Tenoxicam

Pharmacological properties

tenoxicam is an NSAID. It has an analgesic, anti-inflammatory, antipyretic effect.

The basis of the mechanism of action is the non-selective blockade of the activity of COX-1 and COX-2 isoenzymes, which leads to disruption of the synthesis of prostaglandins and thromboxane. Inhibits platelet aggregation.

In vitro studies also indicate that tenoxicam can act as an acceptor of active oxygen in the focus of inflammation and has the ability to inhibit metalloproteinases (stromelysin and collagenase), which cause cartilage destruction.

Pharmacokinetics The bioavailability of tenoxicam with i / m administration and oral administration is similar. With the on / in the introduction of a dose of 20 mg, the concentration of tenoxicam in the blood plasma rapidly decreases over 2 hours, which is associated with the distribution process. After this short period, there is no difference in the concentration of tenoxicam in blood plasma with iv administration and oral administration. To a large extent (99% of the administered dose), tenoxicam binds to blood plasma proteins and penetrates well into the synovial fluid.

The average value of the distribution in the equilibrium phase is 10–12 l. With the recommended regimen of use of 20 mg / day, the equilibrium concentration in the blood plasma is reached within 10-15 days. No cumulation is noted.

Tenoxicam is completely metabolized in the body. About ⅔ of the dose is mainly excreted in the urine as a pharmacologically inactive metabolite of 5-hydroxypyridyl, the rest with bile, mainly in the form of conjugates of hydroxymetabolites with glucuronic acid. T_½ is 72 hours. The total clearance of blood plasma is 2 ml / min.

The pharmacokinetics of tenoxicam is linear in the studied dose range from 10 to 100 mg.

No changes in the pharmacokinetics of tenoxicam depending on the age of the patient were detected, although individual differences, as a rule, are greater in elderly patients.

Indications

Relief of pain and inflammation in osteoarthritis and rheumatoid arthritis; short-term treatment of acute diseases of the musculoskeletal system, including sprains, dislocations and other soft tissue injuries.

With these indications, the drug is used if it is impossible to use tenoxicam in the form of tablets.

Application

The drug is intended for intravenous and / m administration.

Before use, the contents of the vial must be dissolved in 2 ml of water for injection, which is included in the kit. After complete dissolution of the lyophilisate, solution should be used immediately.

Adults The recommended dose is 20 mg / day for the first 1-2 days of treatment, then you should switch to taking pills that need to be taken every day at the same time.

The recommended doses of the drug should not be exceeded, since when using high doses, a more pronounced therapeutic effect is not always achieved, and the risk of adverse reactions increases.

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

Elderly patients. The drug, like other NSAIDs, should be used with caution in elderly patients. They have an increased risk of developing adverse reactions, and they are more likely to receive combination therapy, or they have impaired renal function, liver, and cardiovascular system. If necessary, the drug should be used in elderly patients with a minimum effective dose of 20 mg for the shortest period necessary to control the symptoms of the disease. The condition of such patients should be carefully monitored to detect gastrointestinal bleeding within 4 weeks after the start of therapy.

Patients with impaired renal and / or liver function.In patients with creatinine clearance of 25 ml / min, there is no need to adjust the dosage regimen. The condition of such patients should be carefully monitored.

There are insufficient data for recommendations regarding dosing of tenoxicam in patients with creatinine clearance of 25 ml / min.

There are very few data for recommendations regarding dosing of tenoxicam in patients with liver failure.

The drug is used with caution at low concentrations of albumin (for example, with nephrotic syndrome) or at a high concentration of bilirubin in blood plasma, since tenoxicam binds to a large extent to plasma proteins.

Contraindications

• Hypersensitivity to the active substance or other components of the drug; history of hypersensitivity symptoms (including symptoms of ba, rhinitis, angioedema, urticaria) to acetylsalicylic acid and other NSAIDs; recurrent ulcer / bleeding in an active form or relapse in history (2 or more pronounced episodes of ulcer or bleeding), ulcerative colitis, Crohn’s disease, severe gastritis; the presence of a history of gastrointestinal bleeding (melena, hemathemesis) and perforations associated with previous NSAID therapy; a history of cerebrovascular or other bleeding disorders; severe heart, liver, renal failure; iii trimester of pregnancy; lactation period; childrens age up to (18 years).

Side effects

Criteria for assessing the incidence of adverse drug reactions: very often (1/10); often (from 1/100 to 1/10); infrequently (from 1/1000 to 1/100); rarely (from 1/10 000 to 1/1000); very rarely (1/10 000); the frequency is unknown (cannot be determined from the available data).

Most often, adverse reactions from the digestive tract are manifested - erosive and ulcerative lesions of the digestive tract, including an ulcerogenic effect.

On the part of the blood system and lymphatic system: the frequency is unknown - agranulocytosis, anemia, aplastic anemia, hemolytic anemia, leukopenia, thrombocytopenia, non-thrombocytopenic purpura, eosinophilia.

From the immune system: the frequency is unknown - hypersensitivity reactions, including asthma, anaphylactic shock, angioedema.

From the side of metabolism and nutrition: often - anorexia; rarely - metabolic disorders (hyperglycemia, increase / decrease in body weight).

From the psyche: rarely - sleep disturbance, insomnia, depression, nervousness, anxiety, abnormal dreams; frequency unknown - confusion, hallucinations.

From the nervous system: often - dizziness, headache; frequency unknown - drowsiness, paresthesia, optic neuritis.

From the side of the organ of vision: the frequency is unknown - visual impairment (blurred vision, blurred vision), irritation and swelling of the eyes.

On the part of the organ of hearing and the labyrinth: rarely - vertigo; frequency unknown - tinnitus.

From the side of the heart: rarely - palpitation; frequency unknown - heart failure.

It should be borne in mind the possibility of developing congestive heart failure in elderly patients and patients with impaired cardiac function.

From the vascular system: rarely - arterial thrombosis (myocardial infarction, stroke); frequency unknown - vasculitis, hypertension. Long-term use of certain NSAIDs, especially at high doses (150 mg / day), may increase the risk of developing arterial thrombosis, myocardial infarction, or stroke. Currently, there is insufficient data to exclude such a risk for tenoxicam.

From the respiratory system, chest and mediastinal organs: rarely - bronchospasm, exacerbation of asthma, shortness of breath; frequency unknown - nosebleeds.

When using NSAIDs, the development of bronchospasm and exacerbation of asthma has been reported.

From the digestive system: 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, oral ulcers, gastritis, dry mouth, exacerbation of colitis and Crohns disease; very rarely - pancreatitis.

From the hepatobiliary system: infrequently - increased levels of liver enzymes; frequency unknown - hepatitis, jaundice.

On the part of the skin and subcutaneous tissue: infrequently - itching, erythema, exanthema, rash, urticaria; rarely - vesicle-bullous reactions; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis; frequency unknown - photosensitivity.

When using NSAIDs, damage to nails and alopecia have also been reported.

From the urinary system: infrequently - increased levels of creatinine and urea; frequency unknown - nephrotoxicity (renal failure, interstitial nephritis, nephrotic syndrome).

On the part of 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 reactions at the injection site: infrequently - increased fatigue, swelling; frequency unknown - malaise.

special instructions

Adverse reactions of tenoxicam can be minimized by applying a minimum effective dose over a minimum period.

Avoid concomitant use with NSAIDs, including selective COX-2 inhibitors, and other agents that increase the risk of ulcers or bleeding, such as oral GCS, anticoagulants (e.g. warfarin), antiplatelet agents (such as acetylsalicylic acid), selective serotonin reuptake inhibitors ( SSRIs).

Gastrointestinal bleeding, ulcers and perforations. With the use of all NSAIDs, the occurrence of gastrointestinal bleeding, ulcers and perforations, including lethal, which can develop at any time with the use of tenoxicam, with or without warning symptoms, both in the presence of a history of gastrointestinal diseases, and without them.

The risk of such phenomena increases with an increase in the dose of NSAIDs in patients with a history of a digestive tract ulcer, especially complicated by bleeding or perforation, as well as in elderly patients. For such patients, treatment should be started with the lowest possible effective dose. For these patients, as well as patients taking simultaneously low doses of acetylsalicylic acid or other drugs that increase the risk of complications from the digestive tract, the use of combination therapy with drugs such as misoprostol or proton pump inhibitors should be considered.

Patients, especially the elderly, with a history of toxic digestion, should report any unusual symptoms that occur in the digestive tract, especially bleeding. This is very important in the initial stages of treatment.

The drug should be used with caution in patients receiving drugs that increase the risk of ulcers or bleeding, such as oral corticosteroids, anticoagulants (e.g. warfarin), SSRIs, or platelets (such as acetylsalicylic acid).

If gastrointestinal bleeding or ulcers occur, the drug should be discontinued.

The drug should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohns disease), since tenoxicam may exacerbate their manifestations.

Use in patients with systemic lupus erythematosus and mixed connective tissue diseases.When using NSAIDs in such patients, the risk of developing aseptic meningitis is increased.

Dermatological effects. The use of NSAIDs in rare cases can cause skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, including fatal ones. The risk of developing such reactions is highest at the beginning of treatment: in most cases, the first manifestations were noted during the first month of therapy. Patients should be warned of symptoms and closely monitored for such skin reactions.

At the first signs of a skin rash, mucosal lesions, or other signs of hypersensitivity, the drug should be discontinued immediately. The best treatment results for Stevens-Johnson syndrome and toxic epidermal necrolysis are achieved with early diagnosis and discontinuation of any suspected drug. Tenoxicam should not be reused in patients in whom Stevens-Johnson syndrome and toxic epidermal necrolysis were manifested during its administration.

Impaired renal function, liver and cardiovascular system. The use of NSAIDs in rare cases can cause interstitial nephritis, glomerulonephritis, papillary necrosis or nephrotic syndrome due to inhibition of prostaglandin synthesis in the kidneys, which supports renal perfusion in patients with reduced renal blood flow and total blood volume. In such patients, the use of NSAIDs can cause pronounced decompensation of the kidneys, which, after cessation of their use, returns to the state observed before the start of therapy. The greatest risk of such complications is in patients with existing kidney diseases (including diabetes with impaired renal function), nephrotic syndrome, decreased total blood volume, impaired liver function, congestive heart failure, in patients taking diuretics or nephrotoxic drugs at the same time, and in elderly patients age. During the use of the drug in such patients, the function of the kidneys, liver and heart should be constantly monitored. In patients with impaired renal, liver and heart function, the drug should be used in the lowest possible dose.

Respiratory effects. The drug is used with caution in patients with AD or a history of AD, since taking NSAIDs can provoke the development of bronchospasm.

When using NSAIDs, an increase in plasma transaminases or other indicators of liver function is possible. In most cases, such changes are fleeting. In the case of the development of significant and prolonged disorders, the use of the drug should be discontinued and liver function checked. The drug is used with caution in patients with impaired liver function.

Tenoxicam reduces platelet aggregation and prolongs bleeding time, this should be taken into account when performing surgical interventions in the future and in the case of determining the time of bleeding.

Use in elderly patients. With the use of NSAIDs in elderly patients, the incidence of adverse reactions, especially gastrointestinal bleeding and perforations (including lethal), is increased. Ulcers and bleeding are worse tolerated by debilitated patients. Most fatal cases of gastrointestinal upset caused by NSAIDs have been observed in elderly patients and debilitated patients. During the use of the drug in such patients, special care should be taken and the functions of the kidneys, liver and cardiovascular system, as well as the general condition of patients, should be regularly monitored to identify possible interactions with the drugs used simultaneously.

Ophthalmic effects.When applying NSAIDs, violations of the organ of vision were reported. In the case of the development of such disorders during the use of the drug, an ophthalmological examination should be carried out.

Cardiovascular and cerebrovascular effects. During the use of the drug, the condition of patients with AH and / or mild or moderate heart failure in the history should be carefully monitored, since the development of edema and the onset of fluid retention were reported.

The use of certain NSAIDs, especially in high doses (150 mg / day) for a long time, may increase the risk of developing arterial thrombosis, myocardial infarction, or stroke. Currently, there is insufficient data to exclude such a risk for tenoxicam.

In patients with uncontrolled hypertension, congestive heart failure, diagnosed with coronary artery disease, peripheral artery disease and / or cerebrovascular disease, the drug should be used after a thorough analysis of the condition. This analysis must be performed before starting prolonged treatment of patients with risk factors for cardiovascular diseases (such as hypertension, hyperlipidemia, diabetes mellitus, smoking).

Antipyretic effects. Like other NSAIDs, tenoxicam can mask the symptoms of infection.

Data from laboratory research methods. NSAIDs inhibit the synthesis of prostaglandins in the kidneys, therefore, they can negatively affect renal hemodynamics and water-electrolyte balance.

During the use of the drug, careful monitoring of the condition, especially cardiac and renal function (plasma urea, creatinine, development of edema, weight gain), patients with diseases that can increase the risk of developing kidney failure, such as existing kidney disease, impaired renal function, should be carried out. in patients with diabetes, liver cirrhosis, congestive heart failure, reduced total blood volume, concomitant treatment with potentially nephrotoxic drugs, diuretic ami and corticosteroids. These patients are at particular risk in the peri-and postoperative period with extensive surgical interventions due to the possibility of serious blood loss.

Due to the high ability of tenoxicam to bind to plasma proteins, the drug should be used with caution with a pronounced decrease in plasma albumin.

Impact on fertility. The drug is not recommended for women planning to become pregnant. Consideration should be given to stopping the use of the drug in women who have difficulty conceiving or undergoing examination for infertility.

Use during pregnancy and lactation. Period of pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryo / fetal development. Epidemiological studies indicate an increased risk of miscarriages and / or the risk of heart defects and gastroschisis after the use of an inhibitor of prostaglandin synthesis in early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1 to 1.5%. It is possible that the risk increases with increasing dose and duration of treatment. It has been shown that administration of an inhibitor of prostaglandin synthesis in animals leads to an increase in pre- and post-implantation losses and death of the embryo / fetus. In addition, in animals treated with an inhibitor of prostaglandin synthesis during organogenesis, an increased frequency of various malformations, including from the cardiovascular system, was recorded.

In the I and II trimester of pregnancy, the drug can be used only if the expected benefit to the mother outweighs the potential risk to the fetus.

In case of use in women planning to become pregnant, or in the I and II trimester of pregnancy, the drug is used in the minimum effective dose for the shortest period.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can influence as follows:

• on the fetus:

cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

impaired renal function can progress to the development of renal failure with oligohydramnios;

• on mother and newborn, as well as at the end of pregnancy:

possible prolongation of bleeding time; antiplatelet effect, which can be observed even at extremely low doses;

inhibition of uterine contractions, which leads to a delay or prolongation of labor. The drug is contraindicated in the III trimester of pregnancy.

The period of breastfeeding. Tenoxicam passes into breast milk in very small amounts. If necessary, the use of the drug should stop breast-feeding.

Fertility. The use of tenoxicam can worsen the fertility of women, therefore it is not recommended for women planning a pregnancy.

Consideration should be given to stopping the use of the drug in women who have difficulty conceiving or undergoing examination for infertility.

Children. There is no data on the safety of tenoxicam in children, so it should not be used in this category of patients.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. When using NSAIDs, dizziness, drowsiness, fatigue, and visual impairment may develop. In the case of the development of these reactions, one should refrain from driving vehicles or other mechanisms.

Interactions

Other NSAIDs (including cog-2 inhibitors): may increase the risk of adverse reactions. simultaneous use of two or more NSAIDs should be avoided.

Acetylsalicylic acid and other salicylates: it is possible to increase the clearance and distribution of tenoxicam due to competition for protein binding sites. The simultaneous use of these funds should be avoided due to the increased risk of adverse reactions (especially from the gastrointestinal tract).

Anticoagulants (warfarin): may enhance the effects of the latter. With simultaneous use, the effects of anticoagulants should be monitored, especially in the initial stages of treatment with tenoxicam. There are no clinically significant interactions of tenoxicam with low molecular weight heparin.

Cardiac glycosides: increased heart failure, decreased glomerular filtration index, and increased levels of cardiac glycosides in blood plasma are possible. Clinically significant interactions of tenoxicam with digoxin and digitalis preparations have not been recorded.

Cyclosporine: an increased risk of nephrotoxicity is possible. With the combined use of these funds, caution should be exercised.

Quinolones: preclinical evidence suggests that the use of NSAIDs increases the risk of seizures due to quinolones. With the simultaneous use of these funds, an increase in the risk of seizures is possible.

Lithium preparations: a decrease in the elimination of the latter is possible. With the simultaneous use of these funds should regularly monitor the level of lithium in the blood plasma, warn patients about the need to take a sufficient amount of fluid and inform about the symptoms of lithium intoxication.

Diuretics: it is possible to reduce the natriuretic activity of diuretics and increase the risk of nephrotoxicity due to the ability of NSAIDs to trap potassium, sodium and liquid ions. In people with 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 with simultaneous use with tenoxicam.

Antihypertensive agents: possible weakening of the effects of α-adrenergic blockers, ACE inhibitors. Clinically significant interactions of tenoxicam with calcium channel blockers, atenolol, and central α-adrenergic agonists have not been recorded.

Methotrexate: may increase the toxicity of the latter due to a decrease in its elimination. With the simultaneous use of these funds, caution should be exercised.

Oral hypoglycemic agents: although no effect on the clinical effects of glibornuride, glibenclamide, tolbutamide has been reported, while the use of oral antidiabetic agents with tenoxicam, the patients condition should be carefully monitored.

Dextromethorphan: may enhance the analgesic effect of tenoxicam.

Cholestyramine: possibly increased clearance and decreased T_½ tenoxicam.

Probenecid: an increase in plasma levels of tenoxicam is possible. The clinical significance of this phenomenon has not been established.

Mifepristone: possible attenuation of the effects of the latter. NSAIDs should be used 8-12 days after the end of taking mifepristone.

GCS: an increased risk of gastrointestinal bleeding and perforation is possible. With the simultaneous use of these funds, caution should be exercised.

Antiplatelet agents, SSRIs: possibly increased risk of gastrointestinal bleeding.

Tacrolimus: an increased risk of nephrotoxicity is possible.

Zidovudine: possible increased risk of hematologic toxicity. There is evidence of an increased risk of developing hemarthrosis and hematomas in HIV-infected patients with hemophilia while using zidovudine and ibuprofen.

Penicillamine, gold preparations for parenteral use: in a small number of patients taking these drugs at the same time, no clinically significant interaction was observed.

Incompatibility: unknown.

Overdose

Common symptoms manifestations of an overdose of NSAIDs include nausea, vomiting, epigastric pain, gastrointestinal bleeding, tinnitus, headache, blurred vision, dizziness, rarely diarrhea. in isolated cases, more severe disorders were reported, such as convulsions, agitation, drowsiness, hypotension, apnea, coma, electrolyte imbalance and renal failure. exacerbation of the ba is possible.

Treatment. You should stop using the drug. Adequate hydration should be maintained, and liver and kidney function monitored. The patient should be under medical supervision for at least 4 hours after an overdose. If necessary, carry out symptomatic therapy. Hemodialysis is ineffective. There is no specific antidote.

Storage conditions

At a temperature not exceeding 25 ° c.