In short
Allopurinol is the first choice for most people with gout, and febuxostat is the main alternative when allopurinol cannot be used or cannot reach target. Both work through the same enzyme. The decision turns on kidney function, rash risk, cost and one cardiovascular safety question — not on which is stronger.
Reviewed by Dr. Ashish Baweja, DM Clinical Immunology & Rheumatology, AIIMS Rishikesh · last updated October 2026
Search this question and the first page is largely journal papers. That is a fair reflection of how it is argued among doctors and a poor reflection of what a person taking the tablet needs to know.
Both drugs are xanthine oxidase inhibitors: they block the enzyme that makes uric acid, so less is produced. Neither dissolves crystals directly. Both work by holding the level low enough, for long enough, that the deposits already in the joints break down on their own.
Why allopurinol is usually first
It has been in use since the 1960s, which means its behaviour over decades is known rather than estimated. It is inexpensive and available everywhere in India. It can be titrated finely, from 100 mg upwards. And in the large majority of people it gets the level below target if the dose is actually increased until it does.
That last clause carries most of the weight. The commonest reason allopurinol is declared a failure is that it was left at 100 mg and never rechecked. Doses of 300 mg are routine, and higher doses are used under supervision where kidney function allows.
What febuxostat offers
Febuxostat is newer, more expensive, and used mainly in three situations:
- Allopurinol caused a rash or another reaction.
- Allopurinol could not reach target, even at an appropriate dose.
- Kidney impairment makes allopurinol dosing awkward. Febuxostat is cleared more by the liver, so it needs less adjustment in mild to moderate kidney disease.
It is also a simpler prescription — typically 40 mg, increased to 80 mg if the target is not met — which is occasionally the deciding factor in someone already taking a long list of tablets.
The heart safety question, properly stated
This is where the internet becomes unhelpful, so it is worth being precise.
A large randomised trial called CARES compared febuxostat with allopurinol in people with gout who already had cardiovascular disease. Overall major cardiovascular events were similar between the two, but deaths from cardiovascular causes and from all causes were higher in the febuxostat group. On the strength of that, the US regulator added a boxed warning and advised reserving febuxostat for people in whom allopurinol does not work or is not tolerated.
A later European trial, FAST, in a population at lower cardiovascular risk, did not find febuxostat inferior to allopurinol on cardiovascular outcomes.
What a sensible clinician takes from two trials that disagree: in someone with established heart disease, prefer allopurinol unless there is a clear reason not to. In someone without it, febuxostat is a reasonable second line. This is exactly the kind of question to raise directly at an appointment rather than settle from a forum post.
Allopurinol and the rash that matters
Most allopurinol side effects are mild. One is not.
A small number of people develop a severe hypersensitivity reaction, with widespread rash, fever and organ involvement. It is rare and it is serious. Three things reduce the risk:
- Starting at a low dose and increasing slowly, rather than beginning at 300 mg.
- Dose adjustment in kidney impairment, since reduced clearance raises risk.
- **Awareness of HLA-B*58:01**, a genetic variant that raises risk substantially and is commoner in some Han Chinese, Thai and Korean populations. Testing is recommended in those groups in some guidelines; it is not routine practice in India.
Any new widespread rash after starting allopurinol means stopping the tablet and seeking advice the same day. Not waiting to see whether it settles.
What the two have in common
More than separates them.
- Both are started after an attack has settled, not during one. What to do during an attack covers that.
- Both can trigger attacks in the first months as deposits break up, so both are usually given with preventive cover — commonly low-dose colchicine — for three to six months.
- Both are adjusted to a target level, below 6 mg/dL, or below 5 where there are tophi.
- Both are continued long term. Stopping either allows the level to climb and the deposits to re-form.
- Neither should be stopped because an attack occurs.
When urate-lowering treatment is needed at all sets out who should be on one of them in the first place.
Interactions worth knowing
Azathioprine and mercaptopurine are the serious ones. Both allopurinol and febuxostat block the enzyme that clears these drugs, and the combination can cause dangerous bone marrow suppression. If you take azathioprine for inflammatory bowel disease, a transplant or an autoimmune condition, this must be flagged before either drug is started.
Warfarin levels may need closer watching when allopurinol is started.
Diuretics raise urate and work against the treatment; whether they can be changed is a question for whoever manages your blood pressure.
Cost, honestly
Allopurinol is among the cheaper long-term medicines available in India. Febuxostat costs noticeably more, and the difference compounds over a treatment that is measured in years rather than months.
That matters clinically, not just financially: the best urate-lowering drug is the one that is still being taken in three years. A cheaper tablet taken continuously beats a better tablet abandoned after six months.
Why the level has to be rechecked
The single most useful thing you can do on either drug is make sure somebody looks at the number again after the dose is set.
The sequence that works: start low, recheck the urate after two to four weeks, increase if it is above target, recheck again. Repeat until the level is where it should be. Then check periodically — a few times in the first year, annually thereafter — along with kidney function and liver tests.
The sequence that fails: start, never recheck, assume. Years later the level is still above target, attacks continue, tophi grow quietly, and everybody concludes the treatment does not work.
If you are on one of these tablets, you should be able to answer two questions: what is my target, and what was my last reading? If you cannot, that is the thing to fix.
What happens to the deposits
It is worth knowing what success looks like, because it is slow and undramatic.
Once the level is held below the point at which urate crystallises, the deposits already in the joints begin to dissolve. This takes months to years, not weeks, and the lower the level the faster it goes — which is why a lower target is chosen when there are tophi.
Over that period: attacks become less frequent and then stop; visible tophi soften, shrink and eventually disappear; and the joint damage that has already occurred stays, which is the argument for starting earlier rather than later.
People who stop once the attacks settle undo this. The level climbs back within weeks and the deposits re-form over the following year or two, usually quietly, until the next attack.
What good treatment looks like
1. Treatment starts once the joint has settled.
2. A low starting dose, with preventive cover alongside.
3. Urate measured after a few weeks, and the dose increased if it is not under target.
4. Repeat until the target is reached.
5. Then periodic checks of the level and kidney function, and the tablet continued.
If you are on a urate-lowering tablet and have never been told your target level — or have never had the level rechecked after the dose was set — that is worth raising. You can request a callback or book a consultation.
Neither drug is a painkiller, and neither does anything useful for an attack that is happening right now. What they do is make the next one less likely, and the one after that less likely still, until the deposits are gone.
Common questions
Which is better, febuxostat or allopurinol?
For most people, allopurinol, because it is well understood, inexpensive and effective when the dose is increased to target. Febuxostat is the main alternative when allopurinol causes a reaction, cannot reach target, or is awkward because of kidney impairment.
Is febuxostat safe for the heart?
The CARES trial, in people who already had cardiovascular disease, found similar overall major cardiovascular events but higher cardiovascular and all-cause deaths with febuxostat than allopurinol, which led to a regulatory warning. The later FAST trial, in a lower-risk population, did not find febuxostat inferior. In practice, allopurinol is preferred where there is established heart disease.
Can I switch from allopurinol to febuxostat?
Yes, and it is a common change when allopurinol has not reached target or has caused side effects. The switch is made between attacks, and the urate level is rechecked a few weeks later to confirm the new dose is working.
What are the main allopurinol side effects?
Most are mild — stomach upset, or a mild rash. The important one is a rare severe hypersensitivity reaction with widespread rash, fever and organ involvement. Any new widespread rash after starting allopurinol means stopping the tablet and getting advice the same day.
Do I take these tablets during a gout attack?
If you are already established on one, continue it through the attack. Do not start either one in the middle of an attack — beginning urate-lowering treatment while a joint is inflamed can prolong it.
Does febuxostat need a dose change in kidney disease?
Less adjustment than allopurinol in mild to moderate kidney impairment, because it is cleared more by the liver. That is one of the reasons it is chosen in people with reduced kidney function, though the decision also depends on heart disease and cost.
Sources
- American College of Rheumatology — gout rheumatology.org
- NHS — allopurinol www.nhs.uk
- MedlinePlus — allopurinol medlineplus.gov
- NIAMS — gout treatment www.niams.nih.gov
This article is general information and does not replace a consultation.