Ketorolac pills 10 mg Renewal, 20 pcs.

Composition

Active ingredients:Ketorolac (Ketorolac trometamine) – 10.00 mgsupportable substances:microcrystalline cellulose-122.41 mg corn starch-44.76 mg colloidal silicon dioxide (aerosil) – 1.83 mg magnesium stearate-1.00 mg Shell composition:hypromellose-2.91 mgtitan dioxide-1.25 mgmacrogol 400 (polyethylene glycol 400) – 0.68 mgtalk-0.16 mg

. Pharmacological action

Pharmacotherapy group: NSAIDs ATX code: M01AB15

Ketorolac has a pronounced analgesic effect, also has an anti-inflammatory and moderate antipyretic effect.

The mechanism of action is associated with non-selective inhibition of cyclooxygenase enzyme activity (COX-1 and COX-2), mainly in peripheral tissues, which results in inhibition of prostaglandin biosynthesis-modulators of pain sensitivity, thermoregulation, and inflammation. Ketorolac is a racemic mixture of [- ] S and [+]R-enantiomers, and the analgesic effect is due to the [-]S form.

Ketorolac does not affect opioid receptors, does not depress breathing, does not cause drug dependence, does not have a sedative and anxiolytic effect.

The strength of the analgesic effect is comparable to morphine, significantly superior to NSAIDs.

After oral administration, the onset of analgesic action is noted, respectively, in 1 hour, the maximum effect is achieved in 1-2 hours.

Pharmacokinetics:

Suction

When taken orally, ketorolac is well absorbed from the gastrointestinal tract (GIT). Bioavailability – 80-100%. The maximum concentration (Cmax) in blood plasma (0.7-1.1 mcg / ml) is reached 40 minutes after taking ketorolac on an empty stomach at a dose of 10 mg. A fat-rich food reduces the Cmax of the drug in the blood plasma and delays its achievement by 1 hour.

Distribution

Binding to plasma proteins is 99%. With hypoalbuminemia, the amount of free ketorolac in the blood plasma increases.

The time to reach the equilibrium concentration (Css) when taken orally is 24 hours when used 4 times a day (above the subtherapeutic dose). The steady-state plasma concentration after oral administration of 10 mg of ketorolac is 0.39-0.79 mcg / ml. The volume of distribution is 0.15-0.33 l / kg.

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.

Deduction

It is excreted by the kidneys by 91% (40% in the form of metabolites),6% – through the intestine.

After oral administration of 10 mg of ketorolac, the half-life (T 1/2) in patients with normal renal function is on average 5.3 hours (2.4-9 hours). The total ground clearance is 0.025 l / kg / h. It is not excreted during hemodialysis.

Pharmacokinetics in special patient groups

Patients with impaired renal function

In patients with renal insufficiency, the volume of distribution of ketorolac can increase by 2 times, and the volume of distribution of its R-enantiomer-by 20%.

In renal insufficiency with a plasma creatinine concentration of 19-50 mg/l (168-442 mmol/L), T 1/2 is 10.3-10.8 hours, in more severe renal insufficiency – more than 13.6 hours.

Total clearance in renal insufficiency with a plasma creatinine concentration of 19-50 mg / ml when 10 mg of ketorolac is taken orally is 0.016 l/kg/h.

Patients with impaired liver

function Liver function does not affect T 1/2.

Elderly and young patients

T 1/2 lengthens in elderly patients and shortens in young patients.

Nursing mothers

Ketorolac penetrates into breast milk: after taking 10 mg of ketorolac by the mother, the Cmax in milk is reached in 2 hours and is 7.3 ng/ml, respectively,2 hours after taking the second dose of ketorolac (when using the drug 4 times a day) – 7.9 ng/ml.

Indications

Severe to moderate pain syndrome:

• injuries;
• toothache;
• pain in the postpartum and postoperative period;
• cancer;
• myalgia;
• arthralgia;
• neuralgia;
• sciatica;
• dislocations, sprains;
• rheumatic diseases.

Contraindications

• Hypersensitivity (including to other non-steroidal anti-inflammatory drugs);
• complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance of acetylsalicylic acid or other NSAIDs (including in the anamnesis);
• erosive-ulcerative lesions of the gastrointestinal tract (GIT), active gastrointestinal bleeding;
• inflammatory bowel disease (including ulcerative colitis, Crohn’s disease);
• diseases of the bone marrow and blood (leukopenia, including a history of thrombocytopenia, hypocoagulation (including hemophilia)), myelosuppression, bleeding or high risk of their development;
• severe renal insufficiency (creatinine clearance (CC) of less than 30 ml/min), confirmed hyperkalemia;
• severe hepatic impairment or active liver disease;
• status after conducting coronary artery bypass surgery;
• preventive analgesia before and during extensive surgical interventions due to the high risk of bleeding;
• active cerebrovascular disease (including intracranial hemorrhage or suspected it); pregnancy;
• childbirth;
• the period of breastfeeding; children up to age 16 years (safety and efficacy have not been established);
• concurrent use with probenecid;
• the simultaneous use with pentoxifylline; the simultaneous use with acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs (including cyclooxygenase-2 inhibitors);
• concurrent use of lithium salts;
• the simultaneous use of anticoagulants (including warfarin and heparin).

With caution:

Bronchial asthma; presence of factors that increase gastrointestinal toxicity: alcoholism, tobacco smoking and cholecystitis; postoperative period; chronic heart failure; edematous syndrome; arterial hypertension; moderate renal failure (creatinine clearance 30-60 ml/min); cholestasis; active hepatitis; sepsis; systemic lupus erythematosus; coronary heart disease; cerebrovascular diseases; dyslipidemia/hyperlipidemia; diabetes mellitus * peripheral arterial diseases; a history of gastrointestinal ulcers, the presence of Helicobacter pylori infection; long-term use of NSAIDs; severe somatic diseases; thyroid diseases; tuberculosis; simultaneous use of oral glucocorticosteroids (including prednisone), antiplatelet agents (including clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline); elderly (over 65 years of age).

Side effects

the incidence of adverse events (AES) classified according to the recommendations of the world health organization defined as: very often – at least 10%; often – not less than 1% but < 10%; infrequently – no more than 0.1% but < 1%; rarely-not less than 0.01%, but less than 0.1%; very rarely, including isolated cases – less than 0.01%; frequency unknown (frequency cannot be determined based on available data).

From the digestive system

Often (especially in elderly patients older than 65 years with a history of erosive and ulcerative lesions of the gastrointestinal tract) – gastralgia, diarrhea;

rarely – stomatitis, flatulence, constipation, vomiting, feeling of fullness of the stomach;

rarely – nausea, erosive and ulcerative lesions of the gastrointestinal tract (including perforation and/or bleeding, abdominal pain, spasm or burning sensation in the epigastric region, melena, vomiting on the type of coffee ground, nausea, heartburn), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis.

From the urinary system

Rarely-acute renal failure, low back pain, hematuria, azotemia, hemolytic-uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura), frequent urination, oliguria, polyuria, interstitial nephritis, renal edema;

frequency unknown-urinary retention.

From the side of the senses

Rarely – hearing loss, ringing in the ears, visual disturbances (including blurred vision);

frequency unknown-taste disorders.

Respiratory system disorders

Rarely-bronchospasm or dyspnoea, rhinitis, laryngeal edema (shortness of breath, difficulty breathing).

From the central nervous system

Often – headache, dizziness, drowsiness;

rarely-aseptic meningitis (fever, severe headache, convulsions, neck and/or back stiffness), hyperactivity (mood changes, anxiety), hallucinations, depression, psychosis.

From the cardiovascular system

Infrequently-increased blood pressure;

rarely-pulmonary edema, fainting.

From the side of hematopoietic organs

Rarely-anemia, eosinophilia, leukopenia.

From the side of the hemostatic system

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

From the side of the skin

Infrequently-skin rash (including maculopapular rash), purpura;

rarely-exfoliative dermatitis (fever with or without chills, redness, thickening or peeling of the skin, swelling and / or soreness of the palatine tonsils), urticaria, Stevens-Johnson syndrome, Lyell’s syndrome.

Allergic reactions

Rarely – anaphylaxis or anaphylactoid reactions (discoloration of the skin of the face, skin rash, urticaria, pruritus, tachypnea or dyspnea, edema of the eyelids, edema of the tongue, periorbital edema, shortness of breath, difficulty breathing, heaviness in the chest, wheezing).

Other

Frequently – edema (face, legs, ankles, fingers, feet, weight gain);

infrequently – increased sweating;

rarely – fever;

frequency unknown – hyperkalemia, hyponatremia.

Interaction

Concomitant use of ketorolac with acetylsalicylic acid or other NSAIDs, calcium supplements, glucocorticosteroids, ethanol, or corticotropin may significantly increase the risk of adverse reactions, including the formation of gastrointestinal ulcers and the development of gastrointestinal bleeding.

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

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

Concomitant 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 blood plasma and increases its half-life.

The combined use of ketorolac with sodium valproate causes a violation 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 blood plasma.

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

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

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

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 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 the use of mifepristone.

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

Concomitant use of NSAIDs and quinolone 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 developing hematological toxicity.

When used concomitantly 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 ketorolac hematotoxicity.

How to take, course of administration and dosage

Inside, once or repeatedly, depending on the severity of the pain syndrome.

A single dose is 10 mg (1 tablet), with repeated administration 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.

The duration of the course should not exceed 5 days.

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

Overdose

Symptoms: abdominal pain, nausea, vomiting, peptic ulcers of the stomach or erosive gastritis, impaired renal function, metabolic acidosis.

Treatment: gastric lavage, administration of adsorbents (activated charcoal) and symptomatic therapy (maintenance of vital functions in the body). Ketorolac is not sufficiently eliminated by hemodialysis.

Special instructions

Before using the drug, it is necessary to find out about a previous allergy to the drug or other NSAIDs. Due to the risk of developing allergic reactions, the first dose is taken under the careful supervision of a doctor.

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

Patients with blood clotting disorders are prescribed the drug only when the number of platelets is constantly monitored, which is especially important in the postoperative period, when careful monitoring of hemostasis is required.

Hypovolemia increases the risk of developing nephrotoxic adverse reactions.

If necessary, it can 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 course of treatment and an increase in the oral dose of ketorolac more than 40 mg / day.

Concomitant administration of ketorolac with probenecid, pentoxifylline, acetylsalicylic acid and other NSAIDs (including cyclooxygenase-2 inhibitors), lithium salts, anticoagulants (including warfarin and heparin) is contraindicated. It is contraindicated to use ketorolac for preventive pain relief before and during extensive surgical interventions due to the high risk of bleeding. Ketorolac is not recommended for use as a premedication agent and maintenance anesthesia.

Fluid retention, increased blood pressure, and edema have been reported with ketorolac.

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

Concomitant use of ketorolac with other NSAIDs can lead to disorders such as decompensation of heart failure and increased blood pressure.

According to clinical studies, the use of certain NSAIDs in high doses may lead to an increased risk of arterial thrombotic complications (for example, myocardial infarction, stroke). Although no such complications have been reported with ketorolac, existing data are insufficient to rule out the risk of such complications.

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

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

Influence on the ability to drive vehicles and mechanisms:

During treatment, side effects from the central nervous system (drowsiness, dizziness, headache) may develop, which reduces the speed of mental and motor reactions and therefore it is necessary to refrain from driving vehicles and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Storage conditions

Keep out of the reach of children in a dark place, at a temperature not exceeding 25 °C.

Shelf

life is 3 years.

Do not use after the expiration date.

Active ingredient

Ketorolac

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Weight

Weight: 20 g.