Instructions Artoxan lyophilized powder for solution for injection 20 mg vial complete with solvent No. 3
Composition
active ingredient: tenoxicam;
1 vial of lyophilisate for solution for injection contains tenoxicam 20 mg;
excipients: mannitol (E 421); disodium edetate; ascorbic acid; trometamol; sodium hydroxide; sodium hydroxide or diluted hydrochloric acid;
1 ampoule of solvent contains 2 ml of water for injections.
Dosage form
Lyophilisate for solution for injection.
Main physicochemical properties: yellow lyophilized powder.
Solvent (water for injections): clear, colorless solution.
Reconstituted solution: clear yellow-green solution.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Oxycodone. ATX code M01A C02.
Pharmacological properties
Pharmacodynamics
Tenoxicam is a nonsteroidal anti-inflammatory drug (NSAID). It has analgesic, anti-inflammatory, and antipyretic effects.
The mechanism of action is based on non-selective blocking of the activity of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoenzymes, which leads to impaired synthesis of prostaglandins and thromboxanes. Inhibits platelet aggregation.
In vitro studies also indicate that tenoxicam may act as a scavenger of reactive oxygen species at the site of inflammation and has the ability to inhibit metalloproteinases (stromelysin and collagenase) that cause cartilage destruction.
Pharmacokinetics
The bioavailability of tenoxicam is similar after intramuscular and oral administration. After intravenous administration of 20 mg, its plasma level decreases rapidly within 2 hours, which is due to the distribution process. After this short period, there is no difference in the plasma concentration of tenoxicam after intravenous and oral administration. Tenoxicam is highly bound (99%) to plasma proteins and penetrates well into the synovial fluid.
The average volume of distribution at steady state is 10–12 L. At the recommended dose of 20 mg/day, steady state plasma concentrations are reached within 10–15 days. No accumulation is observed.
Tenoxicam is completely metabolized in the body. Approximately 2/3 of the dose taken is excreted mainly in the urine as the pharmacologically inactive metabolite 5-hydroxypyridyl, the rest - in the bile, mainly in the form of glucuronide conjugates of hydroxymetabolites. The half-life is 72 hours. Total plasma clearance is 2 ml/min.
The pharmacokinetics of tenoxicam are linear in the studied dose range from 10 to 100 mg.
No changes in tenoxicam pharmacokinetics were found depending on the patient's age, although individual differences are generally greater in elderly patients.
Indication
Relief of pain and inflammation in osteoarthritis and rheumatoid arthritis.
Short-term treatment of acute musculoskeletal conditions, including sprains, dislocations, and other soft tissue injuries.
For the indicated indications, the drug should be used if it is impossible to use tenoxicam in tablet form.
Contraindication
Hypersensitivity to the active substance or to other excipients of the medicinal products.
History of hypersensitivity symptoms (including asthma symptoms, rhinitis, angioedema, urticaria) to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs).
Recurrent peptic ulcer/bleeding in active form or history of recurrence (2 or more severe episodes of ulcer or bleeding), ulcerative colitis, Crohn's disease, severe gastritis.
History of gastrointestinal bleeding (melena, hematomesis) and perforations related to previous NSAID therapy.
History of cerebrovascular bleeding or other blood clotting disorders.
Severe heart, liver, kidney failure.
Third trimester of pregnancy.
Breastfeeding period.
Children's age (up to 18 years).
Interaction with other medicinal products and other types of interactions
With other NSAIDs (including COX-2 inhibitors) - possible increased risk of adverse reactions. Simultaneous use of 2 or more NSAIDs should be avoided.
With acetylsalicylic acid and other salicylates - possible increase in clearance and distribution of tenoxicam due to competition for binding sites with blood proteins. The simultaneous use of these drugs should be avoided due to an increased risk of adverse reactions (especially from the digestive tract).
With anticoagulants (warfarin) - possible enhancement of the effects of the latter. With simultaneous use, the effects of anticoagulants should be monitored, especially in the initial stages of treatment with tenoxicam. No clinically significant interactions of tenoxicam with low molecular weight heparin have been recorded.
With cyclosporine - possible increased risk of nephrotoxicity. Caution should be exercised when using these drugs simultaneously.
With quinolones - preclinical data suggest that the use of NSAIDs increases the risk of quinolone-induced seizures. Concomitant use of these agents may increase the risk of seizures.
With lithium - possible reduction of the elimination of the latter. When using these drugs simultaneously, the level of lithium in the blood plasma should be regularly monitored and patients should be warned about the need to drink sufficient fluids and informed about the symptoms of lithium intoxication.
With diuretics - possible reduction of natriuretic activity of diuretics and increased risk of nephrotoxicity due to the ability of NSAIDs to retain potassium ions, sodium and fluid. In people with arterial hypertension or heart failure, tenoxicam may worsen the course of these diseases. Clinically significant interactions of tenoxicam with furosemide have not been recorded, however, a decrease in the hypotensive effect of hydrochlorothiazide has been reported when it is used simultaneously with tenoxicam.
With antihypertensive agents - possible weakening of the effects of alpha-blockers, angiotensin-converting enzyme (ACE) inhibitors. Clinically significant interactions of tenoxicam with calcium channel blockers, atenolol and central alpha-adrenergic agonists have not been recorded.
With methotrexate - increased toxicity of the latter is possible due to reduced elimination. Caution should be exercised when using these agents simultaneously.
With oral hypoglycemic agents - although there are no reports of an effect on the clinical effects of glibornuride, glibenclamide, tolbutamide, the patient's condition should be carefully monitored when oral hypoglycemic agents are used simultaneously with tenoxicam.
With dextromethorphan - possible enhancement of the analgesic effect of tenoxicam.
With cholestyramine - possible increase in clearance and decrease in the half-life of tenoxicam.
With probenecid - an increase in tenoxicam plasma levels is possible. The clinical significance of this phenomenon has not been established.
With mifepristone - possible weakening of the effects of the latter. NSAIDs should be used 8–12 days after the end of mifepristone.
With corticosteroids - possible increased risk of gastrointestinal bleeding and perforation. Caution should be exercised when using these agents concomitantly.
With antiplatelet agents, selective serotonin reuptake inhibitors (SSRIs) - there may be an increased risk of gastrointestinal bleeding.
With tacrolimus - possible increased risk of nephrotoxicity.
With zidovudine - possible increased risk of hematological toxicity. There is evidence of an increased risk of hemarthrosis and hematomas in HIV-infected patients with hemophilia when zidovudine and ibuprofen are used concomitantly.
With penicillinamine, gold preparations for parenteral use - in a small number of patients who took these drugs simultaneously, no clinically significant interaction was observed.
Application features
Adverse reactions to tenoxicam can be minimized by using the lowest effective dose for the shortest possible time.
Concomitant use of the medicinal product with NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, and other agents that increase the risk of ulcers or bleeding, such as oral corticosteroids, anticoagulants (such as warfarin), antiplatelet agents (such as acetylsalicylic acid), selective serotonin reuptake inhibitors (SSRIs), should be avoided.
Gastrointestinal bleeding, ulcers and perforations.
Gastrointestinal bleeding, ulceration and perforation, including fatal cases, have been reported with all NSAIDs, and can occur at any time during the use of tenoxicam, with or without warning symptoms, and with or without a history of gastrointestinal disease.
The risk of such events increases with increasing dose of NSAIDs, in patients with a history of gastrointestinal ulceration, especially complicated by bleeding or perforation, and in elderly patients. In such patients, treatment should be started with the lowest possible effective dose. For these patients, as well as for those taking concomitant low-dose acetylsalicylic acid or other agents that increase the risk of gastrointestinal complications, combination therapy with drugs such as misoprostol or proton pump inhibitors should be considered.
Patients, especially the elderly, with a history of toxic gastrointestinal disease should be informed of any unusual symptoms occurring in the gastrointestinal tract, especially bleeding. This is especially important in the initial stages of treatment.
The drug should be used with caution in patients receiving drugs that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (such as warfarin), selective serotonin reuptake inhibitors (SSRIs), or platelet agents (such as acetylsalicylic acid).
The drug should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as tenoxicam may exacerbate their manifestations.
Use in patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases.
When NSAIDs are used in such patients, the risk of developing aseptic meningitis increases.
Dermatological effects.
The use of NSAIDs can rarely cause severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, some of which have been fatal. The risk of developing such reactions is highest at the beginning of treatment: in most cases, the first manifestations were observed during the first month of therapy.
Patients should be warned about the symptoms and closely monitored for such skin reactions.
At the first sign of skin rash, mucosal lesions, or other signs of hypersensitivity, the drug should be discontinued immediately. The best results in the treatment of Stevens-Johnson syndrome and toxic epidermal necrolysis are achieved with early diagnosis and discontinuation of any suspected drug.
Tenoxicam should not be re-administered to patients who have experienced Stevens-Johnson syndrome and toxic epidermal necrolysis during its use.
Cardiovascular, renal and hepatic disorders.
The use of NSAIDs in rare cases can cause interstitial nephritis, glomerulonephritis, papillary necrosis or nephrotic syndrome due to inhibition of renal prostaglandin synthesis, which maintains renal perfusion in patients with reduced renal blood flow and total blood volume. In such patients, the use of NSAIDs can cause severe renal decompensation, which after discontinuation of their use returns to the state that was observed before the start of therapy. The greatest risk of such complications exists in patients with existing kidney disease (including diabetes with impaired renal function), nephrotic syndrome, reduced total blood volume, impaired liver function, congestive heart failure, in patients who are simultaneously using diuretics or nephrotoxic drugs and in elderly patients. During the use of the drug in such patients, renal, hepatic and cardiac function should be constantly monitored. Patients with impaired renal, hepatic, and cardiac function should use the drug at the lowest possible dose.
Respiratory effects.
The drug should be used with caution in patients with bronchial asthma or a history of bronchial asthma, since taking NSAIDs can provoke the development of bronchospasm.
When using NSAIDs, an increase in plasma transaminase levels or other indicators of liver function may occur. In most cases, such changes are transient. In the event of significant and prolonged disorders, the drug should be discontinued and liver function should be checked. The drug should be used with caution in patients with impaired liver function.
Tenoxicam reduces platelet aggregation and increases bleeding time, which should be borne in mind during future surgical interventions and when it is necessary to determine bleeding time.
Use in elderly patients.
Elderly patients are at increased risk of adverse reactions, especially gastrointestinal bleeding and perforation (including fatal cases), when NSAIDs are used. Ulcers and bleeding are less well tolerated in debilitated patients. Most cases of fatal gastrointestinal events associated with NSAIDs have occurred in the elderly and debilitated. When using the drug in such patients, special care should be taken and renal, hepatic and cardiovascular function and the general condition of the patient should be monitored regularly to detect possible interactions with concomitant medications.
Ophthalmological effects.
Visual disturbances have been reported with NSAIDs. If such disturbances develop during use of the medicinal product, an ophthalmological examination should be performed.
Cardiovascular and cerebrovascular effects.
Patients with hypertension and/or a history of mild or moderate heart failure should be carefully monitored during use of the drug, as edema and fluid retention have been reported with NSAID treatment.
The use of some NSAIDs, especially at high doses (150 mg/day) for a long time, may increase the risk of arterial thrombosis, myocardial infarction or stroke. At present, there is insufficient information to exclude such a risk for tenoxicam.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with the drug after careful assessment. This assessment should be performed before initiating long-term treatment in patients with risk factors for cardiovascular disease (such as hypertension, hyperlipidemia, diabetes mellitus, smoking).
Antipyretic effects.
Laboratory tests.
NSAIDs inhibit renal prostaglandin synthesis and therefore may negatively affect renal hemodynamics and water and electrolyte balance.
During the use of the drug, careful monitoring of the condition, especially cardiac and renal function (blood plasma urea, creatinine, edema development, weight gain), should be carried out in patients with diseases that may increase the risk of developing renal failure, such as existing kidney disease, impaired renal function in patients with diabetes, cirrhosis of the liver, congestive heart failure, reduced total blood volume, concomitant treatment with potentially nephrotoxic drugs, diuretics and corticosteroids. These patients are at particular risk in the peri- and postoperative period with major surgical interventions due to the possibility of serious blood loss.
Due to the high ability of tenoxicam to bind to blood plasma proteins, the drug should be used with caution in cases of markedly reduced plasma albumin levels.
Impact on fertility.
The drug is not recommended for use in women attempting to conceive. Discontinuation of the drug should be considered in women who have difficulty conceiving or are undergoing investigation of infertility.
Excipients precautions.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
Pregnancy period.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/foetal development. Epidemiological studies have shown an increased risk of miscarriage and/or cardiac malformations and gastroschisis following administration of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformations has increased from less than 1% to approximately 1.5%. It is possible that the risk increases with increasing dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation losses and embryo/foetal lethality. In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals treated with a prostaglandin synthesis inhibitor during organogenesis.
From the 20th week of pregnancy, the use of tenoxicam may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after the start of treatment and is usually reversible after discontinuation of treatment. In addition, there have been reports of narrowing of the ductus arteriosus following treatment in the second trimester of pregnancy, most of which resolved after discontinuation of treatment.
In the first and second trimesters of pregnancy, the drug should not be used, except in cases of extreme necessity.
When used in women attempting to become pregnant or during the first and second trimesters of pregnancy, the drug should be used at the lowest effective dose for the shortest possible time.
Antenatal monitoring for oligohydramnios and ductus arteriosus should be considered after exposure to tenoxicam for several days, starting from the 20th week of gestation. The drug should be discontinued if oligohydramnios or ductus arteriosus is detected.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may have the following effects:
on the fruit:
cardiopulmonary toxicity (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);
renal dysfunction, which may progress to renal failure with oligohydramnios (see above);
on the mother and newborn, as well as at the end of pregnancy:
possible prolongation of bleeding time; antiplatelet effect, which may be observed even at very low doses;
inhibition of uterine contractions, leading to delayed or prolonged labor.
The drug is contraindicated in the third trimester of pregnancy.
Breastfeeding period.
Tenoxicam passes into breast milk in very small amounts. If necessary, breast-feeding should be discontinued.
Fertility.
The use of tenoxicam may impair female fertility, therefore the drug is not recommended for use in women who wish to become pregnant.
Discontinuation of the drug should be considered in women who have difficulty conceiving or are undergoing investigation of infertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
When using NSAIDs, dizziness, drowsiness, fatigue and visual disturbances may occur. If such reactions occur, you should refrain from driving or using other mechanisms.
Method of administration and doses
The drug is intended for intravenous and intramuscular use.
Before use, the contents of the vial must be dissolved in 2 ml of water for injection, which is included in the package of the medicinal product. After complete dissolution of the lyophilisate, the solution should be used immediately.
Adults.
The recommended doses of the drug should not be exceeded, since the use of higher doses does not always achieve a more pronounced therapeutic effect, and the risk of adverse reactions increases.
The duration of treatment with tenoxicam for acute musculoskeletal disorders usually does not exceed 7 days. In exceptional cases, the duration of therapy may be extended to 14 days.
Elderly patients.
The drug, like other NSAIDs, should be used with special caution in elderly patients. They have an increased risk of developing adverse reactions and are more likely to receive concomitant medications or have impaired renal, hepatic, or cardiovascular function. If necessary, the drug should be used in elderly patients at the lowest effective dose of 20 mg for the shortest period of time necessary to control the symptoms of the disease. Such patients should be carefully monitored for gastrointestinal bleeding for 4 weeks after the start of therapy.
Patients with impaired renal and/or hepatic function.
No dosage adjustment is necessary for patients with creatinine clearance greater than 25 ml/min. These patients should be carefully monitored.
There are insufficient data to make dosing recommendations for tenoxicam in patients with creatinine clearance less than 25 ml/min.
There are insufficient data to make dosing recommendations for tenoxicam in patients with hepatic impairment.
The drug should be used with caution in cases of low albumin concentrations (e.g., 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, so the drug should not be used in this category of patients.
Overdose
Common symptoms of NSAID overdose include nausea, vomiting, epigastric pain, gastrointestinal bleeding, tinnitus, headache, visual disturbances, dizziness, and rarely diarrhea. More serious symptoms such as convulsions, agitation, drowsiness, hypotension, apnea, coma, electrolyte imbalance, and renal failure have been reported in isolated cases. Exacerbation of bronchial asthma is also possible.
Treatment. The drug should be discontinued. Adequate hydration should be maintained, liver and kidney function should be monitored. The patient should be under medical supervision for at least 4 hours after overdose. If necessary, symptomatic therapy should be carried out. Hemodialysis is ineffective. There is no specific antidote.
Side effects
Criteria for assessing the frequency of adverse drug reactions: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (<1/10000); frequency unknown (cannot be determined from available data).
The most common adverse reactions are from the digestive tract – erosive-ulcerative lesions of the digestive tract, including ulcerogenic effects.
From the blood and lymphatic system:
frequency unknown - agranulocytosis, anemia, aplastic anemia, hemolytic anemia, leukopenia, thrombocytopenia, nonthrombocytopenic purpura, eosinophilia.
On the part of the immune system:
frequency unknown - hypersensitivity reactions, including asthma, anaphylactic shock, angioedema.
Metabolism and nutrition:
often - anorexia; rarely - metabolic disorders (hyperglycemia, weight gain/loss).
From the psyche:
Rare: sleep disturbances, insomnia, depression, nervousness, feeling of anxiety, abnormal dreams; frequency unknown: confusion, hallucinations.
From the nervous system:
often - dizziness, headache; frequency unknown - drowsiness, paresthesia, optic neuritis.
On the part of the organs of vision:
frequency unknown - visual disturbances (visual impairment, blurred vision), eye irritation and swelling.
From the side of the organs of hearing and labyrinth:
rarely - vertigo; frequency unknown - tinnitus.
From the heart:
rarely - palpitations; frequency unknown - heart failure.
The possibility of developing congestive heart failure should be considered in elderly patients and in patients with impaired cardiac function.
From the vascular system:
Rare: arterial thrombosis (myocardial infarction, stroke); frequency unknown: vasculitis, hypertension.
Long-term use of some NSAIDs, especially at high doses (150 mg/day), may increase the risk of arterial thrombosis, myocardial infarction, or stroke. There is currently insufficient information to exclude such a risk for tenoxicam.
From the respiratory system, chest organs and mediastinum:
Rare: bronchospasm, asthma exacerbation, dyspnea; frequency unknown: nosebleeds.
Bronchospasm and exacerbation of asthma have been reported with the use of NSAIDs.
From the digestive tract:
very often - gastritis, epigastric pain, abdominal pain and discomfort, dyspepsia, nausea, vomiting, flatulence, constipation, diarrhea, distress syndrome, stomatitis; often - gastrointestinal ulcers, bleeding and perforation, peptic ulcers, hematomesis, melena, mouth ulcers, gastritis, dry mouth, exacerbation of colitis and Crohn's disease; very rarely - pancreatitis.
From the hepatobiliary system:
Skin and subcutaneous tissue disorders:
infrequently - itching, erythema, exanthema, rash, urticaria; rarely - vesiculobullous reactions; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis; frequency unknown - photosensitivity reactions.
Nail damage and alopecia have also been reported with the use of NSAIDs.
From the urinary system:
uncommon - increased creatinine and urea levels; frequency unknown - nephrotoxicity (renal failure, interstitial nephritis, nephrotic syndrome).
From the reproductive system and mammary glands:
Isolated cases of female infertility have been reported with the use of agents that inhibit COX and prostaglandin synthesis.
General disorders and injection site reactions:
infrequently - increased fatigue, edema; frequency unknown - malaise.
Reporting of suspected adverse reactions.
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua.
Expiration date
The finished medicinal product is 3 years.
Solvent - 5 years.
Storage conditions
Store at a temperature not exceeding 25 °C out of the reach of children.
Incompatibility
Unknown.
Packaging
20 mg lyophilisate for solution for injection in a vial;
2 ml of solvent (water for injection) in an ampoule;
3 vials of lyophilisate for solution for injection complete with 3 ampoules of solvent in a contour blister pack; 1 contour blister pack in a cardboard box.
Vacation category
According to the recipe.
Producer
Mefar Ilach San. A.Sh./Mefar Ilac San. AS
Location of the manufacturer and address of its place of business
Ramazanoglu Mach. Ansar Jad. No. 20, 34906 Kurtkoy – Pendik/Istanbul, Turkey/ Ramazanoglu Mah. Ensar Cad. No: 20, 34906 Kurtkoy – Pendik/Istanbul, Turkey.
Applicant
WORLD MEDICINE LLC, Ukraine/WORLD MEDICINE, LLC, Ukraine.
