Published: 6 March 2014

MARC's Remarks: December 2013 Meeting

Prescriber Update 35(1): 14
March 2014

The Medicines Adverse Reactions Committee (MARC) met on 5 December 2013 to review a number of medicine related safety issues.

The MARC reviewed information on clinical outcomes in patients taking both clopidogrel and proton pump inhibitors (PPIs). The MARC concluded that the available evidence suggests this interaction does not translate into adverse clinical outcomes. Further information can be found in this edition of Prescriber Update1.

The MARC reviewed the benefits and risks of bromocriptine when used for the suppression of lactation due to a concern over rare but potentially serious or fatal adverse effects. These included cardiovascular, neurological and psychiatric adverse effects.

The MARC noted that the data sheets for bromocriptine appropriately outlined the risks of these adverse effects.

The MARC concluded that the benefit-risk profile of bromocriptine remained positive. However, the MARC recommended that bromocriptine should be restricted to second-line therapy for the suppression of lactation.

The MARC reviewed the latest update regarding the risk of mortality with tiotropium (Spiriva) (in particular the Respimat device). This review included the recently published trial designed to assess mortality of tiotropium Respimat and HandiHaler (the TIOSPIR trial).

The TIOSPUR randomised, double-blind, parallel group trial conducted by Boehringer Ingelheim found that Respimat (at either 2.5 mcg daily or 5 mcg daily) was non-inferior to HandiHaler (18 mcg daily) with regards to risk of death. Respimat was also not associated with a greater risk of COPD exacerbation compared to HandiHaler.

The MARC noted that the TIOSPIR study was very well-designed. The MARC was reassured that there is no evidence of increased mortality for the Respimat device compared with the HandiHaler device when used at the approved doses.

Due to concerns about the risk of serious cardiovascular events, the MARC reviewed the risks and benefits of using short acting beta agonists (SABAs) to delay delivery in women presenting with premature labour.

The MARC noted that injectable SABAs (including salbutamol) have established efficacy in delaying delivery for at least 48 hours. This allows time for the administration of steroids and/or magnesium, or transfer to a neonatal intensive care unit. However, the MARC noted that tocolysis with SABAs has not been shown to have an independent beneficial effect on neonatal outcomes.

The MARC concluded that the benefits of short term treatment (≤ 48 hours) with intravenous salbutamol outweigh the risks when used in appropriate patients to inhibit premature labour.

However, the MARC agreed with the European Medicines Agency’s (EMA’s) conclusion that the risks associated with maintenance treatment with oral salbutamol outweigh any possible benefits in women presenting with premature labour. The MARC recommended that oral salbutamol be contraindicated for use in obstetric indications. 

Further information on these issues can be found on the Medsafe website ( 


  1. Medsafe. 2014. Update: PPIs and clopidogrel interaction. Prescriber Update 35(1): 7.