Instructions Loxidol solution for injection 15 mg/1.5 ml ampoule 1.5 ml No. 3
Composition
active ingredient: meloxicam;
1 ampoule (1.5 ml) of solution contains 15 mg of meloxicam;
excipients: meglumine, glycofurol, poloxamer 188, glycine, sodium chloride, sodium hydroxide solution, water for injection.
Dosage form
Solution for injection.
Main physicochemical properties: yellow with a greenish tint, transparent solution.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs.
ATX code M01A C06.
Pharmacological properties
Pharmacodynamics
Loxidol is a nonsteroidal anti-inflammatory drug (NSAID) of the enoleic acid class that has anti-inflammatory, analgesic, and antipyretic effects.
Meloxicam has shown high anti-inflammatory activity in all standard models of inflammation. As with other NSAIDs, its exact mechanism of action remains unknown. However, there is a common mechanism of action for all NSAIDs (including meloxicam): inhibition of the biosynthesis of prostaglandins, which are mediators of inflammation.
Pharmacokinetics
Meloxicam is almost completely absorbed after intramuscular administration. The concentration of meloxicam in the blood plasma is proportional to the administered dose. 60 minutes after intramuscular administration of 15 mg of meloxicam, the maximum plasma concentration is approximately 1.62 mg/l.
Meloxicam is highly bound to plasma proteins, especially albumin (90-100%). It penetrates into the synovial fluid, the concentration in the synovial fluid is approximately 50% of the plasma concentration. The volume of distribution is low, averaging 11 liters.
Meloxicam is almost completely metabolized in the liver to form 4 pharmacologically inactive derivatives. The main metabolite, 5'-carboxymeloxicam (60% of the dose), is formed by oxidation of the intermediate metabolite 5'-hydroxymethylmeloxicam, which is also excreted, but to a lesser extent (9% of the dose).
Loxidol is excreted in equal amounts in feces and urine, mainly in the form of metabolites. Less than 5% of the daily dose is excreted unchanged in feces, and only trace amounts of unchanged drug are found in urine.
The average half-life of meloxicam is 20 hours. Plasma clearance is on average 8 ml/min.
In elderly patients, clearance is slightly lower.
Indication
Short-term symptomatic treatment of acute attacks of rheumatoid arthritis and ankylosing spondylitis when oral and rectal routes of administration of meloxicam cannot be used.
Contraindication
- Hypersensitivity to meloxicam or to any of the excipients of the product, or to active substances with similar effects, such as NSAIDs, aspirin. Meloxicam should not be prescribed to patients who have experienced symptoms of bronchial asthma, nasal polyps, angioedema or urticaria after taking aspirin or other NSAIDs;
- history of gastrointestinal bleeding or perforation associated with previous NSAID therapy;
- history of active or recurrent peptic ulcer/bleeding (two or more separate confirmed episodes of ulceration or bleeding);
- severe liver failure;
- severe renal failure without dialysis;
- gastrointestinal bleeding, history of cerebrovascular bleeding or other blood clotting disorders;
- hemostasis disorders or concomitant use of anticoagulants (contraindications related to the route of administration);
- severe heart failure;
- treatment of perioperative pain during coronary artery bypass grafting (CABG);
- 3rd trimester of pregnancy (see section "Use during pregnancy or breastfeeding");
- patient's age is up to 18 years.
Interaction with other medicinal products and other types of interactions
Other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid ≥ 3 g/day. Combination with other NSAIDs including acetylsalicylic acid at anti-inflammatory doses (≥ 1 g single dose or ≥ 3 g total daily dose) is not recommended.
Corticosteroids (e.g. glucocorticoids): Concomitant use with corticosteroids requires caution due to increased risk of gastrointestinal bleeding or ulceration.
Anticoagulants or heparin used in geriatric practice or at therapeutic doses. The risk of bleeding is significantly increased due to inhibition of platelet function and damage to the gastroduodenal mucosa. NSAIDs may enhance the effects of anticoagulants such as warfarin. The concomitant use of NSAIDs and anticoagulants or heparin in geriatric practice or at therapeutic doses is not recommended.
In other cases, heparin should be used with caution due to the increased risk of bleeding. Careful monitoring of the INR (international normalized ratio) is necessary if the combination is proven to be unavoidable.
Thrombolytic and antiplatelet drugs. Increased risk of bleeding through inhibition of platelet function and damage to the gastroduodenal mucosa.
Diuretics, ACE inhibitors and angiotensin II antagonists. NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function), the concomitant use of ACE inhibitors or angiotensin II antagonists and drugs that inhibit cyclooxygenase may lead to further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be used with caution, especially in elderly patients. Patients should be adequately hydrated and renal function should be monitored after initiation of concomitant therapy and periodically thereafter.
Other antihypertensive drugs (e.g. beta-blockers). As with the following drugs, the antihypertensive effect of beta-blockers may be reduced (due to inhibition of vasodilating prostaglandins).
Calcineurin inhibitors (e.g. cyclosporine, tacrolimus). The nephrotoxicity of calcineurin inhibitors may be potentiated by NSAIDs through mediation of the effects of renal prostaglandins. Renal function should be monitored during treatment. Close monitoring of renal function is recommended, especially in elderly patients.
Intrauterine contraceptives: Reduced effectiveness of intrauterine contraceptives has been reported with NSAIDs, but this needs further confirmation.
Lithium. There is evidence that NSAIDs increase the plasma concentration of lithium (by reducing the renal excretion of lithium), which may reach toxic levels. The simultaneous use of lithium and NSAIDs is not recommended. If combination therapy is necessary, careful monitoring of plasma lithium levels is necessary at the beginning of treatment, during dose adjustment and when discontinuing treatment with meloxicam.
Methotrexate. NSAIDs may reduce the tubular secretion of methotrexate, thereby increasing its plasma concentration. For this reason, concomitant use of NSAIDs is not recommended in patients receiving high doses of methotrexate (more than 15 mg/week). The risk of interaction between NSAIDs and methotrexate should also be considered in patients receiving low doses of methotrexate, including patients with impaired renal function. If combined treatment is necessary, blood counts and renal function should be monitored. Caution should be exercised when NSAIDs and methotrexate are administered for 3 consecutive days, as plasma levels of methotrexate may increase and toxicity may be increased. Although the pharmacokinetics of methotrexate (15 mg/week) were not affected by concomitant treatment with meloxicam, it should be considered that the haematological toxicity of methotrexate may increase during treatment with NSAIDs.
Cholestyramine accelerates the elimination of meloxicam by disrupting intrahepatic circulation, so the clearance of meloxicam increases by 50% and the half-life decreases to 13±3 hours. This interaction is clinically significant.
No clinically significant pharmacokinetic interaction was found when co-administered with antacids, cimetidine, and digoxin.
Application features
Adverse reactions can be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section “Dosage and Administration” and information on gastrointestinal and cardiovascular risks below).
The recommended maximum daily dose should not be exceeded in case of insufficient therapeutic effect, nor should additional NSAIDs be used, as this may increase toxicity while the therapeutic benefit has not been proven. The concomitant use of meloxicam with NSAIDs including selective cyclooxygenase-2 inhibitors should be avoided.
If there is no improvement after several days, the clinical benefit of treatment should be reassessed.
Attention should be paid to a history of esophagitis, gastritis and/or peptic ulcer in order to ensure that they are completely cured before starting therapy with meloxicam. Patients treated with meloxicam and patients with a history of such cases should be regularly monitored for possible recurrence.
Gastrointestinal disorders.
As with other NSAIDs, potentially fatal gastrointestinal bleeding, ulceration or perforation may occur at any time during treatment with or without previous symptoms or a history of serious gastrointestinal disease.
Patients with a history of gastrointestinal toxicity, especially elderly patients, should be informed of any unusual abdominal symptoms (especially gastrointestinal bleeding), especially during the initial stages of treatment.
Caution should be exercised in patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as heparin, as radical therapy or in geriatric practice, anticoagulants such as warfarin, or other non-steroidal anti-inflammatory drugs, including acetylsalicylic acid at anti-inflammatory doses (≥ 1 g single dose or ≥ 3 g total daily dose) (see section “Interaction with other medicinal products and other forms of interaction”).
If gastrointestinal bleeding or ulceration occurs in patients taking meloxicam, treatment should be discontinued.
NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated (see section "Adverse reactions").
Liver disorders.
Some patients taking NSAIDs may develop elevations in one or more liver function tests. These laboratory abnormalities may progress, remain stable, or be transient with continued treatment. In addition, rare cases of severe hepatic reactions, including jaundice and fulminant hepatitis, hepatic necrosis, and hepatic failure, some of which were fatal, have been reported.
Patients with symptoms and/or signs of hepatic dysfunction or who have had abnormal liver function tests should be evaluated for the development of symptoms of more severe hepatic insufficiency during therapy with Loxidol. If clinical signs and symptoms are consistent with the development of liver disease or if systemic manifestations of the disease (e.g. eosinophilia, rash, etc.) are observed, the drug should be discontinued.
Cardiovascular disorders.
Close monitoring is recommended in patients with hypertension and/or a history of mild to moderate congestive heart failure, as fluid retention and edema have been reported with NSAID therapy.
Clinical monitoring of blood pressure is recommended in patients with risk factors at the beginning of therapy, especially at the beginning of treatment with meloxicam.
Clinical and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term treatment) may be associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke). There are insufficient data to exclude such a risk for meloxicam.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be treated with meloxicam only after careful evaluation. Such evaluation is necessary before starting long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking).
NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which may be fatal. The increased risk is related to the duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk of thrombotic events.
Skin disorders.
Serious skin reactions, some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely with the use of NSAIDs (see section 4.8). The highest risk of such reactions was observed at the beginning of treatment, with the majority of such reactions occurring within the first month of treatment. Meloxicam should be discontinued at the first appearance of skin rash, mucosal lesions or other signs of hypersensitivity.
Anaphylactic reactions.
As with other NSAIDs, anaphylactic reactions may occur in patients with no known reaction to meloxicam. Loxidol should not be used in patients with the aspirin triad. This symptom complex occurs in patients with asthma who have reported rhinitis with or without nasal polyps or who have experienced severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. Emergency care should be sought if an anaphylactic reaction occurs.
Liver parameters and kidney function.
As with most NSAIDs, isolated cases of increased serum transaminases, serum bilirubin or other liver function parameters, increased serum creatinine and blood urea nitrogen, and other laboratory abnormalities have been reported. In most cases, these abnormalities were minor and transient. If significant or persistent abnormalities occur, meloxicam should be discontinued and follow-up tests should be performed.
NSAIDs, due to inhibition of the vasodilatory effect of renal prostaglandins, can induce functional renal failure by reducing glomerular filtration. This side effect is dose-dependent. At the beginning of treatment or after increasing the dose, careful monitoring of diuresis and renal function is recommended in patients with the following risk factors:
- old age;
- concomitant use with ACE inhibitors, angiotensin II antagonists, sartans, diuretics (see section "Interaction with other medicinal products and other types of interactions");
- hypovolemia (of any origin);
- congestive heart failure;
- renal failure;
- nephrotic syndrome;
- lupus nephropathy;
- severe hepatic dysfunction (serum albumin < 25 g/l or ≥ 10 according to the Child-Pugh classification).
In rare cases, NSAIDs can lead to interstitial nephritis, glomerulonephritis, renal medullary necrosis, or nephrotic syndrome.
The dose of meloxicam for patients with end-stage renal disease on dialysis should not exceed 7.5 mg. In patients with mild to moderate renal impairment (creatinine clearance greater than 25 ml/min), the dose may not be reduced.
Sodium, potassium and water retention.
NSAIDs may increase sodium, potassium and water retention and may interfere with the natriuretic effects of diuretics. In addition, the antihypertensive effect of antihypertensive drugs may be reduced (see section 4.5).
As a result, edema, heart failure, or hypertension may be precipitated or exacerbated in susceptible patients. Therefore, clinical monitoring is recommended in patients at risk of sodium, potassium, and water retention (see sections 4.2 and 4.3).
Hyperkalemia.
Hyperkalemia may be caused by diabetes mellitus or concomitant use of drugs that increase potassium levels (see section 4.5). In such cases, it is necessary to
Regularly monitor potassium levels.
Other warnings and precautions.
Adverse reactions are often worse tolerated in elderly, frail or debilitated patients who require close monitoring. As with other NSAIDs, caution should be exercised in the elderly, who are more likely to have decreased renal, hepatic and cardiac function. Elderly patients have a higher incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).
Meloxicam, like any other NSAID, may mask the symptoms of infectious diseases.
As with intramuscular administration of other NSAIDs, abscess or necrosis may occur at the injection site.
Meloxicam may impair reproductive function and is not recommended in women attempting to conceive. Therefore, in women attempting to conceive or undergoing investigation of infertility, discontinuation of meloxicam should be considered (see section 4.6).
Masking inflammation and fever.
The pharmacological action of meloxicam, aimed at reducing fever and inflammation, may affect diagnostic results when determining complications of a suspected non-infectious painful condition.
Corticosteroid treatment.
Loxidol cannot be a likely substitute for corticosteroids in the treatment of corticosteroid insufficiency.
Hematological effects.
Anemia may occur in patients receiving NSAIDs. This may be due to fluid retention, gastrointestinal bleeding of unknown origin or gross bleeding, or an incompletely described effect on erythropoiesis. Patients on long-term NSAID therapy should have their hemoglobin or hematocrit monitored if they develop symptoms of anemia.
NSAIDs inhibit platelet aggregation and may show prolongation of bleeding time in some patients. In contrast to aspirin, their effect on platelet function is quantitatively smaller, short-lived and reversible. Patients prescribed Loxidol who may have adverse effects related to changes in platelet function, such as coagulation disorders, or patients receiving anticoagulants, require careful monitoring.
Use in patients with existing asthma.
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which may be fatal. Because of cross-reactivity, including bronchospasm, between aspirin and other NSAIDs, Loxidol should not be used in patients who are sensitive to aspirin and should be used with caution in patients with pre-existing asthma.
Use during pregnancy or breastfeeding
Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Epidemiological data suggest an increased risk of miscarriage and of cardiac malformations and gastroschisis following exposure to prostaglandin synthesis inhibitors in early pregnancy. An increase in the absolute risk of cardiac malformations from less than 1% to approximately 1.5% has been reported. This risk is thought to increase with increasing dose and duration of treatment.
During the first and second trimesters of pregnancy, meloxicam should not be used unless clearly necessary. If meloxicam is used by a woman attempting to conceive or during the first and second trimesters of pregnancy, the dosage and duration of treatment should be kept to the lowest possible level.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose a risk to the fetus:
- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
- kidney dysfunction, which may develop into renal failure with oligohydramnios;
possible risks in the last stages of pregnancy for the mother and newborn:
- possibility of prolongation of bleeding time, antiplatelet effect even at very low doses;
- suppression of uterine contractions, leading to delayed or prolonged labor.
Therefore, meloxicam is contraindicated during the third trimester of pregnancy.
Breastfeeding: Although there are no specific data for meloxicam, NSAIDs are known to pass into breast milk. Therefore, use is not recommended in women who are breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
There are no specific data on the effect of the drug on the ability to drive or operate other mechanisms. However, patients who have experienced visual disturbances, including blurred vision, dizziness, drowsiness, vertigo or other central nervous system disorders, are advised to refrain from driving or operating other mechanisms.
Method of administration and doses
Intramuscular use.
One injection of 15 mg once daily.
Do not exceed a dose of 15 mg/day.
Treatment should be limited to a single injection at the beginning of therapy with a maximum duration of up to 2-3 days in justified exceptional cases (e.g. when oral and rectal routes of administration are not possible).
Adverse reactions 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 patient's need for symptomatic relief and response to treatment should be assessed periodically.
The recommended dose for elderly patients is 7.5 mg per day. Patients at increased risk of adverse reactions should start treatment with 7.5 mg per day (half a 1.5 ml ampoule) (see section "Special instructions").
For patients with severe renal insufficiency who are on dialysis, the dose should not exceed 7.5 mg per day (half a 1.5 ml ampoule).
No dose reduction is required in patients with mild to moderate renal impairment (i.e., patients with creatinine clearance above 25 mL/min). For patients with severe renal impairment not requiring dialysis, see section 4.3.
No dose reduction is required in patients with mild to moderate hepatic impairment. For patients with severe hepatic impairment, see section "Contraindications".
Method of application.
The drug should be administered slowly, by deep intramuscular injection into the upper outer quadrant of the buttock, observing strict aseptic technique. In case of repeated administration, it is recommended to alternate the left and right buttock. Before injection, it is important to check that the needle tip is not in a blood vessel.
The injection should be stopped immediately if severe pain occurs during the injection.
In the case of a hip replacement, the injection should be given in the other buttock.
Children
The drug is contraindicated in children (under 18 years of age).
Overdose
Symptoms of acute NSAID overdose are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive therapy. Gastrointestinal bleeding may occur. Severe poisoning may result in hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular failure, and cardiac arrest. Anaphylactoid reactions have been reported with therapeutic use of NSAIDs, which may also occur with overdose.
In case of NSAID overdose, symptomatic and supportive measures are recommended for patients.
There is evidence of accelerated elimination of meloxicam with four oral doses of cholestyramine 3 times daily.
Adverse reactions
Research and epidemiological data suggest that the use of some NSAIDs (especially at high doses and with long-term treatment) may be associated with
associated with a small increased risk of vascular thrombotic events (such as myocardial infarction or stroke) (see section "Special warnings and precautions for use").
Most of the observed side effects are of gastrointestinal origin. Peptic ulcer, perforation or gastrointestinal bleeding, sometimes fatal, especially in elderly patients, may occur (see section "Special warnings and precautions for use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been observed after use (see section "Special warnings and precautions for use"). Gastritis has been observed less frequently.
Criteria for assessing the frequency of adverse drug reactions: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (<1/10000); unknown (cannot be determined from available data).
From the blood and lymphatic system:
infrequently - anemia;
rarely - deviation of blood parameters from the norm (including changes in the number of leukocytes), leukopenia, thrombocytopenia.
Very rare cases of agranulocytosis have been reported.
On the part of the immune system:
infrequently - allergic reactions other than anaphylactic or anaphylactoid;
not known - anaphylactic shock, anaphylactic reaction, anaphylactoid reaction including shock.
Mental disorders:
rarely - mood swings, nightmares;
unknown - confusion, disorientation, insomnia.
From the nervous system:
often - headache;
infrequently - dizziness, drowsiness.
On the part of the organs of vision:
Rare: visual disturbances including blurred vision; conjunctivitis.
From the side of the organs of hearing and vestibular apparatus:
infrequently - dizziness;
rarely – ringing in the ears.
Cardiac disorders:
rarely - feeling of palpitations.
Heart failure has been reported in association with the use of NSAIDs.
Vascular disorders:
infrequently - increased blood pressure (see section "Special instructions for use"), hot flashes.
From the respiratory system, chest organs and mediastinum:
rarely - asthma in patients allergic to aspirin and other NSAIDs;
unknown - upper respiratory tract infections, cough.
From the digestive tract:
often - dyspepsia, nausea, vomiting, abdominal pain, diarrhea;
infrequently - occult or macroscopic gastrointestinal bleeding, stomatitis, gastritis, constipation, flatulence, belching;
rarely - colitis, gastroduodenal ulcer, esophagitis;
very rarely - gastrointestinal perforation.
Gastrointestinal bleeding, ulceration or perforation may be severe and potentially fatal, especially in the elderly (see section 4.4).
Hepatobiliary system disorders:
infrequently - abnormal liver function tests (e.g. increased transaminases or bilirubin);
very rarely – hepatitis;
unknown - jaundice, liver failure.
From the skin and subcutaneous tissue:
infrequently - angioedema, itching, rash;
rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria;
very rarely - bullous dermatitis, erythema multiforme;
unknown - photosensitivity reactions, exfoliative dermatitis.
From the urinary system:
infrequently - sodium and water retention, hyperkalemia, changes in renal function (increased serum creatinine and/or urea);
very rarely - acute renal failure, particularly in patients with risk factors;
not known – urinary tract infections, urinary frequency disorders.
General disorders and administration site conditions:
often - injection site induration, injection site pain;
uncommon - edema, including edema of the lower extremities;
unknown – flu-like symptoms.
On the part of the musculoskeletal system:
not known – arthralgia, back pain, joint-related symptoms.
Certain serious and/or frequent adverse reactions.
Very rare cases of agranulocytosis have been reported in patients taking meloxicam and other potentially myelotoxic drugs (see section "Interaction with other medicinal products and other forms of interaction").
Adverse reactions that were not associated with the use of the drug, but which are generally characteristic of other compounds of the class.
Organic renal damage, possibly leading to acute renal failure: very rare cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome and papillary necrosis have been reported (see section "Special warnings and precautions for use").
Expiration date
4 years.
Storage conditions
Store at a temperature not exceeding 25 ºС in a place inaccessible to children.
Incompatibility
Due to possible incompatibility, Loxidol, solution for injection, should not be mixed with other drugs in the same syringe.
Packaging
1.5 ml of solution in a glass ampoule; 3 ampoules in a contour blister pack; 1 contour blister pack in a cardboard box.
Vacation category
According to the recipe.
Producer
K.O. Rompharm Company SRL, Romania / SC Rompharm Company SRL, Romania.
Location of the manufacturer and its business address
Otopeni city, Eroilor str. № 1A, 075100, jud. Ilfov.
