Colchicine Dosage For Gout Flare Up

Colchicine For Treating Acute Gout Flares

Background

Gout is a very common cause of inflammatory arthritis and is caused by urate crystals forming either within or around joints. Uric acid is a normal waste product that is usually excreted with urine. However, in the case of gout, there is either excessive production of uric acid, or the body is not able to excrete it quickly enough, or a combination of both. An attack of gout usually occurs rapidly and usually resolves within 7 to 10 days.

Colchicine is a drug that is used mainly in gout to treat an acute attack or to prevent an attack while starting uric acid-lowering therapy.

Study characteristics

This Cochrane Review is current to August 2020. We included four trials in this updated review, including two new trials. One three-arm trial compared high-dose colchicine , low-dose colchicine and placebo one trial compared high-dose colchicine with placebo one trial compared low-dose colchicine with non-steroidal anti-inflammatory drugs and one trial compared low-dose colchicine with Chuanhu anti-gout mixture . We selected low-dose colchicine compared with placebo as the primary comparison the low dose is consistent with doses used in practice. Trials were performed in hospital and multicentre settings in four countries, the majority of participants were male, and mean age ranged between 51.2 and 70 years. One trial received funding from a pharmaceutical company that was involved in the study design, data collection, data analysis, and manuscript writing.

Allopurinol And Colchicine May Help Adults Prevent Gout Flares

Date: 03/07/2019 | Topics : Colchicine, Mitigare,

More than eight million Americans are currently living with gout.1 If you are one of them, your doctor may have prescribed you a urate-lowering therapy such as allopurinol. Allopurinol can help to prevent gout flares because it slows down uric acid production in the body.2

Allopurinol is just one part of therapy, however.3 If you take allopurinol, your doctor may also prescribe colchicine.3 Many adults with gout take allopurinol and colchicine or another anti-inflammatory medicine as part of their gout flare prevention treatment program.3

Management Of Gout In Ckd

The management of gout follows the same four principles regardless of the presence of CKD: 1) lower SUA 2) provide prophylaxis while initiating ULT 3) treat gout flares and 4) optimize dietary and lifestyle factors as appropriate. Over a prolonged period of time with adequate management of hyperuricemia, defined as maintenance of a SUA level < 6 mg/dL or < 5 mg/dL for those with tophaceous gout, gout flares will diminish in frequency and severity, with eventual cessation of flares, and tophi can be prevented and/or resolve.

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The Relation Of Uric Acid And Ult To Kidney Outcomes

CKD leads to hyperuricemia due to decreased urinary excretion of UA. Hyperuricemia also may induce kidney dysfunction and contribute to CKD progression through a number of potential mechanisms. It is possible that controlling hyperuricemia, especially if achieved early, may reduce kidney disease risk.

Management Of Gout: Update From The American College Of Rheumatology

Key Points for Practice

During a second gout flare-up in one year, low-dose allopurinol can be started with anti-inflammatory therapy without worsening the flare-up.

Allopurinol is the preferred urate-lowering agent, but HLA testing should be offered to patients of Southeast Asian or African American descent before starting to identify patients at risk for an allergic reaction.

Titrating urate-lowering therapy to reach a serum urate level of 6 mg per dL decreases flare-ups and increases treatment adherence.

During acute flare-ups, low-dose colchicine, NSAIDs, and glucocorticoids delivered orally, intramuscularly, or intra-articularly are similarly effective.

From the AFP Editors

Although effective medications exist to prevent and treat acute flare-ups, gout remains the most common inflammatory arthritis in the United States. Urate-lowering therapy is underused despite previous recommendations from the American College of Rheumatology . The ACR published updated guidelines for gout management focused on improving prevention of flare-ups.

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Use In Specific Populations

• In the presence of mild to moderate renal or hepatic impairment, adjustment of dosing is not required for treatment of gout flare, prophylaxis of gout flare and FMF, but patients should be monitored closely .
• In patients with severe renal impairment for prophylaxis of gout flares, the starting dose should be 0.3 mg/day for gout flares, no dose adjustment is required, but a treatment course should be repeated no more than once every two weeks. In FMF patients, start with 0.3 mg/day, and any increase in dose should be done with close monitoring .
• In patients with severe hepatic impairment, a dose reduction may be needed in prophylaxis of gout flares and FMF patients while a dose reduction may not be needed in gout flares, a treatment course should be repeated no more than once every two weeks .
• For patients undergoing dialysis, the total recommended dose for prophylaxis of gout flares should be 0.3 mg given twice a week with close monitoring. For treatment of gout flares, the total recommended dose should be reduced to 0.6 mg x 1 dose and the treatment course should not be repeated more than once every two weeks. For FMF patients, the starting dose should be 0.3 mg/day and dosing can be increased with close monitoring .
• Females and Males of Reproductive Potential: Advise males that colchicine tablets may transiently impair fertility .
• Geriatric Use: The recommended dose of colchicine should be based on renal function .

Revised: 2/2021

Interactions That Increase Your Risk Of Side Effects

Taking colchicine with certain medications raises your risk of side effects from colchicine. Examples of these drugs include:

• Cholesterol drugs, such as atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, fibrates, or gemfibrozil. Increased side effects can include serious muscle damage. Your doctor may reduce your dosage of colchicine to avoid this.
• Digoxin, an antiarrhythmic drug. Increased side effects can include serious muscle damage. Your doctor may reduce your dosage of colchicine to avoid this.
• Heart drugs, such as verapamil or diltiazem. Increased side effects can include stomach pain, constipation, diarrhea, nausea, or vomiting. Your doctor may reduce your dosage of colchicine to avoid these problems.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

Colchicine oral tablet comes with several warnings.

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Factors To Consider When Taking Colchicine

As some sort of continuation to answering the question how to take colchicine for acute gout, we will now be discussing about the additional thoughts you must take into consideration when you are taking colchicine.

• Is your child breastfeeding from you?
• Have you experienced allergies to other medications?
• Do you have problems with digestion?
• Do you have disorders in your kidneys or liver?
• Do you have blood or bone marrow disorders?
• Are you taking other medications?
• Are you taking other medications?
• Are you taking other medications for gout?
• Are you pregnant or planning to get pregnant?

Furthermore, you must also exercise the following general cautions:

• Since the colchicine isnt a treatment for gout, you must still exercise the essential processes you must undergo in your own gout treatment, just like low purine diet.
• Remember, it is your own medicine, not someone elses. Dont play genius and suggest the medicine to others wholl in turn take your word as a gospel. Your own situation may be different from someone elses. Once more, the colchicine is toxic so if you take it without any prescription, you might end up being sorry.
• Think of telling your doctor if you dont feel any improvement. This means that the pain relief and not the reduction of the uric acid.
• Keep out colchicine out of reach of children, especially because it is toxic.

Frequently Asked Questions About Colchicine

Is it ok to take colchicine every day?

Colchicine can be taken every day at the recommended dose for prevention of gout flares. It should not be taken daily for the treatment of gout flares. The treatment dose should only be taken once every 3 days.

Is colchicine a pain killer?

Colchicine will lower inflammation in your joints to help with gout-related pain. It won’t help with other kinds of pain and shouldn’t be taken as a pain killer.

Is colchicine bad for your kidneys?

Colchicine leaves your body through the kidneys, so if your kidneys are not working at a certain level, your provider may lower your dose to avoid a build-up of the medication and unwanted side effects.

What happens if I drink grapefruit juice while taking colchicine ?

Grapefruit and grapefruit juice will slow down the breakdown of colchicine and cause the medication levels in your body to get too high. Other medications like HIV ARVs, antibiotics, and cholesterol-lowering statins can also have this same effect. High levels of medication raise your risk of unwanted side effects.

What’s the difference between the capsules and the tablets of colchicine ?

Colchicine tablets and capsules include the same medication at the same dose. The capsule is sold under the name Mitigare. The tablets are scored so you can cut them in half, this makes adjusting your dose easier. The price of each may vary at different pharmacies.

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Side Effects Of Colchicine

Colchicine may cause some side effects, such as:

• Diarrhea
• Stomach pain or cramping
• Vomiting

If these persist for hours or are severe, let your doctor know. Also, if you experience any of these side effects, alert your doctors office immediately:

• Muscle pain or muscle weakness
• Signs of an infection: sore throat, fever, chills, body aches u Fatigue or weakness
• Numb fingers or toes

How Much Does Colchicine Cost

Colchicine is available as a generic medication and may be significantly cheaper compared to the brand version. Unless there is a specific reason you need the brand, the generic medication will be a better value. For even more savings, use a GoodRx coupon and pay just a fraction of the retail price.

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What Are The Side Effects

If you suffer from kidney disease, liver disease, bone marrow disorders, inflammatory bowel disease or a low white blood cell count, you should not take colchicine and usually means the elderly should refrain from taking it.

The side effects that I have personally experienced are usually diarrhea, going to the bathroom every few hours and stomach cramps on the days I take 3-4 right after an attack. Other side effects include vomiting and nausea. It is very important to pay attention on how colchicine affects you personally and allopurinol is a better drug for long term treatment of gout.

Also allopurinol should be slowly introduced after a gout attack because in the beginning it can also trigger a gout attack. Remember colchicine stops an attack in its tracks while allopurinol works to reduce the uric acid levels in your body. Colchicine is for limited use while allopurinol is for long term use.

Colchicine is also now available in capsule form in both generic and brand name form. The brand name for a capsule colchicine is Mitigare. Not all pharmacies sell colchicine so make sure to call ahead of time to find out.

Furthermore, on February 2019, it was announced that the FDA approved the first oral solution on colchicine for the treatment of gout flares. So now you can take colchicine orally for those 15% of elderly gout sufferers who have difficulty swallowing capsule or tablet drugs.

Characterization Of Colchicine Pharmacokinetics

Prior to the AGREE trial, the pharmacokinetics of low-dose colchicine , high-dose colchicine , and single-dose colchicine were evaluated in healthy volunteers who had fasted. None of these healthy volunteers participated in the AGREE trial. Colchicine, United States Pharmacopeia 0.6-mg tablets , was provided by URL Pharma . Pharmacokinetic sampling occurred over 96 hours. Analytic data from the samples were used to calculate Cmax, area under the curve 0, and terminal half-life. Statistical analyses were performed using WinNonlin software, version 5.0.1 .

Peak blood levels for single-dose, low-dose, and high-dose colchicine were 2.5, 6.19, and 6.84 ng/ml, respectively, in healthy volunteers, and exposure to colchicine was 14.1, 52.1, and 118.2 nanograms × hours/ml, respectively. The terminal half-lives for single-dose, low-dose, and high-dose colchicine were 6.36, 23.6, and 31.4 hours, respectively .

Figure 1

Pharmacokinetic properties of low-dose, high-dose, and single-dose colchicine in healthy normal volunteers. Peak blood concentrations were similar in the low- and high-dose colchicine groups, while total colchicine exposure was proportional to the total colchicine dose received. Values are the mean.

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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.

Role Of The Study Sponsor

URL Pharma funded the study and choose United BioSource Corporation to be the Contract Research Organization to run the study. Dr. Davis is the Chief Medical Officer for URL Pharma and had key roles in the study design, data collection, data analysis, and writing of the manuscript. Prior to the start of the study, URL Pharma agreed that the authors had full rights to submit the manuscript for publication, URL Pharma approval of the content of the submitted manuscript was not required, and publication of the manuscript was not contingent upon the approval of URL Pharma. The authors had full access to all data, and Dr. Terkeltaub made the final editorial decisions.

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New Evidence To Support The Use Of Low

Recent trial evidence demonstrates that low-dose colchicine is effective when prescribed within 12 hours of onset of an acute gout flare, with a low incidence of gastrointestinal adverse effects .1 A higher dose offered no additional clinical benefit, but increased the risk of gastrointestinal toxicity. This study was conducted in the United States, where colchicine is available as 0.6 mg tablets rather than the 0.5 mg tablets available in Australia.

Table 1 Safety and efficacy of low-dose colchicine in acute gout1

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.

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Preventing Gout Flares With Allopurinol And Colchicine

The American College of Rheumatology Guidelines for Management of Gout suggest that patients begin an anti-inflammatory medicine before or during ULT with medicines such as allopurinol.3 Specifically, the ACR recommends low-dose colchicine as an option for gout flare prevention in adults.3 Colchicine is the active ingredient in a medication called Mitigare® 0.6 mg Capsules, indicated for the prevention of gout flares in adults.8 The safety and effectiveness of Mitigare® for acute treatment of gout flares during prophylaxis has not been studied. Mitigare® is not an analgesic medication and should not be used to treat pain from other causes.

Colchicine 0.6 mg capsules are contraindicated in patients with renal or hepatic impairment who are currently prescribed drugs that inhibit both P-gp and CYP3A4. Combining these dual inhibitors with colchicine in patients with renal or hepatic impairment has resulted in life-threatening or fatal colchicine toxicity. Patients with both renal and hepatic impairment should not be given Mitigare®. The most commonly reported adverse reactions with colchicine are gastrointestinal symptoms, including diarrhea, nausea, vomiting, and abdominal pain. Click here for complete product information, including a patient Medication Guide.

Drug Interactions Increase Risk Of Colchicine Toxicity

Concurrently prescribing colchicine and inhibitors of cytochrome P450 3A4 or P-glycoprotein increases the potential for colchicine toxicity .2,5 The US Food and Drug Administration reported that of 117 cases of fatal colchicine toxicity at therapeutic doses , more than half occurred in patients who were taking clarithromycin at the same time.2 However, a possible role for renal impairment or prolonged colchicine dosing cannot be excluded in these cases.

Fatal and non-fatal colchicine toxicity has occurred in patients taking colchicine and concomitant erythromycin, cyclosporin, statins and calcium-channel blockers, including verapamil and diltiazem.2,12

Box 1Common inhibitors of CYP3A4 and/or P-gp that may increase the risk of colchicine toxicity2,12-14

Antiarrhythmics

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What If I Forget To Take It

If you forget to take your colchicine, take it as soon as you remember. Unless it’s nearly time for your next dose. In which case, skip the missed dose and take the next one at the usual time.

Never have 2 doses at the same time. Never have an extra dose to make up for a forgotten one.

If you forget doses often, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to remember your medicines.