Drug Name

Mobic (Meloxicam)

Pharmacological action

Mobic (Meloxicam) is a non-steroidal anti-inflammatory drug, which has analgesic, anti-inflammatory and antipyretic effects. The mechanism of action is associated with inhibition of prostaglandin synthesis as a result of selective inhibition of cyclooxygenase-2 (COX-2) enzymatic activity, which is involved in the biosynthesis of prostaglandins in the inflammatory area. When used in high doses, prolonged use and individual characteristics of the body COX-2 selectivity decreases. Suppresses the synthesis of prostaglandins in the area of inflammation to a greater extent than in the gastric mucosa or kidneys, which is due to the relatively selective inhibition of COX-2. Less often causes erosive and ulcerative changes of the gastrointestinal tract. To a lesser extent, meloxicam acts on cyclooxygenase-1 (COX-1), which is involved in the synthesis of prostaglandins, protecting the gastrointestinal mucosa and taking part in the regulation of blood flow in the kidneys.

Pharmacokinetics

Well absorbed from the gastrointestinal tract, the absolute bioavailability of Meloxicam is 89%. Simultaneous intake of food does not change absorption. When using the drug orally in doses of 7.5 and 15 mg, its concentrations are proportional to the doses. Equilibrium concentration is reached within 3-5 days. In long-term use of the drug (more than 1 year), the concentrations are similar to those observed after the first achievement of steady state pharmacokinetics. Binding to plasma proteins is more than 99%. The range of differences between maximum and basal concentrations of the drug after its administration once a day is relatively small and is 0.4-1.0 mcg/ml when using 7.5 mg dose, and 0.8-2.0 mcg/ml when using 15 mg dose, (Cmin and Cmax values are given, respectively). Meloxicam penetrates through the histohematic barriers, the concentration in synovial fluid reaches 50% of the Cmax of the drug in plasma. It is almost completely metabolized in the liver to form four pharmacologically inactive derivatives. The main metabolite, 5'-carboxy-meloxicam (60% of the dose value), is formed by oxidation of an intermediate metabolite, 5'-hydroxymethylmeloxicam, which is also excreted, but to a lesser extent (9% of the dose value). In vitro studies have shown that CYP2C9 plays an important role in this metabolic transformation, CYP3A4 isoenzyme has additional importance. Peroxidase, the activity of which probably varies individually, takes part in the formation of two other metabolites (which are 16% and 4% of the drug dose, respectively).

It is excreted equally via the intestine and kidneys, mainly as metabolites.

Less than 5% of the daily dose is excreted unchanged through the intestine, the drug is detected only in trace amounts in the urine. T1/2 of meloxicam is 15-20 h. Plasma clearance averages 8 ml/min. The drug clearance is decreased in elderly people. Vd is low and averages 11 l.

Hepatic or renal insufficiency of moderate severity has no significant effect on the pharmacokinetics of meloxicam.

Contraindications to use

• hypersensitivity to meloxicam or excipients of the drug; the composition includes lactose, so patients with rare hereditary diseases such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take the drug;
• condition after aortocoronary bypass surgery;
• decompensated heart failure;
• anamnestic data about an attack of bronchoobstruction, rhinitis, urticaria after taking acetylsalicylic acid or other NSAIDs (full or partial combination of bronchial asthma, recurrent polyposis of the nose and sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including anamnesis);
• erosive-ulcerative changes of the mucous membrane of the stomach or 12 duodenum, active gastrointestinal bleeding;
• inflammatory bowel disease (ulcerative colitis, Crohn's disease);
• cerebrovascular bleeding or other bleeding disorders;
• Severe hepatic insufficiency or active liver disease;
• chronic renal insufficiency in patients not undergoing dialysis (creatinine clearance less than 30 ml/min), advanced renal disease including confirmed hyperkalemia;
• Pregnancy, breast-feeding;
• children under 12 years of age.

With caution. CHD, cerebrovascular disease, congestive heart failure, dyslipidemia/hyperlipidemia, diabetes mellitus, peripheral artery disease, smoking, history of gastrointestinal ulcers, presence of Helicobacter pylori infection, CKD with creatinine clearance of 30-60 ml/min, elderly age, long-term use of NSAIDs, frequent use of alcohol, severe somatic diseases, concomitant therapy with the following drugs:

• anticoagulants (e.g., warfarin);
• Antiaggregants (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 gastrointestinal adverse events, the lowest effective dose should be used in as short a course as possible.

Administration during pregnancy and lactation

It is not recommended to use the drug during pregnancy and lactation.

Administration in liver dysfunction

It is contraindicated in case of expressed hepatic insufficiency or active liver disease.

Caution should be exercised and the renal function parameters should be monitored while using the drug in patients with liver cirrhosis.

Administration in patients with impaired renal function

It is contraindicated in chronic renal failure in patients without dialysis (creatinine clearance less than 30 ml/min), in progressive renal disease including confirmed hyperkalemia.

Caution: CKD with creatinine clearance 30-60 ml/min.

Dosage regimen adjustment is not required in patients with mild to moderate renal function impairment (creatinine clearance more than 30 ml/min).

Administration in children

Contraindicated in children under 12 years of age.

Administration in elderly patients

Caution should be exercised and the renal function parameters should be controlled if the drug is used in elderly patients.

Indications of the drug Mobic (Meloxicam)

Symptomatic treatment of osteoarthritis;

Symptomatic treatment of rheumatoid arthritis;

Symptomatic treatment of ankylosing spondylitis (Behterev's disease), other degenerative joint diseases accompanied by pain syndrome.

Dosing regimen

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

Recommended dosing regimen:

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

Osteoarthritis: 7.5 mg per day. If ineffective, the dose may be increased to 15 mg per day.

Ankylosing spondylitis: 15 mg per day. The maximum daily dose should not exceed 15 mg.

In patients with increased risk of side effects and in patients with severe renal failure who are on hemodialysis, the dose should not exceed 7.5 mg per day.