The Medicines and Healthcare products Regulatory Agency (MHRA) has published Drug Safety Update for January 2013 (PDF).
This update contains drug safety advice reminding clinicians of the need to monitor cardiac function when starting or re-starting fingolimod (Gilenya®). This issue clarifies that the same first-dose monitoring as for treatment initiation should be repeated if treatment is interrupted as follows:
- 1 day or more during the first 2 weeks of treatment
- more than 7 days during weeks 3 and 4 of treatment
- more than 2 weeks after one month of treatment
It is recommended that patients are made aware to consult a doctor about their medication if they miss doses as described above.
The stop press section advises of the withdrawal of Tredaptive® after a recent study failed to demonstrate that the benefits of therapy outweigh the risks.
This same section also advises of an increased risk of suicidal behaviour and ideation with roflumilast (Daxas®). Roflumilast is licensed for maintenance treatment of severe chronic obstructive pulmonary disease and is already known to increase psychiatric disorders such as insomnia, anxiety, nervousness and depression. Post marketing data has identified an increase in suicidal behaviour also with one instance of completed suicide. It is recommended to avoid use in individuals with a history of depression associated with suicidal ideation or behaviour, for patients to monitor for and report mood changes during treatment and for treatment to be stopped if psychiatric symptoms develop or worsen.
Action: Clinicians will find this publication to be a useful review of current issues in drug safety.
The manufacturer of Tredaptive® (Nicotinic Acid and Laropiprant) has written to healthcare professionals advising that this product is being discontinued and will not be available with effect from 18th January 2013.
This medication was being studied in the HPS2-THRIVE trial. Preliminary results from the study failed to demonstrate a statistically significant reduction in cardiovascular events (heart attacks and strokes). Additionally the study also identified an increased risk of serious adverse events associated with treatment.
The European Medicines Agency have reviewed this new data and concluded that the benefits of this medicine no longer outweigh the risks associated with treatment. The manufacturer has agreed with this assessment and as a result the product is being withdrawn.
Retail pharmacists are being advised to refer patients prescribed this medication back to their doctor for a non-urgent review.
Action: Clinicians should be aware of this product withdrawal. Patients currently prescribed this medicine may present for a review. It may be prudent to run clinical system searches to identify any patients who are currently prescribed this medication and invite them for a review.
The National Institute of Health and Clinical Excellence (NICE) has published new guidance for the month of January 2013. This month there is one clinical guideline and one technology appraisal that impact upon primary care.
The Psychosis and schizophrenia in children and young people guideline offers evidence-based advice on the recognition and management of psychosis and schizophrenia in children and young people under 18.
The Hyperplasia (benign prostatic) – tadalafil technology appraisal was terminated and the treatment with tadalafil is not recommended for the treatment of symptoms associated with benign prostatic hyperplasia. The manufacturer failed to make an evidence submission.
Action: Clinicians should be aware of this month’s new guidance and implement any necessary changes to practice.
The Scottish Medicines Consortium (SMC) has issued its monthly advice on newly licensed medicines.
Budesonide gastro-resistant capsule (Budenofalk®) has been accepted for symptomatic relief of chronic diarrhoea due to collagenous colitis.
Budesonide 9mg gastro-resistant granules (Budenofalk®) have been accepted for the induction of remission in patients with active collagenous colitis.
Dapagliflozin (Forxiga®) has been accepted for restricted use in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control. Recommended use is restricted to use as dual therapy in combination with metformin, when metformin alone with diet and exercise does not provide adequate glycaemic control and a sulphonylurea is inappropriate.
Etoricoxib (Arcoxia®) has been rejected for use in the short-term treatment of moderate pain associated with dental surgery.
Glycopyrronium (Seebri Breezhaler®) has been accepted for use as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).
Hydrocortisone (Plenadren®) has been rejected for the treatment of adrenal insufficiency in adults. The manufacturer failed to make a submission.
Tadalafil (Cialis®) has been rejected for the treatment of the signs and symptoms of benign prostatic hyperplasia in adult males. The manufacturer failed to make a submission.
Vildagliptin (Galvus®) has been accepted for restricted use in the treatment of type 2 diabetes mellitus in adults as monotherapy in patients inadequately controlled by diet and exercise alone. Recommended use is restricted to patients for whom both metformin and sulphonylureas are inappropriate due to contraindications or intolerance.
Action: Clinicians should be aware of the recommendations of the SMC. Routine use of rejected and restricted medicines should be avoided.
The British Medical Journal has published the results of a retrospective case control cohort study that aimed to assess the risk of acute kidney injury in patients prescribed NSAIDs and diuretics, angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB).
The study reviewed data for 487,372 users of antihypertensive drugs using data from the UK Clinical Practice Research Datalink. Average follow up was 5.9 years with 2,215 cases of acute kidney injury identified.
Dual therapy of an NSAID with either a diuretic, an ACEI or an ARB was not associated with an increased risk of acute kidney injury. Triple therapy of NSAID and two of the antihypertensive drugs was associated with a statistically increased risk of acute kidney injury (rate ratio 1.31, 95% confidence interval 1.12 to 1.53). A secondary analysis identified that the greatest risk appears to be in the first 30 days of use (rate ratio 1.82, 1.35 to 2.46).
The authors conclude that, “increased vigilance may be warranted when diuretics and angiotensin converting enzyme inhibitors or angiotensin receptor blockers are used concurrently with NSAIDs“.
The authors note some limitations in this study including accuracy of recording of acute kidney injury in the database systems, residual confounding in observational data and inability to correct of exposure to over the counter NSAIDs.
Action: Clinicians should be aware of this study. A more cautious approach with greater monitoring may be prudent in patients taking combinations of these antihypertensives when NSAID use is unavoidable.