Ketorol Express, 10 mg 20 pcs.

NSAID, has a pronounced analgesic effect, has anti-inflammatory and moderate antipyretic effects. The mechanism of action is associated with non-selective inhibition of COX activity – COX-1 and COX-2, catalyzing formation of prostaglandins from arachidonic acid, which play an important role in the pathogenesis of inflammation, pain and fever.

Ketorolac is a racemic mixture of [-]S- and [+]R-enantiomers with analgesic effect caused by [-]S-form.

The drug does not affect opioid receptors, does not depress respiration, does not cause drug addiction, has no sedative and anxiolytic action.
After oral administration the onset of analgesic effect is noted after 1 hour, the maximum effect is achieved after 1-2 hours.

Pharmacokinetics

Absorption

After oral administration, ketorolac is well absorbed from the GI tract, Cmax in plasma (0.7-1.1 mcg/ml) is reached 40 min after an empty stomach dose of 10 mg. High-fat food decreases Cmax in blood and delays its achieving by 1 h. Bioavailability – 80-100%.

Distribution

Binding to plasma proteins is 99% , with hypoalbuminemia the amount of free substance in blood increases. Time to reach Css (0.39-0.79 mcg/ml), when administered orally 10 mg ketorolac 4 times/day (above subtherapeutic dose), is 24 hours. Vd – 0.15-0.33 l/kg.

Penetrates into breast milk: after maternal administration of 10 mg ketorolac Cmax in breast milk is reached after 2 hours and is 7.3 ng/ml after the first dose and 7.9 ng/ml after the second dose of the drug.

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.

Excretion
Excreted by the kidneys (91%) and through the gut (6%).T1/2 in patients with normal renal function is 2.4-9 h after an oral dose of 10 mg.When taken orally at a dose of 10 mg, total clearance is 0.025 l/h/kg.

Pharmacokinetics in special clinical cases

In patients with renal insufficiency, the Vd of ketorolac may increase twice and the Vd of its R-enantiomer by 20%.T1/2 is increased in older patients and decreased in younger patients.
Liver function disorders have no effect on T1/2. In patients with impaired renal function, with plasma creatinine concentration of 19-50 mg/l (168-442 μmol/l), T1/2 is 10.3-10.8 h, with more severe renal failure – more than 13.6 h.

When administered orally at a dose of 10 mg, total clearance in patients with renal insufficiency (at plasma creatinine concentration of 19-50 mg/l) is 0.016 l/kg.

Not excreted by hemodialysis.

Indications

Pain syndrome of severe to moderate severity:

• trauma;
• dental pain;
• pain in the postoperative period;
• oncology;
• arthralgia;
• neuralgia;
• radiculitis;
• dislocations, sprains;
• rheumatic diseases.

Designed for symptomatic therapy, reducing the intensity of pain and inflammation at the time of use, does not affect the progression of the disease.

Active ingredient

Ketorolac

Composition

Each tablet dispersible in the mouth contains:

Active ingredient:

ketorolaca tromethamine (ketorolaca tromethamol) 10,000 mg;

Associates:

microcrystalline cellulose,

silicon dioxide,

butylhydroxyanisole,

mannitol,

Crosspovidone (type A),

sucralose,

mint flavoring,

quinoline yellow dye (E104),

magnesium stearate.

How to take, the dosage

Put the tablet on the tongue, where it immediately begins to dissolve. Hold the tablet in the mouth for a few seconds until complete dissolution, if desired you can drink liquid.

Taking tablets dispersible in the mouth does not require compulsory water drinking, does not affect the increase in saliva production, allows to take the drug in patients with deviations in the act of swallowing in behavioral and neurological disorders.

Ketorol® Express is orally administered once or repeatedly depending on the severity of the pain syndrome.

A single dose is 10 mg; when administered repeatedly it is recommended to take 10 mg up to 4 times a day, depending on the severity of pain; the maximum daily dose should not exceed 40 mg. In per oral administration the course length should not exceed 5 days.

In order to decrease the risk of side effects the minimum effective dose of ketorolac should be used for the shortest possible course.

When changing from parenteral administration of the drug to oral administration the total daily dose of both dosage forms on the day of transfer should not exceed 90 mg for patients from 16 to 65 years old and 60 mg for patients over 65 years old or with impaired renal function. At the same time, the dose of the drug in tablets on the day of transfer should not exceed 30 mg.

Interaction

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

Simultaneous use of ketorolac with other NSAIDs (including COX-2 inhibitors) may cause fluid retention, decompensation of cardiac activity, increased blood pressure.

Concomitant use of ketorolac with indirect anticoagulants, thrombolytics, antiaggregants, cefoperazone, cefotetan and pentoxifylline increases the risk of bleeding.

Probenecid reduces plasma clearance and distribution volume of ketorolac, increases its plasma concentration and increases its T1/2.Co-administration of ketorolac with valproate causes impairment of platelet aggregation.

Co-administration of ketorolac with other nephrotoxic drugs (including gold preparations) increases the risk of nephrotoxicity. Drugs that block tubular secretion decrease clearance of ketorolac and increase its concentration in blood plasma.

Co-administration of ketorolac with methotrexate increases hepato- and nephrotoxicity of methotrexate. Co-administration of ketorolac and methotrexate is possible only when using low doses of the latter. Against the background of ketorolac use it is possible to decrease clearance of lithium, increase its concentration in blood plasma and increase the toxic effect of lithium.

Simultaneous use with lithium salts is contraindicated.

Ketorolac reduces the effect of hypotensive and diuretic drugs (reduces the synthesis of prostaglandins in the kidneys).

Ketorolac increases the effect of narcotic analgesics. When combining with opioid analgesics the doses of the latter may be significantly reduced.

Ketorolac increases hypoglycemic effect of insulin and oral hypoglycemic drugs, therefore the doses of these drugs should be recalculated.

Ketorolac increases plasma concentrations of verapamil and nifedipine.

Concomitant use of NSAIDs and mifepristone may decrease the effectiveness of mifepristone. It is not recommended that NSAIDs be used within 8-12 days after mifepristone administration.
Concomitant use of NSAIDs and cyclosporine increases the risk of nephrotoxicity.Concomitant use of NSAIDs and quinolone-type antibiotics increases the risk of seizures. Concomitant use of NSAIDs and tacrolimus increases the risk of nephrotoxicity.Concomitant use of NSAIDs and zidovudine increases the risk of hematological toxicity.

In concomitant use with digoxin ketorolac does not impair the binding of digoxin to plasma proteins. Therapeutic concentrations of digoxin do not affect the binding of ketorolac to plasma proteins. Antacids have no effect on absorption of ketorolac. Myelotoxic drugs increase the manifestation of ketorolac haematotoxicity.

Special Instructions

Ketorol® is available in the following dosage forms: gel for external use; film-coated tablets; tablets dispersible in the oral cavity; solution for intravenous and intravenous administration.

Before using the drug it is necessary to find out about the previous allergy to the drug or other NSAIDs. Because of the risk of allergic reactions, the first dose should be taken under close supervision of a physician.

Ketorolac inhibits platelet aggregation and increases blood clotting time. The effect on platelet aggregation ceases 24-48 hours after taking the drug.

In patients with clotting disorders the drug is prescribed only with continuous monitoring of platelet count, which is especially important in the postoperative period when close monitoring of hemostasis is required.
Hypovolemia increases the risk of nephrotoxic adverse reactions.

If necessary it may be used in combination with narcotic analgesics.

Do not use with paracetamol for more than 2 days. The risk of adverse reactions increases with prolongation of the treatment course and increasing of oral dose of ketorolac over 40 mg/day.

Simultaneous use of ketorolac with probenecid, pentoxifylline, acetylsalicylic acid and other NSAIDs (including COX-2 inhibitors), lithium salts, anticoagulants (including warfarin and heparin) is contraindicated.

Ketorolac is contraindicated for prophylactic analgesia before and during major surgical procedures because of the high risk of bleeding.

Ketorolac is not recommended for use as a means for premedication and maintenance anesthesia. When using ketorolac, cases of fluid retention, increased BP and edema have been reported.

Caution should be exercised when prescribing to patients with heart failure, arterial hypertension.

Simultaneous use of ketorolac with other NSAIDs can lead to such disorders as decompensation of heart failure and increased BP. According to clinical studies, the use of some NSAIDs in high doses may lead to an increased risk of arterial thrombotic complications (e.g., myocardial infarction, stroke). Although such complications have not been reported on the use of ketorolac, the existing data are insufficient to exclude the risk of such complications.

To reduce the risk of NSAID-induced gastropathy, the use of antacid drugs, misoprostol, and drugs that reduce gastric secretion (histamine H2-receptor blockers, proton pump inhibitors) is recommended.

To reduce the risk of adverse events the minimum effective dose of ketorolac should be used for the shortest possible course.

Impact on the ability to drive vehicles and mechanisms

During treatment, caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and rapid psychomotor reactions.

Contraindications

• High sensitivity (including to other NSAIDs);
• complete or incomplete combination of bronchial asthma, recurrent nasal and paranasal sinus polyposis and intolerance to acetylsalicylic acid or other NSAIDs (including a history. history);
• gastrointestinal erosive lesions;
• active gastrointestinal bleeding;
• inflammatory bowel disease (including ulcerative colitis.Ulcerative colitis, Crohn’s disease);
• bone marrow and blood diseases (leukopenia, including in anamnesis; thrombocytopenia; hypocoagulation, including in anamnesis;
• diseases of the intestines.ч.
• hemophilia),
• myelosuppression;
• bleeding or high risk of bleeding;
• severe renal failure (CKR less than 30 ml/min);
• confirmed hyperkalemia;
• severe hepatic failure or active liver disease;
• state after coronary artery bypass grafting;
• prophylactic analgesia before and during major surgical procedures because of the high risk of bleeding;
• active cerebrovascular disease (including.ч.
• pregnancy;
• pregnancy;
• partum period;
• breastfeeding period;
• children under 16 years of age (safety and efficacy not established);
• concomitant use with probenecid;
concomitant use with pentoxifylline;
• concomitant use with acetylsalicylic acid other NSAIDs (including selective COX-2 inhibitors);
• concomitant use with lithium salts;
• concomitant use with anticoagulants (including warfarin and heparin).

Cautious

Bronchial asthma; presence of factors that increase toxicity to the GI tract:Alcoholism, tobacco smoking and cholecystitis; postoperative period; chronic heart failure; edema syndrome; arterial hypertension; moderate renal failure (CK 30-60 ml/min); cholestasis; active hepatitis; sepsis; systemic lupus erythematosus; CHD; cerebrovascular disease; dyslipidemia/hyperlipidemia; diabetes mellitus; peripheral arterial disease; history of gastrointestinal ulcers; Helicobacter pylori infection; long-term use of NSAIDs; severe somatic diseases; thyroid disease; tuberculosis; simultaneous use of oral GCS (including prednisolone).Prednisolone), antiplatelet agents (including clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), and older age (over 65 years).

Side effects

Side effect frequency definition: frequent (1-10%), infrequent (0.1-1%), rare (0.01-0.1%), very rare (< 0.01%) and frequency unknown, including individual reports.

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

Urinary system disorders: rare – acute renal failure, low back pain, hematuria, azotemia, hemolytic-uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura), frequent urination, oliguria, polyuria, interstitial nephritis, edema of renal genesis; frequency unknown – urinary retention.

The sensory system: rare – hearing loss, tinnitus, visual impairment (including blurred vision), the frequency is unknown – disorders of taste.

The respiratory system: rare – bronchospasm or shortness of breath, rhinitis, laryngeal edema (shortness of breath, difficulty in breathing).

CNS: often – headache, dizziness, somnolence; rarely – aseptic meningitis (fever, severe headache, seizures, neck and/or back stiffness), hyperactivity (mood changes, anxiety), hallucinations, depression, psychosis.

Cardio-vascular system: infrequent – BP increase, rarely – pulmonary edema, fainting states.

Blood organs: rare – anemia, eosinophilia, leukopenia.

The hemostatic system: rare – bleeding from the post-operative wound, nasal bleeding, rectal bleeding.

Skin: infrequent – skin rash (including maculopapular rash), purpura, rarely – exfoliative dermatitis (fever with or without chills, redness, thickening or peeling of the skin, swollen and/or painful palatine tonsils), urticaria, Stevens-Johnson syndrome, Lyell syndrome.

Allergic reactions: rare – anaphylaxis or anaphylactoid reactions (changes in complexion, skin rash, urticaria, pruritus, tachypnea or dyspnea, edema of the eyelids, swollen tongue, periorbital edema, shortness of breath, difficulty in breathing, heaviness in the chest, wheezing).

Other: often – edema (face, shins, ankles, fingers, feet, weight gain); infrequently – increased sweating; rarely – fever; frequency unknown – hyperkalemia, hyponatremia.

Overdose

Symptoms: abdominal pain, nausea, vomiting, gastrointestinal erosive and ulcerative lesions, renal dysfunction, metabolic acidosis.

treatment: gastric lavage, administration of adsorbents (activated carbon) and symptomatic therapy (maintenance of vital body functions). Hemodialysis is ineffective.