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Geriatrics: Patients older than 65 years and frail or debilitated patients are more susceptible to a variety of adverse reactions from NSAIDs. There may be a greater risk of GI ulcerations, bleeding and perforation in elderly patients and most spontaneous reports of fatal GI events are in this population. Pediatrics (<18 years of age): Safety and efficacy have not been established in pediatric population. THERAPEUTIC INDICATIONS: Monak is indicated for the short-term management of moderate to severe acute pain, including pain following major abdominal, orthopaedic and gynecological operative procedures. DOSAGE AND ADMINISTRATION: Use of Monak should be limited to the lowest effective dose for the shortest possible duration of treatment. The total duration of combined IM and oral treatment should not exceed 5 days. In no case is the duration of Monak treatment to exceed 7 days. Recommended Dose and Dosage Adjustment Adults (>18 years of age): The recommended usual initial dose of Monak in adults (>18 years of age) is 10-30mg, according to pain severity. Subsequent dosing may be 10mg to 30mg every 4-6 hours as needed to control pain. The administra- tion of Monak IM/IV should be limited to short term therapy (not over two days). The total daily dose should not exceed 120mg because of the risk of toxicity appears to increase with longer use at recommended doses. Elderly, Frail or Debilitated Patients: These patients are at increased risk of the serious consequences of adverse reactions. The lower end of the dosage range is recommended. The initial dose should be 10mg. The total daily dose of Monak in the elderly should not exceed 60mg. ADVERSE REACTIONS: The most common adverse reactions encountered with NSAIDs are gastrointestinal, of which peptic ulcer with or without bleeding is the most severe. Fatalities have occurred, particularly in the elderly. Other adverse reactions are somnolence, headache, sweating, dizziness, nausea, vomiting, injection site pain and vasodilation. CONTRAINDICATIONS: A history of peptic ulcer or gastrointestinal bleeding. Suspected or confirmed cerebrovascular bleeding. Haemorrhagic diathesis, including coagulation disorders. Patients with hypersensitivity to ketorolac trometamol or other NSAIDs and patients in whom aspirin or other prostaglandin synthesis inhibitors induced allergic reactions (severe anaphylactic reactions have been observed in such patients). Patients with complete or partial syndrome of nasal polyps, angioedema or bronchospasm. Concurrent use with other NSAIDs and concomitant use with oxpentifylline and probenecid. Hypovolemia from any cause, or dehydration. Moderate to severe renal impairment (serum creatinine > 442 μmol/L and/or creatinine clearance < 30mL/min or 0.5mL/sec) or deteriorating renal disease. Immediately before any major surgery and intraoperatively when hemostasis is critical because of the increased risk of bleeding. Patients on anticoagulants including low dose heparin (2500 to 5000 units 12 hourly). During pregnancy, labour, delivery or lactation. Children under 18 years of age. PRECAUTIONS: To minimize the potential risk of an adverse event, the lowest effective dose should be used for the shortest possible duration. Risk of GI adverse events: Monak is associated with an increased incidence of gastrointestinal adverse events (such as peptic/duodenal ulceration, perforation, obstruction and GI bleeding). Haematologic: NSAIDs inhibiting prostaglandin biosynthesis interfere with platelet function to varying degrees; patients who may be adversely affected by such an action, such as those on anticoagulants or suffering from haemophilia or platelet disorders should be carefully observed when Monak is administered. DESCRIPTION: Monak (Ketorolac Trometamol) is a non-selective COX inhibitor with anti-inflammatory, analgesic and antipyretic activity. Chemically, ketorolac trometamol belongs to the family of heterocyclic acetic acid derivatives compounded with 2-amino-2-(hydroxymethyl)propane-1,3-diol;5-benzoyl-2,3-dihy- dro-1~{H}-pyrrolizine-1-carboxylic acid having molecular formula of C 19 H 24 N 2 O 6 . The structural formula of ketorolac trometamol is: COMPOSITION: Monak (Ketorolac Trometamol) 30mg: Each 1ml ampoule contains: Ketorolac Trometamol USP……... 30mg Product Specs.: USP CLINICAL PHARMACOLOGY: Mechanism of action: The analgesic activity of ketorolac trometamol is produced via a peripheral action in which blockade of pain impulse generation results from decreased prostaglandin activity. The anti-inflammatory activity is due to inhibition of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) which leads to the inhibition of prostaglandin synthesis leading to decreased formation of precursors of prostaglandins and thromboxanes from arachidonic acid. Pharmacokinetics: The pharmacokinetics is linear following single and multiple dosing. Steady state plasma levels are attained after one day of Q.I.D. dosing. The parenteral administration of ketorolac trometamol has not been demonstrated to affect the haemodynamics of anesthetized patients. Absorption: Ketorolac trometamol was rapidly (Tmax ranged from 0.25 to 1.5 hours) and completely absorbed after oral and IM doses (>99%). Distribution: The volume of distribution of ketorolac trometamol was estimated following intravenous dosing and it averaged 0.15L/kg. Ketorolac was highly protein bound (99.2%). Binding was concentration independent. Metabolism: Ketorolac is largely metabolized in the liver. The major metabolic path of ketorolac in humans is glucuronic acid conjugation. P-hydroxylation is an additional minor pathway. The metabolism and excretion patterns of ketorolac and its metabolites were similar following PO, IV and IM dosing in the species studied. Ketorolac and its metabolites were excreted predominantly in the urine averaged 92% in humans. Elimination: The primary route of excretion of ketorolac trometamol and its metabolites (conjugates and the p-hydroxy metabolite) is in the urine (91.4%) with the remainder (6.1%) being excreted in the faeces. SPECIAL POPULATIONS: Pregnant Women: Ketorolac trometamol is contraindicated for use during the third trimester of pregnancy because of risk of premature closure of ductus arteriosus and the potential to prolong parturition. Caution should be exercised in prescribing ketorolac trometamol during the first and second trimesters of pregnancy. Ketorolac trometamol is not recommended in labour and delivery because, through their prostaglandin synthesis inhibitory effect, they may adversely affect fetal circulation and inhibit uterine contractions, thus increasing the risk of uterine haemorrhage. 30mg/ml IM/IV Inj. 120mm O O OH OH OH NH2 HO N (Ketorolac Trometamol) 185mm Monak (Ketorolac Trometamol)
