Kepros®
Ketorolac Tromethamine

COMPOSITION
Kepros® Tablet: Each film coated tablet contains Ketorolac Tromethamine USP 10mg.
Kepros® 30 Injection: Each 1ml sterile solution contains Ketorolac Tromethamine USP 30mg.

PHARMACOLOGICAL INFORMATION:
Pharmacological Action
Kepros® is a potent analgesic of the non-steroidal anti-inflammatory drugs (NSAID). It inhibits the cyclo-oxygenase enzyme system and hence prostaglandin synthesis. Thus it gives minimal inflammatory effect at its analgesic effect. Kepros® is not an anesthetic agent and possesses no sedative or anxiolytic properties; therefore it is not recommended as a preoperative medication for the support of anesthesia when these effects are required. It is not an opioid and has no known effects on opioid receptors. Ketorolac Tromethamine 30mg intramascularly appears to be similar in efficacy to morphine 10mg and superior to pethidine 100mg.

Mechanism of Action

• Peripheral inhibition of prostaglandin synthesis resulting in a decreased amount of prostaglandin to sensitize pain receptors.
• Does not alter the pain threshold or affect existing prostaglandins. Ketorolac's pain attenuation would appear to be a peripheral effect.
• The onset and efficacy of analgesia after systemic administration are claimed to be comparable to that of morphine, but ketorolac causes less drowsiness, nausea, and vomiting.

Pharmacokinetics
Ketorolac tromethamine is a racemic mixture of [-] S- and [+] R-enantiomeric forms, with the S-form having analgesic activity.

CLINICAL INFORMATION:
Therapeutic Indication
Kepros® is indicated to relief pain associated with surgical procedures such as a major abdominal, orthopedic, dental or gynecological surgery; acute and chronic musculoskeletal pain, renal colic, cancer pain.

Dosage & Administration
Injection: For adult patients (< 65 years): Initial dose is 60 IM (single) or 30 mg IV (single). Maintenance dose is 30 mg IM/ IV 6 hourly. Maximum dose is 120 mg/day. For elderly patients (> 65 years): Initial dose is 30 mg IM. Maintenance dose is 60 mg/ day. The duration of treatment should not exceed two days.
Tablets: Ketorolac tablets are recommended for short-term use only (up to 7 days) and are not recommended for chronic use. 10mg every 4 to 6 hours as required. Doses exceeding 40 mg per day are not recommended. For patients receiving parenteral Ketorolac tromethamine, and who are converted to Ketorolac tromethamine oral tablets, the total combined daily dose should not exceed 90 mg (60 mg for the elderly, renally-impaired patients and patients less than 50 kg) and the oral component should not exceed 40 mg on the day the change of formulation is made. Patients should be converted to oral treatment as soon as possible.

Use in children:
Child- under 16 years not recommended.

Contraindication:
Ketorolac tromethamine is contraindicated in patients having hypersensitivity to this drug or other NSAIDs and those patients in whom aspirin or other prostaglandin synthesis inhibitors induce allergic reactions. It is also contraindicated in a history of peptic ulcer or gastro-intestinal bleeding, moderate or severe renal impairment (serum creatinine> 160 micromol/l), a history of asthma, children under 16 years of age. Ketorolac Tromethamine is contraindicated as prophylactic analgesia before surgery due to inhibition of platelet aggregation and is contra-indicated intraoperatively because of the increased risk of bleeding. It is also contraindicated during pregnancy, labor, delivery or lactation.

Use in patients with impaired renal function
Since ketorolac tromethamine and its metabolites are excreted primarily by the kidney, patients with moderate to severe impairment of renal function (serum creatinine greater than 160 micromol/l) should not receive. Fluid retention and oedema have been reported with the use of Ketorolac tromethamine.

Use in patients with impaired hepatic function
Ketorolac Tromethamine should be used with caution in patients with impaired hepatic function, or a history of liver disease.

Use in elderly patients
Patients over the age of 65 years may be at a greater risk of experiencing adverse events than younger patients. Ketorolac tromethamine can cause gastro-intestinal irritation, ulcers or bleeding in patients with or without a history of previous symptoms. Bronchospasm may be precipitated in patients with a history of asthma.

Drug Interaction
Ketorolac tromethamine should not be used with other NSAIDs or in patients receiving aspirin because of the potential for additive side-effects. Care should be taken when administering Ketorolac tromethamine with anti-coagulants since co-administration may cause an enhanced anti-coagulant effect. Ketorolac tromethamine and other non-steroidal anti-inflammatory drugs can reduce the anti-hypertensive effect of beta-blockers and may increase the risk of renal impairment when administered concurrently with ACE inhibitors, particularly in volume depleted patients. Caution is advised when methotrexate is administered concurrently, since some prostaglandin synthesis inhibiting drugs have been reported to reduce the clearance of methotrexate, and thus possibly enhance its toxicity. Probenecid should not be administered concurrently with ketorolac tromethamine because of increases in ketorolac plasma level and half-life.

Use in pregnancy & lactation
Safety in human pregnancy has not been established. Ketorolac has been detected in human milk at low levels. Ketorolac is therefore contraindicated during pregnancy, labour or delivery, or in mothers who are breast feeding.

Undesirable Effects
Commonly occurring side-effects are nausea, vomiting, gastro-intestinal bleeding,melaena, peptic ulcer, pancreatitis, anxiety, drowsiness, dizziness, headache, hallucinations,excessive thirst, inability to concentrate, insomnia, malaise, fatigue, pruritus, urticaria, skin photosensitivity, Lyell's syndrome, Stevens-Johnson syndrome, flushing, bradycardia, hypertension, palpitations, chest pain, infertility in female, dyspnoea, asthma, pulmonary oedema, fever, injection site pain.

PHARMACEUTICAL INFORMATIONS:
Storage Conditions
Store in a cool (below 30ºC) and dry place, away from light. Keep out of reach of children. and dry place, away from light. Keep out of reach of children.

Presentation & Packaging
Kepros® tablet: Each box contains 3X10's tablet in Alu-PVC blister pack.
Kepros® 30 Injection: Each outer box contains 1X5's ampoule in an individual Alu-PVC blister pack.