Artoxan^® (Tablets, Lyophilisate, Gel) Instructions for Use

ATC Code

M01AC02 (Tenoxicam)

Active Substance

Tenoxicam (Rec.INN registered by WHO)

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

Anti-inflammatory and antirheumatic drugs; non-steroidal anti-inflammatory and antirheumatic drugs; oxicams

Pharmacological Action

Tenoxicam is an NSAID, a thienothiazine derivative of oxicam.

In addition to anti-inflammatory, analgesic, and antipyretic effects, the drug also inhibits platelet aggregation.

Tenoxicam exerts its anti-inflammatory effect by suppressing the activity of cyclooxygenase isoenzymes involved in arachidonic acid metabolism, thereby inhibiting prostaglandin synthesis.

Tenoxicam does not affect the activity of lipoxygenases.

Furthermore, Tenoxicam inhibits some leukocyte functions, including phagocytosis and histamine release, and reduces the content of active radicals at the site of inflammation.

Pharmacokinetics

Absorption

Tenoxicam is rapidly absorbed from the gastrointestinal tract unchanged, with a bioavailability of 100%.

When tenoxicam is taken after meals or simultaneously with antacids, the rate, but not the extent, of absorption is reduced.

C_max in plasma after oral administration is reached within 2 hours.

Distribution

In blood, Tenoxicam is 99% bound to proteins.

Tenoxicam penetrates well into synovial fluid, is characterized by low systemic clearance and a long T_1/2, allowing for once-daily administration.

Metabolism

It is almost completely metabolized in the liver by hydroxylation.

Excretion

Two-thirds of the administered tenoxicam is excreted by the kidneys as an inactive 5-hydroxypyridyl metabolite, and the remainder is excreted in the bile as conjugated hydroxymetabolites.

Less than 1% of the administered dose is excreted unchanged by the kidneys.

No accumulation is observed with prolonged use; the serum concentration of tenoxicam in this case is 10-15 µg/ml.

The mean T_1/2 is approximately 72 hours.

Indications

• Rheumatoid arthritis;
• Osteoarthritis;
• Ankylosing spondylitis;
• Articular syndrome in acute gout;
• Bursitis;
• Tenosynovitis;
• Pain syndrome (mild to moderate intensity): arthralgia, myalgia, neuralgia, migraine, toothache and headache, dysmenorrhea;
• Pain from injuries, burns;
• In inflammatory and degenerative diseases of the musculoskeletal system accompanied by pain, such as sciatica, lumbago, epicondylitis.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use; it does not affect the progression of the disease.

ICD codes

Dosage Regimen

Gel

For external use only.

A strip of gel approximately 2-5 cm long (1-2 g of gel) is applied to the skin 1-2 times/day and gently rubbed in.

After applying the drug, hands should be washed.

The duration of treatment depends on the indications and the effectiveness of therapy. After 2 weeks of using the drug, a doctor should be consulted regarding the advisability of continuing therapy.

The drug should not be used for more than 14 consecutive days for soft tissue lesions or rheumatic soft tissue disease and for more than 21 days in the case of arthritis-related pain (unless the doctor has prescribed a different treatment regimen).

If no positive clinical dynamics are observed within 7 days or if the condition worsens, it is necessary to consult a doctor.

Lyophilisate

For IM or IV administration.

IM or IV administration is used for short-term (1-2 days) treatment at a dose of 20 mg once/day. If further therapy is required, a switch is made to oral dosage forms of tenoxicam.

The injection solution is prepared immediately before use by dissolving the contents of the vial with the supplied solvent. After preparation, the needle is replaced.

IM injections are given deep.

The duration of IV administration should not be less than 15 seconds.

Tablets

Orally. 20 mg (1 tablet) once/day, after meals (preferably at the same time). The use of higher doses should be avoided, as their use is generally not accompanied by a more pronounced therapeutic effect but may be associated with a higher risk of adverse events.

For acute musculoskeletal disorders, therapy usually does not need to last more than 7 days, but in severe cases, it can be continued, up to a maximum of 14 days.

The minimum effective dose of the drug should be used for the shortest possible course.

Impaired renal and hepatic function

For CrCl ≥30 ml/min, no dose adjustment is required, but monitoring of the patient’s condition is recommended.

For CrCl less than 30 ml/min, use is contraindicated.

Due to the intensive binding of tenoxicam to plasma proteins, caution is recommended when using tenoxicam in patients with high bilirubin concentrations or with significant reduction in plasma albumin levels (e.g., in nephrotic syndrome).

Elderly patients

In the absence of impaired liver and kidney function, no dose adjustment is required.

Children

Use is contraindicated.

Adverse Reactions

Adverse reactions are grouped by system-organ class with an indication of their frequency of occurrence according to WHO recommendations: very common (≥1/10), common (≥1/100 but <1/10), uncommon (≥1/1000 but <1/100), rare (≥1/10000 but <1/1000), very rare (<1/10000), frequency unknown (cannot be estimated from the available data).

Contraindications

• Hypersensitivity to tenoxicam or excipients of the drug; there is also a possibility of cross-sensitivity to other NSAIDs;
• Erosive and ulcerative lesions of the gastrointestinal tract, including history;
• Gastrointestinal bleeding, including history;
• Inflammatory bowel diseases (Crohn’s disease or ulcerative colitis in the acute phase);
• Severe renal failure, CrCl less than 30 ml/min;
• Progressive kidney disease;
• Severe hepatic failure;
• Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including history);
• Established diagnosis of blood clotting disorders;
• Decompensated heart failure;
• Therapy of perioperative pain during coronary artery bypass grafting;
• Pregnancy;
• Breastfeeding period;
• Children under 18 years of age;
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

With caution gastric and duodenal ulcer, ulcerative colitis and Crohn’s disease not in acute phase, history of liver disease, hepatic porphyria, significant reduction in circulating blood volume (including after surgery), chronic heart failure (CHF), arterial hypertension, diabetes mellitus, coronary artery disease, cerebrovascular diseases, dyslipidemia/hyperlipidemia, peripheral arterial diseases, smoking, chronic renal failure (CrCl 30-60 ml/min), presence of Helicobacter pylori infection, long-term use of NSAIDs, alcoholism, severe somatic diseases, simultaneous use of corticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), age over 65 years (including patients receiving diuretics, debilitated patients and patients with low body weight), bronchial asthma, autoimmune diseases (SLE and mixed connective tissue disease).

Use in Pregnancy and Lactation

Pregnancy

The use of Artoxan^® during pregnancy is contraindicated.

Breastfeeding period

The use of Artoxan^® during breastfeeding is contraindicated.

Fertility

Due to the negative effect on fertility, the use of the drug is not recommended for women wishing to become pregnant. In patients with infertility (including those undergoing examination), it is recommended to discontinue the drug.

Use in Hepatic Impairment

Use of the drug is contraindicated in severe hepatic impairment.

With caution: in patients with a history of liver disease, hepatic porphyria.

Use in Renal Impairment

Use of the drug is contraindicated in severe renal impairment (CrCl less than 30 ml/min), progressive kidney disease.

With caution: in chronic renal failure (CrCl 30-60 ml/min).

Pediatric Use

Use in children under 18 years of age is contraindicated.

Geriatric Use

The drug should be prescribed with caution to patients over 65 years of age.

Special Precautions

During treatment, monitoring of the prothrombin index (while taking indirect anticoagulants), blood glucose concentration (while using hypoglycemic agents), peripheral blood picture, and functional state of the liver and kidneys is necessary.

If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study.

An increase in bleeding time is possible, which should be taken into account during surgical interventions.

The possibility of sodium and water retention in the body when used with diuretics in patients with arterial hypertension and heart failure should be considered. Patients with uncontrolled arterial hypertension, chronic heart failure, peripheral arterial diseases, confirmed coronary artery disease and/or cerebrovascular diseases should take the drug under medical supervision.

A history of kidney disease may lead to the development of interstitial nephritis, papillary necrosis, and nephrotic syndrome.

Adverse effects can be minimized by using the minimum effective dose of the drug for the shortest possible course.

In patients with SLE and mixed connective tissue disease, the risk of aseptic meningitis increases.

Excipients

Artoxan^® contains lactose. Patients with rare hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this drug.

Effect on ability to drive vehicles and operate machinery

One of the adverse effects of the drug is dizziness, which should be taken into account in situations requiring increased attention, when driving vehicles and operating machinery.

Overdose

Symptoms (with a single administration): abdominal pain, nausea, vomiting, erosive and ulcerative lesions of the gastrointestinal tract, impaired renal and liver function, metabolic acidosis.

Treatment is symptomatic (maintenance of vital body functions). Hemodialysis is not very effective.

Drug Interactions

Tenoxicam has a high degree of binding to albumin and may, like all NSAIDs, enhance the anticoagulant effect of warfarin and other anticoagulants. It is recommended to monitor functional and biochemical blood parameters when used concomitantly with anticoagulants and oral hypoglycemic drugs, especially in the initial stages of tenoxicam therapy.

No possible interaction with digoxin has been noted.

As with the use of other NSAIDs, it is recommended to use the drug with caution simultaneously with cyclosporine due to an increased risk of nephrotoxicity.

Concomitant use with quinolones may increase the risk of seizures.

Salicylates may displace Tenoxicam from albumin binding and, accordingly, increase the clearance and volume of distribution of the drug. Simultaneous use of salicylates or two or more NSAIDs should be avoided (thus increasing the risk of gastrointestinal complications).

There is evidence that NSAIDs reduce lithium excretion. Therefore, in patients receiving lithium therapy, lithium blood concentrations should be monitored more frequently.

NSAIDs can cause retention of sodium, potassium, and fluid in the body, interfering with the action of natriuretic diuretics. Caution should be exercised when concomitant use of tenoxicam and sodium-excreting diuretics is necessary in patients with CHF and arterial hypertension.

It is recommended to use NSAIDs with caution in combination with methotrexate, as NSAIDs reduce the excretion of methotrexate and may increase its toxicity.

NSAIDs should not be used within 8-12 hours after using mifepristone, as they may reduce its effect.

The increased risk of gastrointestinal bleeding with concomitant use of corticosteroids should be considered.

Reduces the effectiveness of uricosuric drugs, enhances the effect of anticoagulants, fibrinolytics, side effects of mineralocorticoids and glucocorticoids, estrogens; reduces the effectiveness of antihypertensive drugs and diuretics.

Inducers of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) increase the production of hydroxylated active metabolites.

Concomitant use with antiplatelet agents and selective serotonin reuptake inhibitors increases the risk of gastrointestinal bleeding.

Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides.

No interaction was detected when using tenoxicam with cimetidine.

No clinically significant interaction was detected during treatment with tenoxicam and penicillamine or parenteral gold preparations.

The risk of nephrotoxicity increases with the concomitant use of NSAIDs and tacrolimus.

The risk of hematological toxicity increases with the use of NSAIDs with zidovudine.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.