NPC Archive Item: MHRA Drug Safety Update August 2011

NOTE – This is an archive post from the NPC and has not been updated since first publication. Therefore, some hyperlinks may no longer be working.
MeReC Rapid Review NPC Logo

NHS Evidence accreditation logo The Drug Safety Update is an NHS Evidence accredited provider

15 August 2011

The August 2011 edition of Drug Safety Update (DSU) highlights that use of pioglitazone▼ is associated with a small increased risk of bladder cancer and outlines new warnings and precautions for use in at-risk patients. There is also:

  • notification that Onsenal▼ (celecoxib) is no longer approved in Europe for the reduction of intestinal polyps in familial adenomatous polyposis (FAP)
  • a recall of some batches of Vimpat▼ (lacosamide) 15 mg/mL syrup for the treatment of partial-onset seizures because of a quality defect
  • advice to consumers not to use unlicensed herbal products that contain the herbal ingredient Lei Gong Teng (Tripterygium wilfordi)

Healthcare professionals should follow the advice given in the Drug Safety Update the key messages of which are given below.

Pioglitazone▼: risk of bladder cancer
A Europe-wide review found a small increased risk of bladder cancer in patients taking pioglitazone. However, the benefits continue to outweigh the risks for those who respond to treatment and in whom there are no identified risk factors for bladder cancer. Observational studies report relative risks ranging from 1.12 to 1.33 when people with type 2 diabetes receiving pioglitazone are compared with diabetic patients those receiving other antidiabetic medicines but not exposed to pioglitazone. The increase in absolute risk is therefore likely to be small. Whether the increased risk occurs early in treatment or only after prolonged exposure remains unclear. The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use stated that the small increased risk could be reduced by appropriate patient selection. Therefore, the advice to healthcare professionals is as follows:

  • Patients with active bladder cancer or with a history of bladder cancer, and those with uninvestigated haematuria, should not receive pioglitazone.
  • Prescribers should review the safety and efficacy of pioglitazone in individuals after 3–6 months of treatment to ensure that only patients who are deriving benefit continue to be treated. Pioglitazone should be stopped in patients who do not respond adequately to treatment (e.g. reduction in HbA1c).
  • Before starting pioglitazone, the following known risk factors for development of bladder cancer should be assessed in individuals: age; current or past history of smoking; exposure to some occupational or chemotherapy agents such as cyclophosphamide; or previous irradiation of the pelvic region.
  • Use in elderly patients should be considered carefully before and during treatment because the risk of bladder cancer increases with age. Elderly patients should start on the lowest possible dose and be regularly monitored because of the risks of bladder cancer and heart failure associated with pioglitazone.

The place of pioglitazone in the overall context of care for people with type 2 diabetes is discussed in MeReC Rapid Review 3909. Further related information discussed in the statement on pioglitazone by the EMA can be found in MeReC Rapid Review No. 4090 and 3977.

Onsenal▼ (celecoxib) for familial adenomatous polyposis: withdrawal from EU market
Until recently, celecoxib was authorised as the orphan drug Onsenal for the reduction of intestinal polyps in familial adenomatous polyposis (FAP). At the time of approval of Onsenal, the licence (marketing authorisation) holder committed to do post-authorisation clinical studies. However, failure to recruit sufficient numbers into a clinical trial designed to provide evidence relating to clinically important benefit has resulted in the licence holder voluntarily withdrawing Onsenal. Furthermore, the EMA has reviewed the available data after concerns that celecoxib may continue to be used unlicensed in the treatment of FAP. The review concluded that the clinical benefit of celecoxib in FAP has not been sufficiently demonstrated and is outweighed by the increased risk of cardiovascular and gastrointestinal side effects from celecoxib use at high dose and long term in patients with FAP. Therefore, the advice to healthcare professionals is as follows:

  • Celecoxib is not recommended for the reduction of intestinal polyps in FAP and should not be prescribed for this unlicensed indication.
  • Patients who are taking Onsenal should consult their doctor as soon as possible to discuss alternative treatment options.

Vimpat▼ (lacosamide) 15 mg/mL syrup: recall due to quality defect
Vimpat 15 mg/mL syrup for the treatment of partial-onset seizures will be recalled because of a quality defect in some batches, leading to an uneven distribution of the active substance lacosamide. The recall will begin on Sept 15, 2011, to allow sufficient time for patients to be switched to suitable alternatives.

Traditional Chinese medicines containing Lei Gong Teng: risk of serious side effects
Consumers are advised not to use unlicensed herbal products that contain the herbal ingredient Lei Gong Teng (Tripterygium wilfordii), also known as Thunder God Vine or Seven-step vine) because of concerns about serious side effects on fertility and on the liver, kidneys, immune system, blood, and heart.

Please comment on this rapid review using our feedback form.

Make sure you are signed up to NPC Email updates — the free email alerting system that keeps you up to date with the NPC news and outputs relevant to you