RaitBufen (Tablets) Instructions for Use

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

ATC Code

M01AE14 (Dexibuprofen)

Active Substance

Dexibuprofen (Rec.INN registered by WHO)

Dosage Forms

	RaitBufen	Film-coated tablets 200 mg
		Film-coated tablets 300 mg
		Film-coated tablets 400 mg

Dosage Form, Packaging, and Composition

Film-coated tablets

10 pcs. – jars – cardboard packs (10 pcs.) – Over-the-counter
10 pcs. – contour cell blisters – cardboard packs (10 pcs.) – Over-the-counter
10 pcs. – contour cell blisters (3 pcs.) – cardboard packs (30 pcs.) – Over-the-counter
10 pcs. – contour cell blisters (5 pcs.) – cardboard packs (50 pcs.) – Over-the-counter
10 pcs. – contour cell blisters (6 pcs.) – cardboard packs (60 pcs.) – Over-the-counter
30 pcs. – jars – cardboard packs (30 pcs.) – Over-the-counter
50 pcs. – jars – cardboard packs (50 pcs.) – Over-the-counter

Film-coated tablets

10 pcs. – jars – cardboard packs (10 pcs.) – Over-the-counter
10 pcs. – contour cell blisters – cardboard packs (10 pcs.) – Over-the-counter
10 pcs. – contour cell blisters (3 pcs.) – cardboard packs (30 pcs.) – Over-the-counter
10 pcs. – contour cell blisters (5 pcs.) – cardboard packs (50 pcs.) – Over-the-counter
10 pcs. – contour cell blisters (6 pcs.) – cardboard packs (60 pcs.) – Over-the-counter
30 pcs. – jars – cardboard packs (30 pcs.) – Over-the-counter
50 pcs. – jars – cardboard packs (50 pcs.) – Over-the-counter

Film-coated tablets

10 pcs. – jars – cardboard packs (10 pcs.) – Over-the-counter
10 pcs. – contour cell blisters – cardboard packs (10 pcs.) – Over-the-counter
10 pcs. – contour cell blisters (3 pcs.) – cardboard packs (30 pcs.) – Over-the-counter
10 pcs. – contour cell blisters (5 pcs.) – cardboard packs (50 pcs.) – Over-the-counter
10 pcs. – contour cell blisters (6 pcs.) – cardboard packs (60 pcs.) – Over-the-counter
30 pcs. – jars – cardboard packs (30 pcs.) – Over-the-counter
50 pcs. – jars – cardboard packs (50 pcs.) – Over-the-counter

Pharmacotherapeutic Group

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

Pharmacological Action

Dexibuprofen (S(+)-ibuprofen) is the pharmacologically active enantiomer of ibuprofen, a non-selective NSAID. Ibuprofen, a racemic mixture of S(+) and R(-) enantiomers, non-selectively blocks COX-1 and COX-2, thereby inhibiting prostaglandin synthesis.

Thus, by inhibiting prostaglandin synthesis, it exerts analgesic, anti-inflammatory, and antipyretic effects and reversibly inhibits platelet aggregation.

Pharmacokinetics

After oral administration, Dexibuprofen is absorbed mainly from the upper gastrointestinal tract. C_max in blood plasma is reached approximately 2 hours after oral administration. Plasma protein binding is about 99%.

The main metabolites are 2-hydroxyibuprofen and carboxyibuprofen (and their respective acyl glucuronides), which account for about 25% and 37% of the administered dose excreted in urine, respectively.

The metabolism of S(+)-ibuprofen occurs primarily with the participation of the CYP2C9 isoenzyme, whereas its R(-) antipode is formed more with the participation of CYP2C8.

No differences in the pharmacokinetics of R(-) and S(+) enantiomers of ibuprofen depending on sex were identified, however V_d is approximately 2 times higher in females compared to males.

After metabolic transformation in the liver (hydroxylation, carboxylation), the pharmacologically inactive metabolites are completely eliminated, primarily by the kidneys (90%), but also with bile. T_1/2 is 1.8-3.5 hours.

Indications

For symptomatic therapy: mild to moderate pain syndrome, including headache, migraine, toothache, muscle pain and joint pain; acute pain syndrome during menstrual bleeding (primary dysmenorrhea); pain and inflammation associated with osteoarthritis.

Dosage Regimen

Select the dose according to the severity of the condition and the patient’s complaints.

Administer the tablets orally with a sufficient amount of liquid.

For mild to moderate pain, use a single dose of 200 mg.

If pain persists, increase the single dose to 400 mg.

Do not exceed a maximum single dose of 400 mg.

Maintain an interval of at least 4-6 hours between doses.

Do not exceed a maximum daily dose of 1200 mg.

For osteoarthritis, the recommended daily dose is 600-900 mg in divided doses.

For primary dysmenorrhea, initiate treatment at the onset of pain; the usual dose is 200-400 mg up to three times daily as needed.

Intended for short-term use only.

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

In patients with mild to moderate hepatic impairment, initiate therapy with a lower dose and monitor closely.

In patients with mild to moderate renal impairment (CrCl ≥30 ml/min), initiate therapy with a lower dose.

No dose adjustment is routinely required in elderly patients; consider individual dose reduction due to increased risk of adverse reactions.

Contraindicated in children and adolescents under 18 years of age.

Adverse Reactions

Infections and infestations very rarely – exacerbation of inflammation associated with infection (e.g., development of necrotizing fasciitis), coinciding with NSAID therapy.

Blood and lymphatic system disorders very rarely – anemia, thrombocytopenia, leukopenia, pancytopenia, agranulocytosis.

Immune system disorders uncommon – hypersensitivity reactions such as urticaria, pruritus, purpura and rash, as well as asthma attacks (possibly with a sharp decrease in BP); very rarely – severe generalized hypersensitivity reactions, including facial swelling, swelling of the tongue, inner part of the larynx with airway narrowing, difficulty breathing, tachycardia and decreased BP, development of potentially life-threatening shock; exacerbation of bronchial asthma; angioedema.

Psychiatric disorders uncommon – anxiety; rarely – psychotic reaction, depression, confusion, hallucinations.

Nervous system disorders common – CNS disorders such as headache, dizziness, insomnia, agitation, irritability or drowsiness, vertigo, general weakness; very rarely – aseptic meningitis.

Eye disorders uncommon – visual disturbances; rarely – toxic amblyopia.

Ear and labyrinth disorders uncommon – tinnitus; rarely – hearing impairment.

Cardiovascular system disorders: very rarely – edema, palpitations, heart failure, myocardial infarction, arterial hypertension, vasculitis; frequency unknown – Kounis syndrome.

Respiratory system disorders uncommon – rhinitis; very rarely – bronchospasm (mainly in patients with bronchial asthma).

Gastrointestinal disorders very common – dyspepsia, abdominal pain, nausea, diarrhea, flatulence, constipation, heartburn, vomiting, minor gastrointestinal bleeding (which in exceptional cases may lead to anemia); common – gastrointestinal ulcers, sometimes with bleeding and perforation, melena, vomiting blood, ulcerative stomatitis, colitis, exacerbation of inflammatory bowel diseases, complications of colonic diverticula (perforation, fistula); uncommon – gastritis; very rarely – esophagitis, pancreatitis, occurrence of diaphragm-like intestinal strictures.

Hepatobiliary disorders rarely – changes in liver function (usually reversible); very rarely – impaired liver function, liver damage, especially with long-term treatment, liver failure, acute hepatitis, jaundice.

Skin and subcutaneous tissue disorders uncommon – skin rash; very rarely – erythema multiforme, alopecia, photosensitivity reactions, bullous reactions, including Stevens-Johnson syndrome, acute toxic epidermal necrolysis (Lyell’s syndrome); frequency unknown – drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis.

Renal and urinary disorders uncommon – occurrence of edema, especially in patients with arterial hypertension or renal failure, nephrotic syndrome, interstitial nephritis, which may be associated with renal failure; rarely – renal tissue damage (papillary necrosis) and increased blood urea levels; increased blood uric acid concentration.

Contraindications

Hypersensitivity to dexibuprofen, other NSAIDs; history of hypersensitivity reactions (such as bronchospasm, bronchial asthma, rhinitis, nasal polyps, angioedema or urticaria) associated with the use of acetylsalicylic acid or other NSAIDs; history of gastrointestinal bleeding or gastrointestinal perforation associated with previous NSAID therapy; hematopoiesis disorders of unclear etiology; erosive and ulcerative diseases of the gastrointestinal tract (including peptic ulcer of the stomach and duodenum, Crohn’s disease, ulcerative colitis) or ulcerative bleeding in the active phase or in history (two or more confirmed episodes of peptic ulcer or ulcerative bleeding); cerebral hemorrhage or other active bleeding; hemorrhagic diathesis and other bleeding disorders; severe hepatic failure; severe renal failure (CrCl < 30 ml/min); severe heart failure (NYHA class IV); severe dehydration (e.g., due to vomiting, diarrhea, or insufficient fluid intake); pregnancy, breastfeeding period; age under 18 years.

With caution

Systemic lupus erythematosus and mixed connective tissue disease, due to increased risk of aseptic meningitis; congenital disorders of porphyrin metabolism (e.g., acute intermittent porphyria); history of a single episode of gastrointestinal ulcer or bleeding, as well as history of chronic inflammatory bowel diseases (ulcerative colitis, Crohn’s disease); arterial hypertension and/or mild or moderate heart failure; impaired renal function, as deterioration of renal function is possible; impaired liver function; conditions after extensive surgical intervention; in patients with allergic rhinitis, nasal polyps or chronic obstructive respiratory diseases.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

In patients with mild and moderate hepatic impairment, treatment should be started with a lower dose of dexibuprofen, careful monitoring of the patient’s condition is necessary. Dexibuprofen should not be used in patients with severe hepatic impairment.

Use in Renal Impairment

In patients with mild and moderate renal impairment, treatment should be started with a lower dose of dexibuprofen. Should not be used in patients with severe renal impairment.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

No dose adjustment is required in elderly patients. However, the possibility of individual dose reduction and titration should be considered due to the increased risk of gastrointestinal adverse reactions in elderly patients. Due to the possible development of adverse reactions, careful monitoring of the condition of elderly patients is recommended.

Special Precautions

The risk of developing adverse reactions can be reduced by using the minimum effective dose for the shortest period necessary to relieve symptoms.

With the use of all NSAIDs, at any time during their administration, cases of gastrointestinal bleeding, ulcer formation or perforations, which can be fatal, have been described in patients with or without warning symptoms or a history of previous gastrointestinal complications.

With increasing doses of NSAIDs, the risk of gastrointestinal bleeding, ulcer formation or perforations increases in patients with a history of peptic ulcer, especially complicated by bleeding or perforation, as well as in elderly patients, in patients suffering from alcoholism. Treatment of these patients should be started with the lowest possible doses. For these patients, as well as patients requiring concomitant therapy with low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal damage, the possibility of simultaneous prescription of gastroprotective agents (e.g., misoprostol or proton pump inhibitors) should be considered.

Patients (especially the elderly) with a history of gastrointestinal toxicity should be informed of the need to report any abnormal abdominal symptoms (in particular, symptoms of gastrointestinal bleeding), especially in the initial stages of therapy.

Caution is recommended when treating patients receiving concomitant therapy with drugs that can increase the risk of ulcer formation or bleeding, for example, corticosteroids, anticoagulants (such as heparin and its derivatives, vitamin K antagonists (warfarin, acenocoumarol), rivaroxaban, apixaban, dabigatran), SSRIs or antiplatelet drugs such as acetylsalicylic acid.

In case of gastrointestinal bleeding or ulcer development in patients receiving ibuprofen, it is recommended to discontinue the drug. Careful monitoring of these patients is necessary, including esophagogastroduodenoscopy, complete blood count (hemoglobin determination), fecal occult blood test if necessary.

NSAIDs should be prescribed with caution to patients with a history of inflammatory gastrointestinal diseases (e.g., ulcerative colitis, Crohn’s disease) to avoid exacerbation of symptoms.

Therapy should be discontinued at the first signs of a hypersensitivity reaction after taking dexibuprofen. The patient is advised to consult a doctor immediately.

In patients with bronchial asthma, a history of allergic diseases, bronchospasm may occur when taking dexibuprofen.

In patients with uncontrolled arterial hypertension, congestive heart failure (NYHA functional class II-III), diagnosed coronary artery disease, peripheral arterial disease and/or cerebrovascular disease, Dexibuprofen should be prescribed only after careful assessment of the need for such therapy, while high doses of dexibuprofen (1200 mg/day) should be avoided.

A thorough assessment of the need for treatment should also be carried out before starting long-term use of the drug in patients with risk factors for cardiovascular diseases (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking), especially if high doses of dexibuprofen (1200 mg/day) are required.

Hypersensitivity reactions to the drug can also progress to Kounis syndrome – a serious allergic reaction that can lead to myocardial infarction. Symptoms of this reaction may include chest pain occurring in connection with an allergy to Dexibuprofen.

Dexibuprofen should be used with caution in patients with liver or kidney diseases, the risk of fluid retention, edema and impaired renal function should be taken into account. The minimum effective dose of dexibuprofen should be used in these patients, and regular monitoring of renal function is necessary.

In general, continuous use of analgesics, especially combinations of various painkillers, can lead to long-term kidney damage with the risk of developing renal failure (analgesic nephropathy). Thus, combinations with ibuprofen or other NSAIDs (including over-the-counter NSAIDs and selective COX-2 inhibitors) should be avoided.

Administration of dexibuprofen should be discontinued at the first appearance of skin rashes, mucosal lesions or the development of any other signs of hypersensitivity.

Dexibuprofen may mask the symptoms of an infection, which may lead to a delayed start of appropriate treatment and thereby to a worsening of the outcome of the infection. This has been observed in bacterial community-acquired pneumonia and bacterial complications of chickenpox.

It is recommended to monitor the course of the infection when taking dexibuprofen to relieve pain associated with an infection. The patient should consult a doctor if the symptoms do not disappear or worsen.

In rare cases, severe skin infections and soft tissue complications when taking NSAIDs may be due to chickenpox. Currently, the influence of NSAIDs on the worsening of this infection cannot be ruled out. In this regard, it is recommended to avoid the use of dexibuprofen in chickenpox.

Long-term use of any painkillers for headache can lead to an increase in the severity of symptoms. In this case, the patient should consult a doctor and discontinue dexibuprofen. When diagnosing patients with frequent or daily headaches, despite the regular use of painkillers (or because of their use), the possible development of medication-overuse (abuse) headache should be taken into account.

Elderly patients have a higher risk of developing adverse reactions when taking NSAIDs, especially gastrointestinal bleeding or gastrointestinal perforation, which can be fatal.

As a precaution, it is necessary to monitor the condition of patients receiving long-term therapy with dexibuprofen (monitoring of renal and liver function, complete blood count/leukocyte formula).

Influence on the ability to drive vehicles and mechanisms

During treatment with dexibuprofen, adverse reactions such as dizziness, fatigue, drowsiness and visual disturbances may appear. This should be taken into account when speed of psychomotor reactions is required when driving vehicles and operating machinery. For single or short-term use of dexibuprofen, special precautions are not required.

Drug Interactions

In general, NSAIDs should be used with caution simultaneously with other drugs that increase the risk of developing gastrointestinal ulcerative lesions, gastrointestinal bleeding or impaired renal function.

Acetylsalicylic acid (as antiplatelet therapy): concomitant use may increase the risk of adverse reactions. Preclinical data indicate the ability of ibuprofen to inhibit the effect of low-dose acetylsalicylic acid on platelet aggregation when drugs are used simultaneously. The possibility cannot be excluded that long-term regular use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. It is believed that with intermittent use of ibuprofen, this clinical effect is probably absent. Although data on dexibuprofen are lacking, a similar interaction between dexibuprofen (S(+)-ibuprofen, the pharmacologically active enantiomer of ibuprofen) and low-dose acetylsalicylic acid can be assumed. Concomitant use should be avoided.

Other NSAIDs and salicylates (acetylsalicylic acid as an analgesic): Concomitant use with other NSAIDs, including selective COX-2 inhibitors, should be avoided due to the possible risk of GI ulcers and gastrointestinal bleeding.

Methotrexate: There is evidence of a possible increase in plasma methotrexate concentrations with NSAID use. Administration of dexibuprofen within 24 hours before or after methotrexate administration may lead to increased methotrexate concentrations and enhanced toxic effects. Therefore, concomitant use of NSAIDs and high-dose methotrexate should be avoided.

Anticoagulants: NSAIDs may enhance the effect of anticoagulants such as heparin and its derivatives, vitamin K antagonists (warfarin, acenocoumarol), and oral anticoagulants (rivaroxaban, apixaban, dabigatran).

Antihypertensive drugs (ACE inhibitors, beta-blockers, angiotensin II receptor antagonists) and diuretics: NSAIDs may reduce the effectiveness of drugs in these groups. In some patients with impaired renal function (e.g., dehydrated patients or elderly patients with impaired renal function), concomitant administration of ACE inhibitors, beta-blockers, or angiotensin II receptor antagonists and COX inhibitors may lead to deterioration of renal function, including the development of acute renal failure (usually reversible). This combination should be used with caution, especially in elderly patients. Dehydration in patients should be prevented, and monitoring of renal function should be considered after initiation of such combined treatment and periodically thereafter. Diuretics may increase the nephrotoxicity of NSAIDs.

Corticosteroids: Increased risk of GI ulcers and gastrointestinal bleeding.

Antiplatelet agents and SSRIs: Increased risk of gastrointestinal bleeding.

Digoxin, phenytoin, lithium preparations: Concomitant use with dexibuprofen may increase the plasma concentrations of these drugs. Plasma lithium concentration should be monitored; plasma levels of digoxin and phenytoin should also be monitored.

Methotrexate: When methotrexate is used in low doses, the potential risk of interaction should be considered, especially in patients with renal insufficiency. Renal function monitoring is necessary during concomitant use with dexibuprofen.

Cyclosporine, tacrolimus, sirolimus, aminoglycoside antibiotics: Increased risk of nephrotoxicity when co-administered with NSAIDs due to decreased prostaglandin synthesis in the kidneys. Careful monitoring of renal function is necessary, especially in elderly patients.

Mifepristone: NSAIDs should be administered no earlier than 8-12 days after mifepristone intake, as NSAIDs may reduce the effectiveness of mifepristone.

Zidovudine: Concomitant use of NSAIDs and zidovudine may lead to increased hematotoxicity. There are reports of an increased risk of hemarthrosis and hematoma in HIV-positive patients with hemophilia receiving concomitant therapy with zidovudine and ibuprofen.

Probenecid, sulfinpyrazone: Drugs containing probenecid or sulfinpyrazone may delay the elimination of ibuprofen.

Baclofen: Initiation of ibuprofen therapy may contribute to the manifestation of baclofen toxicity.

Pemetrexed: High-dose NSAIDs may increase blood concentrations of pemetrexed. In patients with mild to moderate renal insufficiency (CrCl 45-79 ml/min), concomitant administration of high-dose dexibuprofen should be avoided for 2 days before and 2 days after pemetrexed administration.

Quinolone antibiotics: In patients receiving concomitant treatment with NSAIDs and quinolone antibiotics, there may be an increased risk of seizures.

CYP2C9 inhibitors: Concomitant use of dexibuprofen and CYP2C9 inhibitors may increase the exposure to dexibuprofen (a CYP2C9 substrate). A study using voriconazole and fluconazole (CYP2C9 inhibitors) demonstrated an approximately 80-100% increase in S(+)-ibuprofen exposure. When dexibuprofen is used concomitantly with strong CYP2C9 inhibitors, a dose reduction of dexibuprofen should be considered, especially when high-dose dexibuprofen is co-administered with voriconazole or fluconazole.

Potassium-sparing diuretics: Concomitant use of ibuprofen with potassium-sparing diuretics may cause hyperkalemia (monitoring of plasma potassium is recommended).

Cefamandole, cefoperazone, cefotetan, valproic acid, plicamycin: Increased incidence of hypoprothrombinemia.

Microsomal oxidation inducers (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants): Increased production of hydroxylated active metabolites, increased risk of severe intoxication.

Sulfonylurea derivatives: Clinical study data have demonstrated the possibility of interaction between NSAIDs and sulfonylurea derivatives. Blood glucose levels should be monitored during concomitant use with dexibuprofen.

Excessive alcohol consumption during NSAID therapy may increase adverse GI reactions.

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

Over-the-Counter

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.