Meloxicam Interactions: Any Limit for Concomitant Use?

Meloxicam Interactions: Introduction

Rheumatoid arthritis (RA) is a painful autoimmune and inflammatory disease that affects the patient’s quality of life. While joint stiffness, tenderness, and swelling limit RA patients in their daily and professional routine and require long-term treatment, the pain is another issue that can be relieved shortly. Non-steroidal anti-inflammatory drugs (NSAIDs), including meloxicam, can be an effective option. (1-2)

Meloxicam is an effective medication that doctors prescribe thanks to its analgesic, antipyretic, and anti-inflammatory activities. However, in the case of RA pain, its use should be considered carefully due to the meloxicam’s interactions with methotrexate and cyclosporine and its possible toxicity. (2)

Moreover, meloxicam interacts with other medications, such as angiotensin-converting enzyme (ACE) inhibitors, lithium, aspirin, and others. This article explains the known interactions that meloxicam has with certain drugs. Some need monitoring by healthcare professionals, while for others, like aspirin, concomitant treatment is not recommended. (2)

Keep reading and learn all you need to know about meloxicam interactions and possible consequences.

How does meloxicam work?

Meloxicam is an NSAID that inhibits the enzyme cyclo-oxygenase (Cox-1 and Cox-2) and prevents prostaglandins synthesis (3). Prostaglandins are hormone-like substances made in the body tissue where inflammation occurs. High levels of prostaglandins cause prolonged inflammation and pain. (4-5)

Meloxicam inhibits Cox-1 and Cox-2 and the process of prostaglandins synthesis. By that, meloxicam reduces swelling, tenderness, stiffness, and joint pain in arthritis. (4-5)

Thanks to its analgesic and anti-inflammatory effects, doctors prescribe meloxicam in Osteoarthritis (OA), Rheumatoid Arthritis (RA), or Juvenile Rheumatoid Arthritis (JRA). (2)

Meloxicam Drug Interactions

Any medication may interact in the body with a medical condition, food, or another medication. Drug-drug interaction may result in changes in the effect of any of the concomitant drugs, either to increase or decrease clinical effects or to increase the risk of possible side effects. If the potential consequences are severe and harmful, concomitant usage of certain drugs is not recommended in such cases. (6)

Keep reading to learn about meloxicam interactions with drugs that you should take care of.

ACE-Inhibitors

NSAIDs interact with ACE inhibitors, and the effect of this interaction is a reduction of antihypertensive effects of the ACE inhibitors. (7-8) Another reason doctors consider when prescribing meloxicam is whether to give it to patients using ACE inhibitors due to the negative effect on kidney function. Combined with renin–angiotensin system inhibitors, NSAIDs increase the risk of acute kidney injury. (8-10)

Tell your doctor if you use ACE inhibitors for blood pressure regulation, and don’t use OTC painkillers before talking with your doctor.

Diuretics

When NSAIDs, including meloxicam, are used for a long time, it can result in a renal injury such as renal papillary necrosis (an injury of a kidney component, the one by which the urine flows into the ureters) or renal insufficiency (a poor function of the kidney). (2, 11)

When renal function is affected, renal prostaglandins help to maintain renal perfusion. However, NSAIDs reduce prostaglandins synthesis and, therefore, negatively affect fluid filtration in the kidney, resulting in salt and water retention. (2)

On the other side, diuretics are used to help the body to eliminate fluids. Using them together, NSAIDs can reduce the effect of furosemide and thiazides in some patients. This interaction was not confirmed in studies with furosemide and meloxicam. Yet, during concomitant diuretic therapy with meloxicam, the doctor will monitor renal function to ensure that the diuretic works and detect signs of renal failure early enough. (2, 12)

Interaction with Aspirin

Meloxicam is selective and inhibits Cox-2 ten-fold over Cox-1. Less inhibition to Cox-1 means that the prostaglandin’s activity in blood clotting and stomach and intestinal tract lining protection from digestive acids, positive effects of the Cox-1 enzyme, remains. This effect makes meloxicam selective NSAIDs with fewer gastrointestinal side effects than non-selective NSAIDs. (13)

Yet, when meloxicam is used with aspirin (1000 mg three times daily), the body will be exposed to a higher concentration than usual. This can potentially increase the side effects of meloxicam. In addition, when aspirin is used in low doses with meloxicam, this concomitant therapy may result in an increased rate of GI ulceration or other complications. For this reason, you may find in patient information that:

“…concomitant administration of meloxicam and aspirin is not generally recommended…” (2)

Meloxicam and Warfarin

Aside from analgesic, antipyretic, and anti-inflammatory effects, meloxicam shows to some level a blood thinning activity. When meloxicam inhibits Cox-1, it affects the prostaglandins responsible for blood thinning. The usage of blood thinners such as warfarin together has a synergistic effect and increases the risk of serious gastrointestinal bleeding more than it is by either drug alone. (2)

Because of this, if the doctor decides to prescribe meloxicam while you are on warfarin or other blood thinners’ therapy, anticoagulant activity will be monitored in the first few days after initiating or changing meloxicam therapy. (2)

Lithium and Meloxicam

Lithium is a medication that decreases the abnormal activities of the brain. Therefore, it is prescribed to people with bipolar disorder to prevent and treat maniac episodes. (14)

In patients who use lithium with the maximal meloxicam dose of 15 mg, the concentration of lithium increases by about one-fifth. Meloxicam inhibits the synthesis of kidney prostaglandins, so lithium is eliminated slower than usual. This lead to higher levels of lithium in the body. (2)

Symptoms of lithium overdose include diarrhea, vomiting, drowsiness, muscle weakness, loss of coordination, blurred vision, ringing in the ears, and frequent urination. (14)

You can take both medications together; still, be aware of the symptoms that might occur in case of toxicity and call your doctor immediately. (2)

Methotrexate

Methotrexate is a medication used to treat severe active rheumatoid arthritis, psoriasis, and certain types of cancer. In RA, when the patients have pain, painkillers can be used. In the case of NSAIDs, studies have shown that NSAIDs may reduce the elimination of methotrexate, resulting in the toxic effect of methotrexate. In a study where patients with RA were on concomitant treatments of methotrexate and meloxicam, meloxicam didn’t show a significant effect on a single methotrexate dose. (2)

Nevertheless, concomitant treatments of methotrexate and meloxicam should be used with caution. Be aware of the possible methotrexate toxicity symptoms, including hair loss, stomach upset, and muscle pain, as well as low blood counts and liver or kidney damage, as more severe side effects. (15)

Cyclosporine

Cyclosporine is a medication that suppresses the immune system and helps the body to accept the transplanted organ and not to reject it. Another use of cyclosporine is in patients with RA if methotrexate cannot give a needed response. (16)

The effect of meloxicam on renal prostaglandins can result in increasing cyclosporine’s nephrotoxicity. Also, in this case, the concomitant use of meloxicam with cyclosporine should be used cautiously. (2)

When Shouldn’t Meloxicam Be Used, or Are Precautions Needed?

The most common side effects of meloxicam are diarrhea, dyspnea, upper respiratory tract infections, headache, dyspepsia, and influenza-like symptoms.

In certain situations, meloxicam should be used cautiously or not at all. Meloxicam is contraindicated when patients experience a hypersensitive reaction. Patients with urticaria, asthma symptoms, or allergic reactions after taking aspirin or other NSAIDs should not use meloxicam. (2)

Meloxicam is contraindicated in patients with coronary surgery for perioperative pain treatment. This is because NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke. Such an event can end fatally. (2)

NSAIDs cause an increased risk of serious gastrointestinal adverse events and are not necessarily warn with symptoms. Ulceration, perforation of the stomach or intestines, and bleeding can lead to complications and be fatal. Elderly people are at higher risk. (2, 17)

Recommended Dosage

Thanks to its long-acting effect, meloxicam has the advantage of being used once daily, compared to frequently used NSAIDs (ibuprofen, naproxen) that are administered twice or more daily. (2)

The initial recommended dose for OA and RA is 7.5 mg. If this dose is insufficient, your doctor may double it. The maintenance dose should not exceed 15 mg daily.

In children with JIA, the dose is calculated based on the patient’s weight (1.5 mg per 12 kg). (2)

Final Thoughts

Read the Medication Guide carefully before starting using meloxicam or any other drug. You can find all the important information about interactions, contraindications, side effects and so on.

Tell your doctor the medications you use, including OTC products. Your doctor will know the best if some of the medications you use interact with meloxicam.

Call your doctor in case you experience any adverse event. You can also report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program) or by phone (1-800-332-1088).

Meloxicam, as any other medication, can help you the best if you use it safely.

1. Centers for Disease Control and Prevention, Rheumatoid arthritis (RA), 2020 Jul, https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html#:~:text=Rheumatoid%20arthritis%2C%20or%20RA%2C%20is,usually%20many%20joints%20at%20once
2. Food and Drug Administration, Mobic® (meloxicam) tablets and oral suspension, 3/2012, Prescribing information, https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020938s022lbl.pdf
3. National Library of Medicine, Meloxicam, 202, Jan, https://www.ncbi.nlm.nih.gov/books/NBK548278/
4. Prostaglandins, Cleveland Clinic, 11/04/2022, https://my.clevelandclinic.org/health/articles/24411-prostaglandins
5. E. Ricciotti, Ph.D. and G.A. Fitzgerald M.D., Prostaglandins and Inflammation, Arteriosclerosis, Thrombosis, and Vascular Biology. 2011;31:986–1000 https://www.ahajournals.org/doi/10.1161/ATVBAHA.110.207449?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
6. Food and Drug Administration, Drug Interactions: What You Should Know, 2013 Sep, https://www.fda.gov/drugs/resources-drugs/drug-interactions-what-you-should-know
7. G. P. Velo, P. Minuz, E. Arosio, M. G. Capuzzo, G. Covi & A. Lechi, Interaction between non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitors in man, Inflammation and Drug Therapy Series, 1987 https://link.springer.com/chapter/10.1007/978-94-010-9772-7_15
8. Cleveland Clinic, ACE inhibitors, 2021 Oct, https://my.clevelandclinic.org/health/treatments/21934-ace-inhibitors
9. T. Dreischulte, D. R. Morales, S. Bell, and B. Guthrie, Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin–angiotensin system inhibitors in the community increases the risk of acute kidney injury, Kidney International (2015) 88, 396–403 https://www.kidney-international.org/article/S2157-1716(15)32163-8/pdf
10. MedlinePlus, Renal papillary necrosis, https://medlineplus.gov/ency/article/000488.htm#:~:text=Renal%20papillary%20necrosis%20is%20a,urine%20flows%20into%20the%20ureters.
11. V. G. Florea, J. N. Cohn., Heart Failure: A Companion to Braunwald’s Heart Disease (Second Edition), 2011, Pages 610-625 https://www.sciencedirect.com/topics/immunology-and-microbiology/kidney-perfusion#:~:text=Renal%20perfusion%20is%20necessary%20to,hypotension%20causes%20decreased%20renal%20perfusion.
12. Cleveland Clinic, COX-2 Inhibitors, 2022 May, https://my.clevelandclinic.org/health/drugs/23119-cox-2-inhibitors
13. MedlinePlus, Lithium, 2017 Apr, https://medlineplus.gov/druginfo/meds/a681039.html
14. Food and Drug Administration, METHOTREXATE tablets, for oral use, Prescribing information, 2020 May, https://www.accessdata.fda.gov/spl/data/cb8dcdb9-da62-9b98-e053-2995a90abae7/cb8dcdb9-da62-9b98-e053-2995a90abae7.xml
15. National Library of Medicine, Cyclosporine, 2023 Mar, https://www.ncbi.nlm.nih.gov/books/NBK482450/#:~:text=Cyclosporine%20is%20an%20immunosuppressive%20agent,not%20adequately%20responded%20to%20methotrexate.
16. Meloxicam, MedlinePlus, 3/15/2021, https://medlineplus.gov/druginfo/meds/a601242.html

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