Rapten DUO (Tablets) Instructions for Use

Marketing Authorization Holder

Hemofarm, A.D. (Serbia)

ATC Code

M01AB05 (Diclofenac)

Active Substance

Diclofenac (Rec.INN registered by WHO)

Dosage Form

Rapten DUO

Modified-release tablets 75 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Modified-release tablets round, biconvex, two-layer; one layer is orange, the second is from white to yellowish-white, with small inclusions of white and orange color on the orange and white layers, respectively.

Excipients : enteric-coated granules – corn starch, lactose monohydrate, sodium carboxymethyl starch, acryl-iz white (methacrylic acid and methyl methacrylate copolymer (1:1), talc, titanium dioxide, triethyl citrate, colloidal silicon dioxide, sodium bicarbonate, sodium lauryl sulfate), simethicone emulsion 30%, magnesium stearate, colloidal silicon dioxide; enteric-coated granules with prolonged release – corn starch, lactose monohydrate, sodium carboxymethyl starch, acryl-iz white (methacrylic acid and methyl methacrylate copolymer (1:1), talc, titanium dioxide, triethyl citrate, colloidal silicon dioxide, sodium bicarbonate, sodium lauryl sulfate), simethicone emulsion 30%, hypromellose, magnesium stearate, colloidal silicon dioxide, aluminum lake based on dye sunset yellow (E110).

10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID, a derivative of phenylacetic acid. Diclofenac has anti-inflammatory, analgesic, antiplatelet and antipyretic effects. By non-selectively inhibiting cyclooxygenase 1 and 2 (COX-1 and COX-2), it disrupts the metabolism of arachidonic acid and reduces the amount of prostaglandins at the site of inflammation. It is most effective for pain of an inflammatory nature.

In rheumatic diseases, the anti-inflammatory and analgesic effect of diclofenac contributes to a significant reduction in the severity of pain, morning stiffness, and swelling of the joints, which improves the functional state of the joint. In case of injuries, in the postoperative period, Diclofenac reduces pain and inflammatory edema.

The drug relieves or reduces pain and inflammation during the treatment of diseases of the musculoskeletal system, while it does not affect the progression of the disease.

Pharmacokinetics

The drug Rapten Duo is a form of diclofenac (sodium salt) in the form of two-layer tablets.

Absorption

After oral administration, Diclofenac is rapidly and completely absorbed from the gastrointestinal tract. After a single dose, C_max in plasma is reached in 20-60 minutes due to the release of 25 mg of diclofenac from the first acid-resistant layer. . From the second layer, 50 mg of diclofenac is slowly released over ≥6 hours, which provides a prolonged effect (12-24 hours). Changes in the pharmacokinetics of diclofenac with repeated administration are not observed. Does not accumulate if the recommended interval between meals is observed.

Distribution

99% of the applied dose is bound to plasma proteins. The drug is well distributed in tissues and tissue fluids. Penetrates into the synovial fluid; C_max in the synovial fluid is observed 2-4 hours later than in plasma. T_1/2 from the synovial fluid is 3-6 hours (the concentration of the active substance in the synovial fluid 4-6 hours after administration of the drug is higher than in plasma and remains higher for another 12 hours). The relationship between the concentration of the drug in the synovial fluid and the clinical efficacy of the drug has not been established.

The drug penetrates the blood-brain barrier and the placental barrier, and is excreted in small amounts in breast milk.

Metabolism

50% of the active substance is metabolized during the “first pass” through the liver. Metabolism occurs as a result of multiple or single hydroxylation and conjugation with glucuronic acid. The enzyme system P450 CYP2C9 is involved in the metabolism of the drug. The pharmacological activity of metabolites is lower than that of diclofenac. Systemic clearance is about 260±50 ml/min, V_d – 550 ml/kg.

Excretion

T_1/2 from plasma averages about 2.5 hours. 65% of the administered dose is excreted by the kidneys as metabolites; less than 1% is excreted unchanged, the rest of the dose (less than 35%) is excreted as metabolites in the bile.

Pharmacokinetics in special clinical cases

In patients with chronic hepatitis or compensated liver cirrhosis, the pharmacokinetic parameters of diclofenac do not change.

Indications

• Symptomatic treatment of diseases of the musculoskeletal system (including rheumatoid arthritis, psoriatic arthritis, juvenile chronic arthritis, ankylosing spondylitis /Bekhterev’s disease/, gouty arthritis, osteoarthritis of peripheral joints and spine, including with radicular syndrome, tenosynovitis, bursitis);
• Pain syndrome of mild or moderate severity: neuralgia, myalgia, lumbago, sciatica, bone pain, post-traumatic and postoperative pain syndrome accompanied by inflammation, pain in cancer, headache, migraine, algodysmenorrhea, adnexitis, toothache;
• As part of complex therapy for infectious and inflammatory diseases of the ENT organs with severe pain syndrome (pharyngitis, tonsillitis, otitis media).

ICD codes

Dosage Regimen

The tablets are taken orally, without chewing, during or after meals, with a sufficient amount of liquid.

The daily dose for adults is 75 mg (1 tab.). The maximum daily dose is 150 mg (1 tab. 2 times/day – preferably the first tablet before breakfast and the second after 12 hours).

To reduce the risk of adverse events from the gastrointestinal tract, the minimum effective dose should be used for the shortest possible course.

Adverse Reactions

Very common – 1-10%; common – 0.1-1%; uncommon – 0.01-0.1%; rare – less than 0.001%, including isolated cases.

From the digestive system: very common – epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, increased activity of aminotransferases; uncommon – gastritis, proctitis, gastrointestinal bleeding (vomiting blood, melena, diarrhea with blood), gastrointestinal ulcers (with or without bleeding or perforation), hepatitis, jaundice, impaired liver function; rare – stomatitis, glossitis, esophagitis, nonspecific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn’s disease, constipation, pancreatitis, fulminant hepatitis.

From the nervous system: very common – headache, dizziness; uncommon – drowsiness; rare – sensitivity disorders, including paresthesia, memory disorders, tremor, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, nightmares, irritability, mental disorders.

From the senses: very common – vertigo; rare – visual impairment (blurred vision, diplopia), hearing impairment, tinnitus, taste disturbance.

From the urinary system: rare – acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis.

From the hematopoietic system: rare – thrombocytopenia, leukopenia, hemolytic and aplastic anemia, agranulocytosis.

Allergic reactions: anaphylactic/anaphylactoid reactions, including severe decrease in blood pressure and shock; uncommon – urticaria; rare – angioedema (including facial).

From the cardiovascular system: rare – palpitations, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction.

From the respiratory system: uncommon – exacerbation of bronchial asthma, shortness of breath; rare – pneumonitis.

Dermatological reactions: very common – skin rash; rare – bullous eruptions, erythema including multiforme, Stevens-Johnson syndrome, Lyell’s syndrome, exfoliative dermatitis, itching, hair loss, photosensitivity, purpura, including allergic.

Other: uncommon – edema.

Contraindications

• 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);
• Erosive and ulcerative changes in the gastric or duodenal mucosa, active gastrointestinal bleeding;
• Inflammatory bowel diseases (nonspecific ulcerative colitis, Crohn’s disease) in the acute phase;
• The period after coronary artery bypass grafting;
• Decompensated heart failure;
• Hematopoiesis disorders, hemostasis disorders (including hemophilia);
• Severe hepatic failure or active liver disease;
• Severe renal failure (creatinine clearance less than 30 ml/min), progressive kidney diseases, including confirmed hyperkalemia;
• Rare hereditary diseases, such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption;
• III trimester of pregnancy;
• Lactation period (breastfeeding);
• Children under 18 years of age;
• Hypersensitivity to the active substance (including to other NSAIDs) or auxiliary components.

With caution the drug should be prescribed for anemia, bronchial asthma, cerebrovascular diseases, coronary artery disease, congestive heart failure, arterial hypertension, peripheral artery diseases, edematous syndrome, hepatic or renal failure (creatinine clearance 30-60 ml/min), history of liver diseases, dyslipidemia/hyperlipidemia, diabetes mellitus, smoking, inflammatory bowel diseases, significant decrease in circulating blood volume (including after extensive surgical intervention), hepatic porphyria, diverticulitis, systemic connective tissue diseases, in the I-II trimesters of pregnancy, with gastric and duodenal ulcers (including in history), in the presence of Helicobacter pylori infection, elderly patients (including those receiving diuretics, debilitated patients and with low body weight), with long-term use of NSAIDs, frequent alcohol consumption, severe somatic diseases, with simultaneous therapy with anticoagulants (for example, warfarin), antiplatelet agents (for example, acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline).

Use in Pregnancy and Lactation

The use of the drug is contraindicated in the III trimester of pregnancy and during lactation. Caution should be exercised when prescribing the drug in the I and II trimesters of pregnancy.

Due to the negative effect on fertility, the drug is not recommended for use in women wishing to become pregnant.

In patients with infertility (including those undergoing examination), it is recommended to discontinue the drug.

Use in Hepatic Impairment

Contraindication: severe hepatic failure or active liver disease.

Use in Renal Impairment

Contraindication: severe renal failure (creatinine clearance less than 30 ml/min), progressive kidney diseases, including confirmed hyperkalemia.

Pediatric Use

Contraindicated: children under 18 years of age.

Special Precautions

To quickly achieve the desired therapeutic effect, Diclofenac is taken 30 minutes before meals. In other cases, it is taken before, during or after meals, without chewing, with a sufficient amount of water.

Due to the important role of prostaglandins in maintaining renal blood flow, special caution should be exercised when prescribing to patients with cardiac or renal failure, as well as when treating elderly patients taking diuretics, and patients who, for any reason, have a decrease in circulating blood volume (for example, after extensive surgery). When prescribing diclofenac to such patients, it is recommended to monitor renal function (as a precaution).

In patients with hepatic insufficiency (chronic hepatitis, compensated liver cirrhosis), the kinetics and metabolism do not differ from those in patients with normal liver function.

During long-term therapy, it is necessary to monitor liver function, peripheral blood picture, and conduct a stool test for occult blood.

If during the drug administration the increase in the activity of liver transaminases persists or increases, if clinical symptoms of hepatotoxicity are noted (including nausea, fatigue, drowsiness, diarrhea, skin itching, jaundice), treatment should be discontinued.

Diclofenac (like other NSAIDs) can cause hyperkalemia.

Patients taking the drug should refrain from drinking alcohol.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, a decrease in the speed of mental and motor reactions is possible, so it is necessary to refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms vomiting, gastrointestinal bleeding, diarrhea, dizziness, tinnitus, convulsions, increased blood pressure; with significant overdose – acute renal failure, hepatotoxic effect, respiratory depression, coma.

Treatment gastric lavage, activated charcoal, symptomatic therapy aimed at eliminating increased blood pressure, impaired renal function, convulsions, gastrointestinal irritation, respiratory depression. Forced diuresis, hemodialysis are ineffective (due to significant binding to proteins and intensive metabolism).

Drug Interactions

Diclofenac, when used simultaneously, increases the plasma concentration of digoxin, methotrexate, lithium preparations and cyclosporine.

Reduces the effect of diuretics; against the background of potassium-sparing diuretics, the risk of hyperkalemia increases.

Against the background of anticoagulants, antiplatelet and thrombolytic agents (alteplase, streptokinase, urokinase), the risk of bleeding (more often from the gastrointestinal tract) increases.

Diclofenac, when used simultaneously, reduces the effects of antihypertensive and hypnotic drugs.

Increases the likelihood of side effects of other NSAIDs and glucocorticosteroids (bleeding in the gastrointestinal tract).

With simultaneous use with diclofenac, the toxicity of methotrexate and the nephrotoxicity of cyclosporine increase.

Acetylsalicylic acid reduces the concentration of diclofenac in the blood.

Simultaneous use with paracetamol increases the risk of nephrotoxic effects of diclofenac.

Diclofenac, when used simultaneously, reduces the effect of hypoglycemic drugs.

Cefamandole, cefoperazone, cefotetan, valproic acid, and plicamycin increase the frequency of hypoprothrombinemia development.

Cyclosporine and gold preparations enhance the effect of diclofenac on prostaglandin synthesis in the kidneys, which increases nephrotoxicity.

Concomitant administration of diclofenac with ethanol, colchicine, corticotropin, selective serotonin reuptake inhibitors, and St. John’s wort preparations increases the risk of gastrointestinal bleeding.

Medicinal products causing photosensitization increase the sensitizing effect of diclofenac to ultraviolet radiation.

Drugs that block tubular secretion increase the plasma concentration of diclofenac, thereby increasing its toxicity.

When used concomitantly with antibacterial agents from the quinolone group, the risk of seizures increases.

Storage Conditions

List B. The drug should be stored in a dry place, protected from light, out of the reach of children, at a temperature between 15°C (59°F) and 25°C (77°F).

Shelf Life

The shelf life is 3 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.