Xefocam Rapid film-coated tablets 8 mg blister 6 pcs

Pharmacodynamics. Lornoxicam is an NSAID with analgesic properties and belongs to the class of oxicams. The mechanism of action of lornoxicam is mainly based on the inhibition of prostaglandin synthesis (COX inhibition), which leads to desensitization of peripheral pain receptors 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 synthesis, the use of lornoxicam, like other NSAIDs, often leads to the development of gastrointestinal complications.

Pharmacokinetics. Absorption. Lornoxicam is rapidly and almost completely absorbed from the gastrointestinal tract. C _max in blood plasma is reached 30 minutes after taking the drug. C _max of the drug Ksefokam Rapid, film-coated tablets, is higher than C _max of the drug Ksefokam, film-coated tablets, and is equivalent to C _max for dosage forms of lornoxicam intended for parenteral administration.

The absolute bioavailability (calculated by AUC) of Xefocam Rapid, film-coated tablets, is 90-100% and is equivalent to the bioavailability of Xefocam, film-coated tablets. The effect of the first passage of the drug is not noted. The average T _½ is 3-4 hours.

There are no data on the simultaneous use of the drug Xefocam Rapid with food. However, based on data on the drug Xefocam, a decrease in C _max and an increase in T _max and a decrease in absorption (AUC) may be noted.

Distribution: Lornoxicam is present in plasma in unchanged form and in the inactive form of the hydroxylated metabolite. The binding of lornoxicam to plasma proteins is 99% and does not depend on its concentration.

Biotransformation. Lornoxicam is extensively metabolized in the liver by hydroxylation, initially to the inactive 5-hydroxylornoxicam. Lornoxicam is metabolized by cytochrome CYP2C9. Due to genetic polymorphism, there are people with slow and intensive metabolism, which can be expressed in a noticeable increase in plasma levels of lornoxicam in individuals with slow metabolism. The hydroxylated metabolite has no pharmacological activity. Lornoxicam is completely metabolized. About ⅔ of the dose 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. No evidence of accumulation of lornoxicam was observed in clinical studies after repeated administration at recommended doses. The absence of accumulation was confirmed by data from safety and efficacy monitoring studies over a period of 1 year.

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

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

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

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

The drug Xefocam Rapid, film-coated tablets, should be taken orally with sufficient liquid.

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

Acute pain. The recommended dose is 8-16 mg (1-2 tablets) per day. The initial dose is 16 mg, after 12 hours another 8 mg should be taken on the first day of treatment. After the first day of treatment, the daily dose should not exceed 16 mg.

Elderly patients (over 65 years of age) do not require dose adjustment, except for patients with impaired liver or kidney function, but Xefocam Rapid should be used with caution due to the possibility of adverse reactions from the digestive tract (see Features of use).

Patients with renal insufficiency are recommended to reduce the dose of Xefocam Rapid and take the drug once a day.

Patients with liver failure are recommended to reduce the dose of Xefocam Rapid and take the drug once a day.

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

Hypersensitivity to lornoxicam or to any of the excipients; thrombocytopenia; hypersensitivity to other non-steroidal anti-inflammatory drugs, including acetylsalicylic acid (symptoms similar to those of barium, rhinitis, angioedema or urticaria); severe heart failure; gastrointestinal bleeding, cerebral vascular bleeding or other hematological disorders; history of gastrointestinal bleeding or perforation associated with previous NSAID use; active peptic ulcer disease or history of recurrent peptic ulcer disease/bleeding (2 or more proven episodes of ulceration or bleeding); severe hepatic failure; severe renal failure (serum 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 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 NSAIDs (see special instructions). Gastritis has been observed less frequently.

It is estimated that approximately 20% of patients treated with lornoxicam may experience side effects. The most common side effects of lornoxicam are nausea, dyspepsia, indigestion, abdominal pain, vomiting, and diarrhea. These symptoms were generally observed in less than 10% of patients in the studies.

Edema, hypertension, and heart failure have been reported to occur as a result of NSAID use.

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

Only in the case of chickenpox have serious infectious complications of the skin and soft tissues been reported.

The following adverse reactions are listed, which in total occurred in more than 0.05% of the 6417 patients treated with the drug during phase II, III and IV clinical trials.

Undesirable effects that may occur when taking the drug Xefocam Rapid 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 determined from the available data).

Infections and infestations: rarely – pharyngitis.

Blood and lymphatic system disorders: rarely – anemia, thrombocytopenia, eosinophilia, leukopenia, coagulation disorders, prolonged bleeding time, pancytopenia; very rarely – ecchymosis. NSAIDs can cause potentially severe hematological disorders typical of this class, such as neutropenia, agranulocytosis, aplastic and hemolytic anemia.

On the part of the immune system: rarely – hypersensitivity reactions, fever, chills, anaphylactoid reactions, anaphylaxis.

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

Metabolism and nutrition disorders: rarely – hyponatremia.

Psychiatric disorders: infrequently – insomnia, depression; rarely – anxiety, impaired consciousness, increased excitability, impaired ability to concentrate, change in attention, cognitive disorders.

From the nervous system: often – mild short-term headache, dizziness; rarely – drowsiness, paresthesia, dysgeusia, tremor, migraine, hyperkinesia, hypoesthesia; very rarely – aseptic meningitis in patients with systemic lupus erythematosus and mixed connective tissue diseases (see Features of use).

On the part of the organ of vision: infrequently – conjunctivitis; rarely – visual disturbances, including blurred vision, impaired color perception, visual field defects, scotoma, amblyopia, diplopia, iridocyclitis.

From the side of the organs of hearing and labyrinth of the ear: infrequently – vertigo, tinnitus.

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

From the respiratory system, chest organs and mediastinum: infrequently – rhinitis; rarely – dyspnea, cough, bronchospasm.

Gastrointestinal tract: often – nausea, abdominal pain, dyspepsia, diarrhea, vomiting; infrequently – constipation, flatulence, belching, dry mouth, gastritis, gastric and duodenal ulcers, upper abdominal pain, bleeding gums, ulcerative stomatitis; rarely – melena, vomiting with blood, aphthous stomatitis, esophagitis, gastroesophageal reflux disease, dysphagia, stomatitis, glossitis, perforation of peptic ulcers, hemorrhoids, gastrointestinal bleeding.

On the part of the hepatobiliary system: 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 and angioedema, alopecia; rarely – dermatitis, eczema, maculopapular rash, purpura; very rarely – edema and bullous reactions, nail changes, psoriasis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders: infrequently – arthralgia; rarely – pain in the bones and back, muscle spasms, muscle weakness, myalgia, synovitis.

From the kidneys and urinary system: rarely – nocturia, urination disorders, increased blood urea nitrogen and creatinine levels; very rarely – lornoxicam can cause acute renal failure in patients with pre-existing 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 characteristic effect of NSAIDs. There are cases of development of papillary necrosis caused by taking NSAIDs.

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

The drug should be prescribed only after careful assessment of the expected benefit of therapy and the possible risk in the following cases:

• Renal impairment. Lornoxicam should be used with caution in patients with mild (serum creatinine level 150-300 μmol/l) and moderate (serum creatinine level 300-700 μmol/l) renal impairment due to the important role of prostaglandins in maintaining renal blood flow. If renal function deteriorates during treatment, lornoxicam therapy should be discontinued;
• Patients after extensive surgery, with heart failure, taking diuretics or drugs that can cause kidney damage, need to carefully monitor kidney function;
• In case of blood clotting disorders, a thorough clinical examination and evaluation of laboratory parameters (activated partial thrombin time) are recommended;
• patients with hepatic insufficiency (e.g. cirrhosis). After using the drug at a dose of 12-16 mg/day, monitoring and laboratory tests are recommended due to the possibility of accumulation of lornoxicam in the body (increased AUC), but no deviations in pharmacokinetic parameters were found in patients with hepatic insufficiency compared to healthy volunteers;
• with long-term treatment (more than 3 months). It is recommended to assess the blood condition (hemoglobin determination), kidney function (creatinine determination) and liver enzymes;
• Elderly patients (over 65 years of age). Monitoring of kidney and liver function is recommended and use 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 (see Method of administration and information on risks from the gastrointestinal tract and cardiovascular system).

Gastrointestinal bleeding, ulcers and perforations: Gastrointestinal bleeding, ulcers and perforations, which can be fatal, may occur with the use of NSAIDs (regardless of the presence of warning symptoms or a history of serious gastrointestinal disorders).

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 elderly patients. These groups of patients should be started with particular caution at the lowest therapeutic dose.

For patients requiring such combination therapy and patients taking concomitant low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications, treatment may be carried out with concomitant protective drugs (e.g. misoprostol or proton pump inhibitors) (see Interactions with other medicinal products). Regular clinical monitoring is recommended.

Patients with a history of gastrointestinal toxicity, especially the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding) during the initial stages of treatment.

Caution should be exercised in patients taking concomitant medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (acetylsalicylic acid) (see Interactions with other drugs).

In case of gastrointestinal bleeding or ulceration 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 (see Side effects).

Elderly patients are at increased risk of 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 taking NSAIDs may cause edema and fluid retention in the body.

Patients with hypertension and/or a history of mild to moderate congestive heart failure should be monitored, as NSAID therapy may be associated with phenomena such as fluid retention and edema.

There are clinical trial and epidemiological data suggesting that the use of some NSAIDs (especially when taken for long periods and/or at high doses) is associated with a slightly increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There are insufficient data to exclude such a risk with lornoxicam.

Lornoxicam should only be prescribed to patients with uncontrolled hypertension, congestive heart failure, coronary artery disease, peripheral arterial disease and/or cerebrovascular disorders after careful evaluation of the indications. Evaluation is also required before prescribing long-term treatment to patients 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, severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, sometimes fatal, have occurred with NSAIDs (see Adverse Reactions). The risk of developing such reactions is highest at the beginning of treatment: in most cases, such reactions occur within 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 patients with bronchial asthma or a history of this disease, as NSAIDs provoke bronchospasm in these patients.

Patients with systemic lupus erythematosus and mixed connective tissue diseases are 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 serum transaminases, serum bilirubin, blood urea and creatinine, and other laboratory abnormalities. If laboratory abnormalities are significant and persist for a long time, treatment should be discontinued and appropriate investigations should be performed.

Lornoxicam, like other drugs that inhibit COX/prostaglandin synthesis, may impair fertility and is 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, severe skin and soft tissue infections may develop in exceptional cases. The effect of NSAIDs on the worsening of these infectious diseases cannot be excluded. It is recommended to avoid the use of lornoxicam in chickenpox.

Use during pregnancy and 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 shown to increase the incidence of 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 absolutely necessary.

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 can progress to renal failure and then to a decrease in the amount of amniotic fluid.

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

• increased 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 breast milk. Relatively high concentrations of lornoxicam are excreted in the milk of lactating rats. Therefore, lornoxicam should not be used during breastfeeding.

Children. The drug is not recommended for use in children (under 18 years of age) due to insufficient clinical data on the efficacy and safety of the drug.

The ability to influence the reaction rate when driving vehicles or other mechanisms. In case of dizziness and/or drowsiness as a result of taking the drug, you should not drive vehicles or work with complex mechanisms.

In the case of simultaneous administration of the drug Xefocam Rapid and other drugs, the following interactions are possible:

• cimetidine: increased plasma concentration of lornoxicam (no interaction between lornoxicam and ranitidine or lornoxicam and antacids has been identified);
• Anticoagulants: NSAIDs may enhance the effects of anticoagulants (e.g. warfarin) (see Precautions). Close monitoring of international normalized ratio is necessary;
• 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 hypotensive effect of ACE inhibitors;
• Diuretics: weakening of the diuretic and hypotensive effect of loop, thiazide and potassium-sparing diuretics;
• β-adrenergic blockers: reduced hypotensive effect;
• angiotensin II receptor blockers: reduced hypotensive effect;
• Digoxin: decreased renal clearance of digoxin;
• corticosteroids: increased risk of gastrointestinal ulcers and 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 serum concentrations of this drug, which leads to increased toxicity. With simultaneous use, careful monitoring of the patient’s condition is necessary;
• selective serotonin reuptake inhibitors: 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. In combination therapy, renal function should be monitored;
• Sulfonylurea derivatives (e.g. glibenclamide): hypoglycemic effect may be enhanced;
• CYP2C9 inducers and inhibitors: lornoxicam (like other nonsteroidal anti-inflammatory drugs that are metabolized by cytochrome CYP2C9) interacts with inducers and inhibitors of CYP2C9 isoenzymes;
• Tacrolimus: 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 (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 Rapid film-coated tablets should not be taken with food if a rapid and effective effect (pain relief) is required.

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

To date, there are no data on drug overdose that would allow to determine its consequences or to suggest specific treatment. In case of overdose of lornoxicam, the following symptoms are possible: nausea, vomiting, cerebral symptoms (dizziness, visual disturbances). In severe cases: symptoms of ataxia, progressing to coma, and convulsions; liver and kidney damage, possible blood clotting disorders.

In case of actual or suspected overdose, the drug should be discontinued. Due to its short T _½, lornoxicam is rapidly eliminated from the body. It is not dialyzable. There is currently no specific antidote. It is necessary to carry out the usual emergency measures, including gastric lavage. Based on general principles, the use of activated charcoal immediately after an overdose of the drug may lead to a decrease in its absorption. For the treatment of gastrointestinal disorders, for example, a prostaglandin analogue or ranitidine can be used.

At a temperature not exceeding 25 °C.