Xefocam film-coated tablets 8 mg blister 10 pcs.

Pharmacodynamics. Lornoxicam – an NSAID with analgesic and anti-inflammatory properties – belongs to the class of oxicams. The mechanism of action of lornoxicam is mainly associated with the inhibition of prostaglandin synthesis (inhibition of the COX enzyme), which leads to desensitization of peripheral nociceptors and suppression of inflammation. A central effect on nociceptors, which is not associated with anti-inflammatory action, is also assumed. Lornoxicam does not affect vital signs (e.g. body temperature, respiratory rate, heart rate, blood pressure, ECG, spirometry). The analgesic properties of lornoxicam have been successfully demonstrated in several clinical studies during the development of the drug.

Due to local irritation of the digestive tract and systemic ulcerogenic effects associated with inhibition of prostaglandin (PG) synthesis, the use of lornoxicam and other nonsteroidal anti-inflammatory drugs often leads to the development of gastrointestinal complications.

Pharmacokinetics. Absorption. Lornoxicam is rapidly and almost completely absorbed from the gastrointestinal tract. C _max is reached 1-2 hours after taking the drug. The bioavailability of lornoxicam is 90-100%. No first-pass effect is noted. The average half-life is 3-4 hours.

When lornoxicam is taken with food, Cmax _is reduced by approximately 30% and Tmax is increased from 1.5 to 2.3 hours. The absorption of lornoxicam (calculated according to the area under the pharmacokinetic curve “concentration / time” (AUC)) may decrease by up to 20%.

Lornoxicam 8 mg powder for injection is intended for IV and IM administration. C _max in blood plasma after IM administration of the drug is achieved after 0.4 hours. Bioavailability (calculated by AUC) after IM administration of the drug is 97%.

Distribution: In plasma, lornoxicam is present in unchanged form and in the inactive form of its hydroxylated metabolite. The binding of lornoxicam to plasma proteins is 99% and is independent of its concentration.

Biotransformation. Lornoxicam is extensively metabolized in the liver by hydroxylation, initially to the inactive 5-hydroxylornoxicam. Lornoxicam is metabolized by cytochrome CYP 2C9. The metabolism of this enzyme due to genetic polymorphisms can be slow or intense in different individuals, which can lead to a marked increase in plasma levels of lornoxicam in individuals with slow metabolism. The hydroxylated metabolite has no pharmacological activity. Lornoxicam is completely metabolized. Approximately ⅔ is excreted through the liver and ^_1/3 – through the kidneys in the form of an inactive compound.

Lornoxicam did not induce hepatic enzymes in animal models. Based on the results of clinical studies, there was no evidence of accumulation of lornoxicam after repeated administration at recommended doses. These results were confirmed by data from the 1-year safety and efficacy monitoring of the drug.

Excretion. T _½ of the parent substance is 3-4 hours. After oral administration, about 50% is excreted in the feces and 42% through the kidneys, mainly in the form of 5-hydroxylornoxicam. T _{½ of} 5-hydroxylornoxicam is about 9 hours, after parenteral administration of the drug 1 or 2 times a day.

In elderly patients (over 65 years of age), clearance is reduced by 30-40%. Apart from the reduction in clearance, there are no significant changes in the kinetic profile of lornoxicam in the elderly.

There is no significant change in the kinetic profile of lornoxicam in patients with renal or hepatic insufficiency, with the exception of cumulation in subjects with chronic liver disease, after 7 days of therapy with daily doses of 12 and 16 mg.

Short-term treatment of acute pain of mild to moderate severity.

For tablets also: symptomatic relief of pain and inflammation in osteoarthritis; symptomatic relief of pain and inflammation in rheumatoid arthritis.

pills

For all patients, the appropriate dosage regimen should be based on individual response to treatment.

pain

The dose of lornoxicam is 8-16 mg/day, divided into 2-3 doses. The maximum recommended daily dose is 16 mg.

Osteoarthritis and rheumatoid arthritis

An initial dose of 12 mg lornoxicam, divided into 2-3 doses, is recommended. The maintenance dose should not exceed 16 mg/day.

Xefocam film-coated tablets are taken orally with sufficient water.

Elderly patients (over 65 years of age), except for those with impaired liver or kidney function: dose adjustment is not required, but lornoxicam should be used with caution due to the possibility of adverse reactions from the gastrointestinal tract.

Renal impairment: For patients with mild to moderate renal impairment, the maximum recommended daily dose is 12 mg, divided into 2-3 doses.

Hepatic impairment: For patients with moderate hepatic impairment, the maximum recommended daily dose is 12 mg, divided into 2-3 doses (see Precautions).

Adverse reactions can be minimized by taking the drug in the lowest effective dose and for the shortest period necessary to control symptoms (see Precautions).

injections

This dosage form is intended for initiation of therapy and for rapid onset of analgesia or when oral medications or suppositories are not feasible. For all patients, the appropriate dosage regimen should be based on individual response to treatment.

For intravenous and intramuscular administration.

The recommended dose is 8 mg IV or IM. Some patients require an additional 8 mg dose in the first 24 hours. The maximum daily dose is 16 mg.

The duration of intravenous administration of the solution should be at least 15 s, intramuscular – at least 5 s. After preparing the solution, the needle should be replaced.

For intramuscular injection, a long needle is required to ensure deep injection. The drug is intended for single use only. The solution for injection should be prepared immediately before use (dissolve the contents of 1 vial (8 mg of lyophilisate) with water for injection (2 ml)).

Elderly patients (over 65 years of age), except for those with impaired liver or kidney function, do not require dose adjustment, but lornoxicam should be used with caution due to the likelihood of adverse reactions from the gastrointestinal tract.

Renal impairment: Patients with mild to moderate renal impairment require a reduced dose.

Hepatic impairment: Patients with moderate hepatic impairment require a reduced dose.

Adverse reactions can be minimized by taking the drug in the lowest effective dose and for the shortest period necessary to control symptoms (see Precautions).

Reconstituted solution: Chemical and physical in-use stability has been demonstrated for 24 hours at 2-8°C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

• Hypersensitivity to lornoxicam or to any of the excipients; thrombocytopenia; hypersensitivity (symptoms similar to those of barium enema, rhinitis, angioedema or urticaria) to other non-steroidal anti-inflammatory drugs, including acetylsalicylic acid; severe heart failure; gastrointestinal bleeding, cerebrovascular or other bleeding; gastrointestinal bleeding or ulcer perforation in history, associated with previous NSAID therapy; active recurrent gastric ulcer/bleeding or recurrent gastric ulcer/bleeding in history (2 or more separate proven episodes of ulceration or bleeding); severe hepatic insufficiency; severe renal insufficiency (plasma creatinine level 700 μmol/l); 3rd trimester of pregnancy (see use during pregnancy and breastfeeding).

The most common adverse reactions of NSAIDs were related to the gastrointestinal tract. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, may occur with the use of NSAIDs, especially in the elderly (see special instructions). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease have been reported with the treatment of NSAIDs. Gastritis has been reported less frequently.

It is estimated that ≈20% of patients treated with lornoxicam may experience adverse events. The most common adverse events of lornoxicam are nausea, dyspepsia, indigestion, abdominal pain, vomiting, and diarrhea. These symptoms were generally observed in 10% of patients in the study. Edema, hypertension, and heart failure have been reported with NSAID treatment.

Clinical trials and epidemiological data suggest that the use of some NSAIDs, particularly at high doses and in prolonged periods, may be associated with an increased risk of arterial thrombotic events, such as myocardial infarction or stroke (see Precautions).

Serious infectious complications of the skin and soft tissues have been reported exclusively during the course of chickenpox.

Adverse effects are classified by frequency of occurrence into the following categories: 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), unknown (frequency cannot be estimated from the available data).

Infections and infestations: rarely – pharyngitis.

Blood and lymphatic system disorders: rarely – anemia, thrombocytopenia, leukopenia, increased bleeding time; very rarely – ecchymosis. NSAIDs can cause class-specific potentially severe hematological disorders, such as neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia.

Immune system disorders: rarely – hypersensitivity reactions, anaphylactoid reactions and anaphylaxis.

Metabolic disorders: infrequently – loss of appetite, changes in body weight.

Mental disorders: infrequently – insomnia, depression; rarely – anxiety, nervousness, agitation.

From the nervous system: often – mild and transient headache, dizziness; rarely – drowsiness, paresthesia, taste disturbances (dysgeusia), tremor, migraine; very rarely – aseptic meningitis in patients with systemic lupus erythematosus and mixed connective tissue disease (see Features of use).

On the part of the organ of vision: infrequently – conjunctivitis; rarely – visual impairment.

From the organs of hearing and balance: infrequently – vertigo, tinnitus.

From the cardiovascular system: infrequently – palpitations, tachycardia, edema, heart failure, facial flushing; rarely – arterial hypertension, hot flashes, hemorrhages, hematomas.

From the respiratory system: infrequently – rhinitis; rarely – dyspnea, cough, bronchospasm.

From the digestive system: often – nausea, abdominal pain, dyspepsia, diarrhea, vomiting; infrequently – constipation, flatulence, belching, dry mouth, gastritis, gastric ulcer, abdominal pain, abdominal pain in the upper abdomen, duodenal ulcer, oral mucosal ulcers; rarely – melena, vomiting with blood, stomatitis, esophagitis, gastroesophageal reflux, dysphagia, aphthous stomatitis, glossitis, ulcer perforation, gastrointestinal bleeding.

From the liver and biliary tract: infrequently – increased levels of liver enzymes (ALT, AST); very rarely – toxic effects on the liver, resulting in the possible development of liver failure, hepatitis, jaundice, cholestasis.

Skin and subcutaneous tissue disorders: infrequently – rash, itching, increased sweating, erythematous rashes, urticaria, angioedema, alopecia; rarely – dermatitis, eczema, purpura; very rarely – edema and bullous reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders: infrequently – arthralgia; rarely – bone pain, muscle spasms, myalgia.

From the kidneys and urinary tract: rarely – nocturia, urination disorders, increased levels of urea nitrogen and creatinine in the blood; very rarely lornoxicam can cause acute renal failure in people with kidney diseases that depend on renal prostaglandins, which play an important role in maintaining renal blood flow (see Features of use). Nephrotoxicity in various forms, including nephritis and nephrotic syndrome, is a class-specific effect of NSAIDs.

General disorders: infrequently – malaise, facial edema; rarely – asthenia.

In such disorders, the drug can be prescribed only after a careful assessment of the ratio of expected benefit from therapy / possible risk.

Lornoxicam should be used with caution in patients with mild renal impairment (serum creatinine level 150-300 μmol/l) and moderate renal impairment (serum creatinine level 300-700 μmol/l) due to the important role of prostaglandins in maintaining renal blood flow. Treatment with the drug should be discontinued if renal function deteriorates.

People after major surgery, with heart failure, taking diuretics or drugs that can cause kidney damage, need to have their kidney function carefully monitored.

A thorough clinical examination and evaluation of laboratory parameters (e.g. activated partial thrombin time) are recommended for patients with coagulation disorders.

In patients with hepatic insufficiency (e.g. cirrhosis) after administration of the drug at a dose of 12-16 mg/day, it is recommended to regularly conduct laboratory tests due to the possibility of accumulation of lornoxicam in the body (increased AUC). However, no deviations in pharmacokinetic parameters were found in patients with hepatic insufficiency compared to healthy volunteers.

With long-term treatment (3 months), it is recommended to assess the blood condition (hemoglobin determination), kidney function (creatinine determination) and liver enzymes.

Elderly people (over 65 years of age) are recommended to monitor kidney and liver function and use the drug with caution after surgical interventions.

Concomitant use of lornoxicam with other NSAIDs, including selective COX-2 inhibitors, should be avoided.

Adverse reactions can be minimized by taking the lowest effective dose of the drug for the shortest period necessary to control the symptoms of the disease.

With the use of any NSAID at any time during treatment, gastrointestinal bleeding, ulceration or perforation may occur (with or without warning symptoms or a history of serious gastrointestinal disorders), which may be fatal.

The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing NSAID dose in patients with a history of ulceration, especially complicated by bleeding or perforation (see Adverse Reactions), and in the elderly. These groups of patients should be started with particular caution at the lowest therapeutic doses.

NSAIDs should be used with caution in the above groups of patients and in those taking low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications (see Interactions with other drugs). For patients requiring such combined therapy, treatment may be carried out with the simultaneous use of protective agents (e.g. misoprostol or proton pump inhibitors). Clinical monitoring at regular intervals is recommended.

Patients with a history of gastrointestinal toxicity, especially the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) early in treatment. Special caution should be exercised in patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid (see Interactions).

If gastrointestinal bleeding or ulceration occurs in patients taking lornoxicam, treatment should be discontinued.

NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), as their condition may worsen. Elderly patients are more likely to experience adverse reactions to NSAIDs, including gastrointestinal bleeding and perforation, which may be fatal (see Adverse Reactions). The drug should be used with caution in patients with a history of hypertension and/or heart failure, as NSAIDs may cause edema and fluid retention.

Patients with hypertension and/or a history of mild to moderate congestive heart failure should be monitored closely, as NSAID therapy may be associated with events such as fluid retention and oedema. There are clinical studies and epidemiological data suggesting that the use of some NSAIDs (particularly long-term therapy and at high doses) 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 lornoxicam.

Lornoxicam should only be administered to patients with uncontrolled hypertension, chronic heart failure, coronary artery disease, peripheral arterial disease and/or cerebrovascular disorders after careful evaluation of the indications. Evaluation is also required before long-term treatment is prescribed to individuals with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking). Concomitant treatment with NSAIDs and heparin increases the risk of spinal/epidural hematoma during spinal or epidural anesthesia (see Interactions with other drugs).

Very rarely, skin reactions including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis have occurred with the use of NSAIDs, some of which have been fatal (see Adverse Reactions). The risk of developing such reactions is highest at the beginning of treatment: in most cases, such reactions occur in the first month of taking the drug. Lornoxicam should be discontinued at the first sign of skin rash, mucosal lesions or other manifestations of hypersensitivity.

Use with caution in individuals with asthma or a history of this disease, as NSAIDs provoke bronchospasm in these patients.

Patients with systemic lupus erythematosus and mixed connective tissue disease may be at increased risk of developing aseptic meningitis.

Lornoxicam inhibits platelet aggregation, increasing blood clotting time.

The drug should be prescribed with caution to patients with a tendency to bleeding.

Concomitant treatment with NSAIDs and tacrolimus may increase the risk of nephrotoxicity due to decreased renal prostacyclin synthesis. Renal function should be closely monitored during such combination therapy.

Like other nonsteroidal anti-inflammatory drugs, lornoxicam may cause occasional elevations in transaminases, serum bilirubin, and blood urea and creatinine concentrations, as well as other laboratory abnormalities. If laboratory abnormalities are significant and persist for a long time, treatment should be discontinued and appropriate investigations should be performed.

This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Lornoxicam, like other drugs that inhibit COX/prostaglandin synthesis, may impair fertility and is therefore not recommended in women attempting to conceive. Lornoxicam should be discontinued in women who have difficulty conceiving or who are undergoing investigation of infertility.

In the presence of chickenpox, in exceptional cases, severe skin and soft tissue infections may develop. At this time, it cannot be ruled out that NSAIDs may worsen the course of these infections. It is recommended to avoid the use of lornoxicam in the presence of chickenpox.

Use during pregnancy or breastfeeding. Pregnancy. Lornoxicam is contraindicated in the third trimester of pregnancy. There are no clinical data on the use of lornoxicam in the first and second trimesters of pregnancy and during childbirth, therefore the drug is not recommended for use during this period.

There are no adequate data from the use of lornoxicam in pregnant women. Animal studies have shown reproductive toxicity.

Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and/or embryo/fetal development. Epidemiological studies have shown an increased risk of miscarriage and heart defects when prostaglandin synthesis inhibitors are used in early pregnancy. The risk increases with increasing dose and duration of therapy. In animals, the use of prostaglandin synthesis inhibitors has been associated with increased pre- and post-implantation fetal death and embryo-fetal mortality. Prostaglandin synthesis inhibitors should not be used in the first and second trimesters of pregnancy. Use is only possible if clearly needed.

In the third trimester of pregnancy, the use of any prostaglandin synthesis inhibitors may have the following effects on the fetus:

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

The pregnant woman and fetus at the end of pregnancy may be exposed to the following effects from the use of prostaglandin synthesis inhibitors:

• possible increase in bleeding duration;
• suppression of uterine contractile function, which can lead to a delay or increase in the duration of labor.

Therefore, the use of lornoxicam is contraindicated in the third trimester of pregnancy (see Side effects).

Breastfeeding. There are no data on the excretion of lornoxicam in human milk. Relatively high concentrations of lornoxicam are excreted in the milk of lactating rats. Therefore, lornoxicam should not be used during breastfeeding.

Children: Lornoxicam is not recommended for use in children under 18 years of age due to a lack of clinical data on the efficacy and safety of the drug.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. In case of dizziness and/or drowsiness due to taking lornoxicam, you should not drive vehicles or work with other mechanisms.

Concomitant use of lornoxicam and the following drugs:

• cimetidine: increased plasma concentration of lornoxicam (no interaction between lornoxicam and ranitidine or lornoxicam and antacids has been identified);
• Anticoagulants: NSAIDs may increase the effects of anticoagulants (e.g. warfarin – see Precautions). Careful monitoring of INR is required;
• Phenprocoumon: the effectiveness of treatment with phenprocoumon is reduced;
• Heparin: NSAIDs increase the risk of spinal/epidural hematoma when used concomitantly with heparin during spinal or epidural anesthesia (see Precautions);
• ACE inhibitors: may reduce the severity of the effect of ACE inhibitors;
• Diuretics: weakening of the diuretic and hypotensive effect of loop, thiazide and potassium-sparing diuretics;
• β-adrenergic blockers: weakening of the hypotensive effect;
• angiotensin II receptor blockers: reduced hypotensive effect;
• Digoxin: decreased renal clearance of digoxin;
• corticosteroids: increased risk of gastrointestinal ulcers or bleeding (see Precautions);
• quinolone antibacterial agents: increased risk of seizures;
• antiplatelet drugs: the risk of gastrointestinal bleeding increases (see Special warnings and precautions for use);
• other NSAIDs: increased risk of gastrointestinal bleeding;
• Methotrexate: increased plasma concentrations of this drug, leading to increased toxicity. Careful monitoring is required when used concomitantly;
• SSRIs: increased risk of gastrointestinal bleeding (see Precautions);
• Lithium: NSAIDs reduce renal clearance of lithium, thus serum lithium concentrations may exceed the toxicity threshold. Serum lithium levels should be monitored, especially at the start of treatment, during dose adjustments and when treatment is discontinued;
• Cyclosporine: increased serum cyclosporine concentration. Possible increased nephrotoxicity of cyclosporine due to effects mediated by renal prostaglandins. Renal function should be monitored during combination therapy;
• sulfonylurea derivatives (e.g. glibenclamide): increased risk of hypoglycemia;
• known inducers and inhibitors of CYP 2C9 isoenzymes: lornoxicam (like other non-steroidal anti-inflammatory drugs dependent on cytochrome P450 2C9 (CYP 2C9 isoenzyme)) interacts with known inducers and inhibitors of CYP 2C9 isoenzymes (see Biotransformation);
• Tacrolimus: increased risk of nephrotoxicity due to decreased renal prostacyclin synthesis. Renal function should be monitored during combination therapy (see Precautions);
• Pemetrexed: NSAIDs may reduce the renal clearance of pemetrexed, resulting in increased renal and gastrointestinal toxicity and myelosuppression.

Since food slows down the absorption of lornoxicam, Xefocam tablets should not be taken with food if a rapid onset of their effective action (pain relief) is required.

Food intake reduces absorption by ≈20% and increases Tmax.

Incompatibility. The drug in the form of a solution for injection should not be mixed with other drugs, except those specified in the instructions for use.

There are currently no data on overdose that would allow us to determine its consequences or to suggest specific treatment. The following symptoms may occur as a result of an overdose of lornoxicam: nausea, vomiting, cerebral symptoms (dizziness, visual impairment). In severe cases: ataxia, with transition to coma and convulsions; liver and kidney damage; possible blood clotting disorders. In case of real or suspected overdose, the drug should be discontinued. Due to the short t½, lornoxicam is rapidly excreted from the body. Dialysis is ineffective. There is currently no specific antidote. It is necessary to carry out the usual emergency measures, including gastric lavage. Based on general principles, only the use of activated charcoal when taken immediately after an overdose of lornoxicam can lead to a decrease in the absorption of the drug. For the treatment of gastrointestinal disorders, you can, for example, use a prostaglandin analogue or ranitidine.

In the original packaging at a temperature not exceeding 25 °C.