INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TEXINOR (TEXINOR)

Composition:

Active substance: tenoxicam;

1 vial of lyophilisate for solution for injection contains 20 mg of tenoxicam;

Excipients: mannitol (E 421), edetate disodium, ascorbic acid, tromethamine, sodium hydroxide, sodium hydroxide or hydrochloric acid diluted;

1 ampoule of solvent contains 2 ml of water for injections.

Medicinal form. Lyophilisate for solution for injection.

Main physicochemical characteristics: yellow lyophilized powder.

Solvent (water for injections): clear, colorless solution.

Reconstituted solution: clear yellow-green solution.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic drugs. Oxicams.

ATC code M01A C02.

Pharmacological Properties

Pharmacodynamics

Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID). It has pronounced analgesic, anti-inflammatory, and antipyretic effects.

The mechanism of action is based on non-selective inhibition of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzyme activity, thereby disrupting the synthesis of prostaglandins and thromboxanes. Tenoxicam inhibits platelet aggregation.

In vitro studies also indicate that tenoxicam may act as an acceptor of active oxygen at the site of inflammation and has the ability to inhibit metalloproteinases (stromelysin and collagenase) responsible for cartilage destruction.

Pharmacokinetics

The bioavailability of tenoxicam following intramuscular and oral administration is similar. After intravenous administration of a 20 mg dose, the plasma concentration of tenoxicam rapidly declines over 2 hours, which is related to the distribution process. After this short period, there is no difference in plasma concentrations of tenoxicam following intravenous, intramuscular, or oral administration. Tenoxicam is highly bound (99%) to plasma proteins and penetrates well into synovial fluid.

The mean volume of distribution at equilibrium is 10–12 L. At the recommended dosage regimen of 20 mg daily, steady-state plasma concentrations are achieved within 10–15 days. No accumulation occurs.

Tenoxicam is completely metabolized in the body. Approximately two-thirds of the administered dose is excreted in urine, primarily as the pharmacologically inactive metabolite 5-hydroxypyridyl, and the remainder is excreted in bile, mainly as glucuronide conjugates of hydroxymetabolites. The elimination half-life is 72 hours. Total plasma clearance is 2 mL/min.

The pharmacokinetics of tenoxicam are linear within the studied dose range of 10 to 100 mg.

No age-related changes in the pharmacokinetics of tenoxicam have been observed, although individual variability is generally greater in elderly patients.

Clinical characteristics

Indications

For relief of pain and inflammation in osteoarthritis and rheumatoid arthritis.
For short-term treatment of acute musculoskeletal disorders, particularly strains, sprains, and other soft tissue injuries.

The medicinal product Texinor should be used when it is not possible to administer tenoxicam in tablet form.

Contraindications

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
History of hypersensitivity reactions (including asthma, rhinitis, angioedema, urticaria) to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs).
Active recurrent peptic ulcer/bleeding or history of recurrent episodes (2 or more distinct episodes of peptic ulcer or bleeding), ulcerative colitis, Crohn's disease, severe gastritis.
History of gastrointestinal bleeding (melena, hematemesis) or perforations associated with previous NSAID therapy.
History of cerebrovascular bleeding or other coagulation disorders.
Severe cardiac, hepatic, or renal failure.
Third trimester of pregnancy.
Breastfeeding period.
Pediatric population (under 18 years of age).

Interaction with other medicinal products and other forms of interaction

With other NSAIDs (including COX-2 inhibitors) — increased risk of adverse reactions. Concomitant use of two or more NSAIDs should be avoided.

With acetylsalicylic acid and other salicylates — possible increase in clearance and altered distribution of tenoxicam due to competition for plasma protein binding sites. Concomitant use of these agents should be avoided due to increased risk of adverse reactions (particularly gastrointestinal).

With anticoagulants (warfarin) — possible potentiation of their effects. When used concomitantly, anticoagulant effects should be monitored, especially during initial stages of tenoxicam therapy. No clinically significant interactions between tenoxicam and low-molecular-weight heparin have been reported.

With cardiac glycosides — possible exacerbation of heart failure, decreased glomerular filtration rate, and increased plasma levels of cardiac glycosides. No clinically significant interactions between tenoxicam and digoxin or digitalis preparations have been reported.

With cyclosporine — increased risk of nephrotoxicity. Caution should be exercised when these agents are used concomitantly.

With quinolones — preclinical data indicate that NSAIDs increase the risk of seizures induced by quinolones. The likelihood of seizures increases when tenoxicam is used concomitantly with quinolones.

With lithium — possible reduction in its elimination. When these agents are used concomitantly, plasma lithium levels should be monitored regularly, and patients should be advised to maintain adequate fluid intake and be aware of symptoms of lithium intoxication.

With diuretics — possible reduction in natriuretic activity of diuretics and increased risk of nephrotoxicity due to the ability of NSAIDs to retain potassium, sodium, and fluid. In patients with arterial hypertension or heart failure, tenoxicam may worsen the course of these conditions. No clinically significant interactions between tenoxicam and furosemide have been reported; however, reduced antihypertensive effect of hydrochlorothiazide has been reported when used concomitantly with tenoxicam.

With antihypertensive agents — possible attenuation of effects of alpha-adrenergic blockers and angiotensin-converting enzyme (ACE) inhibitors. No clinically significant interactions between tenoxicam and calcium channel blockers, atenolol, or central alpha-adrenergic agonists have been reported.

With methotrexate — possible increase in its toxicity due to reduced elimination. Caution should be exercised when these agents are used concomitantly.

With oral hypoglycemic agents — although there are no reports of effects on clinical outcomes of glyburide, glipizide, or tolbutamide, patients should be closely monitored when oral hypoglycemic agents are used concomitantly with tenoxicam.

With dextromethorphan — possible enhancement of the analgesic effect of tenoxicam.

With cholestyramine — possible increased clearance and reduced elimination half-life of tenoxicam.

With probenecid — possible increase in plasma levels of tenoxicam. The clinical significance of this phenomenon has not been established.

With mifepristone — possible reduction in its efficacy. NSAIDs should be administered 8–12 days after completion of mifepristone treatment.

With corticosteroids — increased risk of gastrointestinal bleeding and perforation. Caution should be exercised when these agents are used concomitantly.

With antiplatelet agents, selective serotonin reuptake inhibitors (SSRIs) — increased risk of gastrointestinal bleeding.

With tacrolimus — increased risk of nephrotoxicity.

With zidovudine — increased risk of hematological toxicity. Evidence suggests increased risk of hemarthrosis and hematomas in HIV-infected patients with hemophilia when zidovudine and ibuprofen are used concomitantly.

With penicillamine, parenteral gold preparations — no clinically significant interactions have been observed in a small number of patients receiving these agents concomitantly.

Special precautions for use

The adverse effects of tenoxicam can be minimized by using the lowest effective dose for the shortest possible duration.

Concomitant use of the medicinal product with NSAIDs, particularly selective cyclooxygenase-2 (COX-2) inhibitors, and agents that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), antiplatelet agents (e.g., acetylsalicylic acid), and selective serotonin reuptake inhibitors (SSRIs), should be avoided.

Gastrointestinal bleeding, ulcers, and perforations

Gastrointestinal bleeding, ulcers, and perforations (including fatal cases) have been reported during the use of all NSAIDs. These events can occur at any time during treatment, with or without warning symptoms, and regardless of whether the patient has a history of gastrointestinal disorders.

The risk of such events increases with higher NSAID doses, particularly in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation, and in elderly patients. Treatment in these patients should be initiated with the lowest possible effective dose. For these patients, as well as for those concurrently taking low-dose acetylsalicylic acid or other agents that increase the risk of gastrointestinal complications, consideration should be given to using combination therapy with agents such as misoprostol or proton pump inhibitors.

Patients, particularly elderly individuals and those with a history of gastrointestinal toxicity, should report any unusual gastrointestinal symptoms, especially bleeding. This is particularly important during the initial stages of treatment.

The medicinal product should be used with caution in patients receiving medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors (SSRIs), or platelet agents (e.g., acetylsalicylic acid).

If gastrointestinal bleeding or ulceration occurs, the use of the medicinal product should be discontinued.

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

Use in patients with systemic lupus erythematosus and mixed connective tissue disorders

The use of NSAIDs in such patients increases the risk of developing aseptic meningitis.

Cutaneous effects

Rarely, NSAIDs may cause severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, sometimes with fatal outcomes. The risk of such reactions is highest at the beginning of treatment, with the first manifestations usually occurring within the first month of therapy.

Patients should be informed about the symptoms, and such skin reactions should be closely monitored.

At the first signs of skin rash, mucosal lesions, or other signs of hypersensitivity, the medicinal product should be discontinued immediately. The best outcomes in treating Stevens-Johnson syndrome and toxic epidermal necrolysis are achieved with early diagnosis and discontinuation of any suspected medicinal product.

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

Cardiovascular, renal, and hepatic disorders

Rarely, NSAIDs may cause interstitial nephritis, glomerulonephritis, papillary necrosis, or nephrotic syndrome due to inhibition of renal prostaglandin synthesis, which supports renal perfusion in patients with reduced renal blood flow and blood volume. In such patients, NSAID use may lead to pronounced decompensation of renal function, which usually returns to baseline after discontinuation of therapy. The highest risk of such complications occurs in patients with pre-existing renal disease (including diabetes with impaired renal function), nephrotic syndrome, reduced blood volume, hepatic dysfunction, congestive heart failure, those concurrently taking diuretics or nephrotoxic agents, and in elderly patients. Renal, hepatic, and cardiac functions should be closely monitored during treatment in these patients. The medicinal product should be administered at the lowest possible dose in patients with renal, hepatic, or cardiac impairment.

Respiratory effects

The medicinal product should be used with caution in patients with bronchial asthma or a history of bronchial asthma, as NSAID use may provoke bronchospasm.

Elevated plasma levels of transaminases or other liver function parameters may occur during NSAID use. These changes are usually transient. If significant and persistent abnormalities develop, the medicinal product should be discontinued and liver function should be evaluated. The medicinal product should be used with caution in patients with hepatic impairment.

Tenoxicam reduces platelet aggregation and prolongs bleeding time, which should be considered when planning surgical procedures or when bleeding time needs to be determined.

Use in elderly patients

In elderly patients, NSAID use is associated with an increased frequency of adverse reactions, particularly gastrointestinal bleeding and perforations (including fatal cases). Weakened patients tolerate ulcers and bleeding less well. Most fatal gastrointestinal events associated with NSAID use have occurred in elderly and weakened patients. Particular caution and regular monitoring of renal, hepatic, and cardiovascular functions, as well as the patient’s general condition, to detect possible interactions with concomitant medications, are required when using the medicinal product in such patients.

Ophthalmological effects

Ocular adverse events have been reported during NSAID use. If such disorders occur during treatment, an ophthalmological examination should be performed.

Cardiovascular and cerebrovascular effects

Patients with hypertension and/or a history of mild to moderate heart failure should be closely monitored during treatment, as NSAID therapy has been associated with the development of edema and fluid retention.

The long-term use of some NSAIDs, particularly at high doses (150 mg/day), increases the risk of arterial thrombosis, myocardial infarction, or stroke. At present, there is insufficient information to exclude such risks with tenoxicam use.

The medicinal product should be used with caution in patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease, following careful assessment of the patient’s condition. This assessment should be performed before initiating long-term treatment in patients with cardiovascular risk factors (such as hypertension, hyperlipidemia, diabetes, smoking).

Antipyretic effects

Like other NSAIDs, tenoxicam may mask the signs of infection.

Laboratory tests

NSAIDs inhibit the synthesis of renal prostaglandins and may therefore adversely affect renal hemodynamics and fluid-electrolyte balance.

Careful monitoring, particularly of cardiac and renal function (plasma urea, creatinine, development of edema, weight gain), is required during treatment in patients at increased risk of renal impairment, such as those with renal disease, impaired renal function in diabetes, liver cirrhosis, congestive heart failure, reduced blood volume, or those receiving potentially nephrotoxic agents, diuretics, or corticosteroids. These patients are at particular risk during the peri- and postoperative periods, especially after major surgical procedures with significant blood loss.

Due to the high plasma protein binding of tenoxicam, the medicinal product should be used with caution in patients with markedly reduced plasma albumin levels.

Effect on fertility

The medicinal product is not recommended for women who are trying to conceive. If a woman has difficulty conceiving or is undergoing infertility investigations, discontinuation of the medicinal product should be considered.

Sodium content

The medicinal product contains less than 1 mmol of sodium (23 mg) per dose, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding

Pregnancy

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

From the 20th week of pregnancy, the use of tenoxicam may cause oligohydramnios due to fetal renal dysfunction. This condition may occur soon after the start of treatment and usually resolves after discontinuation. Cases of ductus arteriosus constriction have also been reported after treatment with prostaglandin synthesis inhibitors during the second trimester, which usually resolves after treatment is stopped.

The medicinal product must not be used during the first and second trimesters of pregnancy except in cases of strict medical necessity.

Women who are trying to conceive or who are pregnant during the first and second trimesters should be treated with the lowest effective dose for the shortest possible duration.

After several days of tenoxicam exposure starting from the 20th gestational week, prenatal monitoring for oligohydramnios and ductus arteriosus constriction may be required. If oligohydramnios or ductus arteriosus constriction is detected, the medicinal product should be discontinued.

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 (see above);

on the mother at the end of pregnancy and on the newborn:

prolonged bleeding time; antiplatelet effect, which may occur even with very low doses;
inhibition of uterine contractions, leading to delayed or prolonged labor.

The medicinal product is contraindicated during the third trimester of pregnancy.

Breastfeeding

Tenoxicam passes into breast milk in small amounts. If treatment is necessary, breastfeeding should be discontinued.

Fertility

Tenoxicam may impair female fertility; therefore, the medicinal product is not recommended for women who are trying to conceive.

If a woman has difficulty conceiving or is undergoing infertility investigations, discontinuation of the medicinal product should be considered.

Ability to influence the speed of reactions while driving or operating machinery

Dizziness, drowsiness, fatigue, and visual disturbances may occur during NSAID use. If such reactions occur, patients should refrain from driving or operating machinery.

Administration and Dosage

The medicinal product is intended for intravenous and intramuscular administration.

Before use, the contents of the vial should be dissolved in 2 mL of water for injections provided in the medicinal product kit. After complete dissolution of the lyophilisate, the solution should be used immediately.

Adults

The recommended dose of the medicinal product is 20 mg per day during the first 1–2 days of treatment; thereafter, transition to tablet administration is recommended, with tablets taken daily at the same time each day.

Recommended doses should not be exceeded, as higher doses do not necessarily result in a more pronounced therapeutic effect and may increase the risk of adverse reactions.

The duration of treatment with tenoxicam for acute musculoskeletal disorders usually does not exceed 7 days. In exceptional cases, therapy may be extended up to 14 days.

Elderly Patients

The medicinal product Texinor, like other NSAIDs, should be used with particular caution in elderly patients. These patients are at increased risk of adverse reactions and more frequently receive concomitant medications or have impaired renal, hepatic, or cardiovascular function. If necessary, the medicinal product should be administered to elderly patients at the lowest effective dose of 20 mg for the shortest duration required to control disease symptoms. Such patients should be carefully monitored for gastrointestinal bleeding during the first 4 weeks after initiation of therapy.

Patients with Renal and/or Hepatic Impairment

For patients with creatinine clearance greater than 25 mL/min, no dosage adjustment is required. These patients should be closely monitored (see section "Special Warnings and Precautions for Use").

There are insufficient data to recommend dosage adjustments of tenoxicam for patients with creatinine clearance less than 25 mL/min.

There are also insufficient data to recommend dosage adjustments of tenoxicam for patients with hepatic insufficiency.

The medicinal product should be used with caution in patients with low albumin concentrations (e.g., in nephrotic syndrome) or high plasma bilirubin concentrations, as tenoxicam is highly bound to plasma proteins.

Children

There are no data on the safety of tenoxicam in children; therefore, the medicinal product should not be used in this patient population.

Overdose

Common symptoms of NSAID overdose include nausea, vomiting, epigastric pain, gastrointestinal bleeding, tinnitus, headache, visual disturbances, dizziness, and rarely diarrhea. In isolated cases, more severe effects have been reported, such as seizures, agitation, somnolence, hypotension, apnea, coma, electrolyte imbalance, and renal failure. Exacerbation of bronchial asthma is also possible.

Treatment. Discontinue administration of the medicinal product. Maintain adequate hydration and monitor liver and kidney function. The patient should be under medical supervision for at least 4 hours after overdose. Symptomatic therapy should be administered as needed. Hemodialysis is ineffective. There is no specific antidote.

Adverse Reactions

Criteria for assessing the frequency of adverse drug reactions: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10,000, < 1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from available data).

The most commonly observed adverse reactions are gastrointestinal – erosive and ulcerative lesions, including ulcerogenic effects.

Blood and lymphatic system disorders:

Frequency not known: agranulocytosis, anemia, aplastic anemia, hemolytic anemia, leukopenia, thrombocytopenia, non-thrombocytopenic purpura, eosinophilia.

Immune system disorders:

Frequency not known: hypersensitivity reactions, including asthma, anaphylactic shock, angioneurotic edema.

Metabolism and nutrition disorders:

Common: anorexia; rare: metabolic disturbances (hyperglycemia, weight gain/weight loss).

Psychiatric disorders:

Rare: sleep disorders, insomnia, depression, nervousness, restlessness, abnormal dreams; frequency not known: confusion, hallucinations.

Nervous system disorders:

Common: dizziness, headache; frequency not known: somnolence, paresthesia, optic neuritis.

Eye disorders:

Frequency not known: visual disturbances (blurred vision, clouding of vision), eye irritation and swelling.

Ear and labyrinth disorders:

Rare: vertigo; frequency not known: tinnitus.

Cardiac disorders:

Rare: palpitations; frequency not known: heart failure.

It should be noted that there is a possibility of developing congestive heart failure in elderly patients and in patients with impaired cardiac function.

Vascular disorders:

Rare: arterial thrombosis (myocardial infarction, stroke); frequency not known: vasculitis, hypertension.

Prolonged use of some NSAIDs, particularly at high doses (150 mg/day), increases the risk of arterial thrombosis, myocardial infarction, or stroke. Currently, there is insufficient information to exclude such risk with the use of tenoxicam.

Respiratory, thoracic and mediastinal disorders:

Rare: bronchospasm, asthma exacerbation, dyspnea; frequency not known: epistaxis.

Bronchospasm and asthma exacerbation have been reported during the use of NSAIDs.

Gastrointestinal disorders:

Very common: gastritis, epigastric pain, abdominal pain and discomfort, dyspepsia, nausea, vomiting, flatulence, constipation, diarrhea, distress syndrome, stomatitis; common: gastrointestinal ulcers, bleeding and perforations, peptic ulcers, hematemesis, melena, oral ulcers, gastritis, dry mouth, exacerbation of colitis and Crohn's disease; very rare: pancreatitis.

Hepatobiliary disorders:

Uncommon: increased levels of liver enzymes; frequency not known: hepatitis, jaundice.

Skin and subcutaneous tissue disorders:

Uncommon: pruritus, erythema, exanthema, rash, urticaria; rare: vesiculobullous reactions; very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis; frequency not known: photosensitivity reactions.

With NSAID use, nail damage and alopecia have also been reported.

Renal and urinary disorders:

Uncommon: increased levels of creatinine and urea; frequency not known: nephrotoxicity (renal failure, interstitial nephritis, nephrotic syndrome).

Reproductive system and breast disorders:

Isolated cases of female infertility have been reported with the use of agents that inhibit COX and prostaglandin synthesis.

General disorders and administration site conditions:

Uncommon: fatigue, edema; frequency not known: malaise.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life

Lyophilisate for injection solution – 3 years.

Solvent – 5 years.

Storage conditions. Store at temperatures not exceeding 25 °C, in a place inaccessible to children.

Packaging. 3 vials of lyophilisate for injection solution, together with 3 ampoules of solvent (2 ml each) of water for injections, in a blister pack; 1 blister pack in a cardboard box.

Prescription category. Prescription only.

Manufacturer. UORLД MEDICIN ILAC SAN. VE TİC. A.Ş. / WORLD MEDICINE ILAC SAN. VE TIC. A.S.

Manufacturer's address and location of operations. OPZCH, G.O. Pasha district, 6th street, No.30, Cerkezkoy/Tekirdag, Turkey / COSB G.O.Pasa Mah. 6. Cad. No:30, Cerkezkoy/Tekirdag, Turkey.

Marketing authorization holder. JSC "FarmLiga".

Address of the marketing authorization holder:

48A-304 Antakalnio St., Vilnius, Republic of Lithuania.