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Perfalgan Va

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  • 1. References: 1. Benhamou D, Berti M, Brodner G et al. Postoperative Analgesic Therapy Observational Survey (PATHOS) : A practice pattern study in 7 central/southern European countries. Pain 2008, 136:134-141. 2. Stephens J, Laskin B, Pashos C et al. The burden of acute postoperative pain and the potential role of the COX-2-specific inhibitors. Rheumatol 2003;42(suppl 3): iii40- iii52. 3. Apfelbaum L.J et al., Postoperative Pain Experience: Results from a National Survey Suggest Postoperative Pain Continues to Be Undermanaged. Anesth Analg 2003; 97:534-40 4. Commission on the provision of surgical services. Report of the working party on pain after surgery. London: The royal college of surgeons of England, The college of Anaesthetists, 1990. 5.Lorenz M Fischer et al, Discontinuation of Nonsteroidal Anti-inflammatory Drug Therapy and Risk of Acute Myocardial Infarction. Anch Intern Med. 2004: 164:2472-2476 6. Andrew Moore R et al, Nonsteroidal anti-inflammatory drugs ( NSAIDs), Cyclooxygenase-2 selective inhibitors(coxibs) and gastrointestinal harm: review of clinical trials and clinical practice. BMC Musculoskeletal Disorders 2006, 7:79 7. Giannoudis P.V et al, Nonunion of the femoral diaphysis. J Bone Joint Surg 2000; 82-B: 655-8. 8. http ;//arthritis-symptom.com/arthritis drugs/opioid.htm(1 to 8) 9. Timothy D Warner et al, Cyclooxygenase-3 (COX-3): Filling in the gaps toward a COX continuum? PNAS October 15,2002. Vol 99, No.21: 13371-13373 10. Chandrashekaran .N.V et al, COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression. PNAS. Oct 15,2002, Vol 99, No.21, 13926-13931 11. Olivier Malaise et al, Intravenous paracetamol: a review of efficacy and safety in therapeutic use. Future Neurol 2007. 2(6), 673-688. 12. I Power, Recent advances in postoperative pain therapy. BJA 2005, 95 (1): 43-51 13. Duggan S.t et al, Intravenous Paracetamol, Drugs 2009, 69(1) :101-113. 14. V. Piguet et al, Lack of acetaminophen ceiling effect on R-III nociceptive flexion reflex. Eur J Clin Pharmacol 1998, 53:321-324. 15. M Depre et al, Tolerence and pharmacokineticsof propacetamol, a paracetamol formulation for intravenous use. Fundam Clin Pharmacol 1992, 6: 259 – 262. 16. Bannwarth .B.et al, Plasma and cerebrospinal fluid concentration of paracetamol after a single intravenous dose of propacetamol. Eur J Clin Pharmacol 1992, 34: 79-81. 17. Perfalgan Product Monograph, India 2009. 18. India Product Insert, 2009. 19. Oscier C.D et al, Peri-operative use of paracetamol. Anaesthesia, 2009, 64:65-72. 20. James C. Crews, Multimodal Pain Management Strategies for Office-Based and ambulatory procedures. JAMA, Aug 2002,Vol288. No.5 21. Acute Pain Management: Scientific Evidence, Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. Second edition 2005. 22. Henrich W.L et al, Anal;gesics and Kidney, AJKD, 1996, Vol 27, No.1, 162-165 23. Tian J Zhou et al, Propacetamol versus ketorolac for the treatment of acute postoperative pain after total hip or knee replacement. Anaesth Analg 2001, 92 1569-75 24. Hynes D et al, Analgesic efficacy of parentral paracetamol(propacetamol) and diclofenac in post-operative orthopedic pain. Acta Anaesthesiol Scand 2006: 50: 374-381. 25. Hugo Van Aken et al, Assessing Analgesia in single and repeated administrations of propacetamol for postoperative pain: Comparison with Morphine after Dental Surgery. Anesth Analg 2004: 98:159-65. 26. Alhashemi J.A et al, Intravenous acetaminophen Vs oral ibuprofen in combination with morphine PCIA after Cesarean delivery. Can J Anesth 2006, 53:12: 1200-1206. 27. Lolter Cattabriga et al, Intravenous paracetamol as adjunctive treatment for postoperative pain after cardiac surgery: a double bling randomized controlled trial. Eur J of Cardio-thoracic surgery 2007, 32:527-531. 28. Kehlet H et al, Multimodal strategies to improve surgical outcome. The American Journal of Surgery 2002, 183:630-641. 29. Peduto V.A et al, Efficacy of propacetamol in the treatment of postoperative pain. Acta Anaesthesiol Scand 1998: 42: 293-298. 30. Sinatra R.s et al, Efficacy and safety of single and repeated administration of 1 gram Intravenous Acewtaminophen Injection for pain management after Major Orthopedic Surgery.Anaesthesiology 2005: 102:822-31. 31. Flouvant B et al, Bioequivalence study comparing a new paracetamol solution for injection and propacetamol after single intravenous infusion in healthy subjects Int J Clin Pharmacol Therapeutics. 2004;42(1):50-7 In Post Operative Pain Management September 2009 For Hospital Use Only st PER/016/04-09 Your 1 Step Matters
  • 2. Evidence suggests that post-operative pain is sub-optimally managed1 and is not limited to the immediate recovery period2 3 In POPM* Approximately 80% surgical patients have inadequate pain relief Your st 1 Step CONSEQUENCES OF INADEQUATE PAIN CONTROL FOLLOWING SURGERY ARE Matters SIGNIFICANT AND CAN RESULT IN IMMEDIATE AND LONG-TERM COMPLICATIONS 4 • Hypoxaemia/atelectasis/pneumonitis • Myocardial Ischemia and infarction • Deep venous thrombosis/pulmonary embolus • Urinary retention • Delayed recovery of bowel function • Residual psychological trauma *Post operative pain management
  • 3. Limitations of Current Analgesics Agents in POPM* Limitations of NSAID’s In POPM* 5 Inhibition of Platelet aggregation Impairment of Bone healing 7 6 Your Increased incidence of Gastrointestinal Increased Cardiovascular risk st ulcers6 1 Step Matters Limitations of Opioids 4,8 Respiratory depression Hypotension Restlessness or Nervousness Severe weakness Constipation Nausea and Vomiting Urinary retention Stomach Pain or Cramps *Post operative pain management
  • 4. 1g IV Unleash the True Power & Potential of Unique I.V. Paracetamol Infusion Mode of Action of Analgesics NSAIDs Opioids Inhibition of Inhibition of Activation central Cox-29, peripheral and of Opioid Cox-310 (Inhibition of central PG synthesis) receptors12 Cox-1/Cox-2 (inhibition of PG synthesis)10,12 Interaction with serotoninergic descending inhibitory pathway11 IV ACTS AT BOTH, CENTRAL & PERIPHERAL COMPONENTS OF PAIN PATHWAY13
  • 5. 1g IV Unleash the True Power & Potential of Unique I.V. Paracetamol Infusion IMPROVED PHARMACOKINETICS VS ORAL PROPACETAMOL15 Higher peak plasma paracetamol concentrations14 IV propacetamol Oral propacetamol Bioavailability 100% 82.2% Higher paracetamol concentrations T max 15 min* 1 h 28 min* cross the blood-brain barrier14 C max 12.72 µg/ml* 5.49 µg/ml* AUC 0- 25.53 µg/ml.h* 21.04µg/ml.h* Heightened antinociceptive effects14 *p<0.0001 Plasma and CSF paracetamol concentrations following a single IV dose of paracetamol (2g) in patients with nerve root compression pain16 IV lacks the Ceiling effect observed 16 with oral propacetamol & exerts a Dose- 14 dependent central Antinociceptive effect14 12 Paracetamol (µg/ml) 10 8 CSF concentrations The Analgesic effect of Paracetamol is probably 6 Plasma concentrations dependent on the Rate & Amount of active drug 4 2 reaching the CNS14 0 (adapted from Bannawarth B et al) 3 0 2 4 6 8 10 12 Time (hrs) 31 Paracetamol 1g IV given as propacetamol 2g IV : bio-equivalent formulations therapeutically equivalent
  • 6. 17 Oxygen-Free Manufacturing Process Solubilization (Mannitol+Di sodium Phosphate) Preservative Free Solution pH Adjustment (Terminal Sterilsation) (5.5 for Max. Shelf-life) Oxygen Free Manufacturing (Nitrogen & Argon gas + Cysteine Hydrochloride Monohydrate) 1g IV
  • 7. 1g IV Unleash the True Power & Potential of a Unique I.V. Paracetamol Infusion Characteristics of an Ideal Analgesic Agent in POPM* Characteristics IV Fast Onset of Action 5-10 Minutes18 Usage Flexibility Peri-operative19 Support Balanced Analgesia Yes, Reducing Opioid Usage upto 46%11 Usage in Wide Patient Type Yes Tolerability Yes Dosage Convenience Ready to use Infusion IV is an effective analgesic for acute pain20,21 *Post operative pain management
  • 8. 1g IV Comparable postoperative analgesic efficacy 25 Total Hip or Knee Replacement 23 Dental Surgery 1g IV 1g IV Ketorolac 30mg IV Morphine 10mg IM 1g IV Single Dose 1g IV Single Dose 26 Total Hip Arthroplasty 24 Cesarean Delivery Perfalgan 1g IV is a reasonable alternative to 1g IV Ibuprofen 400mg Oral as an adjunct to morphine patient- Diclofenac 75mg IM controlled analgesia after Cesarean delivery 1g IV, 2 Dose 5 hours apart 1g IV 6 hourly Ibuprofen 400mg 6 hourly Cardiac Surgery: 1g IV provides significant pain reduction in patients undergoing cardiac surgery against placebo27
  • 9. 1g IV An effective partner in balanced Analgesia Balanced analgesia improves Ø 1g : proven opioid- -46% of morphine postoperative pain relief through:28 sparing effect consumption 24-hour morphine consumption in terms of total PCA • Additive or synergistic effects of multiple agents in mg and total number of boluses • Reduction of side-effects (e.g. opioid sparing) 20 i.v. paracetamol (n=42) 17 *** 17.6 *** placebo (n=47) 16 ***p<0.001 12 9.4 Morphine 8 9 Sparing effect* 4 29 43-46% 0 PCA PCA boluses dose (no.) (mg) Hip Arthroplasty * 4g paracetamol saved 8mg of morphine over 24 hours, which is equal to a sparing effect of 43-46% 31 Ø Paracetamol 1g IV given as propacetamol 2g IV : bio-equivalent formulations therapeutically equivalent
  • 10. 1g IV Unleash the True Power & Potential of a Unique I.V. Paracetamol Infusion HAS THE RECOGNIZED SAFETY PROFILE OF PARACETAMOL • Not associated with increased Incidence of nausea, vomiting and respiratory depression observed with opioids30 • Not associated with deleterious gastrointestinal, haematological and renal effects associated 30 with NSAID’s and COX-2 inhibitors • Few drug interactions and contra-indications30 • Recommended by the National Kidney Foundation (US) as the non-narcotic analgesic of choice in patients with underlying renal disease22 29 Renal and Hepatic tolerance at therapeutic doses similar to placebo 30 Historically low incidence of adverse events and drug interactions
  • 11. 1g IV Unleash the True Power & Potential of a Unique I.V. Paracetamol Infusion 18 Safety and Tolerability The overall of adverse events in Perfalgan patients to placebo within the clinical trial set can be observed in the tables bellow.1 Adverse events in adults-greater than 100% (observed in the clinical trial set) Perfalgan % Placebo% Perfalgan % Placebo % n=99 n=102 n=99 n=102 Neurological Psychiatric Dizziness 2.7 2.9 Insomnia - 1.96 Headache 1.3 4.9 Dystonia - - Skin and Appendage Injection site pain 2.0 - Gastrointestinal Injection site reaction 2.67 - Vomiting 4.0 2.9 Post-Operative site reation 2.67 - Dry mouth - - Pruritus 3.3 4.9 Diarrhea 1.3 - Respiratory Constipation 6.7 11.8 Alveolitis Nausea 10.0 8.8 1.3 2.94 Coughing 2.0 - Dyspepsia 1.3 - Enlarged abdomen 2.0 - Endocrine/Metabolic Gastrointestinal disorder 2.0 - Hyperglycemia 1.3 - Haematological Hypokalaemia 1.3 - Anemia 2.7 6.9 General Post operative hemorrhage 2.0 - Fatigue 1.59 - Fever - 5.9 Hepatobiliary Oedema-peripheral Gamma GT - Increase 1.3 - - - Chest pain 1.33 - SGPT - increase 1.3 -
  • 12. 1g IV Unleash the True Power & Potential of a Unique I.V. Paracetamol Infusion Dosage Profile18 Dosing Interval OHrs 4-6Hrs 12Hrs 18Hrs Maximum Daily dose Adults (›50kg) 1g 1g 1g 1g 4g _ Severe renal impairment (creatinine clearance<30ml/min) : 6 hourly dosing schedule It is important to consider the contribution of all paracetamol containing medications, including non-prescription, oral or PR forms of drug to this total daily paracetamol dose prior to administering 1g is convenient and ready-to-use in patients with IV line • Administrated as a 15-minute IV infusion • Store at room temperature, below 30° C • Available in 100ml clear glass vials in packs of 12 vials • Shelf life of 2 years • No need to reconstitute