Taking prescription painkillers with sleeping pills could lead to an overdose, scientists warn.
Combining opiods with benzodiazepines was linked to more hospital visits for the potentially fatal complication, a study found.
Researchers now say opioids should be prescribed cautiously among patients who are also taking benzodiazepines.
They also called for education programmes that warn doctors and patients about the risks of taking both medications at the same time.
In many countries, the increased use of prescription painkillers and the resulting potential for addiction and overdose represent a growing public health concern.
Nearly 30 per cent of fatal 'opioid' overdoses in the US also involve benzodiazepines.
That raises the possibility that some of the increase in opioid related deaths might be caused by simultaneous use of benzodiazepines.
Stanford University researchers set out to identify trends in concurrent use of a benzodiazepine and an opioid.
They wanted to identify the impact of the trends on admissions to hospital and emergency room visits for opioid overdose.
The study involved more than 300,000 people aged 18 to 64 who were prescribed the form of painkiller between 2001 and 2013.
They found that nine per cent of users also had a prescription for a benzodiazepine in 2001. This increased to 17 per cent in 2013.
Several factors that could have affected the results - such as age, sex and presence of other disorders - were then taken into account.