Instructions for Lornado tablets 8 mg No. 10
Composition
active ingredient: lornoxicam;
1 film-coated tablet contains 4 mg or 8 mg of lornoxicam;
excipients: lactose monohydrate; croscarmellose sodium; microcrystalline cellulose; povidone K-25; magnesium stearate; Opadry white 03F180011 (hypromellose, titanium dioxide (E 171), macrogol).
Dosage form
Film-coated tablets.
Main physicochemical properties: oblong, white film-coated tablets, engraved with “L04” on one side on 4 mg tablets and “L08” on 8 mg tablets.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Oxycodone. ATX code M01A C05.
Pharmacological properties
Pharmacodynamics
Lornoxicam is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and anti-inflammatory properties, belonging to the oxicam class. Its mechanism of action is mainly associated with inhibition of prostaglandin synthesis (inhibition of the enzyme cyclooxygenase), which leads to desensitization of peripheral nociceptors 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 (such as body temperature, respiratory rate, heart rate, blood pressure, ECG, spirometry).
The analgesic properties of lornoxicam have been successfully demonstrated in several clinical trials during the development process.
Due to local irritation of the digestive tract and systemic ulcerogenic effect associated with inhibition of prostaglandin synthesis, the use of lornoxicam, like other NSAIDs, often leads to the development of gastrointestinal complications.
Pharmacokinetics
Absorption.
After oral administration, lornoxicam is rapidly and almost completely absorbed from the gastrointestinal tract. The maximum plasma concentration (Cmax) is reached 1–2 hours (Tmax) after administration. The absolute bioavailability of lornoxicam is 90–100%. No first-pass effect was observed. When lornoxicam is taken with food, Cmax is reduced by approximately 30% and Tmax is increased from 1.5 hours to 2.3 hours. The absorption of lornoxicam (calculated according to the area under the pharmacokinetic curve "concentration-time" (AUC)) may be reduced by 20%.
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.
Metabolism.
Lornoxicam is extensively metabolized in the liver by hydroxylation, mainly to inactive 5-hydroxylornoxicam. Lornoxicam undergoes biotransformation with the participation of cytochrome CYP2C9. Due to genetic polymorphism, there are individuals with slow and intensive metabolism of this enzyme, which can be expressed in a noticeable increase in the level of lornoxicam in the blood plasma in individuals 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 - by the kidneys in the form of an inactive compound. In studies on animal models, lornoxicam did not cause induction of liver enzymes. In clinical studies, no data were obtained on the cumulation of lornoxicam after repeated administration of recommended doses. The absence of cumulation was confirmed by data from monitoring the safety and efficacy of drugs in studies for 1 year.
Breeding.
The elimination half-life of the parent compound is 3–4 hours. After oral administration, approximately 50% is excreted in the feces and 42% in the urine, mainly as 5-hydroxylornoxicam. The elimination half-life of 5-hydroxylornoxicam is approximately 9 hours after parenteral administration once or twice daily.
Special categories of patients.
Elderly patients.
In elderly patients (aged 65 years and over), 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.
Patients with impaired liver and/or kidney function.
There is no significant change in the kinetic profile of lornoxicam in patients with renal or hepatic insufficiency, with the exception of accumulation in patients with chronic liver disease, after 7 days of therapy with daily doses of 12 mg and 16 mg.
Indication
Short-term treatment of acute mild to moderate pain.
Symptomatic relief of pain and inflammation in osteoarthritis.
Symptomatic relief of pain and inflammation in rheumatoid arthritis.
Contraindication
Hypersensitivity to the active substance and/or to the excipients of the medicinal product.
Hypersensitivity (symptoms similar to those of asthma, rhinitis, angioedema or urticaria) to other NSAIDs, including acetylsalicylic acid.
Gastrointestinal bleeding, cerebrovascular or other bleeding.
Active recurrent gastric ulcer/bleeding or history of recurrent gastric ulcer/bleeding (two or more separate proven episodes of ulceration or bleeding).
Thrombocytopenia.
Severe form of heart failure.
Severe liver failure.
Severe renal failure (plasma creatinine level > 700 μmol/l).
Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding").
Interaction with other medicinal products and other types of interactions
When used simultaneously with lornoxicam, the following interactions are possible.
Cimetidine.
With simultaneous use, an increase in lornoxicam levels in blood plasma is possible (no interaction between lornoxicam and ranitidine or lornoxicam and antacids has been identified).
Anticoagulants.
Concomitant use may potentiate the effects of anticoagulants, such as warfarin (see section 4.4). In the case of concomitant use of these medicinal products, careful monitoring of the international normalized ratio should be carried out.
Phenprocoumon.
With simultaneous use, the effectiveness of treatment with phenprocoumon is reduced.
Heparin.
With simultaneous use, there may be an increased risk of spinal/epidural hematoma during spinal or epidural anesthesia (see section "Special warnings and precautions for use").
Angiotensin-converting enzyme (ACE) inhibitors.
With simultaneous use, the effect of ACE inhibitors may be reduced.
Diuretics.
With simultaneous use, the diuretic and hypotensive effect of loop, thiazide and potassium-sparing diuretics may be weakened.
Beta-adrenergic blockers.
With simultaneous use, a decrease in the hypotensive effect of beta-adrenergic blockers is possible.
Angiotensin II receptor blockers.
With simultaneous use, a decrease in the hypotensive effect of angiotensin II receptor blockers is possible.
Digoxin.
With simultaneous use, a decrease in renal clearance of digoxin is possible.
Corticosteroids.
With simultaneous use, the risk of gastrointestinal ulcers or bleeding may increase (see section "Special warnings and precautions for use").
Quinolone antibacterial agents.
With simultaneous use, the risk of seizures may increase.
Antiplatelet agents.
With simultaneous use, the risk of gastrointestinal bleeding increases (see section "Special instructions").
Other NSAIDs.
With simultaneous use, the risk of gastrointestinal bleeding increases.
Methotrexate.
Concomitant use increases the level of methotrexate in the blood plasma, which leads to increased toxicity. In the case of simultaneous use of these drugs, careful monitoring of the patient's condition should be carried out.
Selective serotonin reuptake inhibitors (SSRIs).
With simultaneous use, the risk of gastrointestinal bleeding increases (see section "Special instructions").
Lithium preparations.
With simultaneous use, renal clearance of lithium is reduced, so plasma lithium concentrations may exceed the threshold for toxicity. In the case of simultaneous use of these drugs, plasma lithium levels should be monitored, especially at the beginning of treatment, during dose adjustment and discontinuation of treatment.
Cyclosporine.
Concomitant use may increase cyclosporine plasma levels and nephrotoxicity due to renal prostaglandin-mediated effects. Renal function should be closely monitored during concomitant use.
Sulfonylurea derivatives (e.g. glibenclamide).
With simultaneous use, the risk of hypoglycemia increases.
Inducers and inhibitors of CYP2C9 isoenzymes are known.
Lornoxicam (like other NSAIDs dependent on cytochrome P450 2C9 (CYP2C9 isoenzyme)) interacts with known inducers and inhibitors of CYP2C9 isoenzymes (see section "Metabolism").
Tacrolimus.
Concomitant use increases the risk of nephrotoxicity due to decreased renal prostacyclin synthesis. Renal function should be monitored during concomitant use (see section 4.4).
Pemetrexed.
Concomitant use may decrease the renal clearance of pemetrexed, resulting in increased renal and gastrointestinal toxicity and myelosuppression.
Since food intake slows down the absorption of lornoxicam, the drug should not be taken with food if a rapid onset of action (pain relief) is required. Food intake reduces absorption by approximately 20% and increases Tmax.
Application features
In the following cases, the drug should be used only after careful assessment of the expected benefit of therapy and the possible risk.
After major surgery, patients with heart failure who are taking diuretics or medications that can cause kidney damage should have their kidney function closely monitored.
When using the drug in patients with blood clotting disorders, it is recommended to conduct a thorough clinical examination and evaluation of laboratory parameters (e.g., activated partial thrombin time).
When using the drug at a dose of 12-16 mg per day in patients with hepatic insufficiency (e.g., cirrhosis), 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 use of the drug (more than 3 months), it is recommended to assess the blood condition (determination of hemoglobin), kidney function (determination of creatinine) and liver enzymes.
When using the drug in elderly patients, it is recommended to monitor kidney and liver function. The drug should be used with caution in such patients after surgical interventions.
Avoid concomitant use of the drug with other NSAIDs, including selective cyclooxygenase-2 inhibitors.
Adverse reactions can be minimized by taking the lowest effective dose of lornoxicam for the shortest period necessary to control symptoms.
Gastrointestinal bleeding, ulceration or perforation, which may be fatal, may occur with any NSAID (including lornoxicam) at any time during treatment (with or without 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 ulcer, especially complicated by bleeding or perforation (see section 4.3), and in the elderly. The drug should be initiated with caution in such patients and at the lowest therapeutic dose.
The drug should be used with caution in the above-mentioned patient groups and in patients who are simultaneously taking low doses of acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications (see section "Interaction with other medicinal products and other types of interactions").
For patients requiring such concomitant therapy, treatment may be carried out with concomitant protective agents, such as misoprostol or proton pump inhibitors (see section 4.5). Regular clinical monitoring is recommended.
When using the drug in patients with a history of gastrointestinal toxicity, especially elderly patients, any unusual abdominal symptoms (especially gastrointestinal bleeding) should be reported in the initial stages of treatment.
The drug should be used with particular caution in patients who are concomitantly taking medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants - warfarin, SSRIs or antithrombotic drugs, such as acetylsalicylic acid (see section "Interaction with other medicinal products and other types of interactions").
If gastrointestinal bleeding or ulceration occurs in patients taking lornoxicam, the drug should be discontinued.
The drug 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 are at increased risk of adverse reactions to NSAIDs, including gastrointestinal bleeding and perforation, which may be fatal (see Contraindications).
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 in the body.
Patients with a history of hypertension and/or mild to moderate congestive heart failure should be monitored during use of the drug, as NSAID treatment may be associated with phenomena such as fluid retention and edema.
The drug should be used only after careful evaluation of the indications in patients with uncontrolled arterial hypertension, chronic heart failure, ischemic heart disease, peripheral arterial disease and/or cerebrovascular disorders. Evaluation is also required before long-term use of the drug in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking).
Concomitant use of lornoxicam with 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").
During the use of lornoxicam, severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, sometimes fatal, may develop very rarely (see section "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 lornoxicam. The drug should be discontinued at the first signs of skin rash, mucosal lesions or other manifestations of hypersensitivity.
The drug should be used with caution in patients with bronchial asthma or a history of this disease, as NSAIDs have been reported to provoke bronchospasm in such patients.
When using lornoxicam in patients with systemic lupus erythematosus and mixed connective tissue disease, the risk of developing aseptic meningitis may be increased.
Lornoxicam inhibits platelet aggregation, increasing blood clotting time. The drug should be used with caution in patients with a tendency to bleeding.
Concomitant use of lornoxicam with tacrolimus may increase the risk of nephrotoxicity due to decreased renal prostacyclin synthesis. If such a combination is necessary, renal function should be carefully monitored.
During the use of lornoxicam, episodic increases in transaminases, bilirubin in blood plasma, increases in plasma urea and creatinine levels, and other laboratory abnormalities are possible. If the laboratory abnormalities are significant and persist for a long time, the drug should be discontinued and the necessary examination should be performed.
Lornoxicam, like other cyclooxygenase/prostaglandin synthesis inhibitors, may impair fertility and is therefore not recommended in women attempting to conceive. Women who have difficulty conceiving or are undergoing investigation of infertility should discontinue the drug.
In the presence of chickenpox, in exceptional cases, severe skin and soft tissue infections may develop. It is also not possible to exclude the effect of NSAIDs on the worsening of such infections. It is recommended to avoid the use of the drug in the presence of chickenpox.
The medicinal product contains lactose and should not be administered to patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption syndrome.
This medicinal product contains less than 1 mmol (23 mg) sodium/dose, i.e. essentially sodium-free.
Use during pregnancy or breastfeeding
Pregnancy.
The drug 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 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 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 possible only in cases of extreme necessity.
From the 20th week of pregnancy onwards, the use of lornoxicam may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation of treatment. In addition, there have been reports of ductus arteriosus following treatment in the second trimester of pregnancy, most of which resolved after discontinuation of treatment. It is recommended that NSAIDs be avoided from the 20th week of pregnancy onwards.
Antenatal monitoring for oligohydramnios and ductus arteriosus should be considered after exposure to lornoxicam for several days, starting from the 20th week of gestation. The drug should be discontinued if oligohydramnios or 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 dysfunction, which may progress to renal failure with the development of oligohydramnios (see above).
The pregnant woman and fetus at the end of pregnancy may be exposed to the following effects due to 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 the drug is contraindicated in the third trimester of pregnancy (see section "Contraindications").
Breastfeeding period.
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. The drug should not be used during breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
If you experience dizziness and/or drowsiness as a result of using the medicine, you should not drive or operate other machinery.
Method of administration and doses
The medicine is intended for oral use. The tablets should be taken orally with sufficient water.
Adverse reactions can be minimized by taking the lowest effective dose of lornoxicam for the shortest period of time necessary to control symptoms (see section "Special warnings and precautions for use").
For all patients, the appropriate dosage regimen should be based on individual response to treatment.
Pain.
The drug should be used in a dose of 8–16 mg per day, divided into 2–3 doses. The maximum recommended daily dose is 16 mg.
Osteoarthritis and rheumatoid arthritis.
The drug should be used at an initial dose of 12 mg per day, divided into 2-3 doses. The maintenance dose should not exceed 16 mg per day.
Elderly patients.
Elderly patients, except for patients with impaired liver or kidney function, do not require dose adjustment, but the drug should be used with caution in such patients due to the likelihood of adverse reactions from the gastrointestinal tract.
Patients with renal impairment.
For patients with mild to moderate renal impairment, the maximum recommended daily dose of lornoxicam is 12 mg, divided into 2–3 doses.
Patients with liver dysfunction.
For patients with moderate hepatic impairment, the maximum recommended daily dose of lornoxicam is 12 mg, divided into 2-3 doses (see section "Special warnings and precautions for use").
Children
The drug is not recommended for use in children under 18 years of age due to insufficient data on the efficacy and safety of lornoxicam.
Overdose
There are currently no data on overdose that would allow us to determine its consequences or suggest specific treatment. However, the following symptoms may occur as a result of an overdose of lornoxicam: nausea, vomiting, cerebral symptoms (dizziness, visual disturbances); in severe cases - ataxia with transition 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 half-life, lornoxicam is rapidly eliminated from the body. It is not dialyzable. There is currently no specific antidote. The usual emergency measures, including gastric lavage, should be taken. As a general rule, only the use of activated charcoal, if administered immediately after an overdose of lornoxicam, may reduce its absorption. For the treatment of gastrointestinal disorders, a prostaglandin analogue or ranitidine may be used.
Side effects
The most common adverse reactions to NSAIDs have been 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. Gastritis has been observed less frequently.
It is estimated that approximately 20% of patients treated with lornoxicam may experience adverse reactions. The most common adverse reactions are nausea, dyspepsia, indigestion, abdominal pain, vomiting, and diarrhea. These symptoms were generally observed in less than 10% of patients in the study.
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).
Exceptionally, serious infectious complications of the skin and soft tissues have been reported during the course of chickenpox.
Adverse reactions are classified according to the frequency of occurrence in 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); frequency unknown (frequency cannot be estimated from the available data).
Infections and infestations:
rarely – pharyngitis.
Blood and lymphatic system disorders:
Rare: anemia, thrombocytopenia, leukopenia, prolonged bleeding time; very rare: ecchymosis. NSAIDs can cause potentially severe hematological disorders specific to this class of drugs, such as neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia.
On the part of the immune system:
rarely - hypersensitivity reactions, anaphylactoid reactions and anaphylaxis.
Metabolism and nutritional disorders:
infrequently - loss of appetite, changes in body weight.
From the psyche:
infrequently - insomnia, depression; rarely - confusion, nervousness, agitation.
From the nervous system:
Common: mild and transient headache, dizziness; Rare: drowsiness, paresthesia, taste disturbance (dysgeusia), tremor, migraine; Very rare: aseptic meningitis in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (see section "Special warnings and precautions for use").
On the part of the organs of vision:
infrequently - conjunctivitis; rarely - visual impairment.
On the part of the organs of hearing and balance:
infrequently - vertigo, tinnitus.
From the cardiovascular system:
infrequently - palpitations, tachycardia, edema, heart failure, facial flushing; rarely - hypertension, hot flashes, hemorrhages, hematomas.
From the respiratory system, chest organs and mediastinum:
infrequently - rhinitis; rarely - dyspnea, cough, bronchospasm.
From the digestive tract:
often - nausea, abdominal pain, dyspepsia, diarrhea, vomiting; infrequently - constipation, flatulence, belching, dry mouth, gastritis, gastric ulcer, abdominal pain upper, duodenal ulcer, oral mucosal ulcers; rarely - melena, haematemesis, stomatitis, esophagitis, gastroesophageal reflux, dysphagia, aphthous stomatitis, glossitis, peptic 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 rash, 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, urinary disorders, increased blood urea nitrogen and creatinine levels in the blood plasma; very rarely - lornoxicam can cause acute renal failure in patients with renal diseases that depend on renal prostaglandins and play an important role in maintaining renal blood flow (see section "Special instructions"). Nephrotoxicity in various forms, including nephritis and nephrotic syndrome, is an effect specific to NSAIDs.
From the body as a whole:
infrequently - malaise, facial edema; rarely - asthenia.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions that occur after the registration of a medicinal product is very important. This allows for continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national pharmacovigilance system.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 ºС in a place inaccessible to children.
Packaging
Film-coated tablets, 4 mg: 10 tablets in a blister; 1, 2, 5 or 10 blisters in a cardboard box.
Film-coated tablets, 8 mg: 10 tablets in a blister; 1, 2, 5 or 10 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
WORLD MEDICINE ILACH SAN. VE TIJ. A.Sh./WORLD MEDICINE ILAC SAN. VE TIC. AS
Location of the manufacturer and address of its place of business
15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey/15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey.
Applicant
WORLD MEDICINE, LLC, Ukraine.
