Ketofril, 10 mg 20 pcs.

Pharmacotherapeutic group: Non-steroidal anti-inflammatory drug (NSAID)

ATX code: [M01AB15]

Pharmacological action

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

The drug does not influence opioid receptors, does not suppress respiration, does not cause drug addiction and has no sedative and anxiolytic action.

In terms of the analgesic effect, it is comparable with morphine and is considerably superior to other NSAIDs. After oral administration the onset of analgesic effect is noted respectively in 1 hour, the maximum effect is reached after 1-2 hours.

Pharmacokinetics

On oral administration Ketorolac is well absorbed in the gastrointestinal tract – maximum concentration (Cmax) in blood plasma (0.7-1.1 mcg/ml) is reached 40 min after an empty stomach dose of 10 mg. 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 plasma proteins and in case of hypoalbuminemia the amount of free substance in blood increases.

The bioavailability is 80-100%. Time of reaching equilibrium concentration (Css) by oral administration – 24 hours when administered 4 times a day (higher than subtherapeutic) and is 0.39-0.79 mcg/ml after 10 mg oral administration. 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%.

Transfers to 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 h after the second dose of ketorolac (when the drug is used 4 times a day) it 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 91% by the kidneys, 6% – through the intestine.

The half-life (T½ in patients with normal renal function is on average 5.3 h. T½ is longer in older patients and shorter in younger patients. Liver function has no effect on T½ In patients with impaired renal function with plasma creatinine concentration of 19-50 mg/l (168-442 μmol/l) T½ is 10.3-10.8 hours, in more severe renal insufficiency – more than 13.6 hours. It is not excreted during hemodialysis.

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Indications

Pain syndrome of moderate and severe intensity of different genesis (including in the postoperative period, in cancer, etc.)

Active ingredient

Ketorolac

Composition

One tablet contains:

Active ingredient: ketorolaca trometamol (ketorolaca trometamine) – 10 mg

Excipients (core): microcrystalline cellulose, anhydrous lactose, sodium carboxymethyl starch, colloidal silicon dioxide, magnesium stearate.

Excipients (coating): hypromellose. talc, titanium dioxide, macrogol, colloidal silicon dioxide.

How to take, the dosage

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

Interaction

Concomitant use of ketorolac with acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs, calcium preparations, glucocorticosteroids, ethanol, corticotropin may lead to gastrointestinal ulcers and development of gastrointestinal bleeding.

Co-administration with paracetamol increases nephrotoxicity, with methotrexate – hepato- and nephrotoxicity. Co-administration 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 distribution volume of ketorolac, increases its plasma concentration and prolongs its half-life.

Against the background of ketorolac use, methotrexate and lithium clearance may decrease and their toxicity increases.

Simultaneous use with indirect anticoagulants, heparin, thrombolytics, antiaggregants, cefoperazone, cefotetan and pentoxifylline increases the risk of bleeding.

Reduces the effect of hypotensive and diuretic drugs (decreases the synthesis of prostaglandins in the kidneys).

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

Antacids do not affect the completeness of absorption of the drug. Hypoglycemic effect of insulin and oral hypoglycemic agents increases (requires recalculation of the dose).

Co-administration with valproic acid causes platelet aggregation disorders.

Increases the concentration in plasma of verapamil and nifedipine.

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

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

Special Instructions

Effect on platelet aggregation stops after 24-48 hours.

Hypovolemia increases the risk of adverse reactions from the kidneys. If necessary, can be administered in combination with narcotic analgesics.

Do not use simultaneously with paracetamol for more than 5 days. The drug is administered to patients with blood coagulation disorders only with continuous monitoring of platelet count, especially important in the postoperative period, which requires close monitoring of hemostasis. Since a significant proportion of patients with ketorolac have side effects on the central nervous system (drowsiness, dizziness, headache), it is recommended to avoid work that requires increased attention and rapid reaction time (driving, working with machinery, etc.).

Contraindications

Hypersensitivity to the active substance or excipients; anamnestic, evidence of an attack of bronchoobstruction, rhinitis, urticaria after taking acetylsalicylic acid or other NSAIDs (complete or incomplete acetylsalicylic acid intolerance syndrome – rhinosinusitis, urticaria, nasal polyps, bronchial asthma); angioedema, hypovolemia (regardless of its cause), dehydration.

Erotic ulcerative changes of the mucosa of the stomach or 12 duodenum, active gastrointestinal bleeding; inflammatory bowel disease; hypocoagulation (including hemophilia).

Developed hepatic insufficiency or active liver disease; marked renal insufficiency (plasma creatinine above 50 mg/l), advanced renal disease; confirmed hyperkalemia.

Hemorrhagic stroke (confirmed or suspected), hemorrhagic diathesis, concomitant use with other NSAIDs, high risk of development or recurrence of bleeding (including after surgery), hematopoiesis disorders.

Pregnancy, childbirth and lactation.

Children under 16 years of age (effectiveness and safety not established).

The period after aortocoronary bypass surgery;

The drug is not used for pain relief before and during surgical procedures because of the high risk of bleeding, and for the treatment of chronic pain.

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

Anamnestic evidence of gastrointestinal ulcers, Helicobacter pylori infection, long-term use of NSAIDs, frequent use of alcohol, severe somatic diseases, concomitant therapy with the following drugs:

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

To reduce the risk of gastrointestinal adverse events, use the lowest effective dose with the shortest possible course.

Side effects

Often – more than 3%, less often -1-3%, rarely – less than 1%.

The digestive system: often (especially in elderly patients over 65 years old with a history of gastrointestinal erosive ulcers) – gastralgia, diarrhea; less frequently – stomatitis, flatulence, constipation, vomiting, feeling of fullness of the stomach; rarely – nausea, erosive-ulcerative lesions of the gastrointestinal tract (including perforation and/ or bleeding – abdominal pain, spasm or burning of the epigastric region.with perforation and/or bleeding – abdominal pain, epigastric spasm or burning, melena, “coffee grounds” type vomiting, nausea, heartburn, etc.), cholestatic jaundice, hepatitis, hepatomegaly, acute pancreatitis.

Urinary system: rare – acute renal failure, pain in the lower back with or without hematuria and/or azotemia, hemolytic-uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura), frequent urination, increased or decreased volume of urine, nephritis, edema of renal genesis.

Senses: rare: decreased hearing, tinnitus, visual impairment (including blurred vision).

Respiratory system: rare: bronchospasm or dyspnea, rhinitis, laryngeal edema (shortness of breath, difficulty in breathing).

CNS: often – headache, dizziness, somnolence, rarely – aseptic meningitis (fever, severe headache, seizures, neck and/or back stiffness), hyperactivity (mood changes, anxiety), hallucinations, depression, psychosis.

Cardio-vascular system: less frequently – BP increase, rarely – pulmonary edema, fainting.

Blood organs: rarely – anemia, eosinophilia, leukopenia.

The hemostatic system: rare – bleeding from the post-operative wound, nasal bleeding, rectal bleeding.

Skin: less frequently – skin rash (including maculopapular rash), purpura, rarely – exfoliative dermatitis (fever with or without chills, redness, thickening or peeling of the skin, swollen and/or painful palatine tonsils) urticaria, Stevens-Johnson syndrome, Lyell syndrome.

Allergic reactions: rare – anaphylaxis or anaphylactoid reactions (changes in skin color, skin rash, urticaria, itching, tachypnea or dyspnea, edema of eyelids, periorbital edema, shortness of breath, difficulty in breathing, heaviness in the chest, wheezing).

Other: often – edema (face, shins, ankles, fingers, feet, weight gain); less often – increased sweating, rarely – tongue swelling, fever.

Overdose

Symptoms: abdominal pain, nausea, vomiting, occurrence of peptic stomach ulcers or erosive gastritis, impaired renal function, metabolic acidosis.

Treatment: gastric lavage, administration of adsorbents (activated carbon) and symptomatic therapy (maintenance of vital body functions). Not sufficiently eliminated by dialysis.

Similarities

Dolac, Ketorol, Ketonov, Ketorolac, Ketorolac Rompharm