Colchicine and macrolide antibiotics: why the gout medicine dose matters

The NHS describes colchicine as a medicine mainly used to treat gout. It reduces pain and joint inflammation, and is used for a short time to relieve the symptoms of a gout attack and to prevent attacks that may happen when you first start taking other medicines for gout. It is also used to prevent symptoms of familial Mediterranean fever, a rare genetic condition.

The NHS page stresses that colchicine doses must not be taken closer together than your doctor has told you, because this can cause too much medicine to build up in the body and cause serious side effects. That is the same underlying concern as the interaction: anything that makes colchicine accumulate can have the effect of an overdose, even if the person has taken the prescribed amount.

Colchicine is often taken for a short time, which means an antibiotic may be prescribed by a clinician who has not seen the colchicine on the record. Saying so at the time is the simplest safeguard.

The BNF interaction list for colchicine includes entries for three macrolide antibiotics. For clarithromycin it says the antibiotic is predicted to increase the exposure to colchicine and the manufacturer advises avoiding potent CYP3A4 inhibitors or adjusting the colchicine dose. For erythromycin it says exposure is predicted to rise and the manufacturer advises adjusting the dose with moderate CYP3A4 inhibitors. For azithromycin it advises avoiding P-glycoprotein inhibitors or adjusting the dose. All three are rated severe, and the evidence is study for clarithromycin and erythromycin and theoretical for azithromycin.

The wording shows that the macrolides are not all treated identically, and that the advice offers a choice between avoiding the combination and changing the colchicine dose. Which applies is for the prescriber, who will take account of kidney function and the reason for treatment.

The same list contains entries for other medicines, such as verapamil, which is predicted to increase exposure with advice to adjust the dose, and atorvastatin, where colchicine has been reported to cause rhabdomyolysis, with advice of caution or monitoring. The NHS colchicine page names statins and heart medicines such as verapamil, diltiazem and digoxin on its list, so antibiotics are one part of a wider set.

The NHS lists the possible serious side effects of colchicine as too much of the medicine building up in the body, causing stomach pain, feeling sick, being sick and diarrhoea; bone marrow problems, with a high temperature, bruises or bleeding for a long time after an injury; nerve problems, with pain, tingling, loss of feeling and weakness; muscle and kidney problems, with muscle pain, weakness and dark red or brown pee; and allergic reaction.

It says to call 999 for anaphylaxis and NHS 111 for any other serious side effect, and says that if you have taken more than your prescribed dose you should call 111 and, if told to go to A&E, bring the packet and your other medicines and not drive yourself.

• Stomach pain, nausea, vomiting or diarrhoea.

• A high temperature, unusual bruising or prolonged bleeding.

• Muscle pain or weakness, or dark red or brown urine.

• Pain, tingling or loss of feeling.

If you take colchicine and an antibiotic is suggested, say so, and ask whether it is one of the macrolides. The NHS clarithromycin page lists colchicine for gout among the medicines that do not mix well, and asks you to check with a pharmacist or doctor. Do not take extra colchicine because pain has not settled.

The NHS also advises not drinking grapefruit juice while taking colchicine because it can increase the amount of the medicine in the blood, which can be dangerous.

In the NHS, the GP and the community pharmacist can check combinations at the point of prescribing or dispensing, and hospital teams review medicines on admission. Private clinicians work from the same BNF, but they only see the medicines you tell them about, so a written list of everything you take, including short courses and anything bought over the counter, is the safeguard that travels between services.