Meloflex Rompharm - instructions for use, dose, side effects, contraindications

Excipients: meglumine 6.250 mg, glycofurfural 100,000 mg, poloxamer 188-50,000 mg, glycine 5,000 mg, sodium chloride 3.500 mg, 1M sodium hydroxide solution to pH 8.6-9.0, water for injection up to 1,000 ml.

Description:Yellow with a greenish shade of clear solution.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drugs (NSAIDs)

ATX: & nbsp

M.01.A.C.06 Meloksikam

M.01.A.C Oksikamy

Pharmacodynamics:

Meloxicam is a non-steroidal anti-inflammatory drug, it belongs to the derivatives of enolic acid and has an anti-inflammatory, analgesic and antipyretic effect. The pronounced anti-inflammatory effect of meloxicam is established on all standard models of inflammation. The mechanism of action of meloxicam is its ability to inhibit the synthesis of prostaglandins - known inflammatory mediators.

In vivo meloxicam inhibits the synthesis of prostaglandins at the site of inflammation to a greater extent than in the mucous membrane of the stomach or kidneys.

These differences are associated with a more selective inhibition of cyclooxygenase-2 (COX-2) compared to cyclooxygenase-1 (COX-1). It is believed that inhibition of COX-2 provides a therapeutic effect of NSAIDs, whereas inhibition of the constantly present isoenzyme COX-1 can cause side effects on the part of the stomach and kidneys.

The selectivity of meloxicam for COX-2 has been confirmed in various test systems, both in vitro and ex vivo.

The selective ability of meloxicam to inhibit COX-2 is shown when using human whole blood in vitro as a test system. Determined that meloxicam (in doses of 7.5 and 15 mg) more actively inhibited COX-2, having a greater inhibitory effect on the production of prostaglandin E₂, stimulated by lipopolysaccharide (a reaction controlled by COX-2) than by the production of thromboxane participating in the coagulation process (a reaction controlled by COX-1). These effects depended on the size of the dose.

In ex vivo studies, it has been shown that meloxicam in recommended doses did not affect the platelet aggregation and bleeding time.

In clinical trials, side effects from the gastrointestinal tract as a whole occurred less frequently with the use of meloxicam in doses of 7.5 and 15 mg than with other NSAIDs with which the comparison was made. This difference in the frequency of side effects from the gastrointestinal tract is mainly due to the fact that when taking meloxicam, there were less frequent phenomena such as dyspepsia, vomiting, nausea, abdominal pain. The frequency of perforations in the upper gastrointestinal tract, ulcers and bleeding that were associated with the use of meloxicam,was low and depended on the magnitude of the dose of the drug.

Pharmacokinetics:

Suction

Meloksikam is completely absorbed after intramuscular injection. The relative bioavailability compared with the bioavailability with oral administration is almost 100%. Therefore, when switching from injectable to oral forms, dose adjustment is not required. After administration of 15 mg of the drug intramuscularly, the maximum plasma concentration is 1.6-1.8 μg / ml and is reached after approximately 60-90 minutes.

Distribution

Meloxicam binds very 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 (V_d) low, an average of 11 liters. Interindividual differences account for 7-20%.

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 degree (9% of the dose value).In vitro studies have shown that CYP2C9 plays an important role in this metabolic transformation, the CYP3A4 isoenzyme plays an additional role. 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 unaltered form with feces less than 5% of the daily dose is excreted, in the urine in unchanged form the drug is found only in trace amounts. Mean half-life (T_1/2) meloxicam is 13-25 hours.

Plasma clearance is an average of 7-12 ml / min after a single application. Meloksikam demonstrates a linear pharmacokinetics in doses of 7.5-15 mg when administered or administered intramuscularly.

Pharmacokinetics in special clinical cases

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.The rate of excretion of meloxicam from the body is much higher in patients with moderate renal insufficiency. Meloksikam worse binds to plasma proteins in patients with terminal renal failure. 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

Older patients have similar pharmacokinetic parameters in comparison with young patients. In elderly patients, the average plasma clearance during the equilibrium state of pharmacokinetics is slightly lower than in young patients. Older women have higher AUC values (area under the concentration-time curve) and a longer half-life, compared to young patients of both sexes.

Indications:

Start therapy and short-term symptomatic treatment with:

- osteoarthritis (arthrosis, degenerative joint diseases);

- rheumatoid arthritis;

ankylosing spondylitis;

- other inflammatory and degenerative diseases of the musculoskeletal system,such as arthropathy, dorsopathy (for example, sciatica, pain in the lower back, shoulder periarthritis), accompanied by pain.

Contraindications:

- Hypersensitivity to the active ingredient or auxiliary components;

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

- erosive and ulcerative lesions of the stomach and duodenum in the acute stage or recently transferred;

- Inflammatory bowel disease - Crohn's disease or ulcerative colic in the acute stage;

- severe hepatic and cardiac failure;

- Severe renal insufficiency (if hemodialysis is not performed: creatinine clearance less than 30 ml / mi, as well as with confirmed hyperkalemia);

active liver disease;

- active gastrointestinal bleeding, recent cerebrovascular bleeding or an established diagnosis of coagulation system diseases;

- Children's age (up to 18 years);

- Pregnancy;

- the period of breastfeeding;

- therapy of perioperative pain during coronary artery bypass grafting;

- concomitant therapy with anticoagulants (due to the risk of intramuscular hematoma formation).

Carefully:

- Diseases of the gastrointestinal tract (GIT) in the anamnesis (presence of H. pylori infection);

- Chronic heart failure (CHF);

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

- Ischemic heart disease (CHD);

- cerebrovascular diseases;

- dyslipidemia / hyperlipidemia;

- diabetes;

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

- diseases of peripheral arteries;

- elderly age;

- long-term use of NSAIDs;

- Smoking;

- frequent use of alcohol.

Pregnancy and lactation:

Application of the drug Meloflex Rompharm is contraindicated during pregnancy.

Suppressing the synthesis of prostaglandins can have an undesirable effect on pregnancy and fetal development.

It is known that NSAIDs penetrate into breast milk, so Meloflex Rompharm is contraindicated in the period of breastfeeding.At the time of taking the drug, you must stop breastfeeding.

As a drug that inhibits COX / prostaglandin synthesis, Meloflex Rhompharm can affect fertility, and therefore is not recommended for women planning a pregnancy. Meloksikam can lead to a delay in ovulation. In this regard, women who have problems with conception and undergoing examination for such problems, it is recommended to cancel the drug Meloflex Rompharm.

Dosing and Administration:

Osteoarthritis with pain syndrome: 7.5 mg per day. If necessary, this dose can be increased to 15 mg per day.

Rheumatoid arthritis: 15 mg per day. Depending on the therapeutic effect, this dose can be reduced to 7.5 mg per day.

Ankylosing spondylitis: 15 mg per day. Depending on the therapeutic effect, this dose can be reduced to 7.5 mg per day.

In patients with an increased risk of adverse reactions (a history of gastrointestinal disease, the presence of risk factors for cardiovascular disease), it is recommended to start treatment with a dose of 7.5 mg per day (see Special instructions).

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

General recommendations

Since the potential risk of adverse reactions depends on the dose and duration of treatment, the lowest possible dose and duration of use should be used. The maximum recommended daily dose is 15 mg.

Combined application

Do not use the drug simultaneously with other NSAIDs. The total daily dose of meloxicam, used in the form of different dosage forms, should not exceed 15 mg.

Intramuscular injection of the drug is indicated only during the first few days of therapy. Further treatment is continued with the use of oral dosage forms.

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 drug should not be mixed in the same syringe with other medicines.

Side effects:

The following side effects are described, the relationship of which with the use of the drug was regarded as possible. Side effects, registered with postmarketing application, the connection of which with taking the drug was regarded as possible, marked with a "*".Within the system-organizational classes, the following categories are used for the incidence of side effects: 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.

Violations from the blood and lymphatic system:

Infrequently: anemia;

Rarely: leukopenia, thrombocytopenia, changes in the number of blood cells, including changes in the leukocyte formula.

Immune system disorders:

Infrequently, other immediate-type hypersensitivity reactions *;

Not established - anaphylactic shock *, anaphylactoid reactions *.

Disorders of the psyche:

Rarely is a mood change *;

Not established - confusion of consciousness *, disorientation *.

Impaired nervous system:

Often - a headache;

Infrequent - dizziness, drowsiness.

Disturbances on the part of the organs of sight. hearing and labyrinthine disorders:

Infrequently - vertigo;

Rarely - conjunctivitis *, visual impairment, including blurred vision *, tinnitus.

Violations from the heart and blood vessels:

Infrequent - increased blood pressure, a feeling of "tide" of blood to the face;

Rarely - palpitations.

Disturbances from the respiratory system:

Rarely, bronchial asthma in patients with allergy to acetylsalicylic acid and other NSAIDs.

Disorders from the gastrointestinal tract:

Often - abdominal pain, indigestion, diarrhea, nausea, vomiting;

Infrequent - latent or obvious gastrointestinal bleeding, gastritis *, stomatitis, constipation, bloating, eructation *;

Rarely gastroduodenal ulcers, colitis, esophagitis;

Very rarely - perforation of the gastrointestinal tract;

Disorders from the liver and bile ducts:

Infrequent - transient changes in liver function indicators (for example, increased activity of "liver" transaminases or bilirubin);

Very rarely - hepatitis *.

Disturbances from the skin and subcutaneous tissues:

Infrequent - angioedema, * skin itch, skin rash;

Rarely - toxic epidermal necrolysis *, Stevens-Johnson syndrome *, urticaria;

Very rarely - bullous dermatitis *, mulgiiform erythema *;

Not established - photosensitivity.

Disorders from the kidneys and urinary tract:

Infrequent: - Changes in renal function (increased serum creatinine and / or urea concentration), urination disorders, including acute urinary retention *;

Very rarely: acute renal failure *.

Violations of the genitals and mammary glands:

Infrequently - late ovulation *;

Not established - infertility in women *.

General disorders and disorders at the site of administration:

Often - pain and swelling at the injection site;

Infrequent - edema.

Joint application with drugs that depress the bone marrow (for example, methotrexate) can provoke cytopenia. Gastrointestinal bleeding, ulcer or perforation can lead to death.

As for other NSAIDs, the possibility of interstitial nephritis, glomerulonephritis, renal medullary necrosis, nephrotic syndrome is not ruled out.

Overdose:

Symptoms

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

Treatment

The antidote is not known. In case of an overdose of the drug, symptomatic therapy should be used. It is known that colestramine accelerates the excretion of meloxicam. Forced diuresis, alkalization of urine, hemodialysis are ineffective because of the high degree of binding of meloxicam to plasma proteins.

Interaction:

- Other inhibitors of prostaglandin synthesis, including glucocorticosteroids and salicylates - simultaneous reception with meloxicam increases the risk of ulceration in the gastrointestinal tract and gastrointestinal bleeding (due to the synergism of the action). Simultaneous reception with other NSAIDs is not recommended.

- Anticoagulants for oral administration, heparin for systemic use, thrombolytic agents - simultaneous reception with meloxicam increases the risk of bleeding. In the case of simultaneous use, careful monitoring of the blood coagulation system is necessary.

- Antiplatelet agents, serotonin reuptake inhibitors - simultaneous administration with meloxicam increases the risk of bleeding due to inhibition of platelet function. In the case of simultaneous use, careful monitoring of the blood coagulation system is necessary.

- Lithium preparations: NSAIDs increase the concentration of lithium in blood plasma,by reducing the excretion of it by the kidneys. Simultaneous use of meloxicam with lithium preparations is not recommended .. In case of the need for simultaneous use, careful monitoring of lithium concentration in the blood plasma is recommended during the whole course of lithium preparations.

- Methotrexate: NSAIDs decrease the secretion of methotrexate by the kidneys, thereby increasing its concentration in the blood plasma. The simultaneous use of meloxicam and methotrexate (at a dose of more than 15 mg per week) is not recommended. In the case of simultaneous use, careful monitoring of kidney function and the blood formula is necessary. Meloksikam may enhance hematological toxicity of methotrexate, especially in patients with impaired renal function.

- Contraception - There is evidence that NG1VP may reduce the effectiveness of intrauterine contraceptive devices, but this has not been proven.

- Diuretics - application of NSAID1 in case of dehydration of patients is accompanied by a risk of acute renal failure.

Hypotensive drugs (beta-blockers, angiotensin converting enzyme [ACE] inhibitors, vasodilators, diuretics). NSAIDs reduce the effect of antihypertensives, due to the inhibition of prostaglandins, which have vasodilating properties.

- Angiotensin II receptor antagonists, as well as ACE inhibitors when combined with NSAIDs increase the decrease in glomerular filtration, which can lead to the development of acute renal failure, especially in patients with impaired renal function.

- Kolestyramine, tying meloxicam in the gastrointestinal tract, leads to its faster excretion.

- Pemetrexed - with concomitant use of meloxicam and pemetrexed in patients with creatinine clearance from 45 to 79 ml / min, meloxicam should be discontinued five days before the start of pemetrexed and may be resumed 2 days after the end of admission. If there is a need for the combined use of meloxicam and pemetrexed, such patients should be closely monitored, especially with respect to myelosuppression and the occurrence of side effects from the gastrointestinal tract. In patients with creatinine clearance less than 45 ml / min, meloxicam is not recommended together with pemetrexed.

NSAIDs, acting on renal prostaglandins, can enhance the nephrotoxicity of cyclosporine.

When combined with meloxicam, drugs that have a known ability to inhibit CYP2C9 and / or CYP3A4 (or are metabolized by these enzymes), such as sulfonylureas or probenecid derivatives, pharmacokinetic interaction should be considered.

When combined with oral antidiabetic agents (for example, derivatives of sulfonylurea, nateglinide), interactions mediated by CYP2C9 are possible, which may lead to an increase in the concentration of both these drugs and meloxicam in the blood. Patients simultaneously taking meloxicam with preparations of sulfonylurea or nateglinide, should carefully monitor blood sugar levels because of the possibility of developing hypoglycemia.

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

Special instructions:

Patients suffering from diseases of the gastrointestinal tract should be observed regularly.If there is a ulcerative lesion of the gastrointestinal tract or gastrointestinal bleeding, the drug must be canceled.

Gastrointestinal ulcers, perforation or bleeding can occur during the use of NSAIDs at any time, as with the presence of alarming symptoms or information about serious gastrointestinal complications in the history, and in their absence. The consequences of these complications are generally more serious in the elderly.

When applying the drug, such serious skin reactions as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis can develop.

Therefore, special attention should be given to patients reporting the development of undesirable skin and mucous membrane phenomena, as well as hypersensitivity reactions to the drug, especially if similar reactions were observed during previous courses of treatment. The development of such reactions is observed, as a rule, during the first month of treatment. In the case of the appearance of the first signs of skin rash, changes in mucous membranes or other signs of hypersensitivity, the question of discontinuing the use of the drug should be considered.

Cases when taking NSAIDs increase the risk of developing serious cardiovascular thrombosis, myocardial infarction, an attack of angina pectoris, possibly with a fatal outcome are described. 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 latent renal failure. After the abolition of NSAIDs, the kidney function is usually restored to its original level. The elderly patients with dehydration, chronic heart failure, cirrhosis, nephrotic syndrome or acute renal dysfunction, patients concurrently taking diuretics, ACE inhibitors, angiotensin II receptor antagonists, as well as patients, who underwent 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 Meloflex Rompharm (as well as most other NSAIDs), an occasional increase in the activity of "hepatic" transaminases in the serum or other indicators of liver function is possible. 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 observed for identified laboratory changes.

Weakened or debilitated patients can tolerate undesirable events worse, which is why such patients should be carefully observed.

Like other NSAIDs, Meloflex Rhompharm can mask the symptoms of a major infectious disease.

As a preparation inhibiting the synthesis of cyclooxygenase / prostaglandin, Meloflex Rhompharm 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 Meloflex Rompharm.

In patients with mild or moderate renal failure (creatinine clearance more than 25 ml / min), dose adjustment is not required.

In patients with cirrhosis of the liver (compensated), dose adjustment is not required.

Effect on the ability to drive transp. cf. and fur:Special clinical studies of the influence of meloxicam on the ability to control the car 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 disorders from the central nervous system.During the period of treatment, patients need to be careful when driving vehicles and engaging in other potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:Solution for intramuscular injection 10 mg / ml.

Packaging:

For 1.5 ml of the drug in colorless ampoules with a capacity of 2 ml of hydrolytic class 1 glass with a ring for kink. A label is affixed to each ampoule.

For 3 or 5 ampoules are placed in contoured cell packs. On 1 contour acheikova packing together with the instruction on application place in a cardboard pack.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children!

Shelf life:

4 years.

Do not use after the expiration date!

Terms of leave from pharmacies:On prescription

Registration number:LP-000630

Date of registration:23.09.2011 / 04.10.2016

Expiration Date:Unlimited

The owner of the registration certificate:K.O. Ромфарм Компани С.Р.Л.K.O. Ромфарм Компани С.Р.Л. Romania

Manufacturer: & nbsp

S.C. ROMPHARM Company, S.R.L. Romania

Representation: & nbspROMFARM COMPANY ROMFARM COMPANY Romania

Information update date: & nbsp22.04.2018

Illustrated instructions

Instructions

Meloflex Rompharm (Meloflex Rompharm)