Remopain 3%

Clear, colorless to yellowish solution, alcoholic odor and free from visible particles.
Each ml of REMOPAIN 3% solution for injection contains ketorolac tromethamine 30 mg.
Excipients/Inactive Ingredients: Ethanol, sodium hydroxide, sodium chloride, water for injection.

Pharmacotherapeutic group: Nonsteroidal anti-inflammatory drug (NSAID), a pyrrolizine carboxylic acid derivative.
Pharmacology: Pharmacodynamics: Ketorolac is a potent analgesic agent of the NSAID. It is not an opioid and has no known effects on opioid receptors. Its mode of action is to inhibit the cyclooxygenase enzyme system and hence prostaglandin synthesis, and it demonstrates a minimal anti-inflammatory effect at its analgesic dose.
Pharmacokinetics: Onset of action (Intramuscular [IM], Intravenous [IV]): 30 minutes.
Peak effect (IM, IV): ≤2 to 3 hours.
Duration: analgesic 4 to 6 hours.
Absorption (IM): rapid and complete.
Distribution: poor penetration into cerebrospinal fluid.
V_d beta: Children 4 to 8 years: 0.19 to 0.44 L/kg (mean: 0.26 L/kg).
Adults: 0.11 to 0.33 L/kg (mean: 0.18 L/kg).
Protein binding: 99%.
Metabolism: hepatic (hydroxylation and glucuronide conjugation). In children 4 to 8 years, V_dss and plasma clearance were twice as high as adults.
Bioavailability (IM): 100%.
Half-life elimination: Children 4 to 8 years: mean about 6 hours, range 3.5 to 10 hours.
Adults: mean about 5 hours, range 2 to 9 hours.
Prolonged 30% to 50% in elderly.
Renal impairment: mean about 11 hours, range 4 to 19 hours.
Renal dialysis patients: mean about 14 hours, range 8 to 40 hours.
Time of peak, serum (IM, IV): 30 to 60 minutes and 1 to 3 minutes respectively.
Excretion: Urine (92%, 60% as unchanged drug), feces (6%).

Ketorolac tromethamine is indicated for the short-term management of moderate to severe acute postoperative pain.
Treatment should only be initiated in hospitals. The maximum duration of treatment is two days.

Ketorolac tromethamine solution for injection is for administration by intramuscular (IM) or bolus intravenous (IV) injection. Bolus intravenous doses should be given over no less than 15 seconds. IM injection doses should be given slowly. Its analgesic effect begins at 30 minutes, peaks at 1-2 hours, and lasts 4-6 hours. Ketorolac tromethamine solution for injection should not be used for epidural or spinal administration. (See table.)

Click on icon to see table/diagram/image

Symptoms and signs: Single overdoses of ketorolac have been variously associated with abdominal pain, nausea, vomiting, hyperventilation, peptic ulcers and/or erosive gastritis and renal dysfunction which have resolved after discontinuation of dosing.
Gastrointestinal bleeding may occur. Hypertension, acute renal failure, respiratory depression, and coma may occur after the ingestion of NSAIDs but are rare.
Headache, epigastric pain, disorientation, excitation, drowsiness, dizziness, tinnitus, and fainting have also been observed.
Rare cases of diarrhea and occasional convulsions have been reported. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs and may occur following an overdose.
Treatment: Patients should be managed by symptomatic and supportive care following NSAIDs overdose. There are no specific antidotes. Dialysis does not significantly clear ketorolac from the blood stream.
Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.
Good urine output should be ensured. Renal and liver function should be closely monitored. Patients should be observed for at least four hours after ingestion of potentially toxic amounts. Frequent or prolonged convulsions should be treated with intravenous diazepam. Other measures may be indicated by the patient's clinical condition.

Ketorolac is contraindicated in patients with previously demonstrated hypersensitivity to ketorolac, any of its excipients 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). Such reactions have included asthma, rhinitis, angioedema, or urticaria.
Ketorolac is also contraindicated in those with a history of asthma.
Ketorolac is contraindicated in patients with active or a history of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy. Active or history of recurrent peptic ulcer/hemorrhage (two or more distinct episodes of proven ulceration or bleeding).
As with other NSAIDs, ketorolac is contraindicated in patients with severe heart failure, hepatic failure, and renal failure.
Ketorolac is contraindicated in patients with moderate or severe renal impairment (serum creatinine >160 mcmol/l) or in patients at risk for renal failure due to volume depletion or dehydration.
Ketorolac is contraindicated as prophylactic analgesia before surgery due to inhibition of platelet aggregation and is contraindicated intraoperatively because of the increased risk of bleeding.
Ketorolac inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular bleeding, patients who have had operations with a high risk of hemorrhage or incomplete hemostasis and those at high risk of bleeding such as those with hemorrhagic diatheses, including coagulation disorders.
It is also contraindicated in patients on anticoagulants, including warfarin and low dose heparin (2,500-5,000 units 12 hourly).
Ketorolac is contraindicated in patients currently receiving acetylsalicylic acid (ASA) or other NSAIDs (including cyclooxygenase-2 selective inhibitors).
Ketorolac solution for injection is contraindicated for neuraxial (epidural or intrathecal) administration due to its alcohol content.
The combination of ketorolac with pentoxifylline is contraindicated. Concurrent treatment with ketorolac and probenecid or lithium salts is contraindicated.
Ketorolac is contraindicated in patients with the complete or partial syndrome of nasal polyps, angioedema, or bronchospasm.
Use in Pregnancy & Lactation: Ketorolac is contraindicated in pregnancy, labor, delivery, or lactation.

The combined therapy duration (oral and parenteral) should not exceed 5 days due to the increased risk of serious adverse events.
Hematological effects: Inhibits platelet function, contraindication in patients with cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis, and patients at high risk for bleeding.
Platelet adhesion and aggregation may be decreased, may prolong bleeding time. Patients with coagulation disorders or who are receiving anticoagulants should be monitored closely.
Anemia may occur, Patients on long term NSAIDs therapy should be monitored for anemia.
Cardiovascular and cerebrovascular effects: NSAIDs cause an increased risk of serious adverse cardiovascular thrombolytic events, including MI (myocardial infarction) and stroke. Risk may occur early during treatment and may increase with duration of use.
Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease. However, absolute incidence of serious cardiovascular thrombotic events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors and in those receiving higher doses.
New onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics). These occurrences may contribute to cardiovascular events, monitor blood pressure. Use with caution in patients with hypertension.
May cause sodium and fluid retention. Use with caution in patients with edema.
Avoid use in heart failure.
Avoid use in patients with a recent MI unless benefits outweigh risk of cardiovascular thrombolytic events.
Use the lowest effective dose for the shortest duration to reduce risk of cardiovascular events.
Renal Impairment: Ketorolac is contraindicated in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion.
NSAIDs use may compromise existing renal function. Dose-dependent decreases in prostaglandin synthesis may result from NSAIDs use, reducing renal blood flow, which may cause renal decompensation (usually reversible).
Patients at greatest risk of renal toxicity are those with impaired renal function, hypovolemia, heart failure, hepatic impairment, those taking diuretics and ACE inhibitors, and the elderly.
Discontinuation of ketorolac or other nonsteroidal anti-inflammatory therapy is usually followed by recovery to the pre-treatment state.
Hepatic Impairment: Use with caution on patients with hepatic impairment or a history of hepatic disease. Transaminase elevations have been reported with use, closely monitor patients with any abnormal liver function test.
Rare (sometimes fatal) severe hepatic reactions (e.g. jaundice, fulminant hepatitis, hepatic necrosis, hepatic failure) have occurred with NSAIDs use, discontinue immediately if signs or symptoms of hepatic disease develop or if systemic manifestations occur.
Gastrointestinal (GI) ulceration, bleeding and perforation: NSAIDs cause increased risk of serious GI inflammation, ulceration, bleeding, and perforation (may be fatal).
Elderly patients and patients with history of peptic ulcer disease and/or GI bleeding are at greater risk of serious GI events. These events may occur at any time during therapy and without warning.
Avoid use in patients with severe GI bleeding. In patients with history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis.
Use caution with a history of GI ulcers, inflammatory bowel disease, concurrent therapy known to increase the risk of GI bleeding (e.g. aspirin, anticoagulants, and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in the elderly or debilitated patients.
Concomitant gastroprotective therapy (e.g. proton pump inhibitors) is recommended.
Skin reactions: Ketorolac is contraindicated in patients with prior hypersensitivity reaction to aspirin or NSAIDs.
NSAIDs may cause potentially fatal serious skin reactions including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN), may occur without warning. The onset of the reactions occurring in the majority of cases within the first month of treatment. Ketorolac tromethamine should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Hypersensitivity or anaphylactoid reactions may occur, even without prior exposure.
Patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk.
Systemic Lupus Erythematosus (SLE) and mixed connective tissue disease: In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.
Drug abuse and dependence: Ketorolac is devoid of addictive potential. No withdrawal symptoms have been observed following abrupt discontinuation of ketorolac IV.
Use in Pregnancy & Lactation: Precautions related to fertility: The use of ketorolac tromethamine, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. In women who have difficulty conceiving or are undergoing investigation of fertility, withdrawal of ketorolac tromethamine should be considered.
Use in Children: Ketorolac given parenterally is not recommended in children younger than 2 years of age.
Use in the Elderly: Dosage adjustment is required for patients ≥65 years of age.
Elderly patients are at greater risk for serious GI, cardiovascular, and/or renal adverse events. Use with caution. NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (e.g. ACE inhibitors). Monitor potassium closely.

Use in pregnancy: The safety of ketorolac tromethamine during human pregnancy has not been established.
In view of the known effects of NSAIDs on the fetal cardiovascular system (risk of closure of the ductus arteriosus) and on uterine contraction, ketorolac is contraindicated during pregnancy, labor, or delivery.
Use in lactation: Ketorolac and its metabolites have been shown to pass into the fetus and milk of animals. Ketorolac has been detected in human milk at low concentrations; therefore, ketorolac is contraindicated in mothers who are breastfeeding.

Cardiovascular: Edema, hypertension.
Central nervous system: Dizziness, drowsiness, headache.
Dermatologic: Diaphoresis, pruritus, skin rash.
Gastrointestinal: Constipation, diarrhea, dyspepsia, flatulence, gastrointestinal fullness, gastrointestinal hemorrhage, gastrointestinal pain, gastrointestinal perforation, gastrointestinal ulcer, heartburn, nausea, stomatitis, vomiting.
Hematologic & oncologic: Anemia, prolonged bleeding time, purpura.
Hepatic: Increased liver enzymes.
Local: Pain at injection site.
Otic: Tinnitus.
Renal: Renal function abnormality.
Rare but important or life-threatening: Abnormality in thinking, acute pancreatitis, acute renal failure, agranulocytosis, alopecia, anaphylactoid reaction, anaphylaxis, angioedema, aplastic anemia, aseptic meningitis, asthma, azotemia, bradycardia, bronchospasm, bruise, cardiac arrhythmia, cardiac failure, cholestatic jaundice, coma, confusion, conjunctivitis, cough, cystitis, depression, dysuria, eosinophilia, epistaxis, eructation, erythema multiforme, euphoria, exacerbation of urinary frequency, exfoliative dermatitis, extrapyramidal reaction, flank pain, gastritis, glossitis, hallucination, hearing loss, hematemesis, hematuria, hemolytic anemia, hemolytic-uremic syndrome, hepatic failure, hepatitis, hepatotoxicity, hyperglycemia, hyperkalemia, hyperkinesis, hypersensitivity reaction, hyponatremia, hypotension, increased susceptibility to infection, increased thirst, infertility, inflammatory bowel disease, insomnia, interstitial nephritis, jaundice, lack of concentration, laryngeal edema, leukopenia, lymphadenopathy, maculopapular rash, melena, myocardial infarction, nephritis, oliguria, palpitations, pancytopenia, paresthesia, pneumonia, polyuria, proteinuria, psychosis, pulmonary edema, rectal hemorrhage, renal failure, respiratory depression, rhinitis, seizure, sepsis, skin photosensitivity, Stevens-Johnson syndrome, stomatitis (ulcerative), stupor, syncope, tachycardia, thrombocytopenia, tongue edema, toxic epidermal necrolysis, urinary retention, urticaria, vasculitis, weight gain, wound hemorrhage (postoperative).

Avoid concomitant use: Acemetacin, aminolevulinic acid (systemic), aspirin, dexibuprofen, dexketoprofen, floctafenine, ketorolac (nasal), macimorelin, mifamurtide, morniflumate, NSAIDs, omacetaxine, pelubiprofen, pentoxifylline, phenylbutazone, probenecid, talniflumate, tenoxicam, urokinase, zaltoprofen.
Increased effect/toxicity: Ketorolac may increase the effects of: 5-aminosalicylic acid derivatives, agents with antiplatelet properties, aliskiren, aminoglycosides, aminolevulinic acid (systemic and topical), anticoagulants, apixaban, aspirin, bemiparin, bisphosphonate derivatives, cephalothin, collagenase (systemic), cyclosporine (systemic), dabigatran etexilate, deferasirox, deoxycholic acid, desmopressin, dexibuprofen, digoxin, drospirenone, edoxaban, enoxaparin, eplerenone, haloperidol, heparin, ibritumomab, tiuxetan, lithium, metformin, methotrexate, neuromuscular-blocking agents (nondepolarizing), NSAID, obinutuzumab, omacetaxine, pentoxifylline, porfimer, potassium-sparing diuretics, pralatrexate, quinolones, rivaroxaban, salicylates, tacrolimus (systemic), tenofovir products, thrombolytic agents, tolperisone, urokinase, vancomycin, verteporfin, vitamin K antagonists.
The effects of ketorolac may be increased by: Acalabrutinib, acemetacin, alcohol (ethyl), angiotensin II receptor blockers, ACE inhibitors, corticosteroids (systemic), cyclosporine (systemic), desatinib, dexketoprofen, fat emulsion (fish oil based), felbinac, floctafenine, glucosamine, herbs (anticoagulants/antiplatelet properties), ibrutinib, inotersen, ketorolac (nasal), limaprost, loop diuretics, morniflumate, multivitamins/fluoride (with ADE), multivitamins/minerals (with ADEK, folate, iron, with AE, no iron), naftazone, omega-3 fatty acids, pelubiprofen, pentosan polysulfate sodium, phenylbutazone, probenecid, prostacyclin analogues, selective serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, sodium phosphates, talniflumate, tenoxicam, thiazide and thiazide-like diuretics, tipranavir, tolperisone, tricyclic antidepressants (tertiary amine), vitamin E (systemic), zaltoprofen, zanubrutinib.
Decrease Effect: Ketorolac may decrease the effects of: Aliskiren, angiotensin II receptor blockers, ACE inhibitors, aspirin, beta-blockers, eplerenone, hydralazine, loop diuretics, prostaglandins (ophthalmic), salicylates, selective serotonin reuptake inhibitors, sincalide, thiazide and thiazide-like diuretics.
The effects of Ketorolac may be decreased by: Bile acid sequestrants, salicylates.

Store at temperatures below 30°C, protect from light.

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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