INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT KSEFOCAM® RAPID (XEFOCAM® RAPID)

Composition:

Active substance:
lornoxicam;

1 tablet contains 8 mg of lornoxicam;

Excipients:
calcium stearate, hydroxypropylcellulose, sodium hydrocarbonate, low-substituted hydroxypropylcellulose, microcrystalline cellulose, calcium hydrogen phosphate;

Film coating:
propylene glycol, talc, titanium dioxide (E 171), hypromellose.

Medicinal form.
Film-coated tablets.

Main physicochemical properties:
white to light yellow, round, biconvex film-coated tablets.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Oxicams.

ATC code M01A C05.

Pharmacological Properties

Pharmacodynamics

Lornoxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties and belongs to the oxicam class. The mechanism of action of lornoxicam is primarily based on inhibition of prostaglandin synthesis (cyclooxygenase inhibition), which leads to desensitization of peripheral pain receptors and suppression of inflammation. A central effect on nociceptors, unrelated to anti-inflammatory activity, is also presumed.

Lornoxicam does not affect vital parameters (e.g., body temperature, respiratory rate, heart rate, arterial blood pressure, ECG, spirometry).

The analgesic properties of lornoxicam have been successfully demonstrated in several clinical studies during drug development.

Due to local gastrointestinal irritation and systemic ulcerogenic effects associated with inhibition of prostaglandin synthesis, administration of lornoxicam, like other non-steroidal anti-inflammatory drugs (NSAIDs), frequently leads to gastrointestinal complications.

Pharmacokinetics

Absorption
Lornoxicam is rapidly and almost completely absorbed from the gastrointestinal tract. Maximum plasma concentration (C_max) is reached within 30 minutes after administration. The C_max of Xefoсam film-coated tablets is higher than that of Xefocam film-coated tablets and is equivalent to C_max values for parenteral formulations of lornoxicam.

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 has been observed.

There are no data on concomitant administration of Xefocam Rapid with food. However, considering the properties of Xefocam, a decrease in C_max, an increase in T_max, and reduced absorption (AUC) may be expected.

Distribution
In plasma, lornoxicam exists in unchanged form and as the inactive hydroxylated metabolite. Protein binding of lornoxicam to plasma proteins is 99% and is independent of its concentration. It is also detected in synovial fluid after repeated administration.

Biological Transformation
Lornoxicam is actively metabolized in the liver by hydroxylation, initially forming the inactive metabolite 5-hydroxy-lornoxicam. Lornoxicam undergoes metabolism involving the cytochrome CYP2C9. Due to genetic polymorphism, individuals may exhibit either slow or extensive metabolism, which may result in significantly increased plasma levels of lornoxicam in individuals with slow metabolism. The hydroxylated metabolite has no pharmacological activity. Lornoxicam is completely metabolized. Approximately two-thirds is excreted via the liver and one-third via the kidneys as inactive compounds.

In animal models, lornoxicam did not induce hepatic enzymes. Clinical studies provided no evidence of lornoxicam accumulation after repeated administration of recommended doses. The absence of accumulation was confirmed by safety and efficacy monitoring data from 1-year 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 feces and 42% via the kidneys, primarily as 5-hydroxy-lornoxicam. The elimination half-life of 5-hydroxy-lornoxicam after once- or twice-daily parenteral administration is approximately 9 hours. There is no evidence that elimination rate changes with repeated dosing.

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

In patients with renal or hepatic impairment, 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, except for accumulation observed in patients with chronic liver disease.

Clinical characteristics.

Indications.

Short-term symptomatic treatment of mild to moderate acute pain in adults.

Contraindications.

Hypersensitivity to lornoxicam or to any of the excipients;
thrombocytopenia;
hypersensitivity (symptoms similar to those in bronchial asthma, rhinitis, angioneurotic edema, or urticaria) to other nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid;
severe heart failure;
gastrointestinal bleeding, cerebrovascular bleeding, or other hematological disorders;
history of gastrointestinal bleeding or perforation related to previous use of nonsteroidal anti-inflammatory drugs;
active peptic ulcer or recurrent peptic ulcer/bleeding in history (two or more episodes of confirmed ulceration or bleeding);
severe hepatic impairment;
severe renal impairment (serum creatinine level > 700 µmol/L);
third trimester of pregnancy (see section "Use during pregnancy or lactation").

Interaction with other medicinal products and other forms of interaction.

The following interactions may occur when Xefocam Rapid is used concomitantly with other medicinal products:

Cimetidine: increases plasma concentration of lornoxicam, which may increase the risk of lornoxicam adverse effects (no interactions between lornoxicam and ranitidine or between lornoxicam and antacids have been observed).
Anticoagulants: nonsteroidal anti-inflammatory drugs may enhance the effect of anticoagulants (e.g., warfarin) (see section "Special precautions for use"). Close monitoring of INR (International Normalized Ratio) is required.
Phenprocoumon: reduced effectiveness of phenprocoumon treatment.
Heparin: nonsteroidal anti-inflammatory drugs increase the risk of bleeding and development of spinal/epidural hematoma when used concomitantly with heparin during spinal or epidural anesthesia (see section "Special precautions for use").
ACE inhibitors (angiotensin-converting enzyme inhibitors): the antihypertensive effect of ACE inhibitors may be reduced.
Diuretics: reduced diuretic and antihypertensive effect of loop, thiazide, and potassium-sparing diuretics (increased risk of hyperkalemia and nephrotoxicity).
Beta-blockers: reduced antihypertensive effect.
Angiotensin II receptor blockers: reduced antihypertensive effect.
Digoxin: decreased renal clearance of digoxin, increasing the risk of digoxin toxicity.
Corticosteroids: increased risk of gastrointestinal ulcers and bleeding (see section "Special precautions for use").
Quinolone antibiotics (e.g., levofloxacin, ofloxacin): increased risk of seizures.
Antiplatelet agents (e.g., clopidogrel): increased risk of bleeding (see section "Special precautions for use").
Other NSAIDs: increased risk of gastrointestinal bleeding or ulcers.
Methotrexate: increased methotrexate serum concentration, leading to increased toxicity. Close monitoring of the patient is required when used concomitantly.
Selective serotonin reuptake inhibitors (SSRIs): increased risk of bleeding (see section "Special precautions for use").
Lithium preparations: NSAIDs reduce renal clearance of lithium, thus serum lithium concentration may exceed the toxic threshold. Serum lithium levels should be monitored, especially at the beginning of treatment, during dose adjustments, and upon discontinuation of therapy.
Cyclosporine: increased serum concentration of cyclosporine, potentially increasing cyclosporine nephrotoxicity due to effects mediated by renal prostaglandins. Renal function should be monitored during combination therapy.
Sulfonylurea derivatives (e.g., glyburide): hypoglycemic effect may be enhanced.
Inducers and inhibitors of CYP2C9 isoenzymes: lornoxicam (like other NSAIDs metabolized via cytochrome CYP2C9) interacts with inducers and inhibitors of the CYP2C9 isoenzyme.
Tacrolimus: combined treatment with NSAIDs and tacrolimus increases the risk of nephrotoxicity due to reduced synthesis of prostacyclin in the kidneys. Renal function should be closely monitored during such combination therapy (see section "Special precautions for use").
Pemetrexed: NSAIDs may reduce renal clearance of pemetrexed, thereby increasing renal and gastrointestinal toxicity and myelosuppression.

Since food intake slows the absorption of lornoxicam, Xefocam Rapid film-coated tablets should not be taken with food if rapid therapeutic effect (pain relief) is required.

Food intake reduces absorption by approximately 20% and increases Tmax (see section "Pharmacological properties. Pharmacokinetics").

Special precautions for use.

Lornoxicam reduces platelet aggregation and prolongs bleeding time. Therefore, caution should be exercised when prescribing to patients with an increased tendency to bleeding.

Lornoxicam should be prescribed only after careful assessment of the expected benefit of therapy and possible risk to the following patients:

Patients with impaired renal function: 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 (see section "Dosage and administration"). If worsening of renal function occurs during treatment, lornoxicam therapy should be discontinued;
Patients after major surgical procedures, patients with heart failure, and patients taking diuretics or agents that may cause renal damage require careful monitoring of renal function (see section "Interaction with other medicinal products and other forms of interaction");
In patients with coagulation disorders, careful clinical evaluation and laboratory monitoring (e.g., activated partial thromboplastin time) are recommended;
In patients with hepatic insufficiency (e.g., liver cirrhosis), clinical monitoring and laboratory tests are recommended after administration of the drug at a dose of 12–16 mg per day due to the possibility of lornoxicam accumulation in the body (increased AUC) (see section "Pharmacological properties. Pharmacokinetics"). However, liver dysfunction does not affect the pharmacokinetic parameters of lornoxicam compared to those in healthy volunteers;
In elderly patients (aged 65 years and older), monitoring of renal and liver function is recommended. Use with caution after surgical procedures.

Concomitant use of NSAIDs.

The combined use of lornoxicam with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided (see section "Interaction with other medicinal products and other forms of interaction").

Minimization of adverse reactions.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control disease symptoms (see section "Dosage and administration" and information on gastrointestinal and cardiovascular risks below).

Gastrointestinal bleeding, ulcers, and perforation . During NSAID therapy, gastrointestinal bleeding, ulcers, and perforation may occur at any time during treatment (regardless of the presence of warning symptoms or a history of serious gastrointestinal disorders), which may be fatal.

The risk of gastrointestinal bleeding, ulcers, or perforation increases with higher NSAID doses, in patients with a history of ulcers, especially complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. These patient groups should start treatment with the lowest therapeutic doses (see section "Dosage and administration").

For patients requiring such concomitant therapy and patients concurrently taking low-dose acetylsalicylic acid or other drugs increasing the risk of gastrointestinal complications, treatment may be administered with concomitant use of protective agents (e.g., misoprostol or proton pump inhibitors) (see section "Interaction with other medicinal products and other forms of interactions"). Regular clinical monitoring is recommended.

Patients with a history of gastrointestinal toxicity, especially elderly patients, should report any unusual abdominal symptoms (particularly gastrointestinal bleeding) at the beginning of treatment.

The drug should be prescribed with caution to patients who are concurrently using medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (warfarin), selective serotonin reuptake inhibitors, or antithrombotic agents (acetylsalicylic acid) (see section "Interaction with other medicinal products and other forms of interaction").

If gastrointestinal bleeding or ulcers occur in patients taking lornoxicam, treatment must be discontinued.

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as their condition may worsen (see section "Side effects").

Elderly patients.

In elderly patients, the frequency of adverse reactions during NSAID use increases, particularly gastrointestinal bleeding and perforation, which may lead to fatal outcomes (see section "Contraindications").

Cardiovascular and cerebrovascular effects.

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

Clinical trial data and epidemiological evidence suggest that the use of certain NSAIDs, especially with long-term use and/or 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 use.

Lornoxicam should be prescribed to patients with uncontrolled arterial hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disorders only after careful assessment of indications. Assessment is also required before initiating long-term treatment in patients with risk factors for cardiovascular disease (e.g., hypertension, hyperlipidemia, diabetes, smoking).

Concomitant use of NSAIDs and heparin increases the risk of spinal/epidural hematoma during spinal or epidural anesthesia (see section "Interaction with other medicinal products and other forms of interaction").

Skin disorders.

Very rarely, severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, may occur during NSAID use, sometimes resulting in death (see section "Side effects"). The risk of developing such reactions is highest at the beginning of treatment: in most cases, these reactions occur within the first month of drug use. Lornoxicam use should be discontinued at the first signs of skin rash, mucosal lesions, or other manifestations of hypersensitivity.

Respiratory disorders.

Use with caution in patients with bronchial asthma or a history of this condition, as NSAIDs may 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 use of NSAIDs and tacrolimus may increase the risk of nephrotoxicity due to reduced prostacyclin synthesis in the kidneys. Renal function should be carefully monitored during such combination therapy (see section "Interaction with other medicinal products and other forms of interaction").

Laboratory abnormalities.

Like other NSAIDs, lornoxicam may cause occasional elevations in serum transaminases and bilirubin levels, increased blood urea and creatinine concentrations, and other laboratory parameter deviations from normal. If laboratory abnormalities are significant and persistent, treatment should be discontinued and appropriate investigations performed.

Fertility.

Lornoxicam, like other drugs that inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended for women planning pregnancy. Women experiencing difficulty conceiving or undergoing infertility evaluation should discontinue lornoxicam (see section "Use during pregnancy or breastfeeding").

Chickenpox.

In rare cases, severe skin and soft tissue infections may develop in the presence of chickenpox. The influence of NSAIDs on worsening the course of these infectious diseases cannot be excluded. The use of lornoxicam should be avoided in patients with active chickenpox.

Use during pregnancy or breastfeeding.

Pregnancy. Lornoxicam is contraindicated during the third trimester of pregnancy (see section "Contraindications"). There are no clinical data on the use of lornoxicam during the first and second trimesters of pregnancy and during labor; therefore, the drug is not recommended for use during this period.

There is insufficient data on the use of lornoxicam in pregnant women. Animal studies have shown reproductive toxicity.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage and cardiac malformations with the use of prostaglandin synthesis inhibitors in early pregnancy. The risk increases with higher doses and longer duration of therapy. In animals, prostaglandin synthesis inhibitors lead to increased pre- and post-implantation fetal loss and embryofetal mortality. Prostaglandin synthesis inhibitors should not be used during the first and second trimesters of pregnancy. Use is possible only in cases of acute necessity.

The use of lornoxicam from the 20th week of pregnancy may cause oligohydramnios due to impaired fetal renal function. This may occur soon after the start of treatment and is usually reversible after discontinuation of the drug. Additionally, arterial duct constriction in the fetus has been reported after drug use during the second trimester, which mostly resolved after discontinuation of treatment. Therefore, lornoxicam should not be used during the first and second trimesters of pregnancy without urgent need. If lornoxicam is used by a woman trying to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible, and the duration of treatment as short as possible. Prenatal monitoring for oligohydramnios and arterial duct constriction should be considered after lornoxicam exposure for several days starting from the 20th gestational week. Lornoxicam should be discontinued if oligohydramnios or arterial duct constriction is detected.

During the third trimester of pregnancy, the use of any prostaglandin synthesis inhibitors may affect the fetus as follows:

cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
impaired renal function (see above).

Pregnant women and the fetus near term may be affected by prostaglandin synthesis inhibitors as follows:

possible prolongation of bleeding time, anti-aggregatory effect, which may occur even at very low doses; increased bleeding time;
inhibition of uterine contractility, which may lead to delayed or prolonged labor.

Thus, 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 into human breast milk. Relatively high concentrations of lornoxicam are excreted in the milk of lactating rats. Lornoxicam should not be used during breastfeeding.

Fertility.

The use of lornoxicam, like any drug that inhibits cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended for women trying to conceive. Women experiencing difficulty conceiving or undergoing infertility evaluation should consider discontinuing lornoxicam.

Ability to influence reaction speed when driving or operating machinery.

If dizziness and/or drowsiness occur after taking the drug, driving or operating machinery should be avoided.

Method of Administration and Dosage

The appropriate dosage regimen for all patients should be based on individual response to treatment. Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Special Warnings and Precautions for Use"). Xefocam Rapid, film-coated tablets, should be taken orally with sufficient fluid.

Acute pain
The recommended dose is 8–16 mg (1–2 tablets) daily. On the first day of treatment, the initial dose is 16 mg, followed by an additional 8 mg after 12 hours. After the first day, the daily dose should not exceed 16 mg.

Elderly patients (aged 65 years and older) do not require dose adjustment, except for patients with impaired liver or kidney function. However, lornoxicam should be used with caution in elderly patients due to increased susceptibility to gastrointestinal adverse reactions (see section "Special Warnings and Precautions for Use").

Patients with renal impairment
For patients with mild to moderate renal impairment, the dosing frequency of Xefocam Rapid should be reduced to once daily (see section "Special Warnings and Precautions for Use"). 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 "Special Warnings and Precautions for Use"). Lornoxicam is contraindicated in patients with severe hepatic impairment (see section "Contraindications").

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

Overdose

Currently, there are no reported cases of overdose that allow definitive conclusions regarding its consequences or recommendations for specific treatment. However, symptoms following lornoxicam overdose may include nausea, vomiting, and central nervous system effects (dizziness, visual disturbances). In severe cases, ataxia (progressing to coma and convulsions), as well as liver and kidney damage, may occur. Impaired blood coagulation is also a potential risk.

In cases of actual or suspected overdose, administration of the drug should be discontinued immediately. Due to the short elimination half-life, lornoxicam is rapidly cleared from the body. It is not dialyzable. There is no specific antidote available. Standard supportive measures should be implemented. According to general principles, activated charcoal may reduce drug absorption if administered promptly after overdose. For the management of gastrointestinal disturbances, a prostaglandin analogue or ranitidine may be considered.

Side effects.

The most common adverse reactions associated with NSAIDs are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation, or gastrointestinal bleeding may occur during NSAID therapy, sometimes resulting in fatal outcomes, particularly in elderly patients (see section "Special precautions"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbations of colitis and Crohn’s disease have been reported during treatment with NSAIDs (see section "Special precautions"). Gastritis has been observed less frequently.

Approximately 20% of patients treated with lornoxicam may experience adverse events. The most commonly reported adverse effects of lornoxicam are nausea, dyspepsia, digestive disturbances, abdominal pain, vomiting, and diarrhea. These symptoms were generally observed in less than 10% of patients participating in clinical trials.

Edema, arterial hypertension, and heart failure have been reported following the use of NSAIDs.

Clinical trials and epidemiological data suggest that the use of certain NSAIDs, particularly at high doses and during long-term treatment, may be associated with an increased risk of arterial thrombotic events, such as myocardial infarction or stroke (see section "Special precautions").

Rarely, serious skin and soft tissue infections have been reported in cases of varicella (chickenpox).

The adverse reactions listed below were generally observed in more than 0.05% of the 6,417 patients treated with the drug during phase II, III, and IV clinical trials.

Adverse effects that may occur during treatment with Xefocam Rapid, classified by frequency of occurrence, are as follows: very common ( > 1/10), common ( > 1/100 to < 1/10), uncommon ( > 1/1,000 to < 1/100), rare ( > 1/10,000 to < 1/1,000), very rare (< 1/10,000), and not known (frequency cannot be estimated from available data).

Infections and infestations.

Rare: pharyngitis.

Blood and lymphatic system disorders.

Rare: anemia, thrombocytopenia, eosinophilia, leukopenia, coagulation disorders, prolonged bleeding time, pancytopenia.

Very rare: ecchymosis. NSAIDs can cause potentially serious hematological disorders characteristic of this class, such as neutropenia, agranulocytosis, aplastic anemia, and hemolytic anemia.

Immune system disorders.

Rare: hypersensitivity, including fever, chills, anaphylactoid reactions, anaphylaxis.

Metabolism and nutrition disorders.

Uncommon: loss of appetite, changes in body weight.

Metabolism and nutritional disorders.

Rare: hyponatremia.

Psychiatric disorders.

Uncommon: insomnia, depression.

Rare: confusion, restlessness, increased excitability, difficulty concentrating, attention disturbances, cognitive disorders.

Nervous system disorders.

Common: mild, transient headache, dizziness.

Rare: somnolence, paresthesia, dysgeusia, tremor, migraine, hyperkinesia, hypoesthesia.

Very rare: aseptic meningitis in patients with systemic lupus erythematosus and mixed connective tissue diseases (see section "Special precautions").

Eye disorders.

Common: conjunctivitis.

Rare: visual disturbances, including blurred vision, color vision defects, visual field defects, amblyopia, diplopia; scotoma, iridocyclitis.

Ear and labyrinth disorders.

Uncommon: vertigo, tinnitus.

Cardiac disorders.

Uncommon: palpitations, tachycardia, edema, fluid retention, heart failure, facial flushing (see section "Special precautions").

Rare: arterial hypertension, hot flushes, hemorrhage, vasculitis, hematoma.

Respiratory, thoracic and mediastinal disorders.

Uncommon: rhinitis.

Rare: dyspnea, cough, bronchospasm.

Gastrointestinal disorders.

Common: nausea, abdominal pain, dyspepsia, diarrhea, vomiting.

Uncommon: constipation, flatulence, eructation, dry mouth, gastritis, gastric and duodenal ulcers, upper abdominal pain, gingival bleeding, ulcerative stomatitis.

Rare: melena, hematemesis, stomatitis, esophagitis, gastroesophageal reflux disease, dysphagia, aphthous stomatitis, glossitis, peptic ulcer perforation, hemorrhoids, gastrointestinal hemorrhage.

Hepatobiliary disorders.

Uncommon: increased levels of liver enzymes (ALT, AST).

Very rare: hepatotoxicity, which may lead to liver failure, hepatitis, jaundice, cholestasis.

Skin and subcutaneous tissue disorders.

Uncommon: rash, pruritus, increased sweating, erythematous rash, urticaria, angioneurotic edema, alopecia.

Rare: dermatitis, eczema, maculopapular rash, purpura.

Very rare: edema and bullous reactions, nail changes, psoriasis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders.

Uncommon: arthralgia.

Rare: bone and back pain, muscle spasms, muscle weakness, myalgia, synovitis.

Renal and urinary disorders.

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 "Special precautions"). Nephrotoxicity in various forms, including nephritis and nephrotic syndrome, is a characteristic effect of NSAIDs. Cases of papillary necrosis associated with NSAID use have been reported.

General disorders.

Uncommon: malaise, facial edema.

Rare: asthenia.

Shelf life.
2 years.

Storage conditions.
Store at temperatures not exceeding 25°C. Keep out of reach of children!

Packaging.
6 tablets per blister. 1 blister per cardboard box.

Prescription status.
Prescription only.

Manufacturer.
Takeda GmbH, manufacturing site Oranienburg, Germany / Takeda GmbH Betriebsstätte Oranienburg, Germany.

Manufacturer's address and place of business.
Lehnitzstrasse 70-98, 16515 Oranienburg, Germany.

Xefocam® rapid