Ketanov, pills 10 mg 100 pcs.

Composition

One coated tablet contains:

Active ingredient: ketorolac trometamol -10,00 mg.

Auxiliary substances:

corn starch – 44.76 mg, microcrystalline cellulose-122.41 mg, colloidal silicon dioxide-1.83 mg, magnesium stearate-1.00 mg.

Film shell:

hypromellose-2.91 mg, macrogol-400-0.68 mg, purified talc-0.16 mg, titanium dioxide-1.25 mg

. Pharmacological action

Pharmacotherapy group:

nonsteroidal anti-inflammatory drug (NSAID).

ATX code: M 01 AV 15

Pharmacological action:

Pharmacodynamics

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 the activity of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, mainly in peripheral tissues, which results in inhibition of prostaglandin biosynthase – 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.

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 nonsteroidal anti-inflammatory drugs.

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

. Pharmacokinetics

After oral administration, 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 is 0.39-0.79 mcg/ml after oral administration of 10 mg.

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: after the mother takes the first and second doses of ketorolac 10 mg, Cmax in milk is reached in 2 hours and is 7.3 ng/ml and 7.9 g/l, respectively.

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.

Elimination half-life (T 1/2) in patients with normal renal function, it is 2.4-9 hours after oral administration of 10 mg. T 1/2 is prolonged in elderly patients and shortened in young patients. Liver function does not affect T 1/2. In patients with impaired renal function at a plasma creatinine concentration of 19-50 mg / l (168-442 mmol/l)

T1 / 2 is 10.3-10.8 hours, with more severe renal insufficiency – more than 13.6 hours.

Total clearance is 10 mg – 0.025 l/kg/h when taken orally; in renal insufficiency with a plasma creatinine concentration of 19-50 mg / l when taken orally at 10 mg-0.016 l/kg/h.

It is not excreted during hemodialysis.

Indications

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

Use during pregnancy and lactation

The safety of using this drug during pregnancy has not been established. Use of drugs during the third trimester of pregnancy. These drugs, which interfere with prostaglandin synthesis, can cause premature closure of the ductus arteriosus and weakening of the contractility of the uterus. Due to the violation of uterine contractions, labor activity slows down and the risk of uterine bleeding increases.

Ketorolac penetrates into the mother’s milk. Both the mother and child have an increased risk of bleeding.

The use of Ketanov® is contraindicated during pregnancy and lactation.

Contraindications

• Hypersensitivity (including to other nonsteroidal anti-inflammatory drugs);
• Complete or incomplete combination of bronchial asthma. recurrent nasal and paranasal sinus polyposis and intolerance to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (including in the anamnesis);
• Erosive and ulcerative lesions of the gastrointestinal tract and duodenum, active gastrointestinal bleeding, inflammatory bowel diseases:
• Severe renal insufficiency (creatinine clearance below 30 ml / min).
• Liver disease (exacerbation);
• Thyroid diseases;
• Confirmed hyperkalemia;
• Acute myocardial infarction;
• The period after coronary artery bypass grafting;
• Acute cerebral circulatory disorders (ischemic, hemorrhagic stroke);
• Bone marrow and blood diseases (leukopenia, including in the anamnesis, thrombocytopenia, hemophilia), myelosuppression;
• Severe myopathy, myasthenia gravis;
• Pregnancy, breast-feeding period, children’s age (up to 16 years);
• Simultaneous use with probenecid;
• Simultaneous use with pentoxifylline;
• Concomitant use with acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs (including cyclooxygenase-2 inhibitors);
• Simultaneous use with lithium salts;
• Concomitant use with anticoagulants (including warfarin and heparin);

The drug is not used:

– for preventive pain relief before and during extensive surgical interventions due to the high risk of bleeding.

– for the treatment of chronic pain.

With caution:

Peptic ulcer of the stomach and duodenum, ulcerative colitis, Crohn’s disease, a history of liver disease, hepatic porphyria, chronic renal failure (creatinine clearance 30-60 ml/min), chronic heart failure, arterial hypertension, a significant decrease in the volume of circulating blood (including after surgery), elderly patients (including those receiving diuretics, weakened patients and low body weight), bronchial asthma, concomitant use of glucocorticosteroids (including prednisone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), coronary heart disease, cerebrovascular diseases, dyslipidemia/hyperlipidemia, diabetes mellitus diseases of the peripheral arteries, smoking, the presence of Helicobacter pylori infection, long-term use of nonsteroidal anti-inflammatory drugs, tuberculosis, severe osteoporosis, alcoholism, severe somatic diseases, hypotension, hypertension.

Side effects

By frequency, side effects are divided according to WHO criteria into the following categories: very common (>1: 10), common (>>1: 100 and >><1:10), infrequent (>1: 1000 and <1: 10), infrequent (> rare (>1: 10000 and > including individual cases (

CNS disorders: often – headache, dizziness, drowsiness; rarely-aseptic meningitis (fever, severe headache, neck stiffness), hyperactivity, mood swings, anxiety, hallucinations, depression, psychosis.

Disorders of the cardiovascular system: infrequently increased blood pressure; rarely-pulmonary edema, fainting.

Respiratory system disorders: rarely-bronchospasm, shortness of breath, rhinitis, laryngeal edema.

Disorders of 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; infrequently-stomatitis, flatulence, constipation, vomiting, a feeling of fullness of the stomach; rarely-nausea, erosive and ulcerative lesions of the gastrointestinal tract (including with perforation [sharp abdominal pain] and bleeding [vomiting like “coffee grounds”, melena] – conditions that can lead to death), cholestatic jaundice, hepatitis, hepatomegaly. acute pancreatitis.

Excretory system disorders: 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 daily diuresis, nephritis, edema of renal origin.

Sensory disorders: rarely – hearing loss, ringing in the ears, visual impairment (including blurred vision). Disorders of the hemostatic system: rarely-bleeding from a postoperative wound, nosebleeds, rectal bleeding.

Disorders of the hematopoietic system: rarely anemia, eosinophilia, leukopenia.

Skin disorders: infrequently-skin rash (including maculopapular rash), purpura; rarely-exfoliative dermatitis, urticaria, Stevens-Johnson syndrome, Lyell’s syndrome.

Allergic reactions: rarely anaphylactic reactions, anaphylactoid reactions (skin hyperemia, rash, urticaria, pruritus, shortness of breath, difficulty breathing, angioedema).

Other violations: often – edema (face, legs, weight gain); infrequently-increased sweating: rarely-swelling of the tongue, fever.

Interaction

Concomitant use of ketorolac with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including cyclooxygenase-2 inhibitors), calcium supplements, glucocorticosteroids, ethanol, and corticotropin may significantly increase the risk of adverse reactions, including gastrointestinal ulceration and gastrointestinal bleeding. Concomitant use with nonsteroidal anti-inflammatory drugs is contraindicated.

Concomitant use with paracetamol increases nephrotoxicity. with methotrexate – hepatotoxicity and nephrotoxicity.

Concomitant use of ketorolac and methotrexate is possible only when using low doses of the latter (control the concentration of methotrexate in blood plasma) and diuretics (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 absorption of the drug.

Ketorolac increases the hypoglycemic effect of insulin and oral hypoglycemic drugs (dose recalculation is necessary). Simultaneous use with sodium valproate causes a violation of platelet aggregation.

Increases plasma concentrations of verapamil and nifedipine.

When used 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.

Concomitant use with probenecid leads to an increase in the plasma concentration and half-life of ketorolac. Concomitant use with probenecid is contraindicated.

Simultaneous use of lithium salts and certain drugs that inhibit prostaglandin synthesis. it leads to impaired excretion and an increase in the plasma concentration of lithium salts. Concomitant use with lithium salts is contraindicated. Caution is recommended when concomitant use of cyclosporine, tacrolimus and ketorolac (as with other NSAIDs) is associated with an increased risk of nephrotoxicity.

Cases of hematoma formation have been reported in HIV-infected patients with hemophilia treated simultaneously with zidovudine and ibuprofen.

Therefore, caution should be exercised when concomitantly using NSAIDs and zidovudine. Ketorolac does not affect the binding of digoxin to blood proteins.

According to animal studies, the concomitant use of NSAIDs with quinolone antibiotics increases the risk of seizures.

It is not recommended to use NSAIDs for 8-12 days after the use of mifepristone. since it is possible to reduce the effect of mifepristone.

How to take, course of administration and dosage

In the form of tablets, Ketanov® is used 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 functions in the body).

It is not sufficiently excreted by dialysis.

Special instructions

Ketorolac inhibits platelet aggregation and increases blood clotting time. 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.

Ketanov® is not recommended for use as a premedication agent and maintenance anesthesia. Cases of fluid retention, hypertension, and edema have been reported with ketorolac. Caution should be exercised when prescribing to patients with heart failure, arterial hypertension.

Concomitant use with other nonsteroidal anti-inflammatory drugs can lead to such disorders as decompensation of heart failure, increased blood pressure. 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.

According to clinical studies, the use of certain nonsteroidal anti-inflammatory drugs 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. The risk of adverse reactions increases with prolonged treatment and an increase in the oral dose of more than 40 mg / day.

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

Effect of a medicinal product for medical use 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

Store in a dry place, protected from light, 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: 200 gr.