25 July 2011
The European Medicines Agency (EMA) has issued/updated safety information regarding pioglitazone▼, dronedarone▼, varenicline▼, and Pandemrix®▼ influenza vaccine.
Healthcare professionals who are considering prescribing dronedarone, pioglitazone, varenicline, or Pandemrix® should familiarise themselves with the appropriate safety information given by the EMA (summarised below) and follow their recommendations. More information relating to these recommendations can be found in the EMA press releases of 21st July 2011.
Pioglitazone: new contraindications and warnings
The EMA has finalised its review of pioglitazone-containing medicines and the occurrence of bladder cancer. The EMA considers that the benefit-risk balance remains positive in a limited population of type 2 diabetics, but that there is a small increased risk of bladder cancer in patients taking these medicines. However, the CHMP also concluded that the small increased risk could be reduced by appropriate patient selection and exclusion, including a requirement for periodic review of the efficacy and safety of the individual patient’s treatment.
Prescribers are advised:
- Do not use these medicines in patients with current or a history of bladder cancer or in patients with uninvestigated macroscopic haematuria.
- Risk factors for bladder cancer should be assessed before initiating pioglitazone treatment.
- In light of age-related risks, the balance of benefits and risks should be considered carefully both before initiating and during treatment in the elderly.
- Prescribers should review the treatment of patients on pioglitazone after three to six months (and regularly afterwards) to ensure that only patients who are deriving sufficient benefit continue to take it.
Background to this review can be found in MeReC Rapid Review No. 3977.
Dronedarone: advice for regular monitoring while awaiting review
The EMA is currently reviewing benefits and risks of dronedarone (Multaq ®), since preliminary data from a clinical study (PALLAS) have shown an increased risk of cardiovascular (CV) side effects such as CV death, stroke and CV hospitalisation in patients with permanent atrial fibrillation. These new data could have an impact on the use of the medicine in its approved indication, “adult clinically stable patients with a history of, or current, non-permanent atrial fibrillation, to prevent recurrence or to lower ventricular rate” as there may be overlap between the two diagnoses.
Awaiting the finalisation of the current review, prescribers in the European Union are reminded to follow the recommendations in the product information with respect to the indication, contraindications and warnings. Specifically, prescribers are advised to monitor patients regularly in order to ensure that they remain within the authorised indication and do not progress to permanent atrial fibrillation (this is in addition to other monitoring, such as liver function monitoring, see below).
The FDA is also reviewing the use of dronedarone. The FDA is evaluating whether and how the preliminary results of the PALLAS study apply to patients taking dronedarone for paroxysmal or persistent atrial fibrillation or atrial flutter.
The FDA has issued a Drug Safety Communication advising that:
- Patients taking dronedarone should talk to their healthcare professional about whether they should continue to take dronedarone for non-permanent atrial fibrillation.
- Patients should not stop taking dronedarone without talking to a healthcare professional.
- Healthcare professionals should not prescribe dronedarone to patients with permanent atrial fibrillation.
The MHRA have previously published advice for health care professionals; this includes recommendations for regular liver function testing, and advising patients to consult a physician if they experience symptoms of heart failure or hepatoxicity whilst taking dronedarone.
Varenicline: positive benefit-risk balance confirmed
The EMA has confirmed that the benefit-risk balance for varenicline (Champix®) remains positive, despite the results of a recent meta-analysis of CV side effects. The CHMP could not draw robust conclusions from the meta-analysis in view of the limitations of the review. However, the CHMP has asked Pfizer, the marketing-authorisation holder for Champix®, to submit a variation to include more information on CV events in the medicine’s product information.
For more details of this meta-analysis and its limitations see MeReC Rapid Review No. 4073.
Pandemrix®: restricted use in young people
The EMA recommends restricted use of Pandemrix® (a pandemic influenza vaccine ) following a link to very rare cases of narcolepsy in young people. For persons under 20 years of age Pandemrix® may only be used if the recommended seasonal trivalent influenza vaccine is not available and if immunisation against H1N1 is still needed (e.g. in persons at risk of the complications of infection). The CHMP confirmed that overall the benefit-risk balance of Pandemrix® remains positive.
Further information on the safety of swine-flu vaccines can be found on the MHRA Swine Flue webpage.
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