NPC Archive Item: New Drug Safety Update from MHRA/CHM (May 2009)

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7th May 2009

The MHRA and CHM have published the May edition of Drug Safety Update. This edition gives drug safety advice on Aliskiren▼ (Rasilez®), ACE inhibitors and A2RAs during breastfeeding, renal impairment with NSAIDs, orlistat as a non-prescription medicine and oral salicylate gels.

Drug Safety Update (DSU) is an essential read for everyone whose professional practice involves medicines. It is published every month in electronic format only

Aliskiren▼ (Rasilez®): risk of angioedema and renal dysfunction
The MHRA have warned that angioedema may occur with use of aliskiren▼ (Rasilez®), the first of a new class of medicine that directly inhibits renin, and that it should not be used in patients who have previously had angioedema after using it. They also warned that aliskiren should be used with caution in patients taking non-steroidal anti-inflammatory drugs (NSAIDs), or in patients who may be at increased risk of acute renal failure, as there have been reports of acute renal failure in patients with risk factors for renal dysfunction.

The current MHRA warnings about the use of aliskiren and angiodema, renal dysfunction and caution with NSAIDs add to our already cautious view about this product (see previous blog). Data on the long-term safety of aliskiren plus renal and cardiovascular morbidity/mortality are required before its place in therapy can be more clearly determined.

ACE inhibitors and angiotensin II receptor antagonists: recommendations on use during breastfeeding
ACE inhibitors and angiotensin II receptor antagonists (A2RAs) should not be used by breastfeeding mothers in the first few weeks after delivery because of possible profound neonatal hypotension; preterm babies may be at particular risk. In mothers who are breastfeeding older infants, the use of captopril, enalapril, or quinapril may be considered.

An earlier issue of Drug Safety Update (December 2007) warned that ACE inhibitors and A2RAs should not be used at any stage of pregnancy, as exposure during pregnancy has been associated with adverse kidney effects and other congenital anomalies. Use in women who are planning pregnancy should be avoided unless absolutely necessary, in which case the potential risks and benefits should be discussed.

ACE-inhibitors and A2RAs are used in a number of indications, and “increasing low cost prescribing of drugs affecting the renin-angiotensin system” is one of four Better Care, Better Value Indicators relating to prescribing recently released by the NHS Institute for Innovation and Improvement (see previous blog for details). NPC will soon include specific resources which will help prescribers and prescribing teams address therapeutics and implementation issues arising from this indicator. In the interim please see the hypertension section, the post-MI section, the heart failure section, the stroke section and the type 2 diabetes section. ACE inhibitors and A2RAs are also used in chronic kidney disease, for which there is NICE guidance.

Non-steroidal anti-inflammatory drugs: reminder on renal failure and impairment
The MHRA has warned that they continue to receive case reports of renal failure in NSAID users, despite prescribing information for NSAIDs including warnings about renal impairment and renal failure. NSAIDs (including COX-2 inhibitors) may rarely precipitate renal failure, and vulnerable (particularly elderly) patients may be at increased risk. It is estimated that NSAID use accounts for about 15% of all cases of drug-induced acute renal failure. A case-control study estimated an increased relative risk (3.2 [95% confidence interval [CI] 1.8–5.8]) of acute renal failure in otherwise healthy current users of NSAIDs.

Patients at risk of renal impairment or renal failure (particularly elderly people) should avoid NSAIDs if possible. If NSAID treatment is absolutely necessary, then the lowest effective dose for the shortest possible duration should be used to control symptoms. The renal function of such patients should be carefully monitored during NSAID treatment. It is important to consider other concomitant disease states, conditions, or medicines that may precipitate reduced renal function when prescribing NSAIDs.

The February edition of Drug Safety Update, reported that all users of NSAIDs may be at some increased thrombotic cardiovascular (CV) risk, although the absolute risk for ‘healthy’ users is low. Reassuringly, since November 2007, primary care prescribing data in England indicates that there has been a significant decrease in diclofenac prescribing, accompanied by a significant increase in naproxen prescribing. This coincides with our initiatives here at the NPC to encourage medication review and more appropriate prescribing of NSAIDs with better risk profiles, taking into account both their CV and gastrointestinal risks and individual patient risk factors (see MeReC Monthly No 13, April 2009 for details).

Orlistat: key safety information to support pharmacy availability
Following a European recommendation, orlistat 60mg capsules are now available in pharmacies (under the brand name alli) as a non-prescription medicine to aid weight loss in conjunction with a reduced-calorie, lower-fat diet. Orlistat remains available as 120mg capsules on prescription (under the brand name Xenical).

This article in the May edition of Drug Safety Update outlines the key safety information that pharmacists should consider when supplying alli (see the full article for details). alli can be recommended for adults (age 18 years or older) who have a BMI of at least 28kg/m2. It is not suitable for women who are pregnant or breastfeeding. Pharmacists should ensure that patients are not allergic to any of the ingredients in alli, and that they do not have chronic malabsorption syndrome or cholestasis. Training material for staff is available via More information on orlistat can be found on the obesity section of NPC.

New advice on oral salicylate gels for those younger than 16 years
The MHRA has reviewed the safety of oral topical salicylate-containing products after publication of a case report of suspected Reye’s syndrome associated with use of a dental gel that contained choline salicylate in a 20-month-old child. The CHM acknowledged that although there is only a theoretical risk of Reye’s, these products should be contraindicated in those younger than age 16 years in line with other oral salicylate containing preparations. This decision affects four products currently licensed in the UK: Bonjela; Bonjela Cool Mint; Dinnefords Teejel Gel (not marketed); and Pyralvex. More information on this issue can be found in the MHRA press release.

Other articles in this issue of Drug Safety Update include:

  • Patients reporting through the Yellow Card Scheme (see
  • Food Standards Agency warning about the risk of serious liver damage with Fortodol (the food supplement also sold as Miradin)
  • Patient Information Leaflet of the month: Caverject

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