Movasin^® (Solution) Instructions for Use

Marketing Authorization Holder

Biocom Technology, LLC (Republic of Belarus)

Manufactured By

Sintez PJSC (Russia)

Contact Information

SINTEZ OJSC Kurgan Joint Stock Company of Medical Preparations and Products (Russia)

ATC Code

M01AC06 (Meloxicam)

Active Substance

Meloxicam (Rec.INN registered by WHO)

Dosage Forms

	Movasin®	Solution for intramuscular injection 10 mg/1 ml: amp. 1.5 ml 3 or 5 pcs.
		Tablets 7.5 mg: 10 or 20 pcs.
		Tablets 15 mg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Tablets round, flat-cylindrical, with a bevel, without a score, light yellow in color, slight marbling is allowed on the surface.

Excipients: povidone 12600 – 6 mg, lactose monohydrate – 52.5 mg, crospovidone (kollidon CL-M) – 4.5 mg, potato starch – 1.25 mg, talc – 4.5 mg, magnesium stearate – 1.5 mg, microcrystalline cellulose – up to 150 mg.

10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.

Tablets round, flat-cylindrical, with a bevel, with a score, light yellow in color, slight marbling is allowed on the surface.

Excipients: povidone 12600 – 12 mg, lactose monohydrate – 105 mg, crospovidone (kollidon CL-M) – 9 mg, potato starch – 2.5 mg, talc – 9 mg, magnesium stearate – 3 mg, microcrystalline cellulose – up to 300 mg.

10 pcs. – contour cell packs (1) – cardboard packs.
10 pcs. – contour cell packs (2) – cardboard packs.

Solution for intramuscular injection yellow with a greenish tint, transparent or slightly opalescent.

Excipients: glycofurol – 100 mg, glycine – 5 mg, meglumine – 6.25 mg, sodium hydroxide – 0.152 mg, sodium chloride – 3 mg, poloxamer 188 – 50 mg, water for injection – up to 1 ml.

1.5 ml – glass ampoules (3) – contour cell packs (1) – cardboard packs.
1.5 ml – glass ampoules (5) – contour cell packs (1) – cardboard packs.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID. It has analgesic, anti-inflammatory and antipyretic effects. The mechanism of action is associated with inhibition of prostaglandin synthesis as a result of selective suppression of the enzymatic activity of cyclooxygenase-2 (COX-2), which is involved in the biosynthesis of prostaglandins in the area of inflammation. When prescribed in high doses, with long-term use and individual characteristics of the body, selectivity towards COX-2 decreases. It suppresses the synthesis of prostaglandins in the area of inflammation to a greater extent than in the gastric mucosa or kidneys, which is associated with relatively selective inhibition of COX-2. It less often causes erosive and ulcerative diseases of the gastrointestinal tract. Meloxicam has a lesser effect on cyclooxygenase-1 (COX-1), which is involved in the synthesis of prostaglandins that protect the gastrointestinal mucosa and are involved in the regulation of renal blood flow.

Pharmacokinetics

Absorption

After oral administration of the drug, Meloxicam is well absorbed from the gastrointestinal tract, the absolute bioavailability is 89%. Simultaneous administration with food does not change absorption. The concentration of meloxicam when taking the drug orally in doses of 7.5 and 15 mg is proportional to the dose.

After intramuscular injection, the relative bioavailability is almost 100%. After intramuscular injection of the drug at a dose of 5 mg, C_max is 1.62 µg/ml and is achieved within approximately 60 minutes.

Meloxicam demonstrates linear pharmacokinetics at doses of 7.5-15 mg when administered intramuscularly.

Distribution

C_ss are achieved within 3-5 days of regular use. With long-term use of the drug (more than 1 year), the concentrations are similar to those observed after the first achievement of a steady pharmacokinetic state. Binding to plasma proteins (especially albumin) is more than 99%.

The range of differences between the maximum and basal concentrations of the drug after its administration once a day is relatively small and is 0.4-1 µg/ml when using a dose of 7.5 mg, and 0.8-2 µg/ml when using a dose of 15 mg (C_min and C_max values are given, respectively).

Meloxicam penetrates histohematic barriers, the concentration in the synovial fluid reaches 50% of the maximum concentration of the drug in plasma.

V_d is low and is 11 l. Interindividual differences are 30-40%.

Metabolism

Meloxicam is almost completely metabolized in the liver to form four pharmacologically inactive metabolites. 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). In vitro studies have shown that the isoenzyme CYP2C9 plays an important role in this metabolic transformation, and the isoenzyme CYP3A4 is of additional importance. Peroxidase is involved in the formation of two other metabolites (accounting for 16% and 4% of the drug dose, respectively), the activity of which probably varies individually.

Excretion

It is excreted equally through the intestines and kidneys, mainly in the form of metabolites. Less than 5% of the daily dose is excreted unchanged through the intestines; the drug is found in the urine unchanged only in trace amounts. T_1/2 of meloxicam after oral administration is 15-20 hours, after intramuscular injection – 20 hours. Plasma clearance averages 8 ml/min.

Pharmacokinetics in special clinical cases

In elderly individuals, the clearance of the drug is reduced.

Moderate hepatic or renal failure does not have a significant effect on the pharmacokinetics of meloxicam.

Indications

Symptomatic therapy

• Osteoarthritis;
• Rheumatoid arthritis;
• Ankylosing spondylitis (Bekhterev’s disease).

ICD codes

Dosage Regimen

Tablets

The drug is taken orally, with meals, in a daily dose of 7.5-15 mg, once a day.

For rheumatoid arthritis, the recommended dose is 15 mg/day; depending on the therapeutic effect, the dose can be reduced to 7.5 mg/day.

For osteoarthritis, the drug is prescribed at a dose of 7.5 mg/day; if there is no effect, the dose can be increased to 15 mg/day.

For ankylosing spondylitis, the daily dose is 15 mg.

The maximum daily dose of the drug Movasin^® should not exceed 15 mg.

In patients with an increased risk of side effects, as well as in patients with severe renal failure on hemodialysis, the dose should not exceed 7.5 mg/day.

Solution for intramuscular injection

Intramuscular administration of the drug is indicated only for the first 2-3 days. Subsequently, treatment is continued using 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 deep intramuscularly. Intravenous administration of the drug is prohibited!

In patients with an increased risk of adverse reactions, the daily dose should not exceed 7.5 mg.

For intramuscular injection in patients with end-stage renal failure on hemodialysis, and in patients with mild or moderate renal impairment (creatinine clearance more than 30 ml/min) the drug dose should not exceed 7.5 mg.

The dosage regimen of the drug for intramuscular injection in children and adolescents has not been established; this dosage form can only be used in adult patients. The maximum recommended daily dose is 15 mg.

When using various dosage forms of the drug in combination, its maximum daily dose in tablets, suppositories and in the form of an injection solution is 15 mg.

Adverse Reactions

From the digestive system >1% – dyspepsia, incl. nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea; 0.1-1% – transient increase in the activity of liver transaminases, hyperbilirubinemia, belching, esophagitis, gastroduodenal ulcer, gastrointestinal bleeding (including occult), stomatitis; <0.1% - gastrointestinal perforation, colitis, hepatitis, gastritis.

From the hematopoietic organs >1% – anemia; 0.1-1% – changes in the blood count, incl. leukopenia, thrombocytopenia.

From the skin >1% – itching, skin rash; 0.1-1% – urticaria; <0.1% - photosensitivity, bullous eruptions, erythema multiforme, incl. Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the respiratory system:<0.1% - bronchospasm.

From the nervous system >1% – dizziness, headache; 0.1-1% – vertigo, tinnitus, drowsiness; <0.1% - confusion, disorientation, emotional lability.

From the cardiovascular system >1% – peripheral edema; 0.1-1% – increased blood pressure, palpitations, flushing.

From the urinary system 0.1-1% – hypercreatininemia and/or increased serum urea; <0.1% - acute renal failure; connection with meloxicam use has not been established - interstitial nephritis, albuminuria, hematuria.

From the senses<0.1% - conjunctivitis, visual impairment, incl. blurred vision.

Allergic reactions<0.1% - angioedema, anaphylactoid/anaphylactic reactions.

Local reactions: >1% – swelling at the injection site; <0.1% - pain at the injection site

Contraindications

• Condition after coronary artery bypass grafting;
• Decompensated heart failure;
• 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 history);
• Erosive and ulcerative changes in the mucous membrane of the stomach or duodenum, active gastrointestinal bleeding;
• Inflammatory bowel diseases (ulcerative colitis, Crohn’s disease);
• Cerebrovascular bleeding or other bleeding;
• Severe liver failure or active liver disease;
• Chronic renal failure in patients not undergoing dialysis (creatinine clearance less than 30 ml/min), progressive kidney disease (including confirmed hyperkalemia);
• Children under 12 years of age (for tablets);
• Children under 18 years of age (for solution for intramuscular injection);
• Pregnancy;
• Lactation (breastfeeding);
• Hypersensitivity to meloxicam and other components of the drug.

The tablet form of the drug contains lactose, so patients with rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take the drug.

With caution

• Coronary artery disease;
• Cerebrovascular diseases;
• Compensated heart failure;
• Dyslipidemia/hyperlipidemia;
• Diabetes mellitus;
• Peripheral artery diseases;
• Smoking;
• Creatinine clearance 30-60 ml/min;
• History of ulcerative lesions of the gastrointestinal tract;
• Presence of Helicobacter pylori infection;
• Elderly age;
• Long-term use of NSAIDs;
• Frequent alcohol consumption;
• Severe somatic diseases;
• Concomitant therapy with the following drugs: anticoagulants (e.g., warfarin); antiplatelet agents (e.g., acetylsalicylic acid, clopidogrel); oral glucocorticosteroids (e.g., prednisolone); selective serotonin reuptake inhibitors (e.g., citalopram, fluoxetine, paroxetine, sertraline).

To reduce the risk of adverse events from the gastrointestinal tract, the minimum effective dose should be used for the shortest possible course.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation (breastfeeding).

The use of Movasin^®, like other drugs that block the synthesis of prostaglandins, may affect fertility, so it is not recommended to prescribe it to women wishing to become pregnant.

Use in Hepatic Impairment

The drug is contraindicated in severe liver failure.

Use in Renal Impairment

In patients with an increased risk of side effects, as well as in patients with severe renal failure on hemodialysis, the dose should not exceed 7.5 mg/day.

In patients with impaired renal function (creatinine clearance more than 25 ml/min) when taking the drug in tablet form, no dose adjustment is required.

In patients with mild or moderate renal impairment (creatinine clearance more than 30 ml/min) the dose of the drug for intramuscular injection should not exceed 7.5 mg.

The drug is contraindicated in severe renal failure (if hemodialysis is not performed).

Pediatric Use

The drug is contraindicated for use: in children under 12 years of age (for tablets); in children under 18 years of age (for solution for intramuscular injection).

Geriatric Use

The drug should be used with caution in elderly persons.

Special Precautions

Caution should be exercised when using the drug in patients with a history of gastric and duodenal ulcers and in patients receiving anticoagulant therapy, as this category of patients has an increased risk of developing erosive and ulcerative lesions of the gastrointestinal tract.

Caution should be exercised and renal function parameters should be monitored when using the drug in elderly patients, patients with chronic heart failure with signs of circulatory failure, patients with liver cirrhosis, as well as patients with hypovolemia as a result of surgical interventions.

In patients with mild or moderate renal impairment (creatinine clearance more than 30 ml/min), no dose adjustment is required.

Patients taking diuretics and Meloxicam simultaneously should take sufficient fluids.

If allergic reactions occur (itching, skin rash, urticaria, photosensitivity), the drug should be discontinued.

Meloxicam, like other NSAIDs, may mask the symptoms of infectious diseases.

Effect on the ability to drive vehicles and operate machinery

The use of the drug may cause undesirable effects such as headache and dizziness, drowsiness, therefore, during the period of taking the drug, one should refrain from driving vehicles and servicing machines and mechanisms that require concentration.

Overdose

Symptoms impaired consciousness, nausea, vomiting, epigastric pain, gastrointestinal bleeding, acute renal failure, liver failure, respiratory arrest, asystole.

Treatment in case of oral administration – gastric lavage, intake of activated charcoal (within the next hour); if necessary, symptomatic therapy is carried out. Forced diuresis, urine alkalinization, and hemodialysis are ineffective due to the high degree of binding of meloxicam to blood proteins. There is no specific antidote.

Drug Interactions

When used simultaneously with other NSAIDs (including acetylsalicylic acid), the risk of erosive and ulcerative lesions and gastrointestinal bleeding increases.

When used simultaneously with antihypertensive drugs, a decrease in their effectiveness is possible.

When used simultaneously with lithium preparations, accumulation of lithium and an increase in its toxic effect may occur (monitoring of lithium concentration in the blood is recommended).

When used simultaneously with methotrexate, the likelihood of developing toxic effects on hematopoiesis and the occurrence of anemia and leukopenia increases (periodic complete blood count is indicated).

When used simultaneously with diuretics and with cyclosporine, the risk of developing renal failure increases.

When used simultaneously with intrauterine contraceptive devices, a decrease in their effectiveness is possible.

When used simultaneously with anticoagulants (including heparin, ticlopidine, warfarin), as well as with thrombolytic drugs (including streptokinase, fibrinolysin), the risk of bleeding increases (periodic monitoring of blood coagulation parameters is necessary).

When used simultaneously with cholestyramine, the excretion of meloxicam through the gastrointestinal tract increases (due to binding).

When used simultaneously with selective serotonin reuptake inhibitors, the risk of gastrointestinal bleeding increases.

Storage Conditions

List B. The drug in tablet form should be stored in a dry, light-protected place, out of the reach of children, at a temperature not exceeding 25°C (77°F); shelf life – 3 years.

The drug in the form of a solution for intramuscular injection should be stored in a dry, light-protected place, out of the reach of children, at a temperature not exceeding 30°C (86°F); shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.