Saturday, December 3, 2022

Alternative To Colchicine For Gout

How And When To Take It

Colchicine

The usual dose of allopurinol is 100mg to 300mg a day. Follow your doctors advice on how many tablets to take, and how many times a day.

Youll have regular blood tests to monitor your uric acid levels. If your uric acid level does not come down far enough, your doctor may increase your dose .

If you have kidney or liver disease, your doctor may prescribe a lower dose and will monitor you more closely.

Gout And Pseudogout Treatment & Management

  • Author: Bruce M Rothschild, MD Chief Editor: Herbert S Diamond, MD

Gout is managed in the following 3 stages :

  • Treating the acute attack
  • Providing prophylaxis to prevent acute flares
  • Lowering excess stores of urate to prevent flares of gouty arthritis and to prevent tissue deposition of urate crystals

The American College of Rheumatology published guidelines on the treatment and prophylaxis of acute gouty arthritis and the management of hyperuricemia. While those guidelines do describe treatment targets, more recent publications have focused more closely on the treat-to-target concept, although for the most part these recommendations are based on underlying principles and expert opinion rather than trial data.

As a general rule, asymptomatic hyperuricemia should not be treated, though ultrasonographic studies have demonstrated that urate crystal deposition into soft tissues occurs in a minority of patients with asymptomatic hyperuricemia. Patients with levels higher than 11 mg/dL who overexcrete uric acid are at risk for renal stones and renal impairment therefore, renal function should be monitored in these individuals.

Patients who achieved a serum uric acid level below 6 mg/dL had a 37% improvement in renal outcomes . The hazard ratio for kidney damage was 1.08 in patients who received urate-lowering therapy more than 80% of the time and was 1.27 in those who received urate-lowering therapy less than 80% of the time.

Food And Medication Interations

  • Risk factors: Grapefruit & grapefruit juice | Protease inhibitors | Antifungal antibiotics | Calcium channel blockers | Cyclosporine | statins | Digoxin

Many medications can interact with colchicine and can make the medication levels go too high, which can be dangerous. If you have liver or kidney problems, these interactions can be worse. Always make sure your providers have a full list of the medications you’re taking, even if you only take colchicine a few times a year. If you’re taking a medication that interacts with colchicine , your provider will need to adjust your dose.

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Lowering Uric Acid Is Key To Gout Control

Affecting more than 5 million Americans, gout is a chronic arthritic condition characterized by flares of intense pain, redness, inflammation, and warmth in the affected joint. Typically, symptoms begin in the big toe, but gout may strike other joints.

Gout is caused by an accumulation of uric acid crystals in the affected joint. As the disease progresses, these flares may become more frequent and patients may develop joint deformity and large deposits of crystals, which can become visible under the skin .

Uric acid is found naturally in the body. In gout, there is generally a problem with either too much production of uric acid or problems in getting rid of the uric acid, or both.

When you have gout, theres too much uric acid in the body, Wortmann explains to WebMD. Uric acid is like matches, and for some reason, one of these matches strike and you get a hot foot.

We treat the fire with anti-inflammatory drugs or colchicine right away because if not, more matches will catch and the fire will get worse, he explains. Though these medications can put out the fire, it doesnt get rid of the matches so they still can strike.

Enter febuxostat and allopurinol. And getting rid of these matches is what febuxostat appears to do more effectively than allopurinol, according to the new study.

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Existing Concerns About Colchicine Dosing And Toxicity

Gout Medicine Side Effects

Vomiting and diarrhoea commonly occur when colchicine is repeatedly dosed at 1-hour or 2-hour intervals for acute gout.1,3 These are the first signs of colchicine toxicity, and may precede rare adverse effects including muscle damage, neuropathy, multiple organ failure and bone marrow suppression.4 Patients with renal or hepatic impairment may be particularly susceptible to severe colchicine toxicity .2,5-7

Increasing awareness of toxicity led prescribing guidelines to recommend lower colchicine doses and extended dosing intervals.8-10 Case reports and expert opinion suggested that the treatment benefit could be maintained at lower colchicine doses, but no data from controlled trials were available until recently.1,11

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Hepatic Impairment And Gi Bleeding

Patients with cirrhosis should avoid NSAID use due to the potential increased bleeding risk from underlying coagulopathy. Additionally, colchicine clearance may be reduced in patients with severe liver impairment, mandating close surveillance when this agent is used. If hepatic impairment is mild to moderate, judicious use of any of the first-line therapies may be appropriate.

Patients with GI bleeding or a history of peptic ulcer disease should avoid NSAID use because of increased bleeding risk. If an NSAID is used, proton pump inhibitors decrease the risk of NSAID-associated mucosal damage.

The Beginning Of Gout

Most likely, you already know that gout is caused by the crystallization of uric acid in the joints. But, isnt it ironic that gout happens despite the fact that your body is designed to effectively flush excess uric acid out?

Imagine these two scenarios:

Scenario 1

Factory X can produce 100 boxes of products a day. Everyday the factory receives raw materials for 200 boxes of products. Since 200-100 = 100, there will be an excess 100 raw materials everyday. It will be stored to warehouses. If a warehouse only has a capacity of 500 boxes, it will only take five days for it to be full! What will happen if it is full? The factory staff will find ways to store the excess materials. They will store it in places not designed to store. In the case of our body, it is the synovial fluids found in the ball-and-socket joints such as the knee, ankle and wrist.

Scenario 2

Factory Y can produce 100 boxes a day. Everyday, the factory receives 110 raw materials, almost exactly the amount it can process. Unfortunately, the 500 box capacity warehouse have already 490 box of other materials! Hence, a few excess material can make it full and the excess materials will be stored to other places.

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Who Can And Can’t Take Colchicine

Colchicine can be taken by most adults aged 18 and over.

It can sometimes be prescribed for children by a specialist doctor.

Colchicine is not suitable for some people. To make sure it’s safe for you, tell your doctor if you:

  • have ever had an allergic reaction to colchicine or any other medicines
  • have a severe blood disorder
  • have severe kidney or liver problems
  • have problems with your heart or digestive system
  • are pregnant, think you might be pregnant or are trying for a baby

Women who could become pregnant will usually only be prescribed colchicine if they are using suitable contraception.

How Is It Taken

Gout Treatment: Natural Gout Herbs

Allopurinol is taken as a tablet once a day. It is usually better to take it just after eating and the tablet should be swallowed with water. It is important to drink plenty of water during the day because this will help you get rid of more urate through your kidneys.

Your dose of allopurinol may change over time, depending on the amount of urate in your body. Your doctor will monitor your urate levels with blood tests every 2-4 weeks, until they are sure that the dose that youre taking is high enough to reduce the amount of urate in your body.

You may need to remain on a lower dose if you have kidney or liver problems.

Your doctor may recommend that you do not start taking allopurinol until after an attack of gout has passed to avoid triggering further attacks. If this is not possible, it may be started when your inflammation is not too bad.

Allopurinol doesnt treat the immediate pain caused by attacks of gout. But its a long-term treatment to get rid of the urate crystals which causes gout attacks.

It is likely that you will need to take allopurinol for the rest of your life to manage your urate levels. You should keep taking allopurinol even if:

  • you are experiencing more gout attacks, or it doesnt seem to help the pain and inflammation at first
  • you stop having gout attacks stopping your treatment can cause urate crystals to form again, which will lead to more gout attacks.
  • etoricoxib

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What Are Future Possible Treatments Of Gout

Fortunately, present medications are successful in the vast majority of gout patients. But some patients cannot tolerate our present arsenal of gout medications. For others, these agents are not sufficiently effective. Therefore, new treatments are continually being sought. Some of the more promising include anakinra, rilonacept, canakinumab, BCX4208 and arhalofenate.

Metabolism And Adverse Effects

Major mechanisms of colchicine metabolism and excretion

Colchicine is initially absorbed in the jejunum and ileum. P-Glycoprotein on the apical surface of enterocytes secretes a fraction of unchanged colchicine back into the lumen, from which it can be excreted. The remainder enters the systemic circulation and passes through the kidneys, where unchanged colchicine is excreted through glomerular filtration as well as through direct renal P-gp secretion into the proximal tubule. Within hepatocytes, colchicine undergoes demethylation into three distinct metabolites through the action of CYP3A4. These metabolites, along with a portion of unchanged colchicine, are secreted into the bile via hepatic P-gp, and thence into the duodenum for potential excretion.

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Allopurinol And Febuxostat Does Not Flush Uric Acid Away

Allopurinol and febuxostat are xanthine oxidase inhibitors. Ever been fascinated how they magically lower uric acid? The trick here is it they suppress xanthine oxidase. Ooops. Dont stop right there! This is no rocket science. Were just a few paragraphs away from the solution.

When you eat food, certain amount of purine, depending on the food, will go to your body. Eat fruits, theres purine. Eat vegetables, theres purine. Eat meat, theres lots of purine. Drink beer and theres tons of purine! This purine is used by the body to manufacture nucleotides for the DNA, but excess purine will have to be flushed out. Unfortunately, purine can not be flushed out as purine. Xanthine oxidase will react with purine to break it down into uric acid.

Why Doctors Have Failed To Get Rid Of Your Gout

Colchicine And Gout

eternity they are not designed to do so.

Put simply, this meds are designed neither to cure gout nor flush the uric acid out but to mask the pain and inflammation. Some are designed to delay the production of uric acid , but sooner or later the delayed uric acid will emerge with a vengeance.

Here is the good news though: There is a way to halt your gout. You do not have to suffer the side effect.

The pain subsided when I took colchicine. It treats gout!

Allopurinol lowered my uric acid!

Unfortunately, it is not that way.

The following article is the excerpt from a very unique book that is sold at the price of $29.97. As a matter of fact, the true value of the information contained in this book is priceless. This is especially true for those who had been suffering from gout for a very long time. If youve been troubled by the notorious gout pain for years and wonder how you can free yourself from it, read on, you will discover the real truth of gout and how to get rid of it once and for all.

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What Does A Gout Attack Look And Feel Like What Would A Foot Or Toe With Gout Look Like

When gout occurs, the joint tends to be extremely painful and is warm, red and swollen . The inflammation that is part of a gout attack is systemic, so that fever and chills, fatigue and malaise are not uncommonly part of the picture of a gout attack.

Figure 6: Toe with Acute Attack of Gout

Gout attacks can occur in joints that look normal, or in joints that have easily visible deposits of uric acid. These deposits are called tophi and can be in numerous locations, but especially on the feet and elbows. In Figure 9, the little finger of the right hand is bandaged since fluid was just removed from it, which demonstrated innumerable uric acid crystals.

Figure 7a: Tophi on Foot

Figure 7b: Tophus Over Achilles Tendon

Figure 8: Tophus on Elbow

Figure 9: Tophi on Hands

Figure 10: Large Tophus of Finger

While some gout attacks will solve quickly by themselves, the majority will go on for a week, several weeks, or even longer if not treated. Since gout attacks are usually quite painful and often make walking difficult, most gout sufferers will request specific treatment for their painful condition.

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Pathophysiology And Risk Factors

Genetic mutations may be associated with overproductionor more often underexcretionof uric acid because of defects in the renal urate transporter system.6 The prevalence of gout increases with age and peaks at more than 12% in persons older than 80 years.1 Because female sex hormones increase urinary excretion of uric acid, pre-menopausal women have a substantially lower prevalence of gout compared with men .6 Black persons have a higher risk.7 Consuming alcoholic drinks , meat , some seafood , fruit juice, and beverages sweetened with high-fructose corn syrup increases the risk of gout.8,9 Purine-rich foods such as nuts, oatmeal, asparagus, legumes, and mushrooms do not seem to increase the risk.10 Consumption of dairy products appears to confer slight protection from gout10 .

Diuretic use*

Relative risk

50 g per day vs. none

2.53

2 drinks per day vs. none

2.51

2 drinks per day vs. none

1.60

2 drinks per day vs. none

1.05

30 kg per m2 at 21 years of age

2.14

2 drinks per day vs. none

1.85

1,500 mg vs. < 250 mg per day

0.55

6 cups per day vs. none

0.41

*Adjusted for age.

Adapted with permission from Roddy E, Doherty M. Epidemiology of gout. Arthritis Res Ther. 2010 12:223, with additional information from reference 12.

Diuretic use*

*Adjusted for age.

Adapted with permission from Roddy E, Doherty M. Epidemiology of gout. Arthritis Res Ther. 2010 12:223, with additional information from reference 12.

Hard nodules on distal digit.

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What Are The Side Effects Of Colchicine

With any medication, there are risks and benefits. Even if the medication is working, you may experience some unwanted side effects.

The following side effects may get better over time as your body gets used to the medication. Let your doctor know immediately if you continue to experience these symptoms or if they worsen over time.

New Gout Drug Twice As Effective

Allopurinol – Nebraska Medicine

Nov. 16, 2005 — A new treatment for gout is at least twice as effective at lowering uric acid levels as the standard drug allopurinol, according to results from the longest and largest trial of such drugs ever conducted.

The drug, , will likely be the first new agent available to treat gout in more than 40 years, says researcher Robert L. Wortmann, MD, professor and chairman of the department of rheumatology at the University of Oklahoma in Tulsa.

Exactly when the new drug will be approved is not known, but “personally I am optimistic,” he says.

The research was presented at the annual meeting of the American College of Rheumatology in San Diego.

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What Are The Side Effects Of Febuxostat

With any medication, there are risks and benefits. Even if the medication is working, you may experience some unwanted side effects.

Contact your doctor immediately if you experience any of the following:

  • Serious skin reaction: red, swollen, blistered, or peeling skin
  • Liver problems: yellowing of the skin or eyes, nausea, vomiting, stomach upset, dark urine, itchiness
  • Chest pain

The following side effects may get better over time as your body gets used to the medication. Let your doctor know immediately if you continue to experience these symptoms or if they worsen over time.

Gfs Following Ult Initiation

We lack robust data on the prevalence of GFs induced by ULT. Placebo arms from studies conducted with IL-1 blockers and colchicine gave important information on both flares triggered by ULT and their prophylaxis. In three recent placebo-controlled trials evaluating rilonacept, an IL-1 blocker, for preventing acute GFs during the initiation of allopurinol 300 mg/day, the proportion of patients in the placebo arm reporting at least one GF after 16 weeks of ULT ranged from 46.8% to 56.1% . In another randomized, placebo-controlled trial assessing whether colchicine administration could reduce the frequency of flares during the initiation of allopurinol, this proportion reached 77% at 6 months for patients who received the placebo , even though a titration of allopurinol was performed.

Prophylactic treatment can decrease the rate of GFs triggered by the initiation of ULT but does not totally prevent the occurrence of flares, in particular with a sharp decrease in urate levels . Studies of pegloticase and febuxostat have provided additional data on the rate of flares in patients treated with these powerful ULTs when given without slow upward titration. In two recent placebo-controlled trials evaluating pegloticase, known for markedly lowering urate levels, despite patients receiving colchicine 0.6 mg once or twice daily or an NSAID, the rate of GFs in the first 3 months exceeded 75% in both pegloticase groups as compared with 53% in the placebo group .

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