Statins with macrolide antibiotics, azole antifungals and other CYP3A4 inhibitors

CYP3A4 is a family of liver and gut enzymes that handles many medicines. Simvastatin and, to a lesser extent, atorvastatin are cleared this way. If another medicine inhibits CYP3A4, less statin is removed and the blood level rises, increasing the chance of muscle toxicity.

That is why interaction lists for statins contain so many unrelated medicines. They are united by a shared effect on this enzyme rather than by their purpose. The grapefruit story in our other guides is the dietary version of the same principle.

The NHS statins page lists clarithromycin and erythromycin as problematic with statins, and the NHS clarithromycin page names statins such as simvastatin and atorvastatin among the medicines to check. Fusidic acid appears on the simvastatin and atorvastatin lists too.

When one of these antibiotics is needed, a prescriber may choose another antibiotic or advise a temporary pause of the statin. Which is right depends on the infection and the dose, so the decision should be made with the prescriber rather than by the patient.

The NHS simvastatin page lists itraconazole and ketoconazole, the atorvastatin page lists itraconazole or fluconazole, the NHS statins page lists fluconazole, and the NHS fluconazole page names statins among its interacting medicines. Antifungal courses for thrush or nail infections can therefore matter, even though they seem unrelated to the heart.

Tell the prescriber or pharmacist you take a statin before accepting an antifungal, including tablets bought after a pharmacy consultation.

• Itraconazole and ketoconazole with simvastatin.

• Itraconazole and fluconazole with atorvastatin.

• Fluconazole named on the NHS statins page.

Amlodipine, diltiazem and verapamil appear on the simvastatin list, with diltiazem and verapamil on the atorvastatin list. Ciclosporin used after a transplant, HIV and hepatitis C antivirals, nefazodone and danazol complete the simvastatin list, and the atorvastatin page adds fibrates, warfarin and St John's wort.

Many of these are long-term medicines, so a prescriber usually plans the statin choice and dose around them from the start. If a medicine is added later, the statin may need review.

Muscle pain is listed by the NHS as a common side effect of statins. Pain that is new, unexplained, widespread, severe or accompanied by weakness or dark urine after starting a combination warrants prompt medical advice. Our statin muscle problems guide explains how this is assessed.

Do not stop the statin without speaking to a professional unless told to; instead report symptoms quickly so that tests and a decision can be made.

Say you take a statin. Ask: does this interact? Is there an alternative? Do I need to pause the statin, and for how long? Ask the pharmacist to check against your full list, including herbal products, as the NHS atorvastatin page names St John's wort.

Keep a note of the statin name and strength, since different statins have different interaction profiles. A review of the statin choice can be requested if you often need interacting medicines.