Ketorolac

According to the World Health Organization (WHO), adverse events are classified according to their frequency as follows: very common (≥ 10%), common (≥ 1% and < 10%), uncommon (≥ 0.1% and < 1% ), rare (≥ 0.01% and < 0.1%), very rare (< 0.01%), frequency unknown (frequency cannot be determined from available data).

Allergic reactions

: uncommon - anaphylaxis or anaphylactoid reactions (change in facial skin color, skin rash, urticaria, skin itching, tachypnea or dyspnea, swelling of the eyelids, periorbital edema, shortness of breath, difficulty breathing, heaviness in the chest).

Local reactions:

common - burning or pain at the injection site.

From the central nervous system:

very common - headache; frequent - dizziness, drowsiness, increased sweating; uncommon - tremor, unusual dreams, hallucinations, euphoria, extrapyramidal symptoms, vertigo, paresthesia, depression, insomnia, nervousness, pathological thinking, loss of concentration, hyperkinesis, confusion (stupor), aseptic meningitis (fever, severe headache, convulsions, stiffness of the neck and/or back muscles), psychosis, fainting.

From the skin:

common - itching, rash (including maculopapular rash); uncommon - urticaria, toxic epidermal necrolysis (Lyell's syndrome), malignant exudative erythema (Stevens-Johnson syndrome), exfoliative dermatitis (fever with or without chills, flushing, thickening or peeling of the skin, enlargement and/or soreness of the tonsils).

From the urinary system:

uncommon - hematuria, proteinuria, urinary retention, oliguria, polyuria, frequent urination, acute renal failure, low back pain with or without hematuria and/or azotemia, interstitial nephritis, hyponatremia, hyperkalemia, hemolytic uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura).

From the digestive system:

very common - gastralgia, dyspepsia, nausea; frequent - diarrhea, constipation, flatulence, feeling of fullness in the stomach, vomiting, stomatitis; uncommon - increased or decreased appetite, anorexia, erosive and ulcerative lesions of the gastrointestinal tract (including with perforation and/or bleeding - abdominal pain, spasm or burning in the epigastric region, blood in the stool or melena, vomiting with blood or coffee-ground type, nausea, heartburn), cholestatic jaundice, hepatitis, hepatomegaly. acute pancreatitis, polydipsia, dry mouth: frequency unknown - exacerbation of ulcerative colitis or Crohn's disease.

From the hematopoietic organs:

common - purpura; uncommon - anemia, eosinophilia.

From the respiratory system:

Uncommon: bronchospasm or shortness of breath, pulmonary edema, rhinitis, laryngeal edema (difficulty breathing).

From the senses:

Uncommon: taste disturbance, visual impairment (including blurred vision), hearing loss, ringing in the ears.

From the cardiovascular system:

frequent - increased blood pressure; infrequent - palpitations, pallor of the skin, fainting, hyperemia; frequency unknown - decreased blood pressure, heart failure, myocardial infarction, stroke.

From the hemostasis system:

uncommon - bleeding from a postoperative wound, nosebleeds, rectal bleeding.

Others

: frequent - swelling; uncommon - weight gain, fever, infections, asthenia, increased sweating, swelling of the tongue; frequency unknown - increased concentrations of urea and creatinine in the blood plasma.

Ketorolac, 10 mg, film-coated tablets, 14 pcs.

The simultaneous use of ketorolac with acetylsalicylic acid or other NSAIDs, calcium preparations, glucocorticosteroids, ethanol, corticotropin can lead to a significant increase in the risk of adverse reactions, including the formation of gastrointestinal ulcers and the development of gastrointestinal bleeding.

The simultaneous use of ketorolac with anticoagulants (including warfarin, heparin), other NSAIDs, pentoxifylline and probenecid is contraindicated.

When ketorolac is used simultaneously with other NSAIDs (including cyclooxygenase-2 inhibitors), fluid retention, cardiac decompensation, and increased blood pressure may occur.

The simultaneous use of ketorolac with indirect anticoagulants, thrombolytics, antiplatelet agents, cefoperazone, cefotetan and pentoxifylline increases the risk of bleeding.

Probenecid reduces the plasma clearance and volume of distribution of ketorolac, increases its concentration in the blood plasma and increases its half-life.

The combined use of ketorolac with sodium valproate causes a disorder of platelet aggregation.

When using ketorolac with other nephrotoxic drugs (including gold preparations), the risk of developing nephrotoxicity increases. Combined use with paracetamol increases the nephrotoxicity of ketorolac. Drugs that block tubular secretion reduce the clearance of ketorolac and increase its concentration in the blood plasma.

The combined use of ketorolac with methotrexate increases the hepato- and nephrotoxicity of methotrexate. The combined use of ketorolac and methotrexate is possible only when using low doses of the latter. The clearance of methotrexate may decrease (it is necessary to monitor the concentration of methotrexate in the blood plasma).

With the use of ketorolac, it is possible to reduce the clearance of lithium, increase its concentration in the blood plasma, and increase the toxic effect of lithium. Simultaneous use with lithium salts is contraindicated.

Ketorolac reduces the effect of antihypertensive and diuretic drugs (the synthesis of prostaglandins in the kidneys is reduced).

Ketorolac enhances the effect of narcotic analgesics. When combined with opioid analgesics, the doses of the latter can be significantly reduced.

Ketorolac enhances the hypoglycemic effect of insulin and oral hypoglycemic drugs, and therefore it is necessary to recalculate the dose of these drugs.

Ketorolac increases the plasma concentrations of verapamil and nifedipine.

Concomitant use of NSAIDs and mifepristone may reduce the effectiveness of mifepristone. NSAIDs are not recommended for use within 8-12 days after using mifepristone.

Concomitant use of NSAIDs and cyclosporine increases the risk of nephrotoxicity.

The simultaneous use of NSAIDs and quinolone antibiotics increases the risk of developing seizures.

Concomitant use of NSAIDs and tacrolimus increases the risk of nephrotoxicity.

Concomitant use of NSAIDs and zidovudine increases the risk of hematological toxicity.

When used simultaneously with digoxin, ketorolac does not interfere with the binding of digoxin to plasma proteins. Therapeutic concentrations of digoxin do not affect the binding of ketorolac to plasma proteins.

Antacids do not affect the absorption of ketorolac.

Myelotoxic drugs increase the manifestations of hematotoxicity of ketorolac.

Ketorolac welpharm 30mg/ml 1ml 10 pcs. solution for intravenous and intramuscular administration

Composition and release form Ketorolac welpharm 30 mg/ml 1 ml 10 pcs. solution for intravenous and intramuscular administration

Composition per 1 ml: Active ingredient: ketorolac trometamol (ketorolac tromethamine) - 30 mg.
Excipients: sodium chloride, disodium edetate dihydrate (disodium ethylenediamine-N,N,N',N'-tetraacetic acid 2-aqueous [trilon B]), water for injection. Packaging: Solution for intravenous and intramuscular administration 30 mg/ml, 1 ml in ampoules - 10 pcs per pack.

Description of the dosage form

Solution for intravenous and intramuscular administration

Characteristic

A non-steroidal anti-inflammatory drug (NSAID), has a pronounced analgesic effect, has anti-inflammatory and moderate antipyretic effects.

Pharmacodynamics

Ketorolac is a non-steroidal anti-inflammatory drug (NSAID), has a pronounced analgesic effect, and also has anti-inflammatory and moderate antipyretic effects. The mechanism of action is associated with non-selective inhibition of the activity of cyclooxygenase 1 (COX 1) and cyclooxygenase 2 (COX 2), which catalyzes the formation of prostaglandins (Pg) from arachidonic acid, which play an important role in the pathogenesis of pain, inflammation and fever. Ketorolac is a racemic mixture of [-]S and [+]R enantiomers, and the analgesic effect is due to the [-]S form. The analgesic effect is comparable to morphine and significantly superior to other NSAIDs. The onset of the analgesic effect is noted after 0.5 hours, the maximum effect is achieved after 1-2 hours and lasts about 4-6 hours.

Pharmacokinetics

Absorption: Bioavailability is complete and rapid. After intramuscular administration of 30 mg, the maximum concentration (Cmax) is 1.74-3.1 μg/ml, 60 mg is 3.23-5.77 μg/ml, the time to reach the maximum concentration (TCmax) is 15-73 min and 30 -60 min respectively. After intravenous administration at a dose of 15 mg, Cmax is 1.96-2.98 mcg/ml; at a dose of 30 mg, Cmax is 3.69-5.61 mcg/ml.

Distribution: Communication with plasma proteins - 99%. The time to reach equilibrium concentration (Css) is 24 hours, Css is 0.65-1.13 mcg/ml when administered intramuscularly with 15 mg 4 times a day, 30 mg is 1.29-2.47 mcg/ml.

Volume of distribution - 0.15-0.33 l/kg. In patients with renal failure, the volume of distribution of ketorolac may increase by 2 times, and the volume of distribution of its R-enantiomer by 20%.

Penetrates into breast milk: after administration of 10 mg of ketorolac, Cmax in milk is reached after 2 hours and is 7.3 ng/ml, 2 hours after the administration of the second dose of ketorolac (when using the drug 4 times a day) it is 7.9 ng/ml. l.

Metabolism: More than 50% of the administered dose is metabolized in the liver to form pharmacologically inactive metabolites. The main metabolites are glucuronides, which are excreted by the kidneys, and p-hydroxyketorolac. It is excreted 91% by the kidneys, 6% through the intestines.

Elimination: The half-life (T1/2) in patients with normal renal function averages 5.3 hours (3.5-9.2 hours after intramuscular administration of 30 mg). T1/2 increases in elderly patients and decreases in young ones. Liver function has no effect on T1/2. In patients with impaired renal function with a plasma creatinine concentration of 19-50 mg/l (168-442 µmol/l), T1/2 is 10.3-10.8 hours, with more severe renal failure - more than 13.6 hours. The total clearance with intramuscular administration of 30 mg is 0.023 l/h/kg, with intravenous administration of 30 mg - 0.03 l/kg/h.

Ketorolac is not eliminated by hemodialysis.

Indications for use: Ketorolac welpharm 30 mg/ml 1 ml 10 pcs. solution for intravenous and intramuscular administration

Pain syndrome of severe and moderate severity: injuries, toothache, pain in the postoperative period, cancer, myalgia, arthralgia, neuralgia, radiculitis, dislocations, sprains, rheumatic diseases. Intended for symptomatic therapy, reducing pain and inflammation at the time of use, does not affect the progression of the disease.

Contraindications

hypersensitivity to any component of the drug;
anamnestic data on an attack of bronchial obstruction, rhinitis, urticaria after taking acetylsalicylic acid or other NSAIDs (complete or incomplete combination of bronchial asthma, nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid and other NSAIDs);
hypovolemia (regardless of the cause that caused it);
erosive and ulcerative lesions of the gastrointestinal tract in the acute stage, peptic ulcers, bleeding or a high risk of their development, hypocoagulation (including hemophilia), inflammatory bowel diseases (Crohn's disease, ulcerative colitis);
severe liver failure or active liver disease;
severe renal failure (serum creatinine > 700 µmol/l), progressive kidney disease;
confirmed hypokalemia;
decompensated heart failure, condition after coronary artery bypass grafting;
the drug is not used for pain relief before and during surgical operations due to the high risk of bleeding;
intracranial hemorrhage or suspicion of it;
confirmed hyperkalemia;
pregnancy, childbirth, breastfeeding;
children under 16 years of age (efficacy and safety have not been established).

Carefully:

Hypersensitivity to other NSAIDs, bronchial asthma, the presence of factors that increase gastrointestinal toxicity (alcoholism, smoking, cholecystitis); postoperative period; chronic heart failure (CHF), coronary heart disease (CHD), edema syndrome, arterial hypertension; moderate renal failure (serum creatinine 300-700 µmol/l); cholestasis; sepsis; systemic lupus erythematosus; simultaneous use with other NSAIDs, long-term use of NSAIDs; cerebrovascular diseases; dyslipidemia, hyperlipidemia, diabetes mellitus; peripheral arterial disease; a history of ulcerative lesions of the gastrointestinal tract, the presence of H. pylori infection; severe somatic diseases; systemic connective tissue diseases; inflammatory bowel diseases without exacerbation; simultaneous use of oral glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), elderly age (older 65 years old).

Application Ketorolac welpharm 30 mg/ml 1 ml 10 pcs. solution for intravenous and intramuscular administration during pregnancy and lactation

Do not take the drug during pregnancy (adverse effects on the cardiovascular system of the fetus - premature closure of the ductus arteriosus), during childbirth, in the early postpartum period (inhibits the synthesis of prostaglandins, the drug can adversely affect the blood circulation of the fetus and weaken the contractile activity of the uterus, which increases risk of uterine bleeding) and during breastfeeding (the drug passes into breast milk). If it is necessary to use the drug during lactation, breastfeeding should be stopped.

special instructions

Before prescribing the drug, it is necessary to clarify the issue of a previous allergy to ketorolac or other NSAIDs. Due to the risk of allergic reactions, the first dose is administered under close medical supervision.

Hypovolemia increases the risk of nephrotoxic adverse reactions.

If necessary, can be used with opioid analgesics.

It is not recommended for use as a means of premedication or maintenance of anesthesia.

When taken together with other NSAIDs, fluid retention, cardiac decompensation, and increased blood pressure may occur.

The risk of developing drug complications increases with lengthening of treatment (in patients with chronic pain) and increasing the dose of the drug.

To reduce the risk of developing NSAID gastropathy, antacid medications, misoprostol, and omeprazole are used.

Impact on the ability to drive vehicles and machinery:

During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: abdominal pain, nausea, vomiting, erosive and ulcerative lesions of the gastrointestinal tract, impaired renal function, metabolic acidosis.

Treatment: symptomatic therapy (maintaining vital functions of the body). Not eliminated sufficiently by dialysis.

Side effects Ketorolac welpharm 30mg/ml 1ml 10 pcs. solution for intravenous and intramuscular administration

The frequency of side effects is classified depending on the frequency of occurrence: often (1-10%), sometimes (0.1-1%), rarely (0.01-0.1%), very rarely (less than 0.01%) , including individual messages.

Allergic reactions: rarely - anaphylaxis or anaphylactoid reactions (change in facial skin color, skin rash, urticaria, itching of the skin, shortness of breath, swelling of the eyelids, periorbital edema, difficulty breathing, heaviness in the chest, wheezing).

Local reactions (at the injection site): less often - burning or pain at the injection site.

From the central nervous system: often - headache, dizziness, drowsiness; rarely - aseptic meningitis (fever, severe headache, convulsions, stiffness of the neck and/or back muscles), hyperactivity (mood changes, anxiety), hallucinations, depression, psychosis.

From the skin: less often - skin rash (including maculopapular rash), purpura; rarely - exfoliative dermatitis (fever with or without chills, redness, thickening or peeling of the skin, swelling and/or tenderness of the tonsils), urticaria, Stevens-Johnson syndrome, Lyell's syndrome.

From the urinary system: rarely - acute renal failure, lower back pain with or without hematuria and/or azotemia, hemolytic-uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura), frequent urination, increased or decreased urine volume, nephritis, edema of renal origin.

From the digestive system: often (especially in elderly patients over 65 years of age with a history of erosive and ulcerative lesions of the gastrointestinal tract) - gastralgia, diarrhea; less often - stomatitis, flatulence, constipation, vomiting, feeling of fullness in the stomach; rarely - nausea, erosive and ulcerative lesions of the gastrointestinal tract (including with perforation and/or bleeding - abdominal pain, spasm or burning in the epigastric region, melena, vomiting like “coffee grounds”, nausea, heartburn and others), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis.

From the hematopoietic organs: rarely - anemia, eosinophilia, leukopenia.

From the senses: hearing loss, ringing in the ears, blurred vision (including blurred vision).

From the cardiovascular system: less often - increased blood pressure; rarely - pulmonary edema, fainting.

From the hemostasis system: rarely - bleeding from a postoperative wound, nosebleeds, rectal bleeding.

Other: often - swelling (face, legs, ankles, fingers, feet, weight gain); less often - increased sweating; rarely - swelling of the tongue, fever.

If any of the side effects indicated in the instructions get worse, or if any other side effects not listed in the instructions are noticed, tell your doctor.

Drug interactions

The simultaneous use of ketorolac with other NSAIDs, glucocorticosteroids, ethanol, corticotropin, calcium preparations increases the risk of ulceration of the gastrointestinal mucosa and the development of gastrointestinal bleeding.

Simultaneous use with paracetamol increases the nephrotoxicity of ketorolac, and with methotrexate increases hepato- and nephrotoxicity. Do not use simultaneously with paracetamol for more than 2 days. The combined use of ketorolac and methotrexate is possible only when using low doses of the latter and monitoring its concentration in the blood plasma. When prescribed with other nephrotoxic drugs (including gold preparations), the risk of developing nephrotoxicity increases.

Probenecid reduces the plasma clearance and volume of distribution of ketorolac, increases its concentration in the blood plasma and increases its half-life. Concomitant use with anticoagulants - coumarin and indanediol derivatives, heparin, thrombolytics (alteplase, streptokinase, urokinase), antiplatelet drugs, cephalosporins, valproic acid and acetylsalicylic acid increases the risk of bleeding.

Reduces the effect of antihypertensive and diuretic drugs (reduces the synthesis of prostaglandins in the kidneys).

Drugs that block tubular secretion reduce the clearance of ketorolac and increase its concentration in the blood plasma.

When combined with opioid analgesics, the doses of the latter can be significantly reduced.

Increases the hypoglycemic effect of insulin and oral hypoglycemic drugs (dose recalculation is necessary). Increases the plasma concentration of verapamil and nifedipine.

Myelotoxic drugs enhance the hematotoxicity of the drug.

Concomitant use with lithium salts, pentoxifylline, zidovudine, digoxin, tacrolimus, selective serotonin reuptake inhibitors, antacids, mifepristone is not recommended.

The drug should not be mixed in the same syringe with morphine sulfate, meperidine hydrochloride, promethazine hydrochloride or hydroxyzine hydrochloride (ketorolac precipitates from solution). Pharmaceutically incompatible with tramadol solution and lithium preparations.