Meloxicam, or brand name Mobic, is a type of nonsteroidal anti-inflammatory drug (NSAID) that is used most often in the management of acute pain, which may arise due to multiple causes. Some approved indications include osteoarthritis, rheumatoid arthritis, and juvenile rheumatoid arthritis. It may be prescribed outside of these indications for its ability to improve symptoms such as pain, stiffness, swelling, and tenderness of the joints. Unlike many other NSAIDs, which are available over-the-counter (OTC), meloxicam is a prescription drug. This limits access to use for more serious short-term pain than a typical pulled muscle, for which many might head to their local pharmacy for a different NSAID.
Unique to most NSAIDs, which are available in various oral formulations, meloxicam can also be given as an injection. Additionally, meloxicam stands apart from other NSAIDs because it is considered a partially selective NSAID, blocking the COX-2 enzyme much more efficiently than other non-selective NSAIDs, which block COX-1 and COX-2 enzymes.
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The fact that many NSAIDs are available OTC, like ibuprofen and naproxen, diminishes the risk many people put themselves in due to a lack of appreciation of the serious interactions with other medications and other things we consume, like alcohol. There are known interactions that have the potential to both decrease the efficacy of meloxicam as well as enhance its known adverse effects. Understanding which medications and foods to avoid while taking NSAIDs like meloxicam is crucial in avoiding preventable bad outcomes.
Key takeaways:
- Meloxicam use can result in serious adverse effects, such as cardiovascular issues as well as gastrointestinal ulcer formation, tears, and bleeding.
- Meloxicam, and all NSAIDs, can also increase the risk of a heart attack or stroke, which can result in death. NSAIDs should be avoided after a recent heart attack due to the risk of another heart attack unless advised otherwise by a healthcare provider.
- All NSAIDs, including meloxicam, should be avoided immediately before and especially after a certain type of heart surgery, known as coronary artery bypass graft surgery or a CABG, due to cardiac safety concerns. In 2005, the Food and Drug Administration (FDA) issued a boxed warning against the administration of NSAIDs in this specific scenario.
- The risk of known adverse effects may be further increased when meloxicam is taken with interacting medications, such as a compounded risk elevation of developing an ulcer or bleeding when also taken with medications like corticosteroids, antiplatelet drugs, anticoagulants, SSRIs, or SNRIs.
- Aside from broad classes of medications interacting with NSAIDs, individual medications are also known to cause interactions. For example, very specific drug interactions are known to occur with methotrexate and lithium, which can cause very serious or permanent side effects.
- Less severe interactions can happen, such as when meloxicam is taken with bile acid sequestrants, which simply may decrease the absorption and desired effect experienced by the patient.
- Avoiding drug interactions with meloxicam is of utmost importance, but awareness of the signs and symptoms associated with an interaction is equally important. In the event of meloxicam interaction, it is always best to discuss the next steps directly with a medical professional.
Meloxicam-drug interactions
Meloxicam’s most serious drug-drug interactions will occur when taken in combination with other medications known to also cause the same type of serious adverse effects as meloxicam. Medications or supplements that can also increase the risk of developing gastrointestinal ulcers, esophageal tears, or those that can increase the risk of bleeding events are one such interacting group of medications. Similarly, meloxicam can increase the risk of certain adverse reactions from other drug classes, like many taken for high blood pressure or heart failure.
Corticosteroids
Meloxicam, and other NSAIDs, should be taken in combination with corticosteroids cautiously as both drug classes independently increase the risk of gastrointestinal (GI) adverse effects. When taken together, the risk is further increased. Corticosteroid use on its own has been associated with the development of gastrointestinal ulceration, and its use has been identified as a significant risk factor for gastrointestinal complications when used in combination with NSAIDs like meloxicam. Both corticosteroids and NSAIDs have been found to cause gastrointestinal injury through multiple mechanisms, including direct irritant effects on the protective layer of the GI tract, impairment of protective mechanisms such as suppression of gastric prostaglandin production, and reduced blood flow which interferes with the body’s repair response. The interaction is severe enough that prescribing information for meloxicam warns against the concomitant use of corticosteroids in an FDA issued Medication Guide. It is best to avoid this combination of medications entirely. However, short courses of combination therapy are likely to be safe.
Corticosteroids compromise class of medications, which includes:
- Betamethasone
- Dexamethasone
- Fludrocortisone (Florinef)
- Hydrocortisone (Cortef)
- Methylprednisolone (Medrol)
- Prednisolone (Orapred)
- Prednisone
Symptoms of stomach ulcers include heartburn, nausea, and burning stomach pain. The abdominal pain may resolve by eating certain foods or taking an acid-suppressive medication, but the pain will return. More serious symptoms of ulcers include vomiting blood, which may appear red or black and characterized as looking like coffee grounds, and dark blood in stools, which may be characterized as being black and tarry stools. Experiencing any of these symptoms warrants a check-in with a healthcare provider. Still, any vomiting of blood or observed blood in stools is best evaluated by seeking care at the emergency room (ER).
It is important to differentiate that this interaction is increased when NSAIDs and corticosteroids are taken together systemically; topical applications of both of these drug classes through available creams, lotions, and ointments do not cause the same degree of increased risk. If taking corticosteroids, an option for patients requiring an NSAID may be to attempt pain relief with a topical preparation to minimize this additive interaction.
Antiplatelet and Anticoagulant drugs
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NSAIDs like meloxicam exert a degree of inhibition on a specific enzyme known as cyclooxygenase (COX). Inhibition of this enzyme has a downstream effect on platelets by blocking the formation of a product known as thromboxane A2. The significance of thromboxane A2 is its function to lead to platelet aggregation and, ultimately, clot formation in the presence of an injury. Aspirin and many other platelets also interfere with platelet aggregation, so it comes to no surprise that studies have demonstrated an elevated risk of bleeding when antiplatelets are used in conjunction with NSAIDs.
- Antiplatelet drugs include:
- Aspirin
- Cilostazol (Pletal)
- Clopidogrel (Plavix)
- Dipyridamole (Persantine)
- Dipyridamole extended-release/aspirin (Aggrenox)
- Prasugrel (Effient)
- Ticregrelor (Brilinta)
- Vorapaxar (Zontivity)
Anticoagulants independently increase the risk of bleeding, as their main purpose is to thin blood. Combining therapy with an NSAID will further increase that risk. A comprehensive risk-to-benefit assessment should be conducted for all patients before concurrent use of an anticoagulant and NSAID. The risks of combination may vary based on the specific NSAID, its dose, duration of use, and other underlying health conditions like liver disease.
- Anticoagulant drugs include:
- Apixaban (Eliquis)
- Dabigatran (Pradaxa)
- Edoxaban (Savaysa)
- Rivaroxaban (Xarelto)
- Warfarin (Coumadin)
SSRIs and SNRIs
Multiple studies have reported significant increases in episodes of gastrointestinal bleeding when NSAIDs are used concurrently with antidepressants categorized as serotonin reuptake inhibitors, which can include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Medical professionals should use caution in combining these therapies and consider altering the NSAID or the serotonin reuptake inhibitor. While the exact mechanism of this interaction remains unclear, a review of available literature suggests that increased gastric secretion contributes to the increased stomach bleeding risk. Therefore, if no other options are available and the combination of these two drug classes must be used, adding an ulcer-protective drug to this regimen should be considered.
- Selective Serotonin Reuptake Inhibitors (SSRIs) include:
- Citalopram (Celexa)
- Escitalopram (Lexapro)
- Paroxetine (Paxil)
- Fluoxetine (Prozac)
- Vortioxetine (Trintellix)
- Vilazodone (Viibryd)
- Sertraline (Zoloft)
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) include:
- Duloxetine (Cymbalta)
- Venlafaxine (Effexor)
- Desvenlafaxine (Pristiq)
- Levomilnacipran (Fetzima)
- Milnacipran (Savella)
ACE inhibitors and ARBs
Combining meloxicam with antihypertensives like Angiotensin Converting Enzyme (ACE) inhibitors or Angiotensin II Receptor Blockers (ARBs) may decrease renal function. NSAIDs may also decrease the antihypertensive effects of these medications. Blood pressure changes may occur as soon as one hour following an initial dose of meloxicam in a patient on a long-term ACE inhibitor or ARB, likely related to the mechanism of NSAIDs in reducing the production of renal prostaglandins that support vasodilation. This may also be the rationale for an observed risk for acute kidney injury. Therefore, alternatives to NSAIDs should be employed in patients taking ACE inhibitors or ARBs, especially those with congestive heart failure, where the negative consequences of concurrent use should be avoided (e.g., fluid retention and weight gain, which could then cause trouble breathing).
- Angiotensin converting enzyme inhibitor (ACE-inhibitors) include:
- Benazepril (Lotensin)
- Captopril
- Enalapril (Vasotec)
- Fosinopril
- Lisinopril (Zestril)
- Quinapril (Accupril)
- Ramipril (Altace)
- Trandolapril (Mavik)
- Angiotensin II receptor blockers (ARBs) include:
- Azilsartan (Edarbi)
- Candesartan (Atacand)
- Irbesartan (Avapro)
- Losartan (Cozaar)
- Olmesartan (Benicar)
- Telmisartan (Micardis)
- Valsartan (Diovan)
Diuretics
The diuretic drug class is another medication class that encompasses subclasses based on mechanism of action and includes loop diuretics or thiazide diuretics. In general, any diuretic use in conjunction with meloxicam should occur with great caution, given the concern for decreased efficacy of the diuretic. This interaction can be especially concerning in those requiring the diuretic for certain medical conditions like heart failure or severe liver disease, like cirrhosis. The alterations experienced in fluid balance due to decreased efficacy with loop diuretics can trigger additional problems in these individuals, sometimes requiring hospitalization. In addition, several reports also suggest the risk of developing kidney problems when NSAIDs are used with loop diuretics, likely having to do with meloxicam’s mechanism of action on inhibiting prostaglandin synthesis (as diuretics may reap some of their therapeutic effects by increasing prostaglandin concentrations).
- Loop diuretics include:
- Bumetanide (Bumex)
- Ethacrynic acid (Edecrin)
- Furosemide (Lasix)
- Torsemide (Demadex)
More specific to thiazide diuretics, which are used more for blood pressure control than loop diuretics, those adding meloxicam to their regimen may experience a decrease in efficacy, and one might see an increase in measured blood pressure. The exact mechanism of this reaction remains undefined but may have to do with NSAID action at the primary site in kidneys where thiazides exert their effects. Those taking thiazide diuretics with meloxicam should monitor their blood pressure and use the lowest dose possible for the shortest period of time. In addition to the decreased efficacy on blood pressure, the combination may increase the risk of kidney injury observed with NSAIDs.
- Thiazide diuretics include:
- Chlorothiazide (Diuril)
- Chlorthalidone (Thalitone)
- Hydrochlorothiazide (Dyazide)
- Metolazone (Zaroxolyn)
Methotrexate
Methotrexate is a chemotherapeutic agent. It can be used in high doses in the management of certain oncologic conditions. Still, it can be used on a weekly regimen for those with certain autoimmune disorders, such as rheumatoid arthritis. The severity of the drug interaction between meloxicam and methotrexate is dose-dependent, so coadministration of NSAIDs and higher doses of methotrexate used in oncologic disorders should be avoided altogether. The combination in this clinical scenario with high dose methotrexate can further increase blood methotrexate levels by decreasing its elimination mechanisms, which has potentially fatal gastrointestinal and hematologic toxicity. Signs of methotrexate toxicity include skin rash, photosensitivity, and hair loss; more severe side effects include blood disorders, liver damage, kidney damage, ulcers in the mouth and gastrointestinal tract, and severe allergic reactions. Any of these should warrant seeking medical advice from a healthcare professional immediately. Co-administration with lower doses of methotrexate, such as for autoimmune disorders, may be permissible. but it’s best to limit this to as short of a course as possible to avoid issues.
Lithium
Lithium is a medication used in psychiatric disorders, including bipolar disorder and major depressive disorder. Lithium is a very interesting and complicated medication and requires close monitoring of blood levels of the medication. Lithium toxicity can occur at doses, resulting in blood levels very close to the known therapeutic range, and many medications are known to impact lithium serum levels. Specific NSAIDs, including meloxicam and celecoxib, may increase the lithium levels more than others. In addition, the interaction is difficult to predict since it doesn’t occur in all patients or to the same extent. Side effects of elevated lithium levels to monitor include skin reactions, excessive urination or thirst, changes in appetite resulting in weight gain or loss, and impaired coordination. If meloxicam must be used in a patient on lithium, it is best to consider a reduction in the dose of lithium upon initiation of the NSAID, with close monitoring for lithium toxicity; similarly, if a patient is on both medications and the NSAID is discontinued or the dose decreased, monitoring for changes in the effects of lithium should be monitored.
Cyclosporine
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Cyclosporine is an immunosuppressant agent used in multiple conditions, such as aplastic anemia, graft-versus-host disease, psoriasis, and others. One of the adverse effects of cyclosporine is its tendency to impact renal function by causing the construction of renal vessels. NSAIDs, including meloxicam, also have a propensity to cause constriction of blood vessels in the kidneys through their inhibition of prostaglandins. Therefore, when taken together, each medication will enhance the nephrotoxic effect of the other drug. In addition, NSAIDs may increase the serum concentrations of cyclosporine, and vice versa, further exacerbating the interaction. Fortunately, the mechanism by which both drugs impact renal function is reversible, such that discontinuing the medications should result in a resolution of kidney function and not long-term kidney disease.
Meloxicam-food interactions
Given Meloxicam’s propensity to constrict blood vessels by inhibiting prostaglandin synthesis throughout the body and within the kidney, patients may experience sodium and fluid retention. It is important to be mindful of salt intake when taking NSAIDs long-term, as the combination of a diet high in salt with chronic NSAID use could cause elevations in blood pressure, heart disease, and even heart failure. Monitoring sodium and water retention through a sudden weight gain is important to identify this interaction.
Other meloxicam interactions
Supplements known to possess antiplatelet activity, such as ginkgo biloba, garlic, ginger, ginseng, and turmeric, also have the potential to interact with NSAIDs like meloxicam.
Meloxicam can also interact with cigarette smoking, resulting in a further risk of gastrointestinal bleeding, development of ulcers, or tears.
Meloxicam and alcohol
Drinking alcohol while taking meloxicam is best avoided. This combination can increase many gastrointestinal side effects discussed, specifically developing an ulcer and possible subsequent bleeding. Chronic NSAID use is advised against regular drinkers, especially heavy drinkers (e.g., three or more alcoholic drinks per day). The risk of damaging effects on the gastric mucosal barrier in heavy alcohol users occurs in a dose-dependent manner of NSAID use. If you’re not a heavy drinker, it’s still best to wait four to six hours between taking meloxicam and having a drink, or vice versa, to minimize liver injury.
Meloxicam and caffeine
The effects of meloxicam may be enhanced by consuming it with caffeine because caffeine may interfere with the metabolism of the NSAID. Despite this perceived benefit, it’s best not to try to reap additional benefits by consuming the two together consistently. Everyone is affected differently by caffeine and NSAIDs, which may cause some additional stomach upset.
Meloxicam and medical conditions
Those with certain health conditions, including liver disease or kidney problems, high blood pressure, asthma, are pregnant or plan to become pregnant, and are breastfeeding or plan to breastfeed, should avoid using meloxicam. The risk-to-benefit safety ratio of developing an adverse effect due to using meloxicam does not warrant use in these conditions.
How to minimize meloxicam interactions
Always carry a complete list of medications, including supplements, on your person. Any time you’re inquiring about medical advice, provide this list so that a thorough review and drug information assessment can be performed to minimize the risk of drug interactions. Anytime you start a new medication and new signs or symptoms arise, however mild they might be, it’s best to review them with your healthcare professional.
When to talk to a healthcare provider about meloxicam interactions
This article is not a complete list of meloxicam interactions. Be mindful of the risk of meloxicam and other NSAIDs when used in combination with prescription and over-the-counter medications. Communicate with a healthcare professional anytime you are using meloxicam for more than a day or two so that a comprehensive review of interactions can occur, including interference with any known medication conditions, to ensure proper management and monitoring.
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