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

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13th March 2009

The MHRA and CHM have published the March edition of Drug Safety Update. This issue focuses on two drugs used for ADHD providing updated guidance on the safe and effective use of methylphenidate and details on the risk of psychotic or manic symptoms with atomoxetine. Drug safety advice is also given on the use of antipsychotics in elderly patients with dementia, the risk of severe pancreatitis and renal failure with exenatide and atypical stress factures with bisphosphonates.

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

The benefits of methylphenidate continue to outweigh the risks when it is used, according to its licensed indication, to treat attention deficit hyperactivity disorder (ADHD) in children aged six years or older and adolescents. This was concluded by the EMEA in a review of the safety of methylphenidate in the treatment of ADHD (see previous MeReC Stop Press Blog).

This issue of the DSU provides detailed updated prescribing information for methylphenidate on contraindications, pretreatment screening and continued monitoring of patients during treatment. Treatment must be under the supervision of a specialist in childhood behavioural disorders and patients should receive ongoing monitoring. Also, treatment should be interrupted at least once a year to determine whether continuation is necessary. There is a lack of data on the long-term effects of methylphenidate, and its long-term safety remains under close review.

Case reports have suggested that, at normal doses, atomoxetine can be associated with treatment-emergent psychotic or manic symptoms (e.g. hallucinations, delusional thinking, mania, or agitation) in children and adolescents without a history of psychotic illness or mania. If such symptoms occur, consideration should be given to a possible causal role of atomoxetine and to stopping treatment. It is possible that atomoxetine might exacerbate pre-existing psychotic or manic symptoms.

NB NICE guidance on ADHD was issued in September 2008 (see previous MeReC Stop Press Blog).

Antipsychotics: use in elderly patients with dementia
There is a clear increased risk of stroke and a small increased risk of death when antipsychotics (typical or atypical) are used in elderly people with dementia. Risperidone▼ is the only antipsychotic licensed for treating dementia-related behavioural disturbances: and then only for short-term use (up to six weeks) for persistent aggression in Alzheimer’s-type dementia, unresponsive to non-drug approaches and where there is risk of harm to the patient or others. The balance of risks and benefits associated with risperidone▼ treatment should be carefully assessed for every patient, taking into consideration the known increased mortality rate associated with antipsychotic treatment in the elderly. Prescribers should carefully consider the risk of cerebrovascular events before treating any patient who has a history of stroke or transient ischaemic attack with risperidone▼. Consideration should also be given to other risk factors for cerebrovascular disease such as hypertension, diabetes, smoking and atrial fibrillation. In view of this, the CHM has added risperidone▼ to the list of black triangle medicines. Therefore, all suspected side-effects to risperidone▼ that occur when it is used to treat elderly patients with dementia should be reported via the yellow card system.

A previous MeReC Rapid Review Blog has discussed the safety of antipsychotics when used in elderly patients with dementia.

Suspected adverse reaction reports of necrotising and haemorrhagic pancreatitis have been received in association with exenatide▼. Some of these have had a fatal outcome. If pancreatitis is suspected, treatment with exenatide▼ should be suspended immediately. If pancreatitis is diagnosed, exenatide▼ should be permanently discontinued. Reports of renal impairment, including acute renal failure and worsened chronic renal failure have also been received. Therefore, exenatide▼ is not recommended for use in patients with end-stage renal disease or severe renal impairment. Exenatide▼ is an incretin-based therapy indicated for type 2 diabetes. The NICE clinical guideline on type 2 diabetes includes a minor role for exenatide▼ and further information on its use is expected in the guideline on newer agents which is currently in development.

Atypical stress factures of the proximal femoral shaft have been reported in patients treated long-term with alendronic acid (in most cases, time to onset ranged from 18 months to 10 years). Fractures occurred after minimal or no trauma and some patients experienced thigh pain weeks to months before presenting with a completed femoral fracture. Patients who develop stress factures should discontinue alendronic acid and receive no further bisphosphonate treatment unless the benefits for the individual are thought to clearly outweigh the risk of harm. The product information for alendronic acid will be updated to include a warning about this.

Limited data are available for the other bisphosphonates to support a causal association with atypical stress fractures, but this might reflect their lower usage and the limited long-term data available. Therefore, an increased risk of atypical stress fractures with other bisphosphonates cannot be excluded.

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Yellow card scheme
Please remember you can report suspected adverse events involving medicines using a yellow card at

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