HERTFORDSHIRE MEDICINES MANAGEMENT COMMITTEE (HMMC)

RACECADOTRIL FOR THE TREATMENT OF ACUTE DIARRHOEA NOT RECOMMENDED

Name: What it is Indication Date Decision NICE / SMC generic Decision Status Guidance (trade) last revised Racecadotril intestinal antisecretory symptomatic treatment Nov 2013 Final NICE - No (Hidrasec ®) enkephalinase inhibitor of acute diarrhoea (for Guidance - reduces intestinal up to 7 days) SMC – Not secretion of water and recommended electrolytes

HMMC Recommendation:

NOT RECOMMENDED for prescribing in adults or children

EFFICACY SAFETY • RCTs (with limitations) in adults have • Racecadotril appears to be well tolerated. suggested that racecadotril and loperamide • The Summary of Product Characteristics in are similarly effective in reducing duration of adults reports the most common adverse diarrhoea and number of stools produced. effect with racecadotril as headache and in • Meta-analysis (9 RCTs - with limitations) in children reports uncommon adverse events as children has suggested that racecadotril plus tonsillitis, rash and erythema oral rehydration salt (ORS) solution improves • RCTs in adults have suggested that recovery rates at 2 days, reduces duration of racecadotril has fewer adverse effects, diarrhoea & volume and frequency of stool particularly constipation, than loperamide output more than ORS solution alone or with placebo. • No studies undertaken in the UK setting.

COST PATIENT FACTORS • Racecadotril is more expensive than • Prevention or reversal of dehydration is the alternative antimotility agents (current first-line priority in acute diarrhoea and gastroenteritis. options in adults). Cost of 7 days treatment: Most infectious diarrhoea is a self-limited, £8 racecadotril vs £1 loperamide. usually viral illness. Nearly half last less than • Not recommended for use by SMC & AWMSG one day. in children (no application for use in adults) as • The majority of children in the UK recover the company did not present a sufficiently from acute diarrhoea without treatment or by robust economic analysis. using ORS solution alone and it is unclear • No NHS cost-effectiveness analysis available when or whether adjunctive therapy is in adult population. necessary.

This HMMC recommendation is based upon the evidence available at the time of publication. The recommendation will be reviewed upon request in the light of new evidence becoming available. Page 1 of 2

Assessment against Ethical Framework

Evidence of Clinical Effectiveness • Refer to efficacy and safety boxes. • The exact place in therapy is uncertain. • Unclear if racecadotril reduces inpatient or outpatient visits or need for IV rehydration. • Limited data on use in older children and the elderly.

Cost of treatment and Cost Effectiveness • Refer to cost box. • Unclear whether the benefits of racecadotril are sufficiently clinically important to warrant additional cost. • No studies undertaken in the UK setting and hence cost effectiveness analysis for children have used models using results from studies applied to the UK setting: o Scottish Medicines Consortium (SMC) and All Wales Medicines Strategy Group (AWMSG) - racecadotril is NOT recommended for use in children – the submitting company did not present a sufficiently robust economic analysis. o Cost utility analysis from the UK NHS perspective (sponsored by the manufacturer) in children <5 years suggested that racecadotril plus ORS is associated with lower overall costs compared with ORS.

The needs of the population The needs of the population appear to be low. Prevention or reversal of dehydration is the priority in acute diarrhoea and gastroenteritis. Most infectious diarrhoea is a self-limited, usually viral illness. Nearly half last less than one day. The majority of children in the UK recover from acute diarrhoea without treatment or by using ORS solution alone and it is unclear when or whether adjunctive therapy is necessary. In adults alternative lower cost antimotility agents are available.

The needs of the community The needs of the community are considered moderate. The use of racecadotril instead of less costly antimotility agents or as an addition to ORS solution would create a cost pressure which may have an impact on the local health economy which already has to identify savings. Any potential savings from reductions in inpatient or outpatient visits or admissions or the need for IV rehydration do not appear to have been adequately studied and demonstrated in the UK setting.

Equity No impact anticipated.

Policy Drivers • Racecadotril was not considered appropriate for a NICE technology appraisal and is not currently planned into any other NICE work programme. • Adults - NICE has not published guidance on managing acute diarrhoea due to gastroenteritis. • Children – NICE CG 84, Diarrhoea and vomiting caused by gastroenteritis: diagnosis, assessment and management in children younger than 5 years: o Low-osmolarity oral rehydration salt (ORS) solution is recommended for children with dehydration and those at risk of dehydration. The guideline does not recommend using antidiarrhoeal drugs. • Not recommended for use by SMC and AWMSG

Implementability No issues identified.

References • NICE Evidence Summary: new medicine (ESNM11) – acute diarrhoea in adults – Mar 2013 – evidence and key issues summary: http://www.nice.org.uk/mpc/evidencesummariesnewmedicines/ESNM11.jsp • NICE Evidence Summary: new medicine (ESNM12) – acute diarrhoea in children – Mar 2013 – evidence and key issues summary: http://www.nice.org.uk/mpc/evidencesummariesnewmedicines/ESNM12.jsp • Scottish Medicines Consortium (SMC) – December 2012 – only considered the 3 European studies and includes health economic evidence http://www.scottishmedicines.org.uk/files/advice/racecadotril_Hidrasec_FINAL_November_2012_for_website.pdf • All Wales Medicines Strategy Group (AWMSG) – Feb 2013 – considered the meta-analysis and includes health economic evidence http://www.awmsg.org/awmsgonline/app/appraisalinfo/1546 • Rautenberg TA, Zerwes U, Foerster D et al. (2012) Evaluating the cost utility of racecadotril for the treatment of acute watery diarrhoea in children: the RAWD model. ClinicoEconomics and Outcomes Research 4: 109–16 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345933/

Produced by Hertfordshire Pharmacy and Medicines Optimisation Team Hertfordshire, Bedfordshire and Luton Commissioning Support NHS Central Eastern Commissioning Support Unit This HMMC recommendation is based upon the evidence available at the time of publication. The recommendation will be reviewed upon request in the light of new evidence becoming available. Page 2 of 2