Lornoliof rompharm

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LORNOLIOF ROMPHARM

Composition:

Active substance:
lornoxicam;

1 vial with powder contains 8 mg of lornoxicam;

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

1 ampoule of solvent contains 2 ml of water for injections.

Pharmaceutical form.
Powder for solution for injection.

Main physicochemical properties:
yellow powder or compacted mass.

Pharmacotherapeutic group. Nonsteroidal anti-inflammatory and antirheumatic drugs. Oxicams. ATC code M01A C05.

Pharmacological Properties

Pharmacodynamics

Lornoxicam is a non-steroidal anti-inflammatory drug 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 reduction of inflammation. A central effect on nociceptors, unrelated to its anti-inflammatory action, is also presumed. Lornoxicam does not affect vital parameters (e.g., body temperature, respiratory rate, heart rate, blood pressure, ECG parameters, spirometry values).

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 (PG) synthesis, the use of lornoxicam, like other non-steroidal anti-inflammatory drugs (NSAIDs), frequently leads to gastrointestinal complications.

Pharmacokinetics

Absorption.
Lornoxicam in the form of 8 mg powder for injection is intended for intravenous and intramuscular administration. The maximum plasma concentration (Cmax) after intramuscular administration is reached approximately within 0.4 hours. The absolute bioavailability (calculated based on 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 plasma protein binding of lornoxicam is 99% and is independent of its concentration. It is also detected in synovial fluid after repeated administration.

Metabolism.
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 two-thirds are excreted via the liver and one-third via the kidneys as inactive compounds.

In animal model studies, 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 1-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 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.

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

There is no substantial 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

For 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, cerebrovascular, or other bleeding;
• history of gastrointestinal bleeding or perforation, associated with previous NSAID therapy;
• active recurrent peptic ulcer / gastrointestinal bleeding or history of recurrent peptic ulcer / gastrointestinal bleeding (two or more separate episodes of proven 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 (contents of 1 vial [8 mg lyophilisate] dissolved in water for injections [2 mL]). The appearance of the reconstituted preparation is a clear yellow solution, free from visible particles.

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

Interaction with other medicinal products and other forms of interaction

When used concomitantly with lornoxicam:

• Cimetidine: increases plasma concentration of lornoxicam, thereby increasing the risk of adverse effects of lornoxicam (no interactions between lornoxicam and ranitidine or lornoxicam and antacids have been observed).
• Anticoagulants: NSAIDs may enhance the effect of anticoagulants such as warfarin (see section "Special warnings and precautions for use"). Close monitoring of the international normalized ratio (INR) is required.
• Phenprocoumon: reduced effectiveness of phenprocoumon treatment.
• Heparin: nonsteroidal anti-inflammatory drugs 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 warnings and precautions for use").
• Angiotensin-converting enzyme (ACE) inhibitors: the effect of ACE inhibitors may be reduced.
• Diuretics: the diuretic and antihypertensive effects of loop, thiazide, and potassium-sparing diuretics are diminished (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 or bleeding (see section "Special warnings and precautions for use").
• Quinolone group antibacterial agents (e.g., levofloxacin, ofloxacin): increased risk of seizures.
• Antiplatelet agents (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 methotrexate concentration in blood serum, leading to increased toxicity. Careful monitoring is required during concomitant use.
• Selective serotonin reuptake inhibitors (SSRIs): increased risk of bleeding (see section "Special warnings and 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 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., glyburide): increased risk of hypoglycemia.
• Inducers and inhibitors of CYP2C9 isoenzymes: lornoxicam (like other NSAIDs metabolized by cytochrome P450 2C9 [CYP2C9 isoenzyme]) interacts with inducers and inhibitors of CYP2C9 isoenzymes (see subsection "Biotransformation" above).
• Tacrolimus: increased risk of nephrotoxicity due to decreased renal prostacyclin synthesis. Renal function should be monitored during combination therapy (see section "Special warnings and precautions for use").
• 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 is required 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 in such 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 renal insufficiency (serum creatinine level 300–700 µmol/L) due to the important role of prostaglandins in maintaining renal blood flow (see section "Method of administration and dosage"). If renal function deteriorates, lornoxicam therapy should be discontinued.
• Patients after extensive surgical procedures, with heart failure, those taking diuretics or agents that may cause renal damage: renal function should be carefully monitored (see section "Interaction with other medicinal products and other forms of interaction").
• Patients with coagulation disorders: careful clinical examination and assessment of laboratory parameters (e.g., activated partial thromboplastin time) are recommended.
• Patients with hepatic insufficiency (e.g., liver cirrhosis): after administration of the drug at a dose of 12–16 mg per day, regular laboratory tests are recommended due to the possibility of lornoxicam accumulation in the body (increased AUC) (see section "Pharmacological properties. Pharmacokinetics"). However, no deviations in pharmacokinetic parameters were observed in patients with hepatic insufficiency compared to healthy volunteers.
• Elderly individuals (aged 65 years and older): monitoring of renal and hepatic function is recommended. Use with caution after surgical procedures.

Concomitant use of NSAIDs.
Avoid simultaneous use of lornoxicam with other NSAIDs, including selective cyclooxygenase-2 inhibitors (see section "Interaction with other medicinal products and other forms of interaction").

Minimization of adverse reactions.
Adverse reactions can be minimized by taking the lowest effective dose for the shortest duration necessary to control disease symptoms (see section "Method of administration and dosage" and the information below regarding gastrointestinal and cardiovascular risks).

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

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses in patients with a history of peptic ulcers, especially those 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 "Method of administration and dosage").

NSAIDs should be used with caution in treating the above-mentioned patient groups and patients 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 concomitant use of protective agents (e.g., misoprostol or proton pump inhibitors). 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.

Particular caution is required when prescribing the drug to patients who are simultaneously using medicinal products that increase the risk of ulceration or bleeding, such as: oral corticosteroids, anticoagulants — warfarin, selective serotonin reuptake inhibitors, 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.

Elderly patients.
In elderly patients, the frequency of adverse reactions during NSAID use increases, particularly gastrointestinal bleeding and perforation, which may be fatal (see section "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 fluid retention and edema.

Clinical studies and epidemiological data suggest that the use of certain NSAIDs, particularly long-term therapy and high doses, may increase the 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 only after careful evaluation of indications in patients with uncontrolled hypertension, chronic heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disorders. A similar assessment is also required before prescribing long-term treatment to patients with risk factors for cardiovascular diseases (e.g., hypertension, hyperlipidemia, diabetes, smoking).

Concomitant therapy 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 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 taking the drug. 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.
Use with caution in patients with systemic lupus erythematosus and mixed connective tissue disease, as the risk of aseptic meningitis may increase.

Nephrotoxicity.
Concomitant therapy with NSAIDs and tacrolimus increases 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 transaminase and bilirubin levels, 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 conception 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 during chickenpox. At present, the influence of NSAIDs on worsening the course of these infectious diseases cannot be excluded. The use of lornoxicam is not recommended during 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 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 congenital heart defects with the use of prostaglandin synthesis inhibitors in early pregnancy. The risk increases with higher doses and duration of therapy.

In animals, administration of prostaglandin synthesis inhibitors leads to increased pre- and post-implantation loss and embryofetal mortality.

From the 20th week of pregnancy, the use of lornoxicam may cause oligohydramnios due to fetal renal dysfunction. This condition may occur soon after starting treatment and is usually reversible upon discontinuation of therapy. Additionally, there have been reports of arterial duct constriction after second-trimester treatment, which in most cases resolved after stopping therapy. Therefore, lornoxicam should not be prescribed during the first and second trimesters 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 as low as possible and the duration of treatment as short as possible. Prenatal monitoring for oligohydramnios and arterial duct constriction may be advisable if lornoxicam exposure occurred for several days starting from the 20th gestational week. If oligohydramnios or arterial duct constriction is detected, the drug should be discontinued.

During the third trimester of pregnancy, the use of any prostaglandin synthesis inhibitors may have the following effects on the fetus:

• Cardio-pulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
• Impaired renal function, which may progress to renal failure with the development of oligohydramnios (see above).

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

• Prolonged bleeding time;
• Inhibition of uterine contractility, which may lead to delayed or prolonged labor.

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

Breastfeeding period.
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 attempting to conceive. Lornoxicam should be discontinued in women experiencing difficulties with conception or undergoing infertility evaluation.

Ability to affect reaction speed when driving or operating machinery.
If dizziness or drowsiness occurs after taking lornoxicam, driving or operating machinery should be avoided.

Method of Administration and Dosage

Dosage

This pharmaceutical form of the drug is used for initiating therapy and when rapid achievement of analgesic effect is required, or when administration of oral dosage forms 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").

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

Route of Administration

This pharmaceutical form is intended for intravenous and intramuscular administration.

The intravenous injection should be administered over a period of not less than 15 seconds; intramuscular injection should last not less than 5 seconds.

After reconstitution, 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 reconstitution, a clear yellow solution should be obtained. If the medicinal product shows signs of degradation, it should be disposed of according to local requirements.

Special Patient Populations

Elderly patients (over 65 years of age) without hepatic or renal impairment do not require dose adjustment; however, lornoxicam should be used with caution in this population, as gastrointestinal adverse reactions are less well tolerated in elderly patients.

Patients with renal impairment. Patients with mild to moderate renal impairment require dose reduction. Lornoxicam is contraindicated in patients with severe renal dysfunction (see section "Contraindications").

Patients with hepatic impairment. Patients with moderate hepatic impairment require dose reduction. Lornoxicam is contraindicated in patients with severe hepatic impairment (see section "Contraindications").

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

Overdose

Currently, there are no reported cases of lornoxicam overdose sufficient to determine its consequences or to recommend specific treatment. However, symptoms of overdose may include nausea, vomiting, and central nervous system effects (dizziness, visual disturbances). In severe cases, ataxia (progressing to coma and convulsions), hepatotoxicity, nephrotoxicity, 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. No specific antidote is currently known. 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, sometimes fatal, may occur during NSAID therapy, 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 treatment with NSAIDs. Gastritis has been observed less frequently.

Approximately 20% of patients treated with lornoxicam may experience adverse effects. The most commonly reported adverse events 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 indicate that the use of certain NSAIDs, particularly at high doses and during long-term treatment, is associated with an increased risk of arterial thrombotic events such as myocardial infarction or stroke (see section "Special Warnings and Precautions for Use").

Very rarely, serious skin and soft tissue infections have been reported during varicella (chickenpox).

The adverse effects listed below were generally observed in more than 0.05% of the 6,417 patients who received treatment in Phase II, III, and IV clinical trials.

Adverse effects are classified by frequency of occurrence as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); very rare (< 1/10,000); 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 may cause class-specific potentially severe hematological disorders 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, restlessness.

Nervous system disorders

Common: mild and transient headache, dizziness.

Rare: somnolence, paresthesia, taste disturbances (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").

Eye disorders

Common: conjunctivitis.

Rare: visual disturbances.

Ear and labyrinth disorders

Uncommon: vertigo, tinnitus.

Cardiac disorders

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

Rare: hypertension, hot flushes, hemorrhage, hematomas.

Respiratory, thoracic and mediastinal disorders

Uncommon: rhinitis.

Rare: dyspnea, cough, bronchospasm.

Gastrointestinal disorders

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

Uncommon: constipation, flatulence, belching, 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 enzyme levels (ALT, AST).

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

Skin and subcutaneous tissue disorders

Uncommon: rash, pruritus, increased sweating, erythematous rash, urticaria, angioneurotic edema, 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 a class-specific effect of NSAIDs.

General disorders

Uncommon: malaise, facial edema.

Rare: asthenia.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients 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 has been demonstrated for 24 hours at 25 °C.

From a microbiological standpoint, the solution should be used immediately. If not used immediately, the responsibility for storage conditions and duration lies with the user.

Incompatibilities

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

Storage conditions

Keep out of the reach and sight of children.

Store in the original packaging to protect from light at a temperature not exceeding 25 °C.

Packaging

1 vial of powder and 1 ampoule with 2 mL of solvent (water for injections) in a set, packed in a blister pack. Packs of 1, 5, 6, or 10 sets in a cardboard box.

Prescription status

Prescription only.

Manufacturer/Marketing Authorization Holder

K.T. Rompharm Company S.R.L.

Address of manufacturer and location of business operations

Str. Eroilor No. 1A, Otopeni, 075100, Ilfov County, Romania – Rompharm 1 and Rompharm 2 buildings.