DYNASTAT

Posology The recommended dose is 40 mg administered intravenously (IV) or intramuscularly (IM), followed every 6 to 12 hours by 20 mg or 40 mg as required, not to exceed 80 mg/day. As the cardiovascular risk of COX-2 specific inhibitors may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used.

1). Concomitant use with opioid analgesics Opioid analgesics can be used concurrently with parecoxib, dosing as described in the paragraph above. In all clinical assessments parecoxib was administered at a fixed time interval whereas the opioids were administered on as needed basis.

Elderly No dose adjustment is generally necessary in elderly patients (≥65 years). 2). 2). No dosage adjustment is generally necessary in patients with mild hepatic impairment (Child- Pugh score 5-6). This medicine should be introduced with caution and at half the usual recommended dose in patients with moderate hepatic impairment (Child-Pugh score 7-9) and the maximum daily dose should be reduced to 40 mg.

2). ). Paediatric population The safety and efficacy of parecoxib in children under 18 years old have not been established. No data are available. Therefore, parecoxib is not recommended in these patients. Method of administration The IV bolus injection may be given rapidly and directly into a vein or into an existing IV line.

The IM injection should be given slowly and deeply into the muscle. 6. Precipitation may occur when this medicine is combined in solution with other medicinal products and therefore this medicine must not be mixed with any other medicinal product, either during reconstitution or injection.

In those patients where the same IV line is to be used to inject another medicinal product, the line must be adequately flushed prior to and after this medicine’s injection with a solution of known compatibility. 45%) and glucose 50 mg/ml (5%) solution for injection/infusion; or • Ringer-Lactate solution for injection.

Injection into an IV line delivering glucose 50 mg/ml (5%) in Ringer-Lactate solution for injection, or other IV fluids not listed above, is not recommended as this may cause precipitation from solution.

Summary of the safety profile The most common adverse reaction for this medicine is nausea. The most serious reactions occur uncommonly to rarely, and include cardiovascular events such as myocardial infarction and severe hypotension, as well as hypersensitivity events such as anaphylaxis, angioedema, and severe skin reactions.

1), deep surgical infections, and sternal wound healing complications. Tabulated list of adverse reactions The following adverse reactions were reported for patients who received parecoxib (N=5,402) in 28 placebo-controlled clinical trials.

Reports from post-marketing experience have been listed as “frequency not known” because the respective frequencies cannot be estimated from the available data. Within each frequency grouping, adverse reactions are listed using MedDRA terminology and presented in order of decreasing seriousness.

Adverse Drug Reaction Frequency Very Common ( ≥1/10) Common ( ≥1/100 to <1/10) Uncommon ( ≥1/1000 to <1/100) Rare ( ≥1/10,000 to <1/1000) Not known Infections and infestations Pharyngitis, alveolar osteitis (dry socket) Abnormal sternal serous wound drainage, wound infection Blood and lymphatic system disorders Anaemia postoperative Thrombocytopenia Immune system disorders Anaphylactoid reaction Metabolism and nutrition disorders Hypokalaemia Hyperglycaemia, anorexia Psychiatric disorders Agitation, insomnia Nervous system disorders Hypoaesthesia, dizziness Cerebrovascular disorder Ear and labyrinth disorders Ear pain Adverse Drug Reaction Frequency Very Common ( ≥1/10) Common ( ≥1/100 to <1/10) Uncommon ( ≥1/1000 to <1/100) Rare ( ≥1/10,000 to <1/1000) Not known Cardiac disorders Myocardial infarction, bradycardia Circulatory collapse, congestive heart failure, tachycardia Vascular disorders Hypertension, hypotension Hypertension (aggravated), orthostatic hypotension Respiratory, thoracic and mediastinal disorders Respiratory insufficiency Pulmonary embolism Dyspnoea Gastrointestinal disorders Nausea Abdominal pain, vomiting, constipation, dyspepsia, flatulence Gastroduodenal ulceration, gastrooesophageal reflux disease, dry mouth, gastrointestinal sounds abnormal Pancreatitis, oesophagitis, oedema mouth (perioral swelling) Skin and subcutaneous tissue disorders Pruritus, hyperhidrosis Ecchymosis, rash, urticaria Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis Musculoskeletal and connective tissue disorders Back pain Arthralgia Renal and urinary disorders Oliguria Renal failure acute Renal failure, General disorders and administration site conditions Oedema peripheral Asthenia, injection site pain, injection site reaction Hypersensitivity reactions including anaphylaxis and angioedema Investigations Blood creatinine increased Blood CPK increased, blood LDH increased, SGOT increased, SGPT increased, BUN increased.

This medicine has been studied in dental, orthopaedic, gynaecologic (principally hysterectomy) and coronary artery bypass graft surgery. 1). g. intra-articular, intrathecal) have not been studied and should not be used. 2). 1). If, during treatment, patients deteriorate in any of the organ system functions described below, appropriate measures should be taken and discontinuation of parecoxib therapy should be considered.

Cardiovascular COX-2 inhibitors have been associated with increased risk of cardiovascular and thrombotic adverse events when taken long term. The exact magnitude of the risk associated with a single dose has not been determined, nor has the exact duration of therapy associated with increased risk.

g. 1). Appropriate measures should be taken and discontinuation of parecoxib therapy should be considered if there is clinical evidence of deterioration in the condition of specific clinical symptoms in these patients. This medicine has not been studied in cardiovascular revascularization procedures other than coronary artery bypass graft (CABG) procedures.

Studies in types of surgery other than CABG procedures included patients with American Society of Anaesthesiology (ASA) Physical Status Class I-III only. Acetylsalicylic acid and other NSAIDs COX-2 inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular thrombo-embolic diseases because of their lack of antiplatelet effects.

1). 5). The concomitant use of parecoxib with other non- acetylsalicylic acid NSAIDs should be avoided. 1). 3). Caution should be exercised with respect to monitoring the incision for signs of infection in surgical patients receiving this medicine.

Gastrointestinal Upper gastrointestinal (GI) complications (perforations, ulcers or bleedings [PUBs]), some of them resulting in fatal outcome, have occurred in patients treated with parecoxib. Caution is advised in the treatment of patients most at risk of developing a gastrointestinal complication with NSAIDs; the elderly, or patients with a prior history of gastrointestinal disease, such as ulceration and GI bleeding, or patients using acetylsalicylic acid concomitantly.

1. 8). Active peptic ulceration or gastrointestinal (GI) bleeding. Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid or nonsteroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors.

3). Severe hepatic impairment (serum albumin <25 g/l or Child-Pugh score ≥ 10). Inflammatory bowel disease. Congestive heart failure (NYHA II-IV). 1). Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease.