Ketonal^® UNO (Capsules) Instructions for Use

Marketing Authorization Holder

Lek d.d. (Slovenia)

ATC Code

M01AE03 (Ketoprofen)

Active Substance

Ketoprofen (Rec.INN registered by WHO)

Dosage Form

Ketonal® UNO

Extended-release capsules 200 mg: 10, 20, or 30 pcs.

Dosage Form, Packaging, and Composition

Extended-release capsules with a transparent body and a blue cap; the capsule contents are orange-red pellets.

Excipients: microcrystalline cellulose.

Pellet coating composition methacrylic acid and ethyl acrylate copolymer (2:1) (Eudragit NE 30D, contains 1.5% nonoxinol-100 as an emulsifier), methacrylic acid and ethyl acrylate copolymer (1:1) (Eudragit L30 D-55, contains 0.7% sodium lauryl sulfate and 2.3% polysorbate 80), talc, iron oxide red dye.
Capsule body composition gelatin.
Capsule cap composition patent blue dye, titanium dioxide, gelatin.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID. Has analgesic, anti-inflammatory, and antipyretic effects.

By inhibiting COX-1 and COX-2, and partially lipoxygenase, Ketoprofen suppresses the synthesis of prostaglandins and bradykinin, and stabilizes lysosomal membranes.

Ketoprofen does not have a negative effect on articular cartilage.

The capsules contain pellets with extended release, which provides a prolonged action of the drug.

Pharmacokinetics

Absorption

After oral administration, Ketoprofen is well absorbed from the gastrointestinal tract. After oral administration, C_max in blood plasma ranges from 3.1 to 3.4±1.2 mg/L and is reached within 5 hours.

The bioavailability of ketoprofen is 90%.

Food intake does not affect the overall bioavailability of ketoprofen but reduces the absorption rate.

Effective concentrations of ketoprofen are detected in the blood even 24 hours after its administration.

Distribution

The binding of ketoprofen to plasma proteins (mainly albumin) is 99%. V_d – 0.1 L/kg. Ketoprofen penetrates well into the synovial fluid, where it reaches 30% of the plasma concentration.

Metabolism and excretion

Ketoprofen undergoes intensive metabolism with the participation of liver microsomal enzymes. It is conjugated with glucuronic acid and excreted as a glucuronide. There are no active metabolites of ketoprofen. T_1/2 – less than 2 hours.

Plasma clearance – 0.8 L/kg body weight/hour.

Approximately 80% of ketoprofen is excreted in the urine, mainly as a glucuronide metabolite. 10% is excreted in the feces.

Pharmacokinetics in special clinical cases

In patients with hepatic insufficiency, the plasma concentration of ketoprofen is increased by 2 times, probably due to hypoalbuminemia (and consequently a high level of unbound active ketoprofen); such patients should be prescribed the drug at the minimum therapeutic dose.

In patients with renal insufficiency, the clearance of ketoprofen is reduced, which requires dose adjustment.

In elderly patients, the metabolism and excretion of ketoprofen are slowed down, but this is clinically significant only for patients with reduced renal function.

Indications

Symptomatic treatment of painful and inflammatory processes of various origins.

Inflammatory and degenerative diseases of the musculoskeletal system

• Rheumatoid arthritis;
• Seronegative arthritides (ankylosing spondylitis, psoriatic arthritis, reactive arthritis /Reiter’s syndrome/);
• Gout, pseudogout;
• Osteoarthritis.

Pain syndrome

• Headache;
• Tendinitis, bursitis, myalgia, neuralgia, radiculitis;
• Post-traumatic pain;
• Postoperative pain;
• Primary dysmenorrhea;
• Pain syndrome in oncological diseases.

ICD codes

Dosage Regimen

Administer the standard adult dose as one 200 mg extended-release capsule once daily.

Swallow the capsule whole; do not crush or chew the pellets.

Take during or immediately after a meal with a full glass of water or milk (at least 100 ml).

The maximum daily dose is 200 mg; do not exceed this dose.

For geriatric patients and those with mild to moderate hepatic or renal impairment, initiate therapy at the lowest effective dose for the shortest possible duration.

Use the minimum effective dose for the shortest duration necessary to control symptoms.

Monitor renal and hepatic function, as well as blood counts, with long-term therapy, particularly in elderly patients.

Discontinue treatment if signs of gastrointestinal bleeding or ulceration occur.

This medication is contraindicated in children under 15 years of age, in the third trimester of pregnancy, and during breastfeeding.

Adverse Reactions

The frequency of adverse effects is characterized as very common (>10%), common (>1% <10%), uncommon (>0.1% <1%), rare (>0.01% < 0.1%), and very rare (< 0.01%).

From the digestive system common – dyspepsia (nausea, diarrhea or constipation, flatulence, vomiting, decreased or increased appetite), abdominal pain, stomatitis, dry mouth; uncommon (with long-term use in high doses) – ulceration of the gastrointestinal mucosa, impaired liver function; rare – perforation of the gastrointestinal tract, exacerbation of Crohn’s disease, melena, gastrointestinal bleeding, transient increase in liver enzyme levels.

From the central nervous system common – headache, dizziness, sleep disturbance, fatigue, nervousness, nightmares; rare – migraine, peripheral polyneuropathy; very rare – hallucinations, disorientation, and speech disorder.

From the sensory organs rare – tinnitus, taste alteration, blurred vision, conjunctivitis.

From the cardiovascular system uncommon – tachycardia, arterial hypertension, peripheral edema.

From the hematopoietic system decreased platelet aggregation; rare – anemia, thrombocytopenia, agranulocytosis, purpura.

From the urinary system rare – impaired renal function, interstitial nephritis, nephrotic syndrome, hematuria (more often develop in people taking NSAIDs and diuretics for a long time).

Allergic reactions common – skin reactions (itching, urticaria); uncommon – rhinitis, dyspnea, bronchospasm, angioedema, anaphylactoid reactions.

Other: rare – hemoptysis, menometrorrhagia.

Contraindications

• Bronchial asthma, rhinitis, urticaria in history, caused by taking acetylsalicylic acid or other NSAIDs;
• Peptic ulcer of the stomach and duodenum in the acute phase;
• Ulcerative colitis, Crohn’s disease in the acute phase, inflammatory bowel diseases in the acute stage;
• Hemophilia and other bleeding disorders;
• Severe hepatic insufficiency;
• Severe renal insufficiency (including accompanied by hyperkalemia);
• Progressive kidney diseases;
• Decompensated heart failure;
• Postoperative period after coronary artery bypass grafting;
• Gastrointestinal, cerebrovascular and other bleedings (or suspicion of bleeding);
• Chronic dyspepsia;
• Children under 15 years of age;
• Third trimester of pregnancy;
• Lactation period (breastfeeding);
• Hypersensitivity to ketoprofen or other components of the drug, as well as to salicylates or other non-steroidal anti-inflammatory drugs.

With caution the drug should be prescribed for a history of peptic ulcer, a history of bronchial asthma, clinically significant cardiovascular, cerebrovascular diseases and peripheral artery diseases, dyslipidemia, progressive liver diseases, hyperbilirubinemia, alcoholism, renal insufficiency, chronic heart failure, arterial hypertension, blood diseases, dehydration, diabetes mellitus, anamnestic data on the development of ulcerative gastrointestinal lesions, presence of Helicobacter pylori infection, smoking, concomitant therapy with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., acetylsalicylic acid), oral corticosteroids (e.g., prednisolone), selective serotonin reuptake inhibitors (e.g., citalopram, sertraline), long-term use of NSAIDs.

Use in Pregnancy and Lactation

The use of ketoprofen in the third trimester of pregnancy is contraindicated. In the first and second trimesters of pregnancy, the drug can be prescribed only if the intended benefit to the mother outweighs the potential risk to the fetus.

If the drug is taken during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

The drug is contraindicated in severe hepatic insufficiency.

Use in Renal Impairment

The drug is contraindicated in severe renal insufficiency.

Pediatric Use

The drug is contraindicated in children under 15 years of age.

Geriatric Use

With long-term use of NSAIDs, it is necessary to monitor the state of the blood, as well as the function of the kidneys and liver, especially in elderly patients (over 65 years of age).

Special Precautions

With long-term use of NSAIDs, it is necessary to monitor the state of the blood, as well as the function of the kidneys and liver, especially in elderly patients (over 65 years of age).

It is necessary to exercise caution and monitor blood pressure more frequently when using ketoprofen to treat patients suffering from hypertension, cardiovascular diseases that lead to fluid retention in the body.

Like other NSAIDs, Ketoprofen may mask the signs of infectious diseases.

Effect on the ability to drive vehicles and operate machinery

There are no data on the negative effect of Ketonal^® UNO in recommended doses on the ability to drive a car or operate machinery. However, patients who experience non-standard effects when taking Ketonal^® UNO should exercise caution when engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms nausea, vomiting, abdominal pain, vomiting blood, melena, impaired consciousness, respiratory depression, convulsions, impaired renal function and renal failure.

Treatment: in case of overdose, gastric lavage and administration of activated charcoal are indicated. Symptomatic therapy is carried out. The effect of ketoprofen on the gastrointestinal tract can be mitigated with histamine H₂-receptor blockers, proton pump inhibitors, and prostaglandins.

Drug Interactions

Ketoprofen may weaken the effect of diuretics and antihypertensive agents, and enhance the effect of oral hypoglycemic and some anticonvulsant drugs (phenytoin).

Concomitant use with other NSAIDs, salicylates, corticosteroids, ethanol increases the risk of adverse events from the gastrointestinal tract.

Simultaneous administration with anticoagulants, thrombolytics, antiplatelet agents increases the risk of bleeding.

When NSAIDs are taken simultaneously with diuretics or ACE inhibitors, the risk of impaired renal function increases.

Increases the plasma concentration of cardiac glycosides, slow calcium channel blockers, lithium preparations, cyclosporine, methotrexate.

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

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature not exceeding 30°C (86°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

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.