How does meloxicam affect blood pressure. Can NSAIDs like meloxicam raise blood pressure in people with normal readings. What precautions should patients take when using meloxicam for pain and inflammation.

The Link Between Meloxicam and Elevated Blood Pressure

Meloxicam, a nonsteroidal anti-inflammatory drug (NSAID), is widely prescribed for pain and inflammation associated with conditions like arthritis. However, recent reports have shed light on a concerning side effect: its potential to significantly raise blood pressure, even in individuals with previously normal readings.

A reader shared a startling experience where meloxicam raised their blood pressure from a typical 120/75 to an alarming 210/131 after just one day of use. This dramatic increase highlights the importance of understanding the cardiovascular risks associated with NSAIDs like meloxicam.

Why Does Meloxicam Affect Blood Pressure?

Meloxicam, like other NSAIDs, can impact blood pressure through various mechanisms:

• Fluid retention
• Decreased kidney function
• Interference with blood pressure medications
• Changes in prostaglandin production

These effects can lead to both new-onset hypertension and worsening of existing high blood pressure.

NSAIDs and Hypertension: A Widespread Concern

The issue of NSAIDs raising blood pressure extends beyond meloxicam. Common over-the-counter medications like ibuprofen and naproxen, as well as prescription drugs such as celecoxib (Celebrex) and diclofenac (Voltaren), can all contribute to elevated blood pressure.

A study published in JAMA Internal Medicine in November 2021 found that 18% of US adults with hypertension reported taking medications that may cause elevated blood pressure, including NSAIDs. The use of these medications was associated with increased odds of uncontrolled hypertension and greater use of antihypertensive medications.

Are Some People More at Risk?

While anyone taking NSAIDs may experience an increase in blood pressure, certain groups may be at higher risk:

1. Individuals with pre-existing hypertension
2. Older adults
3. Those with kidney disease
4. Patients taking certain blood pressure medications
5. People with cardiovascular risk factors

It’s crucial for these individuals to closely monitor their blood pressure when starting or changing NSAID therapy.

The FDA’s Black Box Warning for Meloxicam

The US Food and Drug Administration (FDA) mandates a black box warning for meloxicam and other NSAIDs, highlighting the potential cardiovascular risks. This warning states that NSAIDs may increase the risk of serious cardiovascular events, including myocardial infarction and stroke, which can be fatal.

The FDA also requires specific cautions regarding blood pressure in the official prescribing information for meloxicam. These warnings emphasize the need for careful blood pressure monitoring during NSAID treatment, especially in patients with hypertension or those taking certain blood pressure medications.

Is This Information Reaching Patients?

Despite these warnings, there’s concern that many patients may not be fully aware of the potential blood pressure risks associated with NSAIDs. This is particularly troubling for over-the-counter medications, which consumers often perceive as inherently safe.

Real-World Experiences: Patients Report Blood Pressure Spikes

Several readers have shared their experiences with NSAIDs and blood pressure:

• One individual saw their blood pressure rise from 120/80 to 190/144 over three years of meloxicam use.
• Another reported that both meloxicam and ibuprofen contributed to high blood pressure, which normalized after discontinuing the medications.
• A patient taking ibuprofen for shingles pain discovered elevated blood pressure during a routine check-up.

These anecdotes underscore the importance of regular blood pressure monitoring for anyone taking NSAIDs, even if they’ve never had hypertension before.

Monitoring Blood Pressure While Taking Meloxicam

Given the potential for significant blood pressure increases, it’s crucial for patients taking meloxicam or other NSAIDs to monitor their blood pressure regularly. This is especially important during the first few days of treatment or when changing dosages.

How Often Should Blood Pressure Be Checked?

For patients starting meloxicam:

• Check blood pressure daily for the first week
• Continue monitoring 2-3 times per week for the next month
• If stable, reduce to weekly checks
• Report any significant increases to your healthcare provider immediately

Remember, early detection of blood pressure changes can prevent serious complications like stroke or heart attack.

Alternatives to Meloxicam for Pain Management

For patients concerned about the blood pressure effects of meloxicam, or those who have experienced hypertension while taking it, alternative pain management strategies may be worth exploring:

Non-Pharmacological Approaches

• Physical therapy
• Acupuncture
• Heat or cold therapy
• Exercise and stretching routines
• Weight management
• Stress reduction techniques

Alternative Medications

• Acetaminophen (Tylenol) – generally doesn’t affect blood pressure
• Topical NSAIDs – may have less systemic absorption
• Low-dose aspirin – if appropriate and recommended by a healthcare provider
• Prescription medications like duloxetine or gabapentin for certain types of pain

Always consult with a healthcare provider before making changes to your pain management regimen, especially if you have chronic conditions or take other medications.

The Importance of Open Communication with Healthcare Providers

The experiences shared by patients highlight a critical need for improved communication between healthcare providers and patients regarding the potential side effects of NSAIDs like meloxicam.

What Should Patients Discuss with Their Doctors?

When prescribed meloxicam or any NSAID, patients should:

• Ask about potential blood pressure effects
• Discuss their current blood pressure status and any history of hypertension
• Inquire about the frequency of blood pressure monitoring
• Report any changes in blood pressure or new symptoms promptly
• Review all current medications to check for potential interactions

Open dialogue can help ensure that the benefits of pain relief are balanced against potential cardiovascular risks.

Balancing Pain Relief and Cardiovascular Health

The challenge for both patients and healthcare providers is finding the right balance between effective pain management and minimizing cardiovascular risks. This often requires a personalized approach, taking into account individual risk factors, medical history, and the severity of pain or inflammation.

Strategies for Safe NSAID Use

To minimize risks while using meloxicam or other NSAIDs:

1. Use the lowest effective dose for the shortest duration possible
2. Regularly reassess the need for continued NSAID therapy
3. Consider alternating or combining with non-NSAID pain relief methods
4. Stay well-hydrated to support kidney function
5. Maintain a heart-healthy lifestyle (diet, exercise, stress management)
6. Adhere to recommended blood pressure monitoring schedules

By following these strategies, patients can work with their healthcare providers to achieve pain relief while safeguarding their cardiovascular health.

Future Directions in Pain Management and Cardiovascular Safety

As awareness grows about the potential blood pressure effects of NSAIDs like meloxicam, researchers and pharmaceutical companies are exploring new avenues for safer pain management options.

Emerging Research and Developments

Some promising areas of investigation include:

• Novel NSAID formulations with reduced cardiovascular risks
• Targeted pain therapies that don’t affect blood pressure
• Advanced monitoring technologies for early detection of cardiovascular changes
• Personalized medicine approaches to predict individual NSAID response

These developments may offer hope for future pain management strategies that provide relief without compromising cardiovascular health.

In conclusion, while meloxicam and other NSAIDs remain valuable tools for managing pain and inflammation, their potential to raise blood pressure necessitates caution and vigilance. By understanding the risks, monitoring blood pressure regularly, and maintaining open communication with healthcare providers, patients can make informed decisions about their pain management while protecting their cardiovascular health. As research continues, we may see new options emerge that offer the benefits of NSAIDs without the associated blood pressure risks, paving the way for safer, more effective pain relief strategies.

Meloxicam Raised Blood Pressure Through the Roof!

Tens of millions of people take oral NSAIDs (nonsteroidal anti-inflammatory drugs) every day. We are talking about celecoxib, diclofenac, ibuprofen, meloxicam and naproxen. Most people realize that such drugs can be irritating to the digestive tract. Indigestion or stomach ulcers are not uncommon. What is less well realized is that these drugs can raise blood pressure. Many doctors and pharmacists may assume that this only occurs in people with existing hypertension. But even people with normal blood pressure can be affected. This reader discovered that meloxicam raised blood pressure way too high!

A Scary Situation!

Q. I was prescribed meloxicam for pain and inflammation. After just one day, my blood pressure went from my typical reading of 120/75 up to 210/131.

I discontinued the prescription immediately. The same thing had happened to my mother when she was prescribed Celebrex.

Anyone prescribed NSAID-type arthritis medicines ought to be very careful. You should self-monitor your blood pressure closely in the first few days, because by the time you get back in to see your provider you could have already had a stroke or heart attack.

A. You describe a well-known but often overlooked adverse drug reaction. Nonsteroidal anti-inflammatory drugs (NSAIDs) can raise blood pressure. This includes OTC pain relievers such as ibuprofen or naproxen as well as prescription medications like celecoxib (Celebrex), diclofenac (Voltaren) and meloxicam (Mobic). Your suggestion to measure blood pressure when taking NSAIDs is really important!

An article in JAMA Internal Medicine (Nov. 22, 2021) noted that people taking antidepressants, NSAIDs, steroids or estrogens are more likely to have uncontrolled hypertension or need extra BP medicines. Here are the conclusions of this study:

“In this nationally representative survey study, 18% of US adults with hypertension reported taking medications that may cause elevated BP. The use of these medications was associated with increased odds of uncontrolled hypertension among individuals not taking antihypertensives and greater use of antihypertensives among both patients with controlled and uncontrolled hypertension.”

This reader is not the only person to discover that meloxicam raised blood pressure.

From Normal to Hypertension on Meloxicam

Q. After diagnosing my arthritis, my doctor prescribed meloxicam. During the three years I took it, my blood pressure went from 120/80 to 190/144. Unfortunately, he wasn’t monitoring it.

When I found I had such high blood pressure, I got off the meloxicam and was put on lisinopril. Six months later, my BP is stable at 130/86. I do want it lower, so the fight is still on. Please monitor your blood pressure while you are on meloxicam.

A. Great advice to anyone taking an NSAID (nonsteroidal anti-inflammatory drug). That includes OTC pain relievers like ibuprofen and naproxen as well as prescription arthritis drugs like celecoxib, diclofenac or meloxicam.

The Black Box Warning with Meloxicam

The FDA mandates the following warning with meloxicam and other NSAIDs.

“NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.”

Meloxicam Raised Blood Pressure:

The FDA also requires this caution in the official prescribing information:

“NSAIDs, including meloxicam, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV [cardiovascular] events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including meloxicam, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.”

We are not sure whether most prescribers share this information with their patients. And we fear that people taking over-the-counter drugs like ibuprofen or naproxen may not take such a warning to heart. After all, OTC drugs are supposed to be safe.

Readers Report Meloxicam Raised Blood Pressure:

Jane has RA (rheumatoid arthritis) and is in pain:

“I took NSAIDS (meloxicam or ibuprofen) for RA pain for a year. These drugs gave me high blood pressure. As soon as I got off these NSAIDs, my blood pressure went back to normal. However, there are so few drugs that doctors will prescribe for pain. I feel abandoned.”

Ralph also developed blood pressure problems with ibuprofen:

“I was suffering from shingles and took a lot of ibuprofen for several months. On a visit to the doctor for the condition, my blood pressure was 179/100.

“I am 73 years old, and have consistently had blood pressure in the range of 120/70 my entire adult life. I researched The People’s Pharmacy website and a man my age reported his sudden rise in blood pressure, saying when he quit taking ibuprofen, his blood pressure quickly dropped to normal.

“I bought a blood pressure cuff so I could test, quit taking Ibuprofen, and my blood pressure was back to normal in two days.”

Judi had a scary encounter with naproxen:

“Last year my surgeon put me on naproxen before it became necessary for him to do neck surgery on me. On day 21 of taking naproxen my blood pressure spiked to 234/180 and I went to the ER. I will never take NSAIDS again.”

Pat also got into trouble with naproxen:

“I haven’t been prescribed meloxicam, but I have been prescribed naproxen for arthritis pain. I have also noticed elevated blood pressure since taking this. So, what does the doctor do? Prescribe a diuretic-type drug to lower blood pressure. I decided to stop NSAIDs altogether, even the OTC type.”

What’s a Person To Do if NSAIDs Raise Blood Pressure?

Most people take NSAIDs because they are in pain. But if such drugs raise blood pressure, they are inappropriate. Taking another medication to treat hypertension brought on by a pain reliever is not the answer.

Anyone caught in this situation may wish to consult our eGuides to Alternatives for Arthritis and Blood Pressure Treatment.

Tough Time of Year:

This is the time of year people start sniffling and sneezing because of colds and influenza. Oral decongestants such as phenylephrine or pseudoephedrine can also raise blood pressure. Here is a link to our article on other medications that can increase blood pressure. You will be surprised that hemorrhoid remedies can also do this!

To learn more about drugs that can make it harder to control hypertension and a variety of strategies to manage it, you might want to consult our eGuide to Blood Pressure Solutions. All our eGuides can be found in the Health eGuides section of this website.

General pharmacology of meloxicam–Part II: Effects on blood pressure, blood flow, heart rate, ECG, respiratory minute volume and interactions with paracetamol, pirenzepine, chlorthalidone, phenprocoumon and tolbutamide

. 1996 Jun;27(4):679-88.

doi: 10.1016/0306-3623(95)02035-7.

G Engelhardt 
¹
, D Homma, K Schlegel, C Schnitzler, R Utzmann

Affiliations

Affiliation

• ¹ Department of Pharmacologic Research, Dr. Karl Thomae GmbH, Biberach/Riss, Germany.

• PMID:

  8853305

• DOI:

  10. 1016/0306-3623(95)02035-7

G Engelhardt et al.

Gen Pharmacol.

1996 Jun.

. 1996 Jun;27(4):679-88.

doi: 10.1016/0306-3623(95)02035-7.

Authors

G Engelhardt 
¹
, D Homma, K Schlegel, C Schnitzler, R Utzmann

Affiliation

• ¹ Department of Pharmacologic Research, Dr. Karl Thomae GmbH, Biberach/Riss, Germany.

• PMID:

  8853305

• DOI:

  10.1016/0306-3623(95)02035-7

Abstract

The pharmacodynamic properties of meloxicam, a new nonsteroidal antiinflammatory drug (NSAID), that go beyond those typical of an NSAID were examined. The extent to which meloxican shows NSAID-like interactions with paracetamol, pirenzepine, chlorthalidone, phenprocoumon and tolbutamide was also investigated. In the dose range studied, meloxicam had no influence on the blood pressure of the unanaesthetized rat, blood flow, heart rate, ECG and respiratory minute volume of the anaesthetized cat or on the blood pressure, heart rate and respiratory minute volume of the anaesthetized dog. The acute toxicity level of meloxicam after oral and parenteral administration to the rat and mouse proved considerably lower than that of indomethacin. Meloxicam showed excellent tissue tolerability following parenteral administration. The effects against inflammatory pain and acute antiexudative effects of meloxicam were enhanced by simultaneous low doses of paracetamol. Pirenzepine showed an antagonistic effect on the ulcerogenicity of meloxicam in the rat stomach. The diuretic effect of chlorthalidone in the rat was not influenced by high doses of meloxicam. The effect of phenprocoumon in the rat was enhanced by high doses of meloxicam. However, the hypoglycaemic effect of tolbutamide in the rabbit was not influenced by meloxicam.

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MeSH terms

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Tolerability and safety of meloxicam | Badokin V.

V.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used drugs in clinical practice. In Europe, this class of pharmacological agents in polyclinic practice is prescribed by 82% of general practitioners and 84% of rheumatologists, and in the hospital they are used in 20% of patients. The main property of NSAIDs is to suppress the inflammatory process or significantly reduce its intensity. In addition, they have a distinct analgesic and antipyretic effect.

NSAIDs are most widely used in the treatment of inflammatory and degenerative diseases of the joints and spine, diffuse connective tissue diseases, microcrystalline arthropathies, extra-articular soft tissue diseases, a large group of diseases accompanied by pain in the lower back, osteoporosis and other bone diseases accompanied by pain. They are also used in cardiology for inflammatory cardiopathy and as a means of preventing thrombosis, in preoperative preparation and management of patients after “small” operations, with headaches, oligomenorrhea, and many other inflammatory processes accompanied by fever and pain. Their positive effect in oncology as a means of preventing colonorectal cancer or metastasis of malignant tumors, in neurology in the treatment of Alzheimer’s dementia, as well as their preventive effect on the development of atherosclerosis, especially in patients with immunoinflammatory diseases, are discussed.
In rheumatology, NSAIDs are the main symptom-modifying drugs for short-term and long-term therapy of a large number of diseases, as well as drugs of choice for the initial therapy of arthritis of various origins. Recently, there have been isolated reports that NSAIDs have not only a symptomatic effect. It is believed that they are able to slow down the progression of certain diseases, such as ankylosing spondylitis and osteoarthritis. In one of the papers published at 1999, it was indicated that among the direct costs of treatment in patients with rheumatoid arthritis, 75% are accounted for by NSAIDs [1]. The generally accepted point of view on the need for basic anti-inflammatory therapy at an early stage of rheumatoid arthritis and the introduction of high technologies in the complex therapy of this disease have, of course, reduced this percentage, but it remains quite significant in the structure of the cost of treating this inflammatory joint disease, like many other diseases.
The main mechanism of action of NSAIDs is the suppression of prostaglandin biosynthesis. As is known, prostaglandins are characterized by a wide range of biological effects (Table 1). [2,3].
The pharmacological activity of NSAIDs is not limited to the suppression of prostaglandin production. In addition, they inhibit the synthesis of leukotrienes, the formation of superoxide radicals and the release of lysosomal enzymes, affect the activation of cell membranes, the aggregation and adhesion of neutrophils, the functions of lymphocytes, and the synthesis of leukotrienes. Hence it is clear why NSAIDs have not only a positive (therapeutic) effect, but also have a fairly large range of adverse events (Table 2). The most frequently observed gastrointestinal disorders of varying severity – from mild to incompatible with life. NSAIDs have nephro- and hepatotoxicity, contribute to fluid retention, the development of heart failure, arterial hypertension, and have a dystrophogenic effect on the myocardium. They affect the metabolism of brain cells and cause severe headaches and other manifestations of cerebral toxicity. Hematological disorders are possible, up to the development of severe cytopenias, hypo- and aplastic anemia, inhibition of platelet aggregation, impaired hemostasis with massive bleeding. NSAIDs often cause a variety of allergic reactions and broncho-obstructive syndrome (“aspirin” asthma), which is associated with their effect on the synthesis and release of leukotrienes.
When choosing an NSAID and its daily dose, one should take into account their anti-inflammatory activity and tolerability, the possibility of combination with other types of therapy, the presence of concomitant diseases, metabolic features in the body, pharmacokinetics, COX (cyclooxygenase) – selectivity. Of great importance is the identification of risk factors for adverse events of NSAIDs, which include older age, a history of gastrointestinal pathology, concomitant diseases (arterial hypertension, heart failure, liver and kidney disease), taking high doses of NSAIDs, combined therapy of NSAIDs with glucocorticoids, low doses of acetylsalicylic acid or indirect anticoagulants. It is generally accepted that selective COX-2 inhibitors, which include meloxicam (Movasin et al.), have a higher safety.
Meloxicam is a derivative of enoliconic acid. It, like all other NSAIDs, has anti-inflammatory, analgesic and antipyretic activity. More than 99.5% of meloxicam is protein bound. In the synovial fluid, its concentration is 2 times less than in the blood plasma, but still high enough to suppress the inflammatory process in the tissues of the joint. Its half-life is 20 hours, and this gives rise to a single dose during the day. It is excreted from the body in urine and feces. The drug has a cumulative property, while its maximum concentration occurs on the 3-5th day of admission. For a faster therapeutic effect, it is advisable to carry out the so-called “stepwise” therapy, which consists in intramuscular administration of 15 mg of meloxicam in the first three days of treatment, followed by transfer of the patient to oral administration of the drug [4]. The daily dose of meloxicam is 15 mg. A lower dose is indicated for patients with erosive gastritis, gastric ulcer or decreased glomerular filtration rate, as well as for elderly patients who have a decrease in the excretion of many drugs. Meloxicam in the body does not interact with other drugs, including cytostatics, diuretics, cardiac glycosides, b-blockers, and others, which is of great importance for the rational treatment of patients with concomitant (comorbid) diseases.
High clinical efficacy of meloxicam has been demonstrated in patients with rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, pain in the lower back and many other diseases. The evidence base for meloxicam is based on numerous randomized, placebo-controlled trials in which its efficacy and tolerability were compared with placebo and the main NSAIDs – COX-selective and COX-non-selective [5-7]. The duration of therapy in these studies ranged from 4 weeks. up to 18 months Significant improvement, which occurred after 2 weeks. from the start of therapy with meloxicam, lasted for 18 months, i. e. the entire observation period. In terms of its effectiveness, meloxicam was not inferior to diclofenac, naproxen and piroxicam. Good results of treatment with meloxicam were obtained not only in patients with rheumatoid arthritis, but also with ankylosing spondylitis in its 12 months. application. According to its therapeutic activity, 15 mg of meloxicam had the same effect as 20 mg of piroxicam, and a further increase in the daily dose (up to 22.5 mg/day) was not accompanied by an increase in its anti-inflammatory and analgesic effect.
The greatest number of studies on the clinical efficacy and safety of meloxicam has been carried out in osteoarthritis. The expediency of prescribing meloxicam in osteoarthritis is dictated by its positive effect on the metabolism of hyaline cartilage, the main springboard for the development of the pathological process in this disease [8,9]. Meloxicam has an anabolic effect, inhibits interleukin-1, expresses growth factors, including transforming growth factor-1, inhibits the degradation of aggrecan, neutralizes the action of metalloproteinases and inhibits chondrocyte apoptosis, i. e. actively intervenes in the development of the pathological process in this disease [10,11].
Most of the studies evaluating meloxicam in osteoarthritis met the current requirements for approbation of drug preparations. They were multicenter, prospective, double-blind and performed according to a single protocol [12–14]. Meloxicam led to a significant decrease in the subjective manifestations of the disease with a decrease in the intensity of pain when walking and at rest. In some cases, there was complete relief of pain, a significant decrease in the intensity of morning stiffness or its cessation, resolution of manifestations of secondary (reactive) synovitis, and improvement in the function of the affected joints.
The efficacy of meloxicam in patients with osteoarthritis was studied in the MELISSA (Meloхicam Large Scale International Study Safety Assessment) and SELECT (Safety and Efficacy Large scale Evaluation of COX inhibiting Therapies) studies, in which the therapeutic activity of meloxicam (7. 5 mg/day) was compared with diclofenac (100 mg/day) or piroxicam (20 mg/day) [12,13]. Nearly 20,000 patients participated in these two trials. Meloxicam was found to be equivalent in clinical efficacy to diclofenac and piroxicam. Cancellation of the drug due to its low efficiency in the groups of diclofenac, piroxicam and meloxicam did not exceed 1.7%.
In the treatment of NSAIDs, a wide range of adverse events are observed. Prevention and treatment of these complications is one of the most important iatrogenic problems of modern medicine. The most common is gastrotoxicity. Every year, 100,000 patients develop adverse events associated with taking NSAIDs, which can have serious consequences due to the possible development of profuse bleeding, perforation of the wall of the stomach or intestines [15]. NSAID gastropathy is largely due to the half-life of individual drugs, differences in their systemic absorption, the basic pH of gastric juice, but above all, the degree of suppression of prostaglandin synthesis. Adverse events that develop when taking COX-non-selective drugs in 30% of patients are manifested by gastric and intestinal dyspepsia, 15% – endoscopically confirmed gastric ulcers, 1.7% – perforations or hemorrhages. Such severe prognostic gastroenterological complications as bleeding, perforation and ulcers in most cases occur without pain, which makes their timely diagnosis difficult, and in some patients lead to death.
NSAID-induced lesions of the gastrointestinal tract extend to all its departments and are characterized by polymorphism of manifestations. The mechanisms underlying such damage to the gastrointestinal tract are diverse and are associated with a decrease in blood flow in the mucosa and a violation of its trophism, the basic pH of gastric juice, the difference in systemic absorption of NSAIDs and adhesion of neutrophils. The direct toxic effect of NSAIDs on the digestive tract is an important component only at the beginning of treatment. The importance of genetic factors in the genesis of gastrointestinal bleeding caused by NSAIDs is discussed. Apoptosis of cells, especially the gastric mucosa, is also important. But the main cause of gastrointestinal complications of NSAIDs is associated with suppression of prostaglandin synthesis.
However, selective COX-2 inhibitors can also lead to severe complications. Interestingly, the relative risk of gastrointestinal bleeding in the appointment of specific COX-2 inhibitors is more pronounced than in the treatment of conventional NSAIDs. Thus, this indicator in patients over 65 years of age treated with lumiracoxib is 3.18, and with non-selective COX – 2.3, in males – 2.6 and 1.7, respectively. A high risk of bleeding was noted in patients who take combination therapy with lumiracoxib and aspirin (2.89) [16]. The presented data are the key to the prevention of gastropathy, possible bleeding and other serious complications in the treatment of NSAIDs. These measures should be carried out in all patients with risk factors and should include the appointment of selective NSAIDs and proton pump inhibitors, as well as monitoring for possible adverse events.
NSAID-gastropathy is significantly less common when taking meloxicam. The European pharmacoepidemiological multicentre prospective study evaluated the tolerance of meloxicam and other NSAIDs in patients with rheumatic diseases [10]. The duration of therapy was 6 months. Groups of patients in individual centers were randomized according to the main parameters of the pathological process. In the treatment with meloxicam, adverse events such as abdominal pain, gastritis, dyspepsia were significantly less common, and gastrointestinal bleeding was registered only in two out of 2530 patients, while other NSAIDs led to such a complication in 10 out of 1996 patients.
Interesting data were obtained in the MELISSA study, in which the tolerability of meloxicam 7.5 mg / day was studied in a comparative aspect. and diclofenac 100 mg/day. in 9323 patients with osteoarthritis. The duration of therapy was 4 weeks. This study involved 27 countries, including Russia [4,13]. The overall frequency of gastrointestinal adverse events in the appointment of diclofenac was significantly higher than in the treatment of meloxicam (19 and 13%, respectively), and according to E. S. Tsvetkova – in 22.2 and 6.8%, respectively [9]. Gastric dyspepsia, abdominal pain, nausea and vomiting, and diarrhea were significantly less common. Due to the development of adverse events, 2 times more patients stopped treatment with diclofenac than with meloxicam. The overall tolerability of meloxicam, according to doctors, was good in 91% and satisfactory in 9%, and the tolerability of diclofenac was good (84%), satisfactory (9%) and unsatisfactory (7%). Similar results were obtained in the SELECT study, in which meloxicam 7.5 mg/day. compared with piroxicam 20 mg/day. in 8227 patients with osteoarthritis.
It is interesting to note that when using meloxicam, the risk of developing gastrointestinal complications was also lower in individuals who simultaneously took acetylsalicylic acid to prevent thromboembolic complications (10.3% and 15.4%). A meta-analysis of a large number of studies showed that meloxicam compared with traditional NSAIDs (diclofenac, piroxicam and naproxen) reduces the risk of drug withdrawal due to the development of gastrointestinal complications by 41%, the risk of serious adverse reactions (perforation, ulceration, bleeding) – by 48% and the risk of intestinal dyspepsia – by 27%.
When taking NSAIDs, damage to the small intestine is more common than damage to the stomach. Enteropathy can develop rapidly, for example, after 14 days from the start of NSAID therapy. It is manifested by nonspecific edema, diaphragmatitis, ulcers, penetration, strictures, intestinal dyspepsia, bleeding, and iron deficiency anemia [17]. Selective COX-2 inhibitors reduce the risk of enteropathy by 50% compared with standard NSAIDs. Intestinal endoscopy using special capsules or double balloon endoscopy allows a detailed analysis of pathological changes in the small intestine when prescribing this group of drugs.
Recently began to pay close attention to NSAID-colonopathy, which occurs relatively often. Morphologically, damage to the large intestine is manifested by ischemic or collagenous colitis. The clinical stigmata of such colonopathy are ulcers, perforations, strictures of ischemic origin, obstructions, and recurrent irritable bowel syndrome [18]. In rare cases, massive intestinal bleeding is observed. Standard NSAIDs are 2 times more likely to lead to NSAID colonopathy compared to selective COX-2 inhibitors.
One of the complications of NSAID therapy is hepatotoxicity [19]. An increase in aminotransferases by 3 times or more is detected both with the appointment of standard and selective COX-2 inhibitors. Genetic factors, in particular the expression of cytochrome P450, are also involved in the induction of hepatotoxicity. Meloxicam has less hepatotoxicity than the widely used diclofenac. So, when taking meloxicam, an increase in AST was registered in 3%, and diclofenac – in 9% [9,12].
Much attention is paid to the cardiovascular adverse events of NSAIDs, in particular myocardial infarction and cerebrovascular accident [20, 21]. It should be noted that all traditional and selective NSAIDs are COX-2 inhibitors, although, of course, to varying degrees, and all of them dose-dependently increase the risk of thromboembolic complications [22]. On the other hand, almost all NSAIDs, both non-selective and selective, contribute to an increase in blood pressure, which, in turn, can also lead to thrombosis. However, there is no doubt that the higher the COX-2 selectivity, the more likely the development of cardiovascular and cerebral thrombotic complications. This primarily applies to specific COX-2 inhibitors – coxibs. According to Layton (2003), cardiovascular thrombotic complications during long-term treatment with meloxicam are observed in 0.1% of patients, celecoxib – in 0.16% and rofecoxib – in 0.14%, and cerebrovascular – in 0.27%, 0.39% and 0.48%, respectively. According to the FDA and the European Medical Agency, a contraindication to the use of specific COX-2 inhibitors is coronary heart disease or a history of stroke. With great caution, they should be used in individuals with risk factors for coronary heart disease and in elderly people.
Meloxicam differs from other selective COX-2 inhibitors in its effect on platelet aggregation, which is explained by the peculiarities of its structure. In particular, it binds to the upper part of the COX-2 channel, and highly selective coxibs – to the side pocket of the COX-2 channel, while they inhibit thromboxane to a lesser extent, and this explains the increased risk of thromboembolic complications in their use, t. to. thromboxane is actively involved in platelet aggregation.
NSAID prostaglandin inhibition leads to cardiorenal effects, which include impaired water and salt metabolism, arterial hypertension, congestive heart failure, nephrotic syndrome, acute renal failure. Some of these effects are associated with impaired cerebral circulation, and above all with arterial hypertension. Cerebral strokes against the background of long-term use of NSAIDs are associated not so much with an increase in diastolic blood pressure as systolic and, even more so, with the value of pulse pressure. Individual NSAIDs that increase systolic blood pressure include ibuprofen, rofecoxib, and etoricoxib. These three drugs are considered risk factors for ischemic stroke. Meloxicam is the least likely to increase blood pressure, both systolic and diastolic. In this regard, it is close to diclofenac, which also does not lead to an increase in blood pressure [23].
G. Singh et al. conducted a large study involving 3. 1 million people [data presented at the EULAR congress in Barcelona in 2007]. The vast majority of individuals included in this study were taking NSAIDs for various diseases. In this work, 15659 cases of cerebrovascular accident were identified. The relative risk of ischemic stroke for rofecoxib and indomethacin was 1.26, piroxicam -1.25, naproxen – 1.24, ibuprofen – 1.19, diclofenac – 0.98, celecoxib – 0.97. The value of this risk for meloxicam was 0.88, and it was the same as in the control group, not taking NSAIDs. Thus, meloxicam is not a risk factor for stroke. A positive feature of this drug is the lack of interaction with antihypertensive drugs when they are used together.
Often, NSAIDs contribute to the development of skin reactions, which are among the most common adverse events in the appointment of this group of drugs. Skin reactions are characterized by polymorphism of their manifestations and are divided into characteristic and uncharacteristic. The former include allergic contact dermatitis, photoallergic contact dermatitis, acute urticaria or angioedema, recurrent chronic urticaria, contact urticaria, fixed drug rash, and the uncharacteristic ones include bullous vasculitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS– syndrome (drug rash with eosinophilia and systemic manifestations).
Most often, skin rashes are caused by standard NSAIDs – acetylsalicylic acid, ketoprofen, ibuprofen, piroxicam, but reactions to selective COX-2 inhibitors are also possible. These reactions are based on an immunological mechanism. In Stevens-Johnson syndrome and toxic epidermal necrolysis, massive apoptosis of epidermal cells is observed, caused by cytotoxic T cells that release perforin and grancime B. The development of acute urticaria on NSAIDs is a consequence of immunoglobulin E (IgE)-dependent reaction. In such cases, they act as a hapten. Repeated exposure of the drug leads to an immune-dependent reaction with the formation of antibodies directed to a specific NSAID.
With the appointment of COX-1 inhibitors, an increased production of leukotrienes (LTA4) is observed. Therapy with leukotriene receptor antagonists can block NSAID-induced urticaria or significantly reduce their severity. COX-2 selective drugs show good tolerance in patients with chronic urticarial rash and aspirin-induced asthma, which fully applies to meloxicam [24].
Thus, meloxicam not only has a pronounced anti-inflammatory and analgesic effect, but is also characterized by good tolerability and high safety. The spectrum of adverse events is much lower than that of non-selective and selective COX inhibitors. These properties, along with its high clinical efficacy, have contributed to its widespread introduction into the complex therapy of not only inflammatory and degenerative rheumatic diseases, but also many other pathological conditions.

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Meloxicam

STYLAB offers meloxicam and meloxicam-D3 standards, as well as their mixtures with other non-steroidal anti-inflammatory drugs for their analysis in food raw materials and food products in accordance with GOST 32881-2014.

Meloxicam is a non-steroidal anti-inflammatory drug of the oxicam group. It is used both in medicine and in veterinary medicine for joint pain and inflammatory diseases. In the Russian Federation for 2019, 5 drugs containing meloxicam were registered. Most of them are intended for the treatment of dogs and cats. In other countries it is also used for cattle, sheep and exotic animals.

Meloxicam inhibits cyclooxygenase-2 to a greater extent than cyclooxygenase-1. This mechanism of action causes a reduced risk of ulceration and bleeding from the gastrointestinal tract relative to less selective NSAIDs. At the same time, meloxicam exhibits a fairly strong analgesic, antipyretic and anti-inflammatory effect.

Meloxicam is rapidly and well absorbed in the gastrointestinal tract. At the same time, after a single dose, two peaks of the concentration of meloxicam in the blood are observed: after 4-5 hours and 12-14 hours after administration. This is because meloxicam is metabolized in the liver, excreted in the small intestine, and from there it is reabsorbed into the blood. In the liver, 4 inactive metabolites of meloxicam are formed, which are then excreted in the faeces and urine. The half-life of this substance is 15-20 hours. Meloxicam is able to overcome the blood-brain and placental barriers, and is also excreted in milk.

The side effects of meloxicam in humans are well known. Nausea, vomiting, ulcers in the gastrointestinal tract and bleeding from the stomach or intestines occur less frequently than when taking NSAIDs, which equally intensively inhibit cyclooxygenase 1 and 2. Meloxicam can cause headaches, dizziness, drowsiness, visual and hearing impairment. Among its side effects, an increase in blood pressure, an acceleration of the heartbeat, changes in the composition of the blood, impaired kidney function up to failure, skin and allergic reactions were also noted. With an overdose, side effects are more pronounced. The oral LD50 of meloxicam for mice is 470 mg/kg body weight, for rabbits it is 320 mg/kg body weight.

In animal studies, meloxicam did not show carcinogenic and mutagenic properties, and also did not reduce the fertility of males. However, in female rats and rabbits treated with this drug 2 weeks before mating and during pregnancy, the embryos died more often than in the control group. In addition, meloxicam also showed a teratogenic effect in rabbits: the frequency of cardiac septal defects increased. Reception of meloxicam in the III trimester in animals leads to a delay in labor. Therefore, this drug is not recommended during pregnancy. In addition, meloxicam increases the risk of developing cardiovascular disease in people with hypertension, diabetes, or high blood cholesterol.

Meloxicam interacts with many substances. It reduces the effectiveness of drugs that lower blood pressure and intrauterine contraceptives, and also contributes to the accumulation of lithium in the body, which can lead to poisoning. When taking meloxicam with aspirin or other NSAIDs, the risk of ulcers and bleeding from the gastrointestinal tract increases.

Meloxicam is moderately capable of bioconcentrating in living organisms, including aquatic animals. At the same time, it does not undergo hydrolysis and photolysis and, therefore, it remains in the environment for a long time. Meloxicam is toxic to aquatic animals.

In the Russian Federation, the EAEU countries and the European Union, the maximum allowable levels of meloxicam in food products have not been established. In Canada and Australia, the following MRLs apply: no more than 10 µg/kg for mutton, no more than 60 µg/kg for sheep liver, no more than 20 µg/kg for sheep kidney, and no more than 5 µg/kg for milk.

STYLAB offers pure standards of meloxicam and meloxicam-D3 and their mixtures with other NSAIDs for setting up the method and performing analyzes in accordance with GOST 32881-2014 “Food products, food raw materials. Method for determining the residual content of non-steroidal anti-inflammatory drugs using high-performance liquid chromatography with a mass spectrometric detector. Manufacturers of certified standards are accredited in accordance with ISO 17034:2016.