TAVOCTAME

Posology The dose and frequency of TAVOCTAME depends on the severity and localisation of the infection and expected pathogens. 5 g tazobactam given every eight hours. 5 g tazobactam administered every six hours. This regimen may also be applicable to treat patients with other indicated infections when particularly severe.

5 g Severe pneumoniaEvery six hours Neutropenic adults with fever suspected to be due to a bacterial infection. 25g should be administered following each dialysis period, because haemodialysis removes 30%-50% of piperacillin in four hours.

2). Dose in elderly patients No dose adjustment is required for the elderly with normal renal function or creatinine clearance values above 40 ml/min. 5 g per dose over 30 minutes. Renal impairment The intravenous dose should be adjusted to the degree of actual renal impairment as follows (each patient must be monitored closely for signs of substance toxicity; medicinal product dose and interval should be adjusted accordingly): Creatinine clearance (ml/min) TAVOCTAME (recommended dose) > 50 No dose adjustment needed.

75 mg tazobactam / kg every eight hours. For children on haemodialysis, one additional dose of 40 mg piperacillin / 5 mg tazobactam / kg should be administered following each dialysis period. Use in children aged below 2 years The safety and efficacy of TAVOCTAME in children 0- 2 years of age has not been established.

No data from controlled clinical studies are available. Treatment duration The usual duration of treatment for most indications is in the range of 5-14 days. However, the duration of treatment should be guided by the severity of the infection, the pathogen(s) and the patient's clinical and bacteriological progress.

25 g is administered by intravenous infusion (over 30 minutes). 6.

The most commonly reported adverse reaction is diarrhoea (occurring in 1 patient out of 10). Among the most serious adverse reactions pseudo-membranous colitis and toxic epidermal necrolysis occur in 1 to 10 patients in 10,000. The frequencies for pancytopenia, anaphylactic shock and Stevens-Johnson syndrome cannot be estimated from the currently available data.

In the following table, adverse reactions are listed by system organ class and MedDRA-preferred term. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. System Organ Class 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 Frequency not known (cannot be estimated from available data) Infections and infestations candidiasis* pseudo- membranous colitis Blood and lymphatic system disorders thrombocytopen ia, anaemia* leukopenia, agranulocytosis, Pancytopenia*, neutropenia, haemolytic anaemia*, eosinophilia*, thrombocytosis * Immune system disorders anaphylactoid reaction*, anaphylactic reaction*, anaphylactoid shock*, anaphylactic shock*, hypersensitivity * Metabolism and nutrition disorders hypokalaemia, Psychiatric disorders insomnia delirium* Nervous system disorders headache, insomnia seizure* Vascular disorders hypotension, thrombophlebiti s, phlebitis, flushing Respiratory, thoracic and mediastinal disorders epistaxis eosinophilic pneumonia Gastrointestina l disorders diarrhoea abdominal pain, vomiting, nausea, constipation, dyspepsia stomatitis Hepatobiliary disorders Hepatitis*, jaundice, Skin and subcutaneous tissue disorders rash, pruritus erythema multiforme*, urticaria, rash maculopapular* toxic epidermal necrolysis* Stevens- Johnson syndrome*, dermatitis exfoliative, drug reaction with eosinophilia and systemic symptoms (DRESS)*, acute generalised exanthematous pustulosis (AGEP)*, dermatitis bullous purpura Musculoskeleta l and connective tissue disorders arthralgia, myalgia Renal and urinary disorders renal failure, tubulointerstitial nephritis* General disorders and administration site conditions pyrexia, injection site reaction chills Investigations alanine aminotransferas e increased, aspartate aminotransferas e increased, protein total decreased, blood albumin decreased, Coombs direct test positive, blood creatinine increased, blood alkaline phosphatase increased, blood urea increased, activated partial thromboplastin time prolonged blood glucose decreased, blood bilirubin increased, prothrombin time prolonged bleeding time prolonged, gamma- glutamyltransfer ase increased *ADR identified post marketing Piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.

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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

The selection of piperacillin/tazobactam to treat an individual patient should take into account the appropriateness of using a broad-spectrum semi-synthetic penicillin based on factors such as the severity of the infection and the prevalence of resistance to other suitable antibacterial agents.

g. cephalosporin, monobactam or carbapenem) and other allergens. Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid [including shock]) reactions have been reported in patients receiving therapy with penicillins, including Piperacillin/Tazobactam.

These reactions are more likely to occur in persons with a history of sensitivity to multiple allergens. Serious hypersensitivity reactions require the discontinuation of the antibiotic, and may require administration of epinephrine and other emergency measures.

8). If patients develop a skin rash they should be monitored closely and TAVOCTAME discontinued if lesions progress.

Haemophagocytic lympohistiocytosis (HLH):

Cases of HLH have been reported in patients treated with piperacillin/tazobactam, often following treatment longer than 10 days. , fever, hepatosplenomegaly, hypertriglyceridaemia, hypofibrinogenaemia, high serum ferritin, cytopenias and haemophagocytosis).

Patients who develop early manifestations of pathologic immune activation should be evaluated immediately. If diagnosis of HLH is established piperacillin/tazobactam treatment should be discontinued. Antibiotic-induced pseudomembranous colitis may be manifested by severe, persistent diarrhoea which may be life-threatening.

The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment. In these cases TAVOCTAME, should be discontinued. Therapy with TAVOCTAME may result in the emergence of resistant organisms, which might cause super-infections.

Bleeding manifestations have occurred in some patients receiving beta-lactam antibiotics. These reactions sometimes have been associated with abnormalities of coagulation tests, such as clotting time, platelet aggregation and prothrombin time, and are more likely to occur in patients with renal failure.

If bleeding manifestations occur, the antibiotic should be discontinued and appropriate therapy instituted. Leukopenia and neutropenia may occur, especially during prolonged therapy. Therefore, periodic assessment of a full blood count should be performed.

8). Hypokalaemia may occur in patients with low potassium reserves or those receiving concomitant medicinal products that may lower potassium levels; periodic electrolyte determinations may be advisable in such patients. 8), TAVOCTAME should be used with care in patients with renal impairment or in hemodialysis patients.

2). In a secondary analysis using data from a large multicenter, randomized- controlled trial when glomerular filtration rate (GFR) was examined after administration of frequently used antibiotics in critically ill patients, the use of TAVOCTAME was associated with a lower rate of reversible GFR improvement compared with the other antibiotics.

This secondary analysis concluded that TAVOCTAME was a cause of delayed renal recovery in these patients. 5). 7 mmol (108 mg) of sodium. To be taken into account by patients on a controlled sodium diet.

1. g. cephalosporin, monobactam or carbapenem).