Dexolitin (Tablets) Instructions for Use

Marketing Authorization Holder

Forp, JSC (Russia)

Manufactured By

Pharmproekt, JSC (Russia)

ATC Code

M01AE17 (Dexketoprofen)

Active Substance

Dexketoprofen (Rec.INN registered by WHO)

Dosage Form

Dexolitin

Film-coated tablets, 25 mg: 10, 20, 30, 40 or 50 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets round, biconvex, white, with a score on one side; the core is white or almost white on the cross-section.

Excipients: microcrystalline cellulose type 102, pregelatinized starch, sodium carboxymethyl starch, magnesium stearate.

Film coating composition: Opadry II 85F48105 white (polyvinyl alcohol, macrogol MW 3350, titanium dioxide).

10 pcs. – contour cell blisters (1) – cardboard packs.
10 pcs. – contour cell blisters (2) – cardboard packs.
10 pcs. – contour cell blisters (3) – cardboard packs.
10 pcs. – contour cell blisters (4) – cardboard packs.
10 pcs. – contour cell blisters (5) – 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

After a single oral dose, the time to reach C_max of dexketoprofen in blood plasma averages 30 minutes (15-60 minutes). Simultaneous food intake slows down the absorption of dexketoprofen. AUC values after single and repeated doses are similar, indicating no accumulation of the active substance. Plasma protein binding is 99%. The mean V_d is less than 0.25 l/kg, the distribution half-life is about 0.35 hours. The main pathway of dexketoprofen metabolism is its conjugation with glucuronic acid followed by renal excretion. The T_1/2 of dexketoprofen is 1.65 hours. In elderly individuals, an increase in T_1/2 up to 48% and a decrease in the total clearance of dexketoprofen are observed.

Pharmacokinetics

After oral administration, C_max of dexketoprofen in humans is reached on average in 30 minutes (15-60 minutes). Plasma protein binding is 99%. Mean V_d is less than 0.25 l/kg. T_1/2 is 1.65 hours. It undergoes metabolism. It is excreted mainly by the kidneys as metabolites.

Indications

For oral administration: mild to moderate pain syndrome in the following diseases and conditions: acute and chronic inflammatory diseases of the musculoskeletal system (rheumatoid arthritis, spondyloarthritis, arthrosis, osteochondrosis); dysmenorrhea; toothache.

ICD codes

Dosage Regimen

Administer orally. The average single dose is 12.5 mg (half a tablet) taken 1 to 6 times per day at intervals of 4 to 6 hours as needed for pain relief.

Alternatively, a 25 mg dose (one tablet) can be taken 1 to 3 times per day at intervals of 8 hours.

Do not exceed the maximum daily dose of 75 mg.

Limit the duration of treatment to no more than 3 to 5 days.

For patients with impaired liver or kidney function, and for elderly patients, initiate therapy with an initial dose not exceeding 50 mg per day.

Take the tablet with a sufficient amount of water. To minimize gastrointestinal discomfort, administer during or after a meal.

Adverse Reactions

From the hematopoietic system very rarely – neutropenia, thrombocytopenia.

From the immune system rarely – laryngeal edema; very rarely – anaphylactic reactions, including anaphylactic shock.

From the nervous system infrequently – headache, dizziness, drowsiness; rarely – paresthesia, syncope (transient brief fainting).

From the psyche infrequently – insomnia, feeling of anxiety.

From the hearing organ and labyrinthine disorders infrequently – vertigo; very rarely – tinnitus.

From the organ of vision very rarely – blurred vision.

From the cardiovascular system infrequently – palpitations, feeling of heat, skin hyperemia; rarely – increased blood pressure; very rarely – tachycardia, decreased blood pressure.

From the respiratory system rarely – bradypnea; very rarely – bronchospasm, dyspnea.

From the gastrointestinal tract frequently – nausea, vomiting, abdominal pain, dyspepsia, diarrhea; infrequently – gastritis, constipation, dry mouth, flatulence; rarely – anorexia, erosive and ulcerative lesions of the gastrointestinal tract, ulcer bleeding or perforation; very rarely – pancreatic damage.

From the liver and biliary tract rarely – hepatitis, increased activity of liver enzymes, including AST and ALT; very rarely – liver damage.

From the urinary system rarely – polyuria, acute renal failure; very rarely – nephritis or nephrotic syndrome.

From the reproductive system rarely – in women, menstrual cycle disorders, in men, transient prostate function disorders with long-term use.

From the musculoskeletal system rarely – back pain.

From the skin and subcutaneous tissues infrequently – skin rash; rarely – urticaria, acne, increased sweating; very rarely – severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), angioedema of the face, allergic dermatitis, photosensitivity, skin itching.

Other infrequently – increased fatigue, asthenia, chills, general malaise; very rarely – peripheral edema.

As with the use of other NSAIDs, the following side effects may develop: aseptic meningitis, developing mainly in patients with systemic lupus erythematosus or other systemic connective tissue diseases, hematological disorders (thrombocytopenic purpura, aplastic and hemolytic anemia, in rare cases – agranulocytosis and bone marrow hypoplasia).

Contraindications

Hypersensitivity to dexketoprofen; 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 lesions of the gastrointestinal tract in the acute stage; gastrointestinal bleeding or perforation in history, including those associated with previous use of NSAIDs; gastrointestinal bleeding and other active bleeding (including suspected intracranial hemorrhage); inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) in the acute stage; severe hepatic failure (10-15 points on the Child-Pugh scale); progressive kidney diseases, confirmed hyperkalemia; chronic kidney disease: stages 3a (GFR 45-59 ml/min/1.73 m²), 3b (GFR 30-44 ml/min/1.73 m²) and 4 (GFR <30 ml/min/1.73 m²); period after coronary artery bypass grafting; severe heart failure (III-IV class according to NYHA classification); hemorrhagic diathesis and other blood clotting disorders; age under 18 years; pregnancy, breastfeeding period.

With caution

Peptic ulcer of the stomach and duodenum, ulcerative colitis, Crohn’s disease, history of liver diseases, hepatic porphyria, chronic kidney disease, stage 2 (GFR 60-89 ml/min/1.73 m²), chronic heart failure, arterial hypertension, significant decrease in circulating blood volume (including after surgery), bronchial asthma, simultaneous use of glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), coronary artery disease, cerebrovascular diseases, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral artery diseases, presence of Helicobacter pylori infection, systemic lupus erythematosus and other systemic connective tissue diseases, long-term use of NSAIDs, tuberculosis, severe osteoporosis, severe somatic diseases, alcoholism, smoking, elderly patients over 65 years (including those receiving diuretics, debilitated patients and patients with low body weight).

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding is contraindicated.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency. For patients with impaired liver function, the initial dose is no more than 50 mg/day.

Use in Renal Impairment

Contraindicated in renal insufficiency. For patients with impaired kidney function, the initial dose is no more than 50 mg/day.

Pediatric Use

The drug is contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Caution should be exercised when prescribing the drug to elderly patients. For elderly individuals, the initial dose is no more than 50 mg/day.

Special Precautions

Undesirable side effects can be minimized by using dexketoprofen at the lowest effective dose for the minimum duration necessary to relieve pain.

The risk of gastrointestinal complications increases in patients with a history of gastrointestinal ulcers, in elderly patients, with an increase in the dose of NSAIDs, so the use of this agent in this category of patients should be started with the lowest recommended dose.

Patients from the categories listed above, as well as patients who require simultaneous use of low-dose acetylsalicylic acid or other agents that increase the risk of gastrointestinal complications, are recommended to additionally use gastroprotective agents (misoprostol or proton pump inhibitors) simultaneously.

In patients simultaneously taking antiplatelet agents or anticoagulants, glucocorticosteroids, the risk of gastrointestinal bleeding also increases.

Patients with gastrointestinal disorders or a history of gastrointestinal diseases should be under close medical supervision. In case of gastrointestinal bleeding or ulcerative lesions, the use of dexketoprofen should be discontinued.

Dexketoprofen should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), as these diseases may worsen.

All NSAIDs can inhibit platelet aggregation and increase bleeding time by inhibiting prostaglandin synthesis. In this regard, the use of dexketoprofen in patients simultaneously taking drugs that affect the hemostatic system, such as warfarin, coumarin derivatives and heparins, is not recommended.

Like other NSAIDs, Dexketoprofen can increase the concentration of creatinine and nitrogen in blood plasma. Like other inhibitors of prostaglandin synthesis, it can have a side effect on the urinary system, which can lead to the development of glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure. Caution should be exercised when using this agent in patients simultaneously using diuretics and patients who may develop hypovolemia, due to an increased risk of nephrotoxicity.

As with the use of other NSAIDs, during therapy with the drug Flamadex^®, a slight transient increase in the activity of liver enzymes may be observed. In elderly patients, monitoring of liver and kidney function is necessary. In case of a significant increase in the corresponding indicators, the use of the drug Flamadex^® should be discontinued.

Like other NSAIDs, Dexketoprofen can mask the symptoms of infectious diseases. If signs of infection are detected or if the condition worsens during the use of the drug Flamadex^®, the patient should immediately consult a doctor.

The drug can cause fluid retention in the body, so in patients with arterial hypertension, renal and/or heart failure, Flamadex^® should be used with particular caution. In case of deterioration of the condition, the use of the drug must be discontinued.

In patients with uncontrolled arterial hypertension, coronary artery disease, congestive heart failure, peripheral artery diseases and/or cerebrovascular diseases, the drug should be used with caution. A similar approach applies to patients with risk factors for cardiovascular diseases (arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

Caution should be exercised when prescribing the drug Flamadex^® to patients with a history of cardiovascular diseases, especially patients with heart failure, due to the possible risk of progression.

Clinical studies and epidemiological data allow us to conclude that NSAIDs, especially in high doses and with long-term use, can lead to a slight risk of developing acute myocardial infarction or stroke. There is insufficient data to exclude the risk of these events when using dexketoprofen.

Elderly patients are especially susceptible to adverse reactions when using NSAIDs, including the risk of gastrointestinal bleeding and perforations, which are life-threatening to the patient, and decreased function of the kidneys, liver and heart. When using the drug Flamadex^® in this category of patients, proper clinical monitoring is necessary.

There are data on the occurrence of rare cases of skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) when using NSAIDs. At the first manifestations of skin rash, damage to mucous membranes or other signs of an allergic reaction, the patient should immediately stop using the drug Flamadex^® and consult a doctor.

Effect on ability to drive vehicles and mechanisms

Due to the possible occurrence of dizziness and drowsiness during the use of dexketoprofen, the ability to concentrate and the speed of psychomotor reactions in patients may decrease, especially in the first hour after administration. Therefore, during the use of the drug Flamadex^®, caution should be exercised when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

The drug interactions listed below are characteristic of all NSAIDs, including Dexketoprofen.

Undesirable combinations

With other NSAIDs, including salicylates in high doses (more than 3 g/day) simultaneous use of several NSAIDs due to a synergistic effect increases the risk of gastrointestinal bleeding and ulcers.

With anticoagulants Dexketoprofen, like other NSAIDs, can enhance the effect of anticoagulants such as warfarin, due to the high degree of binding to plasma proteins, inhibition of platelet aggregation and damage to the gastrointestinal mucosa. If simultaneous use is necessary, careful monitoring of the patient’s condition and regular monitoring of laboratory parameters is necessary.

With heparin when used simultaneously, the risk of bleeding increases (due to inhibition of platelet aggregation and damaging effect on the gastrointestinal mucosa). If simultaneous use is necessary, careful monitoring of the patient’s condition and regular monitoring of laboratory parameters is necessary.

With glucocorticosteroids when used simultaneously, the risk of gastrointestinal ulcers and bleeding increases.

With lithium preparations NSAIDs increase the concentration of lithium in blood plasma up to toxic levels, therefore this indicator must be monitored when used simultaneously with dexketoprofen, when changing the dose, as well as after discontinuation of the NSAID.

With high-dose methotrexate (15 mg/week and more) an increase in the hematological toxicity of methotrexate is possible due to a decrease in its renal clearance with the simultaneous use of NSAIDs.

With hydantoins and sulfonamides an increase in their toxic effect is possible.

Combinations requiring caution

With diuretics, ACE inhibitors, antibiotics from the aminoglycoside group, angiotensin II receptor antagonists simultaneous use with NSAIDs is associated with the risk of acute renal failure in patients with dehydration (decreased glomerular filtration due to reduced synthesis of prostaglandins). When used simultaneously, NSAIDs may reduce the antihypertensive effect of some drugs. With the simultaneous use of dexketoprofen and diuretics, it is necessary to ensure that the patient has no signs of dehydration, and also to monitor renal function at the beginning of simultaneous use.

With low-dose methotrexate (less than 15 mg/week) an increase in the hematological toxicity of methotrexate is possible due to a decrease in its renal clearance against the background of simultaneous use with NSAIDs. A blood cell count is required at the start of concomitant use. In the presence of impaired renal function, even of a mild degree, as well as in elderly persons, careful medical supervision is necessary.

With pentoxifylline an increase in the risk of bleeding is possible. Careful clinical monitoring and regular checking of bleeding time (blood clotting time) are necessary.

With zidovudine there is a risk of increased toxic effects on red blood cells due to effects on reticulocytes, with the development of severe anemia one week after the start of NSAID use. A complete blood count with a reticulocyte count is necessary 1-2 weeks after the start of NSAID therapy.

With oral hypoglycemic agents NSAIDs may enhance the hypoglycemic effect of sulfonylurea drugs due to the displacement of sulfonylurea from plasma protein binding sites.

Combinations to be taken into account

With beta-blockers when used simultaneously with NSAIDs, the antihypertensive effect of beta-blockers may decrease due to inhibition of prostaglandin synthesis.

With cyclosporine and tacrolimus NSAIDs may increase nephrotoxicity, which is mediated by the action of renal prostaglandins. When used simultaneously, renal function should be monitored.

With thrombolytics the risk of bleeding increases.

The risk of gastrointestinal bleeding increases with simultaneous use with selective serotonin reuptake inhibitors (citalopram, fluoxetine, sertraline) and anticoagulants.

With probenecid an increase in the plasma concentration of NSAIDs is possible, which may be due to the inhibitory effect of probenecid on renal tubular secretion and/or conjugation with glucuronic acid; adjustment of the NSAID dose may be required.

With cardiac glycosides simultaneous use with NSAIDs may lead to an increase in the plasma concentration of cardiac glycosides.

With mifepristone due to the theoretical risk of changes in the effectiveness of mifepristone under the influence of prostaglandin synthesis inhibitors, NSAIDs should not be used earlier than 8-12 days after discontinuation of mifepristone.

With quinolones data obtained in experimental animal studies indicate a high risk of seizures with the simultaneous use of NSAIDs with high doses of quinolones.

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.