{"text_format":"1","workbook":"xlsx","n_sheets":4,"sheets":["Cover sheet-Comparator","Dosing calculator","Safety Profile","PI"],"not_rendered":{"charts":0,"images":7,"macros":1,"external_links":3,"defined_names":95,"comments":2,"pivot_tables":0},"unopened":[],"bounds":{"document_bytes":16777216,"sheet_cells":100000,"rows_first":2000,"rows_last":500,"rows_between":2000,"halvings":0,"cell_chars":16384,"cell_head_chars":4096},"cells_cut":0,"cells_raw":0,"read":"whole","date_system":"1900"}

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[null,null,null,null,"4 - Factor Prothrombin Complex Concentrate (PCC) Comparative Dose Calculator: Bleeding and perioperative prophylaxis of bleeding during vitamin K antagonist treatment"]
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[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
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[null,null,null,"Prothromplex® 500 IU (human prothrombin complex) licensed indication"]
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[null,null,null,"Treatment of bleeding and perioperative prophylaxis of bleeding in acquired deficiency of prothrombin complex coagulation factors, such as a deficiency caused by treatment with vitamin K antagonists or in case of overdose with vitamin K antagonists, when rapid correction of the deficiency is required.\n\nTreatment and perioperative prophylaxis of haemorrhages in congenital deficiency of vitamin K-dependent coagulation factors, when purified specific coagulation factor concentrate is not available.\n\nProthromplex® TOTAL is indicated in adults. There are insufficient paediatric data to recommend the administration of Prothromplex® in children.\n\nFor information on tolerability profile and special warnings and precautions for use, please see the 'Safety Profile' tab."]
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[null,null,null,"How to use the calculator"]
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[null,null,null,"This calculator allows the user to calculate and compare the dose of Prothromplex® TOTAL required for the treatment of bleeding and perioperative prophylaxis of bleeding during vitamin K antagonist treatment based on Summary of Product Characteristics (SmPC) dose recommendations with the recommended doses of Octaplex and Beriplex.\n\nThe user enters the patient's body weight in Kg and the initial International Normalised Ratio (INR), and the calculator generates the dose required for Prothromplex® TOTAL 500 IU.\n\nIn order to correct the INR, it is not necessary to exceed the dose of 50 IU/kg. If the severity of bleeding requires a higher dose, the risk/benefit has to be evaluated by the treating physician."]
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[null,null,null,"Assumptions and limitations"]
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[null,null,null,"There are no published head-to-head studies comparing Prothromplex® 500 IU with other PCCs.  Any and all calculations that are based on treatment units are for estimating the dose required and not for clinical comparisons of safety and/or efficacy. The dosing for the different 4PCCs is based on each individual treatment's SmPC. \n\nAll calculations that are based on treatment units are for estimating the dose required for Prothromplex® TOTAL 500 IU according to the initial INR measurement based on SmPC dose recommendations. \n\nThis dose calculator is intended for presentation or demonstration purposes only. Please refer to the posology and method of administration in the Summary of Product Characteristics (SmPC) before prescribing.\n\nMinimum and maximum body weight for this dose calculator is 40 - 100 kg and the minimum INR is 2."]
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[null,null,null,"Instructions"]
[null,null,null,null,null,"Editable cells"]
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[]
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[null,null,null,null,"Job code: C-APROM/GB/PROT/0056"]
[null,null,null,null,"Date of preparation: March 2024"]
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[null,null,null,null,"©2024 Takeda Pharmaceutical Company Limited. All rights reserved.\nTakeda® and the Takeda Logo® are registered trademarks of Takeda Pharmaceutical Company Limited."]

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[null,null,"4 - Factor Prothrombin Complex Concentrate (PCC) Dose Calculator: Bleeding and perioperative prophylaxis of bleeding during vitamin K antagonist treatment"]
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[]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,""]
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[]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,null,{"$f":"IF(G11=\"Northern Ireland\",\"Northern_Ireland\",G11)","v":0}]
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[null,null,null,null,"Patient Body weight (Kg)",null,null,75,{"$f":"IF(Q24=4,_xlfn.XLOOKUP(TRUE,K67:K70,#REF!),IF(Q24=5,_xlfn.XLOOKUP(TRUE,K67:K70,#REF!),_xlfn.XLOOKUP(TRUE,E67:E69,C67:C69)))","v":25}]
[null,null,null,null,"Patient INR",null,null,3]
[]
[]
[null,null,null,null,null,null,null,"Prothromplex®1","Beriplex®2 ","Octaplex®  (Min range) 3","Octaplex®  (Max range)3"]
[null,null,null,null,"Vial for reconstitution (IU)",null,null,500,{"$f":"IF(Q68=1,250,IF(Q68=2,500,1000))","v":500},{"$f":"IF(Q69=1,500,1000)","v":500},{"$f":"IF(Q69=1,500,1000)","v":500}]
[null,null,null,null,"Volume for reconstitution (ml)",null,null,17,{"$f":"IF(I28=250,10,IF(I28=500,20,40))","v":20},{"$f":"IF(J28=500,20,40)","v":20},{"$f":"IF(K28=500,20,40)","v":20}]
[null,null,null,null,{"$f":"IF(Q24=4,\"Dose (ml per Kg)\",IF(Q24=5,\"Dose (ml per Kg)\",\"Dose (IU per Kg)\"))","v":"Dose (IU per Kg)"},null,null,{"$f":"_xlfn.XLOOKUP(TRUE,E67:E69,C67:C69)","v":25},{"$f":"_xlfn.XLOOKUP(TRUE,E67:E69,C67:C69)","v":25},{"$f":"_xlfn.XLOOKUP(TRUE,K67:K70,I67:I70)","v":40},{"$f":"_xlfn.XLOOKUP(TRUE,K67:K70,J67:J70)","v":47.5}]
[null,null,null,null,"Recommended dose (IU)",null,null,{"$f":"H23*H30","v":1875},{"$f":"H23*I30","v":1875},{"$f":"H23*J30","v":3000},{"$f":"H23*K30","v":3562.5}]
[null,null,null,null,"Recommended dose (ml)",null,null,{"$f":"ROUND(((H31*H29)/H28),0)","v":64},{"$f":"(I31*I29)/I28","v":75},{"$f":"IF((J31*J29)/J28>120,120,(J31*J29)/J28)","v":120},{"$f":"IF((K31*K29)/K28>120,120,(K31*K29)/K28)","v":120}]
[null,null,null,null,"Recommended dose (IU)",null,null,{"$f":"IF((H23*H30)>(5000),(5000),(H23*H30))","v":1875},{"$f":"IF((H23*I30)>(5000),(5000),(H23*I30))","v":1875},{"$f":"IF((J34*J28)/J29>3000,3000,(J34*J28)/J29)","v":3000},{"$f":"IF((K34*K28)/K29>3000,3000,(K34*K28)/K29)","v":3000}]
[null,null,null,null,"Recommended dose (ml)",null,null,{"$f":"ROUND(((H33*H29)/H28),0)","v":64},{"$f":"(I33*I29)/I28","v":75},{"$f":"IF((J31*J29)/J28>120,120,(J31*J29)/J28)","v":120},{"$f":"IF((K31*K29)/K28>120,120,(K31*K29)/K28)","v":120}]
[]
[null,null,null,null,"Number of vials required",null,null,{"$f":"ROUNDUP(H33/H28,0)","v":4},{"$f":"ROUNDUP(I33/I28,0)","v":4},{"$f":"ROUNDUP(J33/J28,0)","v":6},{"$f":"ROUNDUP(K33/K28,0)","v":6}]
[null,null,null,null,"Volume wasted (ml)",null,null,{"$f":"(H36*H29)-H34","v":4},{"$f":"(I36*I29)-I34","v":5},{"$f":"(J36*J29)-J34","v":0},{"$f":"(K36*K29)-K34","v":0}]
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[null,null,null,null,"Infusion rate(ml/min)",null,null,2,{"$f":"IF(H23<70,(0.12*H23),8)","v":8}]
[null,null,null,null,"Time required (minutes)",null,null,{"$f":"H34/H40","v":32},{"$f":"I34/I40","v":9.375},{"$f":"J34/J40","v":{"$error":"#DIV/0!"}},{"$f":"K34/K40","v":{"$error":"#DIV/0!"}}]
[null,null,null,null,null,null,null,null,null,"For Octaplex - The infusion should start at a speed of 1 mL per minute, followed by 2-3 mL per minute"]
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[null,null,"For Beriplex:  Dose is based on body weight up to but not exceeding 100 kg. For patients weighing more than 100 kg, the maximum single dose should therefore not exceed 2500 IU for an INR of 2.0-3.9, 3500 IU for an INR of 4.0-6.0 and 5000 IU for an INR of > 6.0"]
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[null,null,"For Octaplex: The single dose should not exceed 3000 IU (120 mL Octaplex)"]
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[null,null,"References:"]
[null,null,"1. Prothromplex 500 IU powder and solvent for solution for injection Summary of Product Characteristics (Last accessed March 2024)"]
[null,null,"2. Beriplex P/N 500 IU Summary of Product Characteristics (Last accessed March 2024)"]
[null,null,"3. Octaplex 500 IU powder and solvent for solution for injection Summary of Product Characteristics (Last accessed March 2024)"]
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["WILL BE HIDDEN"]
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[null,null,null,null,null,"Max dose IU",null,{"$f":"A76 & \"IU\"","v":"Octaplex®IU"}]
["INR ",null,"Dose ( IU/Kg)",null,null,{"$f":"A74","v":"Prothromplex® "},{"$f":"A75&\" IU\"","v":"Beriplex® IU"},"INR ","Dose (IU/Kg)","MAX"]
["2.0 - 3.9",null,25,null,{"$f":"IF($H$24<2,\"NA\", IF($H$24<4,TRUE,FALSE))","v":true},null,2500,"2.0 - 2.5",22.5,32.5,{"$f":"IF($H$24<2,\"NA\", IF($H$24<2.5,TRUE,FALSE))","v":false}]
["4.0 - 6.0",null,35,null,{"$f":"IF(AND($H$24>3.9,$H$24<6.1),TRUE,FALSE)","v":false},null,3500,"2.5 - 2.9",32.5,40,{"$f":"IF(AND($H$24>2.4,$H$24<3),TRUE,FALSE)","v":false},null,null,null,null,null,2]
["> 6.0",null,50,null,{"$f":"IF($H$24>6,TRUE,FALSE)","v":false},"50 IU/Kg",5000,"3.0 - 3.5",40,47.5,{"$f":"IF(AND($H$24>2.9,$H$24<3.5),TRUE,FALSE)","v":true},null,null,null,null,null,1]
[null,null,null,null,null,null,null,">3.5",50,50,{"$f":"IF($H$24>3.4,TRUE,FALSE)","v":false},null,null,null,null,null,{"$f":"IF(G13=A74,1,IF(G13=A75,2,3))","v":3}]
[]
["50 IU/kg"]
[]
["Prothromplex® ","Prothomplex capped at 5000 Ius"]
["Beriplex®","Beriplex capped by INR "]
["Octaplex®","Octaplex capped by maximum dose of 120ml"]

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[null,null,"Safety Profile"]
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[]
[null,null,"Adverse reactions "]
[null,null,"Common adverse reactions (frequency: ≥1% to <10%)"]
[]
[null,null,null,null," "]
[null,null,"Cardiac",null,null,null,null,null,null,null,null,null,null,null,"Blood and lymphatic system"]
[null,null,"Heart failure",null,null,null,null,null,null,null,null,null,null,null,"Disseminated intravascular"]
[null,null,"Acute myocardial infarction‡",null,null,null,null,null,null,null,null,null,null,null,"coagulation"]
[null,null,"Tachycardia",null,null,null,null,null,null,null,null,null,null,null,"Inhibitors to one or more of"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,"the prothrombin complex"]
[null,null,"Vascular",null,null,null,null,null,null,null,null,null,null,null,"factors (Factors II, VII, IX, X)†"]
[null,null,"Arterial thrombosis"]
[null,null,"Venous thrombosis‡",null,null,null,null,null,null,null,null,null,null,null,"Respiratory"]
[null,null,"Hypotension",null,null,null,null,null,null,null,null,null,null,null,"Pulmonary embolism"]
[null,null,"Flushing",null,null,null,null,null,null,null,null,null,null,null,"Dyspnoea"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Wheezing"]
[null,null,"Immune system"]
[null,null,"Anaphylactic shock/reaction",null,null,null,null,null,null,null,null,null,null,null,"Skin and subcutaneous tissue"]
[null,null,"Hypersensitivity",null,null,null,null,null,null,null,null,null,null,null,"Urticaria"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Rash erythematous"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Pruritus"]
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[null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Nervous system"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Cerebrovascular accident"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Headache"]
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[null,null,null,null,null,null,null,null,null,null,null,null,null,null,"General"]
[null,null,null,null,null,null,null,null,null,null,null,null,null,null,"Pyrexia‡"]
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[null,null,"† Development in patients with congenital deficient factors. ‡ Reported from the clinical study."]
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[null,null,"Reference: Prothromplex® TOTAL 500 IU Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/15237/smpc. Accessed March 2024"]
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[null,null,"Special warnings and precautions for use"]
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[null,null,"Thromboembolism, disseminated intravascular coagulation, fibrinolysis"]
[null,null,"There is a risk of thromboembolic episodes, following the administration of human prothrombin complex. In each situation, the potential benefit of treatment should be "]
[null,null,"weighed against the risk of complications."]
[null,null,"Particularly close monitoring should be exercised when administering PCCs to:"]
[null,null,null,"Patients with a history of coronary heart disease"]
[null,null,null,"Patients with liver disease"]
[null,null,null,"Pre or post-operative patients"]
[null,null,null,"Neonates, or"]
[null,null,null,"Other patients at risk of thromboembolic events or disseminated intravascular coagulation"]
[null,null,"Virus safety"]
[null,null,"When medicinal products prepared from human blood or plasma are administered, infectious diseases due to transmission of infective agents cannot be totally excluded."]
[null,null,"It is strongly recommended that every time that Prothromplex TOTAL is administered to a patient, the name and batch number of the product are recorded in order to "]
[null,null,"maintain a link between the patient and the batch of the product."]
[null,null,"Inhibitory antibodies"]
[null,null,"Replacement therapy with human PCCs, including therapy with Prothromplex® TOTAL, may result in the formation of circulating antibodies inhibiting one or more of the "]
[null,null,"human prothrombin complex factors. If such inhibitors occur, the condition will manifest itself as a poor clinical response."]
[null,null,"Class reactions"]
[null,null,"Skin and subcutaneous tissue disorders: Angioedema, Paraesthesia"]
[null,null,"General disorders and administrative site conditions: Infusion site reaction"]
[null,null,"Nervous system disorders: Lethargy"]
[null,null,"Psychiatric disorders: Restlessness"]
[null,null,"Sodium"]
[null,null,"This medicinal product contains 68 mg sodium per vial or 0.14 mg sodium per International Unit equivalent to 3.4 % of the WHO recommended maximum daily intake of "]
[null,null,"2 g sodium for an adult."]
[null,null,"Heparin"]
[null,null,"Heparin may cause allergic reactions and reduced blood cell counts, which may affect the blood clotting system. Patients with a history of heparin-induced allergic "]
[null,null,"reactions should avoid the use of heparin-containing medicines."]
[null,null,"Paediatric population"]
[null,null,"There are insufficient data to recommend the administration of Prothromplex TOTAL in children."]
[]
[null,null,"For full details of special warnings, precautions and safety profile please see the Summary of Product Characteristics"]
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[]
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[null,null,"Reference: Prothromplex® TOTAL 500 IU Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/15237/smpc. \n"]
[null,null,"Accessed March 2024"]

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[null,"Prescribing Information"]