NPC Archive Item: EMEA issues new warning for etoricoxib▼, epoetins and ergot-derived dopamine agonists

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Following reviews of the risks and benefits of several drugs, the European Medicines Agency (EMEA) has recommended that:

  • warnings and contraindications should be strengthened for etoricoxib for the treatment of rheumatoid arthritis and ankylosing spondylitis, following concerns about cardiovascular (CV) safety
  • epoetins should not be used first-line for anaemia in cancer patients who have a good prognosis
  • new warnings and contraindications should be added for ergot-derived dopamine agonists because of the risk of fibrosis of the heart valves and elsewhere in the body.

Following an application for a license extension for the treatment of ankylosing spondylitis, concerns were raised about the CV safety of extoricoxib, when used at a dose of 90mg daily for long periods. The EMEA’s Committee for Medicinal Products for Human Use (CHMP) assessed the long-term benefits and risks of etoricoxib in patients with rheumatoid arthritis or ankylosing spondylitis and concluded that the benefits outweighed the risks in these conditions, when used at a dose of 90mg daily. Patients’ whose blood pressure is persistently above 140/90 mmHg and not adequately controlled should not take etoricoxib. Blood pressure should be monitored for two weeks after treatment is initiated and regularly thereafter.

The EMEA is closely monitoring the safety of epoetin-containing medicines following evidence that they may be associated with an increased risk of venothrombolic events, an increased risk of tumour progression, and overall shorter survival times, when used in cancer patients. The CHMP concluded that, in cancer patients with a reasonably long life expectancy, the benefit of using epoetins to avoid blood transfusions does not outweigh the risks. They advised that blood transfusion should be the preferred option for treating anaemia in cancer patients who have a good prognosis. Epoetins should only be used following an informed assessment on an individual basis, when the benefits clearly outweigh the risk of tumour progression and shorter survival. These warnings do not apply when epoetins are used to treat anaemia in patients with chronic renal failure.

Ergot-derived dopamine agonists
The CHMP has reviewed the risk of fibrosis, including cardiac fibrosis, associated with ergot-derived dopamine agonists (bromocriptine, cabergoline, dihydroergocryptine, lisuride, pergolide) and concluded that the risk does not appear to be the same for all five of these medicines.

The risk of fibrosis of the heart valves with cabergoline and pergolide is well-established (seen in more than 1 in 10 patients taking either drug) and the CHMP recommended that additional warnings should be added to the prescribing information. Patients should be monitored for signs of fibrosis with echocardiography before treatment is initiated and regularly during treatment. In addition, the maximum recommended dose of these drugs should not exceed 3mg daily.

There was not enough evidence to determine whether bromocriptine, dihydroergocryptine or lisuride increase the risk of fibrosis of the heart valves. The CHMP recommended that warnings of a possible risk when high doses are taken for long periods should be added to the prescribing information. In addition, the maximum daily dose of bromocriptine should be restricted to 30mg daily.

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