Monday, 12 January 2015

Acne drug Dianette (Diane-35) obtains new depression and suicide risk warning

Foreword to readers:

Thanks to women who contacted APRIL and those who have heeded our request to report side-effects for Dianette (Diane-35).

It is due to the efforts of APRIL for many years requesting the Medicines & Healthcare Products Regulatory Agency to review the emails we received from women, with detailed explanations of the way Dianette affected them, that eventually the MHRA reviewed the drug for safety issues. This review, started in 2006, led to the manufacturers adding an additional warning about depression which previously had been listed under MILD side effects.

The MHRA requested APRIL to urge these women to report using the Yellow Card system. Compliance with this request has led to reports of psychiatric adverse drug reactions (ADRs) soaring in a few years from 3% of all reports to 33% of all reports by 2011. Due to the increased number of reports recorded on Drug Analysis Prints by the MHRA the manufacturer has added the warning as mentioned below in this post.

Dianette, the hormonal acne treatment manufactured by the German pharmaceutical company Bayer, has had a label change in the UK, following a number of reports of depression and suicidal thoughts.

Patient Information Leaflets should now include this warning in each box of Dianette:

“Post-marketing reports of severe depression (including very rare reports of suicidal ideation or behaviour) in patients using Dianette have been received.  However, a causal relationship between clinical depression and Dianette has not been established.”

The drug is prescribed to 62,000 British women and millions of women worldwide each year for acne and excessive body hair (hirsutism). Hundreds of adverse drug reactions and some fatalities have been reporting for people taking Dianette, also known as Diane-35 and other generic names.

In the USA the medication has not been approved by the Food and Drug Administration (FDA), and France banned the drug altogether in 2013** after its links to at least four French deaths from blood clots and 125 patients suffering serious side effects. The European medicines agency released a statement reported on BBC News (27 February 2013) about the decision of the French medicines agency ANSM to stop distribution:

“ANSM considered that Diane-35 and its generics carry a risk of thromboembolism which has been well known for many years, while their effectiveness in treating acne was only moderate and alternative treatments for acne are available.”

Dianette can be taken off-label as a contraceptive pill, but is unlicensed for this purpose due to its significantly higher risk of blood clots compared to other pills. Professor Dominique Maraninchi, director-general of the ANSM, believes doctors are giving women the drug as a contraceptive off-label too often, saying:

"Diane-35 is an acne treatment that also blocks ovulation. We have several inquiries going on that show that this non-authorised use is significant."

Between 2010 and 2013, the MHRA revealed that seven women in the United Kingdom have died whilst taking the drug, with 83 reports of side effects such as thrombosis and depression.

Last year, a Dutch report revealed up to 27 women, most of whom under 30, died from blood clots believed to be caused by Dianette.

Despite being listed as a Black Triangle Drug under further review by the medicine’s regulator, Dianette and its generic counterparts remain on license in the UK.

Earlier this year Jessica Eales, a young sailing champion, took her life after her 17th birthday, following 4 months of using Dianette as an acne treatment. The coroner Graham Short could not conclude any links between her suicide and the drug as she had not presented any noticeable signs of depression before this. The coroner quoted the European Medicines Agency review of Dianette in his report, which had concluded the benefits of the drug outweigh its risks. However, the EU report only took into account the risks in respect of thrombosis; the risk of depression and suicidal thoughts and actions was not considered in this review.

Following the death of Charlotte Porter, who died of a blood clot in 2010 whilst on Dianette, an MHRA spokesman announced: ‘Dianette is an effective medicine for treating the distressing conditions of severe acne and excessive hair […] Despite recent developments in France, we have no new concerns.’ German manufacturer Bayer said: ‘Bayer believes that Dianette has a favourable benefit-risk profile when used in accordance with the label.’

Prior to the publicity instigated by APRIL, we were told of many instances where antidepressants were prescribed to women who complained of depression, and left uninformed of the link or told to stop taking Dianette. APRIL’s research on patient safety collated 102 adverse drug reaction reports sent in by 2011 by women on their use of Dianette. Several personal accounts document that once removing themselves from the drug, their mood clears, following severe depression in some instances.  One patient described how “The cloud lifted when I stopped taking Dianette”. Woman’s hour described similar stories in their programme about contraceptive pills and mood.

This change in patient information is one step forward to informing the patient of the risks to their mental health when taking Dianette. Once a change in a patient leaflet is made, however, the GP may not be aware of the new information. However, we are hopeful that following this change in labelling, there may be further consideration of Dianette’s psychiatric side effects taken by prescribers as well as by coroners.

Crucially we urge those affected to report adverse side-effects using the Yellow Card reporting system in the UK. From this, we can build a stronger and more accurate profile of this drug for both prescribers and the prescribed to be aware of its risks.

Jacqueline Bond 

** Edit: The ANSM's decision to suspend Dianette was overruled as the European Commission's decision to maintain marketing authorisation was implemented in all EU Member states.

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