Meloxicam

Meloxicam is a Cyclooxygenase-1 and 2 (COX-1 and 2) inhibitor belonging to non-steroidal anti-inflammatory drugs (NSAIDs).

Meloxicam is an NSAID used to treat osteoarthritis in adults, rheumatoid arthritis in adults, and juvenile rheumatoid arthritis in pediatrics.

Meloxicam is Well absorbed from the gastrointestinal tract. Its Bioavailability is 89% (tablet, capsule, oral susp). Time taken to reach peak plasma concentration after Oral administration is 4-5 hours. The volume of distribution of meloxicam is 10-15L. Because of its high binding to albumin, it is likely to be distributed in highly perfused tissues, such as the liver and kidney. Meloxicam concentrations in synovial fluid, measured after an oral dose, is estimated at 40% to 50% of the concentrations measured in the plasma. This drug is known to cross the placenta in humans. Meloxicam is almost completely metabolized. CYP2C9 is the main enzyme responsible for the metabolism of meloxicam with minor contributions from CYP3A4. Meloxicam has 4 major metabolites with no activity determined. About 60% of the ingested dose is metabolized to 5'-carboxy meloxicam from hepatic cytochrome enzyme oxidation of an intermediate metabolite, 5’-hydroxymethyl meloxicam. Two other metabolites are likely produced via peroxidation. Meloxicam is excreted via urine mainly as inactive metabolites; <1% as meloxicam and in faeces mainly as inactive metabolites; <5% as meloxicam.

Meloxicam shows side effects like Diarrhea, constipation, gas, sore throat.

Meloxicam is available in the form of Oral Tablet, Oral Capsule, Oral suspension and Injectable solution.

Meloxicam is available in India, US, Philippines, Australia, Singapore, Canada, Germany, France, Italy, Spain, and Malaysia.

Meloxicam is a non-steroidal anti-inflammatory drug (NSAIDs) belonging to the class Cyclooxygenase-1 and 2 (COX-1 and 2) inhibitor.

Meloxicam inhibits prostaglandin synthetase (cyclooxygenase 1 and 2) enzymes leading to a decreased synthesis of prostaglandins, which normally mediate painful inflammatory symptoms. As prostaglandins sensitize neuronal pain receptors, inhibition of their synthesis leads to analgesic and inflammatory effects. Meloxicam preferentially inhibits COX-2, but also exerts some activity against COX-1, causing gastrointestinal irritation.

The effect of Meloxicam and its duration of action is not clinically established.

Meloxicam is available in the form of Oral Tablet, Oral Capsule, Oral suspension and Injectable solution.

Meloxicam Tablet, Capsule, suspension taken orally while Injectable solution is given via intravenous route.

Meloxicam is used to relieve pain and swelling in conditions such as osteoarthritis and rheumatoid arthritis. Meloxicam should be used with extreme caution in patients with a history of cardiovascular diseases due to the increased risk of severe adverse effects.

Meloxicam is a Cyclooxygenase-1 and 2 (COX-1 and 2) inhibitor belonging to non-steroidal anti-inflammatory drugs (NSAIDs).

Meloxicam is approved for use in the following clinical indications

• Acute pain
• Gout, treatment
• Osteoarthritis
• Rheumatoid arthritis
• Juvenile idiopathic arthritis

• Acute pain

IV Dose: 30 mg once daily.

Capsule Dose: Oral: 5 mg to 10 mg once daily; maximum dose: 10 mg/day.

Orally disintegrating tablet: Oral: 7.5 mg to 15 mg once daily; maximum dose: 15 mg/day.

Suspension: Oral: 7.5 mg to 15 mg once daily; maximum dose: 15 mg/day.

Tablet: Oral: 7.5 mg to 15 mg once daily; maximum dose: 15 mg/day.

• Gout, treatment

Tablet: Oral: 15 mg once daily; initiate within 24 to 48 hours of flare onset; discontinue 2 to 3 days after resolution of clinical signs; usual duration: 5 to 7 days.

• Osteoarthritis

Capsule: Oral: Initial: 5 mg once daily; may increase to a maximum of 10 mg once daily.

Orally disintegrating tablet: Oral: Initial: 7.5 mg once daily; may increase to a maximum of 15 mg once daily.

Suspension: Oral: Initial: 7.5 mg once daily; may increase to a maximum of 15 mg once daily.

Tablet: Oral: Initial: 7.5 mg once daily; may increase to a maximum of 15 mg once daily.

• Rheumatoid arthritis

Orally disintegrating tablet: Oral: Initial: 7.5 mg once daily; may increase to a maximum of 15 mg once daily.

Suspension: Oral: Initial: 7.5 mg once daily; may increase to a maximum of 15 mg once daily.

Tablet: Oral: Initial: 7.5 mg once daily; may increase to a maximum of 15 mg once daily.

• Juvenile idiopathic arthritis

Oral suspension:

Children ≥2 years and Adolescents: Oral: 0.125 mg/kg once daily; maximum dose: 7.5 mg/dose.

Orally disintegrating tablets

Children and Adolescents weighing ≥60 kg: Oral: 7.5 mg once daily.

Tablets:

Children and Adolescents weighing ≥60 kg: Oral: 7.5 mg once daily.

Meloxicam is available in various strengths as 5mg, 7.5mg, 10mg, 15mg, 7.5 mg/5 mL and 30mg/mL.

Meloxicam is available in the form of Oral Tablet, Oral Capsule, Oral suspension and Injectable solution.

• Dosage Adjustment in Kidney Patient

IV:

eGFR ≥60 mL/minute/1.73 m²: No dosage adjustment necessary.

eGFR <60 mL/minute/1.73 m²: Use is not recommended; contraindicated in patients who are at risk for renal failure due to volume depletion.

Oral:

Altered kidney function:

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl >30 to <60 mL/minute: No dosage adjustment necessary.

CrCl ≤30 mL/minute: Avoid use due to increased risk of acute kidney injury.

• Dosage Adjustment in Hepatic impairment Patient

IV:

Mild to severe impairment: There are no dosage adjustments provided.

Oral:

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided.

Meloxicam is contraindicated in patients with

• Allergic Reactions

Meloxicam is contraindicated in patients with known hypersensitivity (e.g., anaphylactoid reactions and serious skin reactions) to meloxicam. Meloxicam should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.

• Coronary Surgery

Meloxicam is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.

• Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three 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. Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. 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.

• Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation

NSAIDs, including Meloxicam, can cause serious gastrointestinal (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 one in five 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 to 6 months, and in about 2% to 4% of patients treated for one 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. Prescribe NSAIDs, including Meloxicam, with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 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, use the lowest effective dose for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during Meloxicam therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of Meloxicam until a serious GI adverse event is ruled out. For high-risk patients, consider alternate therapies that do not involve NSAIDs.

• Hepatic Effects

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Meloxicam. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported. A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with Meloxicam. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue Meloxicam.

• Hypertension

NSAIDs, including Meloxicam, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. NSAIDs, including Meloxicam, 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. Patients taking ACE inhibitors, thiazides, or loop diuretics may have impaired response to these therapies when taking NSAIDs.

• Congestive Heart Failure and Edema

Fluid retention and edema have been observed in some patients taking NSAIDs. Use Meloxicam with caution in patients with fluid retention, hypertension, or heart failure.

• Renal Effects

Long-term administration of NSAIDs, including Meloxicam, can result in renal papillary necrosis, renal insufficiency, acute renal failure, and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, ACE inhibitors, and angiotensin II receptor antagonists, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. A pharmacokinetic study in patients with mild and moderate renal impairment revealed that no dosage adjustments in these patient populations are required. Patients with severe renal impairment have not been studied. The use of Meloxicam in patients with severe renal impairment with CrCl less than 20 mL/min is not recommended. A study performed in patients on hemodialysis revealed that although overall Cmax was diminished in this population, the proportion of free drug not bound to plasma was increased. Therefore it is recommended that meloxicam dosage in this population not exceed 7.5 mg per day. Closely monitor the renal function of patients with impaired renal function who are taking Meloxicam, Use caution when initiating treatment with Meloxicam in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with Meloxicam. Caution is also recommended in patients with pre-existing kidney disease. The extent to which metabolites may accumulate in patients with renal impairment has not been studied with Meloxicam. Because some Meloxicam metabolites are excreted by the kidney, monitor patients with significant renal impairment closely.

• Anaphylactoid Reactions

As with other NSAIDs, anaphylactoid reactions have occurred in patients without known prior exposure to Meloxicam. Meloxicam should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs Seek emergency help in cases where an anaphylactoid reaction occurs.

• Adverse Skin Reactions

NSAIDs, including Meloxicam, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin manifestations and discontinue use of the drug at the first appearance of skin rash or any other sign of hypersensitivity.

• Pregnancy

Starting at 30 weeks gestation, avoid the use of Meloxicam because it may cause premature closure of the ductus arteriosus.

• Corticosteroid Treatment

Meloxicam cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Slowly taper patients on prolonged corticosteroid therapy if a decision is made to discontinue corticosteroids.

• Masking of Inflammation and Fever

The pharmacological activity of Meloxicam in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

• Hematological Effects

Anemia may occur in patients receiving NSAIDs, including Meloxicam. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Meloxicam, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia. NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Carefully monitor patients treated with Meloxicam who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants.

• Use in Patients with Pre-existing Asthma

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, Meloxicam should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma.

• Monitoring

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, Meloxicam should be discontinued.

Consumption of alcohol is not recommended during treatment with this medicine due to an increase in the risk of serious adverse effects such as gastrointestinal bleeding, dizziness, weakness, etc.

It is not known whether this drug is excreted in human milk; however, meloxicam was excreted in the milk of lactating rats at concentrations higher than those in plasma. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Meloxicam, a decision should be made whether to discontinue nursing or to discontinue the drug, considering the importance of the drug to the mother.

There are no adequate and well-controlled studies in pregnant women. Meloxicam crosses the placental barrier. Prior to 30 weeks gestation, use Meloxicam during pregnancy only if the potential benefit justifies the potential risk to the fetus. Starting at 30 weeks gestation, avoid Meloxicam and other NSAIDs, in pregnant women as premature closure of the ductus arteriosus in the fetus may occur. If this drug is used during this time in pregnancy, inform the patient of the potential hazard to a fetus.

Common

• Anaphylactoid reactions, new-onset or exacerbation of hypertension, edema, Na and fluid retention, cardiac failure, decreased platelet adhesion and aggregation, prolonged bleeding time, increased risk of hemorrhage, anemia (particularly with long term use), transaminase elevations (mild and transient), hyperkaliemia, blurred or decreased vision, interstitial nephritis (with or without nephrotic syndrome), impaired renal function, renal papillary, severe blood dyscrasias (e.g. agranulocytosis, thrombocytopenia, aplastic anemia), Vertigo, Nausea, vomiting, diarrhea, dyspepsia, abdominal pain, constipation, flatulence, stomatitis, gastritis, eructation, exacerbation of colitis and Crohn’s disease, Abnormal renal function test (e.g. increased serum creatinine and/or serum urea),Headache, dizziness, somnolence, Rash, pruritus, angioedema, Flushing.

Rare

• CV thrombotic events including MI and stroke (increased risk with higher doses and prolonged use), gastrointestinal bleeding, ulceration, and perforation; drug reaction with eosinophilia and systemic symptoms (DRESS)/multiorgan hypersensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis. Rarely, severe hepatic reactions (e.g. fulminant hepatitis, hepatic necrosis, hepatic failure).

• ACE-inhibitors

NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking Meloxicam concomitantly with ACE-inhibitors.

• Aspirin

When Meloxicam is administered with aspirin (1000 mg three times daily) to healthy volunteers, an increase in the AUC (10%) and Cmax (24%) of meloxicam was noted. The clinical significance of this interaction is not known; however, as with other NSAIDs concomitant administration of meloxicam and aspirin is not generally recommended because of the potential for increased adverse effects. Concomitant administration of low-dose aspirin with Meloxicam may result in an increased rate of GI ulceration or other complications, compared to use of Meloxicam alone. Meloxicam is not a substitute for aspirin for cardiovascular prophylaxis.

• Diuretics

Clinical studies, as well as post marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. However, studies with furosemide agents and meloxicam have not demonstrated a reduction in natriuretic effect. Furosemide single and multiple dose pharmacodynamics and pharmacokinetics are not affected by multiple doses of meloxicam. Nevertheless, during concomitant therapy with Meloxicam, patients should be observed closely for signs of renal failure, as well as to ensure diuretic efficacy.

• Lithium

In a study conducted in healthy subjects, mean pre-dose lithium concentration and AUC were increased by 21% in subjects receiving lithium doses ranging from 804 to 1072 mg twice daily with meloxicam 15 mg every day as compared to subjects receiving lithium alone. These effects have been attributed to inhibition of renal prostaglandin synthesis by Meloxicam. Closely monitor patients on lithium treatment for signs of lithium toxicity when Meloxicam is introduced, adjusted, or withdrawn.

• Methotrexate

NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. Therefore, NSAIDs may reduce the elimination of methotrexate, thereby enhancing the toxicity of methotrexate. Use caution when Meloxicam is administered concomitantly with methotrexate.

• Cyclosporine

Meloxicam, like other NSAIDs, may affect renal prostaglandins, thereby altering the renal toxicity of certain drugs. Therefore, concomitant therapy with Meloxicam may increase cyclosporine's nephrotoxicity. Use caution when Meloxicam is administered concomitantly with cyclosporine.

• Warfarin

The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone. Monitor anticoagulant activity, particularly in the first few days after initiating or changing Meloxicam therapy in patients receiving warfarin or similar agents, since these patients are at an increased risk of bleeding than with the use of either drug alone. Use caution when administering Meloxicam with warfarin since patients on warfarin may experience changes in INR and an increased risk of bleeding complications when a new medication is introduced.

• Kayexalate® (sodium polystyrene sulfonate)

Cases of intestinal necrosis (possibly fatal) have been described in patients who received concomitant sorbitol and Kayexalate® (sodium polystyrene sulfonate). Due to the presence of sorbitol in Meloxicam Oral Suspension, use with Kayexalate® is not recommended.

The common side effects of Meloxicam include the following

• Common side effects

Diarrhea, constipation, gas, sore throat.

• Rare side effects

Fever, blisters, rash, skin blisters or peeling, hives, itching, swelling of the eyes, face, tongue, lips, or throat, difficulty breathing or swallowing, hoarseness, pale skin, fast heartbeat, shortness of breath or difficulty breathing, unexplained weight gain, swelling in the abdomen, ankles, feet, or legs, nausea, excessive tiredness, lack of energy, yellowing of the skin or eyes, pain in the right upper part of the stomach, flu-like symptoms, cloudy, discolored, or bloody urine, back pain ,difficult or painful urination.

• Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Meloxicam crosses the placental barrier. Prior to 30 weeks gestation, use Meloxicam during pregnancy only if the potential benefit justifies the potential risk to the fetus. Starting at 30 weeks gestation, avoid Meloxicam and other NSAIDs, in pregnant women as premature closure of the ductus arteriosus in the fetus may occur. If this drug is used during this time period in pregnancy, inform the patient of the potential hazard to a fetus.

• Nursing Mothers

It is not known whether this drug is excreted in human milk; however, meloxicam was excreted in the milk of lactating rats at concentrations higher than those in plasma. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Meloxicam, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• Pediatric Use

The safety and effectiveness of meloxicam in pediatric JRA patients from 2 to 17 years of age has been evaluated in three clinical trials.

• Geriatric Use

As with any NSAID, caution should be exercised in treating the elderly (65 years and older). Of the total number of subjects in clinical studies, 5157 were age 65 and over (4044 in OA studies and 1113 in RA studies). No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Symptoms: Drowsiness, lethargy, nausea, vomiting, epigastric pain, gastrointestinal bleeding; convulsions, hypertension, CV collapse, cardiac arrest, acute renal failure, hepatic dysfunction, respiratory depression, coma; anaphylactic reactions.

Management: Symptomatic and supportive treatment. Consider emesis or administering activated charcoal and/or osmotic cathartic in symptomatic patients seen within 4 hours of ingestion or in large overdoses. May give colestyramine to increase clearance.

• Pharmacodynamic

Meloxicam is an anti-inflammatory, analgesic analgesic with antipyretic effects in fever. Prostaglandins are substances that contribute to inflammation. This drug also exerts preferential actions against COX-2, which may reduce the possible gastrointestinal effects of this drug. In humans, meloxicam has demonstrated the ability to decrease erythrocyte sedimentation rate (ESR) in patients with rheumatoid arthritis, and to decrease ESR, C-reactive protein (CRP), as well as aquaporin-1 expression. As with other NSAIDS, prolonged use of meloxicam can result in renal or cardiovascular impairment or thrombotic cardiovascular events.

• Pharmacokinetics

Absorption

Meloxicam is Well absorbed from the gastrointestinal tract. Its Bioavailability is 89% (tablet, capsule, oral susp). Time taken to reach peak plasma concentration after Oral administration is 4-5 hours.

Distribution

The volume of distribution of meloxicam is 10-15L. Because of its high binding to albumin, it is likely to be distributed in highly perfused tissues, such as the liver and kidney. Meloxicam concentrations in synovial fluid, measured after an oral dose, is estimated at 40% to 50% of the concentrations measured in the plasma. This drug is known to cross the placenta in humans.

Metabolism and Excretion

Meloxicam is almost completely metabolized. CYP2C9 is the main enzyme responsible for the metabolism of meloxicam with minor contributions from CYP3A4. Meloxicam has 4 major metabolites with no activity determined. About 60% of the ingested dose is metabolized to 5'-carboxy meloxicam from hepatic cytochrome enzyme oxidation of an intermediate metabolite, 5’-hydroxymethyl meloxicam. Two other metabolites are likely produced via peroxidation. Meloxicam is excreted via urine mainly as inactive metabolites; <1% as meloxicam and in faeces mainly as inactive metabolites; <5% as meloxicam.

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