Nearly one in five patients on a common statin are also prescribed contraindicated drugs that could increase the risk of side effects, a New Zealand study has found.

The University of Otago study, published in the New Zealand Medical Journal today, found that New Zealand prescribers do not always follow guidelines when prescribing other medicines to patients taking the common statin, simvastatin,

Simvastatin is one of the three main cholesterol-lowering statins prescribed in New Zealand to prevent major cardiovascular events such as heart attacks and stroke. But prescribers have to be careful to follow guidelines as some contraindicated medicines can inhibit the enzyme (CYP3A4) that metabolises simvastatin – leading to high levels of simvastatin in the blood and the risk of adverse side effects.

The study cohort used national datasets to analyse the prescribing records for 350,000 patients who initiated simvastatin therapy in New Zealand between 2006 and 2013. The median duration on simvastatin was 2.1 years.

The study looked at the how many people on simvastatin were prescribed medicines that were CYP3A4 inhibitors – either completely ‘contraindicated’ in users of simvastatin or those that should only be ‘used with caution’ and careful management of simvastatin dose.

The researchers found that despite the existence of prescribing guidelines and patient management software – which alerts prescribers to potential drug interactions – 11 per cent of patients were dispensed a contraindicated medicine during the first two years of simvastatin use and 16 per cent were dispensed a use-with-caution medicine.

These proportions increased over time and by seven years, 17 per cent of patients had been dispensed a contraindicated medicine and 26 per cent had been dispensed a use-with-caution medicine.

In the majority of cases, the prescriber of simvastatin and the contraindicated or use-with-caution medicine were the same.

One of the study’s authors, Dr Lianne Parkin of the Department of Preventive and Social Medicine, says a large number of patients received a contraindicated or use-with-caution medicine on more than one occasion.

“These co-prescribing events were not always isolated incidents – for many patients they occurred more than once.”

The study found that the most common contraindicated drugs co-prescribed with simvastatin were: clarithromycin, erythromycin, fluconazole, itraconazole, miconazole, and the combination therapy of omeprazole, amoxicillin and clarithromycin.  The most common use-with-caution drugs co-prescribed were amiodarone, amlodipine, bezafibrate, diltiazem and verapamil.

The researchers also found that substantial proportions of the patients co-prescribed use-with-caution medicines were taking simvastatin at a higher daily dose than recommended at the time of the dispensing.

Co-investigator, Joshua Quon, a student at the Dunedin School of Medicine, says it was important to undertake this research because overseas studies had found concerning levels of use of CYP3A4 inhibitors in people taking certain cholesterol-lowering drugs, but it was not known what was happening in New Zealand.

Further work is required to explore and address the reasons for such co-prescribing, he says.

The study was was funded by a Strategic Research Grant from the Department of Preventive and Social Medicine and the Phyllis Paykel Memorial Summer Scholarship.

Publication details:
Quon J, Parkin L, Sharples K, Barson D. Co-prescribing of contraindicated and use-with-caution drugs in a national cohort of new users of simvastatin: how well are prescribing guidelines followed? New Zealand Medical Journal 2018;131:1474

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