Movalis, pills 15mg, 10pcs

Composition

Active ingredient:

meloxicam 15 mg;

Auxiliary substances:

sodium citrate;

lactose;

MCC;

povidone (collidone 25),

colloidal silicon dioxide;

crospovidone;

magnesium stearate.

Pharmacological action

Pharmaceutical Group:

NSAIDs.

Pharmaceutical action:  

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

In vivo, meloxicam inhibits prostaglandin synthesis at the site of inflammation to a greater extent than in the gastric mucosa or kidneys. These differences are associated with more selective inhibition of cyclooxygenase-2 (COX-2) compared to cyclooxygenase-1 (COX-1). It is believed that COX-2 inhibition provides a therapeutic effect of NSAIDs, while inhibition of the constantly present COX-1 isoenzyme can cause side effects from the stomach and kidneys.

The selectivity of meloxicam for COX-2 was confirmed in various test systems, both in vitro and ex vivo. The selective ability of meloxicam to inhibit COX-2 has been shown when used as an in vitro human whole blood test system. Ex vivo studies showed that meloxicam (at doses of 7.5 and 15 mg) more actively inhibited COX-2, exerting a greater inhibitory effect on the production of prostaglandin E2 stimulated by lipopolysaccharide (COX-2 controlled reaction) than on the production of thromboxane involved in blood clotting (COX-1 controlled reaction). These effects were dose-dependent.

Ex vivo studies showed that meloxicam at the recommended doses did not affect platelet aggregation and bleeding time, in contrast to Indometacin, diclofenac, ibuprofen and naproxen, which significantly suppressed platelet aggregation and increased bleeding time. In clinical studies, gastrointestinal (GI) side effects were generally less likely to occur with meloxicam 7.5 and 15 mg than with other NSAIDs compared. This difference in the frequency of gastrointestinal side effects is mainly due to the fact that when taking meloxicam, such phenomena as dyspepsia, vomiting, nausea, and abdominal pain were less often observed. The frequency of perforations in the upper gastrointestinal tract, ulcers and bleeding associated with the use of meloxicam was low and depended on the dose of the drug.

Pharmacokinetics:

Meloxicam is well absorbed from the gastrointestinal tract, as evidenced by its high absolute oral bioavailability (89%).

With a single dose of Movalis in tablet form, the average maximum plasma concentration is reached within 5-6 hours. With repeated use, a stable state of pharmacokinetics is achieved within 3 to 5 days.

The range of differences between the maximum (Cmax) and basal concentrations (Cmin) of the drug during the steady state of pharmacokinetics after taking it once a day is relatively small and is 0.4–1.0 mcg/ml for a dose of 7.5 mg, and 0.8 – 2.0 mcg/ml for a dose of 15 mg. The maximum concentration in plasma during the steady state of pharmacokinetics is reached within 5-6 hours when taking tablets.

Concentrations of the drug after continuous use of the drug for more than 6 months are similar to those observed after 2 weeks of oral use of 15 mg per day. If taken for more than 6 months, such differences are unlikely.

Simultaneous food intake does not affect the absorption of the drug.

Movalis suppositories:

Suppositories have been shown to be bioequivalent to tablets. The maximum concentration of the drug in plasma during the steady state of pharmacokinetics is reached approximately 5 hours after the drug is administered. The ranges of differences between maximum (Cmax) and basal concentrations (Cmin) are similar for tablets and suppositories.

Distribution Meloxicam binds well to plasma proteins (with albumins – 99%) Meloxicam penetrates the synovial fluid; local concentrations are approximately 50% of plasma concentrations. The volume of distribution is low, averaging 11 liters. Individual fluctuations – 30-40%.

Metabolism Meloxicam is almost completely metabolized in the liver to form 4 pharmacologically inactive derivatives determined in the urine. The main metabolite,5’ – carboxymeloxicam (60% of the dose), is formed by the oxidation of an intermediate metabolite,5’ – hydroxymethylmeloxicam, which is also excreted, but to a lesser extent (9% of the dose). In vitro studies have shown that CYP 2C9 plays an important role in this metabolic transformation, and the CYP 3A4 isoenzyme plays an additional role. The formation of the other two metabolites (which make up 16% and 4% of the drug dose, respectively) involves peroxidase, the activity of which probably varies individually.

It is excreted equally in the faeces and urine, mainly in the form of metabolites. In unchanged form, less than 5% of the daily dose is excreted in the feces, and in the urine in unchanged form, the drug is detected only in trace amounts. The average elimination half-life of meloxicam is 20 hours.

The average plasma clearance is 8 ml/min. Meloxicam demonstrates linear pharmacokinetics at doses of 7.5 – 15 mg when taken orally.

Insufficient liver and/or kidney function

Hepatic insufficiency, as well as mild or moderate renal insufficiency, does not significantly affect the pharmacokinetics of meloxicam.

In end-stage renal failure, increased volume of distribution may lead to higher concentrations of free meloxicam, so the daily dose should not exceed 7.5 mg in these patients.

Elderly patients

In elderly patients, the mean plasma clearance during steady-state pharmacokinetics is slightly lower than in young patients. During the study of meloxicam in children, the pharmacokinetics of the drug was studied at doses used at the rate of 0.25 mg/kg. When comparing the indicators in children of different ages (2-6 years, n = 7 and 7-14 years, n = 11), a tendency was found to lower the maximum plasma concentration (Cmax, -34%) and AUC0 – ∞ (-28%) in young children, and the drug clearance (adjusted for body weight) in this group of children was higher. Plasma concentrations of meloxicam in older children and adults are similar. In children of both age groups, the plasma half-lives of meloxicam were similar (13 hours) and slightly shorter than in adults (15-20 hours).

Indications

Symptomatic treatment: osteoarthritis (osteoarthritis, degenerative joint diseases), rheumatoid arthritis, ankylosing spondylitis.

Use during pregnancy and lactation

Although no teratogenic effects have been reported in preclinical trials, Movalis should not be administered during pregnancy and lactation.

Contraindications

• hypersensitivity to the active ingredient or auxiliary components of the drug. There is a possibility of cross-sensitivity to acetylsalicylic acid and other NSAIDs;
• the symptoms of asthma, nasal polyps, angioedema or urticaria after ingestion of acetylsalicylic acid or other NSAIDs in history;
• peptic ulcer/perforation of stomach and duodenum in the acute stage or recently transferred;
• Crohn’s disease or ulcerative colitis in the acute stage;
• severe hepatic impairment;
• severe renal insufficiency (if not possible hemodialysis, Cl creatinine less than 30 ml/min, and when confirmed hyperkalemia), progressive kidney disease;
• acute gastrointestinal bleeding recent cerebrovascular bleeding or established diagnosis of diseases of the blood coagulation system;
• severe uncontrolled heart failure;
• pregnancy;
• breastfeeding;
• the treatment of perioperative pain in the conduct of bypass grafting of the coronary arteries.

Side effects

From the side of hematopoietic organs:  changes in the number of blood cells, including changes in the leukocyte formula, leukopenia, thrombocytopenia, and anemia. A predisposing factor for the occurrence of cytopenia seems to be the simultaneous use of potentially myelotoxic drugs, in particular methotrexate.

From the immune system:  anaphylactic shock, anaphylactoid / anaphylactic reactions, other immediate hypersensitivity reactions.

From the central nervous system:  headache, dizziness, tinnitus, drowsiness, confusion, disorientation, mood swings.

From the gastrointestinal tract:  gastrointestinal perforation, latent or overt gastrointestinal bleeding, possibly fatal, gastroduodenal ulcers, colitis, gastritis, esophagitis, stomatitis, abdominal pain, dyspepsia, diarrhea, nausea, vomiting, constipation, bloating, belching, transient changes in liver function indicators (for example, increased transaminase or bilirubin activity), hepatitis.

From the side of the skin and skin appendages:  toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, bullous dermatitis, erythema multiforme, pruritus, skin rash, urticaria, photosensitization.

Respiratory system disorders:  bronchial asthma in patients allergic to acetylsalicylic acid or other NSAIDs.

From the CCC side: raising Blood pressure, palpitations, flushing of the face, swelling.

From the genitourinary system: acute renal failure, changes in renal function indicators (increased serum creatinine and/or urea), urinary disorders, including acute urinary retention.

From the side of the visual organ: conjunctivitis, visual disturbances, including blurred vision.

Interaction

Other PG synthesis inhibitors, including HA and salicylates, when taken concomitantly with meloxicam increase the risk of gastrointestinal ulceration and gastrointestinal bleeding (due to the synergy of action) and therefore their combination is not recommended. Concomitant use with other NSAIDs is not recommended.

SSRIs — increased risk of gastrointestinal bleeding.

Lithium preparations-NSAIDs increase the concentration of lithium in plasma, by reducing its excretion by the kidneys. It is recommended to monitor the concentration of lithium during the appointment of Movalis®, when changing the dose of lithium preparations and their cancellation.

Methotrexate-NSAIDs reduce the tubular secretion of methotrexate, thereby increasing its plasma concentration and hematological toxicity, while the pharmacokinetics of methotrexate do not change. In this regard, simultaneous use of Movalis® and methotrexate at a dose of more than 15 mg/week is not recommended. The risk of interaction between NSAIDs and methotrexate may also occur in patients using low-dose methotrexate, especially in patients with impaired renal function. Therefore, constant monitoring of the number of blood cells and kidney function is necessary.

Concomitant 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 increases with simultaneous use of NSAIDs.

With the combined use of meloxicam and methotrexate for 3 days, the risk of increased toxicity of the latter increases.

Contraception-NSAIDs reduce the effectiveness of intrauterine contraceptive devices.

Diuretics-the use of NSAIDs in case of dehydration of patients is associated with the risk of acute renal failure.

Adequate hydration should be maintained in patients receiving Movalis and diuretics. Before starting treatment, a study of renal function is necessary.

Antihypertensive drugs (beta-blockers, ACE inhibitors, vasodilators, diuretics — – NSAIDs reduce the effect of antihypertensive drugs, due to the inhibition of PG, which has vasodilating properties.

Angiotensin II receptor antagonists, when co-administered 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. In the case of combination therapy, renal function should be monitored.

NSAIDs that affect the renal function PG, may increase the nephrotoxicity of cyclosporine.

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

The possibility of interaction with hypoglycemic drugs for oral use cannot be excluded.

No significant pharmacokinetic interactions were observed with concomitant use of antacids, cimetidine, digoxin, and furosemide.

How to take, course of use and dosage

Inside, while eating, with water or other liquid; rectally.

Osteoarthritis, rheumatoid arthritis — 7.5 mg / day. If necessary, this dose can be increased to 15 mg / day. Depending on the therapeutic effect, this dose can be reduced to 7.5 mg / day.

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

In patients with an increased risk of adverse reactions, it is recommended to start treatment with a dose of 7.5 mg / day. For patients with severe renal insufficiency who are on hemodialysis, the dose should not exceed 7.5 mg / day.

Teenagers

The maximum dose for adolescents is 0.25 mg / kg.

As a rule, the drug should only be used in adolescents and adults (see the section “Contraindications”). The maximum recommended daily dose is 15 mg.

Rectal suppositories are recommended to be used at a dose of 7.5 mg once a day. In more severe cases, it is possible to use candles in a dose of 15 mg.

Due to the fact that the risk of adverse reactions depends on the size of the dose and the duration of use, the drug should be used for as short a time as possible at the lowest possible effective dose.

Combined use. The total daily dose of Movalis®, used in the form of tablets, suppositories, injections, should not exceed 15 mg.

Overdose

Treatment: gastric lavage and standard auxiliary measures.

The specific antidote is unknown.

During clinical trials, colestyramine was shown to accelerate the elimination of meloxicam.

Special instructions

Movalis should be used with caution in concomitant diseases of the upper gastrointestinal tract, as well as in patients receiving anticoagulant therapy. In case of peptic ulcer or gastrointestinal bleeding, the drug should be discontinued. When prescribing Movalis, gastrointestinal bleeding, ulceration or perforation may develop both if patients have a history of previous symptoms and episodes of similar gastrointestinal complications, and without them. In the elderly, there is a more severe course of these complications.

Special attention should be paid to patients who have experienced undesirable effects from the skin and mucous membranes, in such cases, discontinuation of Movalis should be considered.

NSAIDs inhibit the synthesis of renal prostaglandins, which are involved in maintaining sufficient levels of renal blood flow. The use of NSAIDs in patients with reduced renal blood flow and BCC may accelerate renal decompensation, but after discontinuation of NSAID therapy, renal function usually returns to its previous level.

The risk of adverse reactions is particularly high in patients with dehydration, congestive heart failure, cirrhosis of the liver, nephrotic syndrome and severe kidney diseases, in patients receiving diuretics, as well as in patients who have undergone significant surgery that led to hypovolemia. Such patients need careful monitoring of their diuresis and renal function from the very beginning of treatment.

In rare cases, an increase in serum transaminases or changes in other indicators of liver function have been reported. In most cases, deviations from the norm were minor and transient. If more pronounced or persistent violations of liver function indicators occur, stop taking Movalis and conduct control laboratory tests. In patients with clinically non-progressive cirrhosis of the liver, no dose reduction is required.

Debilitated and emaciated patients may suffer more severe side effects, and such patients should be closely monitored. Movalis should be used with caution in elderly patients who are more likely to have impaired kidney, liver or heart function. NSAIDs can promote sodium, potassium, and water retention and weaken the natriuretic effect of diuretics. As a result, in the presence of predisposing factors, the use of NSAIDs can lead to the progression of heart failure and hypertension.

Influence on the ability to drive motor vehicles and manage mechanisms

During treatment, if visual acuity disorders, dizziness or drowsiness occur, it is necessary to refrain from driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Tablets

Storage conditions

Store in a dark place, at a temperature not exceeding 25°C.

Shelf life

5 years

Active ingredient

Meloxicam

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Osteoarthritis and Arthritis, Osteoarthritis, Rheumatoid Arthritis