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The Drug Safety Update is an NHS Evidence accredited provider
19 March 2010
The MHRA and CHM have published the March edition of Drug Safety Update. Highlights include:
- A warning that the risk of developing progressive multifocal leukoencephalopathy with natalizumab (Tysabri▼) increases after two years of therapy
- A warning of a possible small increased risk of congenital cardiac defects in association with fluoxetine in early pregnancy, similar to that seen with paroxetine
- A reminder for prescribers of sirolimus (Rapamune▼ ) not to use different immunoassays for therapeutic drug monitoring to reduce the risk of incorrect dose adjustment.
Action
Drug Safety Update is an essential read for everyone whose professional practice involves medicines. It is published every month in electronic format only.
Natalizumab (Tysabri▼) :risk of progressive multifocal leukoencephalopathy increases after two years of therapyIn patients being with multiple sclerosis being treated with natalizumab the risk of developing progressive multifocal leukoencephalopathy (PML) increases after two years of therapy. Patients should be informed of the risk before treatment, and again after two years, when the balance between the risks and benefits of treatment should be reconsidered. The risk of developing PML appears to increase with duration of treatment. However, the risk of developing PML beyond three years of treatment is currently unknown.
A baseline MRI is recommended at least three months prior to initiating natalizumab, and annually thereafter. Clinical vigilance for signs and symptoms suggestive of PML is essential, and patients, carers and families should also be aware of these. If PML is suspected natalizumab should be promptly discontinued followed by appropriate evaluation to exclude PML.
It is recommended that patients should be treated with natalizumab as part of a national registry or postmarketing study. As it is the first agent for multiple sclerosis in its class natalizumab is under intensive monitoring and healthcare professionals are reminded to report all suspected adverse reactions promptly via the Yellow Card Scheme.
Possible small risk of congenital cardiac defects with fluoxetine
Meta-analysis of recent epidemiological evidence suggests a possible small increased risk of congenital cardiac defects with fluoxetine use in early pregnancy, similar to that seen with paroxetine. The background incidence of congenital cardiac defects is approximately 1 in 100 pregnancies, whereas the meta-analysis results for fluoxetine were consistent with an increased absolute risk to less than 2 in 100. The studies reported varied cardiac defects, ranging in severity from reversible ventricular septal defects to transposition of great vessels. There are insufficient data to draw conclusions about the risk of congenital cardiac defects with selective serotonin reuptake inhibitors other than paroxetine and fluoxetine. However, a class effect cannot be excluded. The potential increased risk should be considered in the context of the benefits of treating depression in pregnancy.
Sirolimus: risk of incorrect dose adjustment if using different immunoassays for therapeutic drug monitoring
Sirolimus (Rapamune▼) is indicated for the prophylaxis of organ rejection in adult patients at low to moderate immunological risk receiving a renal transplant. Optimal therapy with sirolimus requires therapeutic drug concentration monitoring in all patients. Either reference assay high performance liquid chromatography (HPLC), or an immunoassay is used to establish whole-blood concentrations. Switching between different immunoassays, or between an immunoassay and HPLC, in a single patient can lead to clinically significant differences in results, subsequently leading to incorrect dose adjustments. The potential adverse consequences include allograft rejection, if drug levels are too low, and toxicity if levels are too high.
Additional news includes:-
- Drug Safety Update has been accredited by NHS Evidence, and Drug Safety Update articles will now be available at http://www.evidence.nhs.uk/.
- notification that the MHRA will be hosting a conference for doctors in training on “Unusual Suspects—Patient Safety and the Regulation of Drugs and Medical Devices”
- the patient information leaflet (PIL) of the month is the Human Varicella-Zoster Immunoglobulin vaccine.
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