NPC Archive Item: December Drug Safety Update from MHRA/CHM

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11th December 2008

The MHRA and CHM have published the December edition of Drug Safety Update. This issue gives drug safety advice on two issues. Firstly, neurological and haematological toxic effects with prolonged use of nitrous oxide. Secondly, progressive multifocal leukoencephalopathy with the monoclonal antibodies rituximab and efalizumab▼. There is also an end-of-year quiz highlighting some of the important safety topics from the past year.

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

Topics covered included:

Nitrous oxide

  • Neurological and haematological toxic effects can occur with prolonged use of nitrous oxide. For this reason, nitrous oxide should not be given continuously for more than 24 hours, or more frequently than every 4 days, without close clinical supervision and haematological monitoring.
  • Neurological toxic effects can occur without preceding overt haematological changes.
  • Assessment of vitamin B12 levels should be considered before nitrous oxide anaesthesia in people with risk factors for deficiency of this vitamin. Specialist haematological advice should be sought as appropriate.

Rituximab and efalizumab
Progressive multifocal leukoencephalopathy (PML) has been reported in association with the use of some monoclonal antibodies. Patients should be monitored regularly for neurological symptoms or signs that might suggest PML. If PML is suspected, treatment must be suspended until PML has been excluded.

76 cases of confirmed or suspected PML have been reported in patients treated with rituximab, mainly when used in oncological indications. In June 2008, the first report of PML in a patient with rheumatoid arthritis treated with rituximab was received. PML was diagnosed 18 months after the last dose of rituximab; the patient had also been exposed to chemotherapy for oropharyngeal cancer, which could have been relevant in this case.

Reports of two cases of PML in patients treated with efalizumab (Raptiva) were received in September and November 2008, respectively. The patients had been treated with efalizumab for more than 3 years and died about 2 months after the onset of neurological symptoms.

The September issue of DSU reported two European cases of PML in patients with multiple sclerosis who received natalizumab (Tysabri).

Yellow Card Scheme update
This article highlights notable achievements from 2008 e.g. data from the scheme have been an important source of information about the benefit-risk profiles of varenicline and rimonabant.

An end-of-year quiz to test your drug-safety knowledge.

Conventional (typical) antipsychotics: increased mortality in dementia
The EMEA has concluded that conventional (typical) antipsychotics are associated with increased mortality when used in elderly people with dementia. See related blog for details.

Prograf and Advagraf (tacrolimus): serious medication errors
Prograf and Advagraf contain the immunosuppressant tacrolimus, but are given according to different dosing schedules. Medication errors have resulted in patients being dosed incorrectly, which has caused serious adverse reactions. Particular care should be taken in prescribing and dispensing the correct brand of tacrolimus (i.e., Prograf or Advagraf) and substitution should be made only under close supervision of a transplant specialist.

Norfloxacin: restricted use in urinary infections
The EMEA has advised that norfloxacin (Utinor) should not be used to treat acute or chronic complicated pyelonephritis. The CHMP concluded that this indication should be withdrawn because efficacy has not been adequately shown for this type of infection, and because the benefits of norfloxacin do not outweigh the potential risks in this indication.

Hedrin: keep treated hair away from sources of fire
Pharmacists are asked to remind parents and patients who purchase Hedrin (which contains dimeticone and is used in the treatment of headlice) to ensure that hair is kept away from sources of fire e.g. cigarettes while treatment is under way.

Melanotan: an unlicensed medicine, the risks of which are unknown
Melanotan I and II are types of peptide hormones that increase the levels of the pigment melanin in the body. The MHRA is aware that melanotan is being sold, against the law, on various websites and in some tanning salons and gyms as an injectable product that gives the effect of a ‘suntan’. Melanotan is an unlicensed medicine in the UK: its quality, safety, and efficacy have not been established. In addition, it has to be reconstituted with water for injection before subcutaneous administration. Therefore, the risk to public health is potentially high. The MHRA advise that if you are aware of a patient who has used melanotan and who may have had a side-effect from it, please report the case to the MHRA using a Yellow Card. Anonymous reports of any commercial sites that sell or advertise melanotan can also be made.

Tigecycline reformulation affects compatibility: correction
This article in the November issue of DSU originally contained statements about the indication of this drug that went beyond the regulatory position. These statements were removed,and an updated version of the article was published.

Patient Information Leaflet of the month: sertraline, Molipaxin (trazodone), and amisulpiride.

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