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Can you take etodolac with ibuprofen: Etodolac and ibuprofen Drug Interactions


Etodolac and ibuprofen Drug Interactions

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Using ibuprofen together with etodolac is generally not recommended. Combining these medications may increase the risk of side effects in the gastrointestinal tract such as inflammation, bleeding, ulceration, and rarely, perforation. Gastrointestinal perforation is a potentially fatal condition and medical emergency where a hole forms all the way through the stomach or intestine. You should take these medications with food to lessen the risk. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact. Your doctor may also be able to recommend medications to help protect the stomach and intestine if you are at high risk for developing serious gastrointestinal complications. You should seek immediate medical attention if you experience any unusual bleeding or bruising, or have other signs and symptoms of bleeding such as dizziness; lightheadedness; red or black, tarry stools; coughing up or vomiting fresh or dried blood that looks like coffee grounds; severe headache; and weakness. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Switch to professional interaction data

Drug and food interactions

No interactions were found. This does not necessarily mean no interactions exist. Always consult your healthcare provider.

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition.
This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit.
It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy,
and can have potentially adverse consequences.

The recommended maximum number of medicines in the ‘nonsteroidal anti-inflammatories’ category to be taken concurrently is usually one.
Your list includes two medicines belonging to the ‘nonsteroidal anti-inflammatories’ category:

Note: The benefits of taking this combination of medicines may outweigh any risks associated with therapeutic duplication.
This information does not take the place of talking to your doctor.
Always check with your healthcare provider to determine if any adjustments to your medications are needed.

Drug Interaction Classification
These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Which Is Better for Arthritis Pain?

Ibuprofen and etodolac are two types of non-steroidal anti-inflammatory drugs (NSAIDs) used to treat arthritis pain. Being of the same pharmaceutical class, there’s much that they have in common. Both reduce inflammation and pain sensation, easing the severity of symptoms. That said, there are also a number of crucial differences.

Etodolac, a prescription-only generic drug previously sold under the discontinued brand name Lodine, is typically only indicated for osteoarthritis and rheumatoid arthritis. Ibuprofen is available in numerous over-the-counter (OTC) and prescribed forms and takes on a wider range of pain, including arthritis.

As with any medication, it’s important to be careful when using etodolac and ibuprofen, as they can interact with other drugs or supplements. In particular, the chances of adverse effects increase if these two drugs—or any two NSAIDs—are taken together. It’s important to understand how to use these drugs safely.

FatCamera / E+ / Getty Images

How Etodolac and Ibuprofen Are Similar

Like all NSAIDs, both etodolac and ibuprofen prevent the activity of enzymes called cyclooxygenases (COX), which help your body produce prostaglandins. These hormone-like chemicals are essential for pain and swelling in the body, so inhibiting their activity eases symptoms. Each is often prescribed for rheumatoid arthritis and osteoarthritis.

Since etodolac and ibuprofen function in this way, their side effects are also similar. While there are more for etodolac, common side effects of both include:

  • Constipation
  • Diarrhea
  • Gas and/or bloating
  • Dizziness
  • Nervousness
  • Ringing in the ears

Not only that, severe side-effects for these drugs, which include allergic reactions such as breathing difficulties, facial swelling, and hives, among others, are also identical.

How Etodolac and Ibuprofen Are Different

Though there are similarities between these NSAIDs, there are also a number of key differences. Here’s a quick breakdown:

  • Availability: Ibuprofen, sold under a wide range of names, including Motrin, Advil, Midol, and others, comes in both over-the-counter and prescribed formulations. In contrast, etodolac is only available with a prescription in faster-acting and more slow-release forms.
  • Indications: While some doctors may prescribe etodolac for other painful conditions, it’s approved only for the management of osteoarthritis and rheumatoid arthritis. Ibuprofen is indicated for a wider range of conditions, including everything from headache, menstrual pain, toothaches, and others.
  • Half-lives: Etodolac has a much longer half-life—the time it takes for half of the substance to be metabolized—of six to eight hours, which means people will need fewer pills to manage pain and other symptoms. Ibuprofen, in contrast, gets to this point between one and three hours.
  • Typical dosages: For arthritis, etodolac doses range from 300 milligrams two to three times a day, to one 400- to 1,000-milligram tablet daily. Higher and more frequent doses of ibuprofen achieve the same effect: 400 to 800 milligrams three to four times a day.
  • Safe populations: While both of these drugs are considered generally safe for adults, forms of ibuprofen are safe for those as young as 6 months old. Etodolac, however, isn’t recommended for those under 6 years old.

Which Is Better for Treating Arthritis Pain? 

What makes arthritic conditions difficult is that there is no outright cure for them. Treatment of these conditions is a matter of long-term management of symptoms, of which ibuprofen and etodolac may both play a part. But it’s important ask: Is one better than the other?

The answer is a little complicated, though etodolac seems to have an edge. A formative, double-blind study conducted in 1997 directly comparing the two for rheumatoid arthritis found them to be equally effective for the first two months, with ibuprofen showing less efficacy over the long run. For up to three years of therapy, etodolac offered better management of symptoms.

However, it should also be noted that ibuprofen has consistently been found to be among the safest of NSAIDs, and certainly safer than etodolac. Especially in moderate doses, it’s been shown to lead to relatively few adverse events. No doubt, this is why this medication is so widespread and has such a long history.

Is It Safe to Take Ibuprofen With Etodolac? 

Whenever you’re prescribed a medication, it’s important to be aware of what, if any, other drugs, supplements, or herbs you can safely take at the same time. This is especially important when managing chronic conditions like arthritis, as you may need to take medications for a long period of time.

When taking any NSAID, using another one at the same time significantly increases the chance of adverse side effects. This would certainly be the case if you tried to mix ibuprofen and etodolac, which is why the Food and Drug Administration (FDA) specifically warns against doing so.

If you’re taking prescription or over-the-counter medications for your arthritis and still struggling with pain and inflammation, be sure to let your doctor know. The management of chronic conditions often requires a multifaceted approach.

NSAID Warnings

The use of NSAIDs, though common and widespread, comes with risks. Most significantly, according to the FDA, there is a chance that this class of drugs can lead to heart attack and stroke in the following cases:

  • Duration of use: Doctors have documented cardiovascular effects within two weeks of starting NSAIDs, and this risk rises with prolonged use.
  • Higher doses: Chances of stroke and heart attack also grow with higher concentrations and dosages of NSAIDs.
  • Present conditions: NSAIDs have been found to increase the risk of adverse cardiovascular events even in those with no history of heart problems. Those with heart disease or other issues have a higher likelihood of developing these severe reactions.

In addition, NSAIDs can also affect gastrointestinal health, leading to intestinal bleeding, stomach ulcers, and perforation of ulcers. The risk of any of these occurring rises with age, and prompt medical attention is necessary if they arise.

Finally, the use of ibuprofen, etodolac, or other NSAIDs may also lead to:

  • Skin reactions: Rashes and other skin conditions may be signs of adverse reactions.
  • Liver damage: Taking medications like ibuprofen or etodolac can also damage the liver, leading to jaundice (yellowing of skin and eyes), liver failure, fatigue, nausea, flu-like symptoms, and others.
  • Heart failure: Use can also cause insufficient heart-pumping activity, leading to swelling, shortness of breath, and sudden weight gain.
  • Fetal toxicity: NSAIDs like ibuprofen and etodolac may also be problematic in pregnancy after 30 weeks. Those who take them after 20 weeks need to be carefully monitored to ensure safety.

When to Call Your Doctor

Some side-effects of NSAID use are so dangerous as to constitute medical emergencies. If you experience any of the following, call for help as soon as you can:

  • Breathing difficulties
  • Rapid heartbeat
  • Chest pain
  • Swelling in the abdomen, hands, feet, ankles, and legs
  • Skin rashes, blisters, hives
  • Fever and chills
  • Jaundice (yellowing of skin and eyes)
  • Abdominal pain
  • Loss of appetite
  • Cloudy urine
  • Pain while urinating
  • Sudden weight gain

A Word From Verywell

Managing osteoarthritis or rheumatoid arthritis is challenging, but you’re far from alone if you experience these conditions. As common and widespread as these conditions are, it’s important to remember that there are many effective means of managing them, of which ibuprofen and etodolac both have their utility.

If you take these NSAIDs—or any other medication—it’s absolutely essential to understand how they work and how to use them safely. The secret weapon against arthritis is something we all have: knowledge.

The more you know about your condition and your approach to treatment, the better off you’ll be. Never hesitate to ask your doctor about your options.

Tp24.it ,le notizie di Trapani, Marsala, Mazara, Alcamo e Belice

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A comparison of the effects of etodolac and ibuprofen on renal haemodynamics, tubular function, renin, vasopressin and urinary excretion of albumin and α-glutathione- S -transferase in healthy subjects: a placebo-controlled cross-over study

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to be potentially nephrotoxic agents. NSAIDs inhibit the enzyme cyclo-oxygenase and thereby block the prostaglandin synthesis in the kidneys. Cyclo-oxygenase exists in two isoforms (COX-1 and COX-2). It has been proposed that NSAIDs with preferential COX-2 selectivity have fewer renal side effects than drugs with preferential COX-1 selectivity. Etodolac is a relative selective inhibitor of COX-2, while ibuprofen has a higher potency against COX-1 than COX-2.
In this study, we compared the effects of etodolac and ibuprofen on renal function, plasma renin, plasma arginine vasopressin and the urinary excretion of albumin and alpha-glutathione-S-transferase (alpha-GST).
In a randomised, double-blind, three-way crossover study with placebo, we compared the effects of 2 weeks of treatment with ibuprofen and etodolac on renal haemodynamics [glomerular filtration rate (GFR), renal plasma flow (RPF) and filtration fraction (FF)], tubular function and plasma concentrations of the hormones renin (PRC) and arginine vasopressin (AVP) in 18 healthy subjects. In addition, we examined the effects on the urinary excretion of albumin and alpha-GST as markers of renal injury.
No differences were found between the three treatments, placebo, ibuprofen and etodolac, in the effects on GFR, RPF, FF, free water clearance, urinary output or fractional excretion of potassium and sodium. However, ibuprofen, in contrast to etodolac, caused a significant decrease in both lithium clearance (-16% versus placebo) and the fractional excretion of lithium (-17% versus placebo), suggesting an increase in the reabsorption in the proximal tubuli. PRC was reduced significantly by ibuprofen (-32% versus placebo) but not etodolac. None of the drugs changed AVP. Fourteen days of treatment with ibuprofen caused a significant decrease (-47% versus placebo) in the urinary excretion of alpha-GST, while no changes were seen after etodolac. None of the drugs changed the urinary excretion of albumin.
In conclusion, a 14-day administration of etodolac or ibuprofen in therapeutic doses did not affect the renal haemodynamics, the net excretion of electrolytes or the urinary excretion of albumin in healthy subjects. However, ibuprofen, in contrast to etodolac, caused a reduction in PRC, suggesting that COX-1 is involved in basal renin release in humans. Furthermore, ibuprofen decreased lithium excretion suggesting that COX-1 is involved in the re-absorption of sodium and/or water in the proximal tubuli. The reduction in the urinary excretion of alpha-GST by ibuprofen may be caused by an inhibition of the detoxification enzyme by ibuprofen. Overall the study indicates that only small differences in the effects of the two drugs on renal function in healthy subjects exist during a treatment period of 2 weeks.

My doctor recently started me on lithium and told me there are lots of drug interactions with this m

My doctor recently started me on lithium and told me there are lots of drug interactions with this medication. My pharmacist is very good at telling me about interactions with prescription medications but how do I know which non-prescription or over-the-counter medications to avoid?

Great question! First, if you have any questions regarding non-prescription medications (also known as over the counter medications) or herbal medications, your pharmacist can help answer those questions for you. Pharmacists are experts on both prescription and non-prescription medications. Never be afraid to ask your pharmacist a question; we love to help.

Your doctor is right about lithium having many drug interactions. It is always important that you let ALL your doctors, including dentists and pharmacists, know you are taking lithium in order to avoid potential drug interactions.

As for over-the counter medications that can interact with lithium, the most common drug interactions with lithium are with the Nonsteroidal Anti-Inflammatory Agents (NSAIDs) that are often used to treat aches and pains. When combined with lithium, NSAIDs can increase lithium levels in the blood resulting in an increased risk for serious adverse effects like confusion, tremor, slurred speech, and vomiting. Examples of non-prescription NSAIDs include:

  • Ibuprofen (Advil® or Motrin®)
  • Naproxen (Naprosyn®, Aleve®)

There are also many prescription NSAIDs such as the following:

  • Celecoxib (Celebrex®)
  • Diclofenac (Voltaren® or Cataflam®)
  • Etodolac (Lodine®)
  • Indomethacin (Indocin®)
  • Ketoprofen (Orudis®)
  • Ketorolac (Toradol®)
  • Meloxicam (Mobic®)
  • Nabumetone (Relafen®)
  • Oxaprozin (Daypro®)
  • Piroxicam (Feldene®)
  • Tolmetin (Tolectin®)

In general, it is best to avoid the NSAIDS listed above when taking lithium. Certainly, they should not be used frequently or on a regular basis without consultation with your doctor(s).

If you do need a pain reliever while taking lithium, acetaminophen (Tylenol®) is a safe alternative. Sulindac (Clinoril®), a prescription pain reliever, can also be used as an alternative.

Also, too much caffeine can decrease the effectiveness of lithium and possibly increase your symptoms.

When buying any non-prescription medication it is very important to look at the active ingredients on the package.  Many non-prescription medications, such as those used to treat the cold and flu, contain multiple active ingredients and may interact with your medication. For example, Advil Cold and Flu® contains ibuprofen which can increase your lithium level. Also, read the labeling information on all non-prescription medications; this may help avoid drug interactions. When reading the active ingredients list on non-prescription medications or when in doubt about any drug interaction, ask your pharmacist!

Back to questions

Prescription Nonsteroidal Anti-Inflammatory Medicines

Nonsteroidal anti-inflammatory drugs (NSAIDs) are medicines you can take for pain relief. They are often sold over-the-counter (OTC). This means you can buy them without a prescription from your doctor. Some common brand names are Advil, Motrin, or Aleve. But these medicines are available by prescription, as well.

Path to improved health

How do prescription NSAIDs work?

NSAIDs stop a certain kind of enzyme in your body from working. These are called cyclooxygenase enzymes (also called COX enzymes). COX enzymes speed up your body’s production of hormone-like substances called prostaglandins. Prostaglandins irritate your nerve endings and cause you to feel pain. They are also part of the system that helps your body control its temperature.

By reducing the level of prostaglandins in your body, NSAIDs help relieve pain from conditions like arthritis. They also help reduce inflammation (swelling), lower fevers, and prevent blood from clotting.

There are 2 classes of prescription NSAIDs: traditional and COX-2 inhibitors.

Traditional NSAIDs include:

  • diclofenac
  • etodolac
  • fenoprofen
  • flurbiprofen
  • ibuprofen
  • indomethacin
  • meclofenamate
  • mefenamic Acid
  • meloxicam
  • nabumetone
  • naproxen
  • oxaprozin
  • piroxicam
  • sulindac
  • tolmetin

COX-2 inhibitors include:

If you need to take a prescription NSAID, your doctor will help you find one that is right for you.

What’s the difference between traditional NSAIDs and COX-2 inhibitors?

You have 2 types of COX enzymes in your body: COX-1 and COX-2. Researchers believe that one of the jobs of COX-1 enzymes is to help protect your stomach lining. The COX-2 enzyme doesn’t play a role in protecting your stomach.

Traditional NSAIDs stop both COX-1 and COX- 2 enzymes from doing their jobs. When COX-1 enzymes are blocked, pain and inflammation is reduced. But the protective lining of your stomach is also reduced. This can cause problems such as upset stomach, ulcers, bloating, and bleeding in your stomach and intestines.

COX-2 inhibitors only stop COX-2 enzymes from working. The COX-2 enzyme doesn’t help to protect your stomach. So COX-2 inhibitors may be less likely to irritate your stomach or intestines.

Things to consider

Like all medicines, prescription NSAIDs can cause side effects. However, the side effects usually are not severe and are not experienced very often.

Common side effects of prescription NSAIDs may include:

  • dizziness
  • headache
  • nausea
  • diarrhea
  • excess gas
  • constipation
  • extreme weakness or fatigue
  • dry mouth

Serious, but rare, side effects of prescription NSAIDs may include:

  • Allergic reaction. This could include difficulty breathing, hives, and swelling of the lips, tongue, or face.
  • Muscle cramps, numbness, or tingling.
  • Rapid weight gain.
  • Black, bloody, or tarry stools.
  • Bloody urine or bloody vomit.
  • Decreased hearing or ringing in the ears (also called tinnitus).
  • Jaundice (the yellowing of the skin and the whites of the eyes).
  • Abdominal cramping.
  • Heartburn.
  • Indigestion.

In addition to the side effects listed above, people taking a COX-2 inhibitor may be at risk for:

  • Swelling or water retention.
  • Skin rash or itching.
  • Unusual bruising or bleeding.
  • Difficulty sleeping (insomnia).

Call your doctor as soon as possible if your side effects become severe.

Is it safe to take NSAIDs for a long period of time?

People who take NSAIDs increase their risk of developing severe bleeding in their stomachs. They may also be at risk for heart attacks and strokes. These risks get worse if they take higher doses. It also gets worse if they take these medicines for a long period of time. If you need to take pain medicine for longer than a week, you should discuss this risk with your family doctor. You may want to explore other pain treatment options.

What is a drug interaction?

If you use 2 or more medicines at the same time, the way your body processes each one can change. When this happens, the risk of side effects from each one increases. Each medicine may not work the way it should. This is called a drug-drug interaction. For example, NSAIDs thin the blood. If you take a blood thinning medicine such as warfarin and you take an NSAID, there could be a drug-drug interaction. Vitamins and herbal supplements can affect the way your body processes medicines, too.

Certain foods or drinks can also prevent your medicine from working the way it should. Or they can make side effects worse. This is called a drug-food interaction. For example, if you’re taking a traditional NSAID, drinking alcohol can increase your risk of liver disease or stomach bleeding.

Drug-drug interactions and drug-food interactions can be dangerous. Be sure that your doctor knows all of the medicines you are taking. This includes OTC and prescription medicines, vitamins, and herbal supplements. Also, talk to your doctor before you take any new OTC or prescription medicine, vitamin, or supplement.

It’s important to take medicines exactly as your doctor prescribes. Ask your doctor whether you need to avoid any foods or drinks while using a prescription NSAID.

Questions to ask your doctor

  • What is the difference between an OTC NSAID and a prescription NSAID?
  • What is the best NSAID for me?
  • What are the side effects?
  • How long is it safe for me to take a prescription NSAID?
  • Are there any drug-drug or food-drug interactions I need to watch out for?

Copyright © American Academy of Family Physicians

This information provides a general overview and may not apply to everyone. Talk to your family doctor to find out if this information applies to you and to get more information on this subject.

Before Your Procedure | UI Health

Before Your Procedure

Please arrange a ride from the clinic for injections performed on site.

Take your medications on the day of the procedure, especially blood pressure and diabetes medications.

If you are having sedation:

  • Inform our scheduler
  • Do not eat anything for 8 hours prior to the injection
  • You can drink Gatorade or apple juice up to two hours before the injection

Please tell us if you have an infection, are on antibiotics, have a new rash, or have an open wound. We will reschedule your injection once the infection is resolved.

Blood Thinners

Please tell us if you take any of these:

1. Aspirin:

  • If you are taking Aspirin for heart health and have NEVER had a heart attack, stroke, or blood clot, (ASPIRIN HAS NOT BE PRESCRIBED BY A DOCTOR), then you can stop it for FOUR days prior to the procedure. Also ask the doctor when you can restart the medications.
  • If you are taking Aspirin because you have had a heart attack, stroke, or a blood clot, you will have to discuss stopping the medication with your primary care doctor, neurologist or cardiologist. We will need a note from your doctor documenting the plan for aspirin
    • There are some procedures we will do while you are on aspirin and others that we won’t do. There is an increased of bleeding if these injections are done on aspirin. You should inform us if your doctor does NOT want you to stop the aspirin.
      • Cervical or neck injections cannot be done while on aspirin- Please discuss with your pain doctor
      • Lumbar or lower back injections can be done while on aspirin but may increase your risk of bleeding.
      • Sacroiliac joint injection and facet injections can be done on aspirin
      • Peripheral joint injections: Hips/knee/shoulder can be done on aspirin
    • Full dose Aspirin may be reduced to 81mg for injections except neck- Discuss with your MD
    • If there are any concerns, we should see you for a follow-up appointment after discussing this with your doctor


Ibuprofen should be stopped TWO days prior to the injection

There are some procedures we will do while you are on ibuprofen and others that we won’t do. There is an increased of bleeding if these injections are done on ibuprofen.

  • Cervical or neck injections CANNOT be done while on ibuprofen
  • Lumbar or lower back injections can be done while on ibuprofen but may increase your risk of bleeding.
  • Sacroiliac joint injection and facet injections can be done on ibuprofen
  • Peripheral joint injections: Hips/knee/shoulder can be done on ibuprofen

3. Other Anti-inflammatories:

  • Diclofenac, Voltaren, Cambia, Solaraze, Zipsor, Pennsaid, Cataflam, Flector – stop for 1 day
  • Midol, Aleve, Naprelan, Naprosyn, Anaprox, Ec-Naprosyn, Select, and Naproxen:- stop for 4 days
  • Meloxicam- stop for 4 days
  • Etodolac (Lodine)- stop for 2 days

4. Coumadin, Lovenox, Ticlid, Plavix, Heparin, Fondaparinux, Xeralto, Pradaxa, Eliquis, Aggrenox, Persantin, Fragmin

  • Make an appointment to discuss this with us before stopping the above medication
  • We will NOT perform any injections while you are on any of the above medications

Memorial Sloan Kettering Cancer Center

This document, provided by Lexicomp ® , contains all the information you need to know about the drug, including the indications, route of administration, side effects and when you should contact your healthcare provider.

Trade names: USA


Trade names: Canada

NU-Etodolac [DSC]; TARO-Etodolac


  • This drug may increase the risk of heart and blood vessel problems, such as heart attack and stroke.These effects can be deadly. This risk may be increased if you have heart disease or have risk factors for such diseases. However, the risk may be increased even for people who do not have or are not at risk of developing heart disease. The risk may arise during the first weeks of using this drug and may increase with higher doses or with long-term use. This drug should not be used immediately before or after coronary artery bypass surgery.
  • This drug may increase the likelihood of severe and sometimes fatal stomach or intestinal problems such as ulcers or bleeding. The risk is increased in the elderly and in people who have previously had ulcers or bleeding in the stomach or intestines. Such violations can occur suddenly.

What is this drug used for?

  • Used to treat some types of arthritis.
  • Used to relieve pain.

What should I tell my doctor BEFORE taking this drug?

  • If you are allergic to this drug, any of its ingredients, other drugs, foods or substances. Tell your doctor about your allergy and how it manifested itself.
  • If you are allergic to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen.
  • If you have any of the following health problems: gastrointestinal bleeding or kidney problems.
  • If you have any of the following health conditions: Heart failure (weak heart) or have recently had a myocardial infarction.
  • If you are taking NSAIDs, a salicylate such as aspirin, or pemetrexed.
  • If you are taking phenylbutazone.
  • If you are unable to get pregnant or are checking if you are able to get pregnant.
  • If you are pregnant, plan to become pregnant, or become pregnant while taking this drug. If you take this drug after 20 weeks of pregnancy, it can cause fetal harm.If you are between 20 and 30 weeks pregnant, take this drug only as directed by your doctor. Do not use this drug after 30 weeks of pregnancy.

This list of drugs and diseases that may be adversely associated with this drug is not exhaustive.

Tell your doctor and pharmacist about all medicines you take (both prescription and over-the-counter, natural products and vitamins) and your health problems.You need to make sure that this drug is safe for your medical condition and in combination with other drugs you are already taking. Do not start or stop taking any drug or change the dosage without your doctor’s approval.

What do I need to know or do while taking this drug?

  • Tell all healthcare providers that you are taking this drug.These are doctors, nurses, pharmacists and dentists.
  • With long-term use of the drug, a blood test must be performed. Talk to a medical professional.
  • This drug may interfere with some laboratory tests. Tell all healthcare providers and laboratory staff that you are taking this drug.
  • The use of this type of drugs has been associated with high blood pressure. Monitor your blood pressure as directed by your doctor.
  • Consult a physician before drinking alcohol.
  • If you smoke, consult your doctor.
  • Do not take the drug in higher doses than the doctor prescribed. Taking more than the prescribed amount of the drug increases the risk of serious side effects.
  • Do not take this drug for longer than your doctor prescribed.
  • If you have asthma, consult your doctor. You may be more sensitive to the drug.
  • There is an increased likelihood of bleeding. Be careful and avoid injury. Use a soft toothbrush and electric shaver.
  • The risk of developing heart failure is increased with the use of drugs of this kind. People with heart failure have an increased risk of myocardial infarction, hospitalization for heart failure, and death. Consult your doctor.
  • People who have had myocardial infarction and are taking drugs of this kind have an increased risk of recurrence of myocardial infarction and death due to heart problems.People who took drugs of this kind after their first heart attack were also more likely to die one year after myocardial infarction compared with those who did not take these drugs. Consult your doctor.
  • If you are taking aspirin to prevent myocardial infarction, consult your doctor.
  • Liver dysfunctions have been reported while taking drugs of this kind. Sometimes these cases were fatal.Call your doctor right away if you have signs of liver dysfunction, such as dark urine, tired feeling, lack of appetite, nausea or abdominal pain, light colored stools, vomiting, yellow skin or eyes.
  • Severe and sometimes fatal reactions have occurred with other drugs of this nature. In most cases, this reaction was accompanied by symptoms such as fever, rash, inflammation of the lymph nodes, and dysfunction of various organs such as the liver, kidneys, blood, heart, muscles, joints and lungs.If you have any questions, please consult your doctor.
  • If you are 65 years of age or older, use this drug with caution. You may have more side effects.
  • Non-steroidal anti-inflammatory drugs (NSAIDs), such as this drug, can interfere with egg release (ovulation). This can negatively affect your ability to get pregnant. As a rule, the ovulation process is restored after you stop taking this drug. Consult your doctor.
  • Tell your doctor if you are breastfeeding. It is necessary to consult if the drug poses any risk to the child.

What side effects should I report to my doctor immediately?

WARNING. In rare cases, some people with this drug can have serious and sometimes deadly side effects. Call your healthcare professional or get medical attention right away if you have any of the following signs or symptoms, which may be associated with serious side effects:

  • Signs of an allergic reaction such as rash, hives, itching, reddened and swollen skin with blistering or scaling, possibly associated with fever, wheezing or wheezing, tightness in the chest or throat, difficulty breathing, swallowing or speaking, unusual hoarseness, swelling in the mouth, face, lips, tongue, or throat.
  • Signs of bleeding such as vomiting or coughing up blood; vomiting like coffee grounds; blood in the urine; black, red, or tarry stools; bleeding from the gums; non-cyclic vaginal bleeding; bruising that occurs or increases for no reason; bleeding that you cannot stop.
  • Signs of kidney problems, including lack of urination, change in urine volume, blood in the urine, or rapid weight gain.
  • Signs of elevated potassium levels such as a feeling of disturbed heartbeat, confusion, feeling weak or dizzy, feeling light-headed, feeling numb or tingling, or shortness of breath.
  • Signs of high blood pressure, such as very severe headache, or dizziness, or loss of consciousness, or blurred vision.
  • Shortness of breath, sudden weight gain, or swelling of the arms or legs.
  • Chest pain or pressure or heart palpitations.
  • Weakness on one side of the body, difficulty speaking or thinking, trouble maintaining balance, drooping one side of the face, or blurred vision.
  • Feeling extremely tired or weak.
  • Ringing in the ears.
  • Flu-like symptoms.
  • Swelling of the gland.
  • Possible severe skin reaction (Stevens-Johnson syndrome / toxic epidermal necrolysis). This can lead to serious and permanent health problems and sometimes death. Get immediate medical attention if you experience symptoms such as redness, skin swelling with blistering or scaling (with or without a high fever), redness or irritation of the eyes, and ulceration in the mouth, throat, nose, or eyes.

What are some other side effects of this drug?

Any medicine can have side effects. However, many people have little or no side effects. Call your doctor or get medical help if these or any other side effects bother you or do not go away:

  • Constipation, diarrhea, abdominal pain, nausea or vomiting.
  • Heartburn.
  • Gas.
  • Feeling dizzy, tired, or weak.
  • Headache.

This list of potential side effects is not exhaustive. If you have any questions about side effects, please contact your doctor. Talk to your doctor about side effects.

You can report side effects to the National Health Office.

You can report side effects to the FDA at 1-800-332-1088. You can also report side effects at https: // www.fda.gov/medwatch.

What is the best way to take this drug?

Use this drug as directed by your healthcare practitioner. Read all the information provided to you. Follow all instructions strictly.

All forms of issue:

  • Take with or without food. Take with food if the medicine causes nausea.
  • Take this drug with a full glass of water.

Extended release tablets:

  • Swallow whole.Do not chew, break, or crush.

What should I do if a dose of a drug is missed?

All forms of issue:

  • If you are taking this medication regularly, take the missed dose as soon as you can.
  • If it is time for your next dose, do not take the missed dose and then return to your normal dose schedule.
  • Do not take 2 doses at the same time or an additional dose.

Short-acting preparations:

  • In most cases, this drug is used as needed. Do not take this medicine more often than prescribed by your doctor.

How do I store and / or discard this drug?

  • Store at room temperature in a dry place. Do not store in the bathroom.
  • Store all medicines in a safe place. Keep all medicines out of the reach of children and pets.
  • Dispose of unused or expired drugs. Do not empty into toilet or drain unless directed to do so. If you have any questions about the disposal of your medicinal products, consult your pharmacist. Your area may have drug recycling programs.

General information on medicinal products

  • If your health does not improve or even worsens, see your doctor.
  • You should not give your medicine to anyone and take other people’s medicines.
  • Some medicines may have different patient information sheets. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
  • A separate patient instruction sheet is attached to the product. Please read this information carefully. Reread it each time you replenish your supply.If you have questions about this drug, talk with your doctor, pharmacist, or other healthcare professional.
  • If you think there has been an overdose of a drug, call a Poison Control Center immediately or seek medical attention. Be prepared to tell or show which drug you took, how much and when it happened.

Use of information by the consumer and limitation of liability

This information should not be used to make decisions about taking this or any other drug.Only the attending physician has the necessary knowledge and experience to make decisions about which drugs are appropriate for a particular patient. This information does not guarantee that the drug is safe, effective, or approved for the treatment of any disease or specific patient. Here are only brief general information about this drug. It does NOT contain all available information on the possible use of the drug with instructions for use, warnings, precautions, information about interactions, side effects and risks that may be associated with this drug.This information should not be construed as a guide to treatment and does not replace the information provided to you by your healthcare professional. Check with your doctor for complete information on the possible risks and benefits of taking this drug. Use of this information is governed by the Lexicomp End User License Agreement available at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.


© UpToDate, Inc.and its affiliates and / or licensors, 2021. All rights reserved.

90,000 Etodolac vs Ibuprofen: Differences, Similarities and What’s Best for You – Drug Vs. Friend

Drug Vs. Friend

Drug Review and Main Differences | Treatment conditions | Efficiency | Insurance coverage and cost comparison | Side Effects | Drug Interactions | Warnings | Frequently Asked Questions

No one wants to live with discomfort or pain for an extended period of time, or at all for that matter.Fortunately, prescription and over-the-counter pain relievers are available at your local pharmacy. Although they are not as powerful as opioid pain relievers, which require more medical examination and prescription, NSAIDs such as etodolac or ibuprofen are effective for treating mild to moderate pain.

Also known as nonsteroidal anti-inflammatory drugs, NSAIDs block the production of prostaglandins. Your body can respond to certain diseases by producing prostaglandins, which are chemicals that cause pain, inflammation, and fever.NSAIDs block prostaglandin-producing enzymes – COX-1 and COX-2 – to control the body’s inflammatory response and reduce pain.

Etodolac and ibuprofen are NSAIDs. However, they have several important differences.

What are the main differences between etodolac and ibuprofen?

Etodolac is sometimes known by its (now discontinued) trade name Lodine. It is available as a generic drug and can only be obtained with a doctor’s prescription.

Etodolac has a half-life of six to seven hours and reaches peak blood concentrations one to two hours after ingestion. It is usually taken two to three times a day for arthritis pain. There is also an extended-release etodolac tablet that has a longer half-life, about eight hours, and can be taken once a day.

Ibuprofen is a more common NSAID available over the counter (OTC). Higher doses of ibuprofen are also available with a doctor’s prescription.Popular ibuprofen brands include Advil, Motrin, and Midol.

I’ll show on drug test

Ibuprofen peaks in blood within one to two hours after ingestion. However, unlike etodolac, ibuprofen has a shorter half-life, approximately two hours. Prescription ibuprofen comes in pills that are usually taken three to four times a day. The over-the-counter version comes in oral tablets, capsules, and liquid suspensions.



Main differences between etodolac and ibuprofen
Etodolac Ibuprofen
Brand / generic status Generic available (brand discontinued) Brands and generics available
What is a brand? Lodin Advil, Motrin, Midol
In what form (s) is the drug included? Oral Capsules
Oral Tablet
Oral Tablet, Extended Release
Oral Capsules
Oral Tablet
Oral Liquid
Injection (Neo
For pain: 200 to 400 mg every 6 to 8 hours as needed.Do not exceed the maximum dose of 1200 mg per day.

For osteoarthritis or rheumatoid arthritis: immediate release 300 mg two to three times daily or 400-500 mg twice daily. Extended release 400 to 1000 mg once daily. Do not exceed the maximum dose of 1200 mg per day.

For pain: 200 to 400 mg every 4-6 hours as needed. Do not exceed the maximum dose of 1200 mg per day unless directed by your doctor.

For osteoarthritis or rheumatoid arthritis: 400 to 800 mg three to four times a day.Do not exceed the maximum dose of 3200 mg per day.

How long does a typical treatment take? The duration of treatment depends on the state of health, the severity of the pain, and other factors. Treatment can be short term or long term. The duration of treatment depends on the state of health, the severity of the pain, and other factors. Treatment can be short term or long term.
Who usually takes this medicine? Adults and children 6 years and older Adults and children 6 months and older

Conditions treated with etodolac and ibuprofen

Etodolac and ibuprofen are intended to relieve pain.They are usually taken to relieve mild to moderate acute pain during dental procedures, migraines, or muscle pain (myalgia).

Etodolac and ibuprofen are particularly useful and FDA approved for the treatment of pain and inflammation in osteoarthritis and rheumatoid arthritis. Stronger medications are usually needed to treat more severe joint pain or bone pain associated with arthritis. In some cases, children over the recommended age may also be treated with these NSAIDs for juvenile idiopathic arthritis.

Over-the-counter ibuprofen is indicated for the treatment of fever and menstrual cramps (primary dysmenorrhea). An injectable form of ibuprofen called NeoProfen is used to treat patent ductus arteriosus (PDA) in premature babies.



Condition Etodolac Ibuprofen
Pain yes yes
Juvenile idiopathic arthritis yes yes
Fever No yes
Primary dysmenorrhea No No No

Are etodolac or ibuprofen more effective?

Both etodolac and ibuprofen are effective NSAIDs for pain relief.They both block the enzymes cyclooxygenase (COX) to control inflammation and reduce pain in people with arthritis. However, the effect of etodolac lasts a little longer. Therefore, some people may prefer etodolac due to its lower intake frequency.

In a double-blind study comparing etodolac and ibuprofen, 1,446 patients with rheumatoid arthritis received 150 mg of etodolac twice daily, 500 mg of etodolac twice daily, or 600 mg of ibuprofen four times daily. Both doses of etodolac were found to be similar in effectiveness to the dose of ibuprofen.In terms of side effects, those who took etodolac experienced less indigestion, rashes, and stomach bleeding than those who took ibuprofen. However, this could be related to the amount of medication the patients were giving.

While no other clinical trials have directly compared etodolac and ibuprofen, various studies have compared other NSAIDs with etodolac or ibuprofen. One meta-analysis showed that the maximum daily dose of diclofenac is more effective than the maximum daily dose of ibuprofen, naproxen, and celecoxib (but the lowest effective dose of NSAIDs is always recommended).Another meta-analysis found that some NSAIDs such as piroxicam and azapropazone have a high risk of toxicity while low doses of ibuprofen have a low risk of toxicity. In general, it can be said that NSAIDs tend to differ in safety rather than effectiveness.

Due to the large number of pain management options, it is important to consult with your doctor to determine the best treatment option. A doctor or health care provider can provide appropriate medical advice for certain conditions.

Coverage and cost comparison for etodolac and ibuprofen

Generic pills of etodolac are usually covered by Medicare and insurance plans. If you have a medical condition such as arthritis, insurance is likely to cover this pain relief. The average retail price of etodolac can vary by dose, but you can pay around $ 50 for etodolac using a SingleCare coupon at participating pharmacies.

Because ibuprofen is sold without a prescription, some forms may not be covered by insurance plans.However, most Medicare Part D and insurance plans must cover prescription ibuprofen pills, depending on the treatment regimen. In general, ibuprofen is more affordable than etodolac. Use the SingleCare coupon for ibuprofen if you have a prescription from your healthcare provider.

Etodolac Ibuprofen
Usually covered by insurance? yes Yes (prescription pills)
Usually covered by Medicare Part D? yes yes
Standard dosage 300 mg 2-3 times a day 400-800 mg 3-4 times a day
Typical Medicare co-pay 0– US $ 76 US $ 0-22
SingleCare cost US $ 40-80 US $ 4-24

Common side effects of etodolac versus ibuprofen

Most common side effects NSAIDs, including etodolac and ibuprofen, are nausea, indigestion (indigestion), constipation, diarrhea, and abdominal or abdominal pain.In addition to gastrointestinal side effects, NSAIDs can also cause dizziness, swelling of the hands or feet (edema), headache, rashes, and ringing in the ears (tinnitus). Most of the side effects of etodolac and ibuprofen are mild and go away on their own.

Serious side effects of NSAIDs may include allergic reactions, such as severe rash or anaphylaxis, from active or inactive ingredients. Other serious side effects include gastrointestinal side effects such as stomach bleeding and peptic ulcers.Check with your healthcare professional if you notice blood in your stools, weight loss, or severe abdominal pain.


This may not be a complete list of side effects that you may experience.Please talk to your doctor or healthcare provider to find out more.

Source: DailyMed (Etodolac), DailyMed (Ibuprofen)

Drug Interactions Etodolac and Ibuprofen

Because they block the enzyme COX-1, which plays a role in platelet production and blood clots, NSAIDs can affect the blood … NSAIDs can increase the risk of bleeding due to antiplatelet drugs such as aspirin and anticoagulants such as warfarin.

Etodolac and ibuprofen may cause fluid retention and affect kidney function. As a result, these NSAIDs can raise blood pressure. If you are also taking medicines for high blood pressure (antihypertensives) such as lisinopril or losartan, you may need to monitor your blood pressure while taking NSAIDs.

Etodolac and ibuprofen may interfere with the elimination of cyclosporin, digoxin or methotrexate from the body. Taking NSAIDs may increase the risk of cyclosporine, digoxin, or methotrexate toxicity.

Find other possible drug interactions below.

How high should blood sugar be after a meal

Etodolac Ibuprofen
Side effect Applicable? Frequency Applicable? Frequency
Nausea yes 1% –10% yes 1% –3%
Abdominal pain yes yes 1% –3%
Indigestion yes 1% –10% yes 1% –3%
Constipation yes 1% –10% 1% –3%
Diarrhea yes 1% –10% yes 1% –3%
Dizziness yes 1% –10% yes 1% –3%
Edema yes 1% –10% yes 1% –3%
Headache yes 1% –10% yes 1% –3%
Rash yes 1% –10% yes 1% –3%
Tinnitus yes 1% –10% yes 1% –3%


0234 Pemetrexed

902 other possible drug interactions.

Etodolac and ibuprofen warnings

Etodolac and ibuprofen, like other NSAIDs, may increase the risk of serious cardiovascular thrombotic events such as heart attack and stroke. Use of NSAIDs should be avoided or monitored in people with cardiovascular problems, heart failure, heart disease, and high blood pressure.

The use of etodolac or ibuprofen may lead to an increased risk of serious gastrointestinal (GI) adverse events such as stomach bleeding and gastric ulcer.Without proper treatment, inflammation and bleeding in the gastrointestinal tract can be fatal. Older adults may have a higher risk of serious gastrointestinal side effects.

NSAIDs should not be used immediately before or after a cardiac procedure called coronary artery bypass grafting (CABG).

People with kidney disease may be at increased risk of further kidney problems when taking NSAIDs.

Talk to your healthcare professional about other precautions before taking NSAIDs.

Frequently asked questions about etodolac and ibuprofen

What is etodolac?

Etodolac is a non-steroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation. It is FDA approved for the treatment of osteoarthritis and rheumatoid arthritis in adults. Generic etodolac can only be obtained with a prescription.

What is ibuprofen?

Ibuprofen is widely known under brands such as Advil and Motrin. It is available over the counter for mild to moderate pain relief, fever, and menstrual cramps.Stronger ibuprofen can be obtained with a prescription to treat pain and inflammation in osteoarthritis and rheumatoid arthritis.

Are etodolac and ibuprofen the same?

Etodolac and ibuprofen are not the same thing. Although they are both NSAIDs, they have differences in dosage and route of administration. Etodolac is a prescription drug primarily used for adults with arthritis. Ibuprofen is more readily available as an over-the-counter medicine for mild pain and fever.

Is etodolac or ibuprofen better?

The best NSAID depends on the dose you are taking and what you are taking it for. Compared to ibuprofen, etodolac lasts longer in the body, so it can be taken less frequently throughout the day. However, it can be more expensive than ibuprofen. Depending on your general condition, your doctor may recommend one remedy over the other.

Can I use etodolac or ibuprofen during pregnancy?

Etodolac and ibuprofen are generally not recommended during pregnancy.The use of NSAIDs during pregnancy is associated with an increased risk of birth defects or miscarriage, especially during late pregnancy. Check with your doctor if you are considering treatment options during pregnancy.

Can I use etodolac or ibuprofen with alcohol?

When taking NSAIDs, it may sometimes be normal to have minimal alcohol consumption. However, excessive alcohol consumption can lead to an increased risk of gastrointestinal side effects with NSAIDs.Alcohol and NSAIDs can irritate the stomach and intestinal lining, which can lead to ulcers or bleeding.

Is Etodolac a pain reliever?

Etodolac is an effective pain reliever. It is most effective in treating pain and inflammation caused by arthritis. It is also useful for relieving acute pain after certain procedures, such as dental surgery.

Is etodolac stronger than naproxen?

The effectiveness of NSAIDs depends, among other things, on the dose taken.All other things being equal, etodolac and naproxen are comparable in effectiveness. According to double-blind studies, etodolac and naproxen are equally effective in treating rheumatoid arthritis. Both drugs are also well tolerated in terms of side effects.

90,000 The choice of a non-steroidal anti-inflammatory drug for the symptomatic treatment of rheumatic diseases: focus on nimesulide uMEDp

Nimesulide is the golden mean of the class of non-steroidal anti-inflammatory drugs.That is why it is firmly entrenched in the arsenal of rheumatologists, therapists, family doctors and doctors of other specialties. The drug combines a high analgesic and anti-inflammatory potential, a good safety profile. In addition, it is available in various dosage forms.


Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the symptomatic treatment of diseases associated with pain, fever, and inflammation [1].The unique combination of analgesic, anti-inflammatory and antipyretic effects determines the advantage of NSAIDs over drugs such as paracetamol and opioids [2].

In addition, NSAIDs differ in a variety of dosage forms and an affordable price.

Currently, there are about 20 international non-proprietary NSAIDs registered in Russia. If we take into account the large number of generics and different dosage forms, the number of drugs will exceed a hundred.

NSAIDs are especially in demand in rheumatic pathologies. The experience of their use in such patients has more than 100 years [3].

The drugs of this group are practically indispensable in the treatment of osteoarthritis (OA) and nonspecific pain in the lower back [4, 5]. Despite the fact that paracetamol is indicated as the first analgesic for OA in international guidelines [6], it is NSAIDs that are often prescribed as the main pain reliever due to their higher efficacy and safety [7, 8].

In autoimmune inflammatory rheumatic diseases such as rheumatoid arthritis (RA), the role of NSAIDs also remains significant. The therapy of RA necessarily includes drugs that alleviate the main symptoms, primarily pain, since the effect of the use of basic anti-inflammatory drugs does not develop immediately. So, when using synthetic drugs, a significant improvement is noted not earlier than after one or two months [9]. The use of genetically engineered biological drugs also does not allow abandoning symptomatic therapy [10].

The analgesic, antipyretic and anti-inflammatory effects of NSAIDs are due to the inhibition of cyclooxygenase (COX), which catalyzes the synthesis of prostanoids, including thromboxane and prostaglandins, and thereby mediates various biological effects [11].

The main pharmacological properties of NSAIDs are associated with the suppression of the activity of COX-2. This enzyme provides a rapid increase in the local concentration of prostaglandin H2, which is a substrate for the synthesis of one of the central mediators of pain and inflammation, prostaglandin E2 [9].

COX-2-dependent processes include the appearance and intensification of pain due to any tissue damage, the development of chronic pain syndrome, local and systemic inflammatory response, local and systemic hyperthermia, catabolic processes, neoangiogenesis, etc. The release of pro-inflammatory substances, primarily prostaglandin E2, is associated with the effect of NSAIDs on the central mechanisms of transmission of the pain impulse.

COX-1-dependent processes include platelet aggregation.Inhibition of this enzyme by acetylsalicylic acid helps prevent thrombosis. At the same time, undesirable effects such as erosive and ulcerative lesions of the upper gastrointestinal tract are traditionally associated with the suppression of the physiological form of COX-1, which plays an important role in maintaining many parameters of homeostasis, including the protective potential of the mucous membrane of the gastrointestinal tract (GIT). and gastrointestinal bleeding.

It should be noted that NSAIDs are comparable in effectiveness, but differ in the safety profile in relation to the gastrointestinal tract, cardiovascular system, liver and kidneys [12].

All NSAIDs, with the exception of acetylsalicylic acid, are associated with an increased risk of adverse cardiovascular events [1, 11].

In this regard, it seems relevant to compare the safety of two types of NSAIDs: non-selective COX-1 and COX-2 inhibitors (traditional NSAIDs) and selective COX-2 inhibitors (coxibs).

Although the hypothesis of COX-2 selectivity to explain the risk of prothrombotic changes due to NSAID administration is often disputed [13], there is evidence that the use of coxibs, as well as traditional NSAIDs with high selectivity for this enzyme, can significantly increase the risk of serious cerebrovascular and cardiovascular events (especially when using high doses and / or long-term treatment) [1, 11].

A meta-analysis of the results of randomized trials showed that the relative risk for coxibs is 1.37 with a 95% confidence interval (CI) -1.14–1.66, for diclofenac – 1.41 (95% CI 1.12–1 , 78) compared with placebo [13]. Similar results were obtained when conducting a meta-analysis of the results of observational studies [14].

It has also been established that the relative risk of adverse cardiovascular events with NSAIDs may not depend on the initial cardiovascular risk [15].Currently, the use of NSAIDs for the symptomatic treatment of diseases of the musculoskeletal system with a high cardiovascular risk [11] is limited. The exception is when other methods of pharmacotherapy (for example, paracetamol with or without weak opioids) are ineffective. In this case, the lowest effective dose is used and the shortest treatment times are established.

Inappropriate use of NSAIDs can be a public health problem, especially in high baseline risk groups [1].We are talking, in particular, about elderly patients in whom cardiovascular diseases are combined with pathologies of the musculoskeletal system [16]. The choice of drug in this situation can be critical.

Features of the pharmacology of nimesulide

One of the most widely used NSAIDs in Russia is nimesulide.

Nimesulide was introduced into clinical practice in the early 1980s. During the period of use, it has established itself as an effective, well-tolerated and affordable drug [3, 17, 18].

The nimesulide molecule, unlike the molecules of other NSAIDs, has alkaline properties. This allows the substance to easily penetrate into the foci of inflammation and accumulate in them at a higher concentration than in the blood plasma [3, 19]. Within 30 minutes after oral administration, the concentration of the drug in the blood reaches 25–80% and the analgesic effect begins to develop. The peak concentration and, consequently, the maximum analgesic effect is observed one to three hours after ingestion [20-23].A faster analgesic effect is possessed by nimesulide in granular form (Nimesil®), which is extremely important for the relief of both acute pain and acute gouty arthritis [23, 24].

Nimesulide is characterized by a fairly high, but not absolute, selectivity for COX-2. According to some experts, according to this indicator, it occupies an intermediate position between meloxicam and celecoxib [11].

In addition to the main pharmacological action, nimesulide has effects that do not depend on the class-specific effect on prostaglandin synthesis: it inhibits the synthesis of pro-inflammatory cytokines, the activity of metalloproteinases (responsible, in particular, for the destruction of the glycoprotein complex of cartilage tissue in OA), blocks phosphodiesterase 4, thereby reducing the activity cells of inflammatory aggression (macrophages and neutrophils), has an antihistamine effect [18, 21, 25, 26].This determines its therapeutic specificity.


The rapid analgesic effect of nimesulide has been confirmed in patients who underwent maxillofacial surgery, as well as in patients with dysmenorrhea [19, 27].

The pronounced analgesic and anti-inflammatory effect of nimesulide in diseases of the musculoskeletal system has been demonstrated in a number of randomized clinical trials.Thus, in 122 patients with shoulder rotator tendinitis and / or subacromial bursitis, who were prescribed nimesulide 200 mg / day or diclofenac 150 mg / day for 14 days for the treatment of acute pathology of periarticular soft tissues for 14 days, the first drug was more effective than the second [28 ]. At the same time, 96.8% of patients characterized the tolerability of nimesulide as good or excellent. Among those who received diclofenac, such was 72.9% (p

In a study that included 102 patients with acute lower back pain who took nimesulide 100 mg twice a day or ibuprofen 600 mg three times a day for ten days, the advantage of nimesulide over ibuprofen was also noted (p = 0.02 ) in relation to pain relief and influence on spinal function.In addition, during the period of therapy, side effects from the gastrointestinal tract in those receiving nimesulide were recorded less frequently [29].

The effectiveness of nimesulide in the symptomatic treatment of RA was confirmed in a four-week study [30]. Thus, 268 patients with early stage RA used 400 and 200 mg of nimesulide per day. Diclofenac at doses of 200 and 100 mg / day was chosen as a control drug. Against the background of the therapy, all patients showed a statistically significant decrease in the number of inflamed joints and morning stiffness.However, nimesulide was found to be more effective than diclofenac in relieving pain. Thus, a pain reduction of> 50% on a visual analogue scale was recorded in 44.8% of those receiving nimesulide and 40.8% of those receiving diclofenac.

The pronounced analgesic and anti-inflammatory effect of nimesulide in the form of granules (Nimesil®) in RA patients was demonstrated in a Russian multicenter study [31]. Side effects were observed only in 15.3% of patients, they were reversible and did not depend on the dose of the drug.

Nimesulide in various dosage forms, including granular (Nimesil®), has shown high efficacy in gouty arthritis [29, 30]. It should be noted that Nimesil® had a more pronounced anti-inflammatory effect [24, 32, 33].

Of particular interest are the results of a study that compared the rate of onset of analgesic and anti-inflammatory effects with the use of different forms of nimesulide and diclofenac [34].The study included 90 patients with gout, in whom previous NSAID therapy was ineffective.

Study participants were randomized into three treatment groups – 30 patients each. The first group received granular nimesulide (Nimesil®) in a sachet at a dose of 100 mg twice a day, the second – tableted nimesulide according to a similar scheme, the third – diclofenac at a dose of 75 mg twice a day. The duration of therapy was seven days.

Assessment of the rate of onset of the analgesic effect during the first three hours showed a clear advantage of nimesulide in various forms over diclofenac.At the same time, patients taking granular nimesulide noted a decrease in the severity of pain as early as 20 minutes after taking the first dose of the drug.

Seven days later, an attack of gouty arthritis was arrested in 24 (80%) patients who received nimesulide in the form of granules, 11 (36%) – nimesulide in the form of tablets and four (13%) – diclofenac.


The use of NSAIDs is associated with the risk of developing class-specific side effects [9], primarily NSAID gastropathies, pathologies of the upper gastrointestinal tract – erosions, ulcers and gastrointestinal disasters (bleeding and perforation).

The likelihood of developing gastropathy in patients receiving NSAIDs more than quadruples and ranges from 0.5 to 1.0 episodes per 100 patients per year. Regularly taking NSAIDs die from gastrointestinal bleeding and perforation of ulcers three to four times more often than those who do not receive drugs in this group [35, 36].

In the EVIDENCE study [37], which assessed the incidence of complications in 4144 patients who started using NSAIDs for OA, RA, or ankylosing spondylitis, it was found that the incidence of uncomplicated gastrointestinal pathologies is 18.5 per 100 patients per year, serious complications, including bleeding – 0.7.

The risk of NSAID gastropathy can be significantly reduced [2]. It should be borne in mind that this pathology in the overwhelming majority of cases develops in patients with a history of peptic ulcer disease, over 65 years of age and taking drugs that affect the blood coagulation system (low doses of aspirin, other antiplatelet drugs, direct and indirect anticoagulants). To prevent the development of this complication, such patients should be prescribed safer selective COX-2 inhibitors or proton pump inhibitors.This will reduce the risk of developing dangerous complications by 40-60% [35, 36].

NSAID therapy is also associated with the development of complications from the cardiovascular system: destabilization of arterial hypertension, progression of heart failure and an increased risk of cardiovascular accidents (myocardial infarction and ischemic stroke) [36, 38].

The results of randomized clinical trials indicate that the incidence of cardiovascular complications is not only equal to, but also superior to NSAID gastropathy.Thus, in the MEDAL study, 34,700 patients with OA or RA took the selective NSAID etoricoxib at doses of 60 and 90 mg / day or diclofenac 150 mg / day for one and a half years. The overall incidence of dangerous gastrointestinal complications (ulcers, bleeding, perforation) while taking etoricoxib was 1.0%, diclofenac – 1.4%. Bleeding and perforation accounted for 0.45% each. Moreover, serious cardiovascular complications were recorded in 1.9% of patients in both groups, cerebrovascular complications – in 0.53 and 0.48% of patients, respectively [39].

The overwhelming majority of cardiovascular accidents while taking NSAIDs is observed in patients with diagnosed cardiac pathologies, type 2 diabetes mellitus and a high calculated cardiovascular risk [36, 38].

… for the gastrointestinal tract

Unlike other representatives of NSAIDs, nimesulide is well tolerated [9]. This is evidenced not only by the results of Russian and foreign studies, but also by the data of clinical practice.

The study of the frequency of gastrointestinal complications with the use of diclofenac (n = 3553), nimesulide (n = 3807) and ibuprofen (n = 1470) in real clinical practice [40] showed that their total frequency with the use of nimesulide is significantly less than with the appointment of diclofenac (12.1%), and does not differ from that of ibuprofen (8.1 and 8.6%, respectively).

Analysis of 10,608 reports of serious adverse reactions due to therapy with various NSAIDs [41] received from 1988 to 2000., demonstrated that nimesulide was the cause of the development of certain complications from the gastrointestinal tract half as often as other NSAIDs. Thus, the number of reports on the development of side effects during therapy with nimesulide was 10.4%, diclofenac – 21.2%, ketoprofen – 21.7%, piroxicam – 18.6%.

The risk of gastrointestinal bleeding with the use of different NSAIDs has been assessed in a large epidemiological study [42]. The authors of the study analyzed 2,813 episodes of dangerous gastrointestinal bleeding.The control group consisted of 7193 patients without gastrointestinal bleeding. The groups were matched for gender and age.

The relative risk of gastrointestinal bleeding for nimesulide was 3.2, diclofenac – 3.7, meloxicam – 5.7.

The safety of nimesulide has also been actively studied in Russia.

Thus, in a study on the safety of granular nimesulide (drug Nimesil®) [43], the frequency of recurrence of NSAID-induced ulcers was assessed while taking nimesulide.The drug was prescribed at a dose of 200 mg / day to 20 patients who completed the course of treatment for ulcers or multiple (more than ten) erosions of the stomach and / or duodenum resulting from the use of other NSAIDs. The control group consisted of 20 patients who, after healing of NSAID-induced ulcers and multiple erosions, were prescribed diclofenac 100 mg / day in the form of rectal suppositories. The groups were matched for gender, age, and underlying disease.

After two months of follow-up, ulcer recurrence was recorded in only one (5.6%) patient taking nimesulide, and in a third (33.3%) of patients using suppositories with diclofenac (p

In a multicenter study PRINCIPLE, the results of which were recently published [44], it was demonstrated that in real practice, not only the safety indicators of nimesulide treatment, but also the incidence of such adverse reactions as dyspepsia, peripheral edema and increased blood pressure, are comparable to those of celecoxib. meloxicam, aceclofenac and naproxen.Dyspepsia with the use of nimesulide was recorded much less frequently than with the use of diclofenac.

Both in foreign [45–47] and in domestic literature [48, 49], the issue of hepatotoxicity of nimesulide is actively discussed. However, in a European epidemiological study, which included about 400 thousand patients taking NSAIDs, there were no significant differences in this indicator between nimesulide and other drugs in this group, such as diclofenac and ibuprofen [47].An assessment of the relative risk of developing acute liver failure showed that nimesulide is less dangerous than paracetamol and ibuprofen, and is comparable in terms of the degree of risk with diclofenac and ketoprofen [50]. The data of Russian studies and analysis of domestic literature do not confirm the high hepatotoxicity of nimesulide [51, 52].

Currently, hepatotoxicity is not recognized as a feature of nimesulide [3].

… for the cardiovascular system

An extensive population study conducted in Finland (33,309 episodes of acute myocardial infarction, control – 138,949 persons without myocardial infarction) showed that while taking nimesulide, the risk of cardiovascular accidents is not higher than when using meloxicam, nabumeton and etodolac, coxibs and non-selective NSAIDs [53].

According to our data, in patients with gout, including those suffering from arterial hypertension, when using nimesulide, there is no significant increase in blood pressure [54].

The results of a number of clinical studies indicate that in patients with OA and arterial hypertension who took nimesulide, the indicators of systemic hemodynamics and endothelial function are comparable to the baseline values. This substantiates the advisability of using this drug in the complex treatment of patients with OA suffering from essential arterial hypertension [55, 56].

Recently published follow-up of 511,989 patients 65 years of age or older who were diagnosed with cardiovascular disease between 2008 and 2011 indicate that the frequency of regular use of NSAIDs in this cohort varies from 20.8% to 47.8%, depending on from the region (mainly for the treatment of diseases of the musculoskeletal system) [57]. The most commonly used nimesulide (9.6%), less often diclofenac (7.5%), only 3.8% of patients receive coxibs.However, when assessing the average daily consumption of drugs, nimesulide and coxibs are in the lead. The data obtained are additional confirmation of the high safety of nimesulide, including in elderly patients with concomitant cardiovascular pathology.


When choosing a drug from the NSAID group, especially for elderly patients with comorbid conditions, it is necessary, firstly, to assess the analgesic and anti-inflammatory potential of the drug, and secondly, its safety, including cardiovascular safety.In this regard, nimesulide represents the golden mean of the NSAID class. An additional factor influencing the choice of the drug, undoubtedly, should be the presence of a large domestic and international experience of use, as well as progressive dosage forms (Nimesil®), providing ease of use and high bioavailability.

oil refinery products and vibration-free therapy

Summary. Guidance material of assignments to the analysis of impulses of optimal antiapalnic and analgesic drugs (from nonselective non-steroidal antiapalnic drugs (NSAP) to cyclooxygenase (COX) -2-specific).It has also been shown that the steps of the COX-2 selectivity of the refinery are far from being devoid of baking. There is an oil refinery, but there are a number of additional, non-COX-fallen defects, the significance of which in the therapy bagatokh is ill can overwhelm the loss of COG.

Summary. This material is devoted to the analysis of the search for optimal anti-inflammatory and analgesic drugs (from non-selective non-steroidal anti-inflammatory drugs (NSAIDs) to cyclooxygenase (COX) -2-specific).It has also been shown that not only the degree of COX-2 selectivity of NSAIDs determines their safety. There are NSAIDs that have a number of additional, non-COX-dependent effects, the significance of which in the treatment of many diseases can be surpassed only by inhibition of COX.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most successful groups of drugs that are most widely used, reflecting their effectiveness and clinical significance. Due to the versatility and prevalence of the inflammatory process, NSAIDs are today the most prescribed class of drugs, including in Ukraine (according to the third level of ATC classification based on the results of 9 months of 2017., according to the project “Rx test – Monitoring of drug prescriptions”). This group has anti-inflammatory, analgesic and antipyretic properties at the same time.

The use of NSAIDs plays a fundamental role in controlling inflammation and relieving pain. These drugs inhibit the synthesis of prostaglandins (PG) through inhibition of cyclooxygenase (COX) -1 and COX-2, enzymes responsible for the synthesis of PG.

The inflammatory process is activated by various antigenic stimuli: viruses, bacteria, parasites, endotoxins, autoantigens, etc.(fig. 1).

Fig. 1.

Activation of the inflammatory process by various antigenic stimuli

As a result of the interaction of the above agents with macrophages, an increase in the synthesis of proinflammatory cytokines (tumor necrosis factor (TNF), interleukin (IL) -1, IL-6, etc.) and platelet-activating factor (TAF) occurs, which in membrane phospholipids (osteoblasts of endothelial cells , chondrocytes, synoviocytes, renal mesangial cells, etc.) lead to the activation of phospholipase A 2 , which is accompanied by the release of lysosomal enzymes, TAF, metabolites of arachidonic acid (thromboxanes, leukotrienes, lysophosphatides, superoxide oxygen radicals), which determines the severity of the inflammatory process [one].

The picture of physiological and inflammatory processes is shown in Fig. 2.

Fig. 2.

Picture of physiological and inflammatory processes

Wayne’s hypotheses regarding the different roles of COX-1 and COX-2 in physiological and pathological processes led to the creation of new anti-inflammatory drugs and contributed to a complete reassessment of existing NSAIDs. In pharmacodynamics, NSAIDs differ in their ability to inhibit COX-1 and COX-2 to varying degrees.COX-1 is constitutive and actively participates in the physiological mechanisms of regulation of homeostasis (production of protective factors of the mucous membrane of the gastrointestinal tract (GIT) -prostacyclins, blood coagulation processes, regulation of renal circulation). COX-2 is inducible (inactive under normal conditions), showing its effects mainly when an inflammatory process occurs. Therefore, it is logical that the search for new, safer NSAIDs was in the direction of selectivity for COX-2.They showed both moderate (4 – meloxicam, 7 – celecoxib) and high (36 – rofecoxib) selectivity to COX-2 [2] and, according to a number of clinical studies, had a higher gastrointestinal safety.

This is relevant, since complications from the gastrointestinal tract are one of the most frequent associated with the use of NSAIDs. So, according to the Canadian Register of Side Effects Monitoring (2015), the average incidence of adverse reactions from the gastrointestinal tract against the background of the use of NSAIDs is 8.5% [3].

Recently, the use of coxibs has caused concern among physicians due to the fact that it is associated with fatal cardiovascular events. So, in 2004, rofecoxib was withdrawn due to the increased risk of fatal cardiovascular events, even when used in standard doses. According to the APPROVe study, the risk of developing such with rofecoxib was 92% higher than with placebo [4] (Fig. 3).

Fig. 3.

The risk of developing fatal cardiovascular events with the use of rofecoxib according to the APPROVe study

According to the already mentioned Canadian Register of Side Effects Monitoring, the incidence of embolism with the use of NSAIDs is underestimated.They account for 30% of all adverse reactions [3]. Thus, cardiovascular side effects are noted more than 3 times more often than gastrointestinal side effects.

Although the absolute risk of developing adverse reactions from the cardiovascular system with the use of NSAIDs is relatively low, their widespread use allows NSAIDs to have a significant impact on the incidence of cardiovascular pathology worldwide [5].

Cardiovascular diseases are the leading cause of death, and Ukraine is no exception.According to the World Health Organization at the end of 2015, 70% of deaths in our country are due to cardiovascular diseases, and 95% of these deaths are caused by heart attacks and strokes.

In its 2005 review, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) concluded that the use of selective COX-2 inhibitors as a whole class of drugs is associated with an increased risk of thrombotic cardiovascular events (such as heart attack and stroke).Therefore, EMEA experts do not recommend prescribing COX-2 inhibitors to patients with coronary artery disease who have had a stroke or who have been diagnosed with peripheral arterial disease.

Selective COX-2 inhibitors are not at all as safe in the gastrointestinal tract as expected. According to a large meta-analysis of 2013, which assessed the risk of developing adverse reactions from the cardiovascular system and the gastrointestinal tract when using diclofenac, ibuprofen and naproxen, coxibs, the latter showed unsatisfactory results in terms of the risk of developing adverse reactions from the gastrointestinal tract, – there, where, in theory, they should have demonstrated an obvious advantage in comparison with non-selective NSAIDs [6].According to the results of this meta-analysis, coxibs did not differ from diclofenac in the frequency of gastrointestinal lesions. Compared to placebo, both drugs were more likely to cause gastrointestinal complications — relative risk (RR) 1.81 (95% confidence interval (CI) 1.17–2.81).

In the USA, the situation with etoricoxib ended with the refusal to register the drug by the FDA (Food and Drug Administration) with the statement that it is not more effective and safer than diclofenac [7].

Regarding the cardiovascular complications of the use of selective NSAIDs, there are several theories to explain them.The first is Fitzgerald’s theory. Normally, the synthesis of thromboxane (a prothrombotic agent) and prostacyclin (an antithrombotic agent) is in physiological equilibrium. Thromboxane is synthesized by platelets, which contain only COX-1. The synthesis of prostacyclin occurs in the endothelium. When COX-2-selective NSAIDs are used, prostacyclin synthesis decreases, but thromboxane does not (since platelet COX-1 remains intact in proportion to the degree of selectivity of the drug). As a result, the dynamic balance is disturbed towards the prevalence of the blood coagulation system [8, 9].The next theory, explaining the risks of embolic complications with the use of NSAIDs, is devoted to the instability of atherosclerotic plaques. Some NSAIDs, in particular etoricoxib and rofecoxib, are capable of causing lipid oxidation [10], which can lead to destabilization of atherosclerotic plaque. This is manifested by saponification of cholesterol filling it, an increase in size, up to rupture of the lid, followed by thrombosis of the plaque itself and secondary embolism. It has also been shown that this effect (decrease in prostacyclin synthesis) can be dose-dependent.Thus, in the APC study, when using celecoxib 200 mg twice a day, the incidence of cardiovascular events was lower after 12 months of therapy compared with celecoxib 400 mg twice a day. Moreover, against the background of the use of acetylsalicylic acid, the risks were not only not lower, but even increased from 2.4 to 3.8 times [11].

Available data indicate that the previously generally accepted distinction between COX-2 as pathological and COX-1 as physiological is rather arbitrary.

So, COX-2, which for many years was traditionally considered responsible exclusively for the development of the pathological process, also performs a number of physiological functions.In particular, COX-2 is involved in the regulation of vascular tone (vasodilation), healing of defects in the mucous membrane of the stomach and intestines, regulation of the ovulation process, pancreatic function, remodeling and regeneration of bone tissue [12-14]. Moreover, not only COX-2, but also COX-1 is a source of inflammatory mediators in rheumatoid arthritis, osteoarthritis, bursitis [13, 14].

It is noteworthy that COX-1 can independently contribute to the development of an inflammatory process of no less intensity than both COXs simultaneously.Thus, in experiments on animals it was shown that even with the removal of the gene encoding COX-2, the severity of the inflammatory process did not decrease [15].

It is safe to say that the functioning of all types of COX is interconnected and is in dynamic equilibrium. As well as the action of NSAIDs should be considered comprehensively, taking into account COX-1, COX-2, as well as non-COX-dependent effects. In this context, attention is drawn to NSAIDs such as diclofenac and nimesulide, which in a balanced manner block both COX-1 and COX-2.And nimesulide has a number of additional effects that are important in treatment.


Diclofenac is the gold standard in assessing the effectiveness of NSAIDs. The mechanism of action, efficacy and safety profile of diclofenac are well understood. The high efficiency of this drug is beyond doubt, but today the attention of researchers and the interest of practicing doctors is focused on the question: “Is diclofenac more effective and safer than selective NSAIDs?”

Diclofenac most effectively inhibits the synthesis of pro-inflammatory PGE 2 [16]. Thus, according to the results of a randomized placebo-controlled clinical trial, the use of diclofenac can reduce the level of PGE 2 by 93%, which is significantly (almost 20%) more effective than similar indicators of both COX-2-selective rofecoxib, meloxicam, and non-selective ibuprofen and naproxen [17].

In addition, diclofenac is clinically more effective than meloxicam.According to the results of the MELISSA study, which involved more than 9 thousand people with osteoarthritis, patients using meloxicam were 38% more likely to refuse treatment due to its ineffectiveness (80 of 4635; p <0.01) compared to the cohort. received diclofenac (48 of 4688) [18].

Another large study showed that diclofenac has one of the lowest risks of developing upper gastrointestinal bleeding.

Thus, a meta-analysis of data from 280 randomized clinical trials, where various NSAIDs were compared with placebo (n = 124 513), and 474 randomized clinical trials, where NSAIDs were compared with other drugs in this group (n = 229 296) [6], showed that when using coxibs compared with placebo, the relative risk (RR) of adverse reactions from the gastrointestinal tract for these drugs was 1.81 (95% CI 1.17–2.81; p = 0.0070), which is comparable to that of diclofenac – 1 , 89 (95% CI 1.16-3.09; p = 0.0106).For comparison, the RR of gastrointestinal complications with ibuprofen was 3.97 (95% CI 2.22–7.10; p <0.0001), and for naproxen it was 4.22 (95% CI 2.71– 6.56; p <0.0001).

Ways of preventing complications

Unfortunately, even having chosen the safest NSAID from the existing ones, we are not immune from the development of class-specific adverse reactions, therefore, it is important to introduce effective methods of prevention.

The use of acetylsalicylic acid is today considered as one of the methods to reduce the risk of cardiovascular thrombotic events when prescribing NSAIDs.

However, according to research results, the use of acetylsalicylic acid with COX-2-selective NSAIDs does not give the expected protective effect, even statistically significantly increasing the risk of cardiovascular events from 2.4 to 3.8 [11].

The concomitant use of diclofenac and acetylsalicylic acid in a cardioprophylactic dose was accompanied by the lowest RR of bleeding from the upper digestive system among patients taking acetylsalicylic acid in comparison with five other NSAIDs used – 5.7 [19].It is also worth noting that the combination of NSAIDs and proton pump inhibitors has a beneficial effect on the gastrointestinal safety profile. In particular, the combination of diclofenac and proton pump inhibitors is accompanied by the lowest RR from the gastrointestinal tract – 0.3 [19].


Considering NSAIDs in view of their so different efficacy and safety, it is very important to remember about non-COX-dependent mechanisms of action.

So, nimesulide, in addition to the balanced blocking of COX-1 and COX-2, also has the following additional effects:

  • blocks superoxide oxygen radicals;
  • blocks the activity of iNO-synthetase and the formation of nitric oxide (NO), peroxynitrite (ONOO ), which are key mediators of the inflammatory process and cartilage destruction;
  • cancels chondrocyte apoptosis;
  • blocks collagenase and stromelysin, which leads to a decrease in the degradation of type II collagen and proteoglycan;
  • activates glucocorticoid receptors, increasing their sensitivity, including to endogenous cortisol;
  • inhibits phosphodiesterase, thereby reducing the production of histamine and the severity of its mediator effects;
  • activates the synthesis of tissue plasminogen activator;
  • blocks the synthesis of platelet-activating factor;
  • plays an important role in the prevention of thromboembolic complications.

Nimesulide was synthesized by Helsin as a trap for oxygen superoxide radicals. Free radicals are important pathogenetic factors in chronic inflammatory processes, so their elimination can significantly enhance the anti-inflammatory effect.

With regard to nimesulide, the inhibition of hydroxyl radicals, as well as superoxide radicals (superoxide anions O 2 and the formation of hypochlorous acid, which activates polymorphonuclear neutrophils), has been proven.A decrease in superoxide levels and phagocytosis has been shown in studies with healthy volunteers after taking a standard dose of nimesulide.

Nimesulide blocks inducible NO-synthetase and, accordingly, the formation of nitric oxide (NO) and peroxynitrite (ONOO), which are responsible for the destruction of cartilage and the development of the inflammatory process in osteoarthritis. Also, nimesulide cancels chondrocyte apoptosis.

When treating patients with diseases of the musculoskeletal system, it is important to remember that nimesulide has an anticollagenase effect.A decrease in the activity of collagenase, as well as stromelysin, was noted in the blood plasma of patients with degenerative diseases of the joints when using nimesulide. This is an important clinical effect that slows down the destruction of articular cartilage [20].

In addition, nimesulide inhibits phosphodiesterase with a corresponding increase in the intracellular level of cyclic adenosine monophosphoric acid, which, in turn, inhibits the synthesis and release of histamine.

Nimesulide activates glucocorticoid receptors, thereby enhancing the anti-inflammatory effects of both endogenous cortisol and glucocorticoid drugs.

It is important that nimesulide is a dual inhibitor of not only COX, but also 5-lipoxygenase (5-LOG). It is known that when the COX is blocked, 5-LOG is activated. Moreover, as a result of the action of 5-LOG, only pro-inflammatory factors are formed, namely leukotrienes, which cause inflammation, ulceration, bronchospasm and allergic reactions.

The metabolism of arachidonic acid is shown in Fig. 4.

Fig. 4.

Metabolism of arachidonic acid

It is with the activation of the metabolism of arachidonic acid along the 5-LOG pathway that the side effects and organotoxicity of NSAIDs are currently associated.Leukotrienes LTC4, LTD4, LTE4 and chemotactic LTB4 accumulate in various organs and cause various side effects of NSAIDs [21]. The more COX is blocked, the more active is 5-LOG and, accordingly, the production of leukotrienes [22].

The use of dual inhibitors of COX and 5-LOG is currently being considered as a new strategy to improve the safety of NSAID therapy . The only known NSAID that blocks both COX and 5-LOG is nimesulide [23]. With this in mind, nimesulide is used as a basic drug for the search for new promising molecules.The biaryl ester of nimesulide, , which is responsible for blocking 5-LOG, is taken as the basis for this search .

The favorable gastrointestinal safety profile of nimesulide was noted as part of a review conducted by EMEA in 2012. Of particular interest in this context are the results of a retrospective epidemiological study, during which the risk of developing complications affecting the upper digestive system in patients using various NSAIDs was assessed.The study included data on 588,827 patients. Of these, more than 250 thousand people used nimesulide, about 225 thousand – diclofenac, more than 150 thousand – ketoprofen, and also in decreasing order – piroxicam, ibuprofen, ketorolac, meloxicam, naproxen and other NSAIDs. This also largely reflects the level of prescription of various NSAIDs in European countries.

According to the results obtained, the RR of gastrointestinal complications, adjusted for age, gender and risk factors, for celecoxib was 1.38, for nimesulide – 1.5, which is 2 times lower compared with ibuprofen and 3 times lower than with meloxicam …Thus, nimesulide is a reasonable choice for patients with moderate to high gastrointestinal risk of complications.

Summing up, it should be noted that nimesulide is the drug of choice for the rapid elimination of pain and inflammation [24]. The drug is indicated for patients with medium and high gastrointestinal and cardiovascular risks.

Also note that, in addition to the favorable profile of gastrointestinal safety, nimesulide is characterized by a low incidence of side effects from the cardiovascular system.According to pharmacovigilance data, the risk of cardiovascular complications with the use of nimesulide is lower than that for selective NSAIDs – meloxicam, celecoxib, as well as non-selective ketoprofen, indomethacin and piroxicam. The incidence of heart attack and stroke with the use of nimesulide was very low (0.01) – significantly lower than that of celecoxib (0.35), indomethacin (0.04), meloxicam, ketoprofen and piroxicam. Based on these data, EMEA experts positively assessed the indicators of cardiovascular safety of nimesulide.

This EMEA 2012 review is also notable for its extensive analysis of the hepatosafety of various NSAIDs. It should be noted that hepatotoxicity is a class-specific adverse reaction for all NSAIDs. In this context, nimesulide and diclofenac compare favorably, as evidenced by the results of a large retrospective study SALT (Study of Acute Liver Transplant), which involved almost 9 thousand patients from 7 European countries (table). According to the results obtained, the relative risk of developing acute liver failure per 1 million years of treatment with the use of nimesulide was 5.64, diclofenac – 4.46.For comparison, the same indicator for paracetamol is 9.80 (95% CI 7.66-12.37), for indomethacin – 13.10, for etodolac – 22.46 and for ketorolac – 58.31.

Table. Hepatotoxicity of NSAIDs according to the results of a large retrospective study SALT (Study of Acute Liver Transplant)

Medicine Class formulation etodolac Ibuprofen
Aspirin 90 268

antiplatelet yes Yes
Warfarin Anticoagulant Yes yes
Angiotensin-converting enzyme (ACE) inhibitor yes yes

Diuretic yes yes
Lithium Mood stabilizer yes yes
Antimetabolite yes yes
Cyclosporine Immunosuppressant yes yes
NSAID Number of daily doses Relative risk per million person-years (95% CI) 90 260
Celecoxib 357 873 149 3.48 [0.10; 19.37]
Diclofenac 1 514 709 881 4.46 [1.45; 10.41]
Ketoprofen 899 161 612 4.67 [0.96; 13.64]
Naproxen 647 295 878 5.35 [0.64; 19.35]
Nimesulide 1 356 255 833 5.64 [2.43; 11.11]
Ibuprofen 1 219 162 429 5.77 [2.77; 10.61]
Indomethacin 80 584 130 13.10 [0.39; 72.98]
Niflumic acid 62 794 037 14.44 [0.43; 80.41]
Etodolac 70 791 098 22.46 [0.67; 125.1]
Ketorolac 38 652 374 58.31 [7.00; 210.8]
Total 8 461 912 281 4.37 [3.02; 6.10]

Ways to further improve the effectiveness and safety of NSAID therapy

Despite the high efficacy of the selected systemic NSAIDs, their anti-inflammatory and analgesic effect may be insufficient, and increasing the dose in some cases is fraught with an increase in the risk of adverse reactions.How to ensure the required level of analgesic and anti-inflammatory action without impairing the safety profile of therapy? The answer to this question can be the use of topical NSAIDs, which makes it possible to increase the effectiveness of therapy without compromising safety indicators. However, in this light, another question becomes relevant: “Is the therapy with local NSAIDs really effective enough?”, Or in this case the placebo effect is more important?

The full scale of the influence of the placebo effect on the well-being of patients is perfectly illustrated by the results of a study of the effectiveness of paracetamol in acute back pain [25].The study involved 1652 patients who were randomized into three groups: patients of the 1st group regularly used paracetamol at 4000 mg / day, the 2nd – used paracetamol on demand, depending on the intensity of pain – up to 4000 mg / day, 3 th – received a placebo. The results were quite surprising – both regular use of paracetamol and on demand did not affect the recovery period for back pain compared with placebo. Thus, paracetamol was found to be as effective as placebo.

Therefore, in order to analyze the effectiveness of a particular drug, it is important to take into account the results of studies with sufficiently large patient samples. Attention is drawn to a review conducted by scientists at the University of Oxford [26], during which the results of 86 clinical studies (more than 10 thousand patients) of the use of topical NSAIDs were analyzed. According to this review, topical NSAIDs are effective in treating acute and chronic pain. Also interesting in light of the study of the efficacy and safety profile of topical NSAIDs in pain are the results of the Cochrane meta-analysis, which combined the data obtained in 7688 patients in 32 studies [27].Thus, a direct comparison did not show differences in efficacy between systemic and local NSAIDs, while the incidence of gastrointestinal adverse reactions with the use of local NSAIDs was comparable to that in patients receiving placebo. Thus, in the absence of systemic adverse reactions, the analgesic efficacy of local NSAIDs is comparable to the efficacy of systemic NSAIDs. One of the most effective topical NSAIDs with an overall favorable safety profile is ketoprofen, as evidenced by the results of a number of studies.Thus, in the course of a large clinical study, it was shown that ketoprofen is the most effective local NSAID in relieving pain [28]. According to the data obtained, ketoprofen is significantly more effective than other local NSAIDs in terms of the integral indicator of the effectiveness of NNT therapy (numbers needed to treat), namely: 58% better than ibuprofen; 80% better than piroxicam and 92% better than diclofenac. Thus, with topical administration, ketoprofen is almost 2 times more effective than topical diclofenac.

Such advantages in the analgesic and anti-inflammatory efficacy of ketoprofen for topical application are due not only to the activity of the molecule, but also to its ability to penetrate into the tissues of the joints and periarticular structures.

The advantage of ketoprofen in comparison with other topical NSAIDs is also confirmed by the results of a study by Japanese authors [29], which examined topical NSAIDs in modern dosage forms of gels and patches. Thus, ketoprofen preparations for topical use have been identified as the most promising.According to the authors of the study, ketoprofen has a higher anti-inflammatory and analgesic activity associated with both the pharmacological characteristics of the molecule and its better penetration through the skin.

A natural question arises as to why ketoprofen is characterized by a favorable safety profile, because if the drug penetrates well through the skin, then the concentration in the blood plasma should also be high. However, this is not the case, since ketoprofen selectively accumulates in the area of ​​application of therapeutic properties – in the tissues of the joints.Thus, it has been shown that the concentration of ketoprofen in blood plasma is about 100 times lower than in the tissues of the joint [30]. It is noteworthy that ketoprofen does not affect the synthesis of the articular cartilage matrix – proteoglycans, even in osteoarthritically altered articular cartilage [31]. And in young cartilage at a concentration of 10 M ketoprofen even increases the synthesis of cartilage matrix.

Thus, ketoprofen is a reasonable choice in combination with systemic diclofenac or nimesulide. According to evidence-based medicine, the drug demonstrates a high efficacy and a favorable safety profile, while not exerting a negative effect on articular cartilage, which is of key importance for long-term use.Ketoprofen reaches the focus of pain and inflammation in the required concentration, providing analgesic and anti-inflammatory effects. At the same time, the concentration of the drug in the blood plasma remains very low and does not cause the development of systemic adverse reactions even in the case of prolonged therapy.


When choosing NSAIDs to relieve pain and inflammation, it is necessary to take into account the effectiveness and safety of the drug, as well as the risk of developing certain adverse reactions in a particular patient:

  • For low cardiovascular and gastrointestinal risks, any NSAID may be the drug of choice, but primarily diclofenac, which remains the gold standard in anti-inflammatory therapy.
  • The drug of choice in the treatment of pathology of the musculoskeletal system, in particular OA, is nimesulide.
  • In the presence of cardiovascular pathology, the drug of choice is nimesulide or diclofenac in combination with acetylsalicylic acid.
  • To enhance the clinical effects of systemic NSAIDs, it is advisable to add local NSAIDs, primarily ketoprofen, which demonstrates high efficacy and low risk of systemic adverse reactions, which is comparable to placebo .


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  • 4. Bresalier R.S., Sandler R.S., Quan H. et al. (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N. Engl. J. Med., 352 (11): 1092-1102.
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  • 6. Bhala N., Emberson J., Merhi A. et al. (2013) Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: metaanalyses of individual participant data from randomized trials. Coxib and traditional NSAID Trialists (CNT) Collaboration. Lancet 382 (9894): 769-779.
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  • 12. Simon L.S. (2000) Are the biologic and clinical erfects of the COX-2-specific inhibitors an advance compared with the effects of traditional NSAIDs? Curr. Opin. Rheumatol. 12: 163-170.
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  • 22. Burnett B.P., Levy R.M. (2012) 5-Lipoxygenase Metabolic Contributions to NSAID-Induced Organ Toxicity. Advances in Therapy, 29 (2): 79–98.
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90,000 How to relieve cat pain? What medications are dangerous for cats?

Relieving a cat’s pain is not easy.Because pain relievers commonly prescribed to humans and dogs can be toxic to cats, pet owners ask themselves, “What pain relievers will be most safe and effective for cats?”

First, pet owners need to be aware of the dangers associated with a range of pain relievers, such as nonsteroidal anti-inflammatory drugs (NSAIDs), that can be found in almost every home. The most common NSAIDs are aspirin and ibuprofen for humans and carprofen, etodolac, and deracoxib for cats.Cats are extremely sensitive to the side effects of NSAIDs, so this class of drugs should be used with extreme caution (if at all) and always under the close supervision of a veterinarian.

Why are NSAIDs harmful to cats?

NSAIDs work by inhibiting the enzyme cyclooxygenase, which is responsible for the production of prostaglandins. Prostaglandins promote inflammation, fever, and pain, but they also have many other functions in the body, including maintaining adequate blood flow in the kidneys, forming a layer of mucus that protects the lining of the gastrointestinal tract from stomach acid, and forming normal blood clots.

Cats are about 2-5 times more sensitive to NSAIDs than dogs. Because of this:

  • Doses of these drugs given to cats are significantly lower than those commonly used.
  • These medications are only given to cats for a short period of time.
  • Medication intervals are much longer in cats than in humans or dogs.
  • 90,017 NSAIDs are generally only used in cats when safer forms of pain relief are not sufficient.

If these guidelines are not followed, or even if they are followed, the cat may develop vomiting, diarrhea, loss of appetite, impaired liver and kidney function, bleeding disorders, and may die regardless of treatment.

For the full slideshow on Are pain relievers safe for cats? visit the petMD website!

90,000 Oral composition containing s (+) – ibuprofen, and a method for its preparation.

1.An organoleptically acceptable oral pharmaceutical composition comprising S (+) – 2- (p-isobutylphenyl) propionic acid, substantially free of R (-) – 2- (n-isobutylphenyl) propionic acid, and an acid component.

2. The pharmaceutical composition according to claim 1, characterized in that the acid component contains one or more acids selected from: citric acid, tartaric acid, malic acid, fumaric acid, lactic acid, adipic acid, ascorbic acid, aspartic acid, d-erythroascorbic acid, glutamic acid, succinic acid.

3. A pharmaceutical composition according to claim 1, further comprising an organoleptically acceptable pharmaceutical carrier.

4. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in powder or granular form.

5. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in the form of a liquid.

6. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in the form of chewable tablets.

7. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in the form of an effervescent preparation.

8. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in the form of lozenges.

9. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in a rapidly disintegrating solid form.

10. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in the form of a chewable preparation used for veterinary medicine.

11. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in the form of a chewing gum.

12. A method for preparing an organoleptically acceptable oral pharmaceutical composition by mixing an active component and a target additive, characterized in that the active component is S (+) – 2- (n-isobutylphenyl) -propionic acid, practically free of R (- ) -2- (p-isobutylphenyl) -propionic acid, as a target additive – an acid component and convert it into a form suitable for oral administration.

1 This invention relates to new compositions of ibuprofen. In particular, this invention relates to organoleptically acceptable solid oral compositions of S (+) ibuprofen. For the purposes of this description, organoleptically acceptable compounds, substances and compositions are those that can contact the taste buds of the mouth of the recipients and which are usually acceptable to the recipient’s sensations, in particular to the taste. In particular, organoleptically acceptable compositions of this invention are those solid oral compositions in which the S (+) ibuprofen component should not have the unpleasant bitter taste commonly associated with racemic ibuprofen mixtures.As used herein, the term pharmaceutical composition includes both therapeutic and prophylactic compositions and refers to compositions for use in the veterinary field as well as for use in the treatment of humans. This invention relates to organoleptically acceptable compositions of ibuprofen. Racemic mixtures of ibuprofen, widely used as an analgesic and antipyretic agent, are believed to be generally bitter and not palatable enough for most uses in which the recipient tastes the ibuprofen mixture.Some flavors such as chocolate, banana, orange, lemon, licorice flavors, root vegetable flavors with nutmeg, etc. Odorless and raspberry flavoring have been suggested for bitter-tasting drugs, but they are usually not reliable in masking unpleasant tastes. Bitter taste is usually difficult to successfully mask if it does not mimic the expected natural flavor of the flavoring agent. For this reason, bitter tasting pharmaceuticals such as ibuprofen in particular have not attempted to be applied to many oral dosage forms such as chewable tablets and oral liquids.Rapidly dissolving dosage forms are described in US Pat. Nos. 4,305,502 and 4,371,516 (both issued to Gregory et al.), They disintegrate in water within seconds and therefore disintegrate rapidly in the saliva of the mouth. Such dosage forms are usually limited for use with drugs that have a neutral taste or taste that is only mildly unpleasant and which can be masked by flavoring agents. US Pat. No. 4,835,186 (Reuter et al.), 4,835,187 (Reuter et al.) And 4,835,188 (Ho et al.) discloses spray-dried ibuprofen compositions in which the ibuprofen is coated and formed into small particles that can pass through the mouth without leaving an unpleasant taste. Ibuprofen is marketed under the name Advil by Wyeth-Ayerst Laboratories, a Division of American Home Products Corporation Wyeth-Ayerst Laboratories also sells Children’s Advil Suspension, which is a fruit-flavored sucrose-sweetened liquid suspension for oral use …Ibuprofen is -2- (pisobutylphenyl) -propionic acid, also known as -methyl-4- (2-methylpropyl) benzeneacetic acid; p-isobutylhydratropic acid or 2- (4-isobutylphenyl) propionic acid having the structure shown below: Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) known to have analgesic and antipyretic activities. It is used in the treatment of pain and inflammation associated with a variety of conditions, including runny nose, toothaches, headaches, back pain, menstrual cramps (Dymennorhea), muscle aches and pains associated with premenstrual syndrome (Premenstrual Syndrom), rheumatoid arthritis and osteoarthritis. and also as an antipyretic agent.Like other NSAIDs, ibuprofen has become widely used in prescription and proprietary formulations for the treatment of pain associated with inflammation, both minor and chronic. One of its drawbacks, however, is that it has an unpleasant bitter taste, which limits its applicability in many oral dosage forms. As mentioned above, methods of mitigating this limitation include attempting to mask the bitter taste by using flavors and / or sweetening media, or by coating (coating) the ibuprofen with substances that prevent it from contacting the taste buds (tubercles) during oral administration.By reducing the bitterness, these solutions do not make the use of oral ibuprofen formulations organoleptically acceptable to all ibuprofen users. In addition, these steps increase the preparation time and cost of preparing many oral ibuprofen compositions. It has been found that the S (+) stereoisomer of ibuprofen, which is also referred to herein 3 as (+) – 2- (p-isobutylphenyl) propionic acid, the ibuprofen eutomer or the eutomer (active enantiomer) of ibuprofen, does not have the unpleasant bitter taste that, is known to possess racemic ibuprofen.It is therefore now understood, and within the scope of the invention, that the use of a single S (+) stereisomer of ibuprofen, referred to herein as the eutomer of ibuprofen, substantially free of its R (-) form, allows a wide variety of ibuprofen compositions to be provided, preferably in oral dosage forms. which are pharmaceutically and organoleptically acceptable for oral administration. Not only does this knowledge enable the person skilled in the art to create organoleptically acceptable ibuprofen compositions, but it is done in such a way that no additional coating or flavor masking steps are required for the ibuprofen component.In many cases, the coating technique for pharmaceutical substances is imperfect, leaving a portion of the compound in question available to the taste buds. Likewise, in chewable formulations, the grinding action of the teeth can pierce the coated particles in the formulations, releasing some unpleasant tasting substance. By virtue of the ingredient in an acceptable flavor base, the compositions of this invention eliminate the chance of unexpected release of unpleasant substances.This improvement not only improves the marketability and reduces the cost of producing such compositions, but can also induce the recipient to follow the prescribed dosage regimen. In view of this knowledge, the present invention includes organoleptically acceptable oral compositions comprising, in whole or in part, the S (+) stereoisomer of ibuprofen. These oral compositions include those orally administered compositions in which the active ingredients or drugs of the composition are typically carried by the taste and odor receptors of the recipient.Such compositions include, but are not limited to, organoleptically acceptable liquid ibuprofen solutions, suspensions, emulsions, syrups, colloids, sachets, tablets, including chewable, buccal or sublingual (sublingual) tablets, powders or granular formulations, effervescent compositions, wafers, troches, or lozenges, pastes, foams, toothpastes and gels. Due to the use of NSAIDs in veterinary medicine, compositions that are organoleptically acceptable to animals, in particular companion animals such as cats and dogs, may fall within the scope of this invention.In its simplest form, the present invention includes the organoleptically acceptable compound 000046 4 positions of ibuprofen, which include the ibuprofen eutomer itself. This compound can be taken orally by itself to relieve the symptoms described above. The ibuprofen eutomer can be taken with water, fruit juices, soft drinks, milk, or other liquids or drinks that are used to facilitate oral administration of the drug. Other simplified forms of administration may include the introduction of the eutomer into food, which can then be consumed in the usual way.These food-related or drinking-related routes of administration may be preferred by any recipient, especially children. Preferably, the compositions of this invention containing the ibuprofen eutomer also contain an acidic component in an amount sufficient to maintain the pH of the composition below 7, preferably from about 2 to about 6, eg below 5.0. Additional examples include cases where the pH is from about 3.0 to about 3.5; about 2.5 to about 3.5; and about 5.0 to about 5.2.Pharmaceutically acceptable acids for use in these compositions include, but are not limited to, commonly used edible acids such as citric acid, tartaric acid, malic acid, fumaric acid, lactic acid, adipic acid, ascorbic acid, aspartic acid, d-erythroascorbic acid, glutamic acid and succinic acid. The compositions containing the ibuprofen eutomer of the present invention can be used in the manner and dosage suggested for ibuprofen tablets and capsules currently on the market.It should be understood by one of ordinary skill in the art that ibuprofen, like other NSAIDs, can differ in response from individual to individual. Therefore, the recommended initial therapeutic dose should be one that is likely to be effective for the majority of recipients, the dosage being adjusted after beneficial and harmful effects on the recipient have been identified. The ibuprofen eutomer of this invention should be administered at the lowest dose that can provide the desired physiological result.It may contain a single dose of 5 to 10 mg, as in infants (up to 12 months), up to 1 g or more for older adults, preferably from about 50 mg to about 800 mg, most preferably from about 100 to about 400 mg of the eutomer. ibuprofen for minor pain relief. Suggested dosages for pain relief associated with chronic problems (diseases) can range from about 600 to 3200 mg per day with regimens of 300 mg four times 5 a day (qid), or 400 mg, 600 mg, or 800 mg three times ( t.i.d.) or twice a day (b.i.d.). The person skilled in the art understands that a medical professional of average skill should directly prescribe this compound, using the composition of the present invention, in accordance with the need and medical situation for each patient individually, and that the maximum daily dose can be increased by a medical professional in excess of 3200 mg per day. if necessary and if tolerated by the patient. It will be appreciated that, despite the indicated amount of the ibuprofen eutomer listed in the following examples, compositions with any dose of the ibuprofen enantiomer described above may be formulated.Although the ibuprofen eutomer of the present invention does not impart undesirable off-flavor to the compositions in which it is used, the compositions described herein may include sweetening or flavoring agents to increase overall odor, taste and desirability of the composition. Such sweeteners can include all pharmaceutically acceptable sweeteners, including, but not limited to, molasses, glycine, corn syrup, sugars such as sucrose, glucose, fructose and confectionery sugar, sorbitol, saccharin, sucrose, sodium saccharin, calcium saccharin, aspartame (preferably under the trade name NutrasweetR, Nutrasweet Company, Deerfield, Illinois), stevioside, neohesperidyl dihydrochalcone, glycyrse, perillaldehyde, xylitol, dextrose, mannitol, and lactose.The compositions provided herein may also include an organoleptically acceptable pharmaceutically acceptable carrier, for example, pharmaceutically acceptable excipients, fillers, diluents, lubricants, disintegrants, suspending or stabilizing agents, and binders, including, but not limited to, magnesium stearate, sodium lauryl sulfate, microcrystalline cellulose, polyvinylpyrrolidone, gelatin, alginic acid, arabic gum, sodium citrate, complex silicates, calcium carbonate, glycine, dextrin, sucrose, sorbitol, dicalcium phosphate, calcium sulfate, lactose, kaolin, mannitol, sodium chloride, talc ( e.g. corn starch, potato starch or starch grits) and powdered sugar.In simple form, the compositions of this invention may include powdered or granular dosage compositions containing the ibuprofen eutomer. For example, the eutomer can be taken orally by itself, in powder or granular form. The recipient can place such a powdery or granular lump 000046 6 in the mouth and wash it off with a liquid or solid food. Due to the relatively small volume of S (+) ibuprofen present in the dosages described herein, it would be preferable to include one or more organoleptically acceptable powdered pharmaceutical ingredients in a powder or granular dosage form.They can be compounds with additional pharmaceutical activities, or fillers, sweeteners, etc. described herein. It should be borne in mind that in this way can be entered any dose of the eutomer of ibuprofen, and the volume of additional components is limited only by the amount that is acceptable to the recipient. When this S (+) stereoisomer of ibuprofen is used, organoleptically acceptable oral liquid dosage forms of ibuprofen, most often with an acidic component, can be formulated and used.Such liquid compositions can be obtained on a water basis. These oral fluids can be comprised of any of the oral liquid compositions using the ibuprofen eutomer, including simply mixing the required dose of the ibuprofen eutomer into commonly consumed amounts of effervescent drinks and drinks, including, for example, but not limited to, sparkling or still water, fruit juices, coffee, tea, soft drinks and milk. Such liquid compositions further preferably contain an acidic component such as described herein in an amount sufficient to maintain the pH of the liquid composition below 7, preferably from about 2 to about 6, for example below 5.0.Additional examples include cases where the pH is from about 3.0 to about 3.5; about 2.5 to about 3.5; and about 5.0 to about 5.2. Due to the relatively small volume occupied by a single dose of the ibuprofen eutomer and the accompanying acidic component, it is preferable to include these substances in a small, easily edible amount of one or more pharmaceutically and organoleptically acceptable substances, such as those described herein. In one preferred embodiment of the oral fluid of this invention, the oral fluid comprises from about 0.8 to about 4% of the enantiomer of ibuprofen based on the total volume weight of the composition, from about 0.1 to about 2% suspension stabilizing agents based on the total volume weight of the composition. , from about 20 to about 70% by weight of one or more flavors based on the total weight of the composition, from about 30 to about 70% water based on the total volumetric weight of the composition, wherein the composition containing 7 contains a pharmaceutically and organoleptically acceptable food acid such as citric acid or phosphoric acid, in an amount from 0.1 to about 2% by volume.Preferably, the suspending agents include xanthanic acid, microcrystalline cellulose, sodium carboxymethyl cellulose and polysorbate 80. Examples 1 and 2 describe how two such compositions can be prepared. Example 1 (Table 1) Ingredient Percent Grams per w / v 15 L Xanthan Gum 0.15 22.5 Microcrystalline 0.75 112.5 Cellulose Sodium Benzoate, NF (Nf) Citric Acid, Monohydrate, USP Sucrose, NF Corn Syrup Eutomer ibuprofen Sodium carboxymethyl cellulose, USP Polysorbate 80, NF Red FDC 40 Color, Disodium edetate, USP Artificial lime-scented oil Phosphoric acid, d.j. A first portion of this liquid oral composition can be prepared by first loading the sorbitol solution and portions of the glycerin into a jacketed stirrer reactor. Then the component – sodium carboxymethyl cellulose is poured into the solution and stirred for 10 minutes until the mixture is completely moistened. The mixture should then be heated to about 70 ° C and stirred until the resin is completely hydrated, after which the mixture is cooled to 45 ° C and the polysorbate 80 component is added.Stirring is continued while cooling the mixture to 30 ° C. The ibuprofen enantiomer is slowly poured into the mixture and stirring is continued for 15 minutes. Then, the obtained second part, by placing the required amount of water in a container equipped with a propeller-type stirrer, and slowly adding xanthan gum, is hydrated by stirring at high speed for 25 minutes. This follows after charging into a separate mixing vessel equipped with a propeller-type stirrer, water in an amount equivalent to about 30 to 40% by volume of 8 of the total charge (4500 to 6000 ml).Then, microcrystalline cellulose is poured onto water and mixed at medium speed for 30 minutes until the cellulose is completely dispersed. The required amount of xanthan gum solution from the aforementioned first part is added to the cellulose suspension with stirring for 15 minutes or until a uniform suspension is obtained. Then add slowly sucrose with stirring for 15 minutes or until the sucrose particles are no longer visible. Colorants such as the aforementioned RedEDC 40 Color can be added and mixed until the colorants are completely dispersed therein.This is followed by the addition of the slurry from the aforementioned first part and slow mixing for 15 minutes. Sodium benzoate, edetate disodium, citric acid and flavoring agents are then added and the mixture is stirred for 5 minutes after each addition. Phosphoric acid is added with stirring until the composition reaches a pH of about 3.0 to about 3.5. The final composition should be balanced with water and stirred until the composition is homogeneous.Example 2. The composition of a liquid composition for oral administration using S (+) ibuprofen is presented in table. 2. Ingredient Xanthan gum Microcrystalline cellulose Sodium benzoate, NF Citric acid aqueous, USP Sucrose, NF Glycerin, USP Sorbitol solution, USP Ibuprofen eutomer Sodium carboxymethylcellulose, USP Polysorbate 80, NF Red dye) (RedFDCP Sodium dye) (RedFDCPate Artificial lemon-scented oil Phosphoric acid, (qs) 9 This preparation can be obtained by measuring a solution of sorbitol and glycerin in a jacketed stirred reactor.Sodium carboxymethyl cellulose is poured into this solution, stirring for 10 minutes or until its particles are completely moistened. The resulting mixture is then heated to about 70 ° C and stirred until the resin is completely hydrated, after which the mixture is cooled to 45 ° C and polysorbate 80 is added. Stirring is then continued while the mixture is cooled to 30 ° C. Then slowly the ibuprofen eutomer is added and stirring is continued for 15 minutes to give an ibuprofen suspension as indicated below.The second solution, which may be referred to as a xanthan gum solution, is prepared as a 1% by weight solution of xanthan gum in water. The xanthan gum should be added slowly to the water and mixed at high speed for approximately 25 minutes. A separate mixing vessel equipped with a stirrer is charged with a volume of water equivalent to 30 to 40% of the total charge volume (4500 to 6000 ml). The microcrystalline cellulose is then poured onto water and mixed at medium speed for 30 minutes or until the microcrystalline cellulose is completely suspended.The required amount of xanthan gum solution is then added to the microcrystalline cellulose suspension with stirring for 15 minutes or until a uniform suspension is formed. The sucrose is then added to the second solution with stirring for 15 minutes or until the sucrose particles are no longer visible. Coloring agents can then be added. Then add the required amount of ibuprofen suspension slowly and mix for 15 minutes. Then sodium benzoate, disodium edetate and citric acid are added sequentially and stirred for 5 minutes after each addition.The hydrochloric acid component is added with stirring until the composition reaches a pH of about 2.5 to about 3.5. The remaining water is then added with stirring until a homogeneous composition is formed. Example 3. Chewable tablets containing the ibuprofen eutomer. It will be appreciated that chewable tablets containing the ibuprofen eutomer and falling within the scope of this invention include chewable tablet compositions known in the art to be pharmaceutically and organoleptically acceptable.These compositions should include: a) the ibuprofen eutomer in the dosage amounts specified herein; b) from about 5 to about 400 mg, preferably from about 10 to about 200 mg, of a solid acidifying component, such as the edible acid components specified herein; and c) from about 50 mg to about 5 g, preferably from about 100 mg to about 1 g, a pharmaceutically and organoleptically acceptable excipient such as dextrates, maltodextrins, lactose, modified food starches, aluminum stearate, gum base and compressed sugars food grade, as well as other substances suitable as a filler and carrier.Optionally, such chewable tablet compositions can contain up to about 100 mg of pharmaceutically acceptable glidants or lubricants. An example of such a chewable tablet is discussed below: Table 3 Ingredients Quantity Loading for w / tablet 1000 tablets, kg Eutomer ibuprofen – 200 mg 0.200 mg per Citric acid, 0.030USP Theoretical tablet weight 916.6 mg Method of preparing chewable tablets of eutomer ibuprofen Precautions: all operations should be carried out at a relative humidity not exceeding 30% and at a temperature not exceeding 27 C (80F).Chewable tablets of this composition can be prepared by mixing ibuprofen eutomer, sorbitol, citric acid, polyethylene glycol 9000 and spearmint flavor in a blender for 10 minutes. This newly formed mixture is then passed through a mill using a No. 14 sieve, medium speed, knife passes. Then, magnesium stearate is added to the mixture and the mixture is stirred for about one minute. This formulated mixture is then compressed into tablets of a predetermined weight using a 5/8 inch flat, round bevel die and die set.The organoleptically acceptable ibuprofen eutomer compositions of this invention 11 also include effervescent or foaming compositions. These compositions include any pharmaceutical formulation that uses the ibuprofen eutomer in an effervescent composition, in particular a composition comprising an effervescent or foaming combination of an organoleptically acceptable acid such as a food grade acid and a carbonate. Pharmaceutically acceptable acids used in these formulations include, but are not limited to, citric acid, tartaric acid, malic acid, fumaric acid, adipic acid, ascorbic acid, aspartic acid, derythroascorbic acid, glutamic acid, and succinic acid.Glycine can also be used as part of the acidic component, if desired, but it is most preferred that glycine does not constitute the majority of the acidic component. Most preferably, to create an effervescent solution with a pH below 7, more preferably below 6, the acidic component of these effervescent compositions is superior to the carbonate component. The carbonate can be any effervescent or foaming carbonate that is pharmaceutically and organoleptically acceptable, including, but not limited to, sodium bicarbonate, potassium carbonate, sodium carbonate, calcium carbonate, aluminum carbonate, magnesium carbonate, etc.n. It is understood that the acidic and carbonate components of these compositions may include one or more suitable acids or carbonates. In its broadest sense, the effervescent or foaming compositions of this invention comprise the active eutomer of ibuprofen plus any active amounts of acidic and carbonate components. Preferably, portions of these three components comprise: a) the required amount of ibuprofen eutomer, b) from about 0.5 to about 50% by weight of the acidic component, and c) from about 0.5 to 50% by weight of the carbonate component.For example, a single dose of this drug may include: a) 50-800 mg of (+) – 2- (p-isobutylphenyl) propionic acid, b) 1-8 g citric acid, or an equivalent amount of one or more of the acceptable acids specified herein, and c) 1-8 g sodium bicarbonate or an equivalent amount of one or more of the acceptable carbonates specified herein. It will be apparent to those skilled in the art that the components of these compositions may vary depending on the required dosage of the drug, the required effervescence or foaming, and the pH of the liquid to which the composition will be added.12 In addition, it is understood that, in addition to these three components, the effervescent or foaming compositions of this invention may include any additional pharmaceutically and organoleptically acceptable components, including, but not limited to, fillers, flavoring agents, coloring agents, sweeteners, binders, pharmaceutically acceptable enhancers. the smell of the product, perfume, etc. These compositions may also include other pharmaceutically active agents such as analgesics, antihistamines, antacids, anti-bloating agents, etc.e. Examples of effervescent and foaming compositions encompassed by this invention include the following: Effervescent Ibuprofen Eutomer Powders One hundred dose batches of effervescent or foaming powder of this invention may be prepared by mixing together any of the following combinations with or without additional components. Example 4. a) 1,000 to 80,000 mg of ibuprofen eutomer b) 100 g of tartaric acid c) 100 g of sodium bicarbonate Example 5. a) 1,000 to 80,000 mg of ibuprofen eutomer d) 100 g of ammonium carbonate Example 7.a) 1000 to 80,000 mg of ibuprofen eutomer h) 5 g of carboxymethylcellulose Effervescent tablets of ibuprofen eutomer Example 8. For the manufacture of one thousand tablets of 200 mg, the ingredients are taken in the amount indicated in Table 4. micronized powder is a powder with a particle size, preferably less than 50 microns. Method of obtaining. Precautions: after stage 1, all processes are carried out in an environment with a relative humidity that does not exceed 30%. 1. Dry the compounds specified in points 1, 2, 3 and 4 at 105 C for 4 hours.2. Mix the compounds specified in points 1, 2, 3 and 4 to obtain a homogeneous powder. 3. Pass the mixture from Step 2 through a 60 mesh screen. 4. Pass the compound of step 5 through a 60 mesh sieve. 5. Add the screened compound from step 5 to the mixture from step 3 and mix until distributed. 6. Compress using a flat, beveled 5/8 inch punch and die into a 2.0 g tablet. Instructions for use: Place the required dose, 200 mg per tablet, in approximately three fluid ounces of water and wait until until the tablet disintegrates completely.Effervescent granules of ibuprofen eutomer. Example 9 Use the ingredients of Example 8 to make 1000 sachets or bags, replace the compound of Item 5 with Orange Flavored Dry Powder (from MacAndrew Forbes Co., Camden, NJ 08104) and replace Step 6 of Example 8 with the following two steps. Step 6 Place the powder from Step 5 in a fluidized bed column and, while the powder is suspended in air, add a sufficient amount of aqueous spray to form granules of approximately 10 mesh.Stage 7. Include heat to dry the granules and remove moisture to a relative humidity of not more than 25%, to be packed in sealed bags of 2.5 g each. Instructions for use. Add the required number of bags to approximately 3 ounces of water (3 x 28 g) and wait until all the granules have disintegrated for oral use. Rapidly Disintegrating Solid Dosage Forms Another form that the organoleptically acceptable compositions of this invention may take are the rapidly dissolving and disintegrating dosage forms described in US Pat. No. 4,371,516, the disclosure of which is referenced herein.These forms are preferably soluble solid forms, which are designed to disintegrate in a few seconds upon contact with liquids such as water or saliva from the mouth of recipients. These forms preferably disintegrate within 10 seconds on contact with liquids. Such compositions are especially useful for administering drugs to children or the elderly, or to others who may not be responsive to treatment and who may try to spit the drug out or hide the non-disintegrating form in their mouth until they throw it away. later.Although the process for preparing rapidly disintegrating solid dosage forms that are used in this invention is detailed in US Pat. -2- (n-isobutylphenyl) -propionic acid, referred to below as eutomer of ibuprofen. Example 10 75 individual, fast-disintegrating doses of 50 mg of ibuprofen eutomer can be prepared as follows: a) A hydrolyzed gelatin solution is prepared by dissolving 30.0 grams of gelatin B.R. in 1000 ml of purified water using heating and constant stirring. The resulting gelatinous solution is then autoclaved at 121 ° C. and 1.055 kg / cm 2 (15 p.s.i.) for one hour. The gelatin solution is then allowed to cool to room temperature. B) An aluminum mold containing 75 cylindrical depressions, each cavity having a diameter of about 0.5 cm and a depth of 1 cm, is cooled to about -192 ° C in liquid nitrogen in a stainless steel tray. become. 100 g ibuprofen eutomer, 20 g ob (obstetric) benzoic acid, 0.25 g yellow dye (F.D.C. Yellow5Coloring Agent), 0.5 g of Norda, spray dried orange flavor, is mixed with the gelatin solution and stirred continuously and, at the same time, 1/2 ml of this mixture is added with a hypodermic syringe to each cavity of the mold. The contents of the depressions are cooled. Then the mold is placed at room temperature under a vacuum of 0.3 mm Hg. Art. at night. The lyophilized formulations (each containing 50 mg of the enantiomer of ibuprofen) are then removed from the mold and stored under sealed conditions.Each composition should dissolve in a few seconds when taken orally or when added to a liquid. One of ordinary skill in the art will appreciate that the above techniques can be used to formulate rapidly disintegrating dosage forms of this invention containing a variety of individual doses of (+) – 2- (p-isobutylphenyl) propionic acid. These solutions may further include a variety of flavoring agents, sweetening agents, coloring agents, etc. to make the solutions more attractive to various recipients.In addition, other carrier materials can be used in place of the partially hydrolyzed gelatin. These include, but are not limited to, polysaccharides such as hydrolyzed dextran, alginates (eg sodium alginate), and dextrin, or mixtures thereof with each other or with other carrier materials, including gum arabic, polyvinyl alcohol, or polyvinyl pyrrolidine. For the preparation of rapidly disintegrating compositions, it is preferred that the (+) – 2- (p-isobutylphenyl) propionic acid used is in the form of a micronized powder in order to avoid the potential squeaky sensation of sand on disintegration of the compositions in the mouth of the recipient.More preferably, (+) – 2- (p-isobutylphenyl) propionic acid is in the form of a micronized powder containing particles of 50 microns or less. It is obvious to one skilled in the art that these compositions, due to the nature of this design, should disintegrate when exposed to moisture, or physical stress, or shock. Therefore, it should be borne in mind that these compositions should be handled with care and filled in containers that minimize the risk of premature deterioration, such as the packaging described in US Pat. No. 4,305,502.Examples 11 to 14 provide a list of combinations of (+) – 2- (p-isobutylphenyl) propionic acid and other components that can be added in the above manner to 1000 ml of gelatin solution or other suitable carriers. B) 30 g fructose c) 10 g benzoic acid Example 12 100 mg ibuprofen eutomer / dose. a) 200 g ibuprofen eutomer (yellow dye) c) 0.5 g Norda spray-dried orange flavor d) 25 g sucrose e) 20 g benzoic acid Example 13.200 mg ibuprofen eutomer / dose a) 400 g ibuprofen eutomer d) 15 g sucrose e) 40 g benzoic acid Example 14.400 mg ibuprofen eutomer / dose – without hydrolyzed gelatin a) 533.33 g ibuprofen eutomer d) 15 g aspartame e) distilled water up to 1000 ml f) 50 g benzoic acid This composition, which contains hydrolyzed gelatin as in the previous examples, can be obtained in recesses of a 220 x 330 mm PVC sheet containing 150 cylindrical recesses, each recess having a depth of about 0.7 cm and a diameter of about 1.4 cm, which is cooled with solid carbon dioxide.The composition can be prepared by suspending the ibuprofen eutomer in water containing sodium alginate, dextran and aspartame listed above using ultrasonic vibrations. Then 0.75 ml of the suspension is placed in each of the recesses of the PVC sheet, where the suspensions can be completely lyophilized into a rapidly disintegrating composition. Example 15 1 g ibuprofen eutomer / dose without hydrolyzed gelatin a) 1333.33 g ibuprofen eutomer f) distilled water up to 1000 ml g) 50 g benzoic acid Another example of a rapidly disintegrating solid composition can be prepared with the above components and carbon dioxide cooling the PVC – sheet as described in the previous example.This can be done by adding polyvinyl alcohol to about 500 ml of hot distilled water 17, which is then cooled. Then add polyvinylpyrrolidine, sucrose and Tween 80 and shake the mixture to dissolve all solids. The ibuprofen eutomer is added and the mixture is dispersed by ultrasonic vibrations. This mixture is then made up to a final volume of 1000 ml by the addition of distilled water. Next, 0.75 ml of this solution is added to each lyophilization well to the final solid composition.Buccal Compositions A buccal (buccal) composition containing the ibuprofen eutomer of this invention can be prepared using the steps set forth in US Pat. No. 4,764,378 (Keith et al.), Which is referred to herein. Most preferably, these buccal compositions contain an acidic component such as a micronized solid food grade acid. Such food-grade acid can be included in an amount of from about 0.1-2.0% by weight of the final buccal composition, although more acid can be added if necessary.Example 16. Compositions in the form of lozenges or lozenges. Compositions in the form of lozenges or lozenges containing the ibuprofen eutomer can be prepared for any of the dosages specified herein by methods known in the art. For example, such lozenges can be obtained by pressing and then drying by evaporating a concentrated syrup containing the ibuprofen eutomer, with added thickeners as needed, such as gum arabic or tragacanth. This type of flatbread is often referred to as a sugared flatbread or lozenge.Using the following ingredients and methodology, candied tortillas can be prepared for any dosage of ibuprofen eutomer specified herein. Below is a composition used to prepare lozenges containing 100 mg of ibuprofen eutomer. Ingredient Amount, g Sucrose Tartar Corn syrup Citric acid (fine powder sieved through a 100 mesh sieve) Ibuprofen eutomer These cakes can be prepared by adding the above sucrose, tartar (optional) and corn syrup to a vessel while stirring, followed by boiling to dissolve the sucrose and wine 18th stone.Heating of these components should be stopped when a strong boil is reached, which occurs at about 143 C (290 F), and when about 30% of the original volume has been removed by evaporation. These components should be mixed until the mass has cooled to approximately 138 C (280F). At this point, citric acid and the ibuprofen eutomer should be added to the resulting mass with stirring, until a homogeneous dispersion is obtained. When the contents have cooled to about 88 ° C (190F), the mass is rolled into a flagellum or columnar shape and cut into 4 g pieces.These pieces can then be placed on a grid to cool to room temperature. Faster disintegrating lozenges or lozenges can be prepared using 9200 g of compressed sugar such as Dipac regular commercial sugar (Domino Sugar Co., New York, NY) and the amounts of tartar (optional) described above, citric acid, and ibuprofen eutomer (or other preferred dose of ibuprofen enantiomer). These components can be homogenized by mixing and compressed into pellets of the desired size, such as the 4 g tablets described above.The compressed sugar, an equivalent amount of sucrose and lactose can be thoroughly mixed with a suitable binder such as sodium alginate in an amount of 525 g and a pharmaceutically acceptable granulating liquid to form a wet mass. This wet mass can be passed through a granulating mill and compressed into pellets of the desired size. From the description and examples provided herein, it will be apparent to those skilled in the art that S (+) – 2- (p-isobutylphenyl) propionic acid, the eutomer of ibuprofen, can be used to prepare a wide variety of organoleptically acceptable oral compositions without departing from the scope of the invention.Compositions for cleaning teeth. Dentifrice compositions known in the art may have S (+) ibuprofen, preferably with an additional acidic component included, to prevent or reduce osteoporosis and / or to promote regrowth of previously lost bone. It will be appreciated that dentifrices are believed to include any dental compositions that can be used to treat and maintain the teeth and tissues of the mouth. These include, but are not limited to, pastes, gels, powders, granular compositions, liquids, etc.e. An example of a toothpaste within the scope of this invention can be prepared by slowly adding the following non-aqueous components to water, followed by conventional mixing with a roller mill. Example 17 Component S (+) ibuprofen Magnesium Aluminum Silicate Citric acid Dicalcium phosphate Mint or other flavoring agent Sodium carboxymethyl cellulose Sodium lauryl sulfate Water Organoleptically acceptable dentifrices, within the scope of this invention, may include any of the known dentifrice compositions , preferably with an acidic component present or added.Compositions for pastes of this type may contain, for example, by weight 10-50% abrasive system, 0.5-10% thickeners, 10-80% humectant, 0.11% sweetener, 0.05-2% flavors, 0.0010 , 02% coloring agents, 1-7.5% surfactant, 0.1-0.8% antimicrobial preservatives and 0.01-5% acidifying agents. The abrasive components of these compositions include calcium pyrophosphate, hydrated silicon dioxide, insoluble sodium metaphosphate, organic polymers, alumina trihydrate, dicalcium phosphate dihydrate, anhydrous dicalcium phosphate, and calcium carbonate.Thickeners include silica airgel, fumed silica, silica precipitates, carboxymethyl cellulose, carboxyvinyl polymers, xanthan gum, and carrageenan. Humectants used include sorbitol, glycerin and polyethylene glycols. Used sweeteners include saccharin, xylitol, cyclamate, aspartame and thaumatin. Flavors can be modified to suit taste and market requirements, but include peppermint, spearmint, winter-lover, cinnamon and aniseed flavors, and natural oils.Any dyes approved for pharmaceutical purposes can be selected for inclusion in such compositions. Surfactants may include sodium lauryl sulfate, sodium lauryl sarcosinate, pluronix, tweens, sodium coco monoglyceride sulfate, sodium dodecyl benzene sulfonate, and dioctyl sodium sulfosuccinate. Antimicrobial agents and preservatives used in the art include parahydroxybenzoates, sorbic acid, and benzoic acid. Acidic components for 20 of these forms include food acids as defined herein, including lactic acid, citric acid, phosphoric acid, and tartaric acid.An example of such a dentifrice can be obtained from the following ingredients. Example 18 (Table 4) Ingredient Eutomer of ibuprofen Xerogel of silicon dioxide Airgel of silicon dioxide Sodium carboxymethyl cellulose Sorbitol Saccharin Sodium monofluorophosphate Sodium lauryl sulfate (29% solution) Aroma of Tutti Frutti (Virginia Dare, AK 27) Equal parts to Ethylparaben, To to minimize any possibility of demineralization of the tooth structure, it is believed that the pH of this composition should be not lower than 5.0.Sodium monofluorophosphate is an appropriate fluoride source used in this desired pH range. Chewing Gum Compositions Another organoleptically acceptable composition within the scope of this invention are types of chewing gum compositions. It is understood that these types of compositions can be prepared by incorporating the ibuprofen eutomer, most preferably together with a suitable acidic component, in any of the organoleptically acceptable chewing gum bases 21.An example of a chewing gum composition of the present invention can be prepared with the components set forth in Example 19 below (see end of description). A chewing gum composition is prepared by heating the above ingredients to a softened state, followed by separate stepwise addition of acidifier, sweetener, ibuprofen eutomer and flavor with stirring to obtain a homogeneous mixture after each addition. The final homogeneous chewing gum composition is then milled with a sizing machine and cut into 3 g pieces using finely ground powdered sucrose for ease of handling, followed by standard packaging and filling.It is understood that other chewing gum compositions may be used without departing from the scope of this invention, and that the components of the above composition may be replaced with equivalent amounts of other functional components, including those described herein, for use with other compositions. Veterinary Compositions It is further understood that the use of organoleptically acceptable compositions is important for veterinary use. While this is true of any mammal for which an NSAID may be recommended by a veterinarian, it is particularly true for companion animals such as dogs and cats where owners and caregivers have appreciated the relative ease of administration of rapidly administered oral dosage formulations. , as opposed to those compositions; to be introduced by means of mechanical retention methods.The veterinary compositions of this invention include any of the aforementioned solid or liquid dosage forms that can be given to animals. These compositions can be administered to food or drink for animals, or given as a separate pharmaceutical form. If given separately, it is recommended that the composition contains an ingredient, preferably a tasty ingredient, which is generally considered pleasing to the animal in question. For example, in the case of cats and dogs, it can be used as the main flavoring component of liver extract, seafood extract, poultry extract, dried liver, soy flour, sugar, liver oil, soybean pulp, fish meat, bones, yeast, pulp 22 wheat seeds and other known food bases or combinations thereof.Such ingredients can be used as flavoring agents in the above compositions and they can be used as fillers in place of the materials described herein. It will be appreciated that the percentages of ingredients in the animal-oriented oral compositions of this invention will be determined in large part by the size of the animal and the size of the composition desired. For example, a relatively small chewable tablet can be composed of a blended and compressed combination of the following ingredients: Example 20.Ingredient Weight% Ibuprofen eutomer 60 Main aroma component 15-25 Microcrystalline cellulose 10-20 Povidone K 29-32 2-6 Aluminum stearate 1-2 Lactic acid 0.1-2.0 To obtain a larger solid composition containing the required dose eutomer of ibuprofen, the number of components, if desired, can be increased as in the following composition. Example 21 Ingredient Weight% Ibuprofen eutomer 60 Base flavor component 35-45 Calcium phosphate dibasic 15-25 Microcrystalline cellulose 15-25 Povidone K 29-32 2-6 Aluminum stearate 1-2 Most preferably these compositions furthermore contain an acidic component such as a solid food acid.For example, an edible acid such as citric acid or malic acid can be present in an amount of 1-5% by weight of the composition, although the amount of the acidic component can be increased if desired. Another desirable solid composition that can be used for administration to animals may be formulated as follows. Example 22. Ingredient mg ​​/ tablet Eutomer ibuprofen 5-500 Whey, dry sweet 2000 Liver, dried 210 Yeast dry 50 Aluminum stearate, NF 50 Citric acid 30 Example 23. A dosage form in the form of a chewable tablet for use in pets can be obtained with the following components and in the following ways.While this example shows the preparation of 200 mg tablets containing the ibuprofen eutomer, it will be appreciated that any required dose can be incorporated into this type of composition. Table 7 Amount Amount / Steam Ingredients per tablet, tia 1000 tablets, g mg Eutomer ibu 200 200 profena 600 600 Sodium starch glycolate, NFU.S.P. lactose Dried 252 252 liver Dry yeast 62 62 Aluminum stearate 45 45 Fumaric acid 100 100 slots Chewable tablets of this composition can be prepared by mixing ibuprofen eutomer, sodium starch glycolate, spray dried lactose, fumaric acid, dried liver and dried yeast in a suitable mixer until a homogeneous mixture is obtained.Then 2/3 of the amount of aluminum stearate is added to the batch, such as about 10% of the mixture of the ingredients just described, with stirring until a uniform mixture is obtained. The remaining mass of ingredients is then added with mixing sufficient to evenly distribute the mass containing aluminum stearate. This mixture is then brought to a medium hardness and calibrated through a rotary granulator using a No. 10 sieve. The remainder of the aluminum stearate is then added to the granulated mixture with stirring.The final tablets of this composition can be compressed using a 1 1/16 inch flat die at 12 to 15 SCU hardness. Tablets of this type can be given either whole or broken into small pieces to deliver a lower dose. Based on the description provided herein, one skilled in the art can use S (+) ibuprofen to create a variety of organoleptically acceptable oral compositions without departing from the scope of this invention. 24 FORMULA OF THE INVENTION 1.An organoleptically acceptable oral pharmaceutical composition comprising S (+) – 2- (p-isobutylphenyl) propionic acid, substantially free of R (-) – 2- (nisobutylphenyl) propionic acid, and an acid component. 2. The pharmaceutical composition according to claim 1, characterized in that the acid component contains one or more acids selected from: citric acid, tartaric acid, malic acid, fumaric acid, lactic acid, adipic acid, ascorbic acid, aspartic acid, d- erythroascorbic acid, glutamic acid, succinic acid.3. The pharmaceutical composition of claim 1, further comprising an organoleptically acceptable pharmaceutical carrier. 4. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in powder or granular form. 5. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in the form of a liquid. 6. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in the form of chewable tablets. 7. The pharmaceutical composition according to any one of paragraphs.1-3, characterized in that it is in the form of an effervescent preparation. 8. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in the form of lozenges. 9. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in a rapidly disintegrating solid form. 10. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in the form of a chewable preparation used for veterinary medicine. 11. A pharmaceutical composition according to any one of claims 1 to 3, characterized in that it is in the form of a chewing gum.12. A method for preparing an organoleptically acceptable oral pharmaceutical composition by mixing an active component and a target additive, characterized in that S (+) – 2- (n-isobutylphenyl) -propionic acid, practically free of R (-) – 2, is used as the active component – (n-isobutylphenyl) -propionic acid, as a target additive – an acid component and convert it into a form suitable for oral administration. Ibuprofen eutomer, micronized Chicl Hydrogenated rosin glycerin ester Sucrose, fine powder Tolu balm Cinnamon oil Gum base Gum base Sweetener Acidifier Flavor

Oral composition containing s (+) – ibuprofen, and the method for its preparation.

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