Ketokam (Tablets) Instructions for Use

Marketing Authorization Holder

Simpex Pharma, Pvt. Ltd. (India)

ATC Code

M01AB15 (Ketorolac)

Active Substance

Ketorolac (Rec.INN registered by WHO)

Dosage Form

Ketokam

Film-coated tablets 10 mg: 10, 20, 100, 200, or 1000 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blisters (1) – carton packs.
10 pcs. – blisters (2) – carton packs.
10 pcs. – blisters (10) – carton packs.
10 pcs. – blisters (10) – group packaging.
10 pcs. – blisters (20) – group packaging.
10 pcs. – blisters (100) – group packaging.

Clinical-Pharmacological Group

NSAIDs with pronounced analgesic action

Pharmacotherapeutic Group

Anti-inflammatory and antirheumatic agents; non-steroidal anti-inflammatory and antirheumatic agents; acetic acid derivatives and related substances

Pharmacological Action

NSAID, has a pronounced analgesic effect, also has anti-inflammatory and moderate antipyretic effects.

The mechanism of action is associated with non-selective inhibition of the activity of COX-1 and COX-2 enzymes, mainly in peripheral tissues, resulting in inhibition of the biosynthesis of prostaglandins – modulators of pain sensitivity, inflammation and thermoregulation. Ketorolac is a racemic mixture of R(+) and S(-)-enantiomers, with the analgesic effect due to the S(-)-enantiomer.

Ketorolac does not affect opioid receptors, does not depress respiration, does not cause drug dependence, and does not have sedative or anxiolytic effects.

In terms of the strength of the analgesic effect, it is comparable to morphine and significantly exceeds other NSAIDs.

After oral administration, the onset of analgesic (pain-relieving) action is noted after 1 hour, respectively, the maximum effect is achieved after 2-3 hours.

Pharmacokinetics

When taken orally, Ketorolac is well absorbed from the gastrointestinal tract. Bioavailability is 80-100%. C_max in blood plasma is 0.7-1.1 µg/ml and is reached 40 minutes after taking the drug on an empty stomach at a dose of 10 mg. Food rich in fats reduces the C_max of ketorolac in the blood and delays its achievement by 1 hour.

Binding to blood plasma proteins is 99%. In hypoalbuminemia, the amount of free substance in the blood increases.

V_d is 0.15-0.33 l/kg.

The time to reach C_ss when taken orally is 24 hours when used 4 times/day (above subtherapeutic). C_ss after oral administration at a dose of 10 mg is 0.39-0.79 µg/ml.

It poorly passes through the blood-brain barrier, penetrates the placental barrier (10%).

Excreted in breast milk: when the mother takes 10 mg of ketorolac orally, C_max in breast milk is reached 2 hours after taking the first dose and is 7.3 ng/ml, 2 hours after taking the second dose of ketorolac (when using the drug 4 times/day) C_max 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 and p-hydroxyketorolac.

Excreted in urine – 91% (40% as metabolites), in feces – 6%. It is not excreted by hemodialysis.

After oral administration, T_1/2 in patients with normal renal function is 2.4-9 hours (on average 5.3 hours).

In patients with renal failure, the V_d of ketorolac may double, and the V_d of its R-enantiomer may increase by 20%. In patients with impaired renal function with plasma creatinine concentration of 19-50 mg/l (168-442 µmol/l), T_1/2 is 10.3-10.8 hours, with more severe renal failure – more than 13.6 hours.

Liver function does not affect T_1/2.

Indications

Pain syndrome of severe and moderate intensity: injuries, toothache, pain in the postoperative period, oncological diseases, myalgia, arthralgia, neuralgia, radiculitis, dislocations, sprains, rheumatic diseases.

Intended for symptomatic therapy, reducing pain and inflammation at the time of use, does not affect the progression of the disease.

ICD codes

Dosage Regimen

Set individually, depending on the severity of the pain syndrome. Ketorolac should be taken orally as a single dose or repeatedly. A single dose is 10 mg; when taken repeatedly, it is recommended to take 10 mg up to 4 times/day, depending on the severity of the pain. The maximum daily dose should not exceed 40 mg. When taken orally, the duration of the course should not exceed 5 days.

When switching from parenteral administration to oral administration, the total daily dose of ketorolac in both dosage forms on the day of transition should not exceed: 90 mg for adults under 65 years of age and children over 16 years of age, and 60 mg for elderly patients over 65 years of age or with impaired renal function. In this case, the dose of ketorolac for oral administration on the day of transition should not exceed 30 mg.

Adverse Reactions

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

From the urinary system: rarely – acute renal failure, lower back pain, hematuria, azotemia, hemolytic-uremic syndrome (hemolytic anemia, renal failure, thrombocytopenia, purpura), frequent urination, increase or decrease in urine volume, nephritis, edema of renal origin.

From the nervous system: often – headache, dizziness, drowsiness; rarely – aseptic meningitis (including fever, severe headache, convulsions, rigidity of the neck and/or back muscles), hyperactivity (including mood changes, anxiety), hallucinations, depression, psychosis.

From the cardiovascular system: less often – increased blood pressure; rarely – fainting.

From the respiratory system: rarely – bronchospasm, dyspnea, rhinitis, pulmonary edema, laryngeal edema (including shortness of breath, difficulty breathing).

From the sensory organs rarely – hearing loss, ringing in the ears, visual impairment (including blurred vision).

From the hematopoietic system: rarely – anemia, eosinophilia, leukopenia.

From the blood coagulation system rarely – bleeding from the postoperative wound, nosebleed, rectal bleeding.

From the skin and subcutaneous tissues less often – skin rash (including maculopapular), purpura; rarely – exfoliative dermatitis (including fever with/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 or anaphylactoid reactions (including facial skin discoloration, skin rash, urticaria, skin itching, tachypnea or dyspnea, swelling of the eyelids, periorbital edema, shortness of breath, difficulty breathing, chest tightness, wheezing).

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

Contraindications

Hypersensitivity to ketorolac and other NSAIDs; complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in history); urticaria, rhinitis caused by taking NSAIDs (in history); intolerance to drugs of the pyrazolone series; dehydration, hypovolemia (regardless of the cause); bleeding or high risk of their development; condition after coronary artery bypass surgery; confirmed hyperkalemia; inflammatory bowel diseases; erosive and ulcerative lesions of the gastrointestinal tract in the acute stage, peptic ulcers; hypocoagulation (including hemophilia); severe renal failure (creatinine clearance less than 30 ml/min); severe hepatic failure or active liver disease; hemorrhagic stroke (confirmed or suspected); hemorrhagic diathesis; impaired hematopoiesis; pregnancy; childbirth; lactation period (breastfeeding); children under 16 years of age (efficacy and safety have not been established).

Not used as a means for premedication, maintenance anesthesia, pain relief before and during surgical operations (including in obstetric practice) due to the high risk of bleeding.

Not indicated for the treatment of chronic pain.

With caution

Bronchial asthma; cholecystitis; chronic heart failure; arterial hypertension; impaired renal function (plasma creatinine below 50 mg/l); cholestasis; active hepatitis; sepsis; systemic lupus erythematosus; elderly age (over 65 years); polyps of the nasal mucosa and nasopharynx, simultaneous use with other NSAIDs; presence of factors that increase gastrointestinal toxicity: alcoholism, tobacco smoking; postoperative period, edematous syndrome, coronary artery disease, cerebrovascular diseases, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral artery diseases, creatinine clearance less than 60 ml/min, history of ulcerative lesions of the gastrointestinal tract, presence of Helicobacter pylori infection, long-term use of NSAIDs, severe somatic diseases, simultaneous use of oral glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline).

Use in Pregnancy and Lactation

The use of ketorolac is contraindicated during pregnancy and during childbirth, and during the period of breastfeeding.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency.

Should be used with caution in cholecystitis, cholestasis, active hepatitis.

Use in Renal Impairment

Contraindicated in renal failure (plasma creatinine >50 mg/l).

Should be used with caution in impaired renal function (plasma creatinine < 50 mg/l).

Pediatric Use

Contraindicated in children and adolescents under 16 years of age (efficacy and safety have not been established).

Geriatric Use

Should be used with caution in elderly patients (over 65 years of age).

Special Precautions

When used concomitantly with other NSAIDs, fluid retention, decompensation of cardiac activity, and arterial hypertension may be observed.

To reduce the risk of developing NSAID gastropathy, antacids, misoprostol, and omeprazole are prescribed.

The effect on platelet aggregation persists for 24-48 hours.

Hypovolemia increases the risk of adverse reactions from the kidneys.

If necessary, it can be prescribed in combination with opioid analgesics.

Do not use simultaneously with paracetamol for more than 5 days.

In patients with bleeding disorders, use only with constant monitoring of platelet count, especially in the postoperative period, requiring careful monitoring of hemostasis.

Effect on ability to drive vehicles and mechanisms

Since a significant proportion of patients develop side effects from the central nervous system (drowsiness, dizziness, headache) when using ketorolac, it is recommended to avoid performing work that requires increased attention and quick reactions (driving vehicles, working with mechanisms).

Drug Interactions

Simultaneous use of ketorolac with acetylsalicylic acid or other NSAIDs, calcium preparations, glucocorticosteroids, ethanol, corticotropin can lead to the formation of gastrointestinal ulcers and the development of gastrointestinal bleeding.

Concomitant use with paracetamol increases nephrotoxicity, with methotrexate – hepato- and nephrotoxicity.

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

Against the background of ketorolac use, a decrease in the clearance of methotrexate and lithium and an increase in the toxicity of these substances are possible.

Simultaneous administration with indirect anticoagulants, heparin, thrombolytics, antiplatelet agents, cefoperazone, cefotetan and pentoxifylline increases the risk of bleeding.

Reduces the effect of antihypertensive and diuretic drugs (synthesis of prostaglandins in the kidneys is reduced).

When used simultaneously with opioid analgesics, the doses of the latter can be significantly reduced, as their effect is enhanced.

When used simultaneously, it enhances the hypoglycemic effect of insulin and oral hypoglycemic drugs (dose recalculation is necessary).

Concomitant use with valproic acid causes impaired platelet aggregation.

Increases the concentration of verapamil and nifedipine in blood plasma.

When prescribed with other nephrotoxic drugs (including gold preparations), the risk of nephrotoxicity increases.

Probenecid and drugs that block tubular secretion reduce the clearance of ketorolac and increase its concentration in blood plasma.

Myelotoxic drugs enhance the manifestations of hematotoxicity of ketorolac.

Pharmaceutically incompatible with tramadol solution, lithium preparations.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.