL solution per vial.
• To avoid excessive foaming, it is recommended that sterile WFI should be added carefully, along the walls of the vials.
• The vial should be swirled gently to avoid foaming and ensure that all of the powder is completely reconstituted in solution.

Dilution: Glucose 5% (D5W) or sodium chloride 9 mg/mL (0.9%) intravenous bag should be used for dilution.

Dilution:

• Withdraw and and discard 40 mL from a 250 mL D5W or 0.9% sodium chloride intravenous bag.
• Withdraw 40 mL from the reconstituted vial and add to D5W or 0.9% sodium chloride intravenous bag to bring the bag volume to 250 mL. This yields a concentration of 4.8mg/mL of oritavancin. PP (Polypropylene) or PVC (Polyvinyl chloride) bags should be used for administration preparation.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Refer to Tenkasi 400 mg for relevant information on the other oritavancin medicinal product.

7 MARKETING AUTHORISATION HOLDER

Menarini International Operations Luxembourg S.A.

1, Avenue de la Gare

L-1611, Luxembourg

Luxembourg

8 MARKETING AUTHORISATION NUMBER(S)

PLGB 16239/0065

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

16/05/2024

10 DATE OF REVISION OF THE TEXT

16/05/2024