Ketanov MD oral dispersible pills 10mg, 20pcs

Composition

One tablet contains:

Active ingredient:

Ketorolac trometamol 10.00 mg

Auxiliary substances:

Mannitol* 115.56 mg

Microcrystalline Cellulose (Avicel PH 112) 18.00 mg

Corn starch 18,00 mg

Aspartame 3.60 mg

Crospovidone 9.00 mg

Propyl Gallate 0.50 mg

Indigo carmine dye 3.00 mg

Peppermint flavor 0.54 mg

Magnesium stearate 1.80 mg

* The amount is regulated taking into account the actual content of ketorolac trometamol to maintain a constant value of “tablet weight”

Pharmacological action

Pharmacotherapy group: nonsteroidal anti-inflammatory drug.

ATX Code: M01AB15

Pharmacological properties

Pharmacodynamics

Nonsteroidal anti-inflammatory drug (NSAID), 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 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 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 use, the onset of analgesic action is noted, respectively, after 1 h, the maximum effect is achieved in 1-2 h

. Pharmacokinetics

After oral use, ketorolac is well absorbed in the gastrointestinal tract – the maximum concentration (Withmgax) in blood plasma (0.7-1.1 mcg / ml) is reached in 0.4 hours after taking 10 mg of ketorolac in the dosage form of tablets dispersed in the oral cavity on an empty stomach. High-fat food reduces the maximum concentration of the drug in the blood and delays its achievement by 1 h. 99% of the drug binds to plasma proteins, with hypoalbuminemia, the amount of free substance in the blood increases. Bioavailability – 80-100%. The time to reach the equilibrium concentration-C_ss (0.39-0.79 mcg / ml), with oral use of 10 mg of ketorolac 4 times a day (the dose is higher than the subtherapeutic one), is 24 hours.

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 10 mg of ketorolac_{, max} in breast milk is reached in 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 intestines (6%).

The elimination half-life (T_1/2) in patients with normal renal function is 2.4-9 hours after oral use of a dose of 10 mg. T_1/2 is prolonged in elderly patients and shortened in young patients. Impaired 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) T_1/2 is 10.3-10.8 hours, with more severe renal failure – more than 13.6 hours.

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

It is not excreted during hemodialysis.

Indications

Pain syndrome of moderate and severe intensity of various genesis. It is intended for symptomatic therapy, reducing the intensity of pain and inflammation at the time of application, and does not affect the progression of the disease.

Use during pregnancy and lactation

Pregnancy

The use of the drug during pregnancy is contraindicated. The safety of using this drug during pregnancy has not been established. The use of drugs that disrupt prostaglandin synthesis during the third trimester of pregnancy can cause premature closure of the arterial (Botall) duct in the fetus, weakening of the contractility of the uterus with a slowdown in labor. Both the mother and child have an increased risk of bleeding.

Breast-feeding period

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

The use of ketorolac during breastfeeding is contraindicated.

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, active gastrointestinal bleeding, inflammatory bowel diseases (including ulcerative colitis, Crohn’s disease);
• Severe renal insufficiency (creatinine clearance below 30 ml / min).
• Severe liver failure;
• Acute diseases or conditions accompanied by impaired liver function or exacerbation of chronic liver diseases;
• 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, conditions accompanied by hypocoagulation, including 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

Gastric ulcer and duodenal ulcer, ulcerative colitis, Crohn’s disease, liver disease, a history of hepatic porphyria, chronic renal failure (creatinine clearance 30-60 ml/min), chronic heart failure, arterial hypertension, a significant decrease of circulating blood volume (including after surgery), elderly patients older than 65 years (including receiving diuretics, debilitated patients and those with a low body weight), bronchial asthma, concomitant use of corticosteroids (including prednisone), selective inhibitors of serotonin reuptake (including citalopram, fluoxetine, paroxetine, and sertraline), ischemic heart disease, cerebrovascular disease, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral artery disease, Smoking, infection with Helicobacter pylori, long-term use of nonsteroidal anti-inflammatory drugs, tuberculosis, severe osteoporosis, alcoholism, severe somatic disease, hypotension, hypertension.

Side effects

The frequency of side effects is divided according to the who criteria as follows: very often (≥ 1: 10); often (≥ 1: 100 and <1: 10); infrequently

(≥ 1: 1000 and <1: 100); rare (≥ 1: 10000 and <1: 1000); very rare (<1: 10000), the unknown frequency (frequency cannot be assessed according to the 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 [sharp pain in the abdomen] and bleeding [type vomiting “coffee grounds”, melena]), 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 daily diuresis, nephritis, edema of renal origin.

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, dyspnoea, shortness of breath, rhinitis, laryngeal edema

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, syncopal states.

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

Other disorders

Often – 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 nonsteroidal 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. Simultaneous use 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.

Concomitant use with indirect anticoagulants, heparin, thrombolytics, antiplatelet agents, cefoperazone, cefotetane and pentoxifylline increases the risk of bleeding. Concomitant use with anticoagulants (including warfarin and heparin) and pentoxifylline is contraindicated. 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 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. The simultaneous use of lithium salts and certain drugs that inhibit prostaglandin synthesis 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, as the effect of mifepristone may decrease.

How to take, course of use and dosage

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

Keep the tablet in your mouth for several seconds until the tablet is completely dissolved, after which, if necessary, the drug can be washed down with water. Taking tablets dispersed in the oral cavity does not require mandatory washing down with water.

A single dose is 10 mg (1 tablet), with repeated use it is recommended to take 10 mg. It is allowed 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 should not exceed 40 mg.

The duration of use of the drug 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.

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

Overdose

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

Treatment: gastric lavage, use of adsorbents (activated charcoal) and symptomatic therapy (maintenance of vital body functions).

Hemodialysis is ineffective.

Description

Tablets are blue in color, interspersed, flat, round, with a beveled edge, with the inscription “K 17” on one side and smooth on the other.

Special instructions

Before using the drug, it is necessary to clarify the question of possible allergies in the anamnesis when using drugs containing ketorolac or other NSAIDs. Due to the possible 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 adverse reactions from the kidneys.

If necessary, the drug can be used in combination with narcotic analgesics.

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 prolongation of the course of treatment and increasing the dose of ketorolac more than 40 mg / day.

It is contraindicated to use ketorolac for preventive pain relief before and during extensive surgical interventions due to the high risk of bleeding.

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 (histamine H-receptor blockers, 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 may develop (drowsiness, dizziness, headache), 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.

Form of production

Tablets dispersed in the oral cavity,10 mg.

10 tablets in a blister of OPA/AL/PVC foil and AL foil.

1 or 2 blisters together with the instructions for use in a cardboard pack.

Storage conditions

At a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 4 years. Do not use after the expiration date.

Active ingredient

Ketorolac

Conditions of release from pharmacies

Prescription