Meloxicam injection solution 15mg/1.5ml Danapha treat osteoarthritis pain (10 tubes)

ATC code: M1AC06

Meloxicam is an nonsteroidal anti -inflammatory drug, derivative of oxicam. The drug has anti -inflammatory, analgesic, antipyretic effects. Meloxicam inhibits the synthesis of prostaglandin, intermediate substances that play an important role in the pathogenesis of inflammation, fever, pain.

Pharmacokinetics

absorption

Meloxicam is completely absorbed after intramuscular injection. Relative bioavailability compared to oral road is approximately 100 %. No need to adjust the dose when changing from intramuscular treatment to oral form. After intramuscular injection of 15 mg, the maximum concentration in plasma is about 1.6 - 1.8 µg/ml, achieved in about 1 - 6 hours.

Distribution

Meloxicam is strongly linked to plasma proteins, mainly albumin (99 %). Meloxicam penetrates well into joint fluid and achieves a concentration of approximately half of plasma concentrations.

Low distribution volume, an average of 11 liters after intramuscular injection or intravenous injection, the difference between individuals is about 7-20 %. The distribution volume after taking multiple doses of Meloxicam (7.5 to 15 mg) is about 16 liters with a coefficient of oscillation of 11 - 32 %.

Metabolism

Meloxicam is strongly metabolized in the liver. The four different metabolites of Meloxicam have been determined in urine without medicinal activity. Main metabolites, 5'-carboxymeloxicam (equivalent to 60 % of the dose) formed by oxidation of intermediate metabolites 5'-hydroxymethylmeloxicam, are also eliminated at a lesser level (equivalent to 9 % dose). In vitro research shows that CYP2C9 plays an important role in this metabolism, with a small contribution of isenzyme CYP3A4. Peroxidase activity can produce two other metabolites, equivalent to 16 % and 4 % of the dose.

Elimination

Meloxicam is excreted mainly in the form of metabolites, half through urine and half through stool. Under 5 % of the dose is discharged in feces in a constant form, while only a very small amount is discharged in the urine.

Average waste sale time is about 13-25 hours after drinking, intramuscularly and intravenously.

Average total plasma clearance is about 7 - 12 ml/min after taking a single dose of intravenous or rectal placement.

linear/non -linear

Linear pharmacokinetics in the treatment dose range from 7.5 mg to 15 mg oral as well as intramuscularly.

Special patient groups

Liver failure/kidney failure

Hepatic failure or renal failure at a mild to moderate period does not significantly affect Meloxicam's pharmacokinetics. Patients with renal impairment The average level has significantly higher drug clearance. It has not been noted for significant reduction in protein bonds in patients with end -stage renal failure. In case of severe renal failure, increasing distribution volume may increase the concentration of freelance meloxicam.

Elderly patients

Patients with elderly men have average pharmacokinetic parameters equivalent to young men. Patients with elderly women show higher AUC values ​​and longer selling time than young and female young patients.

Average clearance in a state of stability in the elderly is slightly lower than young people.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.

What to do when overdose? Gastrointestinal bleeding can occur. Serious overdose can lead to hypertension, acute renal failure, liver damage, respiratory failure, coma, convulsions, cardiovascular collapse and cardiac arrest. Anaphylaxis has been reported during treatment with NSAID and can occur in case of overdose.

Handling: In case of overdose with NSAID, it is advisable to conduct appropriate symptomatic treatment. In a clinical trial, Meloxicam was quickly eliminated after taking Cholestyramine (4 g, 3 times daily).

In an emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when you forget 1 dose? However, if the time to relax with the next dose is too short, skip the dose and continue the calendar of the drug. Do not use double dose to compensate for missed dose.

Be cautious when using

Use the lowest possible dose in the shortest time to reduce unwanted effects.

Do not overdose the maximum recommended and should not be combined with other NSAIDs because of the risk of increasing toxicity and not increasing the effectiveness of treatment.

Should avoid simultaneous use of Meloxicam with other NSAIDs, including selective inhibitors Cycloxygenase 2 (COX-2).

Meloxicam is not suitable for acute pain treatment.

If not effective after a few days of treatment, it is necessary to re -evaluate the medication.

If there is a history of esophagitis, stomach ulcers, must be completely cured before using Meloxicam. These patients who are or are using Meloxicam, need to monitor the recurrence of esophageal and stomach ulcers.

Effects on gastrointestinal effects

Hemorrhage, ulcers or gastrointestinal perforation, sometimes death, has been recorded with all NSAIDs during treatment that may occur at any time, not necessarily a warning sign or a serious history of the digestive system.

The risk of bleeding, ulcers or gastrointestinal perforation increases in patients with a history of ulcer, especially in the elderly or complications such as bleeding or perforation. In these patients, it is recommended to start treatment at the lowest possible doses. Mucus protection treatment (for example:

Misoprostol or proton pump inhibitors) should be considered for these patients, as well as patients who are in need of low -dose aspirin or drugs that can increase risks on the digestive tract.

Patients with a history of gastrointestinal tract, especially the elderly, should be reported when there are abdominal symptoms (especially gastrointestinal bleeding), especially at the beginning of treatment.

In patients being treated with heparin or the elderly, using other nonsteroidal anti -inflammatory drugs, or high -dose aspirin ≥ 500 mg/dose or ≥ 3 g/day, it is not recommended to use in combination with meloxicam because it can increase the risk of ulcer or bleeding.

Patients who are using Meloxicam if ulcers or bleeding, should stop treatment. In patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease), NSAID should be used carefully under the close supervision due to the risk of getting worse.

Risk of venous thrombosis

Non -steroid anti -inflammatory drugs (NSAID), non -aspirin, use systemic sugar, may increase the risk of cardiovascular thrombosis, including myocardial and stroke, which can lead to death. This risk can appear early in the first few weeks of taking the drug and can increase over time. The risk of cardiovascular thrombosis is recorded mainly at high doses.

Doctors need to periodically evaluate the appearance of cardiovascular events, even if the patient has no symptoms of the previous cardiovascular events. Patients should be warned of symptoms of serious cardiovascular events and need to visit the doctor as soon as they appear.

To minimize the risk of adverse events, it is necessary to use Meloxicam injection 15 mg/1.5 ml at the lowest daily dose effective in the shortest possible time.

influence on the heart and cerebrovascular

Need to monitor and recommend adequate in patients with a history of hypertension and/or mild to moderate heart failure, with salt, sodium and edema status that have been reported related to NSAID therapy.

Recommended blood pressure monitoring in patients at risk, especially when starting treatment with Meloxicam.

Clinical studies and epidemiological data show that the use of some NSAIDs (especially with high doses and for a long time) may be related to slight increase in risk of thrombosis (for example, myocardial infarction or stroke). There is currently not enough data to eliminate this risk for Meloxicam.

Patients with uncontrolled hypertension, congestive heart failure, myocardial ischemia, peripheral artery disease and/or a history of stroke (including transient ischemia) should only be treated with meloxicam after careful consideration.

Be careful when using meloxicam for a long time in patients at risk of cardiovascular disease (hypertension, hyperlipidemia, diabetes or smoking).

skin reaction

Life-dangerous skin reactions, Stevens-Johnson syndrome and Lyell syndrome have been reported when using Meloxicam. Patients should be notified of the signs and symptoms of the disease, and closely monitor the skin reactions. The risk of Stevens-Johnson syndrome or the highest lyell syndrome in the first weeks of treatment. If there are symptoms or signs of the Stevens-Johnson syndrome or Lyell syndrome (for example, a rash, usually combined with blisters or mucosal damage), should stop treatment with Meloxicam. Early diagnosis and stop suspected drugs to be able to control the Stevens-Johnson syndrome well and Lyell syndrome. The stopping of early suspicits for better prognosis. If the patient appears Stevens-Johnson syndrome or Lyell syndrome when treated with Meloxicam, does not use Meloxicam for that patient.

Liver and kidney function parameters

For most NSAIDs, there has been an increase in transient serum transaminase, increased blood bilirubin or other indicators of liver function, increased serum creatinine, uric acid and abnormalities in other biological parameters. In most cases, the slight increase is on normal and transient limits. If abnormalities become serious or persistent, Meloxicam should be stopped and require appropriate tests.

Renal impairment

NSAID can cause impaired renal function by reducing glomerular filtration level, due to inhibition of vasodilation effect of kidney prostaglandin. This unwanted effect depends on the dose.

Advantage to closely monitor kidney function including the amount of urine at the beginning of treatment or when increasing the dose in patients with the following risk factors:

In some rare cases, NSAIDs can cause interstitial nephritis, glomerulonephritis, kidney necrosis or nephrotic syndrome.

Meloxicam dose must not exceed 7.5 mg in patients with end -stage renal disease being dialysis. There is no need to reduce the dose in patients with mild or medium renal failure (creatinine clearance> 25 ml/min).

Keeping sodium, potassium and water

NSAIDs can cause sodium, potassium and water holder as well as prevent the stimulating effect on sodium secretion in urine of diuretics. In addition, it may reduce the effects of antihypertensive drugs. Therefore, edema, heart failure or hypertension may appear or worsen in sensitive patients. Therefore, clinical monitoring in patients at risk.

Hemorrhage

Hemorrhage often appears in the case of diabetes or when treated simultaneously with drugs that have a hyperkalemia effect. Regular monitoring of potassium concentration is recommended in these cases.

involves Pemetrexed

In patients with mild to moderate mild renal failure being treated with Pemetrexed, Meloxicam should not be used at least five days ago, during and at least two days after using Pemetrexed.

Warnings and cautions

Elderly, sick or depressed patients often suffer from unwanted effects, so it is necessary to strengthen monitoring. Like other NSAIDs, need to be cautious in the elderly, people with impaired renal, liver and heart function.

Elderly patients have many risks of unwanted effects of NSAID, especially gastrointestinal bleeding and gastric perforation, can be fatal.

As all NSAID, Meloxicam can hide the symptoms of basic infections. Like any NSAID using intramuscular, abscess and necrotic can occur at the injection site.

Meloxicam may affect fertility. Do not recommend use in women who want to get pregnant.

In women who are difficult to conceive or are being diagnosed with infertility, it is advisable to consider stopping Meloxicam treatment.

The drug contains less than 1 mmol of sodium (23 mg of sodium) in 1.5 ml, which is considered without sodium.

The effect of the drug on driving and operating machinery

There is no specific research on the effect of the drug on the ability to drive and operate machinery. Based on the pharmacokinetics and side effects reported, Meloxicam does not affect the ability to drive or use machines. However, in case of vision loss, drowsiness, dizziness or other central neurological disorders, do not drive or operate machinery.

Use drugs for women during pregnancy and lactation

Pregnant women

Prostaglandin synthesis inhibitors can affect pregnant mothers and/or embryo development. Data from epidemiological studies show an increase in the risk of miscarriage, heart defects and abdominal hernia after using prostaglandin synthetic inhibitors in the early stage of pregnancy. The risk of heart defects increases from less than 1 % to about 1.5 %. It is thought that this risk increases with the dose and treatment time. In animals, treatment with general inhibitors prostaglandin shows increased miscarriage, after nesting and increased pregnancy death rate.

In addition, the rate of other malformations including cardiovascular disease is reported on experimental animals using prostaglandin inhibitors during the formation of organs.

Unless it is really necessary, avoid using meloxicam for the first 3 months and the middle 3 months of pregnancy. If used, Meloxicam should be used in the lowest doses in the shortest possible time.

In the last 3 months of pregnancy, all Prostaglandin synthesis inhibitors can cause

The fetus: toxicity on the lungs (early closed arteriosclerosis and pulmonary hypertension), renal dysfunction, can lead to kidney failure, less amniotic fluid.

Mothers and fetuses at the end of pregnancy. Extend the bleeding time even at very low doses, inhibiting uterine contractions slowing down labor time.

Therefore, contraindicated use of Meloxicam in pregnant women.

breastfeeding women

There is no specific data on the use of meloxicam during breastfeeding. However, NSAID is known to go into breast milk. Therefore, Meloxicam should not be used while breastfeeding.

fertility

The use of Meloxicam, like any drug inhibits Cycloxygenase/Prostaglandin synthesis, can impair fertility and are not recommended for use in pregnant women. Meloxicam can delay ovulation. Therefore, it is advisable to consider stopping meloxicam in women who are difficult to conceive, or are being diagnosed with infertility.

Drug interaction

Risks related to hyperkalemia

Some drugs have the ability to increase potassium potassium: Potassium salt, hyperkalemia, enzyme inhibitors, angiotensin II receptor antagonists, nonsteroidal anti -inflammatory drugs, heparin (low or non -segmented molecular weight), cyclosporin, tacrolimus and trimethoprim. The onset of hyperkalemia may depend on the relevant factors.

This risk increases as the above drugs are used in combination with Meloxicam.

Pharmacological interaction

Other NSAIDs and aspirin

It is not recommended to simultaneously use Meloxicam with other NSAIDs or aspirin at a dosage of> 500 mg/time or> 3 g/day.

corticosteroid (eg glucocorticoid)

Be cautious when used simultaneously with corticosteroids due to increased risk of ulcer and gastrointestinal bleeding.

anticoagulant or heparin

significantly increases the risk of bleeding, due to inhibition of platelet function and damaging the gastric - duodenum mucosa.

NSAIDs can increase the effects of anticoagulants, like warfarin.

It is not recommended to use NSAIDs simultaneously with anticoagulant or heparin drugs in the elderly or with treatment.

In other cases (for example, with a prophylactic dose), it is necessary to be cautious when using heparin because it increases the risk of bleeding.

Medications that soluble thrombosis and anti -platelets

Increased risk of bleeding, due to inhibition of platelet function and damage to the peptic mucosa.

Selective Serotonin Restrain Inhibitors (SSRI)

Increased risk of gastrointestinal bleeding.

Diuretics, enzyme inhibitors and Angiotensin II NSAID receptor antagonists can reduce the effects of diuretics and other antihypertensive drugs. In some patients with impaired renal function (for example, dehydrated patients or the elderly), the combination of enzyme inhibitors or Angiotensin II receptor antagonists with cyclo-oxygenase inhibitors can impair renal function, including acute renal failure, often recovered. Therefore, it is necessary to be careful in the elderly.

Patients need to be provided with enough water and monitor the kidney function at the beginning of treatment and periodically.

Other antihypertensive drugs (including beta blockers)

may reduce the hypotension effect of beta blockers (due to inhibition of prostaglandin stretches).

Calcineurin inhibitors (for example: cyclosporin, tacrolimus)

NSAID can increase the toxicity of the kidneys of calcineurin inhibitors, through the effects depending on the kidney prostaglandin. When used combined, need to monitor kidney function, especially in the elderly.

Deferasirox

Be careful when using Meloxicam and Deferasirox simultaneously because it can increase the risk of side effects on the digestive tract.

pharmacokinetic interaction

Meloxicam's effect on the pharmacokinetics of other drugs:

lithium

NSAIDs have been recorded in an increase in plasma lithium levels (due to reducing lithium secretion), which can lead to toxicity. It is not recommended to simultaneously use lithium and NSAID. If it is necessary to combine, lithium concentration should be monitored in the early stages, adjusting and discontinuing Meloxicam treatment.

methotrexate

NSAIDs can reduce methotrexate excretion through the renal tubules leading to increased methotrexate levels in plasma. Therefore, it is not recommended to use NSAID in patients treated with high doses of methotrexate (> 15 mg/week).

The risk of interaction between NSAID and Methotrexate should also be considered in patients treated with lower doses of methotrexate, especially in patients with impaired renal function.

If used combining, it is necessary to monitor blood formula and kidney function. Especially need to be cautious when using methotrexate and NSAID for three consecutive days, due to the risk of toxicity when the concentration of methotrexate in plasma increases.

pemetrexed

In patients with creatinine clearance from 45 to 79 ml/min, do not use meloxicam at least five days ago, the same day and at least two days after using Pemetrexed. If it is necessary to use Meloxicam and Pemetrexed simultaneously, patients should be monitored by the kidneys, due to the risk of marrow failure and harmful reactions on the gastrointestinal tract. In patients with severe renal failure (creatinine clearance

In normal kidney function patients (Creatinine clearance ≥ 80 ml/min), dose of 15 mg of Meloxicam can reduce Pemetrexed clearance, thus increasing the appearance of side effects. Therefore, be careful when using 15 mg of Meloxicam with Pemetrexed in these patients.

The effect of other drugs on Meloxicam's pharmacokinetics

cholestyramin

Cholestyramin accelerates the process of eliminating meloxicam by stopping the intestinal diverse cycle, thus increasing Meloxicam's clearance to 50 % and reducing the sale time to 13 ± 3 hours.

The influence of Meloxicam combining with other drugs is dynamic

Anti -diabetes oral diabetes (sulfonylurea, nateganid)

Meloxicam is excreted mainly through the metabolism in the liver, of which about 2/3 through the intermediaries of cytochrom enzymes (CYP) P450 (most CYP2C9 and one part CYP3A4) and 1/3 through other mechanisms such as oxidation by peroxidase. It is necessary to consider the risk of pharmacokinetic interaction when using Meloxicam simultaneously with inhibited drugs or metabolized by CYP2C9 and/or CYP3A4. Interactive through CYP2C9 can occur when used in combination with oral diabetes drugs (sulfonylurea, nateganid), as it can increase the concentration of these drugs and meloxicam in plasma. Patients using Meloxicam simultaneously with sulfonylurea or nateganid should be closely monitored on the risk of hypoglycemia.

There is no clinical directly muticism with antacids, cimetidine and digoxin drugs.

Children

Interactive studies have not been conducted in children.