Eplerenone and ketoconazole: a combination the BNF says to avoid

The NHS says eplerenone is usually taken for heart failure. It helps to keep symptoms under control and reduce the risk of the heart getting weaker by reducing blood pressure, controlling the amount of salt and water in the body and improving heart function. It works by blocking the action of a hormone called aldosterone.

Eplerenone also affects potassium. The NHS says taking it can raise the level of potassium in the blood, which can cause muscle cramps and diarrhoea, and that blood tests are done regularly. Anything that raises the amount of eplerenone in the body can add to that effect, which is why the list of interacting medicines is taken seriously.

The NHS interactions page for eplerenone lists a long set of medicines to discuss with a doctor or pharmacist before starting. It includes ramipril, enalapril, losartan and candesartan, tacrolimus or ciclosporin, antibiotics such as trimethoprim, clarithromycin, erythromycin or rifampicin, digoxin, lithium, painkillers such as ibuprofen, antifungals such as itraconazole or fluconazole, epilepsy medicines, spironolactone or amiloride, and warfarin.

Many people know ketoconazole as a cream or shampoo for athlete's foot, dandruff and similar skin problems. The NHS page for ketoconazole describes it as an antifungal medicine used to treat skin infections caused by a fungus, which is available as a cream or shampoo from pharmacies and shops or on prescription.

The same NHS page says that only tiny amounts are absorbed into the body when it is used as a cream or shampoo, and that these skin treatments can usually be used while taking most medicines. That is a reassuring point, but it is not a statement that covers eplerenone specifically, so a person with heart failure who is unsure should ask a pharmacist.

The page also notes that ketoconazole tablets usually only treat a rare condition called Cushing's syndrome, are available on prescription only, and are not covered on the page. The BNF interaction concerns the medicine as a whole, and the relevance is greatest for the form that is swallowed.

The BNF interaction list for eplerenone states that ketoconazole is predicted to markedly increase the exposure to eplerenone, that the manufacturer advises avoid, and that the severity is severe, with the evidence type given as study.

The same list uses the avoid wording for itraconazole and clarithromycin, and says erythromycin is predicted to increase eplerenone exposure with advice to adjust the dose. Taken together, the entries point to a group of medicines that slow the breakdown of eplerenone, so a prescriber choosing an antifungal or antibiotic for someone with heart failure has to check which one is being proposed.

If you take eplerenone and are prescribed an antifungal tablet or capsule, mention the eplerenone at the time and ask the pharmacist to check the choice against the BNF. If you only plan to use an over-the-counter cream or shampoo, ask the pharmacist, who can advise on that product.

• Carry a current list of your medicines, including supplements.

• Avoid potassium supplements and salt substitutes unless advised, because the NHS says they can push potassium too high with eplerenone.

• Do not stop eplerenone on your own. The NHS says it is important to keep taking it even if you feel well.

• Keep your blood test appointments, since they are how potassium and kidney function are tracked.

The NHS lists muscle cramps and diarrhoea as possible effects of high potassium with eplerenone. The sources read for this guide do not give a specific emergency symptom list for this pair, so ordinary safety advice applies. Contact your GP, pharmacist or NHS 111 if you develop muscle weakness, cramps, a very irregular heartbeat or feel unwell after a new medicine, and call 999 for collapse, chest pain or severe breathlessness.

In the NHS the heart failure team, GP and pharmacist share the job of keeping the medicine list safe. Private clinicians should be given the same list.