Tenkasi (previously Orbactiv)

HOS-097060 · has-adverse-reaction-information · PDF-Seite 7

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 3: Frequency of adverse reactions by system organ class System organ class Frequency Adverse Reactions Infections and infestations Common Cellulitis, abscess (limb and subcutaneous) Uncommon Osteomyelitis Blood and lymphatic system disorders Common Anaemia Uncommon Eosinophilia, thrombocytopenia Immune system disorders Uncommon Hypersensitivity (see sections 4.3 and 4.4), anaphylactic reaction Unknown Anaphylactic shock Metabolism and nutrition disorders Uncommon Hypoglycaemia, hyperuricaemia Nervous system disorders Common Headache, dizziness Rare Tremor* Cardiac disorders Common Tachycardia 7  Respiratory, thoracic and mediastinal disorders Uncommon Bronchospasm, wheezing, dyspnoea* Rare Hypoxia* Gastrointestinal disorders Common Nausea, vomiting, diarrhoea, constipation Uncommon Abd

Auszug; vollständigen Abschnitt im Original lesen.

HOS-097066 · has-adverse-reaction-information · PDF-Seite 21

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 System organ class Frequency Adverse Reactions Infections and infestations Common Cellulitis, abscess (limb and subcutaneous) Uncommon Osteomyelitis Blood and lymphatic system disorders Common Anaemia Uncommon Eosinophilia, thrombocytopenia Immune system disorders Uncommon Hypersensitivity (see sections 4.3 and 4.4), anaphylactic reaction Unknown Anaphylactic shock Metabolism and nutrition disorders Uncommon Hypoglycaemia, hyperuricaemia Nervous system disorders Common Headache, dizziness Rare Tremor* Cardiac disorders Common Tachycardia Respiratory, thoracic and mediastinal disorders Uncommon Bronchospasm, wheezing, dyspnoea* Rare Hypoxia* Gastrointestinal disorders Common Nausea, vomiting, diarrhoea, constipation Uncommon Abdominal pain* Hepatobiliary disorders Common

Auszug; vollständigen Abschnitt im Original lesen.

HOS-097062 · has-contraindication-information · PDF-Seite 17

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).

HOS-097056 · has-contraindication-information · PDF-Seite 4

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).

HOS-097055 · has-indication-information · PDF-Seite 2

Tenkasi is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) in adults and paediatric patients aged 3 months and older (see sections 4.2, 4.4 and 5.1). Consideration should be given to official guidance on the appropriate use of antibacterial agents.

HOS-097061 · has-indication-information · PDF-Seite 16

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.

HOS-097058 · has-interaction-information · PDF-Seite 5

Substances metabolised by cytochrome P450 5 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 Cmax. 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 2). Table 2: Coagulation tests affected by oritavancin Assay Duration of interference Prothrombin time (PT) Up to 12 hours International normalized ratio (INR) Up to 12 hours Activated partial thromboplastin time (aPTT) Up to 120 hours Activated clotting time (ACT) Up to 24 hours Silica clot time (SCT) Up to 18 hours Dilute Russell’s viper venom time (DRVVT) Up to 72 hours

HOS-097064 · has-interaction-information · PDF-Seite 19

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 19 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 Cmax. 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 Assay Duration of interference Prothrombin time (PT) Up to 12 hours International normalized ratio (INR) Up to 12 hours Activated partial thromboplastin time (aPTT) Up to 120 hours Activated clotting time (ACT) Up to 24 hours Silica clot time (SCT) Up to 18 hours Dilute Russell’s viper venom time (DRVVT) Up to 72 h

Auszug; vollständigen Abschnitt im Original lesen.

HOS-097065 · has-pregnancy-information · PDF-Seite 20

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.

HOS-097059 · has-pregnancy-information · PDF-Seite 6

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 Tenkasi during pregnancy unless the clinical condition of the woman requires treatment with oritavancin. Breastfeeding 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. 6 A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from Tenkasi therapy taking into account the benefit of breastfeeding 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.

HOS-097057 · has-warning-information · PDF-Seite 4

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 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. If reactions do occur, stopping or slowing the infusion may result in cessation of these symptoms (see section 4.8). 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, •

Auszug; vollständigen Abschnitt im Original lesen.

HOS-097063 · has-warning-information · PDF-Seite 17

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. 17 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 i

Auszug; vollständigen Abschnitt im Original lesen.