Ketorol film-coated tablets 10 mg 20 pcs.

Pharmacodynamics. Ketorol is an NSAID with pronounced analgesic, antipyretic and anti-inflammatory effects. The mechanism of action is associated with the blockade of the COX enzyme in peripheral tissues, resulting in inhibition of the biosynthesis of prostaglandins – modulators of pain sensitivity, thermoregulation and inflammation. Ketorol is a racemic mixture of [-] s and [+] r-enantiomers, while the analgesic effect is due to the [-] s-form. Ketorol does not affect opioid receptors and respiratory function, does not have a sedative and anxiolytic effect, does not cause drug dependence. Ketorolac also inhibits platelet aggregation. The ability of platelets to aggregate is restored after 24-48 hours. The drug does not cause withdrawal syndrome after stopping its administration.

After oral administration, Ketorolac is rapidly and completely absorbed from the gastrointestinal tract. Cmax _in blood plasma is reached on average 44 minutes after taking 10 mg and is 0.7-1.1 μg/ml.

After intravenous administration of 30 mg of Ketorol, its C _max in blood plasma is reached 50 min after a single administration and is 2.2-3 μg/ml. T _½ of the final breakdown products of Ketorol in adult young patients is 5.3 h, the average total clearance is 0.023 ml/min/kg. After a single administration of 10 mg of Ketorol, C _max in blood plasma is reached 5.4 min and is 2.4 μg/ml. T _½ is 5.1 h, the average volume of distribution is 0.15 l/kg, the total clearance is 0.35 ml/min/kg.

In patients over 65 years of age, the T½ _of ketorolac end products increases to 7 hours (4.3-8.6 hours) compared to young healthy volunteers. Total plasma clearance decreases to 0.019 l/kg.

The pharmacokinetics of ketorolac after single and repeated administration does not change and is linear. Equilibrium concentrations of the drug in the blood plasma are achieved when the drug is administered every 6 hours during the day. The clearance of the drug with repeated administration remains constant. Ketorolac is 99% bound to blood plasma proteins, the degree of binding does not depend on the concentration of the drug in the blood.

Ketorolac metabolites are excreted from the body by the kidneys, 94% of the administered dose is excreted in the urine, 6% is excreted in the feces.

In patients with impaired renal function, the elimination of ketorolac is slowed, which is manifested by a prolongation of T _½ and a decrease in clearance compared to young healthy individuals.

In patients with impaired liver function, no changes in the pharmacokinetics of ketorolac were noted, but the time to reach C _max of the drug in blood plasma and T _½ are slightly increased compared to young healthy volunteers.

Tablets. relief of moderate and severe pain in the postoperative period for a short time.

R-r. Relief of moderate and severe pain in the postoperative and post-traumatic period inclusive.

Ketorol is not indicated for the treatment of chronic pain syndrome, but is used only in case of acute pain.

Tablets. Adults and children over 16 years of age Ketorol tablets are prescribed 10 mg every 4-6 hours if necessary. The maximum daily dose is 40 mg. When transferring patients from parenteral treatment to oral administration of the drug, the total daily dose of ketorolac should not exceed 90 mg for adults and 60 mg for patients over 65 years of age, patients with impaired renal function and patients weighing 50 kg. On the day of transfer from parenteral administration to taking tablets, the daily dose of tablets should not exceed 40 mg. The duration of treatment with Ketorol in tablet form is no more than 7 days.

R-r. Adults and children over 16 years of age are prescribed Ketorol in / m or in / in an initial dose of 10 mg with subsequent doses of 10-30 mg every 4-6 hours if necessary. The maximum daily dose is 90 mg for adults and 60 mg for patients over 65 years of age, patients with impaired renal function and patients with a body weight of 50 kg. The maximum duration of parenteral use of the drug is 2 days. When transferring patients from parenteral treatment to oral administration of the drug, the total daily dose of ketorolac should not exceed 90 mg for adults and 60 mg for patients over 65 years of age, patients with impaired renal function and patients with a body weight of 50 kg. On the day of transfer from parenteral administration to taking tablets, the daily dose of tablets should not exceed 40 mg. The duration of combined use of the drug parenterally and orally should not exceed 5 days.

Hypersensitivity to ketorolac or other drugs belonging to the group of nonsteroidal anti-inflammatory drugs, allergic reactions to acetylsalicylic acid; bacteremia; gastric and duodenal ulcers in the active phase, as well as a history of perforation or gastrointestinal bleeding; severe renal dysfunction; high risk of postoperative bleeding, incomplete hemostasis, hemorrhagic stroke; congestive heart failure (fluid retention in the body is noted); a history of erosive-ulcerative diseases of the gastrointestinal tract; hemorrhagic diathesis, including blood clotting disorders; concomitant administration of anticoagulants, including low doses of heparin (2500-5000 units every 12 hours); a history of nasal polyposis syndrome, angioedema, bronchospasm; simultaneous use of other nonsteroidal anti-inflammatory drugs, oxpentifillin, probenecid or lithium salts; use before and during surgery, pregnancy and breastfeeding, age up to 16 years.

Gastrointestinal: nausea, vomiting, dyspepsia, abdominal pain, taste changes, erosive-ulcerative lesions of the gastrointestinal tract, bleeding, ulcer perforation, diarrhea, dry mouth, severe thirst, flatulence, constipation, cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis, stomatitis, feeling of fullness of the stomach, gastritis, esophagitis, belching, hematemesis, melena, exacerbation of colitis and Crohn’s disease, liver failure.

From the side of the central nervous system: drowsiness, impaired concentration, euphoria, headache, dizziness, anxiety, asthenic syndrome, increased sweating, paresthesias, insomnia, malaise, fatigue, agitation, unusual dreams, confusion, vertigo, hyperkinesia, rarely – aseptic meningitis (fever, severe headache, convulsions, stiffness of the neck and/or back muscles), hyperactivity (mood swings, restlessness), hallucinations, depression, psychosis, unconsciousness.

Cardiovascular: bradycardia, hot flashes, purpura, pallor, palpitations, chest pain. Edema, hypertension and heart failure have also been reported in association with the use of nonsteroidal anti-inflammatory drugs. Clinical and epidemiological data have shown that the use of some NSAIDs, especially in high doses and for a long time, may increase the risk of arterial thromboembolic complications, such as myocardial infarction or stroke.

From the side of the hematopoietic system: aplastic anemia, hemolytic anemia, agranulocytosis, leukopenia, thrombocytopenia.

Respiratory system: bronchospasm, dyspnea, pulmonary edema, laryngeal edema, asthma, exacerbation of asthma.

From the urinary system: nephrotic syndrome, oliguria, dysuria, increased frequency of urination, hyponatremia, hyperkalemia, increased creatinine and urea levels, interstitial nephritis, urinary retention, back pain, acute renal failure, hematuria, azotemia, hemolytic uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura).

Skin: rash (including macular rash), purpura, exfoliative dermatitis (hyperemia, thickening or peeling of the skin, enlargement and / or tenderness of the tonsils), photosensitivity, Lyell’s syndrome.

From the hemostatic system: bleeding from the postoperative wound, nosebleeds, rectal bleeding, increased bleeding time.

From the reproductive system: female infertility.

Allergic reactions: urticaria, Stevens-Johnson syndrome, pemphigus, anaphylaxis or anaphylactoid reactions, angioedema.

From the sensory organs: hearing loss, tinnitus, optic neuritis.

General disorders: increased sweating, edema, muscle pain, pain at the injection site.

Changes in laboratory parameters: eosinophilia, increased activity of hepatic transaminases.

Others: weight gain, increased body temperature.

NSAIDs should be used with caution in patients with a history of ulcerative colitis and Crohn’s disease.

The use of ketorolac, like other prostaglandin synthesis inhibitors, may lead to an increase in serum urea, creatinine and potassium levels even after the first dose.

The use of the drug in patients with hypertension, congestive heart failure, established ischemic heart disease, peripheral artery disease and cerebrovascular disease is possible after careful risk/benefit assessment. It is also necessary to weigh the benefit/risk ratio before starting long-term therapy in patients with risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, diabetes mellitus, smoking.

Patients with systemic lupus erythematosus and connective tissue diseases have an increased risk of developing aseptic meningitis. Elderly patients are more susceptible to side effects, so it is necessary to pay increased attention to such patients and prescribe the drug in low doses. For patients over 65 years of age, the daily dose is 60 mg. For patients with impaired renal function or a history of kidney disease, the daily dose is 60 mg. The use of the drug may cause an increase in the activity of liver enzymes in the blood serum. In patients with pre-existing liver dysfunction, such a reaction may cause more serious liver diseases. If abnormal liver test values ​​are detected, the use of ketorolac should be discontinued. Ketorolac affects platelet aggregation, so the condition of patients with impaired blood coagulation should be carefully monitored.

Use during pregnancy and breastfeeding. The safety and efficacy of the drug in pregnant and breastfeeding women have not been established, therefore the use of the drug in this category of patients is not recommended.

Children. The drug is not used in children under 16 years of age.

Effects on the ability to drive or use machines. Given the possibility of side effects such as drowsiness, dizziness, and impaired concentration, driving and operating machinery that require increased attention should be avoided.

Ketorolac slightly reduces the binding of warfarin to plasma proteins. In vitro studies have shown that at therapeutic concentrations of salicylate, the binding of ketorolac to plasma proteins decreases from 99.2 to 97.5%, which may lead to an increase in the content of free ketorolac. Ketorolac reduces the diuretic effect of furosemide by approximately 20%. With the combined appointment of probenecid and Ketorol, an increase in the concentration of ketorolac in the blood plasma and an extension of its half-life from the body are noted. With simultaneous use with lithium preparations, inhibition of renal clearance of lithium is possible, therefore the content of lithium in the blood plasma may increase. Ketorolac may interact with non-depolarizing muscle relaxants, which may lead to respiratory failure. Simultaneous use of ketorolac with ACE inhibitors may increase the risk of developing renal dysfunction, especially in patients with hypovolemia.

Concomitant use of ketorolac with anticoagulants may increase the risk of bleeding.

The drug should not be administered simultaneously with the following drugs: other NSAIDs, including selective COX-2 inhibitors, due to increased side effects. NSAIDs should not be used within 8-12 days after taking mifepristone, as this may reduce the severity of the effects of mifepristone.

Drugs that can be used with caution with ketorolac. Cardiac glycosides, since heart failure may be aggravated and plasma concentrations of cardiac glycosides may increase. Ketorolac and other NSAIDs may reduce the hypotensive effect of β-adrenoceptor blockers. When used simultaneously with cyclosporine, nephrotoxicity increases. There is a risk of nephrotoxicity when used simultaneously with tacrolimus. When used simultaneously with corticosteroids, the risk of gastrointestinal ulcers and bleeding increases. When used simultaneously with selective serotonin reuptake inhibitors and oxpentifylline, the risk of bleeding increases. The drug should be prescribed with caution with methotrexate, since there have been reports of a decrease in the clearance of methotrexate when used simultaneously with some prostaglandin synthesis inhibitors, which may increase its toxicity. When used simultaneously with quinolines, the risk of convulsions increases. NSAIDs increase hematological toxicity when used concomitantly with zidovudine. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-positive hemophiliacs treated concomitantly with zidovudine and ibuprofen.

Symptoms: abdominal pain, nausea, vomiting, the development of gastric ulcer or erosive gastritis, impaired renal function. Specific antidote is unknown. In case of overdose, gastric lavage with the administration of sorbents (activated charcoal) and symptomatic therapy are recommended.

Tablets – in a dry, dark place at a temperature of 15-25 °C. Solution – in a dark place at a temperature of 2-25 °C.