Does tramadol affect blood pressure. Can tramadol cause hypertension or hypotension. What are the potential interactions between tramadol and blood pressure medications. How does tramadol impact cardiovascular health.

Understanding Tramadol: An Overview of the Synthetic Opioid

Tramadol is a synthetic opioid pain reliever used to treat moderate to moderately severe pain. As a centrally acting analgesic, it works by binding to opioid receptors in the brain and altering the perception of pain signals. While effective for pain management, tramadol’s effects on other bodily systems, including cardiovascular function, warrant careful consideration.

Key Facts About Tramadol:

• Generic name: Tramadol
• Brand names: ConZip, Qdolo, Ultracet, Ultram, Ultram ER
• Drug class: Synthetic opioid analgesic
• Available forms: Immediate-release tablets, extended-release tablets/capsules, oral solution
• Prescription status: Controlled substance (Schedule IV)

Tramadol’s Impact on Blood Pressure: What Does the Research Say?

The relationship between tramadol and blood pressure is complex and can vary among individuals. While not a common side effect, tramadol has been associated with both increases and decreases in blood pressure in some patients.

Tramadol and Hypertension

Clinical studies have reported a low incidence of high blood pressure (hypertension) in patients taking tramadol:

• Extended-release formulations: 1-5% of patients experienced hypertension
• Immediate-release formulations: A very small number of patients developed hypertension

Tramadol and Hypotension

Low blood pressure (hypotension) is an even rarer occurrence with tramadol use:

• Less than 1% of patients in clinical trials experienced hypotension
• Some cases of postural (orthostatic) hypotension were reported, though causality was not definitively established

Can tramadol cause significant changes in blood pressure? While possible, substantial blood pressure fluctuations are not common when the medication is taken as prescribed. However, individual responses may vary, and certain factors like dosage, duration of use, and underlying health conditions can influence the drug’s effects on blood pressure.

Tramadol and Blood Thinning: Separating Fact from Fiction

A common misconception is that tramadol may have blood-thinning properties. However, it’s important to clarify this misconception.

Is tramadol a blood thinner? No, tramadol is not classified as an anticoagulant or blood thinner. Its primary mechanism of action is related to pain relief rather than affecting blood clotting factors. However, there have been isolated reports of potential interactions between tramadol and certain blood thinners, particularly warfarin.

Potential Interaction with Blood Thinners

While tramadol itself doesn’t thin the blood, patients taking blood thinners should be aware of possible interactions:

• Warfarin: Some case reports suggest tramadol may enhance the anticoagulant effect of warfarin
• Other anticoagulants: The potential for interactions with newer anticoagulants is less clear and requires further study

Should patients on blood thinners avoid tramadol? Not necessarily, but close monitoring and consultation with a healthcare provider are essential to manage any potential risks.

Drug Interactions: Tramadol’s Complex Pharmacology

Tramadol’s unique pharmacological profile makes it susceptible to numerous drug interactions. Understanding these interactions is crucial for safe and effective use of the medication.

Common Drug Interactions with Tramadol:

• Antidepressants (especially SSRIs and SNRIs)
• Appetite suppressants
• Certain antifungal medications
• Some antibiotics
• Other opioids
• Seizure medications
• Migraine medications (triptans)
• Antimalarial drugs
• Certain heart medications
• Blood thinners (as previously mentioned)

Why are these interactions important? Some of these interactions can alter tramadol’s effectiveness, increase the risk of side effects, or potentially lead to severe complications like serotonin syndrome or respiratory depression.

Alcohol and Tramadol

The combination of alcohol and tramadol can be particularly dangerous. Both substances can depress the central nervous system, potentially leading to severe respiratory depression, cognitive impairment, and other serious side effects.

Is it safe to drink alcohol while taking tramadol? No, it is strongly advised to avoid alcohol consumption while using tramadol due to the increased risk of adverse effects and potential for overdose.

Tramadol and Cardiovascular Health: Beyond Blood Pressure

While the direct effects of tramadol on blood pressure may be limited, its impact on overall cardiovascular health deserves attention. As an opioid, tramadol can influence various aspects of the cardiovascular system.

Potential Cardiovascular Effects of Tramadol:

• Heart rate changes: Some patients may experience tachycardia (increased heart rate)
• Arrhythmias: Rare cases of irregular heartbeats have been reported
• Fluid retention: May occur in some individuals, potentially impacting cardiovascular function
• Chest pain: Uncommon but reported in some cases

How does tramadol affect cardiovascular risk in patients with pre-existing heart conditions? Patients with a history of heart disease or other cardiovascular risk factors should be closely monitored when using tramadol. The drug’s effects on heart rate and blood pressure, while generally mild, could potentially exacerbate underlying conditions.

Safety Considerations: Who Should Exercise Caution with Tramadol?

While tramadol can be an effective pain management tool for many patients, certain individuals should use caution or avoid the medication altogether.

Populations at Higher Risk:

• Individuals with a history of substance abuse
• Patients with severe respiratory conditions
• Those with a history of seizures
• Individuals with liver or kidney dysfunction
• Elderly patients (due to increased sensitivity to opioids)
• Pregnant or breastfeeding women

Are there absolute contraindications for tramadol use? Yes, tramadol should not be used in patients with:
– Known hypersensitivity to tramadol or other opioids
– Severe respiratory depression
– Acute or severe bronchial asthma in an unmonitored setting
– Known or suspected gastrointestinal obstruction

Monitoring and Managing Tramadol Use: Best Practices for Patients and Healthcare Providers

Ensuring safe and effective use of tramadol requires a collaborative approach between patients and healthcare providers. Regular monitoring and open communication are key to minimizing risks and optimizing pain management outcomes.

Recommendations for Patients:

• Follow prescribed dosage and schedule carefully
• Report any unusual symptoms or side effects promptly
• Inform healthcare providers of all medications, supplements, and herbal products being used
• Avoid alcohol and other central nervous system depressants
• Be aware of potential signs of dependence or addiction

Guidelines for Healthcare Providers:

• Conduct thorough patient assessments before prescribing tramadol
• Consider starting with lower doses in opioid-naive patients
• Monitor blood pressure, heart rate, and other vital signs regularly
• Be vigilant for signs of misuse, abuse, or diversion
• Educate patients on proper use, potential side effects, and warning signs

How often should patients on long-term tramadol therapy be evaluated? Regular follow-up appointments are crucial, with the frequency determined by individual patient factors, dosage, and duration of therapy. Many providers recommend evaluations every 1-3 months for stable patients on long-term tramadol therapy.

Alternative Pain Management Strategies: When Tramadol May Not Be the Best Option

While tramadol can be an effective pain reliever for many patients, it’s not always the most appropriate choice. Exploring alternative pain management strategies can help minimize risks associated with opioid use and potentially provide more targeted relief for certain conditions.

Non-Opioid Pain Management Options:

• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Acetaminophen
• Topical analgesics
• Physical therapy and exercise
• Cognitive behavioral therapy
• Acupuncture
• Massage therapy
• Mindfulness and relaxation techniques

Which pain management approach is most effective? The optimal strategy often involves a multidisciplinary approach tailored to the individual patient’s needs, underlying condition, and overall health status. Combining pharmacological and non-pharmacological methods can often provide superior pain relief with fewer side effects.

Emerging Therapies in Pain Management

Research into novel pain management techniques continues to evolve, offering potential alternatives to traditional opioid medications like tramadol:

• Targeted nerve blocks
• Neuromodulation techniques
• Regenerative medicine approaches (e.g., stem cell therapy)
• Novel pharmaceutical agents with improved safety profiles

As our understanding of pain mechanisms and treatment options expands, the role of medications like tramadol in pain management may continue to evolve. Staying informed about the latest research and treatment options is crucial for both patients and healthcare providers in navigating the complex landscape of chronic pain management.

In conclusion, while tramadol can be an effective tool in the management of moderate to moderately severe pain, its use requires careful consideration of potential cardiovascular effects, drug interactions, and individual patient factors. By understanding these complexities and working closely with healthcare providers, patients can make informed decisions about their pain management strategies, balancing the benefits of pain relief with the need for overall health and safety.

Does tramadol raise or lower blood pressure?

Medically reviewed by Sally Chao, MD. Last updated on Oct 24, 2022.

Tramadol is a synthetic opioid pain reliever that has been linked to both high blood pressure and low blood pressure. But, neither adverse reaction is common when the medicine is taken as directed.

• Studies on tramadol have reported that between 1% and 5% of people taking the extended-release version and a very small number of people taking the fast-acting version developed high blood pressure (hypertension).
• Less than 1% of people taking tramadol developed low blood pressure (hypotension) in studies.

Those who had low blood pressure in the studies sometimes had what’s called postural or orthostatic hypotension. Postural hypotension occurs when blood pressure drops when someone stands up from sitting or lying down. Whether it was caused by tramadol is unclear.

Tramadol doesn’t seem to interact with high blood pressure medications, but other interactions are possible.

Taking other drugs can interfere with the way your body processes tramadol or cause other interactions. For instance, tramadol is not a blood thinner, but there are some reports that it may interact with blood thinners, like warfarin.

Many drugs may interact with tramadol, including:

• Certain antidepressants
• Appetite suppressant drugs
• Certain antifungal medications
• Certain antibiotics
• Other opioids
• Seizure medications
• Some migraine medications
• Malaria drugs
• Some heart medications
• Blood thinners

While blood pressure changes are not a common side effect of tramadol, some medication interactions can lead to extreme changes in blood pressure.

There are many possible drug interactions for tramadol that can be discussed with your doctor and searched on a drug interactions checker before taking the drug.

People taking tramadol should avoid drinking any alcohol or taking additional opioid medications.

Additionally, there are some people who generally should not take tramadol. These include:

• People who are allergic to the drug
• People with slowed breathing
• People who have acute or severe asthma

Tramadol is the drug’s generic name. It’s sold under several brand names, including:

• ConZip
• Qdolo
• Ultracet
• Ultram
• Ultram ER

References

1. Food and Drug Administration (FDA). Highlights of prescribing information: Tramadol hydrochloride extended-release capsules. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022370s000lbl.pdf. [Accessed September 2, 2020].
2. MedlinePlus. Tramadol. https://medlineplus.gov/druginfo/meds/a695011.html. [Accessed September 18, 2020].
3. Food and Drug Administration (FDA). Highlights of prescribing information: Ultram (tramadol hydrochloride) tablets. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020281s041lbl.pdf. [Accessed September 9, 2020].
4. Drugs.com. Drug Interactions between Cymbalta and tramadol. Available at: https://www.drugs.com/drug-interactions/cymbalta-with-tramadol-949-2273-2221-0.html. [Accessed September 18, 2020].
5. Drugs.com. Tramadol tablets. September 1, 2019. Available at: https://www.drugs.com/pro/tramadol-tablets.html#s-34090-1. [Accessed September 14, 2020].

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Drug information

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Medical Disclaimer

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Tramadol for osteoarthritis | Cochrane

This translation is out of date. Please click here for the latest English version of this review.

This summary of the Cochrane Review presents what we know from research on the effects of tramadol on osteoarthritis. The review shows that:

There is gold level evidence that for the treatment of osteoarthritis, taking tramadol for up to three months can reduce pain, stiffness, and improve function and overall well-being. Tramadol can cause side effects such as nausea, vomiting, dizziness, constipation, fatigue and headache.

The benefits of tramadol are negligible and the side effects may cause people to stop taking it, which may limit the benefit of tramadol in the treatment of osteoarthritis.

What is osteoarthritis and what drugs are used to treat it?

Osteoarthritis (OA) is the most common form of arthritis and can affect the hands, hips, shoulders, and knees. In OA, the cartilage that protects the ends of bones breaks down and causes pain and swelling. There are two main types of drug treatment for OA. Painkillers (such as acetaminophen/paracetamol and opioids) are used to relieve pain but do not affect swelling. Non-steroidal anti-inflammatory drugs (NSAIDs such as ibuprofen and COX-II inhibitors) are used to reduce pain and swelling. Tramadol is one of the opioids most used in OA. It does not cause bleeding from the stomach and intestines, and does not cause kidney problems that can occur with other painkillers. It also does not affect the cartilage at the ends of bones. But tramadol does not reduce swelling and may not be effective with long-term use. Therefore, it is important to know the benefits and harms of tramadol.

What are the results of this review?

People in the studies took about 200 mg of tramadol per day, or a placebo (fake pill or powder), or an NSAID, or other pain medication. People took the medicines for one week to three months.

Benefits of tramadol

in people with osteoarthritis:

tramadol can reduce pain more than placebo

– tramadol can reduce pain by more than 8. 5 points on a scale of 0 to 100

tramadol may improve overall well-being more than placebo

– 50 out of 100 people may improve with placebo
– 69 out of 100 people may improve with tramadol

tramadol may reduce stiffness somewhat and improve function more than placebo

– function may improve by 0.32 points on a scale of 0 to 10 with tramadol

It is not known whether tramadol improves osteoarthritis symptoms more than other drugs. It is also unknown if tramadol is still effective with long-term use. This is due to the fact that the observations in the studies were short.

Harm of tramadol

in people with osteoarthritis:

tramadol may cause minor side effects in more people than placebo, such as nausea, vomiting, dizziness, constipation, fatigue, and headache

– 18 out of 100 people may have minor side effects when placebo
– 39 out of 100 people may have minor side effects when taking tramadol

tramadol can cause serious side effects that would cause people to stop taking it

– 8 out of 100 people had serious side effects with placebo
– 21 out of 100 people had serious side effects with tramadol

It is not known if tramadol causes more side effects than other osteoarthritis medications.

If you found this evidence helpful, please consider donating to Cochrane. We are a charity that produces accessible evidence to help people make health and care decisions.

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Translation notes:

Translation notes: Translation: Aleksandrova Elvira Grigoryevna. Editing: Gamirova Rimma Gabdulbarovna, Ziganshina Lilia Evgenievna. Russian translation project coordination: Kazan Federal University. For questions related to this transfer, please contact us at: [email protected]

ARCOXIA® (Etoricoxib) – a revolution in the treatment of acute and chronic pain

From time to time in the history of medicine, discoveries occur that radically change approaches to the treatment of certain diseases. These include the discovery of pathogens of infectious diseases, blood groups and the Rh factor, the first successful vaccination, the invention of insulin, penicillin, vitamin B ₁₂ . Although they all belong to different areas of healthcare, they have one thing in common – each such event allows you to solve some serious, as a rule, socially significant problem that was previously difficult to deal with.

This autumn will probably be remembered by Ukrainian doctors as such an event. After all, this fall, the revolutionary drug ARCOXIA ^® (etoricoxib), a non-steroidal anti-inflammatory drug (NSAID) with a pronounced analgesic effect and the most favorable safety profile, appeared on the domestic pharmaceutical market.

The presentation of the drug took place on September 7 in the Pushcha-Ozernaya sanatorium near Kiev, during which the country’s leading experts on diseases of the musculoskeletal system Vladislav Povoroznyuk , Head of the Department of Clinical Physiology and Pathology of the worker of science and technology of Ukraine, and Volodymyr Klimovitsky , director of the Research Institute of Traumatology and Orthopedics, shared with colleagues the positive experience of using ARKOXIA ^® for the relief of chronic pain in diseases of the joints.

The effect develops after 24 minutes and lasts 24 hours

And just a week later, on September 16–17, in Dnepropetrovsk, the advantages of a new drug for Ukraine were actively discussed at the XV Congress of Orthopedic Traumatologists. The congress participants traditionally paid special attention to the problem of effective and safe relief of pain in patients with chronic diseases of the musculoskeletal system. As you know, they are accompanied by severe pain, for the relief of which patients are forced to take painkillers for life, most often NSAIDs. Chronic pain is characterized by the development of specific neurophysiological reactions and an increase in the influence of personality-psychological factors on the course of the pathological process. The experts agreed that ARKOXIA ^® , being a specific (highly selective) inhibitor of cyclooxygenase (COX)-2, has a pronounced anti-inflammatory, analgesic and antipyretic effect, while the drug does not affect platelet function and does not inhibit the synthesis of prostaglandins in the stomach. The advantage of the drug ARCOXIA ^® also lies in a very rapid increase in its concentration in blood plasma and the rapid achievement of an analgesic effect that persists for 24 hours. a dosage of 150 mg, and when using the latter, complications from the digestive tract are much more often noted.

The effect develops after 24 minutes and lasts 24 hours

These statements are based on a very serious evidence base, which we bring to the attention of readers.

Modern rheumatology has achieved great success in the treatment of the most common, socially significant diseases of the musculoskeletal system, primarily of an inflammatory nature, such as rheumatoid arthritis (RA). The introduction of biological agents into clinical practice and the strategy of early aggressive therapy with the use of basic anti-inflammatory drugs (DMARDs) have made it possible to achieve stable clinical remission in a significant proportion of patients. Nevertheless, symptomatic analgesics retain their most important position in this pathology.

In particular, this is shown by a meta-analysis of the results of 3 known studies on the effectiveness of tumor necrosis factor (TNF)-α inhibitors (infliximab, adalimumab, etenercept): RA – BeSt, PREMIER and TEMPO. By the 2-30th year from the start of treatment, remission was achieved in approximately 50%. This is a wonderful result; however, almost half of the patients, even with the use of timely active pathogenetic therapy, retained clinical signs of the disease, and hence the need for symptomatic analgesics.

Unfortunately, in real clinical practice, most of the patients with RA are people who suffer from this disease for a long time, in whom basic therapy did not achieve success or was not carried out for various reasons. These are disabled patients with severe joint deformities, accompanied by significant functional impairment. In such a situation, symptomatic therapy is the most important direction of therapeutic intervention.

The main class of drugs used for symptomatic treatment of pain and inflammation are, of course, NSAIDs. Their use makes it possible to achieve a significant reduction in the severity of pain and an improvement in the general condition by 25–50% in about half of RA patients. A good confirmation of this can be the results of a study conducted by M. Greenwald et al. (2009). In this study, the study group consisted of 761 patients with RA, of which 178 received complex therapy using biological agents (etanercept, anakira, adalimumab, natalizumab, infliximab, and abatacept). The authors evaluated the therapeutic effect of a new NSAID, etoricoxib, administered at an effective anti-inflammatory dose (90 mg) or at a lower dose (10–60 mg) for 12 weeks. The control group consisted of patients receiving placebo. According to the results obtained, regardless of the use of biological agents, the best treatment outcome was noted against the background of a high dose of NSAIDs. So, in contrast to placebo, in this group, the average dynamics of pain (according to the visual analogue scale – VAS) for those receiving biological preparations was 12.9mm, and for those who did not receive -15.5 mm, respectively. In the group where NSAIDs were used at a lower dosage, the difference from placebo was much less pronounced: -6. 7 and -5.5 mm, respectively.

The main users of NSAIDs are patients suffering from the most common rheumatic disease – osteoarthritis (OA). Unfortunately, both non-drug methods and modern pathogenetic therapy for OA (“oral chondroprotectors”, hyaluronic acid preparations) do not eliminate the need to use fast-acting symptomatic agents. According to the available recommendations, the first-line drug for pain relief in OA is a simple analgesic paracetamol, the most important advantage of which is a relatively low risk of complications. However, even at the maximum dosage (4 g / day), paracetamol is inferior in its effectiveness to NSAIDs.

The effectiveness of the drug was studied in the MEDAL study, which involved 34 thousand people

The high analgesic potential of NSAIDs, combined with the anti-inflammatory effect, provide their obvious superiority over paracetamol. Moreover, “soft” opioid drugs (tramadol, codeine, etc.), often recommended as an alternative to NSAIDs, according to a series of randomized clinical trials (RCTs), do not show any benefit in diseases such as OA and lower back pain. parts of the back. At the same time, the disadvantages of opioids are obvious: the difficulty of prescribing (which is especially important for the countries of the post-Soviet space), the absence of anti-inflammatory and antipyretic effects, and frequent complications from the central nervous system.

It should be noted that adequate treatment for chronic pain is a positive factor that reduces the risk of progression of diseases of the cardiovascular system. According to T. Lee et al. (2007), who observed a cohort of 565,454 US veterans, patients with OA who regularly took NSAIDs died significantly less frequently (> 20%) from cardiovascular accidents, compared with people who did not use these drugs. A similar result was obtained by N. Goodson when observing a cohort of 923 patients with inflammatory arthritis. Since the creation of the register (1990–1994) there were 203 deaths, 85 of which were due to cardiovascular complications. It turned out that the regular use of NSAIDs, which were initially received by 66% of patients, reduced the risk of death from cardiovascular accidents.

However, the use of NSAIDs itself can cause serious side effects. Of fundamental importance here is the suppression of the activity of the “structural” enzyme COX-1, which occurs when using non-selective NSAIDs (n-NSAIDs). This is a key point in the pathogenesis of NSAID gastropathy, a specific pathology of the upper gastrointestinal tract (GIT), characterized by the development of erosions, ulcers, and “gastrointestinal catastrophes” – bleeding and perforation. The incidence of serious gastrointestinal complications in people who regularly take NSAIDs is approximately 0.5-1 episode per 100 patient-years. Equally important is the negative effect of NSAIDs on the blood pressure regulation system and the blood coagulation system, which can be realized in the form of cardiovascular complications – destabilization of arterial hypertension and existing heart failure, as well as an increased risk of developing myocardial infarction and ischemic stroke. Both n-NSAIDs and selective COX-2 inhibitors (s-NSAIDs) can cause similar complications. According to the results of a meta-analysis by T. Aw et al. (2005), who studied data from 52 RCTs, taking coxibs was associated with an increase in systolic pressure by an average of 3.85, diastolic – by an average of 1.06 mm Hg. Art., taking n-NSAIDs – by 2.81 and 1.34 mm Hg. Art. respectively.

The appearance on the domestic pharmacological market of the latest generation of c-NSAIDs, etoricoxib, allows us to take a fresh look at the issue of the use of such drugs in rheumatological practice.

The pharmacological properties of this drug are very favorable. This is the most selective COX-2 inhibitor (the ratio of the inhibitory concentration of COX-1 / COX-2 is 344), which surpasses all other NSAIDs in this indicator. It has a high (about 100%) bioavailability, which ensures the achievement of peak blood concentration within 1-3 hours after oral administration, and, accordingly, the maximum speed. The half-life of etoricoxib is 22 hours; therefore, within 1 day after its single dose, a stable analgesic and anti-inflammatory effect is maintained.

The high analgesic potential of etoricoxib was revealed by K. Malmstrom et al. In the study, 201 patients experiencing severe pain after extraction of ≥2 teeth received etoricoxib 120 mg, naproxen 550 mg, a combination drug containing 60 mg of codeine and 600 mg of paracetamol, or placebo. Already after 30 minutes, patients who received any active drug noted relief. However, after 8 hours, complete relief of toothache was noted in 20.9% and 21.3% after taking etoricoxib and naproxen, and against the background of using a combination of codeine and paracetamol – only in 11.5% (p<0.001). In the placebo group, a similar effect was noted only in 5.4% (p<0.001).

In general, etoricoxib has established itself as an effective agent for urgent pain relief in orthopedic and band surgery, as well as in acute injuries.

One of the most striking evidence of the high therapeutic potential of etoricoxib is the experience of its use for the treatment of gout, because the relief of microcrystalline arthritis is primarily associated not with analgesic, but with anti-inflammatory action. Therefore, indomethacin, a drug with the most pronounced anti-inflammatory effect, has long been considered the gold standard for the treatment of acute gouty arthritis.

It was indomethacin at a dose of 150 mg/day that became the reference drug in two RCTs of the same type, which determined the efficacy of etoricoxib 120 mg/day for the relief of acute gouty arthritis. So, in the work of H. Schumacher et al., 150 patients with this pathology received etoricoxib 1 time per day or indomethacin – 50 mg 3 times a day. Both drugs were equally effective: by the 8th day of observation, 89 and 90% of patients, respectively, had relief of arthritis. At the same time, serious side effects, such as gastric ulcer and bleeding, were not observed in patients taking etoricoxib, but developed in 3 patients who used indomethacin. This result was confirmed in the study by B. Rubin et al. (n=189). The rate of onset of the effect, the suppression of inflammation and the dynamics of the general condition of patients while taking etoricoxib and indomethacin practically did not differ, and there was no difference in the main criterion for the effectiveness of therapy – the dynamics of pain in the affected joints. However, the number of side effects while taking etoricoxib was 2 times less – a total of 16.5 and 37.2%, respectively.

The therapeutic potential of etoricoxib in the most common chronic rheumatic diseases has been proven by a series of well-designed, large-scale and long-term studies. Etoricoxib provided a stable reduction in the severity of pain, inflammatory activity and improved well-being of patients. In general, its effectiveness in this pathology is not inferior or slightly exceeds the therapeutic effect of n-NSAIDs and other c-NSAIDs.

ARCOXIA ^® 120 mg after orthopedic surgery had a more pronounced analgesic effect than tramadol 200 mg.

The experience with etoricoxib in OA is very indicative. Two identical placebo-controlled studies conducted by C. Wiesenhutter et al. (n=528) and A. Puopolo et al. mg/day). In both studies, etoricoxib was in no way inferior to ibuprofen in terms of pain reduction and dysfunction (WOMAC, Likert scale). Moreover, according to certain indicators, in particular, a smaller amount of additional analgesic (paracetamol) used, etoricoxib was significantly superior to the reference drug.

The safety of etoricoxib has been extensively tested. The relatively low risk of developing dangerous gastrointestinal complications while taking etoricoxib is confirmed by the results of a meta-analysis of data from a series of long-term RCTs (involving 5441 patients) completed by 2003. the frequency of gastrointestinal bleeding, perforations and clinically pronounced ulcers was 1.24% – 2 times less compared with patients receiving various n-NSAIDs – a total of 2.48% (p<0.001).

Two large-scale studies were conducted to investigate the effect of etoricoxib on the development of endoscopic ulcers, including 1422 patients with RA and OA treated with etoricoxib 120 mg/day, ibuprofen 2400 mg/day, naproxen 1000 mg/day, or placebo. All patients underwent endoscopic examination before and after the end of the course of therapy lasting 12 weeks. The total frequency of gastric and duodenal ulcers while taking etoricoxib was at least 2 times less and amounted to 8.1% and 7.4% (17% and 25. 3% in the control groups; p<0.001).

Evidence for the relatively low incidence of dyspepsia comes from a meta-analysis of 9 RCTs in which etoricoxib was administered to patients with RA, OA, and low back pain. With the use of this drug, the frequency of discontinuation of therapy due to the development of dyspepsia was 1.5 per 100 patient-years – 2 times less than with n-NSAIDs (2.7 per 100 patient-years; p = 0.007).

Etoricoxib is the most selective of all NSAIDs. Therefore, the risk of complications from the cardiovascular system in patients using this drug draws close attention of researchers and organizers of medicine. However, the results of a series of pre-registration studies that evaluated the comparative efficacy and safety of etoricoxib in patients with RA, OA, ankylosing spondylitis and low back pain, and control were placebo and n-NSAIDs (n≈6500), did not show a significant increase in the risk of such complications. . Thus, the relative risk (RR) of myocardial infarction was 1. 11 (0.32–3.81). At the same time, the use of etoricoxib was associated with a lower incidence of cardiovascular events compared with ibuprofen and diclofenac (RR 0.83; 0.26–2.64), although the rates were inferior to naproxen (RR 1.70; 0.91–3.18).

Taking the minimum dose of ARCOXIA ^® 60 mg in terms of pain relief is comparable to taking the maximum dose of 150 mg of diclofenac fenac sodium Gastrointestinal tolerability and Effectiveness), EDGE II and MEDAL — in a double-blind method, the COX-2 inhibitor etoricoxib (etoricoxib) was studied in comparison with the classic representative of the NSAID class diclofenac. The study simulated real clinical practice, since patients with risk factors for the development of complications from the gastrointestinal tract were recommended to take a proton pump inhibitor (PPI), and patients with a risk of developing cardiovascular complications – low-dose acetylsalicylic acid. MEDAL was the first long-term program established to evaluate the safety of the selective COX-2 inhibitor etoricoxib with respect to thrombotic events. During 2002–2004 34,701 patients with OA (72% of the population) or RA (28%) aged ≥50 years were enrolled in 1380 centers in 46 countries. Participants were randomized to receive etoricoxib (60–90 mg/day; n=17412) and diclofenac (150 mg/day; n=17289). PPI gastroprotection was strongly recommended in patients at high risk of gastrointestinal complications (age >65 years, history of gastrointestinal ulceration or bleeding, concomitant use of corticosteroids, anticoagulants, or antiplatelet drugs). The use of acetylsalicylic acid at a low dose (≤100 mg/day) was recommended for persons with established cardiovascular or cerebrovascular pathology, as well as with diabetes mellitus. During the study (mean 18 months), an independent committee recorded all complications from the gastrointestinal tract. Serious complications included perforation, intestinal obstruction, complicated bleeding, and minor complications were uncomplicated bleeding or ulcer.

In the MEDAL program, etoricoxib 60 and 90 mg/day and diclofenac 150 mg/day showed similar efficacy in the treatment of OA and RA (Global Disease Status Score (IGADS). The risk of developing thrombotic events while taking etoricoxib and diclofenac was comparable. The hazard ratio for etoricoxib versus diclofenac was 0.95 (CI 0.81–1.11). The most common thrombotic event in both treatment groups was nonfatal or fatal myocardial infarction (0.43 events per 100 patient years treated with etoricoxib and 0.49events per 100 patient-years treated with diclofenac. The study demonstrated a significant reduction in the incidence of clinically important, primarily uncomplicated, gastrointestinal complications when using the selective COX-2 inhibitor etoricoxib compared with diclofenac. A positive gastroprotective effect of etoricoxib was also noted in subgroups of patients taking PPIs or low-dose acetylsalicylic acid. In addition, COX-2 inhibitor therapy was better tolerated and resulted in a lower rate of early discontinuation due to gastrointestinal and hepatic complications.

The results of published randomized placebo-controlled trials, summarized in meta-analyses, revealed the risk of developing cardiovascular complications while taking selective COX-2 inhibitors. The data obtained required a more detailed assessment of the risk of cardiovascular accidents for n-NSAIDs as a class. A meta-analysis of 12 RCTs revealed an increased risk of myocardial infarction for all n-NSAIDs by (RR) 1.19 (from 1.08 to 1.31), except for naproxen (RR for myocardial infarction was 0.98).

In 2005, the FDA recommendations were adopted, which indicate that all NSAIDs should have indications in the annotations of the risk of cardiovascular events and gastrointestinal bleeding (special warning – Black box warning for NSAIDs).

Thus, from the data obtained, a conclusion follows about the class-specific effect of NSAIDs in relation to increased cardiovascular risk. The theoretical basis for considering this issue was the hypothesis of an antagonistic effect on platelet-vascular homeostasis of two COX products – thromboxane A ₂ and prostaglandin I ₂ (prostacyclin). Specific inhibitors of COX-2, reducing the production of prostacyclin without affecting the synthesis of thromboxane A ₂ , can enhance the effects of thromboxane A ₂ , facilitate the interaction of platelets and neutrophilic granulocytes with the vascular wall and thereby contribute to the development of thrombosis and increase the risk of cardiovascular events.

An increase in selectivity for COX-2 is associated with an increase in cardiovascular risk, and an increase in selectivity for COX-1 is associated with a risk of gastrointestinal complications.

This is essential for understanding the results of clinical trials. For example, the Vioxx Gastrointestinal Outcomes Research (VIGOR) study found evidence of an increased risk of cardiovascular events for the COX-2 inhibitor rofecoxib compared to naproxen, which is more of a COX-1 inhibitor. In contrast, when comparing etoricoxib with diclofenac in the EDGE study (Etoricoxib versus Diclofenac sodium Gastrointestinal tolerance and Effectiveness), which is part of the MEDAL study, an equal level of effect of two drugs on the development of cardiovascular events was obtained, since these drugs are at a close level of the selectivity line for inhibition of COX-2.

It has recently been shown that the addition of acetylsalicylic acid to n-NSAIDs and coxibs prevents the development of cardiovascular events. Information on this subject was presented at the EULAR congress (The European League Against Rheumatism – European Antirheumatic League) in 2006 in the report of G. Singh et al. COX-2 inhibitors and non-selective NSAIDs”, based on an analysis of 2,356,885 patient-years from the California Medicaid Database. In these patients, 15,343 cases of myocardial infarction were registered, of which 1233 (8%) were fatal. In patients who did not take acetylsalicylic acid, rofecoxib increased the risk of myocardial infarction by 1.31, indomethacin – by 1.65, meloxicam – by 1.52, sulindac – by 1.47, while celecoxib and ibuprofen worsened cardiovascular prognosis to a much lesser extent, by 1.12 and 1.08, respectively. In cases where acetylsalicylic acid was added to rofecoxib, celecoxib, meloxicam and sulindac, almost complete leveling of the increased risk of myocardial infarction under the influence of these drugs was recorded (1.03; 0.88; 0.53 and 0.77, respectively). But this cannot be attributed to ibuprofen: against the background of a combination of ibuprofen and acetylsalicylic acid, the risk of developing myocardial infarction increased by 20%. Therefore, ibuprofen should be avoided in individuals requiring acetylsalicylic acid.

Amended American Heart Association guidelines for the use of NSAIDs (2007) for the management of pain in patients with OA and RA recommend using drugs of this class only in the absence of the effect of acetaminafen (paracetamol) and acetylsalicylic acid, as well as the development of hepatotoxicity while taking acetaminafen in high doses. Selective COX-2 inhibitors in patients with cardiovascular disease should only be used at recommended doses and for the shortest possible time necessary to control pain. Since the use of COX-2 inhibitors may worsen renal perfusion, sodium retention, increase in blood pressure, treatment should be carried out under the control of blood pressure and kidney function. Even a low degree of selectivity for COX does not exclude the risk of developing cardiovascular complications. Thus, all drugs of the NSAID class should be prescribed after a weighted assessment of the balance between benefit and risk.

ARKOXIA ^® (etoricoxib), which has recently become available on the Ukrainian market, is currently used in more than 60 countries around the world. The following indications for its use are registered in our country: symptomatic therapy of OA, RA, ankylosing spondylitis, acute gouty arthritis, to reduce the severity of acute and chronic pain.

The decision to prescribe a selective COX-2 inhibitor should be based on an individual patient risk assessment.

ARCOXIA is administered orally, with or without food. The onset of the effect of the drug occurs faster when taken on an empty stomach, which should be considered if it is necessary to quickly reduce the severity of symptoms.

Arthritis

Osteoarthritis. The recommended dose is 30 mg once daily. In some patients, with insufficient reduction in the severity of symptoms, increasing the dose to 60 mg / day may lead to a more pronounced effect.

Rheumatoid arthritis and ankylosing spondylitis. The recommended dose is 90 mg once daily. Acute gouty arthritis. The recommended dose is 120 mg once a day. ARCOXIA ^® at a dose of 120 mg/day should be used during the acute symptomatic period and for a limited period of maximum 8 days of treatment.

Pain relief

Acute pain. The recommended dose is 120 mg once daily. ARCOXIA ^® at a dose of 120 mg / day should be used in the acute symptomatic period and for a limited time – a maximum of 8 days of treatment.

Chronic pain. The recommended dose is 60 mg once daily.

Doses above those recommended for each indication either have no additional efficacy or have not been studied. Therefore:

• OA dosage should not exceed 60 mg once daily;
• dosing in RA and ankylosing spondylitis should not exceed 90 mg 1 time per day;
• dosing for acute gout should not exceed 120 mg once daily;
• dosing for acute pain should not exceed 120 mg once daily;
• dosing for chronic pain should not exceed 60 mg once daily.

Thus, ARCOXIA ^® (etoricoxib) is a powerful and fast analgesic with pronounced anti-inflammatory properties, with a persistent and long-lasting effect. This universal drug can be successfully used both for urgent pain relief and as a component of symptomatic therapy for chronic rheumatic diseases. A wide range of effective doses (from 60 to 120 mg/day) and a convenient once-daily regimen should undoubtedly attract the attention of practitioners and patients.

Etoricoxib may cause class-specific cardiovascular complications. In particular, special attention is required when using this drug in patients with arterial hypertension. However, there was no significant increase in the risk of developing cardiovascular accidents, as well as associated mortality. However, etoricoxib is much safer than traditional NSAIDs in terms of the development of gastrointestinal pathology, which determines the possibility of its use in the presence of appropriate risk factors and expands the possibilities of symptomatic therapy for rheumatic diseases.