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Identification
NameMeloxicam
Accession NumberDB00814  (APRD00529)
Typesmall molecule
Groupsapproved
Description

Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve the symptoms of arthritis, primary dysmenorrhea, fever; and as an analgesic, especially where there is an inflammatory component. It is closely related to piroxicam. In Europe it is marketed under the brand names Movalis, Melox, and Recoxa. In North America it is generally marketed under the brand name Mobic. In Latin America, the drug is marketed as Tenaron. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
MeloxicamGermanINN
MéloxicamFrenchINN
MeloxicamSpanishINN
MeloxicamumLatinINN
SaltsNot Available
Brand names
NameCompany
AchefreeAchefree
ActicamAcromax Dominicana
AflamidAnchor
AfloxxLusa
AglanZentiva
AinecoxCheminter
AldoronIvax
AlentumLafrancol
AlgiflexBiogen
AliviodolCentrum
AnaxicamCaferma
AnposelMedipharm
AntrendLabormed
AponipPharmatec
ArelogerGerard
AremilMagma
ArmexQintar Pharma
ArroxXepa-Soul Pattinson
ArsitecArsmedendi
ArtexPharmedic
ArthrobicMekophar
ArthroxPharmanel
ArticamStandpharm
ArtiproHelix
ArtricloxGarmisch
ArtrifilmG&R
ArtriflamSherfarma
ArtrilomPro.Med.CS
ArtriloxCombiphar
ArtroxPharmaBrand
AspicamBiofarm
AtiflamDoctor Andreu
AtrozanPharmstandard
AuroxicamAurora
AxiusHersil
MobicBoehringer Ingelheim
Brand mixtures
Brand NameIngredients
Aldoron FlexMeloxicam and Pridinol
Artrifilm FlexMeloxicam and Pridinol
Categories
CAS number71125-38-7
WeightAverage: 351.401
Monoisotopic: 351.034747299
Chemical FormulaC14H13N3O4S2
InChI KeyInChIKey=ZRVUJXDFFKFLMG-UHFFFAOYSA-N
InChI
InChI=1S/C14H13N3O4S2/c1-8-7-15-14(22-8)16-13(19)11-12(18)9-5-3-4-6-10(9)23(20,21)17(11)2/h3-7,18H,1-2H3,(H,15,16,19)
IUPAC Name
4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-2H-1$l^{6},2-benzothiazine-3-carboxamide
SMILES
CN1C(C(=O)NC2=NC=C(C)S2)=C(O)C2=C(C=CC=C2)S1(=O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzothiazines
SubclassNot Available
Direct parentBenzothiazines
Alternative parents2,5-disubstituted Thiazoles; Aminothiazoles; Benzene and Substituted Derivatives; Sulfonamides; Secondary Carboxylic Acid Amides; Polyamines; Carboxylic Acids; Enolates
Substituents2,5-disubstituted 1,3-thiazole; 1,3-thiazolamine; benzene; sulfonic acid derivative; azole; sulfonamide; thiazole; carboxamide group; secondary carboxylic acid amide; carboxylic acid derivative; polyamine; enolate; carboxylic acid; organonitrogen compound; amine
Classification descriptionThis compound belongs to the benzothiazines. These are organic compounds containing a benzene fused to a thiazine ring (a six-member ring with four carbon atoms, one nitrogen atom and one sulfur atom).
Pharmacology
IndicationFor symptomatic treatment of arthritis and osteoarthritis.
PharmacodynamicsMeloxicam is an nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Prostaglandins are substances that contribute to inflammation of joints. Meloxicam inhibits prostaglandin synthetase (cylooxygenase 1 and 2) and leads to a decrease of the synthesis of prostaglandins, therefore, inflammation is reduced.
Mechanism of actionAnti-inflammatory effects of meloxicam are believed to be due to inhibition of prostaglandin synthetase (cylooxygenase), leading to the inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, inhibition of their synthesis may be associated with the analgesic and antipyretic effects of meloxicam.
AbsorptionAbsolute bioavailability = 89%
Volume of distribution
  • 10 L
Protein binding99.4% bound, primarily to albumin
Metabolism

Meloxicam is almost completely metabolized into inactive metabolites by the cytochrome P450 (CYP450) isozymes. CYP2C9 is primarily responsible for metabolism of meloxicam while CYP3A4 plays a minor role. An intermediate metabolite, 5'-hydroxymethyl meloxicam, is further metabolized to 5'-carboxy meloxicam, the major metabolite. Peroxidase activity is thought to produce the two other inactive metabolites of meloxicam.

SubstrateEnzymesProduct
Meloxicam
    5'-carboxy meloxicamDetails
    Meloxicam
      5'-hydroxymethyl meloxicamDetails
      Route of eliminationMeloxicam is almost completely metabolized to four pharmacologically inactive metabolites. Meloxicam excretion is predominantly in the form of metabolites, and occurs to equal extents in the urine and feces. Only traces of the unchanged parent compound are excreted in the urine (0.2%) and feces (1.6%). The extent of the urinary excretion was confirmed for unlabeled multiple 7.5 mg doses: 0.5%, 6% and 13% of the dose were found in urine in the form of meloxicam, and the 5'-hydroxymethyl and 5'-carboxy metabolites, respectively.
      Half life15-20 hours
      Clearance
      • 8.8 mL/min [Healthy Male Adults (Fed) oral 7.5 mg tablets]
      • 9.9 mL/min [Eldery Male (Fed) oral 15 mg capsules]
      • 5.1 mL/min [Eldery Female (Fed) oral 15 mg capsules]
      • 19 mL/min [Renal Failure (Fasted) oral 15 mg capsules]
      • 11 mL/min [Hepatic Insufficiency (Fasted) oral 15 mg capsules]
      ToxicityLD50, Acute: 84 mg/kg (Rat); Oral 470 mg/kg (Mouse); Oral 320 mg/kg (Rabbit)
      Affected organisms
      • Humans and other mammals
      Pathways
      PathwayCategorySMPDB ID
      Meloxicam Action PathwayDrug actionSMP00106
      SNP Mediated EffectsNot Available
      SNP Mediated Adverse Drug ReactionsNot Available
      ADMET
      Predicted ADMET features
      Property Value Probability
      Human Intestinal Absorption + 0.9156
      Blood Brain Barrier - 0.9811
      Caco-2 permeable + 0.8484
      P-glycoprotein substrate Substrate 0.5181
      P-glycoprotein inhibitor I Non-inhibitor 0.7516
      P-glycoprotein inhibitor II Non-inhibitor 0.7491
      Renal organic cation transporter Non-inhibitor 0.9275
      CYP450 2C9 substrate Substrate 0.5637
      CYP450 2D6 substrate Non-substrate 0.9117
      CYP450 3A4 substrate Non-substrate 0.6649
      CYP450 1A2 substrate Non-inhibitor 0.9271
      CYP450 2C9 substrate Inhibitor 0.5511
      CYP450 2D6 substrate Non-inhibitor 0.9322
      CYP450 2C19 substrate Non-inhibitor 0.8948
      CYP450 3A4 substrate Non-inhibitor 0.8191
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7316
      Ames test Non AMES toxic 0.8576
      Carcinogenicity Non-carcinogens 0.7052
      Biodegradation Not ready biodegradable 0.9312
      Rat acute toxicity 3.4619 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.9579
      hERG inhibition (predictor II) Non-inhibitor 0.7999
      Pharmacoeconomics
      Manufacturers
      • Boehringer ingelheim pharmaceuticals inc
      • Actavis totowa llc
      • Apotex inc etobicoke site
      • Aurobindo pharma ltd
      • Beijing double crane pharmaceutical co ltd
      • Beijing yabao biopharmaceutical co ltd
      • Breckenridge pharmaceutical inc
      • Caraco pharmaceutical laboratories ltd
      • Carlsbad technology inc
      • Corepharma llc
      • Dr reddys laboratories inc
      • Genpharm inc
      • Glenmark generics ltd
      • Lupin pharmaceuticals inc
      • Mutual pharmaceutical co inc
      • Mylan pharmaceuticals inc
      • Roxane laboratories inc
      • Strides arcolab ltd
      • Taro pharmaceutical industries ltd
      • Teva pharmaceuticals usa
      • Unichem laboratories ltd
      • Watson laboratories inc
      • Zydus pharmaceuticals usa inc
      Packagers
      Dosage forms
      FormRouteStrength
      SuspensionOral7.5 mg/5 ml
      TabletOral15 mg
      TabletOral7.5 mg
      Prices
      Unit descriptionCostUnit
      Meloxicam 7.5 mg/5ml Suspension 100ml Bottle86.99USDbottle
      Meloxicam bp powder56.61USDg
      Mobic 15 mg tablet7.37USDtablet
      Meloxicam 15 mg tablet4.94USDtablet
      Mobic 7.5 mg tablet4.74USDtablet
      Meloxicam 7.5 mg tablet3.23USDtablet
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      Patents
      CountryPatent NumberApprovedExpires (estimated)
      United States61842201999-09-252019-09-25
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      melting point254 dec °CPhysProp
      water solubility7.15 mg/LNot Available
      logP3.43AVDEEF,A (1997)
      Caco2 permeability-4.71ADME Research, USCD
      pKa4.08MERCK INDEX (1996)
      Predicted Properties
      PropertyValueSource
      water solubility1.54e-01 g/lALOGPS
      logP2.28ALOGPS
      logP1.6ChemAxon
      logS-3.4ALOGPS
      pKa (strongest acidic)4.47ChemAxon
      pKa (strongest basic)0.47ChemAxon
      physiological charge-1ChemAxon
      hydrogen acceptor count5ChemAxon
      hydrogen donor count2ChemAxon
      polar surface area99.6ChemAxon
      rotatable bond count2ChemAxon
      refractivity88.62ChemAxon
      polarizability34.25ChemAxon
      number of rings3ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterYesChemAxon
      Veber's ruleNoChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      SpectraNot Available
      References
      Synthesis Reference

      Laura Coppi, “Crystalline forms of meloxicam and processes for their preparation and interconversion.” U.S. Patent US20030109701, issued June 12, 2003.

      US20030109701
      General ReferenceNot Available
      External Links
      ResourceLink
      KEGG DrugD00969
      KEGG CompoundC08169
      PubChem Compound5281106
      PubChem Substance46506624
      ChemSpider4444553
      BindingDB50056998
      Therapeutic Targets DatabaseDAP000971
      PharmGKBPA450353
      Drug Product Database2248031
      RxListhttp://www.rxlist.com/cgi/generic/mobic.htm
      Drugs.comhttp://www.drugs.com/cdi/meloxicam.html
      WikipediaMeloxicam
      ATC CodesM01AC06
      AHFS Codes
      • 28:08.04.92
      PDB EntriesNot Available
      FDA labelshow(45.4 KB)
      MSDSshow(35.7 KB)
      Interactions
      Drug Interactions
      Drug
      AcenocoumarolMeloxicam may increase the anticoagulant effect of acenocoumarol.
      AnisindioneMeloxicam may increase the anticoagulant effect of anisindione.
      Azilsartan medoxomilIncreases toxicity of each. May deteriorate renal function, particularly in volume depleted or elderly patients. Decreases effects of azilsartan by antagonism.
      ColesevelamBile acid sequestrants may decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Monitor for decreased serum concentrations/therapeutic effects of nonsteroidal anti-inflammatory agents (NSAID) if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.
      DicoumarolMeloxicam may increase the anticoagulant effect of dicumarol.
      EltrombopagIncreases levels of Meloxicam via metabolism decrease. UDP-glucuronosyltransferase inhibition with unclear significance.
      Ginkgo bilobaAdditive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
      LithiumMeloxicam increases serum levels of lithium
      PralatrexateNSAIDs increase the risk of toxicity due to impairment of renal clearance of pralatrexate thus increasing exposure. Monitor for adverse effects or adjust dose of pralatrexate.
      TelmisartanConcomitant use of Telmisartan and Meloxicam may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
      TimololThe NSAID, Meloxicam, may antagonize the antihypertensive effect of Timolol.
      TrandolaprilThe NSAID, Meloxicam, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Meloxicam is initiated, discontinued or dose changed.
      TreprostinilThe prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Meloxicam. Monitor for increased bleeding during concomitant thearpy.
      VoriconazoleVoriconazole may increase the serum concentration of meloxicam by decreasing its metabolism via CYP2C9 and CYP3A4. Monitor for changes in the therapeutic and adverse effects of meloxicam if voriconazole is initiated, discontinued or dose changed.
      WarfarinThe antiplatelet effects of meloxicam may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.
      Food Interactions
      • Take without regard to meals.

      1. Prostaglandin G/H synthase 2

      Kind: protein

      Organism: Human

      Pharmacological action: yes

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Prostaglandin G/H synthase 2 P35354 Details

      References:

      1. Poulsen Nautrup B, Horstermann D: [Pharmacodynamic and pharmacokinetic aspects of the non-inflammatory non-steroidal agent meloxicam in dogs] Dtsch Tierarztl Wochenschr. 1999 Mar;106(3):94-100. Pubmed
      2. Tegeder I, Lotsch J, Krebs S, Muth-Selbach U, Brune K, Geisslinger G: Comparison of inhibitory effects of meloxicam and diclofenac on human thromboxane biosynthesis after single doses and at steady state. Clin Pharmacol Ther. 1999 May;65(5):533-44. Pubmed
      3. Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F: Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol. 1999 Jun;26(6):1366-73. Pubmed
      4. Panara MR, Renda G, Sciulli MG, Santini G, Di Giamberardino M, Rotondo MT, Tacconelli S, Seta F, Patrono C, Patrignani P: Dose-dependent inhibition of platelet cyclooxygenase-1 and monocyte cyclooxygenase-2 by meloxicam in healthy subjects. J Pharmacol Exp Ther. 1999 Jul;290(1):276-80. Pubmed
      5. Gross JM, Dwyer JE, Knox FG: Natriuretic response to increased pressure is preserved with COX-2 inhibitors. Hypertension. 1999 Nov;34(5):1163-7. Pubmed
      6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

      2. Prostaglandin G/H synthase 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      Prostaglandin G/H synthase 1 P23219 Details

      References:

      1. Blanco FJ, Guitian R, Moreno J, de Toro FJ, Galdo F: Effect of antiinflammatory drugs on COX-1 and COX-2 activity in human articular chondrocytes. J Rheumatol. 1999 Jun;26(6):1366-73. Pubmed
      2. Panara MR, Renda G, Sciulli MG, Santini G, Di Giamberardino M, Rotondo MT, Tacconelli S, Seta F, Patrono C, Patrignani P: Dose-dependent inhibition of platelet cyclooxygenase-1 and monocyte cyclooxygenase-2 by meloxicam in healthy subjects. J Pharmacol Exp Ther. 1999 Jul;290(1):276-80. Pubmed

      1. Cytochrome P450 2C9

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Cytochrome P450 2C9 P11712 Details

      References:

      1. Chesne C, Guyomard C, Guillouzo A, Schmid J, Ludwig E, Sauter T: Metabolism of Meloxicam in human liver involves cytochromes P4502C9 and 3A4. Xenobiotica. 1998 Jan;28(1):1-13. Pubmed
      2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
      3. Ludwig E, Schmid J, Beschke K, Ebner T: Activation of human cytochrome P-450 3A4-catalyzed meloxicam 5’-methylhydroxylation by quinidine and hydroquinidine in vitro. J Pharmacol Exp Ther. 1999 Jul;290(1):1-8. Pubmed
      4. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
      5. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

      2. Cytochrome P450 3A4

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 3A4 P08684 Details

      References:

      1. Chesne C, Guyomard C, Guillouzo A, Schmid J, Ludwig E, Sauter T: Metabolism of Meloxicam in human liver involves cytochromes P4502C9 and 3A4. Xenobiotica. 1998 Jan;28(1):1-13. Pubmed
      2. Ludwig E, Schmid J, Beschke K, Ebner T: Activation of human cytochrome P-450 3A4-catalyzed meloxicam 5’-methylhydroxylation by quinidine and hydroquinidine in vitro. J Pharmacol Exp Ther. 1999 Jul;290(1):1-8. Pubmed
      3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

      3. 6-phosphogluconate dehydrogenase, decarboxylating

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: inhibitor

      Components

      Name UniProt ID Details
      6-phosphogluconate dehydrogenase, decarboxylating P52209 Details

      References:

      1. Akkemik E, Budak H, Ciftci M: Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study. J Enzyme Inhib Med Chem. 2010 Mar 17. Pubmed
      2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

      4. Cytochrome P450 2C8

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Cytochrome P450 2C8 P10632 Details

      References:

      1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

      1. Multidrug resistance-associated protein 4

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Multidrug resistance-associated protein 4 O15439 Details

      References:

      1. Uchida Y, Kamiie J, Ohtsuki S, Terasaki T: Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007 Dec;24(12):2281-96. Epub 2007 Oct 16. Pubmed

      Comments
      Drug created on June 13, 2005 07:24 / Updated on November 09, 2013 17:33