Ketofreel pills 10 mg, 20 pcs.

Composition

One tablet contains:Active ingredient: Ketorolac trometamol (ketorolac trometamine) – 10 mgsupport substances (core): microcrystalline cellulose, anhydrous lactose, sodium carboxymethyl starch, colloidal silicon dioxide, magnesium stearate. Excipients (shell): hypromellose. talc, titanium dioxide, macrogol, colloidal silicon dioxide.

Pharmacological action

Pharmacotherapy group:

nonsteroidal anti-inflammatory drug (NSAID)

ATX code: [M 01 AB 15]

Pharmacological action

Pharmacodynamicaketorolac 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 1 and 2 enzyme activity, mainly in peripheral tissues, which results in inhibition of prostaglandin biosynthesis-modulators of pain sensitivity, thermoregulation, and inflammation. Ketorolac is a racemic mixture of the [- ] S and [+]R enantiomers, and the analgesic effect is due to the [- ] S form.

The drug does not affect opioid receptors, does not depress respiration, 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 other NSAIDs. After oral administration, the onset of analgesic action is noted, respectively, in 1 h, the maximum effect is achieved in 1-2 h

. Pharmacokinetics

When taken orally, Ketorolac is well absorbed in the gastrointestinal tract -the maximum concentration (Cmax) in blood plasma (0.7-1.1 mcg / ml) is reached 40 minutes after taking a 10 mg dose on an empty stomach. High-fat foods reduce the maximum concentration of the drug in the blood and delay its achievement by 1 hour.

99% of the drug binds to plasma proteins and with hypoalbuminemia, the amount of free substance in the blood increases.

Bioavailability – 80-100%. The time to reach the equilibrium concentration (Css) with oral administration is 24 hours when prescribed 4 times a day (above subtherapeutic) and amounts to 10 mg – 0.39-0.79 mcg/ml after oral administration. The volume of distribution is 0.15-0.33 l / kg. In patients with renal insufficiency, the volume of distribution of the drug may increase by 2 times, and the volume of distribution of its R-enantiomer-by 20%.

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

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 by 91% of the kidneys,6% – through the intestines.

The elimination half-life (Half-life in patients with normal renal function is on average 5.3 hours) is prolonged in elderly patients and shortened in young patients. Liver function does not affect the half-life In patients with impaired renal function at a plasma creatinine concentration of 19-50 mg / l (168-442 mmol/l) Half-life is 10.3-10.8 hours, with more severe renal insufficiency-more than 13.6 hours. It is not excreted during hemodialysis.

Indications

Moderate and severe pain syndrome of various origins (including in the postoperative period, cancer, etc. )

Contraindications

Hypersensitivity to the Active ingredient or auxiliary components; anamnestic data on an attack of bronchial obstruction, rhinitis, urticaria after taking acetylsalicylic acid or other NSAIDs (complete or incomplete acetylsalicylic acid intolerance syndrome-rhinosinusitis, urticaria, nasal mucosal polyps, bronchial asthma); angioedema, hypovolemia (regardless of the cause), dehydration.

Erosive and ulcerative changes in the gastric or duodenal mucosa, active gastrointestinal bleeding; inflammatory bowel diseases; hypocoagulation (including hemophilia).

Severe hepatic insufficiency or active liver disease; severe renal insufficiency (plasma creatinine above 50 mg / L), progressive kidney disease; confirmed hyperkalemia.

Hemorrhagic stroke (confirmed or suspected), hemorrhagic diathesis, concomitant use with other NSAIDs, high risk of developing or relapsing hemorrhagic stroke (including after surgery), hematopoietic disorders.

Pregnancy, childbirth, and lactation.

Children under 16 years of age (efficacy and safety have not been established).

The period 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, as well as for the treatment of chronic pain.

With caution – bronchial asthma; cholecystitis; chronic heart failure; coronary heart disease, cerebrovascular diseases, arterial hypertension; dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral arterial diseases, smoking, impaired renal function (plasma creatinine below 50 mg/l); cholestasis; active hepatitis; sepsis; systemic lupus erythematosus; elderly (over 65 years); nasal and nasopharyngeal mucosal polyps.

Anamnestic data on the development of ulcerative lesions of the gastrointestinal tract, the presence of Helicobacter pylori infection, long-term use of NSAIDs, frequent alcohol consumption, severe somatic diseases, concomitant therapy with the following drugs:

• anticoagulants (e. g., warfarin), antiplatelet agents (e. g., acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (e. g., prednisone), selective serotonin reuptake inhibitors (e. g., citalopram, fluoxetine, paroxetine, sertraline).

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

Side effects

Often-more than 3%, less often-1-3%, rarely-less than 1%. From the digestive system: often (especially in elderly patients over 65 years of age who have a history of erosive and ulcerative lesions of the gastrointestinal tract)-gastralgia, diarrhea; less often-stomatitis, flatulence, constipation, vomiting, a feeling of fullness of 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, coffee grounds vomiting, nausea, heartburn, etc. ), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis. From the urinary system: rarely – acute renal failure, low 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 side of the senses: rare: hearing loss, ringing in the ears, visual impairment (including blurred vision). 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: less often-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: 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 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, itchy skin, tachypnea or dyspnea, edema of the eyelids, periorbital edema, shortness of breath, difficulty breathing, heaviness in the chest, wheezing). Other services: often – edema (face, shins, ankles, fingers, feet, weight gain); less often – increased sweating, rarely – swelling of the tongue, fever.

Interaction

Concomitant use of ketorolac with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs, calcium supplements, glucocorticosteroids, ethanol, corticotropin can lead to the formation of gastrointestinal ulcers and the development of gastrointestinal bleeding. Co-administration with paracetamol increases nephrotoxicity, with methotrexate-hepatotoxicity and nephrotoxicity. Co-administration of ketorolac. and methotrexate is possible only when using low doses of the latter (monitor the concentration of methotrexate in blood plasma). Probenecid reduces the plasma clearance and volume of distribution of ketorolac, increases its concentration in blood plasma and increases its half-life. When using ketorolac, it is possible to reduce the clearance of methotrexate and lithium and increase the toxicity of these substances. Concomitant administration with indirect anticoagulants, heparin, thrombolytics, antiplatelet agents, cefoperazone, cefotetane, and pentoxifylline increases the risk of bleeding.Reduces the effect of antihypertensive and diuretic drugs (reduces the synthesis of prostaglandins in the kidneys). When combined with opioid analgesics, the doses of the latter can be significantly reduced. Antacids do not affect the completeness of drug absorption. The hypoglycemic effect of insulin and oral hypoglycemic agents increases (dose recalculation is necessary). Co-administration with valproic acid causes a violation of platelet aggregation. Increases plasma concentrations of verapamil and nifedipine. When prescribed with other nephrotoxic drugs (including gold preparations), the risk of developing nephrotoxicity increases. Drugs that block tubular secretion reduce the clearance of ketorolac and increase its concentration in blood plasma.

How to take, course of administration and dosage

Ketofreel® is administered orally once or repeatedly, depending on the severity of the pain syndrome. A single dose is 10 mg, 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. When taken orally, the duration of the course should not exceed 5 days.

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 body functions). It is not sufficiently excreted by dialysis.

Special instructions

The effect on platelet aggregation stops after 24-48 hours. Hypovolemia increases the risk of adverse reactions from the kidneys. If necessary, it can be prescribed in combination with narcotic analgesics. Do not use simultaneously with paracetamol for more than 5 days. Patients with blood clotting disorders are prescribed the drug only with constant monitoring of platelet count, especially important in the postoperative period, which requires careful monitoring of hemostasis. Since a significant number of patients develop side effects from the central nervous system (drowsiness, dizziness, headache) when prescribing ketorolac, it is recommended to avoid performing work that requires increased attention and rapid reaction (driving vehicles, working with mechanisms, etc. ).

Storage conditions

At a temperature not exceeding 30°C in a dry place protected from light. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Ketorolac

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Weight

Weight: 19 gr.