Other Prostaglandin Synthetase Inhibitors (PSI) including glucocorticoids and salicylates (acetylsalicylic acid): Co-administration of PSIs may increase the risk of gastro-intestinal 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 tid) to healthy volunteers tended to increase the AUC (10%) and Cmax (24%) of meloxicam. The clinical significance of this interaction is not known.
Oral anticoagulants, systemically administered heparin, thrombolytics: increased risk of bleeding if such co-prescribing cannot be avoided, close monitoring of their effects on coagulation is required (for solution for injection: see Contraindications)
Antiplatelet drugs, and Selective Serotonin Reuptake 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 (more than 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 MOBIC and diuretics should be adequately hydrated and be monitored for renal function prior to initiating treatment.
Antihypertensives (e.g. beta-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 pre-existing renal impairment this may lead to acute renal failure.
Cholestyramine binds meloxicam in the gastro-intestinal 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.
Pemetrexed: For the concomitant use of meloxicam with pemetrexed in patients with creatinine clearance from 45 to 79 ml/min, the administration of meloxicam should be paused for 5 days before, on the day of, and 2 days following pemetrexed administration. If a combination of meloxicam with pemetrexed is necessary, patients should be closely monitored, especially for myelosuppression and gastro-intestinal adverse reactions. In patients with creatinine clearance below 45 ml/min the concomitant administration of meloxicam with pemetrexed is not recommended.
Meloxicam is eliminated almost entirely by hepatic metabolism, of which approximately two thirds are mediated by cytochrome (CYP) P450 enzymes (CYP 2C9 major pathway and CYP 3A4 minor pathway) and one-third by other pathways, such as peroxidase oxidation. The potential for a pharmacokinetic interaction should be taken into account when meloxicam and drugs known to inhibit, or to be metabolised by, CYP 2C9 and/or CYP 3A4 are administered concurrently. Interactions via CYP 2C9 can be expected in combination with medicinal products such as oral antidiabetics (sulphonylureas, nateglinide), which may lead to increased plasma levels of these drugs and meloxicam. Patients concomitantly using meloxicam with sulfonylureas or nateglinide should be carefully monitored for hypoglycaemia.
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.