Movi-Cox

Meloxicam.

Meloxicam is 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide.

Pharmacology: Movi-Cox is a nonsteroidal anti-inflammatory drug (NSAID) of the enolic acid class which has shown anti-inflammatory, analgesic and antipyretic properties in animals. Movi-Cox showed anti-inflammatory activity in all standard models of inflammation. A common mechanism for the previously mentioned effects may exist in the ability of Movi-Cox 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 confirmed the 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 PGE₂ 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, diclofenac, ibuprofen and naproxen significantly inhibited platelet aggregation and prolonged bleeding.
In clinical trials, gastrointestinal (GI) adverse events overall were reported less frequently with meloxicam 7.5 and 15 mg than with the NSAIDs with which it has been compared, due predominantly to a lower reporting incidence of events eg, dyspepsia, vomiting, nausea and abdominal pain. The incidence of upper GI 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 GI perforation, obstruction or bleeds between meloxicam and other NSAIDs. A pooled analysis has been conducted involving patients treated with meloxicam in 35 clinical trials in the indications osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Exposure to meloxicam in these trials ranged from 3 weeks-1year (most patients were enrolled in 1-month studies). Almost all patients participated in trials that permitted enrollment of patients with a prior history of GI perforation, ulcer or bleed.
The incidence of clinically significant upper GI perforation, obstruction or bleed (POB) was assessed retrospectively following independent blinded review of cases.
Results are shown in the table:


Click on icon to see table/diagram/image


Pharmacokinetics: Absorption: Oral Administration: Meloxicam is well-absorbed from the GI tract, which is reflected by a high absolute bioavailability of 89% following oral administration.
Following single dose administration of meloxicam, mean maximum plasma concentrations are achieved within 5-6 hrs with solid oral dosage forms (tablets).
With multiple dosing, steady-state conditions were reached within 3-5 days. Once-daily dosing leads to drug plasma concentrations with a relatively small peak-trough fluctuation in the range of 0.4-1 mcg/mL for 7.5 mg doses and 0.8-2 mcg/mL for 15 mg doses, respectively (C_min and C_max at steady-state, correspondingly).
Maximum plasma concentrations of meloxicam at steady-state, are achieved within 5-6 hrs.
Extent of absorption for meloxicam following oral administration is not altered by concomitant food intake or the use of inorganic antacids. Dose linearity was demonstrated after oral administration in the therapeutic dose range of 7.5-15 mg.
Distribution: Meloxicam is very strongly bound to plasma proteins, essentially albumin (99%). Meloxicam penetrates into synovial fluid to give concentrations approximately half of those in plasma. Volume of distribution is low, on average 11 L. Interindividual variation is the order of 7-20%.
The volume of distribution following administration of mulitple oral doses of meloxicam (7.5-15 mg) is about 14-17 L with coefficients of variation ranging from 24-32%.
Biotransformation: Meloxicam undergoes extensive hepatic biotransformation. Four different metabolites of meloxicam were identified in urine, which are all pharmacodynamically inactive. The major metabolite, 5'-carboxymeloxicam (60% of dose), is formed by oxidation of an intermediate metabolite 5'-hydroxymethylmeloxicam, which is also excreted to a lesser extent (9% of dose). In vitro studies suggest that CYP2C9 plays an important role in this metabolic pathway, with a minor contribution from the CYP3A4 isoenzyme. The patient's peroxidase activity is probably responsible for the other 2 metabolites, which account for 16% and 4% of the administered dose, respectively.
Elimination: Meloxicam is excreted predominantly in the form of metabolites and occurs to equal extents in urine and faeces. Less than 5% of the daily dose is excreted unchanged in faeces, while only traces of the parent compound are excreted in urine.
The mean elimination half-life varies between 13 and 25 hrs after oral, IM and IV administration.
Total plasma clearance amounts about 7-12 mL/min following single doses orally, IV or rectally administered.
Linearity/Nonlinearity: Meloxicam demonstrates linear pharmacokinetics in the therapeutic dose range of 7.5-15 mg following per oral or IM administration.
Special Populations: Hepatic/Renal Insufficiency: Neither hepatic insufficiency, nor mild to moderate renal insufficiency have a substantial effect on meloxicam pharmacokinetics. In terminal renal failure, the increase in the volume of distribution may result in higher free meloxicam concentrations and a daily dose of 7.5 mg must not be exceeded.
Elderly: Elderly male subjects exhibited similar mean pharmacokinetic parameters but the elimination half-life is significantly longer compared to those of young male subjects. Elderly female patients showed higher AUC values and longer elimination half-lives compared to those of younger subjects of both genders. Mean plasma clearance at steady state in elderly subjects was slightly lower than that reported for younger subjects.
Children: In a study of 36 children, kinetic measurements were made in 18 children at doses of 0.25 mg/kg body weight. Maximum plasma concentration C_max (-34%) as well as AUC_0-∞ (-28%) tended to be lower in the younger age group (aged 2-6 years, n=7) as compared to the older age group (7-14 years, n=11) while weight normalized clearance appeared to be higher in the younger age group. A historical comparison with adults revealed that plasma concentrations were at least similar for older children and adults. Plasma elimination half-lives (13 hrs) were similar for both groups and tended to be shorter than in adults (15-20 hrs).

Short-term symptomatic treatment of acute exacerbation of osteoarthritis and long-term symptomatic treatment of rheumatoid arthritis (chronic polyarthritis).
Symptomatic treatment of ankylosing spondylitis.

Rheumatoid Arthritis and Ankylosing Spondylitis: 15 mg daily. According to the therapeutic response, the dose may be reduced to 7.5 mg daily.
Osteoarthritis: 7.5 mg daily. If necessary, the dose may be increased to 15 mg daily.
In patients with increased risks of adverse reactions, start treatment at the dose of 7.5 mg daily.
In dialysis patients with severe renal failure, the dose should not exceed 7.5 mg daily.
As the potential for adverse reactions increases with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used.
Adolescents: The maximum daily dose is 15 mg.
In general, usage should be restricted to ≥15 years (see Contraindications).
The total daily dose of tablets should be taken as a single dose and should be swallowed with water or other fluid in conjunction with food.

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.

Known hypersensitivity to meloxicam or to any of the excipient of Movi-Cox. There is a potential for cross-sensitivity to acetylsalicylic acid and other NSAIDs.
Patients who have developed signs of asthma, nasal polyps, angioedema or urticaria following the administration of acetosal or other NSAIDs.
Treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
Active or recent GI ulceration/perforation; active inflammatory bowel disease (Crohn's disease or ulcerative colitis); severe hepatic insufficiency; non-dialysed severe renal insufficiency; overt GI bleeding, recent cerebrovascular bleeding or established systemic bleeding disorders; severe uncontrolled heart failure.
In case of rare hereditary conditions that may be incompatible with an excipient of the product (see Precautions), and pregnancy and lactation, children and adolescents <15 years, the use of Movi-Cox is contraindicated.
Effects on the Ability to Drive or Operate Machinery: No studies on the effect on the ability to drive and use machines have been performed. However, patients should be advised that they may experience undesirable effects like visual disturbance including blurred vision, dizziness, somnolence, vertigo and other central nervous system disturbances.
Therefore, caution should be recommended when driving a car or operating a machinery.
If patients experience any of these events, they should avoid potentially hazardous tasks eg, driving or operating machinery.
Use in pregnancy & lactation: Movi-Cox is contraindicated during pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or the embryofoetal development. Data from epidemiological studies suggest an increased risk of miscarriage, cardiac malformation and gastrochisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from <1% up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In preclinical studies, administration of a prostaglandin synthesis inhibitor has been shown to result an increase in pre- and post-implantation loss and embryofoetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in preclinical studies given a prostaglandin synthesis inhibitor during the organogenetic period.
During the 3rd trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to: Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure with oligo-hydroamniosis; the mother and the neonate, at the end of pregnancy, to: Possible prolongation of bleeding time, an antiaggregating effect which may occur even at very low doses; inhibition of uterine contractions resulting in delayed or prolonged labour.
While no specific experience exists for Movi-Cox, NSAIDs are known to pass into mother's milk. Administration therefore is contraindicated in women who are breastfeeding.
The use of meloxicam, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Meloxicam may delay ovulation. Therefore, in women who have difficulties conceiving, or who are undergoing investigation of infertility, withdrawal of meloxicam should be considered.

Cardiovascular Effects: Cardiovascular Thrombotic Events: Clinical trials of several COX-2 selective and nonselective NSAIDs of up to 3 years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see Warnings).
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see Contraindications).
Hypertension: NSAIDs, including Movi-Cox, can lead to onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Movi-Cox, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Congestive Heart Failure and Edema: Fluid retention and edema have been observed in some patients taking NSAIDs. Movi-Cox should be used with caution in patients with fluid retention or heart failure.
Gastrointestinal Effects: Risk of Ulceration, Bleeding and Perforation: NSAIDs, including Movi-Cox, can cause serious GI adverse events including inflammation, bleeding, ulceration and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only 1 in 5 patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of patients treated for 1 year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or GI bleeding. Patients with a prior history of peptic ulcer disease and/or GI bleeding who use NSAIDs have a >10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.

As with other NSAIDs, caution should be exercised when treating patients with a history of upper GI disease and in patients receiving treatment with anticoagulants. Patients with GI symptoms should be monitored. Movi-Cox should be withdrawn if peptic ulceration or GI bleeding occurs.
As with other NSAIDs, GI bleeding, ulceration or perforation can occur at any time during treatment, with or without warning symptoms or a previous history of serious GI events. The consequences of such events are generally more serious in the elderly.
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the 1st month of treatment. Movi-Cox should be discontinued at the 1st appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
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 pre-treatment state upon discontinuation of NSAID therapy. Patients at greatest risk of such a reaction are elderly individuals, dehydrated patients, those with congestive heart failure, liver cirrhosis, nephrotic syndrome and overt renal disease, those receiving a concomitant treatment with diuretic, ACE inhibitor or angiotensin II receptor antagonist or those having undergone major surgical procedures which led to hypovolemia. In such patients, the volume of diuresis and the renal function should be carefully monitored at the beginning of therapy.
In rare instances, NSAIDs may be the cause of interstitial nephritis, glomerulonephritis, renal medullary necrosis or nephrotic syndrome.
The dose of Movi-Cox in patients with end-stage renal failure on haemodialysis should not be higher than 7.5 mg. No dose reduction is required in patients with mild or moderate renal impairment (ie, in patients with a CrCl >25 mL/min). 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, Movi-Cox 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.
For patients at risk, clinical monitoring is recommended.
Meloxicam, as any other NSAID, may mask symptoms of an underlying infectious disease.
The use of meloxicam, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Therefore, in women who have difficulties conceiving, or who are undergoing investigation of infertility, withdrawal of meloxicam should be considered.
For relevant drug interactions that require particular attention, see Interactions.
There are no specific studies about effects on the ability to drive vehicles and to use machinery. Patients who experience visual disturbances, drowsiness or other central nervous system disturbances should refrain from these activities.
Movi-Cox 7.5 and 15 mg contains lactose 47 and 20 mg per maximum recommended daily dose, respectively. Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take Movi-Cox.
Cardiovascular Risk: NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. (See Warnings). Movi-Cox is contraindicated for the treatment of perioperative pain in the setting of CABG surgery (see Warnings).
Gastrointestinal Risk: NSAIDs can cause an increased risk of serious GI adverse events including bleeding, ulceration and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious GI events. (See Warnings).

Movi-Cox is contraindicated during pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or the embryofoetal development. Data from epidemiological studies suggest an increased risk of miscarriage, cardiac malformation and gastrochisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from <1% up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy. In preclinical studies, administration of a prostaglandin synthesis inhibitor has been shown to result an increase in pre- and post-implantation loss and embryofoetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in preclinical studies given a prostaglandin synthesis inhibitor during the organogenetic period.
During the 3rd trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to: Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure with oligo-hydroamniosis; the mother and the neonate, at the end of pregnancy, to: Possible prolongation of bleeding time, an antiaggregating effect which may occur even at very low doses; inhibition of uterine contractions resulting in delayed or prolonged labour.
While no specific experience exists for Movi-Cox, NSAIDs are known to pass into mother's milk. Administration therefore is contraindicated in women who are breastfeeding.
The use of meloxicam, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair fertility and is not recommended in women attempting to conceive. Meloxicam may delay ovulation. Therefore, in women who have difficulties conceiving, or who are undergoing investigation of infertility, withdrawal of meloxicam should be considered.

Clinical trial and epidemiological data suggests that use of some NSAIDs (particularly at high doses and in long-term treatment) may be associated with a small increased risk of arterial thrombotic events (eg, myocardial infarction or stroke).
Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment.
The most commonly-observed adverse reactions are gastrointestinal in nature. Peptic ulcers, perforation or GI bleedings, sometimes fatal, particularly in the elderly, may occur. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration. Less frequently, gastritis has been observed.
The frequencies of adverse drug reactions given as follows are based on corresponding occurrences of reported adverse reactions in 27 clinical trials with a treatment duration of at least 14 days. The information is based on clinical trials involving 15,197 patients who have been treated with daily oral doses of 7.5 or 15 mg meloxicam tablets or capsules over a period of up to 1 year.
Adverse drug reactions that have come to light as a result of reports received in relation to administration of the marketed product are included.
Adverse reactions have been ranked under headings of frequency using the following convention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (1/10,000), not known (can not be estimated from the available data).
Blood and Lymphatic System Disorders: Uncommon: Anaemia. Rare: Abnormal blood count (including differential white cell count), leukopenia, thrombocytopenia. Very Rare: Agranulocytosis.
Immune System Disorders: Unknown: Allergic reactions other than anaphylactic or anaphylactoid reactions. Not Known: Anaphylactic and anaphylactoid reaction.
Psychiatric Disorders: Rare: Altered mood, nightmares. Not Known: Confusional state, disorientation.
Nervous System Disorders: Common: Headache. Uncommon: Dizziness, somnolence.
Eye Disorders: Rare: Visual disturbance including blurred vision, conjunctivitis.
Ear and Labyrinth Disorders: Uncommon: Vertigo. Rare: Tinnitus.
Cardiac Disorders: Rare: Palpitations. Cardiac failure has been reported in association with NSAID treatment.
Vascular Disorders: Uncommon: Increased blood pressure, flushing.
Respiratory, Thoracic and Mediastinal Disorders: Rare: Asthma in individuals allergic to aspirin or other NSAIDs.
Gastrointestinal Disorders: Very Common: Dyspepsia, nausea, vomiting, abdominal pain, constipation, flatulence, diarrhoea. Uncommon: Occult or macroscopic GI haemorrhage, stomatitis, gastritis, eructation. Rare: Colitis, gastroduodenal ulcer, oesophagitis. Very Rare: GI perforation and haemorrhage. Ulceration or perforation may sometimes be severe or potentially be fatal, especially in the elderly.
Hepatobiliary Disorders: Uncommon: Abnormal liver function test (eg, raised transaminases or bilirubin). Very Rare: Hepatitis.
Skin and Subcutaneous Tissue Disorders: Uncommon: Angioedema, pruritus, rash. Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria. Very Rare: Bullous dermatitis, erythema multiforme. Not Known: Photosensitivity reaction.
Renal and Urinary Disorders: Uncommon: Sodium and water retention, hyperkalaemia, abnormal renal function test (increased serum creatinine and/or serum urea). Very Rare: Acute renal failure particularly in patients with risk factors.
General Disorders and Administration Site Conditions: Uncommon: Oedema including oedema of the lower limbs.

Other Prostaglandin Synthetase Inhibitors (PSI) Including Glucocorticoids and Salicylates (Acetylsalicylic Acid): Co-administration of PSIs may increase the risk of GI ulcers and bleeding, via a synergistic effect and is not recommended. The concomitant use of meloxicam with other NSAIDs is not recommended.
Concomitant administration of aspirin (1000 mg 3 times daily) to healthy volunteers tended to increase the AUC (10%) and C_max (24%) of meloxicam. The clinical significance of this interaction is not known.
Oral Anticoagulants, Antiplatelet Drugs, Systemically Administered Heparin, Thrombolytics and Selective Serotonin Re-Uptake Inhibitors (SSRIs): Increased risk of bleeding, via inhibition of platelet function.
Lithium: NSAIDs have been reported to increase lithium plasma levels (via decreased renal excretion of lithium), which may reach toxic values. The concomitant use of lithium and NSAIDs is not recommended. If this combination appears necessary, lithium plasma concentrations should be monitored carefully during the initiation, adjustment and withdrawal of meloxicam treatment.
Methotrexate: NSAIDs can reduce the tubular secretion of methotrexate thereby increasing the plasma concentrations of methotrexate. For this reason, for patients on high dosages of methotrexate (>15 mg/week) the concomitant use of NSAIDs is not recommended. The risk of an interaction between NSAID preparations and methotrexate, should be considered also in patients on low dosage of methotrexate, especially in patients with impaired renal function. In case combination treatment is necessary blood cell count and the renal function should be monitored. Caution should be taken in case both NSAID and methotrexate are given within 3 days, in which case the plasma level of methotrexate may increase and cause increased toxicity. Although the pharmacokinetics of methotrexate (15 mg/week) were not relevantly affected by concomitant meloxicam treatment, it should be considered that the haematological toxicity of methotrexate can be amplified by treatment with NSAID drugs.
Contraception: A decrease of the efficacy of intrauterine devices by NSAIDs has been previously reported but needs further confirmation.
Diuretics: Treatment with NSAIDs is associated with the potential for acute renal insufficiency in patients who are dehydrated. Patients receiving Movi-Cox and diuretics should be adequately hydrated and be monitored for renal function prior to initiating treatment.
Antihypertensives (eg, β-Blockers, ACE Inhibitors, Vasodilators, Diuretics): A reduced effect of the antihypertensive drug by inhibition of vasodilating prostaglandins has been reported during treatment with NSAIDs.
NSAIDs and angiotensin-II receptor antagonists as well as ACE inhibitors exert a synergistic effect on the decrease of glomerular filtration. In patients with preexisting renal impairment this may lead to acute renal failure.
Cholestyramine binds meloxicam in the GI tract leading to a faster elimination of meloxicam. Nephrotoxicity of cyclosporine may be enhanced by NSAIDs via renal prostaglandin-mediated effects. During combined treatment renal function is to be measured.
Meloxicam is eliminated almost entirely by hepatic metabolism, of which approximately ²/₃ are mediated by cytochrome (CYP) P-450 enzymes (CYP2C9 major pathway and CYP3A4 minor pathway) and ¹/₃ by other pathways eg, peroxidase oxidation. The potential for a pharmacokinetic interaction should be taken into account when meloxicam and drugs known to inhibit, or to be metabolized by, CYP2C9 and/or CYP3A4 are administered concurrently.
No relevant pharmacokinetic drug-drug interactions were detected with respect to the concomitant administration of antacids, cimetidine, digoxin and furosemide.
Interactions with oral antidiabetics cannot be excluded.

Store below 30°C. Protect from light.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AC06 - meloxicam ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, oxicams.

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