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Meloxicam

Pronunciation

Class: Other Nonsteroidal Anti-inflammatory Agents
Chemical Name: 1,1-Dioxide-4-Hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide
CAS Number: 71125-38-7
Brands: Mobic

Warning(s)

  • Cardiovascular Risk
  • Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).1 Risk may increase with duration of use.1 Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.1 (See Cardiovascular Effects under Cautions.)

  • Contraindicated for the treatment of pain in the setting of CABG surgery.1

  • GI Risk
  • Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).1 Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.1 Geriatric individuals are at greater risk for serious GI events.1 (See GI Effects under Cautions.)

Introduction

NSAIA referred to as a “preferential” rather than “selective” cycloogenase-2 (COX-2) inhibitor; oxicam derivative; structurally related to piroxicam.1 2 3 4 5 6 7 8 9 10

Uses for Meloxicam

Consider potential benefits and risks of meloxicam therapy as well as alternative therapies before initiating therapy with the drug.1 Use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.1

Osteoarthritis

Symptomatic treatment of osteoarthritis.1 Effect comparable to that of other NSAIAs (piroxicam, diclofenac).1 11 12 13 14 15

Slideshow: Fact or Fiction? The Top 15 Osteoarthritis Myths

Rheumatoid Arthritis in Adults

Symptomatic treatment of rheumatoid arthritis in adults.1 18 19

Juvenile Arthritis

Symptomatic management of pauciarticular or polyarticular course juvenile rheumatoid arthritis in children ≥2 years of age.1 23 Effect comparable to that of naproxen.1 23

Cardiovascular Risk Reduction

Not a substitute for aspirin in the prevention of adverse cardiovascular events (MI).1

Meloxicam Dosage and Administration

General

  • Consider potential benefits and risks of meloxicam therapy as well as alternative therapies before initiating therapy with the drug.1

Administration

Oral Administration

Administer orally once daily without regard to meals.1

Agitate the suspension well prior to administration of each dose.1

Formulation Considerations

Meloxicam oral suspension is the preferred dosage form for children weighing <60 kg because of suitability for providing the calculated dosage.1

Dosage

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient’s treatment goals.1 Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.1

Pediatric Patients

Juvenile Arthritis
Oral

Children ≥2 years of age: 0.125 mg/kg (maximum 7.5 mg) once daily.1 Higher dosages not associated with additional benefit.1 23

Adults

Osteoarthritis
Oral

7.5 mg once daily; may increase to 15 mg once daily.1

Rheumatoid Arthritis
Oral

7.5 mg once daily; may increase to 15 mg once daily.1

Prescribing Limits

Pediatric Patients

Oral

Maximum 7.5 mg daily.1

Adults

Oral

Maximum 15 mg daily.1

Special Populations

Hepatic Impairment

Dosage adjustment not necessary in patients with mild to moderate hepatic impairment; not studied in those with severe impairment.1

Renal Impairment

Dosage adjustment not necessary in patients with mild to moderate renal impairment (Clcr >15 mL/minute); not recommended in those with severe impairment.1

Cautions for Meloxicam

Contraindications

  • Known hypersensitivity to meloxicam or any ingredient in the formulation.1

  • History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.1

  • Treatment of perioperative pain in the setting of CABG surgery.1

Warnings/Precautions

Warnings

Cardiovascular Effects

Selective COX-2 inhibitors have been associated with an increased risk of serious adverse cardiovascular thrombotic events in certain situations.1 Several prototypical NSAIAs also have been associated with an increased risk of cardiovascular events.26 27 28 Current evidence suggests that use of meloxicam might be associated with increased cardiovascular risk.26 28

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events), and at the lowest effective dosage for the shortest duration necessary.1

Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).24

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.1 (See Specific Drugs under Interactions.)

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.1 Use with caution in patients with hypertension; monitor BP.1 Impaired response to certain diuretics may occur.1 (See Specific Drugs under Interactions.)

Fluid retention and edema reported.1 Caution in patients with fluid retention or heart failure.1

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.1

Lower incidence of adverse GI effects compared with other prototypical NSAIAs (e.g., diclofenac, naproxen, piroxicam) in some studies.16 17

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.1

Potential for overt renal decompensation.1 Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in patients with volume depletion, in geriatric patients, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.1 20 29 (See Renal Impairment under Cautions.)

Correct dehydration before initiating meloxicam therapy.1

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions reported.1

Immediate medical intervention and discontinuance for anaphylaxis.1

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.1

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.1 Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).1

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.1

Elevations of serum ALT or AST reported.1

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.1 Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.1

Hematologic Effects

Anemia reported rarely.1 Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.1

Notable effects on platelets or bleeding times not observed.3 8 9

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.1

May mask certain signs of infection.1

Obtain CBC and chemistry profile periodically during long-term use.1

Specific Populations

Pregnancy

Category C.1 Avoid use in third trimester because of possible premature closure of the ductus arteriosus.1

Lactation

Distributed into milk in rats; not known whether distributed into milk in humans.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established in children <2 years of age.1

Safety and efficacy in pediatric patients 2–17 years of age with juvenile rheumatoid arthritis supported by evidence from controlled studies.1 23

Abdominal pain, vomiting, diarrhea, headache, and pyrexia reported more frequently in children than adults.1

Geriatric Use

Caution advised.1 Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.1

Hepatic Impairment

Not studied in patients with severe hepatic impairment (Child-Pugh class III).1

Renal Impairment

Use with caution in renal disease.1 Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.1

Common Adverse Effects

Abdominal pain, diarrhea, dizziness, dyspepsia, edema, flatulence, headache, nausea, rash, upper respiratory tract infection, influenza-like illness, musculoskeletal and connective tissue signs and symptoms (back pain, muscle spasms, musculoskeletal pain).1

Interactions for Meloxicam

Metabolized by CYP isoenzymes, mainly by CYP2C9 and to a lesser extent by CYP3A4.1

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Reduced BP response to ACE inhibitor1

Possible deterioration of renal function in individuals with renal impairment29

Monitor BP1

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonist29

Possible deterioration of renal function in individuals with renal impairment29

Monitor BP29

Antacids

Pharmacokinetic interaction unlikely1

Administer meloxicam without regard to antacids1

Aspirin

Increased plasma meloxicam concentrations1

Increased risk of GI ulceration and other complications1

No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs1

Clinical importance of pharmacokinetic interaction unknown1

Manufacturer states that concomitant use not recommended1

Cholestyramine

Increased meloxicam clearance1

Clinical importance not established1

Cimetidine

Pharmacokinetics of meloxicam not altered1

Digoxin

No protein-binding interaction; pharmacokinetics of digoxin not altered1

Diuretics (furosemide, thiazides)

Reduced natriuretic effects possible1

Monitor for diuretic efficacy and renal failure1

Lithium

Increased plasma lithium concentrations1

Monitor for lithium toxicity1

Methotrexate

Possible toxicity associated with increased plasma methotrexate concentrations1

Caution advised1

Warfarin

Possibility of bleeding complications and increases in PT1

Monitor anticoagulant activity; caution advised1

Meloxicam Pharmacokinetics

Absorption

Bioavailability

Well absorbed following oral administration; bioavailability is about 89%.1 Peak plasma concentration usually attained within about 4–5 hours.1

Commercially available tablets and oral suspension are bioequivalent.1

Food

No clinically important effect.1

Special Populations

In patients with mild or moderate hepatic impairment (Child-Pugh class I or II), no important differences in plasma concentrations compared with healthy individuals; not studied in patients with severe hepatic impairment (Child-Pugh class III).1

In patients with mild or moderate renal impairment, some pharmacokinetic values altered (total plasma concentrations decreased, free concentrations unchanged); not studied in patients with severe renal impairment.1

Systemic exposure in children 2–6 years of age lower than that in children 7–16 years of age.1 Systemic exposure in children 7–16 years of age similar to or slightly lower than that in adults.1

Distribution

Extent

Total meloxicam concentrations in synovial fluid are 40–50% of plasma concentrations; free fraction in synovial fluid exceeds that in plasma.1

Plasma Protein Binding

99.4% (principally albumin).1

Elimination

Metabolism

Extensively metabolized to inactive metabolites by CYP isoenzymes, mainly by CYP2C9 and to a lesser extent by CYP3A4.1

Elimination Route

Undergoes biliary secretion and enterohepatic recirculation.1 2 3 4 8 10 Excreted to an equal extent in urine and feces as metabolites.1

Half-life

Adults: 15–20 hours.1

Children 2–6 years of age: 15.2 hours.1

Children 7–16 years of age: 13 hours.1

Stability

Oral

Suspension or Tablets

25°C (may be exposed to 15–30°C).1

Actions

  • Inhibits COX-2 to a greater extent than COX-1;2 3 5 6 8 10 selectivity is dose dependent and is diminished at higher dosages.5 6 7 8 9

  • Pharmacologic actions similar to those of other NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.1 2 3 4 5 6 7 8 9 10

Advice to Patients

  • Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.1

  • Risk of serious cardiovascular events with long-term use.1

  • Risk of GI bleeding and ulceration.1

  • Risk of serious skin reactions.1 Risk of anaphylactoid and other sensitivity reactions.1

  • Risk of hepatotoxicity.1

  • Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.1

  • Not a substitute for aspirin in the prevention of adverse cardiovascular events.1

  • Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.1

  • Importance of discontinuing meloxicam and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.1 Importance of seeking immediate medical attention if an anaphylactic reaction occurs.1

  • Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Importance of avoiding meloxicam in late pregnancy (third trimester).1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Meloxicam

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

7.5 mg

Mobic (with povidone)

Boehringer Ingelheim,

15 mg

Mobic (with povidone)

Boehringer Ingelheim,

Suspension

7.5 mg/5 mL

Mobic

Boehringer Ingelheim

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Meloxicam 15MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 90/$16.96 or 180/$18.92

Meloxicam 7.5MG/5ML Suspension (ROXANE): 100/$86.99 or 200/$169.98

Meloxicam 7.5MG Tablets (ZYDUS PHARMACEUTICALS (USA)): 30/$15.99 or 90/$42.95

Mobic 15MG Tablets (BOEHRINGER INGELHEIM): 30/$230.00 or 90/$659.97

Mobic 7.5MG Tablets (BOEHRINGER INGELHEIM): 30/$154.99 or 90/$441.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Boehringer Ingelheim. Mobic (meloxicam) tablets prescribing information. Ridgefield, CT; 2006 Jul 10.

2. Anon. Meloxicam (Mobic) for osteoarthritis. Med Lett Drugs Ther. 2000; 42:47-8. [PubMed 10859731]

3. Noble S, Balfour JA. Meloxicam. Drugs. 1996; 51:424-30. [PubMed 8882380]

4. Boehringer Ingelheim. Product information form for American hospital formulary service: Mobic (meloxicam). Ridgefield, CT; 2000.

5. Jackson LM, Hawkey CJ. COX-2 selective nonsteroidal anti-inflammatory drugs: do they really offer any advantages? Drugs. 2000; 59:1207-16.

6. Tegeder I, Lotsch J, Krebs S et al. Comparison of inhibitory effects of meloxicam and diclofenac on human thromboxane biosynthesis after single doses and at steady state. Clin Pharmacol Ther. 1999; 65:533-44. [IDIS 425542] [PubMed 10340919]

7. Noble SL, King DS, Olutade JI. Cyclooxygenase-2 enzyme inhibitors: place in therapy. Am Fam Physician. 2000; 61:3669-76. [IDIS 449104] [PubMed 10892637]

8. Kaplan-Machlis B, Klostermeyer BS. The cyclooxygenase-2 inhibitors: safety and effectiveness. Ann Pharmacother. 1999; 33:979-88. [IDIS 436184] [PubMed 10492503]

9. de Meijer A, Vollaard H, de Metz M et al. Meloxicam, 15 mg/day, spares platelet function in healthy volunteers. Clin Pharmacol Ther. 1999; 66:425-30. [IDIS 435521] [PubMed 10546927]

10. Davies NM, Skjodt NM. Clinical pharmacokinetics of meloxicam; a cyclo-oxygenase-2 preferential nonsteroidal anti-inflammatory drug. Clin Pharmacokinet. 1999; 36:115-26. [PubMed 10092958]

11. Prouse PJ, Bevis PJ, Bluhmki E et al. Evaluation of the safety, tolerability, and efficacy of meloxicam tablets in patients with osteoarthritis. Clin Ther. 1996; 18:429-39. [IDIS 370948] [PubMed 8829018]

12. Linden B, Distel M, Bluhmki E. A double-blind study to compare the efficacy and safety of meloxicam 15 mg with piroxicam 20 mg in patients with osteoarthritis of the hip. Br J Rheumatol. 1996; 35:35-8. [PubMed 8630634]

13. Hosie J, Distel M, Bluhmki E. Meloxicam in osteoarthritis: a 6-month, double-blind comparison with diclofenac sodium. Br J Rheumatol. 1996; 35:39-43. [PubMed 8630635]

14. Hosie J, Distel M, Bluhmki E. Efficacy and tolerability of meloxicam versus piroxicam in patients with osteoarthritis of the hip or knee: a six-month double-blind study. Clin Drug Invest. 1997; 13:175-84.

15. Yocum D, Fleischmann R, Dalgin P et al. Safety and efficacy of meloxicam in the treatment of osteoarthritis: a 12-week, double-blind, multiple-dose, placebo-controlled trial. Arch Intern Med. 2000; 160:2947-54. [IDIS 455190] [PubMed 11041902]

16. Schoenfeld P. Gastrointestinal safety profile of meloxicam: a meta-analysis and systematic review of randomized controlled trials. Am J Med. 1999; 107:48-54S.

17. Hawkey C, Kahan A, Steinbruck K et al. Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. Br J Rheumatol. 1998; 37:937-45. [PubMed 9783757]

18. Anon. Drug for rheumatoid arthritis. Med Lett Drugs Ther. 2000; 42:57-64. [PubMed 10887424]

19. Lemmel EM, Bolten W, Burgos-Vargas R et al. Efficacy and safety of meloxicam in patients with rheumatoid arthritis. J Rheumatol. 1997; 24:282-90. [IDIS 379868] [PubMed 9034984]

20. Novartis Pharmaceuticals. Diovan (valsartan) capsules prescribing information (dated 1997 Apr). In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:2013-5.

21. Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31:315-24. [PubMed 3358796]

22. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum. 2002; 46:328-46. [IDIS 476480] [PubMed 11840435]

23. Ruperto N, Nikishina I, Pachanov ED. A randomized, double-blind clinical trial of two doses of meloxicam compared with naproxen in children with juvenile idiopathic arthritis: short- and long-term efficacy and safety results. Arthritis Rheum. 2005; 52:563-72. [IDIS 529974] [PubMed 15692986]

24. Food and Drug Administration. Analysis and recommendations for agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. 2005 Apr 6.

25. Cush JJ. The safety of COX-2 inhibitors: deliberations from the February 16-18, 2005, FDA meeting. From the American College of Rheumatology web site (). Accessed 2005 Oct 12.

26. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006; 296: 1633-44. [PubMed 16968831]

27. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006; 332: 1302-5. [PubMed 16740558]

28. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk; the seduction of common sense. JAMA. 2006; 296:1653-6. [PubMed 16968830]

29. Merck & Co. Clinoril (sulindac) tablets prescribing information. Whitehouse Station, NJ; 2006 Feb.

30. Chou R, Helfand M, Peterson K et al. Comparative effectiveness and safety of analgesics for osteoarthritis. Comparative effectiveness review no. 4. (Prepared by the Oregon evidence-based practice center under contract no. 290-02-0024.) . Rockville, MD: Agency for Healthcare Research and Quality. 2006 Sep. Available at: .

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