Class: Musculoskeletal System
Dosage Form: Tablets
Description: Selective COX-II inhibitor
Manufacturer: Boehringer Ingelheim
Mobic is a non-steroidal anti-inflammatory drug (NSAID) of the enolic acid class, which has shown anti-inflammatory, analgesic and antipyretic properties in animals. Meloxicam showed potent anti-inflammatory activity in all standard models of inflammation. A common mechanism for the above effects may exist in the ability of meloxicam to inhibit the biosynthesis of prostaglandins, known mediators of inflammation.
Comparison of the ulcerogenic dose and the anti-inflammatory effective dose in the rat adjuvant arthritis model confirmed a superior therapeutic margin in animals over standard NSAIDs. In vivo, meloxicam inhibited prostaglandin biosynthesis more potently at the site of inflammation than in the gastric mucosa or the kidney.
These differences are thought to be related to a selective inhibition of COX-2 relative to COX-1 and it is believed that COX-2 inhibition provides the therapeutic effects of NSAIDs whereas inhibition of constitutive COX-1 may be responsible for gastric and renal side effects.
The COX-2 selectivity of meloxicam has been confirmed both in vitro and ex vivo in a number of test systems. In the human whole blood assay, meloxicam has been shown in vitro to inhibit COX-2 selectively. Meloxicam (7.5 and 15 mg) demonstrated a greater inhibition of COX-2 ex vivo, as demonstrated by a greater inhibition of lipopolysaccharide-stimulated PGE; production (COX-2) as compared with thromboxane production in clotting blood (COX-1). These effects were dose-dependent. Meloxicam has been demonstrated to have no effect on either platelet aggregation or bleeding time at recommended doses ex vivo. while indomethacin inhibited platelet aggregation and prolonged bleeding. In clinical trials, gastrointestinal adverse events overall were reported less frequently with meloxicam 7.5 mg and 15 mg than with the NSAIDs with which it has been compared, due predominantly to a lower reporting incidence of events such as dyspepsia, vomiting, nausea and abdominal pain. The incidence of upper gastrointestinal perforation, ulcers, and bleeds reported in association with meloxicam is low and dose dependent.
There is no single study powered adequately to detect statistically differences in the incidence of clinically significant upper gastrointestinal perforation, obstruction, or bleeds between meloxicam and other NSAIDs.
A pooled analysis has been conducted involving patients treated with meloxicam daily in 35 clinical trials in the indications osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Exposure to meloxicam in these trials ranged from 3 weeks to one year (most patients were enrolled in one-month studies). Almost all patients participated in trials that permitted enrollment of patients with a prior history of gastrointestinal perforation, ulcer or bleed. The incidence of clinically significant upper gastrointestinal perforation, obstruction, or bleed (POB) was assessed retrospectively following independent blinded review of cases.
Short term symptomatic treatment of acute exacerbation of inflammatory rheumatism.
Known hypersensitivity to meloxicam or any excipient of the product.
There is a potential for cross sensitivity to aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs).
Mobic should not be given to patients who have developed signs of asthma, nasal polyps, angioedema or urticaria following the administration of aspirin or other NSAIDs.
Mobic ampoules should not be used in patients treated with anticoagulants as intramuscular hematomas may occur.
- Active peptic ulcer
- Severe hepatic insufficiency
- Non-dialysed severe renal insufficiency
- Children and adolescents aged less than 15 years
- Pregnancy or breastfeeding
The following interactions are to be noted:
- Other NSAIDs including salicylates: concomitant administration of more than one NSAID may increase the risk of gastrointestinal ulceration and bleeding through synergistic action.
- Lithium: NSAIDs have been reported to increase serum lithium levels. It is recommended that plasma lithium levels be monitored when initiating, adjusting and discontinuing MOBIC.
- Methotrexate: As other NSAIDs MOBIC may increase the haematologic toxicity of methotrexate. In this situation, strict monitoring of blood cell count is recommended.
- Contraception: NSAIDs have been reported to decrease the efficacy of intrauterine devices.
- Diuretics: Treatment with NSAIDs is associated with the potential for acute renal insufficiency in patients who are dehydrated. Patients receiving MOBIC and diuretics should be adequately hydrated and be monitored for renal function prior to initiating treatment.
- Cyclosporin nephrotoxicity may be enhanced by NSAIDs via renal prostaglandin mediated effects. During combined treatment renal function is to be measured.
- Antihypertensives (e.g. beta-blockers, ACE-inhibitors, vasodilators, diuretics): A reduced effect of the antihypertensive drug by inhibition of vasoacting prostaglandins has been reported during treatment with NSAIDs.
- Cholestyramine binds meloxicam in the gastrotestinal tract leading to a faster elimination of meloxicam
Meloxicam is eliminated almost entirely by hepatic metabolism, of which approximately two thirds are mediated by cytochrome (CYP) P450 enzymes (CYP 2C9 major pathway and CYP 3A4 minor pathway) and one-third by other pathways, such as peroxidase oxidation. The potential for a pharmacokinetic interaction should be taken into account when meloxica and drugs known to inhibit, or to be metabolised by, CYP 2C9 and/or CYP3A4 are administered concurrently.
No relevant pharmacokinetic drug-drug ineractions were detected with respect to the concomitant administration of antacids, cimetidine, digoxin and furosemide.
Interactions with oral antidiabetics can’t be excluded. Mobic ampoules must not be mixed with other drugs in the same syringe since there is no information about possible incompatibilities.
The following adverse events which may be causally related with the administration of Mobic have been reported. The frequencies given below are based on corresponding occurrences in clinical trials, regardless of any causal relationship.The information is based on clinical trials involving 3750 patients who have been treated with daily oral doses of 7.5 or 15 mg Mobic tablets or capsules over a period of up to 18 months (mean duration of treatment 127 days), and on 254 patients who have been treated with intramuscular injections of Mobic for up to seven days.
The incidence of adverse events which may be causally related to the administration of Mobic that have come to light as a result of reports received in relation to administration of oral formulations of the marketed product are difficult to quantify. All are assumed to occur with a frequency of less than 0.1%.
- More frequent than 1%: dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhea
- Between 0.1 and 1 %: transitory abnormalities of of liver function parameters (e.g. raised transaminases or bilirubin), eruction, oesophagitis, gastroduodenal ulcer, occult or macroscopic gastrointestinal bleeding
- Less frequent than 1%: gastrointestinal perforation, colitis, hepatitis, gastritis
- More frequent than 1%: Anemia
- Between 0.1 and 1%: Disturbances of blood count, including differential white cell count, leukopenia and thrombocytopenia. Concomitant administration of a potentially myelotoxic drug, in particular methotrexate, appears to be a predisposing factor to the onset of a cytopenia.
- More frequent than 1%: Pruritus, skin rash stomatitis, urticaria
- Less frequent than 1%: Photosensitisation. On rare occasions bullous reactions, erythema multiforme, Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis may develop
- Less frequent than 0.1%: Onset of acute asthma has been reported in certain individuals following the administration of aspirin or other NSAIDs, including Mobic
5. Central Nervous System:
- More frequent than 1%: Lightheadedness, headache
- Between 0.1 and 1%: Vertigo, tinnitus, drowsiness
- Less frequent than 0.1%: Confusion and disorientation, alteration of mood
- More frequent than 1%: Edema
- Between 0.1 and 1%: Increase of blood pressure, palpitations, flushes
- Between 0.1 and 1%: Abnormal renal function parameters (increased serum creatinine and/or serum urea)
- Less frequent than 0.1%: Acute renal failure
8. Vision disorders:
- Less frequent than 0.1%: Conjunctivitis, visual disturbances including blurred vision
9. Hypersensitivity reactions:
- Less frequent than 0.1%: Angioedema and immediate hypersensitivity reactions, including anaphylactoid/anaphylactic reactions
10. Application site disorders:
- More frequent than 1%: Injection site mass
- Between 0.1 and 1%: Injection site pain
Dosage and Administration:
1.Dosage and Administration:
Intramuscular administration should only be used during the first few days of treatment. For continuation of treatment, oral (tablets or capsules) formulations should be used.
The recommended dosage of Mobic is 7.5 mg or 15 mg once daily, depending on the pain intensity and severity of inflammation.
Mobic should be administered by deep intramuscular injection.
Because of the possibility of incompatibilities Mobic ampoules should not be mixed with other drugs in the same syringe.
The maximum daily dose of Mobic in patients with severe renal failure on hemodialysis should not be higher than 7.5 mg.
Mobic ampoules should not be administered intravenously.
As a dosage in children and adolescents has not yet been established, usage of the ampoules should be restricted to adults.
2. Combined Administration:
The total daily dose of Mobic administered as capsules, tablets, suppositories and injections should not exceed 15 mg.
In case of overdose the standard measures of gastric evacuation and general supportive measures should be used as there is no known antidote. It has been shown in a clinical trial that cholestyramine accelerates the elimination of meloxicam.
Pregnancy and Lactation:
Although no teratogenic effects were seen in pre-clinical testing, Mobic should not be used during pregnancy and breastfeeding.
As with other NSAIDs caution should be exercised when treating patients with a history of upper gastrointestinal disease. Patients with gastrointestinal symptoms should be monitored. Mobic should be withdrawn if peptic ulceration or gastrointestinal bleeding occurs. Gastrointestinal bleeding, ulceration or perforation can occur at any time during treatment, with or without warning symptoms or a previous history of serious gastrointestinal events. The consequences of such events are generally more serious in the elderly.
Special attention should be paid in patients reporting mucocutaneous adverse events and consideration given to discontinuing Mobic. NSAIDs inhibit the synthesis of renal prostaglandins which play a supportive role in the maintenance of renal perfusion. In patients whose renal blood flow and blood volume are decreased, administration of an NSAID may precipitate overt renal decompensation which is typically followed by recovery to pretreatment state upon discontinuation of non-steroidal anti-inflammatory therapy. Patients at greatest risk of such a reaction are dehydrated patients, those with congestive heart failure, liver cirrhosis, nephrotic syndrome and overt renal disease, those receiving a diuretic or those having undergone major surgical procedures which led to hypovolaemia. In such patients the volume of diuresis and the renal function should be carefully monitored at the beginning of therapy.
In rare instance NSAIDs may be the cause of interstitial nephritis, glomerulonephritis renal medullary necrosis or nephrotic syndrome.
As with most other NSAIDs, occasional elevations of serum transaminases or other parameters of liver function have been reported. In most cases these have been small and transient increases above the normal range. If the abnormality is significant or persistent, Mobic should be stopped and follow up tests carried out. No dose reduction is required in patients with clinically stable liver cirrhosis.
Frail or debilitated patients may tolerate side effects less well and such patients should be carefully supervised. As with other NSAIDs, caution should be used in the treatment of elderly patients who are more likely to be suffering from impaired renal, hepatic or cardiac function.
Induction of sodium, potassium and water retention and interference with the natriuretic effects of diuretics may occur with NSAIDs. Cardiac failure or hypertension may be precipitated or exacerbated in susceptible patients as a result.
Effects on ability to drive and use machinery
There are no specific studies about effects on the ability to drive and use machinery. Patients who experience visual disturbances, drowsiness or other central nervous system disturbances should refrain from these activities.
Strips of 10 tablets each.
Store at room temperature, below 25°C.