Lornelia

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LORNELIA (LORNELIA)

Composition:

Active substance: lornoxicam;

1 vial contains 8 mg of lornoxicam;

Excipients: mannitol (E 421), trometamol, disodium edetate.

Pharmaceutical form. Powder for solution for injection.

Main physicochemical properties: lyophilized yellow powder.

Pharmacotherapeutic group

Non-steroidal anti-inflammatory and anti-rheumatic drugs. Oxicams. ATC code M01A C05.

Pharmacological Properties

Pharmacodynamics

Lornoxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and anti-inflammatory properties, belonging to the oxicam class. The mechanism of action of lornoxicam is primarily related to inhibition of prostaglandin synthesis (inhibition of the enzyme cyclooxygenase), leading to desensitization of peripheral nociceptors and inhibition 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, blood pressure, ECG, spirometry).

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

Due to local gastrointestinal irritation and systemic ulcerogenic effects associated with inhibition of prostaglandin (PG) synthesis, the use of lornoxicam, as with other NSAIDs, frequently leads to gastrointestinal complications.

Pharmacokinetics

Absorption. Lornoxicam in the form of 8 mg injection powder is intended for intravenous and intramuscular administration. The maximum plasma concentration (Cmax) after intramuscular administration is reached in approximately 0.4 hours. The absolute bioavailability (calculated from the area under the plasma concentration-time curve (AUC)) after intramuscular administration is 97%.

Distribution. In plasma, lornoxicam is present in unchanged form and as 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 actively metabolized in the liver via hydroxylation, primarily into the inactive metabolite 5-hydroxy-lornoxicam. Lornoxicam undergoes biotransformation involving the cytochrome CYP2C9. The metabolism of this enzyme may be slow or extensive in different individuals due to genetic polymorphism, potentially leading to a significant increase in plasma lornoxicam levels in individuals with slow metabolism. The hydroxylated metabolite has no pharmacological activity. Lornoxicam is completely metabolized. Approximately 2/3 is excreted via the liver and 1/3 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. These findings were confirmed by safety and efficacy monitoring data from one-year-long studies.

Elimination. The elimination half-life of the parent compound is 3–4 hours. After oral administration, approximately 50% is excreted in feces and 42% via the kidneys, mainly as 5-hydroxy-lornoxicam. The elimination half-life of 5-hydroxy-lornoxicam is approximately 9 hours after parenteral administration once or twice daily. There is no evidence that elimination rate changes with repeated dosing.

Special Patient Populations

Elderly Patients

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.

Patients with Impaired Hepatic and/or Renal Function

There is no significant change in the kinetic profile of lornoxicam in patients with renal or hepatic impairment, except for accumulation observed in patients with chronic liver disease after 7 days of therapy with daily doses of 12 mg and 16 mg.

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 (asthma-like symptoms, rhinitis, angioedema, or urticaria) to other NSAIDs, including acetylsalicylic acid;
• severe heart failure;
• gastrointestinal bleeding, cerebrovascular or other bleeding;
• history of gastrointestinal bleeding or perforation related to previous NSAID therapy;
• active recurrent peptic ulcer/gastrointestinal bleeding or history of recurrent peptic ulcer/gastrointestinal bleeding (two or more separate 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 breastfeeding").

Special precautions

The injection solution is prepared immediately before use (the contents of one vial (8 mg lyophilisate) is dissolved in 2 mL of water for injections). The appearance of the medicinal product after reconstitution is a clear yellow solution, practically free from visible particles.

If visible signs of deterioration of the medicinal product are present, it should be disposed of according to local requirements.

Interaction with other medicinal products and other forms of interaction

The following interactions may occur when lornoxicam is used concomitantly:

• Cimetidine: increases plasma concentration of lornoxicam, which may increase the risk of adverse effects of lornoxicam (no interactions between lornoxicam and ranitidine or between lornoxicam and antacids have been observed).
• Anticoagulants: NSAIDs may enhance the effect of anticoagulants, such as warfarin (see section "Special instructions"). Close monitoring of the international normalized ratio (INR) is required.
• Phenprocoumon: reduced efficacy of phenprocoumon treatment.
• Heparin: NSAIDs increase the risk of bleeding and the occurrence of spinal/epidural hematoma when used concomitantly with heparin during spinal or epidural anesthesia (see section "Special instructions").
• ACE inhibitors: may reduce the effect of ACE inhibitors.
• 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: reduced renal clearance of digoxin, increasing the risk of digoxin toxicity.
• Corticosteroids: increased risk of gastrointestinal ulcers or bleeding (see section "Special instructions").
• Quinolone antibiotics (e.g., levofloxacin, ofloxacin): increased risk of seizures.
• Antiplatelet agents (e.g., clopidogrel): increased risk of bleeding (see section "Special instructions").
• Other NSAIDs: increased risk of gastrointestinal bleeding or ulcers.
• Methotrexate: increased methotrexate concentration in blood serum, leading to increased toxicity. Close monitoring is required when used concomitantly.
• Selective serotonin reuptake inhibitors (SSRIs): increased risk of bleeding (see section "Special instructions").
• 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 adjustment, and upon discontinuation of treatment.
• Cyclosporine: increased cyclosporine concentration in serum. Possible increase in cyclosporine nephrotoxicity due to effects mediated by renal prostaglandins. Renal function should be monitored during combination therapy.
• Sulfonylurea derivatives (e.g., glibenclamide): increased risk of hypoglycemia.
• Known inducers and inhibitors of CYP2C9 isoenzymes: lornoxicam (like other NSAIDs dependent on cytochrome P450 2C9 (CYP2C9 isoenzyme)) interacts with known inducers and inhibitors of CYP2C9 isoenzymes (see section "Biotransformation").
• Tacrolimus: increased risk of nephrotoxicity due to reduced synthesis of prostacyclin in the kidneys. Renal function should be monitored during combination therapy (see section "Special instructions").
• Pemetrexed: NSAIDs may reduce renal clearance of pemetrexed, thereby increasing renal and gastrointestinal toxicity and myelosuppression.

Special precautions for use

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

Lornoxicam should be prescribed only after careful assessment of the expected benefit of therapy and possible risk in the following patient groups:

• Patients with renal impairment: lornoxicam should be used with caution in patients with mild (serum creatinine level 150–300 µmol/L) and moderate renal insufficiency (serum creatinine level 300–700 µmol/L) due to the important role of prostaglandins in maintaining renal blood flow (see section "Dosage and administration"). In case of renal function impairment, lornoxicam treatment should be discontinued.
• Patients after extensive surgical procedures, with heart failure, or those taking diuretics or medicinal products that may cause renal damage, require careful monitoring of renal function (see section "Interaction with other medicinal products and other forms of interaction").
• Patients with coagulation disorders are recommended to undergo careful clinical examination and laboratory parameter assessment (e.g., activated partial thromboplastin time).
• Patients with hepatic insufficiency (e.g., liver cirrhosis) are recommended to undergo regular laboratory tests 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, no deviations in pharmacokinetic parameters in patients with hepatic insufficiency compared to healthy volunteers have been observed.
• Elderly patients (aged 65 years and older) are recommended to be monitored for kidney and liver function. Use with caution after surgical procedures.

Concomitant use of NSAIDs

Concomitant 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 the information below regarding gastrointestinal and cardiovascular risks).

Gastrointestinal bleeding, ulcers, and perforation

During treatment with any NSAID at any time, gastrointestinal bleeding, ulcers, or perforation may occur (with or without warning symptoms or 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 those complicated by bleeding or perforation (see section "Contraindications"), as well as in elderly patients. These patient groups should start treatment with the lowest therapeutic doses (see section "Dosage and administration").

NSAIDs should be used with caution in the treatment of the above-mentioned patient groups and patients who are concurrently taking low-dose acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications (see section "Interaction with other medicinal products and other forms of interaction").

For patients requiring such concomitant therapy, treatment may be administered with simultaneous use of protective agents (e.g., misoprostol or proton pump inhibitors). Clinical monitoring at regular intervals is recommended.

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

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

If gastrointestinal bleeding or ulceration occurs 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 "Adverse reactions").

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 congestive heart failure should be monitored, as NSAID therapy may be associated with fluid retention and edema.

Clinical studies and epidemiological data suggest that the use of some NSAIDs, particularly over long periods or at high doses, may be associated with an increased risk of arterial thrombotic events (such as 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, chronic heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disorders only after careful assessment of indications. Assessment is also required before prescribing long-term treatment to patients with risk factors for cardiovascular diseases (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, 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 "Adverse reactions"). The risk of developing such reactions is highest at the beginning of treatment: most cases occur within the first month of drug use. Lornoxicam should be discontinued at the first signs 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 condition, as NSAIDs have been reported to provoke bronchospasm in such patients.

Systemic lupus erythematosus and mixed connective tissue disease

The medicinal product should be used with caution in patients with systemic lupus erythematosus and mixed connective tissue disease, as the risk of developing aseptic meningitis may increase.

Nephrotoxicity

Concomitant treatment with 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 transient elevations in serum transaminases and bilirubin, as well as 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 therefore not recommended for women attempting to conceive. Women experiencing difficulties in conceiving or undergoing infertility evaluation should discontinue lornoxicam (see section "Use during pregnancy or breastfeeding").

Chickenpox

In the presence of chickenpox, severe skin and soft tissue infections may develop in exceptional cases. At present, the influence of NSAIDs on the worsening of these infectious diseases cannot be excluded. It is recommended to avoid the use of lornoxicam in patients with active 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 during the first and second trimesters of pregnancy and during labor; therefore, the drug is not recommended during this period.

There are 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, the use of prostaglandin synthesis inhibitors leads to increased pre- and post-implantation fetal loss and embryofetal lethality. Prostaglandin synthesis inhibitors should not be used during the first and second trimesters of pregnancy. Use is possible only in cases of extreme necessity.

The use of lornoxicam from the 20th week of pregnancy may cause oligohydramnios due to impaired fetal renal function. This may occur shortly after the start of treatment and is usually reversible after discontinuation of the drug. Additionally, constriction of the fetal arterial duct has been reported after drug use in the second trimester, which mostly resolves after discontinuation of treatment. Therefore, lornoxicam should not be used during the first and second trimesters of pregnancy without strong medical justification. 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 exposure to lornoxicam 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);
• renal dysfunction (see above).

The pregnant woman and the fetus near term may be affected by the use of prostaglandin synthesis inhibitors as follows:

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

Thus, the use of lornoxicam is contraindicated in the third trimester of pregnancy (see section "Contraindications").

Lactation

There are no data on the excretion of lornoxicam into human breast milk. Relatively high concentrations of lornoxicam are excreted into 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 attempting to conceive. Women experiencing difficulties with conception 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 lornoxicam, driving or operating machinery should be avoided.

Method of Administration and Dosage

This medicinal form of the drug is intended for initiating therapy and when rapid achievement of analgesic effect is required, or when administration of oral medications is not possible. In general, treatment should include only one injection to initiate therapy. For all patients, the appropriate dosage regimen 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").

This medicinal form is intended for intravenous and intramuscular administration.

The recommended dose is 8 mg administered intravenously or intramuscularly. The daily dose should not exceed 16 mg. Some patients may require an additional 8 mg dose within the first 24 hours.

The intravenous administration of the solution should take no less than 15 seconds, and intramuscular administration no less than 5 seconds.

After preparing the solution, the needle should be replaced.

For intramuscular injection, a long needle ensuring deep injection is required.

The diluted medicinal product is intended for single use only.

The injection solution should be prepared immediately before use. The contents of one vial (8 mg of lyophilisate) should be dissolved in 2 ml of water for injections. After preparation, a clear yellow solution should be obtained. If the medicinal product shows signs of degradation, it should be disposed of according to local requirements.

Elderly patients (aged 65 years and older) without impaired liver or kidney function do not require dose adjustment; however, lornoxicam should be used with caution, as gastrointestinal adverse reactions are less well tolerated in this patient group.

Renal impairment. Patients with mild to moderate renal impairment require reduced dosage. Lornoxicam is contraindicated in patients with severe renal function impairment (see section "Contraindications").

Hepatic impairment. Patients with moderate hepatic impairment require reduced dosage. Lornoxicam is contraindicated in patients with severe liver dysfunction (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 data on lornoxicam overdose that would allow determination of its consequences or suggest specific treatment. However, symptoms expected following lornoxicam overdose may include nausea, vomiting, and central nervous system symptoms (dizziness, visual disturbances). In severe cases, ataxia (progressing to coma and seizures), liver and kidney damage, and potentially impaired blood coagulation may occur.

In cases of actual or suspected overdose, administration of the drug should be discontinued. Due to the short elimination half-life, lornoxicam is rapidly eliminated from the body. It is not dialyzable. There is currently no specific antidote. For the treatment of gastrointestinal disturbances, for example, a prostaglandin analogue or ranitidine may be used.

Adverse Reactions

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

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

Edema, arterial hypertension, and heart failure have been reported during NSAID therapy.

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

Rarely, severe skin and soft tissue infections have been reported during varicella (chickenpox) infection.

Adverse reactions are classified by frequency of occurrence as follows: very common (> 1/10); common (> 1/100, < 1/10); uncommon (> 1/1000, < 1/100); rare (> 1/10000, < 1/1000); very rare (< 1/10000); not known (frequency cannot be estimated from available data).

Infections and infestations

Rare: pharyngitis.

Blood and lymphatic system disorders

Rare: anemia, thrombocytopenia, leukopenia, prolonged bleeding time.

Very rare: ecchymosis. NSAIDs can induce potentially severe hematological disorders specific to this class of drugs, such as neutropenia, agranulocytosis, aplastic anemia, and hemolytic anemia.

Immune system disorders

Rare: hypersensitivity, including anaphylactoid reactions and anaphylaxis.

Metabolism and nutrition disorders

Uncommon: loss of appetite, weight changes.

Psychiatric disorders

Uncommon: insomnia, depression.

Rare: confusion, nervousness, agitation.

Nervous system disorders

Common: mild and transient headache, dizziness.

Rare: somnolence, paraesthesia, taste disturbances (dysgeusia), tremor, migraine.

Very rare: aseptic meningitis in patients with systemic lupus erythematosus and mixed connective tissue disease (see section "Special Warnings and Precautions for Use").

Eye disorders

Common: conjunctivitis.

Rare: visual disturbances.

Ear and labyrinth disorders

Uncommon: vertigo, tinnitus.

Cardiac and vascular disorders

Uncommon: palpitations, tachycardia, edema, heart failure, facial flushing (see section "Special Warnings and Precautions for Use").

Rare: arterial hypertension, hot flushes, hemorrhage, hematomas.

Respiratory system disorders

Uncommon: rhinitis.

Rare: dyspnea, cough, bronchospasm.

Gastrointestinal disorders

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

Uncommon: constipation, flatulence, eructation, dry mouth, gastritis, gastric ulcer, upper abdominal pain, duodenal ulcer, oral mucosal ulcers.

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

Hepatobiliary disorders

Uncommon: increased liver enzymes (ALT, AST).

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

Skin and subcutaneous tissue disorders

Uncommon: rash, pruritus, increased sweating, erythematous rash, urticaria, angioedema, alopecia.

Rare: dermatitis, eczema, purpura.

Very rare: swelling and bullous reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Musculoskeletal and connective tissue disorders

Uncommon: arthralgia.

Rare: bone pain, muscle spasms, myalgia.

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 renal conditions dependent on renal prostaglandins, which play an important role in maintaining renal blood flow (see section "Special Warnings and Precautions for Use"). Nephrotoxicity in various forms, including nephritis and nephrotic syndrome, is an effect specific to NSAIDs.

General disorders

Uncommon: malaise, facial edema.

Rare: asthenia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as patients’ legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Reconstituted solution: chemical and physical stability of the reconstituted solution has been demonstrated for 24 hours at 2–8 °C. From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage duration and conditions of the reconstituted solution prior to use are the responsibility of the user.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Incompatibilities

This medicinal product should not be mixed with other medicinal products except as specified in the instructions for medical use.

Packaging

Powder for solution for injection in vials; 5 vials in a blister pack, 1 blister pack in a carton.

Prescription category. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and location of business activity

139 Saksahanskoho Street, Kyiv, 01032, Ukraine.