indication

For symptomatic treatment of arthritis and osteoarthritis.

pharmacology

Meloxicam 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 action

Anti-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.

toxicity

LD₅₀, Acute: 84 mg/kg (Rat); Oral 470 mg/kg (Mouse); Oral 320 mg/kg (Rabbit)

biotransformation

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.

absorption

Absolute bioavailability = 89%

half life

15-20 hours

route of elimination

Meloxicam 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.

drug interactions

Acenocoumarol: Meloxicam may increase the anticoagulant effect of acenocoumarol.

Anisindione: Meloxicam may increase the anticoagulant effect of anisindione.

Colesevelam: Bile 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.

Dicumarol: Meloxicam may increase the anticoagulant effect of dicumarol.

Ginkgo biloba: Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.

Lithium: Meloxicam increases serum levels of lithium

Telmisartan: Concomitant use of Telmisartan and Meloxicam may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.

Timolol: The NSAID, Meloxicam, may antagonize the antihypertensive effect of Timolol.

Trandolapril: The 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.

Treprostinil: The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Meloxicam. Monitor for increased bleeding during concomitant thearpy.

Voriconazole: Voriconazole 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.

Warfarin: The 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.