Eurolac

Off white colored round convex film coated tablet with Renata logo engraved on one side and plain on the other side.
Each film coated tablet contains: Ketorolac Trometamol USP 10 mg.

Pharmacology: Pharmacodynamics: Ketorolac is a potent analgesic agent of the non-steroidal, anti-inflammatory class (NSAID). Its mode of action is to inhibit the cyclo-oxygenase enzyme system and hence prostaglandin synthesis, and it demonstrates a minimal anti-inflammatory effect at its analgesic dose. Ketorolac is not an anesthetic agent and possesses no sedative or anxiolytic properties; therefore, it is not recommended as a pre-operative medication for the support of anesthesia when these effects are required. It is not an opioid and has no known effects on opioid receptors.
Pharmacokinetics: Absorption: Ketorolac tromethamine is 100% absorbed after oral administration. Oral administration of ketorolac tromethamine after a high-fat meal resulted in decreased peak and delayed time-to-peak concentrations of ketorolac tromethamine by about 1 hour. Antacids did not affect the extent of absorption.
Distribution: The mean apparent volume (Vβ) of ketorolac tromethamine following complete distribution was approximately 13 liters. This parameter was determined from single-dose data. The ketorolac tromethamine racemate has been shown to be highly protein bound (99%). Nevertheless, plasma concentrations as high as 10 mcg/mL will only occupy approximately 5% of the albumin binding sites. Thus, the unbound fraction for each enantiomer will be constant over the therapeutic range. A decrease in serum albumin, however, will result in increased free drug concentrations. Ketorolac tromethamine is excreted in human milk.
Metabolism: Ketorolac tromethamine is largely metabolized in the liver. The metabolic products are hydroxylated and conjugated forms of the parent drug. The products of metabolism, and some unchanged drug, are excreted in the urine.
Elimination: The principal route of elimination of ketorolac and its metabolites is renal. About 92% of a given dose is found in the urine, approximately 40% as metabolites and 60% as unchanged ketorolac. Approximately 6% of a dose is excreted in the feces. A single-dose study with 10 mg ketorolac tromethamine (n=9) demonstrated that the S-enantiomer is cleared approximately two times faster than the R-enantiomer and that the clearance was independent of the route of administration. This means that the ratio of S/R plasma concentrations decreases with time after each dose. There is little or no inversion of the R- to S-form in humans. The half-life of the ketorolac tromethamine S-enantiomer was approximately 2.5 hours (SD ± 0.4) compared with 5 hours (SD ± 1.7) for the R-enantiomer. In other studies, the half-life for the racemate has been reported to lie within the range of 5 to 6 hours.

Ketorolac tablet is indicated for the short-term management of moderate postoperative pain.

The recommended oral dose of Ketorolac tablet is 10 mg every 4 to 6 hours for pain as required. Doses exceeding 40 mg per day are not recommended. For patients receiving Ketorolac ampoules, and who are converted to Ketorolac 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.
Special dosage instructions: Elderly patients: Ketorolac Tablets: A longer dosing interval, e.g. 6-8 hours, is advisable in the elderly. The lower end of the dosage range is recommended for patients over 65 years of age.
Children: Safety and efficacy yin children have not been established. Therefore, Ketorolac is contraindicated for use in children under 16 years of age.
Renal impairment: Since Ketorolac trometamol and its metabolites are excreted primarily by the kidney, Ketorolac is contraindicated in moderate to severe renal impairment (serum creatinine >160 μmol/L); patients with lesser renal impairment should receive a reduced dose (not exceeding 60 mg per day I.V. or I.M.) and their renal status should be closely monitored.
Combination treatment: Opioid analgesics (e.g. morphine, pethidine) may be used concomitantly and may be required for optimal analgesic effect in the early postoperative period when pain is most severe. Ketorolac trometamol does not interfere with opioid binding and does not exacerbate opioid-related respiratory depression or sedation. When used in association with Ketorolac ampoules, the daily dose of opioid is usually less than that normally required. However, opioid side effects should still be considered, especially in day-case surgery.

Doses of 360 mg given intramuscularly over an 8-hour interval for 5 consecutive days have caused abdominal pain and peptic ulcers which have healed after discontinuation of dosing. Two patients recovered from unsuccessful suicide attempts. One patient experienced nausea after 210 mg Ketorolac, and the other hyperventilation after 300 mg Ketorolac.

A history of peptic ulcer or gastrointestinal bleeding.
Suspected or confirmed cerebrovascular bleeding.
Hemorrhagic diatheses, including coagulation disorders.
Patients with hypersensitivity to ketorolac trometamol or other NSAIDs and patients in whom aspirin or other prostaglandin synthesis inhibitors induce allergic reactions (severe anaphylactic-like reactions have been observed in such patients).
Patients with the complete or partial syndrome of nasal polyps, angio-edema or bronchospasm.
Concurrent treatment with other NSAIDs, oxpentifylline, probenecid or lithium salts.
Hypovolemia from any cause, or dehydration.
Moderate or severe renal impairment (serum creatinine >160 μmol/L).
A history of asthma.
Patients who have had operations with a high risk of hemorrhage or incomplete hemostasis.
Patients on anticoagulants including low-dose heparin (2,500-5,000 units 12-hourly).
During pregnancy, labor, delivery or lactation.
Children under 16 years of age.

Physicians should carefully weigh the potential risks and benefits of its use on a long term basis. Patients should be instructed to watch for signs of serious GI adverse events and they should be monitored more closely than if they were on another NSAID. For the short-term management of pain (other than postoperative). Ketorolac I.M. is not recommended for longer use (more than 5 days) because of the possibility of increased frequency and severity of adverse reactions associated with the recommended doses and Ketorolac tablet is not recommended for use beyond 7 days & is not recommended for chronic use. Dose should be reduced in elderly and in those weighing less than 50 kg. Ketorolac injection is not recommended as a preoperative medication for support of anesthesia because it inhibits platelet aggregation and may prolong bleeding time and because it possesses no sedative or anxiolytic properties.
In patients with symptoms and signs suggesting liver dysfunction or in whom an abnormal liver test has occurred as a result of ketorolac trometamol therapy the administration of the drug should be discontinued. High oral doses (e.g. 80 or 120 mg/day) are not recommended because risk of serious adverse events are greater with daily dose exceeding the recommended 40 mg (4 tablets) oral per day. Serious G.I. toxicity such as bleeding ulceration and perforation can occur at any time with or without warning symptoms in patients with NSAIDs.
Physicians should be aware that in some patients pain relief may not occur until upwards of 30 minutes after I.V or I.M. administration.
Physicians should be aware of the pharmacological similarity of ketorolac to other NSAIDs that inhibit cyclo-oxygenase and the risk of bleeding particularly in the elderly. It should not be used for epidural or spinal administration.

It is detected in human milk. Safety in pregnancy has not been established. It is not recommended during pregnancy, labor or delivery and in mothers who are breast-feeding.
(There was no evidence of teratogenicity in rats or rabbits studied at maternally-toxic doses of ketorolac trometamol. Prolongation of the gestation period and/or delayed parturition were seen in the rat. Ketorolac trometamol and its metabolites have been shown to pass into the fetus and milk of animals.)

Gastrointestinal tract: abdominal discomfort, constipation, diarrhea, dyspepsia, eructation, flatulence, fullness, gastritis, gastrointestinal bleeding, gastrointestinal pain, nausea, pancreatitis, peptic ulcer, perforation, stomatitis, vomiting.
Central nervous/musculoskeletal systems: abnormal dreams, abnormal taste and vision, abnormal thinking, aseptic meningitis, convulsions, depression, dizziness, drowsiness, dry mouth, euphoria, excessive thirst, functional disorders, hallucinations, headache, hearing loss, hyperkinesia, inability to concentrate, insomnia, myalgia, nervousness, paresthesia, stimulation, sweating, tinnitus, vertigo.
Urinary tract and kidneys: acute renal failure, flank pain (with or without hematuria), glomerular nephritis, hemolytic uremic syndrome, hyperkalemia, hyponatremia, increased urinary frequency, interstitial nephritis, nephrotic syndrome, oliguria, raised serum urea and creatinine, renal papillary necrosis.
Cardiovascular/hematological systems: bradycardia, flushing, hypertension, pallor, purpura, thrombocytopenia.
Respiratory system: asthma, dyspnea, pulmonary edema.
Skin: exfoliative dermatitis, Lyell's syndrome, maculopapular rash, pruritus, Stevens-Johnson syndrome, urticaria.
Hypersensitivity reactions: anaphylaxis, bronchospasm, flushing and rash, hypotension, laryngeal edema. Such reactions may occur in patients with or without known sensitivity to Ketorolac or other NSAIDs.
Bleeding: epistaxis, hematomata, postoperative wound hemorrhage.
Other: abnormal liver function tests, asthenia, edema, injection site pain, weight gain.

Concurrent treatment with probenecid is contraindicated because of increases in ketorolac trometamol plasma level and half-life. Because of an increased tendency to bleeding when oxpentifylline is administered concurrently, this combination is contraindicated. Concurrent treatment with lithium is contraindicated because there is a possible inhibition of renal lithium clearance, increased plasma lithium concentration, and potential lithium toxicity.
Ketorolac should not be used with other NSAIDs because of the potential for additive side effects.
Ketorolac trometamol is highly bound to human plasma protein (>99%) and binding is concentration-independent.
Because ketorolac trometamol is a highly potent drug and present in low concentrations in plasma, it would not be expected to displace other protein-bound drugs significantly.
Ketorolac trometamol did not alter digoxin protein binding.
In-vitro studies indicated that at therapeutic concentrations and above of salicylate (≥300 μg per mL), the binding of ketorolac trometamol was reduced from approximately 99.2 to 97.5%. Therapeutic concentrations of digoxin, warfarin, paracetamol, phenytoin and trometamol did not alter ketorolac trometamol protein binding.
There is no evidence in animal or human studies that ketorolac trometamol induces or inhibits the hepatic enzymes capable of metabolizing itself or other drugs. Hence Ketorolac would not be expected to alter the pharmacokinetics of other drugs due to enzyme induction or inhibition mechanisms.
In normovolemic healthy volunteers, ketorolac trometamol reduces the diuretic response to furosemide by approximately 20%, so particular care should be taken in patients with cardiac decompensation.
There is an increased risk of renal impairment when ketorolac trometamol is 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.

Store at temperatures not exceeding 30°C.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AB15 - ketorolac ; Belongs to the class of acetic acid derivatives and related substances of non-steroidal antiinflammatory and antirheumatic products.

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