Download Project: Abbott Course Title: REDUCTIL Module title/ID: Competition

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Abbott
Course
Title:
REDUCTIL
Module
title/ID:
Competition
MODULE
NO:
5
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Unit 5: Competition
Contents
Aims and objectives
By the end of this unit, you should be able to:

Recognise the current and future competitors to Reductil

Differentiate Reductil from its competitors

Explain the strengths and weaknesses of Reductil and its competitors
Why do I need to know this?
Although Reductil is one of three major mainstream anti-obesity products currently
on the market, the obesity epidemic is driving drug development and the market
place is becoming increasingly competitive. To advise health care professionals on
the benefits of using Reductil, you need to know the relative merits and
disadvantages of the competitor products, so this unit is central to your role.
This unit outlines the strengths and weaknesses of orlistat, in both its prescription
(Xenical) and over the counter (Alli) versions, in relation to Reductil, and describes
the opportunities and threats emerging in the obesity arena.
The information in this unit will provide you with the foundation for differentiating
Reductil from orlistat. It will therefore help you sell Reductil as the anti-obesity agent
of choice that provides efficacy, tolerability and positive changes to the risk factors
associated with obesity.
5.1 Overview of competitors
Pharmacotherapy for weight loss has had a shaky history. A number of agents have
been used in the treatment of obesity over the years but were subsequently found to
have unacceptable side effects and, in some cases, there were even reports of
deaths. However, the safety and efficacy of three of the currently available agents,
Reductil, Xenical and Alli, have been thoroughly evaluated in a number of clinical
trials.
Furthermore, post-marketing surveillance studies have provided further reassurance
on the safety profiles of these agents.1,2,3 (1. Data on file: Sibutramine: Global
analysis of safety. Abbott Laboratories Ltd. 1999. 2. Xenical, Summary of Product
Characteristics: Roche, 2006. 3. Alli Summary of Product Characteristics: GSK,
2007)
Table 1: A brief history of anti-obesity agents4 (Adapted from Bray and
Greenway, 1999 4. Bray GA, Greenway FL. Current and potential drugs for
treatment of obesity. Endocr Rev
1999;20:805-75.)
(GRAPHICS BRIEF: Will revise and expand this table as follows: 1) Rimonabant:
Outcome text should change to read “Psychiatric problems”; 2) A new line should be
added to the end of the table for Alli. Entry should read as follows: 2007 Alli Effective
and well-tolerated.)
Recorded pharmacotherapy of obesity stretches back over 100 years, when
medicines were unregulated and safety testing was cursory, in those days thyroid
extract was used to treat obesity. The doses required to achieve weight loss resulted
in a degree of hyperthyroidism with detrimental effects on the heart, muscle and
bone.
Safety problems were also seen in the 20th century with dinitrophenol (sold under a
number of names, most recently as ‘fat-burner’ capsules), aminorex or aminoxaphen
(Menocil), digitalis and diuretics, the severe side effects of which led to the
withdrawal of these products as obesity treatments. In addition, amphetamine use
was followed by reports of addiction, a problem that has beset drugs that are
structurally similar to amphetamine, regardless of their actual addictive potential.
REDUCTIL XENICAL AND ALLI
HAVE BEEN RIGOROUSLY
EVALUATED IN CLINICAL TRIALS
More recently, following reports of valvular insufficiency with the combination of
fenfluramine (Ponderax™) and phentermine (Duromine™ and Ionamin™), it became
prudent to withdraw both fenfluramine and dexfenfluramine (Adifax™) from the
market in 2001. 5. (Fenfluramine and dexfenfluramine withdrawn. Current Problems
in Pharmacovigilance 1997; 23:13-16.)
Following an appeal to the European Court of First Instance, phentermine and
another anorectic, amfepramone (Tenuate Dospan, diethylpropion) were reinstated
in 2002. However, an appeal to the EU against the withdrawal of fenfluramine and
dexfenfluramine was dismissed in 2004.
In 2008 the European Medicines Agency (EMEA) recommended that doctors no
longer prescribed rimonabant, (Acomplia). It said that the risk of serious psychiatric
problems and even suicide was too high. 13. (Rimonabant, Summary of Product
Characteristics: sanofi-aventis, 2008; 14. Public statement on Accomplia
(Rimonabant) Withdrawal of the marketing authorisation in the European Union.
30/01/09. EMEA/39457/2009)
Although Reductil and orlistat have established safety profiles, given the
uncomfortable history of anti-obesity pharmacotherapy, healthcare professionals will
have every reason to be wary of new agents without a good safety record in clinical
use. However, it is not only safety considerations that differentiate anti-obesity
products. As you learnt in Unit 3, Reductil and orlistat each have completely different
modes of action (MOA). These different MOAs result in differences in efficacy,
safety and convenience of use.
This unit will review the MOA of orlistat in both its prescription and over-the-counter
forms and briefly discuss the benefits and drawbacks of other therapies. It will also
provide an overview of the published clinical data for orlistat to provide you with the
salient facts about Reductil’s competitors.
Check your understanding
[True or False]
Is this statement true or false?
Reductil and orlistat each act by completely different MOAs, resulting in differences
in efficacy, safety and convenience of use.
[Answer: True]
ANTI-OBESITY AGENTS
ARE DIFFERENTIATED BY
MOA, SAFETY, EFFICACY
AND CONVENIENCE
OF USE
5.2 Orlistat (Xenical)
Orlistat is a gastrointestinal lipase inhibitor, which acts in the gastrointestinal tract to
prevent the absorption of fats. In its prescription form it is known as Xenical.
Figure 1: Orlistat structure
[GRAPHICS BRIEF: This graphic will be revised to include labels explaining what the
various symbols mean]
Indications
Orlistat is indicated for the treatment of obese patients (BMI ≥30 kg/m2) or
overweight patients (BMI ≥28 kg/m2) with associated risk factors, in conjunction with
a mildly hypocaloric (Hypocaloric: referring to a diet that contains less energy than
expended in normal activities) diet .2 (2. Xenical, Summary of Product
Characteristics: Roche, 2006.))
In December 2006 guidance issued by the UK’s National Institute for Clinical
Excellence (NICE) on the use of orlistat6 (6. Obesity. Guidance on the prevention,
identification, assessment and management of overweight and obesity in adults and
children. NICE clinical guideline 43. National Institute for Health and Clinical
Excellence. Issue date: December 2006.) stated that orlistat should be prescribed
only as part of an overall plan for managing obesity in adults who meet one of the
following criteria:

A BMI of ≥28.0 kg/m2 with associated risk factors

A BMI of ≥30.0 kg/m2.
Therapy should be continued beyond 3 months only if the person has lost at least
5% of their initial body weight since starting drug treatment.
Dosing and administration

The recommended dose of orlistat is one 120mg capsule three times a
day.(t.i.d.)

Orlistat should be taken with water immediately before, during or after each
main meal. If a meal is missed or contains no fat, the dose of orlistat should
be omitted.

Treatment with orlistat should be discontinued after 12 weeks if patients have
been unable to lose at least 5% of the body weight measured at the start of
drug therapy.
Orlistat and contraception
The Summary of Product Characteristics for Xenical has recently been changed to
emphasise orlistat’s effect on oral contraceptives. Orlistat may reduce the efficacy of
some oral contraceptives and the use of an additional contraceptive method is
recommended to prevent possible failure of oral contraception that could occur in
case of severe diarrhoea.2 (2. Xenical, Summary of Product Characteristics: Roche,
2006.) By contrast, with Reductil, patients need only ensure that they use adequate
contraception. (7. Reductil, Summary of Product Characteristics: Abbott Laboratories
Limited, 2006.)
WITH ORLISTAT WOMEN
NEED ADDITIONAL
CONTRACEPTIVE
PRECAUTIONS IF USING
THE PILL
Mode of action
Orlistat is a chemically synthesised derivative of lipstatin, a bacterial inhibitor of
lipases.8 (8. Drent ML, van der Veen EA. Lipase inhibition: a novel concept in the
treatment of obesity. Int J)
It is minimally absorbed into the bloodstream, but works locally in the stomach and
small intestine, where it prevents the action of two digestive enzymes, gastric and
pancreatic lipases (Figure 2).2 (2. Xenical, Summary of Product Characteristics:
Roche, 2006. 2. Xenical, Summary of Product Characteristics: Roche, 2006.)
These enzymes normally break down fats that we consume in our diet into fatty
acids (Fatty acids: a degradation product of lipid digestion in the gastric tract) and
monoglycerides (Monoglycerides: an intermediate in the degradation and synthesis
of lipids. Monoglycerides are a major end product of triglyceride degradation) that
can be absorbed through the lining of the intestines into the blood stream.
Figure 2: Orlistat acts by blocking the action of lipases in the stomach and
small intestine
(GRAPHICS BRIEF: Current graphic is fine. No revisions proposed.)
ORLISTAT MEDICALLY
INDUCES
MALABSORPTION OF FAT
IN THE GASTRIC TRACT
Pharmacology of orlistat
Orlistat is detected only sporadically and in very low levels in plasma (<10 ng/ml or
0.02 mmol), with no evidence of accumulation, which is consistent with minimal
absorption.2 ( Xenical, Summary of Product Characteristics: Roche, 2006.)
Metabolism of orlistat occurs mainly in the gastric wall, where it is converted to two
major metabolites (M1 and M3). The metabolites are not thought to be
pharmacologically active. Approximately 97% of the administered dose is excreted in
the faeces, of which 83% is the parent compound.2 (2. Xenical, Summary of Product
Characteristics: Roche, 2006.)
Evidence
A systematic review of clinical trials with orlistat found that trials recruiting obese
patients usually found statistical differences in weight loss between the orlistat-
treated group and the placebo group. However, weight loss was greater in patients
with uncomplicated obesity than in those with type 2 diabetes. (9. O'Meara S,
Riemsma R, Shirran L, Mather L, ter Riet G. A systematic review of the clinical
effectiveness of orlistat used for the management of obesity. Obes Rev 2004;5:5168.)
Figure 3: Weight loss with orlistat (pooled data from clinical trials: weighted
mean difference)
(GRAPHICS BRIEF: Current graphic fine. No revisions proposed.)
ORLISTAT ACTS IN THE
GI TRACT AND IS ONLY
MINIMALLY ABSORBED
Weight maintenance
Orlistat may help in maintaining weight lost after dieting by slowing the regain in
weight. After the end of a 6 month diet (without pharmacotherapy), patients treated
with orlistat regained 32.4% of the weight lost weight, compared with patients on
placebo who regained 56.0% of the weight lost over a 1 year period. (9. O'Meara S,
Riemsma R, Shirran L, Mather L, ter Riet G. A systematic review of the clinical
effectiveness of orlistat used for the management of obesity. Obes Rev 2004;5:5168.)
Tolerability
Orlistat is generally well tolerated with the exception of gastrointestinal events. In the
XENDOS study, during the first year of treatment 91% of patients on orlistat
complained of these adverse events, compared with 65% on placebo.
In the XENDOS study, the incidence of adverse events was highest in the first year
of treatment, but following this study the restriction on duration of treatment with
orlistat in the Summary of Product Characteristics was removed. (10 Torgerson JS,
Hauptman J, Boldrin MN, Sjostrom L. XENical in the prevention of diabetes in obese
subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle
changes for the prevention of type 2 diabetes in obese patients. Diabetes Care
2004;27:155-61.)
Very common adverse events reported with orlistat use (2. Xenical, Summary of
Product Characteristics: Roche, 2006):

Influenza

Hypoglycaemia

Headache

Respiratory infection

Oily spotting from the rectum

Abdominal pain/discomfort

Flatus with discharge

Faecal urgency

Fatty/oily stools

Flatulence

Liquid stools

Oily evacuation

Increased defecation
SOME ORLISTAT WEIGHT
LOSS MAY BE
ATTRIBUTABLE TO
AVOIDANCE OF FAT TO
REDUCE SIDE EFFECTS
Check your understanding
[Multiple choice question]
1. Choose the correct answer from the options below.
Treatment with orlistat should be discontinued if patients have been unable to lose at
least 5% of the body weight measured at the start of drug therapy after:
a) 6 weeks
b) 10 weeks
c) 12 weeks
d) 16 weeks
(Answer: (c) 16 weeks)
[True or False]
2) Is this statement true or false?
A systematic review of orlistat clinical trials found weight loss was greater in patients
with Type 2 Diabetes than uncomplicted obesity.
(Answer: False)
5.3 Orlistat (Alli)
Orlistat is also the active ingredient in Alli (GSK), an over the counter weight loss
drug which gained FDA approval in 2007 and became the first weight loss drug to be
awarded a non-prescription licence in Europe in 2009.
Although Alli has the same active ingredient as Xenical, there are some important
differences between the two drugs:
 Alli is available over the counter

Alli is administered in a 60 mg dose as opposed to 120 mg

Alli is better tolerated than Xenical; gastrointestinal events occur less
frequently and are more manageable
Another important difference is that Alli is supplied with a comprehensive information
pack. The Alli starter pack in the United States includes over 200 pages of materials
designed to guide individuals through the Alli program, set expectations for gradual
weight loss, educate about healthy eating choices, and assist them in monitoring
daily diets and managing treatment effects.
Indications
Alli is indicated for weight loss in adults who are overweight (body mass index, BMI,
28 kg/m2) and should be taken in conjunction with a mildly hypocaloric, lower-fat
diet. (3. Alli, Summary of Product Characteristics: GSK, 2007.)
Treatment should not exceed 6 months.
Dosing and Administration

The recommended dose of Alli is one 60 mg capsule to be taken three times
daily.

Alli, like Xenical, should be taken with water immediately before, during or up
to 1 hour after each main meal. If a meal is missed or contains no fat, the
dose should be omitted. No more than three 60 mg capsules should be taken
in 24 hours.

Patients should consult their doctor if they have been unable to lose weight
after 12 weeks of treatment with Alli.
MOA
Alli works in the same way as 120 mg orlistat. It reduces the amount of fat absorbed
into the blood stream by inhibiting the action of two digestive enzymes (gastric and
pancreatic lipases) which break down fat into fatty acids and monoglycerides.
Pharmacology of Alli
The pharmacokinetic properties of Alli are very similar to those of 120 mg orlistat.
Studies in normal weight and obese volunteers show that absorption is minimal.
Metabolism occurs mainly in the gastrointestinal wall where Allis is converted into
two major metabolites, M1 and M3. Elimination of the unabsorbed active substance
occurs mainly by faecal excretion.
Evidence
Clinical studies suggest that Alli taken three times daily can block the absorption of
approximately 25% of dietary fat.
Two double blind, randomised, placebo-controlled studies which assessed the
efficacy of Alli in adults with a BMI 28 kg/m2 show that Alli can induce greater
weight loss than a placebo when taken three times daily in conjunction with a hyper
caloric diet. Weight loss was assessed over 12 months in both studies, but most
weight loss occurred over the first 6 months.
(GRAPHICS BRIEF: New graphic. We will create at least one new table graphic
based on the clinical trial data in the Pharmacodynamic properties section of the Alli
SPC.)
The weight loss after 6 months of treatment produced other benefits including a
reduction in total cholesterol, LDL cholesterol and weight circumference.
Tolerability
The side effects most commonly observed with Alli are gastrointestinal in nature.
However, compared to 120 mg orlistat these gastrointestinal events are milder and
occur less frequently. In clinical studies, the 60 mg capsule of Alli demonstrated
comparable efficacy and safety profiles to the 120 mg prescription capsule, but had a
lower incidence of side effects. In addition, only a small percentage of trial subjects
withdrew due to gastrointestinal adverse events (5.4% on 120mg compared to only
3.2% on 60-mg).
Common adverse events associated with Alli include:
 Anxiety

Oily spotting

Flatus with discharge

Faecal urgency

Fatty oily stool

Oily evacuation

Flatulence

Soft stools

Abdominal pain

Faecal incontinence

Liquid stools

Increased defaecation
Table 2: Comparison of characteristics of orlistat (Xenical), orlistat (Alli), and Reductil
[2 (Xenical, Summary of Product Characteristics: Roche, 2006.), 3 (Alli, Summary of
Product Characteristics: GSK, 2007), 7 (Reductil, Summary of Product
Characteristics: Abbott Laboratories Limited, 2006.) 12 (Scheen AJ, Ernest P. New
antiobesity agents in type 2 diabetes: overview of clinical trials with sibutramine and
orlistat. Diabetes Metab 2002;28:437-45.)]
(Graphics brief: Table will be revised to remove Rimonabant column. New column for
Alli will be added in its place. Details to follow.)
Check your understanding
[Multiple choice question]
1. Choose the correct answer from the options below.
Which of the following adverse events are commonly associated with Alli? Select all
that apply.
a) Anxiety
b) Hepatitis
c) Oily spotting
d) Bullous eruption
(Answers: a) Anxiety; (c) Oily spotting)
2) Is this statement true or false? (True or false)
Alli is less well tolerated than Xenical and is associated with a greater frequency and
severity of gastrointestinal events..
(Answer: False)
5.3 Other therapies
Rimonabant
In early 2009 the European Medicines Agency officially decided to withdraw the
marketing authorisation for Rimonabant, (Acomplia). The decision was made
primarily because of the risk of depression and suicide associated with the drug.
Recent studies had shown an increased risk of psychiatric disorders in obese or
overweight patients taking Rimonabant compared with placebo. (13 Rimonabant,
Summary of Product Characteristics: sanofi-aventis, 2008; 14. Public statement on
Accomplia (Rimonabant) Withdrawal of the marketing authorisation in the European
Union. 30/01/09. EMEA/39457/2009.)
Rimonabant was developed based on the knowledge that cannabis consumption is
known to stimulate appetite. When people smoke cannabis, the increase in appetite
is due to exogenous cannabinoids. Endogenous cannabinoids, such as anandamide,
are thought to have a role in increasing appetite whether or not any additional
exogenous cannabinoids have been taken. On this premise, the drug’s developers
thought that blocking cannabinoid receptors in the brain might reduce appetite.
Therefore, they developed rimonabant, which blocks a particular subset of
cannabinoid receptors (CB1) in the brain and adipose tissue.
Because the CB1 receptors were thought to play a role in the phenomena of
dependence and habituation, therefore, as well as controlling food consumption, they
were also thought to play a role in nicotine dependence.
Discontinued Therapies
As noted earlier, a number of agents have been used in the treatment of obesity over
the years but have subsequently been withdrawn after being found to have
unacceptable side effects. The table below provides more information about some of
these discontinued therapies:
[Graphic brief: New graphic. Will create a table with the following columns: column 1:
the name of the drug; column 2: Side Effects; column 3: Outcome. The information
that will be presented in this table is summarised below.]
Amphetamine/dextamphetamine: Side effects: Tachacadyia, hypertension, addiction:
Withdrawn
Ephedra: Side effects: Hearing problems, stroke: Withdrawn
Phentermine: Side effects: Arrhythmia, hypertension, convulsions: Withdrawn
Fenfluramine, dexfenfluramine: Side effects: Valvular heart disease: Failed to Gain
Regulatory Approval
Alternative Weight Loss Therapies
Some patients turn to alternative remedies in an attempt to lose weight. There is
limited scientific evidence to support the effects of most of these therapies, and in
some cases they may not have a positive effect.
Herbal Remedies and Dietary Supplements
Most herbal remedies work by suppressing appetite. They can be effective in the
short term, but over the long term may be addictive and cause health problems.
Some of the more commonly used remedies are described below.
Aloe
This is more commonly used as a topical product for healing wounds, but oral forms
of aloe are added to herbal weight-loss products. Oral aloe produces a strong
cathartic response (producing bowel movements), and many aloe weight-loss
products are marketed as "internal cleansers." However, the use of aloe internally
has not been shown to be effective for permanent weight loss. Aloe or aloecontaining products should not be ingested. Doing so can lead to side effects such
as abdominal cramping, diarrhoea, electrolyte disturbances, and decreases in
potassium. In addition, there can be significant drug interactions with some
medications, including digoxin (Lanoxin)..
Cascara
A strong laxative which is often used in herbal weight loss products. Misuse of
cascara can cause disturbances in electrolytes. It may also interact with medications
such digoxin and diuretics.
Dandelion
A natural diuretic that can product weight loss by decreasing body water. It may
cause allergic reactions in some individuals. There are also reports that it may have
carcinogenic (cancer-causing) properties.
Ephedrine (ma-huang)
A common ingredient in herbal dietary supplements used for weight loss. It is also
used to make methamphetamine, better known as speed. Ephedrine can suppress
appetite to a limited extent, but there is little clinical trial evidence to show its
effectiveness as a weight-loss aid. Ephedrine is associated with a number of serious
side effects, including high blood pressure, heart rate irregularities, insomnia,
nervousness, tremors, seizures, heart attacks, strokes, and even death. Ephedrine
can also interact with many prescription and over-the-counter drugs.
Acupuncture
Acupuncture is an alternative therapy from China in which needles are inserted into
specific pressure points on the body. The exact mechanism by which acupuncture
works is unknown, but it is claimed that it releases endorphins which have a calming
and relaxing effect and make it easier to deal with the stress, frustration and anxiety
which can lead to overeating. There have been numerous studies of acupuncture,
but while there is some evidence that it is an effective form of treatment for
conditions such as back pain, dental pain and migraine there is none to suggest that
it is an effective treatment for obesity.
Hypnotherapy
Hypnotherapy is the use of hypnosis for treating conditions such as addition, anxiety,
depression and obesity. Hypnosis is a state of relaxation, which can vary in intensity
from light to deep. The hypnotherapist induces this state through a variety of
methods including eye fixation, progressive relaxation and imagery. Once the patient
is in a relaxed state the therapist uses suggestion to influence behaviour and relieve
symptoms. It is recommended that people with personality disorders and certain
neurological disorders avoid hypnotherapy as evidence suggests it can trigger the
onset of episodes of these disorders.
Ayurveda
Ayurveda is a holistic system of medicine from India. It employs nutritional guidance,
herbal medicine, exercise therapy, transcendental meditation and purification
therapies. The patient is first diagnosed by means of a three point system involving
observation, examination by touch and a detailed questionnaire. Treatment is
designed to soothe and correct imbalances in body type. It typically starts with
guidelines for healthy living and diet, but may also include a course of purification to
eliminate toxins. Other Ayuverdic remedies for weight loss include herbal body
treatments and massage.
[Multiple choice question]
1. Choose the correct answer from the options below.
Which of the following side effects caused Rimonabant to be withdrawn from sale in
Europe?
a) Arrhythmia
b) Depression
c) Hypertension
d) Stroke
(Answer: b) Depression)
5.4 Summary of key points
Orlistat

Orlistat is a gastrointestinal lipase inhibitor, which acts in the gastrointestinal
tract to prevent the absorption of fats.

Dosing is three times daily with food and drink restrictions. In addition,
patients should miss a treatment if a meal contains no fat.

Orlistat results in modest weight loss and is associated with a range of
gastrointestinal adverse events, including oily spotting and flatus with
discharge.

Although orlistat does not affect appetite centres in the brain, patients may
reduce their fat intake to avoid the gastrointestinal side effects, and this may
contribute to weight loss.

It is unclear whether orlistat-treated patients retain changes in eating
behaviour after the end of treatment.

Orlistat treatment improves cardiovascular risk factors, such as LDLcholesterol levels and delays progression to type 2 diabetes.
Alli

Alli is the over-the-counter version of orlistat. It is identical to Xenical except
that it is accessed over the counter rather by prescription and is administered
in 60mg rather than 120mg doses.

Alli is associated with less severe gastrointestinal side effects than
prescription orlistat.
Rimonabant

Rimonabant was made available on prescription in 2006, but was withdrawn
in 2008 due to the risk of serious psychiatric problems, including suicide. (13.
Rimonabant, Summary of Product Characteristics: sanofi-aventis, 2008.)

Rimonabant’s developers thought that blocking cannabinoid receptors in the
brain might reduce appetite. Therefore, they developed rimonabant, which
blocks a particular subset of cannabinoid receptors (CB1) in the brain and
adipose tissue.
Other therapies

Some patients turn to alternative remedies in an attempt to lose weight. There
is limited scientific evidence to support the effects of such therapies, and in
some cases they may not have a positive effect.
Self-assessment – Questions
[Matching exercise]
Fill in the blanks with the correct option from the selection below
1. What was the fate, or is the status, of the following anti-obesity agents?
a) Thyroid extract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
.......................
b) Rimonabant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
................
c) Fenfluramine/phentermine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
............
d) Orlistat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
.....................
e) Rainbow pills . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
..................
f) Reductil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
...................
g) Dinitrophenol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
..................
h) Aminoxaphen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
.................
i) Aloe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
.........
I. Withdrawn following reports of valvular insufficiency
II. Caused psychiatric problems including suicide
III. Caused hyperthyroidism
IV. Caused cataracts and neuropathy
V. Currently available
VI. Caused pulmonary hypertension
VII Causes abdominal cramping and a decrease in potassium
VII. Caused deaths
[Answer: a) Caused hyperthyroidism b) Cause psychiatric problems including suicide
c) Withdrawn following reports of valvular insufficiency d) Currently available e)
Caused deaths f) Currently available g) Caused cataracts and neuropathy h) Caused
pulmonary hypertension i) Causes abdominal cramping and a decrease in potassium
[Multiple choice question]
2. How and by what route is orlistat eliminated from the body?
a) Unchanged, through the kidneys in the urine
b) Unchanged, through the faecal route
c) It is metabolised to its major inactive metabolites (M1 and M3) in the liver and
excreted in the urine
d) It is metabolised to its major metabolites (M1 and M3) in the gut and excreted in
the urine
e) It is metabolised to its major metabolites (M1 and M3) in the gut and excreted in
the faeces
[ Answer: B Unchanged through the faecal route ]
[Multiple select]
3. Choose three of the following options.
Which of the following side effects may be seen with orlistat?
a) Nausea
b) Headaches
c) Dizziness
d) Uncontrolled oily discharge
e) Loose or fatty stools
f) Constipation
[Answer: A, C, D]
[Multiple select]
4. Choose three of the following options.
As well as helping with weight loss, orlistat has been found to
improve which of the following?
a) Atherosclerosis
b) LDL-cholesterol
c) Total cholesterol
d) Cardiovascular morbidity
e) Cardiovascular mortality
f) Progression to type 2 diabetes
[Answer: B, C, F]
[Multiple select]
5. Choose two of the following.
Which of the following tissues have significant levels of CB1 receptors?
a) Adipose tissue
b) Muscle
c) Liver
d) Pancreas
e) Brain
f) Skin
g) Lungs
[Answer: a, e]
[True or False]
6. Are the following statements true or false?
a) Orlistat may help in maintaining weight lost after dieting by slowing the regain in
weight
b) Dosing with orlistat is once daily, with food and drink restrictions
c) Dosing with orlistat is three times a day (t.i.d.), with food and drink restrictions
d) Women on any pharmacological treatment for obesity need to take adequate
contraception
e) Women on orlistat need to use additional contraception if using oral contraception
[Answer: All true ]
Glossary
Fatty acid: A degradation product of lipid digestion in the gastric tract.
Hyperthyroidism: Excessive functioning of the thyroid gland, resulting in increased
metabolic rate, enlargement of the thyroid gland, rapid heart rate and high blood
pressure.
Hypocaloric: Referring to a diet that contains less energy than expended in normal
activities.
Modes of Action (MOA) The way in which a drug works
Monoglyceride: An intermediate in the degradation and synthesis of lipids.
Monoglycerides are a major end product of triglyceride degradation.
Note: The Summary of Product Characteristics for Reductil is available with this
manual for reference.
References
1. Data on file: Sibutramine: Global analysis of safety. Abbott Laboratories Ltd. 1999
2. Xenical, Summary of Product Characteristics: Roche, 2006.
3. Alli, Summary of Product Characteristics: GSK, 2007.
4. Bray GA, Greenway FL. Current and potential drugs for treatment of obesity.
Endocr Rev
1999;20:805-75.
5. Fenfluramine and dexfenfluramine withdrawn. Current Problems in
Pharmacovigilance 1997;
23:13-16.
6. Obesity. Guidance on the prevention, identification, assessment and management
of overweight and obesity in adults and children. NICE clinical guideline 43. National
Institute for Health and Clinical Excellence. Issue date: December 2006.
7. Reductil, Summary of Product Characteristics: Abbott Laboratories Limited, 2006.
8. Drent ML, van der Veen EA. Lipase inhibition: a novel concept in the treatment of
obesity. Int J
Obes Relat Metab Disord 1993;17:241-4.
9. O'Meara S, Riemsma R, Shirran L, Mather L, ter Riet G. A systematic review of
the clinical effectiveness of orlistat used for the management of obesity. Obes Rev
2004;5:51-68.
10. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. XENical in the prevention of
diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an
adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients.
Diabetes Care 2004;27:155-61.
11. Acomplia, Summary of Product Characteristics: sanofi-aventis, 2006.
12. Scheen AJ, Ernest P. New antiobesity agents in type 2 diabetes: overview of
clinical trials with sibutramine and orlistat. Diabetes Metab 2002;28:437-45.
13. Rimonabant, Summary of Product Characteristics: sanofi-aventis, 2008.
14. Public statement on Accomplia (Rimonabant) Withdrawal of the marketing
authorisation in the European Union. 30/01/09. EMEA/39457/2009