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