Shared Care Protocol –remains open to review in light of any new evidence
Amber = To be initiated and titrated to a stable dose in secondary care with follow up prescribing and monitoring by primary
care.
Linaclotide (Constella®)
Shared Care Guideline for the use of Linaclotide in moderate to severe Irritable
Bowel Syndrome with constipation unresponsive to conventional laxatives.
Introduction
Indication/Licensing information
Linaclotide is indicated for the symptomatic treatment of moderate to severe irritable bowel syndrome with
constipation (IBS-C) in adults.
Irritable Bowel Syndrome with
Constipation (IBS-C) diagnosed
Place in therapy:
Give Information
Dietary
Management
First line Laxatives
Physical
Exercise
Second line Laxatives
Complementary and
Alternative Medicines may
be considered, although no
specific treatments have
been assessed or endorsed
by the Area Prescribing
Committee.
Combination Laxatives
Consider trial of Linaclotide.
Pharmacology
Linaclotide is a Guanylate Cyclase-C receptor agonist (GCCA) with visceral analgesic and secretory activities.
Both linaclotide and its active metabolite bind to the GC-C receptor on the luminal surface of the intestinal
epithelium, leading to an increase in concentrations of cyclic guanosine monophosphate (cGMP), both
extracellularly and intracellularly.
Extracellular cGMP decreases pain-fiber activity, resulting in reduced visceral pain in animal models.
Intracellular cGMP causes secretion of chloride and bicarbonate into the intestinal lumen, through activation of
the cystic fibrosis transmembrane conductance regulator (CFTR), which results in increased intestinal fluid
and accelerated transit.
Dosage and administration
The recommended dose is one capsule (290 micrograms) once daily, at least 30 minutes before a meal.
Physicians should periodically assess the need for continued treatment. The efficacy of linaclotide has been
established in double-blind placebo-controlled studies for up to 6 months. If patients have not experienced
improvement in their symptoms after 4 weeks of treatment, the patient should be re-examined and the benefit
and risks of continuing treatment reconsidered.
Constella® is available as hard capsules containing 290micrograms of linaclotide per capsule.
Linaclotide Shared care Guideline
Date Prepared: 30th October 2014 Review Date: 30th October 2016
Page 1 of 6
Shared Care Protocol –remains open to review in light of any new evidence
Amber = To be initiated and titrated to a stable dose in secondary care with follow up prescribing and monitoring by primary
care.
Responsibilities of the specialist initiating treatment
Summary
 To assess the suitability of the patient for treatment.
 To discuss the benefits and side effects of treatment with the patient/carer and the need for long term
monitoring if applicable.
 To perform baseline tests and if appropriate routine tests until the patient is stable.
 To prescribe for the first 12 weeks of treatment
 To ask the GP whether they are willing to participate in shared care.
 To provide the GP with a summary of information relating to the individual patient to support the GP in
undertaking shared care (See Shared care request form in Appendix A).
 To advise the GP of any dosage adjustments required, monitoring required, when to refer back, and when
and how to stop treatment (if appropriate).
 To advise the GP when the patient will next be reviewed by the specialist.
 To monitor the patient for adverse events and report to the GP and where appropriate Commission on
Human Medicines/MHRA (Yellow card scheme).
 To provide the GP with contact details in case of queries.
Baseline Tests
Baseline U&Es will be completed prior to starting treatment with linaclotide.
Routine Tests
There is no routine monitoring necessary with the administration of linaclotide. However, it is advised that
U&E’s are checked periodically in patients predisposed to electrolyte disturbances, should prolonged or
severe diarrhoea occur, or as clinical judgement dictates.
Disease monitoring
Patients will be reviewed by the Specialist team 8 weeks after initiation of treatment with linaclotide, to assess
efficacy and tolerability. If the patient is gaining significant benefit, a further 4 weeks of treatment should be
supplied, and the GP approached to consider shared care.
Continued efficacy and tolerability should be reviewed every 3 months.
Responsibilities of other prescribers
Acceptance of Responsibility by the Primary Care Clinician It is optional for GPs to participate in taking on
responsibility for shared care for the patient. GPs will take on shared care only if they are willing and able.
Summary
 To reply to the request for shared care as soon as possible.
 To prescribe and adjust the dose as recommended by the specialist.
 To ensure there are no interactions with any other medications initiated in primary care.
 To continue monitoring as agreed with secondary care
 To refer back to the specialist where appropriate. For example:
o
Patient or general practitioner is not comfortable to continue with the existing regime due to either
change in condition or drug side effects.
o
Advice in respect of concordance.
o
Special situations, (e.g. Pregnancy)
 Discontinue the drug as directed by the specialist if required
 To identify adverse events if the patient presents with any signs and liaise with the hospital specialist
where necessary. To report adverse events to the specialist and where appropriate the Commission on
Human Medicines/MHRA (Yellow card scheme).
Continued efficacy and tolerability should be reviewed every 3 months.
Linaclotide Shared care Guideline
Date Prepared: 30th October 2014 Review Date: 30th October 2016
Page 2 of 6
Shared Care Protocol –remains open to review in light of any new evidence
Amber = To be initiated and titrated to a stable dose in secondary care with follow up prescribing and monitoring by primary
care.
Clinical Particulars
BNF therapeutic
class
Cautions and
Contraindications
1.6.7 Other drugs used in Constipation (Gastrointestinal System)
Linaclotide is contraindicated in patients with gastrointestinal obstruction. Use in
patients with inflammatory bowel disease is not recommended due to lack of safety
and efficacy data in this patient group.
It should be used with caution in patients predisposed to fluid and electrolyte
disturbances (e.g. elderly, patients with cardiovascular disease, diabetes,
hypertension).
No dosage adjustments are required for elderly patients, or those with hepatic or renal
impairment.
Adverse Drug
Reactions
The most frequently reported adverse reaction associated with linaclotide therapy was
diarrhoea, mainly mild to moderate in intensity, occurring in less than 20% of patients.
In rare and more severe cases, this may – as a consequence – lead to the occurrence
of dehydration, hypokalaemia, blood bicarbonate decrease, dizziness, and orthostatic
hypotension.
Patients should be made aware of the possible occurrence of diarrhoea during
treatment. Should prolonged (e.g. more than 1 week) or severe diarrhoea occur,
medical advice should be sought and temporary discontinuation of linaclotide until
diarrhoea episode is resolved may be considered. Regarding duration of diarrhoea,
duration of more than 28 days was reported in 21% of patients with diarrhoea;
approximately one third of diarrhoea cases resolved within 7 days
Other common adverse reactions (>1%) were abdominal pain, abdominal distension
and flatulence.
Monitoring
There is no routine monitoring necessary with the administration of linaclotide.
It is advised that U&E’s are checked periodically in patients predisposed to electrolyte
disturbances, should prolonged or severe diarrhoea occur, or as other clinical
circumstances dictate.
Interactions
No drug-drug interaction studies have been performed for linaclotide, although the
drug is rarely detectable in plasma following administration of the recommended
clinical doses. In vitro studies have shown that linaclotide is neither a substrate nor an
inhibitor/inducer of the cytochrome P450 enzyme system and does not interact with a
series of common efflux and uptake transporters.
Taking linaclotide with or after food produced more frequent and looser stools, as well
as more gastrointestinal adverse events, than when taking it under fasting conditions.
Concomitant treatment with proton pump inhibitors, laxatives or NSAIDs may increase
the risk of diarrhoea.
In cases of severe or prolonged diarrhoea, absorption of other oral medicinal products
may be affected. The efficacy of oral contraceptives may be reduced and the use of
an additional contraceptive method is recommended to prevent possible failure of oral
contraception. Caution should be exercised when prescribing medicinal products
absorbed in the intestinal tract with a narrow therapeutic index such as levothyroxine
as their efficacy may be reduced.
Linaclotide Shared care Guideline
Date Prepared: 30th October 2014 Review Date: 30th October 2016
Page 3 of 6
Shared Care Protocol –remains open to review in light of any new evidence
Amber = To be initiated and titrated to a stable dose in secondary care with follow up prescribing and monitoring by primary
care.
Communication
Specialist to GP
The specialist will inform the GP when they have initiated linaclotide. When the patient is near completing the
satisfactory initiation period, the specialist will write to the GP to request they take over prescribing and where
possible give an indication as to the expected length of treatment. The Specialist will also send a Shared care
request form to support the GP in undertaking shared care. (Appendix A)
GP to specialist
If the GP has concerns over the prescribing of linaclotide, they will contact the specialist as soon as possible.
Contact names and details
Contact Details
Telephone number
Email
Dr K Kapur, Consultant Gastroenterologist,
BHNFT
01226 432542
Kapil.kapur@nhs.net
Dr A S Soliman, Consultant Gatsroenterologist,
BHNFT
01226 432522
a.soliman@nhs.net
Dr E Said,
BHNFT
Gastroenterologist,
01226 432910
Elmuhtady.said@nhs.net
Debbie West, Lower GI Nurse Specialist, BHNFT
01226 436371
Deborah.west3@nhs.net
Medicines Information Service, BHNFT
01226 432857
medicinesinformation@nhs.net
Gillian Smith, Medicines Information Pharmacist,
BHNFT
01226 432857
gilliansmith2@nhs.net
Consultant
References
1. BNF, accessed online via www.medicinescomplete.com
2. Constella Summary of Product Characteristics (SmPC) accessed online via
http://www.medicines.org.uk/emc/medicine/27499
3. Rao S, Lembo AJ, Shiff SJ et al. (2012) A 12-week, randomized, controlled trial with a 4-week
randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel
syndrome with constipation. American Journal of Gastroenterology 107: 1714–24
4. Chey WD, Lembo AJ, Lavins BJ et al. (2012) Linaclotide for irritable bowel syndrome with constipation:
a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. American
Journal of Gastroenterology 107: 1702–12
5. NICE CG61: Irritable bowel syndrome in adults: diagnosis and management of irritable bowel syndrome
in primary care. Accessed online via http://www.nice.org.uk/guidance/cg61
Development Process
This guidance has been produced by Gillian Smith, Lead Pharmacist for Medicines Information and Cardiology,
BHNFT, in consultation with Dr Kapil Kapur, Consultant Gastroenterologist and Clinical Director for Medicine,
BHNFT, following an AMBER classification status of Linaclotide by the Barnsley Area Prescribing Committee.
This guideline has been subject to consultation and endorsement by the Area Prescribing Committee on 12th
November 2014 and by the LMC on 10th February 2015.
Linaclotide Shared care Guideline
Date Prepared: 30th October 2014 Review Date: 30th October 2016
Page 4 of 6
Shared Care Protocol –remains open to review in light of any new evidence
Amber = To be initiated and titrated to a stable dose in secondary care with follow up prescribing and monitoring by primary
care.
Appendix A – Shared Care request form (Amber)



Specialist to complete when requesting GP to enter a shared care arrangement.
GP to return signed copy of form.
Both parties should retain a signed copy of the form in the patient’s record.
From (Specialist):
To (GP):
Patient details
Name:
ID Number:
Address:
DOB:
Diagnosed condition:
Amber Drug details
Drug name:
Linaclotide
Date of initiation:
Dose:
290mg ONCE daily
Length of treatment:
The patient will be reviewed by the Consultant on:
The patient should be reviewed by the GP by:
Monitoring
The following monitoring should be undertaken by the GP:
Parameter
Results
Frequency
Baseline U&E
Sodium =
Potassium =
Urea =
Creatinine =
Date next due (please specify if not
routinely indicated)
As clinical circumstances dictate.
Consider monthly check in patients
predisposed to electrolyte
disturbances, according to clinical
judgement.
U&E
Linaclotide Shared care Guideline
Date Prepared: 30th October 2014 Review Date: 30th October 2016
Page 5 of 6
Shared Care Protocol –remains open to review in light of any new evidence
Amber = To be initiated and titrated to a stable dose in secondary care with follow up prescribing and monitoring by primary
care.
Communication
Consultant
Telephone number:
Fax number:
Email address:
Specialist Nurse
Telephone number:
Fax number:
Email address:
Confirmation of acceptance of shared care
Specialist (Doctor/Nurse) name:
Specialist (Doctor/Nurse) signature:
Date:
I, Dr …………………………….., can confirm I :
□
accept the request to participate in shared care for the patient named above.
□
reject the request to participate in shared care for the patient named above. The reason for
this being ………………………………………………………………………………………..
GP signature:
Linaclotide Shared care Guideline
Date Prepared: 30th October 2014 Review Date: 30th October 2016
Date:
Page 6 of 6