Bi-ksikam - instructions for use, dose, side effects, contraindications

Excipients: meglumine (N-methylglucamine) - 9.375 mg; glycofurol - 150.0 mg; Pluronic F-68 (Poloxamer 188) - 75.0 mg; sodium chloride - 4.5 mg; glycine - 7.5 mg; sodiumhydroxide (1M sodium hydroxide solution) 0.228 mg; water for injection - a sufficient amount to obtain a solution of 1.5 ml.

Description:Transparent solution of yellow with a green tint of color.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug - NSAIDs

ATX: & nbsp

M.01.A.C.06 Meloksikam

M.01.A.C Oksikamy

Pharmacodynamics:Meloksikam - non-steroidal anti-inflammatory drug, which has anti-inflammatory, analgesic and antipyretic effect. The anti-inflammatory effect is associated with the inhibition of the enzymatic activity of cyclooxygenase-2 (COX-2), involved in the synthesis of prostaglandins in the inflammatory region. Less meloxicam It acts on cyclooxygenase-1 (COX-1) involved in prostaglandin synthesis, protecting the mucosa of the gastrointestinal tract (GIT) and participate in the regulation of blood flow in the kidney.

Pharmacokinetics:

Absorption

Meloksikam is completely absorbed after intramuscular injection. The relative bioavailability is almost 100%. Therefore, when switching from an injection to an oral form, the dose is not required.After administration of 15 mg of the drug intramuscularly, the maximum plasma concentration of Cmax is 1.62 μg / ml, while the time to achieve it (TCmax) is approximately 60 minutes.

Distribution

Meloxicam binds well to plasma proteins, especially albumin (99%). It penetrates into the synovial fluid, the concentration in the synovial fluid is approximately 50% of the concentration in the plasma. The volume of distribution is low, an average of 11 liters. Interindividual differences account for 30-40%.

Metabolism

Meloksikam is almost completely metabolized in the liver with the formation of 4 pharmacologically inactive derivatives. The main metabolite, 5'-carboxymeloxicam (60% of the dose value), is formed by oxidation of the intermediate metabolite, 5'-hydroxymethylmeloxicam, which is also excreted, but to a lesser extent (9% of the dose value). In vitro studies have shown that in this an important role is played by CYP2C9, the isozyme CYP3A4 has an additional significance. In the formation of the other two metabolites (which constitute, respectively, 16% and 4% of the dose), peroxidase takes part, the activity of which probably varies individually.

Excretion

It is excreted equally through the intestines and kidneys, mainly in the form of metabolites.In the unchanged form, less than 5% of the daily dose is excreted through the intestine, in the unchanged form of the urine the drug is detected only in trace amounts. The average half-life (T1 / 2) of meloxicam is 20 hours. Plasma clearance is an average of 8 ml / min. Meloksikam demonstrates a linear pharmacokinetics in doses of 7.5-15 mg when administered intramuscularly.

Liver and / or kidney failure

Lack of liver function, as well as mild to moderate renal failure, does not significantly affect the pharmacokinetics of meloxicam. In terminal renal failure, an increase in the volume of distribution can lead to higher concentrations of free meloxicam, so in these patients the daily dose should not exceed 7.5 mg.

Elderly patients

In elderly patients, the mean plasma clearance during the steady state of pharmacokinetics is slightly lower than in young patients.

Indications:

Symptomatic treatment of pain syndrome and inflammation with: rheumatoid arthritis, osteoarthritis, ankylosing spondylitis.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of application, the progression of the disease is not affected.

Contraindications:

- Hypersensitivity to meloxicam or any component of the drug;

- Complete or incomplete combination of bronchial asthma, recurrent polyposis of the nasal mucosa and paranasal sinuses and intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (including in history);

- Stomach ulcer and duodenal ulcer in the stage of exacerbation;

- Active gastrointestinal bleeding;

- Exacerbation of inflammatory bowel diseases (ulcerative colitis, Crohn's disease);

- Severe hepatic impairment or active liver disease;

- Severe renal insufficiency (creatinine clearance less than 30 ml / min) in patients not undergoing hemodialysis, progressive kidney disease, including confirmed hyperkalemia;

- Cerebrovascular bleeding or other bleeding;

- Severe uncontrolled heart failure;

- The period after aortocoronary shunting;

- Children and adolescence under 18 years.

- Pregnancy, breastfeeding.

Carefully:

- Diseases of the gastrointestinal tract in history, the presence of Helicobacter pylori infection;

congestive heart failure;

- renal failure (creatinine clearance 30-60 ml / min);

- cardiac ischemia;

- cerebrovascular diseases;

- dyslipidemia / hyperlipidemia;

- diabetes;

- concomitant therapy with the following drugs: anticoagulants, oral glucocorticoids, antiaggregants, selective serotonin reuptake inhibitors;

- diseases of peripheral arteries;

- elderly age;

- long-term use of non-steroidal anti-inflammatory drugs NSAIDs;

- Smoking;

- frequent use of alcohol;

- Severe somatic diseases.

Pregnancy and lactation:

Safety of use during pregnancy of this drug is not proven. The effect of delayed synthesis of prostaglandins on embryogenesis during the first two trimesters of pregnancy is not clear. In the last trimester of pregnancy, the mechanism of action of meloxicam is characterized by inhibition of labor,premature closure of Ductus arteriosus Botalli in the fetus, a predisposition to bleeding in the mother and child increases, and the risk of edema in the mother is increased. Meloksikam in small quantities penetrates into the mother's milk, and in the case of breastfeeding meloxicam can be detected in the infant's plasma.

Given this information, the drug is contraindicated during pregnancy and breastfeeding.

As a preparation inhibiting the synthesis of cyclooxygenase / prostaglandin, meloxicam can affect fertility, and therefore is not recommended for women who have difficulty with conception. In this regard, women who are undergoing examination in this regard, it is recommended to cancel the drug.

Dosing and Administration:

Intramuscularly.

Intramuscular injection of the drug is indicated only during the first 2-3 days. Further treatment is continued with the use of oral forms (tablets). The recommended dose is 7.5 mg or 15 mg once a day, depending on the intensity of pain and the severity of the inflammatory process.

The drug is administered via a deep intramuscular injection.The drug can not be administered intravenously.

Given the possible incompatibility, the contents of the ampoules of the drug should not be mixed in one syringe with other medications. In patients with an increased risk of adverse reactions and with severe renal failure who are on hemodialysis, the dose should not exceed 7.5 mg per day.

The maximum recommended daily dose is 15 mg.

Impaired renal function

In patients with severe renal failure who are on hemodialysis, the dose should not exceed 7.5 mg per day.

Combined application. Do not use the drug simultaneously with other NSAIDs. The total daily dose of meloxicam, used in the form of tablets, suppositories, suspension for ingestion and injection, should not exceed 15 mg.

Side effects:

The following side effects are listed according to the frequency of their occurrence: very often (≥ 1/10), often (≥1 / 100 - <1/10), infrequently (≥1 / 1000 - <1/100), rarely ( ≥1 / 10000 - <1/1000), very rarely (<1/10000); not installed.

From the gastrointestinal tract: often - dyspepsia, including abdominal pain, diarrhea, nausea, vomiting; infrequently - latent or obvious gastrointestinal bleeding, gastritis, stomatitis, constipation, bloating,eructation; rarely - gastric and duodenal ulcer, colitis, esophagitis.

From the liver and bile ducts: infrequently - transient changes in liver function (for example, increased activity of transaminases, bilirubin); very rarely - hepatitis.

From the nervous system: often - headache; infrequently - dizziness, drowsiness.

From the side of the psyche: rarely - a change in mood; not established - confusion, disorientation.

On the part of the organs of sight, hearing: infrequently - vertigo; rarely - conjunctivitis, impaired vision, including blurred vision, tinnitus.

From the urinary system: infrequently - changes in renal function (increased serum creatinine and / or urea levels), impaired urination, including acute urinary retention; very rarely acute renal failure.

From the side of the blood and lymphatic system: rarely - changes in the number of blood cells, including changes in the leukocyte formula, anemia, leukopenia, thrombocytopenia.

From the immune system: not established - anaphylactic shock, anaphylactoid / anaphylactic reactions.

From the cardiovascular system: infrequently - increased blood pressure; a sense of "tide" of blood to the face; rarely - a feeling of palpitations.

From the respiratory system: rarely - bronchial asthma in patients with allergy to acetylsalicylic acid and other NSAIDs.

From the skin and subcutaneous fat: infrequently - angio edema, skin rash, itching; rarely - toxic epidermal necrolysis, Stevens-Johnson syndrome, urticaria; very rarely - bullous dermatitis, erythema multiforme; not established - the reaction of photosensitization.

General disorders and disorders at the site of administration: often - pain and swelling at the injection site, infrequently - swelling.

Overdose:

Data on cases of overdose accumulated insufficiently. Presumably, symptoms typical of overdose with NSAIDs will be present in severe cases: drowsiness, impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, changes in blood pressure, respiratory arrest, asystole.

Antidote is unknown, in case of an overdose of the drug should be symptomatic therapy.

Interaction:

- Other inhibitors of prostaglandin synthesis, including glucocorticoids and salicylates, when taken concomitantly with meloxicam, increase the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding (due to synergism of action) and therefore are not recommended. Simultaneous reception with other NSAIDs is not recommended.

- Selective serotonin reuptake inhibitors - increased risk of gastrointestinal bleeding.

- Lithium preparations: NSAIDs increase the concentration of lithium in the plasma by decreasing the renal excretion of lithium. The concentration of lithium in plasma can reach toxic values. The combined use of lithium and NSAIDs is not recommended. If necessary, such combination therapy should monitor the concentration of lithium in the plasma at the beginning of treatment, when choosing a dose and canceling meloxicam.

- Methotrexate: meloxicam can reduce the tubular secretion of methotrexate and thus increase the concentration of methotrexate in the blood plasma. In this regard, patients receiving high doses of methotrexate (more than 15 mg per week), concomitant use with meloxicam is not recommended.The risk of interaction with simultaneous use of methotrexate and meloxicam is also possible in patients receiving low doses of methotrexate, especially in patients with impaired renal function. If necessary, combined therapy should monitor the blood formula and kidney function. Care should be taken if meloxicam and methotrexate apply simultaneously for 3 days, because the concentration of methotrexate in the plasma may increase and, as a consequence, toxic effects may occur. Simultaneous use of meloxicam did not affect the pharmacokinetics of methotrexate at a dose of 15 mg per week, but it should be taken into account that the hematological toxicity of methotrexate is enhanced by the simultaneous administration of meloxicam.

- Contraception: Earlier reports of a decrease in the effectiveness of intrauterine contraceptives in the use of NSAIDs.

- Diuretics: The use of meloxicam increases the risk of acute renal failure in patients with dehydration. In patients receiving meloxicam and diuretics, adequate hydration should be maintained.

- Antihypertensive drugs (for example, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, vasodilators, diuretics): meloxicam reduce the effect of antihypertensive drugs, due to the inhibition of prostaglandins, which have vasodilating properties.

- Joint application of meloxicam and angiotensin II receptor antagonists (as well as ACE inhibitors) enhances the effect of reducing glomerular filtration. In patients with impaired renal function, this can lead to the development of acute renal failure.

- Meloksikam, having an effect on renal prostaglandins, can enhance nephrotoxicity cyclosporine. In the case of combined therapy, kidney function should be monitored.

With the simultaneous use of meloxicam and antacids, cimetidine, digoxin or furosemide, no significant pharmacokinetic interactions were identified.

It is impossible to exclude the possibility of interaction with oral hypoglycemic agents.

When used in combination with meloxicam, drugs that have a known ability to inhibit CYP2C9 and / or CYP3A4 (or are metabolized byparticipation of these enzymes), the possibility of pharmacokinetic interaction should be taken into account.

Special instructions:

Precautions for use

Care should be taken when treating patients with gastrointestinal (GI) diseases in history. Such patients should be under regular control, because of the risk of erosive-ulcerative lesions, bleeding from the gastrointestinal tract. The consequences of these complications are generally more serious in the elderly. Particular attention should be given to patients reporting the development of adverse events from the skin and mucous membranes. In such cases, the issue of discontinuing the use of Bi-xicam should be considered.

Like other NSAIDs, Bi-xicam may increase the risk of developing serious cardiovascular thrombosis, myocardial infarction, angina attack, possibly fatal. This risk increases with prolonged use of the drug, as well as in patients with the aforementioned diseases in the history and predisposed to such diseases.

NSAIDs inhibit the synthesis of prostaglandins in the kidneys, which are involved in maintaining renal perfusion.The use of NSAIDs in patients with reduced renal blood flow or a reduced volume of circulating blood can lead to decompensation of the secretive renal failure. After the abolition of NSAIDs, the kidney function is usually restored to its original level. The elderly patients with dehydration, congestive heart failure, liver cirrhosis, nephrotic syndrome or acute renal dysfunction, patients taking diuretics simultaneously, as well as patients who undergo serious surgical interventions that lead to hypovolemia. In such patients at the beginning of therapy, diuresis and renal function should be carefully monitored. The use of NSAIDs in conjunction with diuretics can lead to a delay in sodium, potassium and water, as well as a decrease in natriuretic action of diuretics. As a result, predisposing patients may have signs of heart failure or hypertension. Therefore, careful monitoring of the condition of such patients is needed, and adequate hydration should be maintained.Before the beginning of treatment it is necessary to study the function of the kidneys. In the case of combined therapy, kidney function should also be monitored. When using the drug, as well as most NSAIDs, it is possible to occasionally increase the activity of transaminases in the blood serum or other indicators of liver function. In most cases, this increase was small and transient. If the changes identified are significant or do not decrease over time, the drug should be withdrawn and monitored for laboratory changes identified.

Weakened or debilitated patients can tolerate undesirable events worse, which is why such patients should be carefully observed. Like other NSAIDs, B-ksikam can mask the symptoms of a major infectious disease.

Effect on the ability to drive transp. cf. and fur:Special studies on the effect of the drug on the ability to drive vehicles and mechanisms were not carried out. However, when driving and working with machinery, one should take into account the possibility of developing dizziness, drowsiness, visual impairment, or other side effects of the CNS.Patients should be careful when driving and controlling machinery.

Form release / dosage:Solution for intramuscular injection 15 mg / 1.5 ml.

Packaging:

For 1.5 ml in neutral glass ampoules with a capacity of 2 ml.

3 or 5 ampoules per box or a pack of cardboard with partitions or a liner of paper.

By 3 or 5 ampoules per contour cell packaging made of polyvinyl chloride film and foil, or without foil.

1 circuit cell pack for 3 or 5 ampoules, or 2 contour packs of 5 ampoules are placed in a pack of cardboard.

In each box or pack, the instructions for use and the opener for opening ampoules or the ampoule scarifier are put.

When using ampoules with incisions or a fracture ring, a scarifier ampoule or a knife for opening ampoules is not inserted.

Storage conditions:At a temperature of no higher than 30 ° C. Keep out of the reach of children.

Shelf life:5 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002280

Date of registration:22.10.2013 / 02.10.2015

Expiration Date:22.10.2018

The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Information update date: & nbsp05.02.2018

Illustrated instructions

Instructions

Bi-ksikam (Bi-Xikam)