Ketoprovel (Tablets) Instructions for Use

Marketing Authorization Holder

Velpharm, LLC (Russia)

ATC Code

M01AE03 (Ketoprofen)

Active Substance

Ketoprofen (Rec.INN registered by WHO)

Dosage Form

Ketoprovel

Film-coated tablets 100 mg: 10, 20, 30, or 50 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white or almost white, round, biconvex; the core on the cross-section is white or almost white.

Excipients: hyprolose (hydroxypropylcellulose), mannitol (mannite), croscarmellose sodium (primellose), microcrystalline cellulose, colloidal silicon dioxide (aerosil), magnesium stearate.

Film coating composition: Opadry 03F180011 white (hypromellose, titanium dioxide, macrogol)

10 pcs. – blister packs (PVC/aluminum foil) (1) – cardboard packs.
10 pcs. – blister packs (PVC/aluminum foil) (2) – cardboard packs.
10 pcs. – blister packs (PVC/aluminum foil) (3) – cardboard packs.
10 pcs. – blister packs (PVC/aluminum foil) (5) – cardboard packs.
10 pcs. – polymer jars (1) – cardboard packs.
20 pcs. – polymer jars (1) – cardboard packs.
30 pcs. – polymer jars (1) – cardboard packs.
50 pcs. – polymer jars (1) – cardboard packs.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

Anti-inflammatory and antirheumatic drugs; non-steroidal anti-inflammatory and antirheumatic drugs; propionic acid derivatives

Pharmacological Action

NSAID. It has anti-inflammatory, analgesic, and antipyretic effects. Ketoprofen blocks the action of the enzyme COX-1 and COX-2 and, partially, lipoxygenase, which leads to the suppression of prostaglandin synthesis (including in the CNS, most likely in the hypothalamus).

It stabilizes lysosomal membranes in vitro and in vivo, and at high concentrations in vitro suppresses the synthesis of bradykinin and leukotrienes. Ketoprofen does not have a negative effect on the condition of the articular cartilage.

Pharmacokinetics

When taken orally, Ketoprofen is rapidly absorbed from the gastrointestinal tract. Bioavailability is 90%. At a dose of 100 mg in the immediate-release dosage form, the C_max in blood plasma is 10.4 µg/ml and is reached after 1 hour 22 minutes.

The binding of ketoprofen to blood plasma proteins is 99%, mainly to the albumin fraction. V_d is 0.1 l/kg. Ketoprofen penetrates into the synovial fluid and after oral administration reaches a concentration there equal to 30% of the concentration in the blood plasma. C_ss of ketoprofen in blood plasma is determined even 24 hours after its administration.

Ketoprofen undergoes intensive metabolism under the action of liver microsomal enzymes. T_1/2 is less than 2 hours. Ketoprofen binds to glucuronic acid and is excreted from the body as a glucuronide. There are no active metabolites of ketoprofen. Up to 80% of ketoprofen is excreted by the kidneys within 24 hours, mainly in the form of ketoprofen glucuronide.

Indications

Symptomatic treatment of pain syndrome, including in inflammatory processes of various origins: rheumatoid arthritis; seronegative arthritis: ankylosing spondylitis (Bekhterev’s disease), psoriatic arthritis, reactive arthritis (Reiter’s syndrome); gout, pseudogout; degenerative diseases of the musculoskeletal system, including osteoarthritis; mild, moderate, and severe pain syndrome in headache, migraine, tendinitis, bursitis, myalgia, neuralgia, radiculitis; post-traumatic and postoperative pain syndrome, including accompanied by inflammation and fever; pain syndrome in oncological diseases; algodysmenorrhea.

ICD codes

Dosage Regimen

Determine the dosage individually based on the indication, severity of symptoms, and patient response.

For adults, the typical oral dose is 100 mg to 200 mg per day, administered in two or three divided doses.

Initiate therapy at the lowest effective dose for the shortest possible duration to control symptoms.

For chronic conditions like rheumatoid arthritis or osteoarthritis, a maintenance dose of 100 mg to 150 mg daily is often sufficient.

For acute pain or dysmenorrhea, take a single 100 mg dose as needed; the maximum single dose is 100 mg.

Do not exceed the maximum daily dose of 200 mg.

Swallow the tablet whole with a sufficient amount of liquid; take during or after meals to minimize gastrointestinal irritation.

In elderly patients and those with renal or hepatic impairment, use a reduced dose and monitor closely.

Avoid use in patients with severe renal impairment (creatinine clearance less than 30 ml/min) or severe hepatic impairment.

Regularly reassess the need for continued therapy, especially during long-term treatment.

Adverse Reactions

From the hematopoietic system rarely – hemorrhagic anemia, hemolytic anemia, leukopenia; frequency unknown – agranulocytosis, thrombocytopenia, bone marrow dysfunction.

From the immune system frequency unknown – anaphylactic reactions (including anaphylactic shock).

From the nervous system often – insomnia, depression, asthenia; infrequently – headache, dizziness, drowsiness; rarely – paresthesia, confusion or loss of consciousness, peripheral polyneuropathy; frequency unknown – convulsions, taste disturbance, emotional lability.

From the sensory organs rarely – blurred vision, tinnitus, conjunctivitis, dryness of the eye mucosa, eye pain, hearing loss; frequency unknown – optic neuritis.

From the cardiovascular system infrequently – tachycardia; frequency unknown – heart failure, increased blood pressure, vasodilation.

From the respiratory system rarely – exacerbation of bronchial asthma, nosebleeds, laryngeal edema; frequency unknown – bronchospasm (especially in patients with hypersensitivity to NSAIDs), rhinitis.

From the digestive system often – nausea, vomiting, dyspepsia, abdominal pain, NSAID-gastropathy; infrequently – constipation, diarrhea, flatulence, gastritis; rarely – peptic ulcer, stomatitis; very rarely – exacerbation of ulcerative colitis or Crohn’s disease, gingival, gastrointestinal, hemorrhoidal bleeding, melena, perforation of gastrointestinal organs; frequency unknown – gastrointestinal discomfort, stomach pain.

From the liver and biliary tract rarely – hepatitis, increased activity of liver enzymes in the blood, increased concentration of bilirubin in the blood.

From the urinary system rarely – cystitis, urethritis, hematuria; very rarely – acute renal failure, interstitial nephritis, nephrotic syndrome, abnormal values of kidney function indicators.

From the skin and subcutaneous tissues infrequently – skin rash, skin itching; frequency unknown – photosensitivity, alopecia, urticaria, exacerbation of chronic urticaria, angioedema, erythema, bullous rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis, purpura.

Other infrequently – peripheral edema, fatigue; rarely – hemoptysis, menometrorrhagia, dyspnea, thirst, muscle twitching.

Contraindications

Hypersensitivity to ketoprofen, as well as to salicylates or 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); peptic ulcer of the stomach or duodenum in the acute phase; ulcerative colitis, Crohn’s disease; hemophilia and other bleeding disorders; severe hepatic insufficiency; severe renal insufficiency (creatinine clearance less than 30 ml/min), confirmed hyperkalemia, progressive kidney diseases; decompensated heart failure; postoperative period after coronary artery bypass surgery; gastrointestinal, cerebrovascular and other bleedings (or suspicion of bleeding); chronic dyspepsia; III trimester of pregnancy; breastfeeding period; children and adolescents under 15 years of age.

With caution

History of peptic ulcer, presence of Helicobacter pylori infection; history of bronchial asthma; clinically significant cardiovascular, cerebrovascular diseases and peripheral artery diseases; dyslipidemia; moderate hepatic insufficiency, hyperbilirubinemia, alcoholic cirrhosis of the liver; chronic renal insufficiency (creatinine clearance 30-60 ml/min); chronic heart failure (NYHA class II-IV); arterial hypertension; blood diseases; dehydration; diabetes mellitus; smoking; elderly age; long-term use of NSAIDs, simultaneous use of anticoagulants (including warfarin), antiplatelet agents (including clopidogrel), oral glucocorticosteroids (including prednisolone), selective serotonin reuptake inhibitors (including fluoxetine, paroxetine, citalopram, sertraline).

Use in Pregnancy and Lactation

Use is contraindicated in the III trimester of pregnancy. Use in the I and II trimesters of pregnancy is possible only if the expected benefit of therapy for the mother outweighs the existing risk to the fetus. In this case, Ketoprofen should be used in the minimum effective dose for the shortest possible course.

Use is contraindicated during breastfeeding.

The use of ketoprofen may affect female fertility, therefore it is not recommended for use in patients with infertility (including those undergoing examination).

Use in Hepatic Impairment

Use is contraindicated in severe hepatic impairment.

Should be used with caution in hepatic impairment, hyperbilirubinemia, alcoholic cirrhosis of the liver.

Use in Renal Impairment

Use is contraindicated in severe renal impairment (creatinine clearance less than 30 ml/min), confirmed hyperkalemia, progressive kidney diseases.

Should be used with caution in chronic renal impairment (creatinine clearance 30-60 ml/min).

Pediatric Use

Contraindicated for use in children and adolescents under 15 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

With long-term use of NSAIDs, it is necessary to periodically evaluate the complete blood count, as well as monitor kidney and liver function, especially in elderly patients (over 65 years of age), and perform a stool test for occult blood. Caution should be exercised and blood pressure should be monitored more frequently when using ketoprofen to treat patients with arterial hypertension, cardiovascular diseases that lead to fluid retention in the body.

If visual disturbances occur, treatment should be stopped immediately.

Like other NSAIDs, Ketoprofen may mask the symptoms of infectious and inflammatory diseases. If signs of infection are detected or if the condition worsens during the use of the product, the patient should immediately consult a doctor.

If there is a history of gastrointestinal contraindications (bleeding, perforation, peptic ulcer), in the case of long-term therapy and the use of ketoprofen in high doses, the patient should be under close medical supervision.

Due to the important role of prostaglandins in maintaining renal blood flow, special caution should be exercised when using ketoprofen in patients with cardiac or renal insufficiency, as well as when treating elderly patients taking diuretics, and patients who, for any reason, have a reduced circulating blood volume (for example, after surgery).

Effect on ability to drive vehicles and operate machinery

During treatment, drowsiness, dizziness, or other unpleasant sensations from the nervous system, including visual impairment, may occur. When using ketoprofen, patients should exercise caution when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Concomitant use of ketoprofen with other NSAIDs (including selective COX-2 inhibitors and salicylates in high doses) is not recommended due to an increased risk of gastrointestinal bleeding and ulceration of the gastrointestinal mucosa.

Simultaneous use with anticoagulants (heparin, warfarin), antiplatelet agents (ticlopidine, clopidogrel) increases the risk of bleeding. If the use of such a combination is unavoidable, the patient’s condition should be carefully monitored.

With simultaneous use with lithium preparations, an increase in the concentration of lithium in the blood plasma up to toxic values is possible. The concentration of lithium in the blood plasma should be carefully monitored and the dose of lithium preparations should be adjusted in a timely manner during and after the use of NSAIDs.

Ketoprofen increases the hematological toxicity of methotrexate, especially when it is used in high doses (more than 15 mg/week). The time interval between the cessation or initiation of ketoprofen therapy and the intake of methotrexate should be at least 12 hours.

Against the background of ketoprofen therapy, patients taking diuretics, especially with the development of dehydration, have a higher risk of developing renal failure due to a decrease in renal blood flow caused by inhibition of prostaglandin synthesis. Before starting the use of ketoprofen in such patients, rehydration measures should be carried out. After the start of treatment, kidney function should be monitored.

Concomitant use of ketoprofen with ACE inhibitors and angiotensin II receptor antagonists (ARA II) in patients with impaired renal function (with dehydration, in elderly patients) may lead to worsening of renal function impairment, including the development of acute renal failure.

During the first weeks of simultaneous use of ketoprofen and methotrexate at a dose not exceeding 15 mg/week, a blood test should be monitored weekly. In elderly patients or if any signs of impaired renal function occur, the study should be performed more often.

Ketoprofen may weaken the hypotensive effect of antihypertensive drugs (beta-blockers, ACE inhibitors, diuretics).

Simultaneous use of ketoprofen with selective serotonin reuptake inhibitors (SSRIs) increases the risk of gastrointestinal bleeding.

Simultaneous use with thrombolytics increases the risk of bleeding.

Simultaneous use of ketoprofen with potassium salts, potassium-sparing diuretics, ACE inhibitors, ARA II, NSAIDs, low molecular weight heparins, cyclosporine, tacrolimus and trimethoprim increases the risk of hyperkalemia.

With simultaneous use with cyclosporine, tacrolimus, there is a risk of developing an additive nephrotoxic effect, especially in elderly patients.

Simultaneous use of several antiplatelet drugs (tirofiban, eptifibatide, abciximab, iloprost) increases the risk of bleeding.

Ketoprofen increases the concentration in the blood plasma of cardiac glycosides, slow calcium channel blockers, cyclosporine, methotrexate and digoxin.

Concomitant use of ketoprofen with glucocorticosteroids, ethanol increases the risk of adverse events from the gastrointestinal tract.

Ketoprofen may enhance the effect of oral hypoglycemic and some anticonvulsant drugs (phenytoin).

Simultaneous use with probenecid significantly reduces the clearance of ketoprofen in the blood plasma.

NSAIDs may reduce the effectiveness of mifepristone. NSAIDs should be started no earlier than 8-12 days after discontinuation of mifepristone.

Ketoprofen is pharmaceutically incompatible with tramadol solution due to precipitation.

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.