Meloxicaminteractions

Drugs that Interfere with Hemostasis (e.g., warfarin, aspirin, SSRIs/SNRIs): Monitor patients for bleeding who are concomitantly taking SYMBRAVO with drugs that interfere with hemostasis. Concomitant use of SYMBRAVO and analgesic doses of aspirin is not generally recommended. ACE Inhibitors, ARBs, or Beta-Blockers: Concomitant use with SYMBRAVO may diminish the antihypertensive effect of these drugs. Monitor blood pressure.

ACE Inhibitors and ARBs: Concomitant use with SYMBRAVO in elderly, volume-depleted, or those with renal impairment may result in deterioration of renal function. In such high-risk patients, monitor for signs of worsening renal function.

Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effects.

Lithium: Monitor for increases in lithium plasma levels Methotrexate: Monitor for increases methotrexate plasma levels..

7.1 Drugs Having

Clinically Important Interactions with SYMBRAVO See Table 2 for clinically significant drug interactions with SYMBRAVO.

Table 2: Clinically Important Drug Interactions with SYMBRAVO Drugs That Interfere with Hemostasis Clinical Impact Meloxicam and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of meloxicam and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention Monitor patients with concomitant use of SYMBRAVO with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding. Caution should be used when administering SYMBRAVO with warfarin since patients on warfarin may experience changes in International Normalized Ratio (INR) and an increased risk of bleeding complications when a new medication is introduced. Aspirin Clinical Impact Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone. Intervention Concomitant use of SYMBRAVO and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding. Meloxicam in SYMBRAVO is not a substitute for low dose aspirin for cardiovascular protection. SSRIs/SNRIs and Serotonin Syndrome Clinical Impact Cases of serotonin syndrome have been reported during co-administration of triptans and SSRIs or SNRIs. Intervention SYMBRAVO treatment should be discontinued if serotonin syndrome is suspected. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta blockers. In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Propranolol has been shown to increase the plasma AUC of rizatriptan. Intervention During concomitant use of SYMBRAVO and ACE-inhibitors, ARBs, or beta blockers, monitor blood pressure to ensure that the desired blood pressure is obtained. During concomitant use of SYMBRAVO and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function. When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter. The concomitant use of SYMBRAVO with propranolol is contraindicated. Diuretics Clinical Impact Clinical studies, as well as postmarketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID 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. Intervention During concomitant use of SYMBRAVO with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects. Lithium Clinical Impact NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis. Intervention During concomitant use of SYMBRAVO and lithium, monitor patients for signs of lithium toxicity. Methotrexate Clinical Impact Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention During concomitant use of SYMBRAVO and methotrexate, monitor patients for methotrexate toxicity. Cyclosporine Clinical Impact Concomitant use of meloxicam and cyclosporine may increase cyclosporine’s nephrotoxicity. Intervention During concomitant use of SYMBRAVO and cyclosporine, monitor patients for signs of worsening renal function. NSAIDs and Salicylates Clinical Impact Concomitant use of meloxicam with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy. Intervention The concomitant use of SYMBRAVO with other NSAIDs or salicylates is not recommended. Pemetrexed Clinical Impact Concomitant use of meloxicam and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information). Intervention During concomitant use of SYMBRAVO and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity. Patients taking SYMBRAVO should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration. In patients with creatinine clearance below 45 mL/min, the concomitant administration of SYMBRAVO with pemetrexed is not recommended. CYP2C9 Inhibitors Clinical Impact In vitro studies indicate that CYP2C9 (cytochrome P450 metabolizing enzyme) plays an important role in the metabolic pathway of meloxicam with a minor contribution of the CYP3A4 isozyme. Thus, concomitant usage of CYP2C9 inhibitors (e.g., amiodarone, fluconazole) may lead to abnormally high plasma levels of meloxicam due to reduced metabolic clearance. Intervention Use of SYMBRAVO in patients undergoing treatment with CYP2C9 inhibitors is not recommended. Ergot-Containing Drugs Clinical Impact Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Intervention Because these effects may be additive with rizatriptan, use of ergotamine-containing or ergot-type medications (e.g., dihydroergotamine or methysergide) and SYMBRAVO within 24 hours is contraindicated. 5-HT 1 Agonists Clinical Impact Vasospastic effects may be additive with co-administration within 24 hours of another 5-HT1 agonists. Intervention Use of SYMBRAVO within 24 hours of another 5HT 1 agonist is contraindicated. Monoamine Oxidase Inhibitors Clinical Impact MAO-A inhibitors increase the systemic exposure of rizatriptan and its metabolite. Intervention SYMBRAVO is contraindicated in patients taking MAO-A inhibitors and non-selective MAO inhibitors.