Instructions for use of Xefocam Rapid film-coated tablets 8 mg No. 6
Composition
active ingredient: lornoxicam;
1 tablet contains 8 mg of lornoxicam;
excipients: calcium stearate, hydroxypropyl cellulose, sodium bicarbonate, low-substituted hydroxypropyl cellulose, microcrystalline cellulose, calcium hydrogen phosphate;
film coating: propylene glycol, talc, titanium dioxide (E 171), hypromellose.
Dosage form
Film-coated tablets.
Main physicochemical properties: round biconvex tablet, film-coated, white to light yellow in color.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Oxycodone.
ATX code M01A C05
Pharmacological properties
Pharmacodynamics.
Lornoxicam is a nonsteroidal anti-inflammatory drug with analgesic properties and belongs to the oxicam class. The mechanism of action of lornoxicam is mainly based on the inhibition of prostaglandin synthesis (cyclooxygenase inhibition), which causes desensitization of peripheral pain receptors and inhibition 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 drug development process.
Due to local irritation of the gastrointestinal tract and systemic ulcerogenic effect associated with inhibition of prostaglandin synthesis, the use of lornoxicam, like other nonsteroidal anti-inflammatory drugs (NSAIDs), often leads to the development of gastrointestinal complications.
Pharmacokinetics.
Absorption. Lornoxicam is rapidly and almost completely absorbed from the gastrointestinal tract. The maximum plasma concentration (Cmax) is reached 30 minutes after taking the drug. Cmax of the drug Xefocam, film-coated tablets, is higher than Cmax of Xefocam in the dosage form of film-coated tablets and is equivalent to Cmax for dosage forms of lornoxicam intended for parenteral administration.
The absolute bioavailability of Xefocam Rapid, film-coated tablets, is 90-100% and is equivalent to the bioavailability of Xefocam, film-coated tablets. No first-pass effect was observed.
There are no data on the simultaneous use of Xefocam Rapid with food. However, given the properties of Xefocam, a decrease in Cmax, an increase in Tmax and a decrease in absorption (AUC) can be expected.
Distribution: Lornoxicam is present in plasma in an unchanged state and in the inactive form of its hydroxylated metabolite. The binding of lornoxicam to plasma proteins is 99% and is independent of its concentration. It is also detected in synovial fluid after repeated administration.
Biotransformation. Lornoxicam is extensively metabolized in the liver by hydroxylation, first 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 people with slow metabolism. The hydroxylated metabolite has no pharmacological activity. Lornoxicam is completely metabolized. Approximately 2/3 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 of the recommended doses. The absence of accumulation was confirmed by data from 1-year drug safety and efficacy monitoring studies.
Elimination. The elimination half-life of the drug is 3 to 4 hours. After oral administration, approximately 50% of the drug is excreted in the feces, 42% by the kidneys, mainly as 5-hydroxylornoxicam. The elimination half-life of 5-hydroxylornoxicam after parenteral administration of the drug once or twice a day is about 9 hours. There is no evidence that the elimination rate changes with repeated doses.
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.
Indication
Short-term symptomatic treatment of acute mild to moderate pain in adults.
Contraindication
Hypersensitivity to lornoxicam or to other components of the drug;
thrombocytopenia;
hypersensitivity (symptoms similar to those of bronchial asthma, rhinitis, angioedema or urticaria) to other non-steroidal anti-inflammatory drugs, including acetylsalicylic acid;
gastrointestinal bleeding, cerebral vascular bleeding or other hematological disorders;
history of gastrointestinal bleeding or perforation associated with previous use of nonsteroidal anti-inflammatory drugs;
active peptic ulcer or history of recurrent peptic ulcer/bleeding (two or more episodes of proven ulceration or bleeding);
severe liver failure;
severe renal failure (serum creatinine level > 700 μmol/l);
III trimester of pregnancy (see section "Use during pregnancy or breastfeeding").
Interaction with other medicinal products and other types of interactions
In the case of simultaneous administration of the drug Xefocam Rapid and other drugs, the following interactions are possible:
Cimetidine: increased plasma concentrations of lornoxicam, which may increase the risk of adverse effects 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 section 4.4). Close monitoring of INR (International Normalized Ratio) is necessary.
Phenprocoumon: the effectiveness of phenprocoumon treatment is reduced.
Heparin: NSAIDs increase the risk of bleeding and spinal/epidural hematomas when used concomitantly with heparin during spinal or epidural anesthesia (see section "Special warnings and precautions for use").
ACE inhibitors (angiotensin-converting enzyme inhibitors): the hypotensive effect of ACE inhibitors may be reduced.
Diuretics: weakening of the diuretic and hypotensive effect of loop, thiazide and potassium-sparing diuretics (increased risk of hyperkalemia and nephrotoxicity).
Beta-adrenergic blockers: reduced hypotensive effect.
Angiotensin II receptor blockers: reduction of the hypotensive effect.
Digoxin: decreased renal clearance of digoxin, increasing the risk of digoxin toxicity.
Corticosteroids: increased risk of gastrointestinal ulcers and bleeding (see section "Special warnings and precautions for use").
Quinolone antibacterial agents (e.g. levofloxacin, ofloxacin): increased risk of seizures.
Antiplatelet drugs (e.g. clopidogrel): increased risk of bleeding (see section "Special warnings and precautions for use").
Other NSAIDs: increased risk of gastrointestinal bleeding or ulcers.
Methotrexate: increased serum concentrations of methotrexate, leading to increased toxicity. Careful monitoring of the patient's condition is necessary when used concomitantly.
Selective serotonin reuptake inhibitors (SSRIs): increased risk of bleeding (see section "Special warnings and precautions for use").
Lithium: NSAIDs reduce the renal clearance of lithium, so serum lithium concentrations may exceed the threshold for toxicity. Serum lithium levels should be monitored, especially at the beginning of treatment, during dose adjustments and during discontinuation of treatment.
Cyclosporine: increased serum cyclosporine concentrations, possible increased nephrotoxicity of cyclosporine due to effects mediated by renal prostaglandins. Renal function should be monitored during combination therapy.
Sulfonylureas (e.g. glibenclamide): hypoglycemic effect may be enhanced.
Inducers and inhibitors of CYP2C9 isoenzymes: lornoxicam (like other NSAIDs metabolized by cytochrome CYP2C9) interacts with inducers and inhibitors of CYP2C9 isoenzymes.
Tacrolimus: Concomitant treatment with NSAIDs and tacrolimus increases the risk of nephrotoxicity due to decreased renal prostacyclin synthesis. Renal function should be closely monitored during such combination therapy (see section 4.4).
Pemetrexed: NSAIDs may reduce the renal clearance of pemetrexed, resulting in increased renal and gastrointestinal toxicity and myelosuppression.
Since food intake 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 (see section "Pharmacological properties. Pharmacokinetics").
Application features
Lornoxicam reduces platelet aggregation and prolongs bleeding time. Therefore, caution should be exercised when prescribing to patients with an increased tendency to bleed.
Lornoxicam should be prescribed only after careful assessment of the expected benefit of therapy and the possible risk to the following patients:
Patients after major surgery, patients with heart failure, patients taking diuretics or drugs that can cause kidney damage should have their renal function carefully monitored (see section "Interaction with other medicinal products and other types of interactions");
Patients with coagulation disorders are recommended to undergo a thorough clinical examination and evaluation of laboratory parameters (e.g., activated partial thrombin time);
In patients with hepatic insufficiency (e.g. cirrhosis) after using the drug at a dose of 12-16 mg per day, clinical monitoring and laboratory tests are recommended due to the possibility of accumulation of lornoxicam in the body (increased AUC) (see section "Pharmacological properties. Pharmacokinetics"). However, impaired liver function does not affect the pharmacokinetic parameters of lornoxicam compared to those in healthy volunteers;
Elderly people (over 65 years of age) are advised to monitor kidney and liver function. Use with caution after surgical interventions.
Concomitant use of NSAIDs.
The concomitant use of lornoxicam with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided (see section "Interaction with other medicinal products and other types of interactions").
Minimizing adverse reactions.
Adverse reactions can be minimized by using the lowest effective dose of the drug for the shortest period necessary to control the symptoms of the disease (see section “Method of administration and dosage” and information on gastrointestinal and cardiovascular risks below).
Gastrointestinal bleeding, ulcers and perforations: Gastrointestinal bleeding, ulcers and perforations, which may be fatal, may occur with NSAIDs at any time during treatment (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 section 4.3), and in the elderly. In these patient groups, treatment with the drug should be initiated with particular caution at the lowest therapeutic dose (see section 4.2).
For patients requiring such concomitant 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 section 4.5). 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 when prescribing the drug to patients who are concomitantly taking medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (warfarin), selective serotonin reuptake inhibitors or antithrombotic drugs (acetylsalicylic acid) (see section "Interaction with other medicinal products and other types of interactions").
In the event 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 section "Adverse reactions").
Elderly patients.
Elderly patients are at increased risk of adverse reactions to NSAIDs, including gastrointestinal bleeding and perforation, which can be fatal (see Contraindications).
Cardiovascular and cerebrovascular effects.
Patients with a history of hypertension and/or mild to moderate congestive heart failure should be monitored, as NSAID therapy may be associated with phenomena such as fluid retention and edema.
There is evidence from clinical trials and epidemiological data to suggest that the use of some NSAIDs, particularly when used for long periods and/or at high doses, is associated with an increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There is insufficient data to exclude such a risk with lornoxicam.
Concomitant treatment with NSAIDs and heparin increases the risk of spinal/epidural hematoma during spinal or epidural anesthesia (see section "Interaction with other medicinal products and other types of interactions").
Skin disorders.
Very rarely, severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, some of which have been fatal, have been reported with NSAIDs (see section 4.8). The risk of such reactions is highest at the beginning of treatment, with most occurring within the first month of treatment. Lornoxicam should be discontinued at the first appearance of skin rash, mucosal lesions or other signs of hypersensitivity.
Respiratory disorders.
Use with caution in patients with bronchial asthma or a history of this disease, as NSAIDs provoke bronchospasm in these patients.
Systemic lupus erythematosus and mixed connective tissue disease.
Use with caution in patients with systemic lupus erythematosus and mixed connective tissue diseases, as the risk of developing aseptic meningitis is increased.
Nephrotoxicity.
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 section 4.5).
Laboratory abnormalities.
Like other NSAIDs, lornoxicam may cause occasional elevations in serum transaminases, serum bilirubin, blood urea and creatinine concentrations, 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.
Fertility.
Lornoxicam, like other drugs that inhibit cyclooxygenase/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 (see section 4.6).
Varicella.
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 the presence of chickenpox.
Use during pregnancy or breastfeeding
Pregnancy. Lornoxicam is contraindicated in the third trimester of pregnancy (see section "Contraindications"). There are no clinical data on the use of lornoxicam in the first and second trimesters of pregnancy and during labor, 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 adversely affect 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 lethality. Prostaglandin synthesis inhibitors should not be used in the first and second trimesters of pregnancy. Use is only possible if clearly needed.
The use of lornoxicam from the 20th week of pregnancy may cause oligohydramnios due to impaired renal function in the fetus. This may occur shortly after the start of treatment and is usually reversible after discontinuation of the drug. In addition, narrowing of the ductus arteriosus in the fetus has been reported after use in the second trimester of pregnancy, which in most cases resolved after discontinuation of treatment. Therefore, lornoxicam should not be used during the first and second trimesters of pregnancy unless clearly necessary. If lornoxicam is used by a woman attempting to conceive or during the first and second trimesters of pregnancy, the dose should be kept as low and the duration of treatment as short as possible. Antenatal monitoring for oligohydramnios and narrowing of the ductus arteriosus should be considered after exposure to lornoxicam for several days, starting from the 20th week of gestation. Lornoxicam should be discontinued if oligohydramnios or narrowing of the ductus arteriosus is detected.
During the third trimester of pregnancy, the use of any prostaglandin synthesis inhibitors may have the following effects on the fetus:
cardiopulmonary toxicity (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension);
renal impairment (see above).
The pregnant woman and fetus at the end of pregnancy may be exposed to the following effects when using prostaglandin synthesis inhibitors:
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 during the third trimester of pregnancy (see section "Contraindications").
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. Lornoxicam should not be used during breast-feeding.
Fertility.
The use of lornoxicam, as with any drug that inhibits cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. In women who have difficulty conceiving or who are undergoing investigation of infertility, discontinuation of lornoxicam should be considered.
Ability to influence reaction speed when driving vehicles or other mechanisms
If you experience dizziness and/or drowsiness as a result of taking the drug, you should not drive or operate other machinery.
Method of administration and doses
For all patients, the appropriate dosage regimen should be based on individual response to treatment. Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special instructions"). Xefocam Rapid, film-coated tablets, is administered orally with sufficient fluid.
Acute pain. The recommended dose is 8-16 mg (1-2 tablets) per day. On the first day of treatment, the initial dose is 16 mg, after 12 hours another 8 mg can be taken. After the first day of treatment, the daily dose should not exceed 16 mg.
Elderly patients (65 years and older) do not require dose adjustment, except in patients with impaired liver or kidney function, but lornoxicam should be used with caution, since gastrointestinal adverse reactions are less well tolerated in this category of patients (see section "Special warnings and precautions for use").
Patients with mild to moderate renal insufficiency are recommended to reduce the frequency of administration of Xefocam Rapid to 1 time per day (see section "Special instructions"). Lornoxicam is contraindicated in patients with severe renal impairment (see section "Contraindications").
Patients with hepatic impairment. For patients with moderate hepatic impairment, the dosing frequency should be reduced to once daily (see section 4.4). Lornoxicam is contraindicated in patients with severe hepatic impairment (see section 4.4).
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.
Overdose
There are currently no data on overdose with the drug that would allow to determine its consequences or to suggest specific treatment. However, it is expected that the following symptoms may occur as a result of overdose with lornoxicam: nausea, vomiting, cerebral symptoms (dizziness, visual disturbances). In severe cases, ataxia (with the development of coma and seizures), liver and kidney damage, and potentially blood clotting disorders are possible.
In case of actual or suspected overdose, the drug should be discontinued. Due to its short half-life, lornoxicam is rapidly eliminated from the body. It is not dialyzable. There is currently no specific antidote. The usual emergency measures should be taken. As a general rule, only the use of activated charcoal, if administered immediately after an overdose of lornoxicam, can reduce the absorption of the drug. For the treatment of gastrointestinal disorders, for example, a prostaglandin analogue or ranitidine can be used.
Side effects
The most common adverse reactions of NSAIDs were related to the gastrointestinal tract. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, especially in the elderly, may occur with NSAIDs (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported with NSAIDs (see section 4.4). Gastritis has been reported less frequently.
It is estimated that approximately 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 less than 10% of patients in the studies.
The occurrence of edema, arterial hypertension, and heart failure due to the use of NSAIDs has been recorded.
Clinical trials and epidemiological data suggest that the use of some NSAIDs, particularly at high doses and in long-term use, may be associated with an increased risk of arterial thrombotic events, such as myocardial infarction or stroke (see section 4.4).
The following adverse reactions are listed, which occurred in a total of 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 (> 1/10000 - < 1/1000), very rare (<1/10000), unknown (frequency cannot be estimated from the available data).
Infections and invasions.
Rare: pharyngitis.
From the blood and lymphatic system.
Rare: anemia, thrombocytopenia, eosinophilia, leukopenia, coagulation disorders, prolonged bleeding time, pancytopenia.
Very rare: ecchymosis. NSAIDs can cause potentially severe haematological disorders typical of this class, such as neutropenia, agranulocytosis, aplastic and haemolytic anaemia.
From the immune system.
Rare: hypersensitivity, including fever, chills, anaphylactoid reactions, anaphylaxis.
On the part of metabolism.
Uncommon: loss of appetite, weight changes.
Metabolism and eating disorders.
Rare: hyponatremia.
Mental disorders.
Uncommon: insomnia, depression.
Rare: confusion, restlessness, increased excitability, impaired ability to concentrate, changes in attention, cognitive disorders.
From the nervous system.
Common: mild short-term headache, dizziness.
Rare: drowsiness, paresthesia, dysgeusia, tremor, migraine, hyperkinesia, hypoesthesia.
Very rare: aseptic meningitis in patients with systemic lupus erythematosus and mixed connective tissue diseases (see section "Special warnings and precautions for use").
From the organs of vision.
Common: conjunctivitis.
Rare: visual disturbances, including blurred vision, colour vision disturbances, visual field defects, amblyopia, diplopia; scotoma, iridocyclitis.
On the part of the organs of hearing and the labyrinth of the ear.
Uncommon: vertigo, tinnitus.
From the cardiovascular system.
Uncommon: palpitations, tachycardia, oedema, fluid retention, heart failure, facial flushing (see section "Special warnings and precautions for use").
Rare: arterial hypertension, hot flashes, hemorrhages, vasculitis, hematomas.
On the part of the respiratory system, chest organs and mediastinum.
Uncommon: runny nose.
Rare: dyspnea, cough, bronchospasm.
From the digestive tract.
Common: nausea, abdominal pain, dyspepsia, diarrhea, vomiting.
Uncommon: constipation, flatulence, belching, dry mouth, gastritis, gastric and duodenal ulcers, upper abdominal pain, bleeding gums, ulcerative stomatitis.
Rare: melena, vomiting with blood, stomatitis, esophagitis, gastroesophageal reflux disease, dysphagia, aphthous stomatitis, glossitis, perforation of peptic ulcers, hemorrhoids, gastrointestinal bleeding.
On the part of the hepatobiliary system.
Uncommon: increased liver enzymes (ALT, AST).
Very rare: toxic effect on the liver, resulting in the possible development of liver failure, hepatitis, jaundice, cholestasis.
On the skin and subcutaneous tissue.
Uncommon: rash, pruritus, increased sweating, erythematous rash, urticaria and angioedema, alopecia.
Rare: dermatitis, eczema, maculopapular rash, purpura.
Very rare: edema and bullous reactions, nail changes, psoriasis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrosis.
On the part of the musculoskeletal system and connective tissue.
Uncommon: arthralgia.
Rare: bone and back pain, muscle spasms, muscle weakness, myalgia, synovitis.
On the part of the kidneys and urinary system.
Rare: nocturia, urinary disorders, increased blood urea nitrogen and creatinine levels.
Very rare: Lornoxicam may cause acute renal failure in patients with pre-existing renal disease dependent on renal prostaglandins, which play an important role in maintaining renal blood flow (see section 4.4). Nephrotoxicity in various forms, including nephritis and nephrotic syndrome, is a characteristic effect of NSAIDs. There are cases of papillary necrosis caused by NSAIDs.
General violations.
Uncommon: malaise, facial swelling.
Rare: asthenia.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children!
Packaging
6 tablets in a blister. 1 blister in a cardboard box.
Vacation category
According to the recipe.
Producer
Takeda GmbH, production site Oranienburg, Germany/ Takeda GmbH Betriebsstätte Oranienburg, Germany.
Location of the manufacturer and its business address.
Lehnitzstrasse 70-98, 16515 Oranienburg, Germany.
