Ketanov MD, 10 mg 20 pcs.

Pharmacotherapeutic group: Non-steroidal anti-inflammatory drug.

Code ATX: M01AB15

Pharmacological properties.

Pharmacodynamics

Non-steroidal anti-inflammatory drug (NSAID), has a pronounced analgesic effect, also has anti-inflammatory and moderate antipyretic effects.

The mechanism of action is related to non-selective inhibition of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-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 [-]S and [+]R enantiomers, and the analgesic effect is due to the [-]S form.

The drug does not affect the opioid receptors, does not depress respiration, does not cause addiction and has no sedative and anxiolytic action. Its analgesic effect is comparable with that of morphine; it is considerably superior to other non-steroidal anti-inflammatory drugs.

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

Pharmacokinetics

After oral administration, ketorolac is well absorbed in the gastrointestinal tract – maximum concentration (C_mah) in plasma (0.7-1.1 µg/mL) is reached 0.4 h after an empty stomach dose of 10 mg of ketorolac in the oral dispersible tablet form. Fat-rich food reduces the maximum blood concentration of the drug and delays its achievement by 1 hour. 99% of the drug is bound to blood plasma proteins; in case of hypoalbuminemia the amount of free substance in blood increases. Bioavailability is 80-100 %. Time to reach equilibrium concentration – C_ss (0.39-0.79 mcg/ml), when administered orally 10 mg ketorolac 4 times daily (dose above subtherapeutic), is 24 hours.

The volume of distribution is 0.15-0.33 l/kg. In patients with renal insufficiency the distribution volume of the drug may increase 2-fold, and the distribution volume of its R-enantiomer – by 20%.

Prevalence in breast milk: after maternal administration of 10 mg of ketorolac C_mah 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.

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 the kidneys (91%) and through the intestine (6%).

The elimination half-life (T_1/2) in patients with normal renal function is 2.4-9 h after an oral dose of 10 mg. T_1/2 is longer in elderly patients and shorter in younger patients. Impaired liver function has no effect on T_1/2. In patients with impaired renal function at a plasma creatinine concentration of 19-50 mg/L (168-442 μmol/L), T_1/2 is 10.3-10.8 h; in more severe renal impairment it is more than 13.6 h.

In an oral dose of 10 mg, the total clearance is 0.025 l/h/kg; in renal failure (plasma creatinine concentration 19-50 mg/l), 0.016 l/h/kg.

It is not excreted by hemodialysis.

Indications

Pain syndrome of moderate to severe intensity of different genesis. Intended for symptomatic therapy, reduction of pain intensity and inflammation at the time of use, does not affect the progression of the disease.

Active ingredient

Ketorolac

Composition

One tablet contains:

The active ingredient:

Ketorolaca trometamol 10.00 mg

Excipients:

Mannitol* 115.56 mg

Microcrystalline cellulose (Avicel PH112) 18.00 mg

Corn starch 18.00 mg

Corn starch/p>

Aspartame 3.60 mg

Crospovidone 9.00 mg

Propyl gallate 0.50 mg

Dye indigo carmine 3.00 mg

/p>

Peppermint flavoring 0.54 mg

Magnesium stearate 1.80 mg

*The amount is adjusted to the actual ketorolac tromethamol content to maintain a constant “tablet weight” value

How to take, the dosage

Place the tablet Ketanov® MD on the tongue where it will immediately begin to dissolve. If necessary, the oral cavity may be moistened with a small amount of water before using the drug.

The tablet is held in the mouth for a few seconds until the tablet is completely dissolved, after which, if necessary, the drug is allowed to drink water. Oral dispersible tablets do not require water.

The single dose is 10 mg (1 tablet); if repeatedly taken, 10 mg is recommended. It is possible to use the drug up to 4 times a day, depending on the severity of the pain syndrome.

The maximum daily dose of the drug must not exceed 40 mg.

The duration of use of the drug should not exceed 5 days.

In order to reduce the risk of adverse events, the lowest effective dose of ketorolac should be used for the shortest possible course.

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

Interaction

Concomitant use of ketorolac with acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (including cyclooxygenase-2 inhibitors), calcium preparations, glucocorticosteroids, ethanol, corticotropin may lead to a significant increase in the risk of adverse reactions, including formation of gastrointestinal ulcers and development of 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 (monitor the plasma concentration of methotrexate).

Probenecid decreases plasma clearance and volume of distribution of ketorolac, increases its plasma concentration and prolongs its half-life.

Concomitant use with indirect anticoagulants, heparin, thrombolytics, antiaggregants, cefoperazone, cefotetan and pentoxifylline increases the risk of bleeding. Concomitant use with anticoagulants (including warfarin and heparin) and with pentoxifylline is contraindicated. Reduces the effect of hypotensive and diuretic drugs (reduces the synthesis of prostaglandins in the kidneys).

When combined with opioid analgesics, doses of the latter may be significantly reduced.

Antacids do not affect absorption of the drug.

Ketorolac increases the hypoglycemic effect of insulin and oral hypoglycemic agents (dose recalculation is necessary).

Concomitant use with sodium valproate causes impaired platelet aggregation.

Enhances plasma concentrations of verapamil and nifedipine.

When used with other nephrotoxic drugs (including gold drugs) the risk of nephrotoxicity increases.

Drugs that block tubular secretion decrease clearance of ketorolac and increase its plasma concentrations.

Concomitant use with probenecid leads to increased plasma concentration and half-life of ketorolac. Concomitant use with probenecid is contraindicated. Concomitant use of lithium salts and some drugs that inhibit prostaglandin synthesis leads to impaired excretion and increased plasma concentration of lithium salts. Concomitant use with lithium salts is contraindicated.

Concomitant use of cyclosporine, tacrolimus with ketorolac (as well as other NSAIDs) is recommended with caution due to the increased risk of nephrotoxicity. Cases of hematoma formation have been reported in HIV-infected patients with hemophilia who received zidovudine and ibuprofen concomitantly. Therefore, caution should be exercised when concomitant use of NSAIDs and zidovudine. Ketorolac does not affect the binding of digoxin to blood proteins.

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

The use of NSAIDs is not recommended for 8-12 days after mifepristone administration, because the effect of mifepristone may diminish.

Special Instructions

Before using the drug, it is necessary to find out about possible allergies in the history of use of drugs containing ketorolac or other NSAIDs. Because of the possible risk of allergic reactions, the first dose should be taken under close medical supervision.

Ketorolac inhibits platelet aggregation and increases blood clotting time. The effect on platelet aggregation ceases 24-48 hours after taking the drug. Patients with blood coagulation disorders are prescribed the drug only with continuous monitoring of platelet count, which is especially important in postoperative period when careful hemostasis control is required.

Hypovolemia increases the risk of renal adverse reactions.

The drug can be used in combination with narcotic analgesics if necessary.

The drug should not be used in obstetric practice.

Do not use simultaneously with paracetamol for more than 2 days.

The risk of adverse reactions increases with prolonging the course of treatment and increasing the dose of ketorolac over 40 mg/day.

The use of ketorolac for prophylactic pain relief before and during major surgical interventions is contraindicated because of the high risk of bleeding.

In cases of fluid retention, increased blood pressure, and edema have been reported with ketorolac.

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

The concomitant use of ketorolac with other NSAIDs may result in abnormalities such as decompensation of heart failure and increased blood pressure.

According to clinical studies, use of some NSAIDs in high doses may increase the risk of arterial thrombotic complications (e.g., myocardial infarction, stroke). Although no such complications have been reported with ketorolac, there is insufficient data to rule out a risk of these complications.

The use of antacids, misoprostol, and drugs that reduce gastric secretion (histamine H-receptor blockers, proton pump inhibitors) is recommended to reduce the risk of NSAID-induced gastropathy. The lowest effective dose of ketorolac should be used in as short a course as possible to reduce the risk of adverse events.

Influence on driving and operating ability

. During the treatment period central nervous system side effects may occur (somnolence, dizziness, headache), which reduces the speed of mental and motor reactions, and therefore it is necessary to refrain from driving vehicles and carrying out other potentially dangerous activities, which require high concentration and quick psychomotor reactions.

Synopsis

The tablets are blue with flecks, flat, round, with a beveled edge, engraved “K17” on one side and smooth on the other.

Contraindications

• Hypersensitivity (including to other non-steroidal anti-inflammatory drugs);
• Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and sinuses, and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including a history);
• Errotic ulcerative lesions of the gastrointestinal tract, active gastrointestinal bleeding, inflammatory bowel disease (including ulcerative colitis, Crohn’s disease);
• Severe renal failure (creatinine clearance below 30 ml/min).
• Severe hepatic insufficiency;
• Acute diseases or conditions accompanied by liver dysfunction or exacerbation of chronic liver disease;
• Thyroid disease;
• Confirmed hyperkalemia;
• Acute myocardial infarction;
• Acute cerebral circulatory disorders (ischemic, hemorrhagic stroke);
• Bone marrow diseasesBone marrow and blood diseases (leukopenia, including in anamnesis, thrombocytopenia, conditions accompanied by hypocoagulation, including hemophilia), myelosuppression;
• Exposed myopathy, myasthenia;
• Pregnancy, breastfeeding period;
• Childhood (under 16 years);
• Simultaneous use with probenecid;
• Simultaneous use with pentoxifylline;
• Simultaneous use with acetylline.Concurrent use with acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (including cyclooxygenase-2 inhibitors);
• Combined use with lithium salts;
• Combined use with anticoagulants (including warfarin and heparin).

The drug is not used:

Preventive analgesia before and during major surgical procedures because of the high risk of bleeding.

– for the treatment of chronic pain.

With caution

. Gastric and duodenal ulcer, ulcerative colitis, Crohn’s disease, liver disease in the history, hepatic porphyria, chronic renal failure (creatinine clearance 30-60 ml/min), chronic heart failure, arterial hypertension, significant reduction in circulating blood volume (including after surgical intervention), elderly patients over 65 years (including those receiving diuretics, impaired and underweight patients), bronchial asthma, concurrent use of glucocorticosteroids (including prednisolone), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), coronary heart disease, cerebrovascular disease, dyslipidemia/hyperlipidemia, diabetes, peripheral arterial disease, smoking, presence of infection Helicobacter pylori infection, long-term use of nonsteroidal anti-inflammatory drugs, tuberculosis, severe osteoporosis, alcoholism, severe somatic diseases, hypotension, hypertension.

Side effects

In terms of frequency, side effects are divided according to WHO criteria into the following categories: very frequently (≥ 1: 10); frequently (≥ 1: 100 and < 1: 10); infrequently

(≥ 1: 1000 and < 1: 100); rare (≥ 1: 10000 and < 1: 1000); very rare (< 1: 10000), frequency unknown (frequency cannot be estimated from available data).

Disorders of the digestive system

Frequently (especially in elderly patients over 65 years with a history of erosive ulcers of the gastrointestinal tract) – gastralgia, diarrhea; infrequent – stomatitis, flatulence, constipation, vomiting, feeling of fullness of stomach; rarely – nausea, erosive-ulcerative lesions of the gastrointestinal tract (includingincluding with perforation [severe abdominal pain] and bleeding [coffee grounds type vomiting, melena]), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis.

Since 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 daily diuresis, nephritis, edema of renal genesis.

Sensory organs

Rarely – decreased hearing, tinnitus, visual disturbances (including blurred vision); frequency unknown – impaired taste.

Involved respiratory system

Rarely – bronchospasm, dyspnea, shortness of breath, rhinitis, laryngeal edema

From the central nervous system

Often – headache, dizziness, somnolence; rarely – aseptic meningitis (fever, severe headache, cramps, neck and/or back muscle stiffness), hyperactivity, mood changes, anxiety, hallucinations, depression, psychosis.

Cardiovascular system

Infrequent – increased blood pressure; rarely – pulmonary edema, syncopal conditions.

Hematopoietic organs

Rarely – anemia, eosinophilia, leukopenia.

Hemostatic system disorders

Rarely – bleeding from the postoperative wound, nasal bleeding, rectal bleeding.

Skin side

Infrequent – skin rash (including maculopapular rash), purpura; Infrequent – exfoliative dermatitis (fever with or without chills, redness, thickening or peeling of the skin, swelling and/or pain of the palatine tonsils), urticaria, Stevens-Johnson syndrome, Lyell syndrome.

Allergic reactions

Rarely – anaphylaxis, anaphylactoid reactions (skin hyperemia, rash, urticaria, skin itching, shortness of breath, difficulty breathing, angioedema).

Other disorders

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

Overdose

Symptoms: abdominal pain, nausea, vomiting, erosive and ulcerative damage of the gastrointestinal tract (including the development of peptic stomach ulcers; erosive gastritis), impaired renal function, metabolic acidosis.

The treatment: gastric lavage, administration of adsorbents (activated charcoal) and symptomatic therapy (maintenance of vital body functions).

Hemodialysis is ineffective.

Pregnancy use

Pregnancy

The use of the drug during pregnancy is contraindicated. The safety of using the drug during pregnancy has not been established. The use during the third trimester of pregnancy of drugs that disrupt prostaglandin synthesis may cause premature closure of the fetal arterial (Botall’s) duct, weakened uterine contractility with delayed labor activity. Both the mother and the baby have an increased risk of bleeding.

Period of breastfeeding

The use of the drug during breastfeeding is contraindicated. Ketorolac penetrates into the breast milk.

The use of ketorolac during breastfeeding is contraindicated.

Similarities

Dolac, Ketorol, Ketonov, Ketorolac, Ketorolac Rompharm