MOVICOL®

Constipation and Faecal Impaction

Dr. Elie Magdalani

Senior Medical Affairs Manager MEA

What is constipation?
v

2
■ Constipation is an acute or chronic condition in which bowel movements occur less
often than usual or consist of hard, dry stools that are painful or difficult to pass

3
 Defining Constipation – The Rome III Criteria

Adults Children (4+ years) Infants (up to 4 years)

• Straining during at least • Fewer than two bowel • Fewer than two bowel
25% of defaecations. movements per week. movements per week.
• Lumpy or hard stools in at • At least one episode of • At least one episode per
least 25% of defaecations. faecal incontinence per week of incontinence after
• Sensation of incomplete week. acquiring toilet skills.
evacuation for at least 25% • History of retentive • History of excessive stool
of defaecations. posturing or excessive retention.
• Sensation of anorectal volitional stool retention. • History of painful or hard
obstruction for at least 25% • History of painful or hard bowel movements.
of defaecations. bowel movements. • Presence of large faecal
• Manual manoeuvres to • Presence of large faecal mass in rectum.
facilitate at least 25% of mass in rectum. • History
v of large diameter
defaecations. • History of large diameter stools that may obstruct the
• Fewer than three bowel stools that may obstruct the toilet.
movements per week. toilet.

A diagnosis of constipation requires two or more of the

symptoms listed.
Plus insufficient criteria for IBS.
5
Prevalence of Constipation

4-20%
General
Community
30-60%
15-17%
Stroke
Adults
patients

30-50%
1-30%
Cancer Constipation Children
patients

v
15-20%
Up to 51% Older
Pregnancy community
Up to 80% population
Nursing
home
patients

6
What are the symptoms of constipation?

Reduction in the
Feeling of being
number of times Straining whilst
unable to completely
individuals pass passing stools
empty your bowels
stools

Stools may be dry, Stomach aches and Feeling bloated

hard and lumpy cramps and/or sick

Loss of appetite

7
What is the impact of constipation?

98% impact on Quality of Life

80% 55% 41%

Physical Wellbeing Choice of Food Appetite

35% 32% 31%

Work Performance Sleep Social Life

8
 Impact of Constipation

Quality of Complication Economic

Symptoms Life (QoL) s Impact
• QoL in chronic
constipation • Exacerbation
• 61162 hospital
patients lower of
admission for
than normal haemorrhoids.
constipation in
• Bloating population. • Exacerbation
the UK alone
• Distention • QoL of anal
(2011).
• Abdominal comparable to fissures.
• Admissions
pain other chronic • Risk factor for
accounted to
• Nausea conditions colorectal
v more than
(e.g. diabetes) cancer.
120000 bed
• In children, • Faecal
days.
QoL lower impaction.
than with IBD.
What causes constipation?

Primary Secondary
Constipation constipation
•Insufficient fibre in the diet •As a result of drugs and
•Inadequate fluid intake surgery. Drugs that are known
•Lack of exercise to cause constipation
v include
opioids (e.g. morphine)
•Environmental issues (e.g. •As a result of an underlying
lack of private toilet illness. Examples include
facilities) Parkinson’s disease and Stroke

10
Faecal Impaction

■ Faecal Impaction A consequence of chronic constipation where there is a large

compacted mass of dried, hard faeces in the rectum or colon that cannot be passed by
the patient.

v
Consequences of Uncontrolled Constipation

Faecal impaction:
Large, compacted
mass of dried, hard
faeces v

Haemorrhoids and anal fissures:

Straining may exacerbate and may
lead to rectal muscle prolapse

12
 Death:
Extreme cases can be a
factor in death

Admissions to hospital: v
Untreated constipation can lead to
patients being admitted to hospital

13
■ A number of patients in a care home have developed diarrhoea.
Due to this, the care home reported an outbreak of Clostridium difficile.

Could these patients be suffering from constipation?

v

Yes!

14
Current Treatment Options for
Constipation
Treatment of Constipation

Laxative How it works Examples

Class

Osmotic Draws fluids and electrolytes Lactulose

from the body into the gut,
which bulks and softens the
stool.

Bulk- Absorb water to increase faecal Methylcellulose,

forming mass which then stimulates ispaghula, sterculia
intestinal motility v

Stimulant Increase intestinal motility by Glycerol, bisacodyl,

stimulation of colonic nerves senna, docusate
sodium
Iso-Osmotic Agents

MOVICOL® Macrogol acts by virtue of

its osmotic action in the
belongs in this gut, which induces a
laxative effect. Macrogols
category. increases the stool volume.

Electrolytes combined with Examples

v include
macrogol are exchanged across
the intestinal barrier with serum MOVICOL®,
electrolytes and excreted in faecal
water without net gain or loss of
Laxido®, Molaxole®,
sodium, potassium or water. Selg®, Isocolan®
Osmotic Agents

Inorganic Agents Organic Agents

•Draw fluid and electrolytes from the body into

•Release the enzyme cholecystokinin, the gut, which bulks and soften the stool.
causing increased motility of the small and •Lactulose is the currently available oral
large intestine, decreased absorption of organic osmotic laxative and is an actively
sodium by the small intestinal mucosa and promoted competitor to MOVICOL®.
•Lactulose comes as a liquid and is easy to
increased secretion of pancreatic
take.
enzymes. v
•However, it has an unpleasant taste, takes up
•They are fast-acting, potent and effective. to 48 hours to work, comes with a risk of
•However, they may cause electrolyte electrolytes disturbances and dehydration,
disturbances, griping pains and diarrhoea. requires increasing dosing requirements and is
•Examples include magnesium hydroxide, commonly accompanied by flatulence, bloating
magnesium sulfate etc. and abdominal pain.
•Brands include Duphalac® etc.
Bulk-Forming Agents

Bulk-forming laxatives They have a low level of

(methylcellulose, ispaghula, systemic side effects, are
sterculia etc.) relieve
constipation by absorbing water
suitable for all ages and
to increase faecal mass which long-term use and can be
then stimulates peristalsis. added to food or fruit juice.

However, they require adequate

v
Examples include:
fluid intake (difficult in children
and elderly), may be Celevac® (methylcellulose),
unpalatable and slow-acting Fibrolax® (ispaghula),
and have been associated with Normacol® (sterculia) etc.
bloating and flatulence.
Stimulants

Stimulant laxatives increase intestinal motility by stimulation of colonic

nerves.

They are effective, moderately fast working, easy to take, can be

given orally or rectally and are cheap.

However, they may be absorbed, the potency of natural extracts may vary, they can cause
colicky/griping pains and with long-term use both damage to the myenteric plexus and
hypokalaemia might occur. v

Examples include: Bonlax® (glycerol), Dulcolax® (bisacodyl), X-Prep®

(senna), Guttalax® (sodium picosulfate) etc.
Faecal Softeners

Ease the process of They are generally not

defaecation by softening the absorbed and are helpful in
stool or lubricating its passage selected groups of patients
through the anus, subsequently such as those who suffer from
reducing straining at haemorrhoids, anal fissures
defaecation. etc.

However, they usually have

poor efficacy when taken orally,
Examples include:
they can potentially result in Dioctyl® (docusate
v
serious side effects, and have
been associated with oily stools
sodium), Liquid
and faecal soiling. Paraffin etc.
Newer Treatment Options

Linaclotide (marketed as Constella®)

• A guanylate cyclase-C (GC-C) receptor agonist which increases fluid
secretion and transit.
• Licensed for moderate to severe IBS with constipation (IBS-C) in adult
patients only.
• Compared to other laxative classes, it reduces abdominal pain seen as a
defining symptom of IBS-C.
• The most common adverse event is diarrhoea.
• Another GC-C receptor agonist is currently in development (plecanatide).

Lubiprostone (marketed as Amitiza®)

• A chloride-channel activator that acts in the gut to increase intestinal fluid
secretion, which increases motility. v
• Licensed for chronic idiopathic constipation in adults whose condition has
not responded adequately to lifestyle changes.
• Shown to significantly improve GI symptoms of IBS with constipation
compared to placebo.
• Most common adverse event is nausea and data from animal studies have
shown that lubiprostone may cause foetal harm.
Newer Treatment Options (2)

Prucalopride (marketed as Resolor®)

•A selective serotonin 5HT4-receptor agonist which stimulates the enteric
nervous system to stimulate gut movement.
•Licensed to treat women with chronic constipation where laxative have failed
to provide relief.
•Shown to improve bowel function compared to placebo.
•Study confirmed non-inferiority of PEG 3350 + electrolytes to prucalopride.
•Common adverse events include headache, abdominal pain, nausea and
diarrhoea.

Methylnaltrexone bromide (marketed as Relistor®)

•A selectively peripherally acting opioid-receptor antagonist that is licensed
for the treatment of opioid-induced constipation in patients receiving
v is insufficient.
palliative care, when response to usual laxative therapy
•Should be used as an adjunct to existing laxative therapy.
•Given as subcutaneous injection not orally.
•Most common adverse events are abdominal pain, nausea, flatulence and
diarrhoea.
Top 10 Laxative Brands by In-Market
Value (€) Sales in MAT Apr-15 in
Norgine Markets
180000000 166896178.49
160000000
140000000
In-Market Value Sales, € mn

120000000
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Source: IMS (All remaining Norgine countries), GERS (France), Insight Health (Germany Retail), FarmINFORM (Netherlands)
MOVICOL - Key Facts
®
 MOVICOL® Constituents and Administration
Each sachet (13.8g) contains:

Macrogol 3350………………..13.1213g
Sodium chloride………………350.7mg
Sodium bicarbonate………….178.5mg
Potassium chloride…………...46.6mg
■ The content of electrolyte ions per sachet when made up to 125 ml of solution is as
follows:
65 mmol/L sodium,
5.4 mmol/L potassium,
53 mmol/L chloride and
17 mmol/L bicarbonate v

■ Different presentations have different amounts.

■ Both the sachet and liquids are dissolved in water before administration (amount of
water depends on presentation).
■ Patients with impaired cardiovascular function, set number of sachets taken in an
hour for faecal impaction.
MODE of Action

27
Mode of Action

MOVICOL® establishes and maintains an osmotic pressure gradient across the

intestinal wall, thereby preventing water absorption from the intestinal lumen and
adding bulk to the colonic contents.

The water and the electrolytes ingested with MOVICOL® are absorbed from
the proximal gastrointestinal tract, and an equivalent amount is then secreted
into the distal tract and excreted with the faeces. No net gain or loss of
electrolytes and water occurs.

v
The increased retention of water in the colon lubricates and softens the stools
and allow a comfortable bowel action.

The increased faecal bulk stretches the bowel wall, triggering peristalsis.

28
Mode of Action

The dehydrated stool

is bulked by hydration

The dehydrated stool

is softened by water

Peristalsis is triggered by
v
bulking the stool and
distending the bowel wall

Bowel motions become more

comfortable because
MOVICOL lubricates

29
 Small Bowel

The electrolytes are reabsorbed

The water ingested with
and actively excreted in the distal
MOVICOL® is passively reabsorbed
part of the bowel

v
Unabsorbed PEG 3350
contributes to the osmotic
pressure of intestinal contents
and results in the reduction of
net water absorption and in
increased intraluminal volume

30
Colon

■ PEG results in the increase of the volume of intestinal fluid that the right colon receives
from the ileum
■ PEG maintains an osmotic gradient across intestinal wall
■ PEG retains water during its progression through the colon
■ The retained water increases faecal bulk and stretches the intestinal wall, so
stimulating peristalsis.
■ The electrolytes are exchanged across the intestinal wall so that vno net loss or gain
occurs.

31
MOVICOL® Presentations

■ There are a number of different MOVICOL® presentations available:

MOVICOL® MOVICOL®
-Half Plain Chocolate

MOVIC MOVICO MOVICO

OL®-Half L® 13.8g L® Liquid
v

MOVICOL®
MOVICO
Paediatric
L® Plain Chocolate
MOVICOL®
Paediatric
Plain
v
MOVICOL® Range

v
MOVICOL® MOVICOL® Plain
• 13.8g sachet • 13.7g sachet
• Lemon and lime flavour • No flavour
• For constipation and faecal • For constipation and faecal impaction
impaction in patients aged 12 in patients aged 12 years and over
years and over

34
 MOVICOL® Liquid
v
MOVICOL Chocolate
®
• Concentrate for use in oral
• 13.9g sachet
solution
• Chocolate flavour
• Orange flavour
• For constipation and faecal
• For constipation in patients aged
impaction in patients aged
12 years and over
12 years and over

35
 MOVICOL® Paediatric
Plain
• 6.9g sachet
• No flavour
• For constipation (ages 2-
11) and faecal impaction
(5-11)

MOVICOL® Half MOVICOL® Paediatric

• 6.9g sachet Chocolate
• Lemon and lime • 6.9g sachet
flavour v
• Chocolate flavour
• For constipation and • For constipation (ages
faecal impaction in 2-11) and faecal
patients aged 12 impaction (5-11)
years and over

36
Key Clinical Studies
Efficacy in Constipation
Attar et al. Comparison of a low dose polyethylene glycol
electrolyte solution with lactulose for treatment of chronic
constipation. Gut 1999;44:226-230

• To evaluate the efficacy of MOVICOL® compared to

Aim
lactulose in the treatment of chronic constipation.

• Multi-centre, randomised study of 115 patients

comparing MOVICOL® with lactulose over a 4-week
Method
period (part A) with the opportunity to continue with
MOVICOL® for 2 months (part B).

• Part A:
• Overall improvement was greater in the MOVICOL®
Results v
group (mean daily stool frequency with MOVICOL ®
increased to 1.3±0.7).
• No serious adverse events.

• This study demonstrated the efficacy and tolerability

Conclusion
of MOVICOL®.
Gruss & Teucher. Treatment of chronic constipation.
Results of a multi-centre observation period on the use of
polyethylene glycol 3350 plus electrolytes.
Der Allgemeinarzt 1999; 21(16):1342-1350
• To observe the efficacy and tolerance of MOVICOL ® in
Aim patients with chronic constipation under conditions in an
out-patient setting.

• Multi-centre, observational study of 2029 chronic

Method constipation patients assessed after 2 and 4 weeks of
MOVICOL® treatment.

• Overall efficacy was ranked as ’good’ to ‘very good’ by

90% of the patients and 92% of vthe doctors.
• Pain on defaecation improved and statements of normal
Results
stool consistency rose.
• Overall, tolerance was evaluated as ‘good’ to ‘very
good’ by majority of patients and doctors.

• MOVICOL® is an effective treatment for chronic

Conclusion
constipation.
Efficacy in Faecal
Impaction
Culbert et al. Highly effective oral therapy (polyethylene
glycol/electrolyte solution) for faecal impaction and severe
constipation. Clin Drug Invest 1998; 16(5):355-360

Aim •To evaluate the efficacy and tolerability of MOVICOL® in patients with faecal impaction and severe constipation.

Method •Open study of 30 patients with a history of chronic constipation and faecal loading treated with MOVICOL® .

Results •All patients who followed the study protocol completely cleared or significantly improved over 3 days.
•No unexpected adverse symptoms. Only associated significant symptom was borborygmi.
v

Conclusion •MOVICOL® is highly effective and an acceptable oral therapy for the treatment of adult faecal impaction.
Chen et al. Evaluation of polyethylene glycol plus
electrolytes in the treatment of severe constipation and
faecal impaction in adults.
Curr Med Res Opin 2005: 21(10):1595-1602
• To evaluate the efficacy and safety of MOVICOL® in the
Aim treatment of severe constipation and faecal impaction in
adults.

• Open label, non-comparative study of 56 patients with

Method severe constipation or faecal impaction treated with
MOVICOL®.

• 89% of patients had a response to treatment, of whom

v
almost 70% had a complete response.
Results • MOVICOL was well tolerated, the most common
®

adverse events being abdominal pain, abdominal

enlargement, flatulence and nausea.

• This is the largest study demonstrating the efficacy and

Conclusion
safety of MOVICOL® in adult faecal impaction.
Long-term Use
Attar et al. Comparison of a low dose polyethylene glycol
electrolyte solution with lactulose for treatment of chronic
constipation. Gut 1999;44:226-230
• To evaluate the efficacy of MOVICOL® compared to
Aim
lactulose in the treatment of chronic constipation.

• Multi-centre, randomised study of 115 patients

comparing MOVICOL® with lactulose over a 4-week
Method
period (part A – see earlier slide) with the opportunity to
continue with MOVICOL® for 2 months (part B).

• Part B:
• No loss of efficacy and mean number of sachets
Results used decreased. v
• No serious adverse events and no significant
changes in laboratory results.

• This study demonstrated the efficacy and tolerability of

Conclusion
MOVICOL® over a 3 month period.
Safety & Tolerance
Wang et al. A randomised, controlled comparison of low
dose polyethylene glycol 3350 plus electrolytes with
ispaghula husk in the treatment of adults with chronic
functional constipation.
Clin Drug Invest 2004; 24(10):569-576
• To compare the efficacy and safety of MOVICOL® with
Aim
ispaghula husk in the treatment of constipation.

• Randomised, controlled, open label, parallel group study

Method of 126 patients randomised to MOVICOL® or ispaghula
husk for two weeks.

v
• 50% of patients on MOVICOL® had a bowel movement
Results within 24 hours and most had a bowel movement within
48 hours.

• Half the patients taking MOVICOL® had a response

Conclusion
within 24 hours and most by 2 days.
Gruss & Teucher. Treatment of chronic constipation.
Results of a multi-centre observation period on the use of
polyethylene glycol 3350 plus electrolytes.
Der Allgemeinarzt 1999; 21(16):1342-1350
• To observe the efficacy and tolerance of MOVICOL ® in
Aim patients with chronic constipation under conditions in an
out-patient setting.

• Multi-centre, observational study of 2029 chronic

Method constipation patients assessed after 2 and 4 weeks of
MOVICOL® treatment.

Results •Average daily dose of MOVICOL® was 1.69 sachets; after 4 weeks this was reduced to 1.55 sachets/day.
•78% of patients continued treatment after observation period with the average daily dose reduce to 1.44 sachets.
v

Conclusion •Tolerance does not develop over time with MOVICOL®.

Movicol® 13.8 g sachet, powder for oral solution -
abridged SmPC
MOVICOL®

Composition: Movicol® active ingredients are macrogol 3350 and selected physiological electrolytes. Each 13.8 g sachet contains
Macrogol 3350 13.125 g, Sodium Chloride 350.7 mg, Sodium Bicarbonate 178.5 mg and Potassium Chloride 46.6 mg. Indications:
Movicol® is an osmotic laxative that acts to increase stool volume, trigger colon motility, soften stools & facilitate defaecation, with no net
gain or loss of sodium, potassium and water. Movicol® is indicated for (1) the treatment of chronic constipation. Movicol® is also effective
in resolving (2) faecal impaction (defined as refractory constipation with faecal loading of the rectum and/or colon). Posology and
method of administration: children (below 12 years old): not recommended. Adults, adolescents and the elderly: each sachet should be
dissolved in 125 ml water. For faecal impaction 8 sachets may be dissolved in 1 litre of water. In chronic constipation a course of
treatment with Movicol® does not normally exceed 2 weeks; 1-3 sachets daily in divided doses, according to individual response. In
chronic constipation a course of treatment with Movicol® does not normally exceed 3 days; 8 sachets daily, all of which should be
consumed within a 6 hour period. Patients with impaired cardiovascular function: For the treatment of chronic constipation the dose
should be divided so that no more than two sachets are taken in anyone hour. Patients with renal insufficiency: no dosage change.
Contraindications: (i) intestinal perforation or obstruction due to structural or functional disorders of the gut wall, ileus and severe
inflammatory conditions of the intestinal tract, such as Crohn’s disease, ulcerative colitis and toxic megacolon; (ii) hypersensitivity to the
active ingredients or any of the excipients. Warnings and precautions: (i) the fluid content of Movicol® when re-constituted with water
does not replace regular fluid intake and adequate fluid intake must be maintained; (ii) diagnosis of impaction/faecal loading of rectum
should be confirmed by physical or radiological examination of the abdomen and rectum; (iii) if patients develop any symptoms indicating
shifts of fluids/electrolytes (e.g. oedema, shortness of breath, increasing fatigue, dehydration, cardiac failure) Movicol® should be stopped
immediately and electrolytes measured, and any abnormality should be treated appropriately; (iv) the absorption of other medicinal
products could transiently be reduced due to an increase in gastro-intestinal transit rate induced by Movicol®. Pregnancy/lactation:
Movicol® can be used during pregnancy and breast-feeding. Undesirable effects: abdominal pain, diarrhoea, vomiting, nausea,
dyspepsia, abdominal distension, borborygmi, flatulence and anorectal discomfort, allergic reactions, including anaphylactic reactions,
v
dyspnoea and skin reactions; allergic skin reactions including angioedema, urticarial, pruritus, rash, erythema; electrolyte disturbances,
particularly hyperkalaemia and hypokalaemia; headache, peripheral oedema. Interactions: (i) macrogol raises the solubility of medicinal
products that are soluble in alcohol and relatively insoluble in water; (ii) there is a possibility that the absorption of other medicinal
products could be transiently reduced during use with Movicol®. There have been isolated reports of decreased efficacy with some
concomitantly administered medicinal products, e.g. anti-epileptics. Presentation: boxes of 2, 6, 8, 10, 20, 30, 50, 60 or 100 sachets. Not
all pack sizes may be marketed. Since indications, dosage forms and strengths may vary from country to country, please consult your
local prescribing information. Full prescribing information, details and literature references are available on request. Latest update of
information: December 2018.

49
MOVICOL® Paediatric
Paediatric Constipation and Faecal Impaction
Constipation in Paediatrics

51
Diagnosis – Rome III Criteria

Children (≥ 4 years) Infants/Toddlers (< 4 years)

•Fewer than two bowel movements per

•Fewer than two bowel movements per week. week.
•At least one episode of faecal incontinence •At least one episode per week of
per week. incontinence after acquiring toilet skills.
•History of retentive posturing or excessive
•History of excessivevstool retention.
volitional stool retention.
•History of painful or hard bowel movements. •History of painful or hard bowel
•Presence of large faecal mass in rectum. movements.
•History of large diameter stools that may •Presence of large faecal mass in rectum.
obstruct the toilet. •History of large diameter stools that may
obstruct the toilet.

A diagnosis of constipation requires two or more of the

symptoms listed.
Plus insufficient criteria for IBS. 52
ROME IV Criteria

53
Aetiology of Paediatric Constipation

Diet

• Low fluid intake

• Too little fibre

Withholding of stools
v
• Not passing entire stool
• Rectum not fully emptied
• Ignore sensation of full rectum

54
 Large hard
stool

Long delay in Stretches and

passing stool may tear anus
v

Avoids
defaecation
because of pain

55
Prevalence

3% hospital outpatient
1-30% (mean 10.4%)
visits

25% children referred to

specialists

56
Faecal Impaction

■ Presents as faecal soiling

■ Problem perceived as behavioural one
■ Impact on child and family
■ Can have financial implications
■ Treatment involves both impaction and prevention of reaccumulation of stools

57
Quality of life

Constipation
Gastroesophagea Inflammatory
l reflux disease bowel disease

58
MOVICOL paediatric specifics

59
MOVICOL® Paediatric Plain

60
Composition

■ Each of 6.9g sachet of MOVICOL® Paediatric Plain contains:

Sodium
Macrogol 3350
chloride
6.563g v
175.4g
MOVICOL® Paediatric Plain does not
contain any excipients.
Sodium hydrogen Potassium
carbonate chloride 61
Indication

For the treatment of chronic constipation in

children 2 to 11 years of age and the treatment
of faecal impaction in children from the age of
five years, defined as refractory constipation with
faecal loading of the rectum and/or colon.
v

62
Dosage

■ Dosage for chronic constipation:

■ The usual starting dose is 1 sachet daily for children aged 2 to 6 years, and 2 sachets
daily for children aged 7 – 11 years.
■ The dose should be adjusted up or down as required to produce regular soft stools.
■ The maximum dose needed does not normally exceed 4 sachets a day.
■ Each sachet to be dissolved in 62.5ml water
v

63
Dosage

for faecal impaction:

■ A course of treatment for faecal impaction with MOVICOL® Paediatric Plain is for up to
7 days as follows:

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

No. of 4 6 8 10 12 12 12
sachets
v

.
■ The daily number of sachets should be taken in divided doses, all of which should be
consumed in a 12 hour period

64
Clinical Efficacy and Safety Studies
in Paediatrics

71
 Professor David Candy,
St Richard’s Hospital, Chichester, UK

Candy et al. Treatment of faecal impaction with polyethylene glycol plus

electrolytes (PEG+E) followed by a double-blind comparison of PEG+E versus
lactulose as maintenance therapy.
J Paediatr Gastroenterol Nutr 2006; 43:65-70

■ Open study of MOVICOL in faecal impaction followed by a double-blind study of

MOVICOL as maintenance therapy

*MOVICOL is unlicensed for the use in children aged <12 years of age.
v
Summary
• To assess the safety and efficacy of MOVICOL ® as
Aim a monotherapy for faecal disimpaction and to
compare with lactulose as maintenance therapy

• Phase 1 – Open study with MOVICOL® given

orally to 63 children (2-11 years) with intractable
constipation requiring hospitalisation for
Method
disimpaction. Phase 2 – Randomised, double-blind
comparison between lactulose and MOVICOL over
3 months
• MOVICOL® treatment for disimpaction was
successful in 92% of children without additional
interventions. v
Results
• Median time for disimpaction was 6 days.
• No children impacted whilst on MOVICOL vs 23%
on lactulose

• MOVICOL® was highly effective in the

management of paediatric faecal impaction and
Conclusion was used as monotherapy for disimpaction
without any negative impact or the need for
invasive interventions. 79
Safety

■ No adverse events during phase I judged to be serious. Most commonly reported were
gastrointestinal disorders that resolved
■ Total incidence rate of adverse events seen was higher in the lactulose group (83%)
than in the MOVICOL® group (64%).

80
Hardikar W, Cranswick N, Heine RG.
Macrogol 3350 plus electrolytes for chronic constipation in
children: a single-centre, open-label study.
J Paed Child Health 2007; 43:527-531

81
Summary

• To evaluate the safety and efficacy of

Aim MOVICOL®-Half in the treatment of chronic
constipation in children.

• Open label, non-comparative, non-randomised

Method study in 78 children (2-11 years) with chronic
constipation.

• Following treatment, the mean number of

spontaneous defaecations per week rose from
Results
1.4±0.54 at baseline to 6.8±3.85 after 14 days.
• Pain on defaecation and reported abdominal pain
significantly reduced.
• Treatment was well tolerated.

• This study supports the efficacy and tolerability

Conclusion of MOVICOL®-Half as a treatment for paediatric
constipation.

89
Conclusion

■ The majority of patients showed a marked improvement in their bowel movements and
hence in their constipation on Movicol

■ In addition, the investigator’s assessment of constipation indicated good improvement

on Movicol

■ Further evidence was provided by the parents’ assessment which also affirmed
Movicol’s efficacy
v

■ There were no safety concerns on treatment and no apparent safety risk during the 12
week treatment period

“Overall Movicol proved to be effective and safe

in the treatment of constipation in children aged 2 - 11 years”
Thomson MA, Jenkins HR, Bisset WM et al.
Polyethylene glycol 3350 plus electrolytes for
chronic constipation in children: a double blind, placebo
controlled, crossover study.
Arch Dis Child 2007; 92:996-1000

91
Summary

• To assess the efficacy of MOVICOL®-Half for the

Aim
treatment of paediatric chronic constipation .

• A randomised, double blind, placebo-controlled

Method crossover study in 51 children (2-11 years) with
chronic constipation.

• Patients treated with MOVICOL®-Half had a

significantly higher number of complete
defaecations per week thanvthose on placebo.
• Significantly less pain on defaecation, less
Results
straining on defaecation, better stool consistency
and lower percentage of hard stools was seen
with MOVICOL®-Half treatment.
• No significant safety issues arose.

• MOVICOL®-Half is a highly efficacious and well-

Conclusion
tolerated therapy.
96
Candy D, Belsey J
Macrogol (polyethylene glycol) laxatives in children with
functional constipation and faecal impaction: a systematic
review.
Arch Dis Child 2009;94:156-60

97
Results
■ The management of childhood constipation has tended to rely on anecdotal
evidence and empirical treatment choice, predominantly due to the lack of high
quality studies. However, recent publication of well-designed randomised
trials allows a more evidence-based approach and shows that PEG-based
treatments have proven efficacy and are a well-tolerated first-line treatment

Conclusion
■ In total, 7 qualifying studies were identified involving 594 children. Five
studies were comparisons of PEG with lactulose, one was a comparison with
v
milk of magnesia and the other was comparing against placebo. Study
durations ranged from 2 weeks up to 12 months. PEG was significantly more
effective than placebo. It was also either equivalent to (two studies) or
superior to (four studies) the active comparator. Meaningful meta-analysis
was not possible due to the differences in study designs.

102
 Movicol® Paediatric Plain 6.9 g sachet, powder for oral
solution abridged SmPC

MOVICOL® PAEDIATRIC PLAIN

Composition: Movicol® Paediatric Plain active ingredients are macrogol 3350 and selected physiological electrolytes. Each 6.9 g sachet contains 6.563 g
macrogol 3350, 0.1754 g sodium chloride, 0.0893 g sodium hydrogen carbonate, 0.0251 g potassium chloride. Indications: Movicol® Paediatric Plain is an
osmotic laxative that acts to increase stool volume, trigger colon motility, soften stools & facilitate defaecation, with no net gain or loss of sodium, potassium
and water. Movicol® Paediatric Plain is indicated for treatment of: (1) chronic constipation in children, aged 2-11 years; (2) faecal impaction (refractory
constipation with faecal loading of rectum &/or colon) in children, aged ≥5 years. Each sachet should be dissolved in 62.5 mL water (the total daily dose may
be prepared & refrigerated - for example, 12 sachets in 750 mL water). Posology and method of administration: in chronic constipation start with 1
sachet/day in children aged 2-6 years, 2 sachets/day in children aged 7-11 years; then adjust dose as required to get regular soft stools – when increasing
dose, increase every 2nd day; maximum dose is 4 sachets/day. Treatment maybe prolonged (6-12 months), with gradual stopping & resuming if constipation
recurs. Safety and efficacy of Movicol® Paediatric Plain has only been proved for a period of up to 3 months. In faecal impaction use an up to 7-day course –
day 1, 4 sachets; day 2, 6; day 3, 8; day 4, 10; day 5, 12; day 6, 12; day 7, 12 – with daily doses split over 12 hours; stop treatment if disimpaction (passage of
large volume of stools) occurs; after disimpaction, child should follow appropriate bowel management program to prevent reimpaction, including Movicol®
Paediatric Plain treatment at dosage given for chronic constipation. For patients aged ≥12 years, use Movicol®. Movicol® Paediatric Plain is not recommended
for faecal impaction in children with impaired cardiovascular or renal function. Contraindications: (i) intestinal perforation or obstruction due to structural or
functional disorder of the gut wall, ileus, severe inflammatory conditions of the intestinal tract, such as Crohn's disease and ulcerative colitis and toxic
megacolon; (ii) hypersensitivity to the active substances. Precautions: (i) the fluid content of reconstituted Movicol® Paediatric Plain should not replace
regular fluid intake, (ii) adequate fluid intake must be maintained, (iii) diagnosis of faecal impaction or faecal loading of the rectum should be confirmed by
physical or radiological examination of abdomen & rectum, (iv) in case of rare occurrence of symptoms of body fluid or electrolytes imbalance (such as
oedema, shortness of breath, increasing fatigue, dehydration, cardiac failure), immediately stop treatment, measure electrolytes & treat any abnormality
appropriately, (v) when used in high doses, administer with caution to children with impaired gag reflex, reflux oesophagitis or diminished levels of
v
consciousness, (vi) Movicol® Paediatric Plain has no calorific value, (vii) absorption of any co-medications may be transiently reduced due to increased
gastrointestinal transit time induced by Movicol® Paediatric Plain. Pregnancy/lactation: Movicol® Paediatric Plain can be used during pregnancy and during
breast-feeding. Undesirable effects: Very common (≥1/10): abdominal pain, borborygmi. Common (≥1/100, <1/10): diarrhoea, vomiting, nausea and anorectal
discomfort. Interactions: (i) medicinal products in solid dose form taken within one hour of administration of large volumes of macrogol preparations (as used
when treating faecal impaction) may be flushed from the gastrointestinal tract and not absorbed; (ii) macrogol raises the solubility of medicinal products that
are soluble in alcohol and relatively insoluble in water; (iii) there is a possibility that the absorption of other medicinal products could be transiently reduced
during use with Movicol® Paediatric Plain. There have been isolated reports of decreased efficacy with some concomitantly administered medicinal products,
e.g. anti-epileptics. Presentation: Sachet is laminated with 4 layers: low density polyethylene (LDPE), aluminium, LDPE, paper. Pack sizes: boxes of 6, 8, 10,
20, 30, 40, 50, 60 or 100 sachets. Not all pack sizes may be marketed. Since indications, dosage forms and strengths may vary from country to country,
please consult your local prescribing information. Full prescribing information, details and literature references are available on request. Latest update of
information: December, 2018.

103
MOVICOL® Pregnancy
Constipation in Pregnancy

105
 Pregnancy

Animal studies do not

indicate direct or indirect
MOVICOL® may be harmful effects with
used during pregnancy respect to pregnancy,
and lactation embryonal/foetal
development, parturition
or post-natal
development

v
No effects during pregnancy are
anticipated, since systemic
exposure to macrogol 3350 is
negligible

Norgine Ltd. MOVICOL® Product Range Company Core

Data Sheet, v 6.0 September 2014
Pregnancy Data

■ Proportion of patients prescribed macrogols for constipation in pregnancy

increased from 13.3% in 2005 to 31.7% in 2009 (UK Cohort study)

■ Observational open-label study evaluating the efficacy of PEG 4000 + E in

pregnant women with constipation:
- 1 spontaneous abortion – unlikely to be related to the study drug
- 2 preterm deliveries – not considered related to the study drug

- No neonatal complications
- Constipation was resolved in 73% patients
v
■ American Gastroenterological Association Institute Clinical Practice and
Economics concluded that PEG should be given if potential benefits outweigh
the risk
- Recommendation based on the absorption and metabolism of PEG and results of animal
teratogenesis studies
• Shafe ACE et al. Ther Adv Gastroenterol 2011; 4:343-363
• Neri I et al. J Midwifery Womens Health 2004; 49:355-358
• Mahadevan U et al. Gastroenterology 2006; 131:283-311
 Prevalence

Up to 51% of women
Rates of constipation
experience constipation at
symptoms vary markedly
some point during their
from study to study
pregnancy

Rates of constipation found to

be higher in the first two
trimesters

108
Causes of Constipation in Pregnancy

■ Multifactorial!

Dietary and life style issues

• Changes in dietary habits and level of physical activity

Hormonal changes

• Hormonal effects on GI tract v

Mechanical changes

• Growing foetus and placenta

Medication side effects

• e.g. antiemetics, antihistamines, iron supplementation,
magnesium sulfate 109
 Develop
No history of
constipation
bowel
for first time
problems
in pregnancy

Symptoms
Constipation
are worse
prior to
when
pregnancy v
pregnant

 Constipation is also an important factor in the development of

uterovaginal prolapse

110
MOVICOL®
SMPC - Pregnancy

111
SmPC Information

■ Limited amount of data from the use of MOVICOL® in pregnant women

■ Indirect reproductive toxicity in animals
■ No effects are anticipated – systemic exposure is negligible
■ MOVICOL® can be used during pregnancy

112
Indirect toxicity in animals

■ Indirect embryofetal effects in rabbits at maternally toxic dose

■ Rabbits are sensitive test species and studies conducted under exaggerated
conditions, which are not clinically relevant
■ No indication of teratogenic effect

113
Existing Claims/Data For Movicol® -
Importance For Pregnancy

114
Gentle, effective and well tolerated laxative that controls constipation to restore and maintain health bowel
function

Works in harmony with the body’s own processes to increase stool volume and assist with
comfortable healthy bowel movements

Well tolerated, passing virtually unchanged through the GI tract with minimal absorption

Minimal net gain or loss of water or electrolytes

Long-term use does not lead to treatment tolerance; efficacy is maintained with a continuous
improvement in symptoms whilst dosage is maintained or reduced

PEG• should be used in preference to lactulose

Supporting papers: SmPC
• Gordon et al, Cochrane Database Systematic Reviews; 2012,CD0094118
• Attar et al, Gut 1999;44:226-30
• Hardikar et al, JPGN 2007;43:527-531
• Gruss & Teucher, The General Practitioner 1999;21:1342-1350
• Gruss & Ulm, Eur J Ger 2004;6:143-160
• Migeon-Duballet et al, CMRO 2006;22:1227-1235
115
• Lee-Robichaud et al, Cochranhe Database Systematic Reviews 2010, CD007570
Clinical Use of MOVICOL® in
Pregnancy

116
Pharmacology of Macrogols

Systemic absorption of macrogol 3350 is negligible in human

subjects

No accumulation of macrogol occurs v

Macrogol 3350 is not metabolised by intestinal microflora

117
Macrogol 4000

■ Licence for Macrogol 4000 (e.g Dulcobalance) suggests it is safe to use in pregnancy
because of the limited systemic exposure
■ Negligible systemic toxicity → negligible amount in mother’s blood → negligible
amount transmitted to developing foetus → low risk of foetal abnormalities,
spontaneous abortions or miscarriage

118
Macrogol 3350 and 4000 – any difference?

Weight chain range: 708 - 13201 Weight chain range: 400 - >8000

Batches of both contain molecules of similar weight

119
■ Macrogols are specified by the mean molecular weight of various chains and there is
overlap in the molecular weight of chains in macrogol 3350 and 4000
■ Material with a mean molecular weight of 3350 may be classified as 4000 in some
countries
■ MOVICOL® contains electrolytes – no suggestion unsafe in pregnancy

120
Macrogol 4000 Study

■ Neri I et al. Polyethylene glycol electrolyte solution (Isocolon) for constipation during
pregnancy: An observational open-label study.
J Midwifery Womens Health 2004; 49:355-358

121
Observational, open-label study in pregnant women with constipation

40 women took 250ml PEG 4000 with electrolytes twice a day until
first evacuation followed by 250ml once a day for 15 days

Ages ranged from 28-34 years, with the gestational age ranging from 8-
37 weeks

122
Results

■ One spontaneous abortion → unlikely related to drug

■ Two preterm deliveries → not related to study drug
■ Mean gestational age at delivery was 39.2 weeks
■ No neonatal complications observed

123
GPRD Laxative Use Study

GP-diagnosed constipation in 2005 (795 pts) 2009 (1648 pts)

pregnancy % %

Treated with laxatives 33.1 44.2

Total per laxative of those treated    

Macrogols 13.3 31.7

Senna 14.8 12.3
Lactulose 81 64.2

Pregnant patients with a diagnosis of constipation,vtreated with

laxatives in 2005 and 2009

Proportion of patients prescribed macrogols for constipation in pregnancy

has increased and the proportion prescribed lactulose and other laxatives
has decreased over a 5 year period

124
Consensus Guidelines

■ Tytgat et al:
- PEG and electrolytes technically meet criteria for an idea laxative in pregnancy → based on lack of
metabolism and animal teratogenesis trials
- Data insufficient to demonstrate conclusively the effects of PEG on foetus
■ American Gastroenterological Association Institute Technical Review:
- PEG should be given if benefits outweigh the risk
v

125
MOVICOL® Update
Elderly Patients
 v

Report developed to uncover the impact of functional constipation amongst older

adults living in care homes and the community across Europe
 ILC Report Key Conclusions

■ Constipation is more common in people over 65 and effects 1 in 5 older adults living in
the community

■ Recent studies indicate up to 80% of adult care home residents >65 are chronically
constipated

■ In UK (2011), 25107 hospital admissions in >65 were as a result vof constipation

■ On average, >65 spend 4.9 days in hospital for a primary diagnosis of constipation

The Burden of Constipation in our Ageing Population. ILC-UK

report. Available from: http://www.burdenofconstipation.com/
Prevalence of Constipation

4-20% of
community

50-74% of
elderly in
15-17% adults
nursing
homes

15-20% of
1-30% children
elderly
What causes constipation?

Primary Secondary
Constipation constipation
•Insufficient fibre in the diet •As a result of drugs and
•Inadequate fluid intake surgery. Drugs that are known
•Lack of exercise to cause constipation
v include
opioids (e.g. morphine)
•Environmental issues (e.g. •As a result of an underlying
lack of private toilet illness. Examples include
facilities) Parkinson’s disease and Stroke

130
 Impact of Constipation

Quality of Complication Economic

Symptoms Life (QoL) s Impact
• QoL in chronic
constipation • Exacerbation
• 61162 hospital
patients lower of
admission for
than normal haemorrhoids.
constipation in
• Bloating population. • Exacerbation
the UK alone
• Distention • QoL of anal
(2011).
• Abdominal comparable to fissures.
• Admissions
pain other chronic • Risk factor for
accounted to
• Nausea conditions colorectal
v more than
(e.g. diabetes) cancer.
120000 bed
• In children, • Faecal
days.
QoL lower impaction.
than with IBD.
Elderly Data for MOVICOL®
Alix et al. Treatment of Constipation in the Elderly: Benefit of Polyethylene Glycol +
Electrolytes. La Revue de Geriatrie 2001; 26(1):65-72
Study 1

Aim •To assess the efficacy, acceptability and optimum dose of MOVICOL® in elderly patients

Method •Open, multi-centre trial in 30 elderly hospitalised patients (average age 84 years) with moderate constipation. Treatment was for 3 months with 2 sachets of MOVICOL® per day

Results
•Mean number of stools was 1 per day
•No water or electrolyte imbalances were reported
•Tolerance was good
Study 2
• To assess the efficacy and safety of
MOVICOL® in treating refractory
Aim constipation with accumulation of stools in
the rectal ampulla in elderly patients

• Open trial in 11 of the initial 30 elderly

hospitalised patients (in study 1). Age range
Method was 65-88 years. Treatment was with 8
sachets of MOVICOL® for 3 days

• 81% of patients reported complete relief

v
• Cumulatively, complete resolution was
100% by day 3 of treatment with
Results MOVICOL®
• Abdominal pain and borborygmi decreased
• No alterations in laboratory safety data
Overall conclusion: MOVICOL® was well-tolerated and
Aim
effective in an elderly population
Any Questions?

134