How long to take colchicine when starting allopurinol

Perspective from David A. McLain, MD, FACP, FACR

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Despite its increased cost in the United States, colchicine use to prevent gout flares while starting treatment with allopurinol remains “very cost effective,” according to findings published in Arthritis Care & Research.

“Allopurinol is the core therapy for gout, and starting it can be challenging because it can actually precipitate flares of gout,” Philip C. Robinson, MBChB, PhD, FRACP, of Royal Brisbane and Women’s Hospital, and the University of Queensland, in Australia, told Healio Rheumatology. “Using colchicine prophylaxis when commencing allopurinol is very important to preventing flares and making sure people continue on the allopurinol, and consequently control their gout. However, it can be very expensive in the United States, and there may be push back from insurers to fund this drug as well as allopurinol.”

Colchicine to prevent gout flares while starting treatment with allopurinol is “very cost effective,” according to findings. Source: Adobe Stock

To examine the cost effectiveness of using colchicine to prevent gout flares while starting allopurinol treatment, Robinson and colleagues performed a series of analyses from the point of view of the third-party payer in both the United States and Australia. Using TreeAge Software, they developed a twoarm decision tree with one arm starting allopurinol with no colchicine prophylaxis, and the other with colchicine.

Model inputs were collected from published literature where available. The researchers then performed a univariate and probabilistic sensitivity analysis to confirm the robust nature of the modeling. The time frame used for the model was 6 months.

Philip C. Robinson

According to the researchers, the colchicine-prophylaxis arm demonstrated a cost of U.S. $1,276 and 0.49 quality-adjusted lifeyears, while the cost in the non-colchicine arm was U.S. $516 and 0.47 quality-adjusted lifeyears, with an incremental costeffectiveness ratio of U.S. $34,004 per quality-adjusted lifeyear gained.

In Australia, where colchicine is much less expensive, the colchicine arm cost AUS $208, compared with AUS $415 in the placebo arm. The researchers’ univariate and probability sensitivity analysis demonstrated that the results were robust to changes in input parameters.

Meanwhile, the probabilistic sensitivity analysis found that the probability of colchicine prophylaxis being the most cost-effective option was 93% in the United States and 100% in Australia.

“The key takeaways are that as well as being very clinically effective at preventing flares, [colchicine] is also very cost effective, and there should be few barriers to prescribe it,” Robinson said. “Along with other work we have done that shows that it is very safe, it should be used if at all possible when commencing allopurinol.”

David A. McLain, MD, FACP, FACR

Colchicine is a naturally occurring compound that has been used since 1500 BC by the pharaohs of ancient Egypt as recorded in an ancient Egyptian medical papyrus. It is considered mankind’s oldest anti-inflammatory medication. Colchicine has been used to treat and prevent acute gout attacks and to prevent attacks of familial Mediterranean fever. It is also used off-label in Behcet’s disease and to prevent pericarditis.

The drug was approved by the FDA in 1961, when many commonly used drugs at that time were ‘grandfathered’ in. However, a controversy occurred in 2009 when colchicine was approved as an NDA by the FDA under the brand name Colcrys from URL Pharma (now Takeda Pharmaceuticals) and all generics were removed from the United States market. This was prompted by the U.S. Unapproved Drug Initiative in 2006 which required older ‘grandfathered’ drugs to undergo modern testing.

As a result, colchicine (as Colcrys) increased 2000% in price, during which time, many patients suffered as they could no longer afford their medication and rheumatologists decreased use of this medication.

The present study used $4.73 for the cost of a colchicine tablet in the U.S. We would tell patients that “colchicine went from 5 cents to 5 dollars per tablet” – in contrast, the cost of colchicine in Australia is US$0.37 per tablet. This study used a prophylactic dose of colchicine of 0.6 mg PO BID, continued for 6 months. Even with the increased U.S. cost of colchicine, the data and modelling in this paper found that colchicine prevented gout flares whilst instituting allopurinol and that it was cost effective; information that can be helpful with insurers and pharmacy benefit managers.

David A. McLain, MD, FACP, FACR

Executive director, Alabama Society for the Rheumatic Diseases

Symposium director, Congress of Clinical Rheumatology

Disclosures: McLain reports no relevant financial disclosures.

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Allopurinol is used for the long-term treatment and prevention of gout. Taken regularly, it can stop attacks of gout and help prevent damage to your joints.

Gout occurs in people who have high levels of urate in their blood. Every day, the body naturally produces urate. This normally dissolves in your blood until it is passed out of the body, mainly in your pee.

But if too much urate is produced, or your body cannot get rid of it properly, urate crystals can form in and around your joints. These crystals can slowly form for years without you knowing. Once many crystals have formed, they can shed into the joint, causing painful inflammation.

Allopurinol works by lowering the amount of urate in your blood. Because of this, it’s sometimes called a urate lowering therapy (ULT). Once your urate level is low enough, new crystals will stop forming and existing crystals will slowly dissolve.

After a few years, all the crystals may dissolve. If this happens, there will be no more joint damage or gout attacks caused by these crystals, as long as you are taking allopurinol.

Because it can take a long time to dissolve the crystals, you may have more attacks of gout while this is happening. This is more likely if your urate levels are very high to begin with, or if you have had gout for a long time.

If this happens to you, it does not mean that the allopurinol is not working.

Allopurinol is often recommended as the first choice of treatment to control gout. If your doctor prescribes it as soon as you are diagnosed, it may prevent future attacks and joint damage.

You will usually be offered allopurinol if blood tests show that your urate level is high enough for urate crystals to form, especially if one or more of the following applies:

you are having frequent attacks of gout.
your joints have been damaged by gout.
your skin has visible deposits of urate crystals. These are firm white lumps, which are called tophi.

You may not be offered allopurinol, or you may be given a lower dose, if you:

have ever had an allergic reaction to allopurinol.
are currently having an attack of gout.
have problems with your liver or kidneys.
are of Han Chinese, Thai or Korean origin.
have thyroid problems.

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 you’re 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 doesn’t treat the immediate pain caused by attacks of gout. But it’s 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 doesn’t 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.

To reduce the effects of gout attacks in the first three to six months of taking allopurinol, your doctor may prescribe a low dose of colchicine or a non-steroidal anti-inflammatory drug (NSAID), such as:

etoricoxib
ketoprofen
naproxen

You should be offered another tablet, known as a proton pump inhibitor, to protect your stomach while taking NSAIDs. If you cannot take NSAIDs, colchicine or steroids may be given instead.

Some drugs interact with allopurinol, so you should discuss any new medication with your doctor before starting it. You should also tell anyone else treating you that you’re taking allopurinol.

Do not use complementary treatments, such as herbal remedies, without discussing this first with your doctor or pharmacist. Some of them could react with allopurinol.

You should avoid taking aspirin while you’re being treated for gout. If you’re in pain, you can take paracetamol and NSAIDs. But remember you should only take one NSAID at a time – so do not take another if you have already been prescribed one to reduce the effects of gout attacks.

Allopurinol can also react with drugs that are often prescribed for high blood pressure, such as bendroflumethiazide, indapamide, lisinopril, ramipril.

Allopurinol reduces the breakdown of azathioprine, which is used to treat conditions such as rheumatoid arthritis and lupus. Your doctor may change your dose of azathioprine to account for this.

It can also reduce the breakdown of the leukaemia drug mercaptopurine, so the dose of mercaptopurine will need to be reduced if you take this drug.

Allopurinol may also increase the risk of developing a rash if you take them with the antibiotics ampicillin or amoxicillin.

Allopurinol may also increase the effect of warfarin and other drugs that thin the blood. These are known as anticoagulants. If you’re taking blood thinners, you may need your clotting time tested more frequently to check you’re still on the right dose.

Vaccinations

You can have vaccinations while on allopurinol.

Having an operation

If you need surgery, your doctor will discuss with you whether you should continue taking allopurinol.

Allopurinol can be continued when you have surgery but, your doctor may recommend that you temporarily stop allopurinol and then restart it again 5-7 days later at the same dose.

If you still have urate crystals in your joints, an operation can trigger an acute attack, usually within the first few days of the surgery, while you are still in hospital.

It's important to discuss any medications with your doctor before having surgery.

Alcohol is not thought to affect allopurinol. However, alcohol increases the amount of urate in the blood, and excessive drinking can trigger an attack of gout.

Guidelines state that adults shouldn’t have more than 14 units a week, and that they should spread them out over the course of the week. In some circumstances your doctor may advise lower limits.

You can find out more about units of alcohol at www.drinkaware.co.uk.

Allopurinol is unlikely to affect your fertility. However, it is not recommended during pregnancy or while you are breastfeeding, because we don’t know what effect it may have on your baby.

Talk to your doctor if you’re planning a family or become pregnant while taking allopurinol, they may be able to recommend a safe alternative treatment.