Oxyliten

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT OXILITEN (OXILITEN)

Composition:

Active substance: tenoxicam;

1 tablet contains 20 mg of tenoxicam;

Excipients: lactose monohydrate; corn starch; talc; magnesium stearate; coating: hypromellose, talc, titanium dioxide (E 171), yellow iron oxide (E 172).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: brownish-yellow, round, biconvex tablets.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory drugs. Oxicams. ATC code M01AC.

Pharmacological properties.

Pharmacodynamics.

Tenoxicam is a nonsteroidal anti-inflammatory drug of the oxicam class. It exerts analgesic and anti-inflammatory effects; the antipyretic effect is less pronounced. The mechanism of action is based on non-selective inhibition of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzyme activity, which disrupts arachidonic acid metabolism, thereby reducing prostaglandin synthesis at the site of inflammation and in other tissues of the body. In addition, tenoxicam reduces leukocyte accumulation at the site of inflammation. It decreases capillary permeability and stabilizes lysosomal membranes; inhibits the release of macroergic compounds (primarily ATP) in oxidative phosphorylation processes; suppresses the synthesis or inactivates inflammatory mediators (prostaglandins, histamine, bradykinins, lymphokines, complement factors, etc.). Tenoxicam blocks the interaction of bradykinin with tissue receptors, restores impaired microcirculation, and reduces pain sensitivity at the site of inflammation. It affects thalamic pain sensitivity centers (local blockade of PgE1, PgE2, and PgF2 alpha synthesis).

Analgesic action is due to reduced concentrations of biogenic amines with algogenic properties and increased pain sensitivity threshold of the receptor apparatus. It suppresses or reduces the intensity of pain syndrome of any etiology, decreases morning stiffness, and improves mobility of affected joints. With prolonged use, it exhibits desensitizing effects. A distinctive feature of tenoxicam is its prolonged duration of action.

Pharmacokinetics.

Tenoxicam is rapidly and completely absorbed from the gastrointestinal tract. Food intake slows the rate of absorption. Bioavailability is 100%. Maximum plasma concentration is reached within 2 hours after administration. The elimination half-life is 60–75 hours. The drug is 99% bound to plasma proteins, penetrates well into synovial fluid, and 67% is excreted in urine. In the liver, it undergoes hydroxylation, forming 5-hydroxytenoxicam. It readily crosses histohematologic barriers. The major portion is excreted as inactive metabolites in urine, the remainder – via bile.

Clinical characteristics.

Indications.

Treatment of pain and inflammation in osteoarthritis and rheumatoid arthritis.

Short-term treatment of inflammatory-degenerative disorders of the musculoskeletal system, including dislocations and other soft tissue injuries.

Contraindications.

Hypersensitivity to tenoxicam, to other components of the drug, to ibuprofen, acetylsalicylic acid, or to other nonsteroidal anti-inflammatory drugs (NSAIDs) (symptoms of bronchial asthma, rhinitis, angioneurotic edema, or urticaria); severe heart, liver, or kidney failure; active peptic ulcer, gastrointestinal bleeding in the acute phase, history of ulcers or bleeding (two or more distinct documented episodes of ulceration or bleeding); gastrointestinal bleeding or perforation (in history) associated with previous use of NSAIDs.

Interaction with other medicinal products and other types of interactions.

Therapeutic doses of tenoxicam have no pharmacokinetic interaction with antacids, cimetidine, oral anticoagulants, or hypoglycemic agents; however, it may enhance the effect of anticoagulants such as coumarin and warfarin.

Probenecid: increases the elimination of tenoxicam.

Cardiac glycosides: no interaction with digoxin has been reported; NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides.

Diuretics: NSAIDs may cause retention of potassium and sodium ions as well as fluid, and reduce the natriuretic effect of diuretics, thereby increasing the risk of nephrotoxicity. Therefore, in patients with arterial hypertension or heart failure, tenoxicam may worsen the course of these conditions.

Lithium: continuous monitoring is recommended. Lithium toxicity may occur due to reduced lithium elimination.

Methotrexate: methotrexate toxicity may occur due to reduced methotrexate elimination.

Cyclosporine: increased risk of nephrotoxicity.

Mifepristone: NSAIDs should not be used within 8–12 days after mifepristone administration, as they may reduce the efficacy of mifepristone.

Other analgesics: concomitant use of two or more NSAIDs should be avoided due to increased risk of gastrointestinal bleeding and ulcers.

Salicylates: it is undesirable to take Oxilithen simultaneously with salicylates, which compete with tenoxicam for protein binding sites, thereby enhancing its clearance and distribution. Concomitant use should be avoided due to the risk of increased adverse reactions (especially gastrointestinal).

Corticosteroids: increased risk of gastrointestinal bleeding.

Anticoagulants: may potentiate the anticoagulant effect of warfarin and other anticoagulants. The effects of anticoagulants and oral hypoglycemic agents should be monitored particularly carefully at the beginning of tenoxicam therapy.

Quinolone antibiotics: increased risk of seizures when used concomitantly.

Antiplatelet agents and serotonin receptor blockers: increased risk of gastrointestinal bleeding.

Special precautions for use.

When using Oxylyten, gastrointestinal function should be monitored. At the first signs of ulcerogenesis or gastrointestinal bleeding, the drug must be discontinued immediately. Use with caution in patients with impaired renal function; continuous monitoring is required in cases of worsening renal insufficiency, concomitant use of diuretics and nephrotoxic drugs, increased blood urea nitrogen, serum creatinine, body weight, diabetic nephropathy, peripheral edema in elderly patients, congestive heart failure, and hypovolemia. In patients with renal insufficiency and creatinine clearance greater than 25 mL/min, medical supervision is required without dose adjustment. Use with caution in patients with impaired liver function, low plasma albumin concentration (e.g., in nephrotic syndrome) or high bilirubin levels. If significant and persistent elevation of transaminases occurs during treatment with Oxylyten, the drug should be discontinued. Oxylyten may cause potassium and lithium retention, as well as fluid retention. Therefore, in patients with arterial hypertension or heart failure, tenoxicam may worsen the course of these conditions. Close monitoring is required for patients with a history of moderate or severe heart failure who develop edema during NSAID therapy. Tenoxicam reduces platelet aggregation and may prolong bleeding time. This should be considered in patients who have undergone major surgery (e.g., joint replacement), and bleeding time should be carefully monitored. Patients receiving oral anticoagulants or hypoglycemic agents must be under close surveillance, and the drug should not be used if monitoring is not feasible.

Oxylyten should not be used concomitantly with other NSAIDs, including selective cyclooxygenase-2 inhibitors.

Respiratory system

Caution is required when treating patients with bronchial asthma or a history of asthma, as the drug may induce bronchospasm in such patients.

Cardiovascular, hepatic, and renal disorders

Rarely, NSAIDs may cause interstitial nephritis, papillary necrosis, glomerulonephritis, and nephrotic syndrome. These agents suppress renal prostaglandin synthesis, which plays a supportive role in maintaining renal perfusion. As a result, blood volume and renal blood flow may decrease. NSAID administration may trigger reversible renal failure, which resolves promptly after discontinuation of the drug. Patients at highest risk include those with pre-existing kidney disease (including diabetic nephropathy), nephrotic syndrome, dehydration, liver disease, congestive heart failure, or those receiving concomitant therapy with diuretics or potentially nephrotoxic drugs. Such patients require careful monitoring of renal, hepatic, and cardiac function, and lower doses should be used compared to other patient groups. NSAIDs should be used cautiously in patients with a history of heart failure or arterial hypertension, as edema associated with NSAID use has been reported with tenoxicam. Cases of elevated serum transaminases or other liver function test abnormalities have been reported. In most cases, these changes were mild and transient. If abnormalities are significant or persistent, Oxylyten should be discontinued and liver function tests should be monitored until values return to normal.

Cardiovascular disorders

Appropriate monitoring and consultation are necessary for patients with a history of arterial hypertension and/or mild to moderate heart failure, as fluid retention and edema have been observed during NSAID therapy. Clinical studies have shown that the use of some NSAIDs (particularly at high doses and during long-term treatment) may be associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). There is insufficient data to exclude such a risk with tenoxicam.

Tenoxicam should be used with caution in patients with uncontrolled arterial hypertension, heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease, following careful assessment of the individual’s condition. This assessment should be performed before initiating long-term treatment in patients with cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

Gastrointestinal bleeding, ulceration, and perforation

There have been reports of gastrointestinal bleeding, ulceration, and perforation during NSAID therapy, which may be fatal.

The risk of gastrointestinal bleeding, ulceration, or perforation is higher with high-dose NSAID use, particularly in patients with a history of peptic ulcer, especially with severe bleeding or perforation. Such patients should start treatment at the lowest dose. For these patients and those requiring concomitant low-dose acetylsalicylic acid or other medications, combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) may be considered to reduce gastrointestinal risk. Patients with a history of gastrointestinal disorders, particularly elderly patients, should inform their physician of any gastrointestinal symptoms (including gastrointestinal bleeding), especially at the beginning of treatment.

The drug should be prescribed cautiously to patients receiving medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or platelet agents (e.g., acetylsalicylic acid).

If gastrointestinal bleeding or ulceration occurs during Oxylyten therapy, treatment should be discontinued immediately.

The drug should be used with caution in patients with a history of gastrointestinal diseases (e.g., ulcerative colitis, Crohn’s disease), as tenoxicam may exacerbate these conditions.

Patients with systemic lupus erythematosus or mixed connective tissue disease have an increased risk of developing aseptic meningitis.

Dermatology

During NSAID use, there have been rare reports of severe skin reactions, some of which were fatal, including exfoliative dermatitis, Stevens–Johnson syndrome, and toxic epidermal necrolysis.

The risk of such reactions is highest during the initial stages of therapy, with manifestations typically occurring within the first months of treatment.

Oxylyten therapy should be discontinued at the first signs of skin rash, mucosal lesions, or other hypersensitivity reactions.

Impairment of fertility

Oxylyten may impair female fertility and therefore is not recommended for women wishing to become pregnant.

Tenoxicam should not be prescribed to women who are unable to conceive or who have diagnosed infertility.

Ophthalmological adverse reactions

Ocular adverse effects have been reported during NSAID use; therefore, patients who develop visual disturbances during Oxylyten therapy should undergo ophthalmological evaluation.

Life-threatening skin reactions (Stevens–Johnson syndrome and toxic epidermal necrolysis) have been reported during tenoxicam use.

Patients with signs of skin reactions should be closely monitored.

The risk of Stevens–Johnson syndrome and toxic epidermal necrolysis is greatest during the first weeks of treatment.

If signs of Stevens–Johnson syndrome or toxic epidermal necrolysis occur (e.g., progressive skin rash, often with blisters, or maculopapular lesions), tenoxicam therapy must be discontinued.

The best outcomes in treating Stevens–Johnson syndrome and toxic epidermal necrolysis are achieved with early diagnosis and immediate discontinuation of any suspected drug.

Tenoxicam must not be re-administered to patients who have previously experienced Stevens–Johnson syndrome or toxic epidermal necrolysis during its use.

The product contains lactose; therefore, it should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding.

Pregnancy

The drug should not be used during pregnancy.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage and congenital heart defects and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increases from less than 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of treatment. Animal studies have shown that prostaglandin synthesis inhibitors increase pre- and post-implantation loss and embryonic/fetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, an increased incidence of various developmental abnormalities, including cardiovascular malformations, has been observed.

If a woman trying to conceive uses tenoxicam, the lowest possible dose for the shortest duration should be prescribed.

From the 20th week of pregnancy, tenoxicam use may cause oligohydramnios due to fetal renal dysfunction.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may have the following effects:

on the fetus:

• cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
• impaired renal function, which may progress to renal failure with oligohydramnios;

on the mother and newborn, near the end of pregnancy:

• possible prolongation of bleeding time; anti-aggregatory effect, which may occur even at very low doses;
• inhibition of uterine contractions, leading to delayed or prolonged labor.

Breastfeeding

Breastfeeding should be discontinued during treatment with the drug, as the effects on infants during breastfeeding are unknown.

Ability to influence reaction rate while driving or operating machinery.

No studies on the effect of the drug on the ability to drive or operate machinery have been conducted. However, considering the drug's adverse effects on the nervous system and visual organs, driving or operating complex machinery is not recommended.

Method of administration and dosage.

Take tablets orally, swallowing with liquid, preferably with food or after meals.

Adults: The recommended dose is 1 tablet (20 mg) once daily at the same time each day.

Recommended doses should not be exceeded, as this does not provide a significant therapeutic effect but increases the risk of adverse effects.

For acute musculoskeletal disorders, the treatment duration usually does not exceed 7 days; however, in severe cases, administration may be continued for up to 14 days.

Elderly patients

Oxilithen, like other NSAIDs, should be used with caution due to lower tolerance to adverse effects compared to younger patients. Elderly patients more frequently receive concomitant medications or have impaired kidney, liver, or cardiovascular function. If NSAID use is necessary, low doses should be prescribed for prolonged periods. Patients should be monitored, as occult gastrointestinal bleeding may occur within 4 weeks after initiation of therapy.

Patients with impaired kidney and liver function

Caution should be exercised in patients with low albumin concentrations (e.g., in nephrotic syndrome) or with high plasma bilirubin levels, since tenoxicam is highly bound to plasma proteins.

There are insufficient data regarding patients with hepatic impairment to recommend dosage adjustments for the drug Oxiliten.

Children.

There are no data on the safety of tenoxicam in children; therefore, it should not be administered to this patient group.

Overdose.

There have been no reports of severe cases of tenoxicam overdose.

Symptoms: headache, dizziness, nausea, vomiting, diarrhea, epigastric pain or discomfort, diarrhea, gastrointestinal bleeding, disorientation, excitement, coma, drowsiness, dizziness, tinnitus, weakness, loss of consciousness, and occasionally seizures. Acute renal or hepatic failure may occur in severe poisonings.

Treatment. If necessary, symptomatic therapy should be administered. Within the first hour after ingestion, gastric lavage should be performed and activated charcoal administered. Adequate urinary output should be maintained. Renal and hepatic functions should be monitored. Patients should remain under medical supervision for at least 4 hours following overdose. In cases of frequent or prolonged seizures, diazepam should be administered intravenously. There is no specific antidote.

Adverse Reactions

The most commonly observed adverse effects are those related to the gastrointestinal tract – erosive and ulcerative lesions of the gastrointestinal tract, including ulcerogenic activity.

Gastrointestinal: nausea, vomiting, diarrhea, constipation, heartburn, dyspepsia, abdominal pain, melena, epigastric distress, hematemesis, flatulence, ulcerative stomatitis, gastrointestinal hemorrhage, gastritis, peptic ulcers, or gastrointestinal bleeding.

Hepatobiliary system: liver function abnormalities, hepatitis, jaundice, possible increase in blood transaminase levels.

Blood and lymphatic system: thrombocytopenia; thrombocytopenic purpura; neutropenia; agranulocytosis; aplastic anemia and hemolytic anemia; decreased hemoglobin levels unrelated to bleeding; leukopenia; eosinophilia.

Metabolic: hyperglycemia, weight gain or weight loss.

Nervous system: excitement, optic neuritis, paresthesia, depression, nervousness, hallucinations (confusion), drowsiness or insomnia, sleep disturbances, tinnitus, malaise, weakness, increased fatigue, headache, dizziness, tremor.

Visual system: eye irritation and swelling, blurred vision.

No cases of visual disturbances have been detected upon examination with a slit lamp or ophthalmoscope.

Cardiovascular system: edema, dyspnea, tachycardia, palpitations. Heart failure and arterial hypertension associated with NSAID therapy may occur. Elderly patients with cardiac functional impairments should use the drug with caution, as increased edema may lead to congestive heart failure.

NSAIDs (at high doses and with prolonged use) may increase the risk of arterial thrombosis (myocardial infarction, stroke).

Urinary system: nephrotoxicity, including interstitial nephritis, nephrotic syndrome, and renal failure.

Hypersensitivity reactions: non-specific allergic reactions, anaphylactic reactions, respiratory tract reactivity including bronchial asthma, bronchospasm, or dyspnea; skin disorders – rash, pruritus, urticaria, angioneurotic edema, bullous dermatitis (including toxic epidermal necrolysis, Stevens-Johnson syndrome, and exfoliative dermatitis); possible alopecia, photosensitization, Lyell's syndrome.

Laboratory findings: increased blood transaminase levels, hyperglycemia, reversible increase in blood urea nitrogen and plasma creatinine.

If any adverse reaction occurs, treatment should be discontinued. Adverse reactions can be minimized by using the lowest effective dose for the shortest possible duration.

Shelf life: 3 years.

Storage conditions

Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging

10 tablets in a blister pack, 1 blister pack in a cardboard box.

Prescription status: Prescription only.

Manufacturer:

Anfarm Hellas S.A.

Manufacturer's address and location of business operations:

61st km National Road Athens-Lamia, Schimatari Viotias, 32009, Greece.