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EMA to carry out four safety reviews

And recommends against combination of medicines affecting RAS system in latest PRAC highlights


The European Medicines Agency (EMA) is to assess the safety of four treatment regimens after concerns about each one were raised by national regulators.

The reviews were announced following the meeting of the EMA's Pharmacovigilance Risk Assessment Committee (PRAC), which also recommended not using the combination of medicines affecting the renin-angiotensin (RAS) system.

Treatments to be reviewed by the EMA include any medicine containing ambroxol or bromhexine, which both are used to clear the airways.

Belgium's medicines regulator the AFMPS requested the review after incidences of allergic reactions increased among people taking ambroxol. The review was widened to include bromhexine as this is converted to ambroxol in the body.

Medicines containing codeine will also be assessed by the EMA after the German medicines agency BfArM requested an EU-wide review due to the risk of morphine toxicity.

The EMA will assess the use of these drugs when used to treat coughs and cold in children. In its review announcement, the EMA said that codeine is concerted into morphine in the body, but some patients have a faster metabolism process meaning a child could end up with higher than normal levels of morphine in the blood.

There area already measures to reduce the risk of such toxicity when codeine is used as pain relief, but the review will determine if this should extend to situations where codeine is used to treat coughs and cold.

The PRAC also upheld a request from the Norwegian medicines agency NOMA to review oral methadone medicines containing povidone following a number of reports of kidney failure in people who abuse the drug.

These oral medicines are meant to be used in rehabilitation programmes in patients dependent on opioids, such as heroin, to prevent or reduce withdrawal symptoms, but some patients are injecting the drug into a vein, potentially leading a dangerous accumulation of povidone inside the cells of vital organs.

Norway has suspended the only methadone-containing oral solution that contains povidone and the EMA will now determine if wider limitations are necessary.

The final review decided by PRAC is that of testosterone-containing medicines after the Estonian medicines agency raised concerns about heart risk of such drugs, which are generally used as replacement therapies for men who do not produce enough testosterone.

As with the other reviews, the EMA will analyse all available data on the treatments and issue an opinion at a later date.

RAS-acting agents can be dangerous in combination

One recommendation already announced by PRAC is its decisions to advise against combining any two of the three main classes of medicines that affect the  body's RAS hormone system – the system to control blood pressure and the volume of fluids in the body.

These classes are: angiotensin-receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors and direct renin inhibitors.

Medicines that fall into this category are often used in combination to treat high blood pressure and congestive heart failure but, according to the EMA's review, combining several RAS-acting agents could increase the risk of high potassium levels in the blood, low blood pressure and poor kidney function.

A particular warning was made that patients with diabetes-related kidney problems should not be given an ARB with an ACE-inhibitor.

The PRAC recommendation will now be forwarded to the EMA's Committee for Medicinal Products for Human Use (CHMP) to adopt a final opinion.

Article by
Thomas Meek

14th April 2014



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