ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
alli 60 mg hard capsules
2.
Each hard capsule contains 60 mg orlistat.
For a full list of excipients, see section 6.1.
3.
Hard capsule
The capsule has a dark blue centre band, and a turquoise cap and body bearing the imprint of “alli”.
4.
alli is indicated for weight loss in adults who are overweight (body mass index, BMI, ≥28 kg/m
2
) and
should be taken in conjunction with a mildly hypocaloric, lower-fat diet.
Posology
Adults
The recommended dose of alli is one 60 mg capsule to be taken three times daily. No more than three
60 mg capsules should be taken in 24 hours.
Diet and exercise are important parts of a weight loss programme. It is recommended that a diet and
exercise programme is started before beginning treatment with alli.
While taking orlistat, the patient should be on a nutritionally balanced, mildly hypocaloric diet that
contains approximately 30% of calories from fat (e.g. in a 2,000 kcal/day diet, this equates to <67 g of
fat). The daily intake of fat, carbohydrate and protein should be distributed over three main meals.
The diet and exercise programme should continue to be followed when treatment with alli is stopped.
Treatment should not exceed 6 months.
If patients have been unable to lose weight after 12 weeks of treatment with alli, they should consult
their doctor or a pharmacist. It may be necessary to discontinue treatment.
Special populations
Elderly (
>
65 years old)
There are limited data on the use of orlistat in the elderly. However, as orlistat is minimally absorbed,
no dose adjustment is necessary in the elderly.
2
Hepatic and renal impairment
The effect of orlistat in individuals with hepatic and/or renal impairment has not been studied.
However, as orlistat is minimally absorbed, no dose adjustment is necessary in individuals with
hepatic and/or renal impairment.
Paediatric population
The safety and efficacy of alli in children below 18 years of age has not been established. No data are
available.
Method of administration
The capsule 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 of orlistat should be omitted.
•
Hypersensitivity to the active substance or to any of the excipients
•
Concurrent treatment with ciclosporin (see section 4.5)
•
Chronic malabsorption syndrome
•
Cholestasis
•
Pregnancy (see section 4.6)
•
Breast-feeding (see section 4.6)
•
Concurrent treatment with warfarin or other oral anticoagulants (see sections 4.5 and 4.8)
Patients should be advised to adhere to the dietary recommendations they are given (see section 4.2).
The possibility of experiencing gastrointestinal symptoms (see section 4.8) may increase when orlistat
is taken with an individual meal or a diet high in fat.
Treatment with orlistat may potentially impair the absorption of fat-soluble vitamins (A, D, E and K)
(see section 4.5). For this reason, a multivitamin supplement should be taken at bedtime.
As weight loss may be accompanied by improved metabolic control in diabetes, patients who are
taking a medicinal product for diabetes should consult a doctor before starting treatment with alli, in
case it is necessary to adjust the dose of the antidiabetic medicinal product.
Weight loss may be accompanied by an improvement in blood pressure and cholesterol levels.
Patients who are taking a medicinal product for hypertension or hypercholesterolaemia should consult
a doctor or pharmacist when taking alli, in case it is necessary to adjust the dose of these medicinal
products.
Patients who are taking amiodarone should consult a doctor before starting treatment with alli (see
section 4.5).
Cases of rectal bleeding have been reported in patients taking orlistat. If this occurs, the patient should
consult a doctor.
The use of an additional contraceptive method is recommended to prevent possible failure of oral
contraception that could occur in case of severe diarrhoea (see section 4.5).
Patients with kidney disease should consult a doctor before starting treatment with alli, as the use of
orlistat may rarely be associated with hyperoxaluria and oxalate nephropathy.
Hypothyroidism and/or reduced control of hypothyroidism may occur when orlistat and levothyroxine
are co-administered (see section 4.5). Patients taking levothyroxine should consult a doctor before
3
starting treatment with alli, as orlistat and levothyroxine may need to be taken at different times and
the dose of levothyroxine may need to be adjusted.
Patients taking an antiepileptic medicinal product should consult a doctor before starting treatment
with alli, as they should be monitored for possible changes in the frequency and severity of
convulsions. If this occurs, consideration could be given to administering orlistat and antiepileptic
medicinal products at different times (see section 4.5).
Ciclosporin
A decrease in ciclosporin plasma levels has been observed in a drug-drug interaction study and also
reported in several cases, when orlistat was administered concomitantly. This could potentially lead to
a decrease of immunosuppressive efficacy. Concurrent use of alli and ciclosporin is contraindicated
(see section 4.3).
Oral anticoagulants
When warfarin or other oral anticoagulants are given in combination with orlistat, international
normalised ratio (INR) values could be affected (see section 4.8). Concurrent use of alli and warfarin
or other oral anticoagulants is contraindicated (see section 4.3).
Oral contraceptives
The absence of an interaction between oral contraceptives and orlistat has been demonstrated in
specific drug-drug interaction studies. However, orlistat may indirectly reduce the availability of oral
contraceptives and lead to unexpected pregnancies in some individual cases. An additional
contraceptive method is recommended in case of severe diarrhoea (see section 4.4).
Levothyroxine
Hypothyroidism and/or reduced control of hypothyroidism may occur when orlistat and levothyroxine
are taken at the same time (see section 4.4). This could be due to a decreased absorption of iodine salts
and/or levothyroxine.
Antiepileptic medicinal products
Convulsions have been reported in patients treated concomitantly with orlistat and antiepileptic
medicinal products e.g. valproate, lamotrigine, for which a causal relationship to an interaction cannot
be excluded. Orlistat may decrease the absorption of antiepileptic medicinal products, leading to
convulsions.
Fat soluble vitamins
Treatment with orlistat may potentially impair the absorption of fat-soluble vitamins (A, D, E and K).
The vast majority of subjects receiving up to 4 full years of treatment with orlistat in clinical studies
had vitamin A, D, E and K and beta-carotene levels that stayed within normal range. However,
patients should be advised to use a multivitamin supplement at bedtime to help ensure adequate
vitamin intake (see section 4.4).
Acarbose
In the absence of pharmacokinetic interaction studies, alli is not recommended to be used by patients
receiving acarbose.
4
Amiodarone
A decrease in plasma levels of amiodarone, when given as a single dose, has been observed in a
limited number of healthy volunteers who received orlistat concomitantly. The clinical relevance of
this effect in patients receiving amiodarone treatment remains unknown. Patients who are taking
amiodarone should consult a doctor before starting treatment with alli. The dose of amiodarone may
need to be adjusted during treatment with alli.
Women of childbearing potential / Contraception in males and females
The use of an additional contraceptive method is recommended to prevent possible failure of oral
contraception that could occur in case of severe diarrhoea (see sections 4.4 and 4.5).
Pregnancy
For orlistat, no clinical data on exposed pregnancies are available. Animal studies do not indicate
direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition
or postnatal development (see section 5.3).
alli is contraindicated in pregnancy (see section 4.3).
Breast-feeding
As it is not known whether orlistat is secreted into human milk, alli is contraindicated during breast-
feeding (see section 4.3).
Fertility
Animal studies do not indicate harmful effects with respect to fertility.
Orlistat has no or negligible influence on the ability to drive and use machines.
Adverse reactions to orlistat are largely gastrointestinal in nature and related to the pharmacologic
effect of the medicinal product on preventing the absorption of ingested fat.
The gastrointestinal adverse reactions identified from clinical trials with orlistat 60 mg of 18 months to
2 years duration were generally mild and transient. They generally occurred early in treatment (within
3 months) and most patients experienced only one episode. Consumption of a diet low in fat will
decrease the likelihood of experiencing adverse gastrointestinal reactions (see section 4.4).
Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as:
very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000
to <1/1,000) and very rare (<1/10,000), not known (cannot be estimated from the available data).
The frequencies of adverse reactions identified during post-marketing use of orlistat are not known as
these reactions were reported voluntarily from a population of uncertain size.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
5
System organ class and frequency
Adverse reaction
Blood and lymphatic system disorders
Not known
Decreased prothrombin and increased INR (see
sections 4.3 and 4.5)
Immune system disorders
Not known
Hypersensitivity reactions including anaphylaxis,
bronchospasm, angioedema, pruritus, rash, and
urticaria
Psychiatric disorders
Common
Anxiety†
Gastrointestinal disorders
Very common
Oily spotting
Flatus with discharge
Faecal urgency
Fatty oily stool
Oily evacuation
Flatulence
Soft stools
Common
Abdominal pain
Faecal incontinence
Liquid stools
Increased defaecation
Not known
Diverticulitis
Pancreatitis
Mild rectal bleeding (see section 4.4)
Renal and urinary disorders
Not known
Oxalate nephropathy
Hepatobiliary disorders
Not known
Hepatitis
Cholelithiasis
Increase in transaminases and in alkaline
phosphatase
Skin and subcutaneous tissue disorders
Not known
Bullous eruption
†It is plausible that treatment with orlistat can lead to anxiety in anticipation of or secondary to
gastrointestinal adverse reactions.
Single doses of 800 mg orlistat and multiple doses of up to 400 mg three times daily for 15 days have
been studied in normal weight and obese subjects without significant clinical findings. In addition,
doses of 240 mg three times daily have been administered to obese patients for 6 months. The
majority of orlistat overdose cases received during post-marketing reported either no adverse reactions
or adverse reactions that are similar to those reported with recommended doses of orlistat.
In the event of an overdose, medical advice should be sought. Should a significant overdose of orlistat
occur, it is recommended that the patient be observed for 24 hours. Based on human and animal
6
studies, any systemic effects attributable to the lipase-inhibiting properties of orlistat should be rapidly
reversible.
5.
5.1 Pharmacodynamic properties
Pharmaco-therapeutic group: antiobesity preparations, excl. diet products, peripherally acting
antiobesity products, ATC code A08AB01.
Orlistat is a potent, specific and long-acting inhibitor of gastrointestinal lipases. It exerts its therapeutic
activity in the lumen of the stomach and small intestine by forming a covalent bond with the active
serine site of the gastric and pancreatic lipases. The inactivated enzyme is thus unavailable to
hydrolyse dietary fat, in the form of triglycerides, into absorbable free fatty acids and monoglycerides.
From clinical studies, it has been estimated that orlistat 60 mg taken three times daily blocks the
absorption of approximately 25% of dietary fat. The effect of orlistat results in an increase in faecal
fat as early as 24 to 48 hours after dosing. Upon discontinuation of therapy, faecal fat content returns
to pre-treatment levels, usually within 48 to 72 hours.
Two double-blind, randomised, placebo-controlled studies in adults with a BMI ≥28 kg/m
2
support the
efficacy of orlistat 60 mg taken three times daily in conjunction with a hypocaloric, lower-fat diet.
The primary parameter, change in body weight from baseline (time of randomisation), was assessed
for body weight over time (Table 1) and the percentage of subjects who lost ≥5% or ≥10% of body
weight (Table 2). Although weight loss was assessed during 12 months of treatment in both studies,
most weight loss occurred within the first 6 months.
Table 1: Effect of 6 months treatment on body weight measured at baseline
Treatment
group
N
Relative mean change
(%)
Mean change
(kg)
Study 1
Placebo
Orlistat 60 mg
204
216
-3.24
-5.55
-3.11
-5.20
a
Study 2
Placebo
Orlistat 60 mg
183
191
-1.17
-3.66
-1.05
-3.59
a
Pooled data
Placebo
Orlistat 60 mg
387
407
-2.20
-4.60
-2.09
-4.40
a
a
p<0.001 versus placebo
Table 2: Responder analysis at 6 months
Lost
≥
5% of baseline body weight
(%)
Lost
≥
10% of baseline body weight
(%)
Placebo
Orlistat 60 mg
Placebo
Orlistat 60 mg
Study 1
30.9
54.6
a
10.3
21.3
b
Study 2
21.3
37.7
a
2.2
10.5
b
Pooled data
26.4
46.7
a
6.5
16.2
a
Comparison versus placebo:
a
p<0.001;
b
p<0.01
The weight loss induced by orlistat 60 mg conferred other important health benefits after 6 months of
treatment in addition to weight loss. The mean relative change in total cholesterol was -2.4% for
orlistat 60 mg (baseline 5.20 mmol/l) and +2.8% for placebo (baseline 5.26 mmol/l). The mean
relative change in LDL cholesterol was -3.5% for orlistat 60 mg (baseline 3.30 mmol/l) and +3.8% for
placebo (baseline 3.41 mmol/l). For waist circumference, the mean change was -4.5 cm for orlistat
60 mg (baseline 103.7 cm) and -3.6 cm for placebo (baseline 103.5 cm). All comparisons against
placebo were statistically significant.
5.2 Pharmacokinetic properties
7
Absorption
Studies in normal weight and obese volunteers have shown that the extent of absorption of orlistat was
minimal. Plasma concentrations of intact orlistat were non-measurable (<5 ng/ml) 8 hours following
oral administration of orlistat 360 mg.
In general, at therapeutic doses, detection of intact orlistat in plasma was sporadic and concentrations
were extremely low (<10 ng/ml or 0.02 µmol), with no evidence of accumulation, which is consistent
with minimal absorption.
Distribution
The volume of distribution cannot be determined because the active substance is minimally absorbed
and has no defined systemic pharmacokinetics. In vitro, orlistat is >99% bound to plasma proteins
(lipoproteins and albumin were the major binding proteins). Orlistat minimally partitions into
erythrocytes.
Biotransformation
Based on animal data, it is likely that the metabolism of orlistat occurs mainly within the
gastrointestinal wall. Based on a study in obese patients, of the minimal fraction of the dose that was
absorbed systemically, two major metabolites, M1 (4-member lactone ring hydrolysed) and M3 (M1
with N-formyl leucine moiety cleaved), accounted for approximately 42% of the total plasma
concentration.
M1 and M3 have an open beta-lactone ring and extremely weak lipase inhibitory activity (1,000- and
2,500-fold less than orlistat, respectively). In view of this low inhibitory activity and the low plasma
levels at therapeutic doses (average of 26 ng/ml and 108 ng/ml, respectively), these metabolites are
considered to be pharmacologically inconsequential.
Elimination
Studies in normal weight and obese subjects have shown that faecal excretion of the unabsorbed active
substance was the major route of elimination. Approximately 97% of the administered dose was
excreted in faeces and 83% of that as unchanged orlistat.
The cumulative renal excretion of total orlistat-related materials was <2% of the given dose. The time
to reach complete excretion (faecal plus urinary) was 3 to 5 days. The disposition of orlistat appeared
to be similar between normal weight and obese volunteers. Orlistat, M1 and M3 are all subject to
biliary excretion.
5.3 Preclinical safety data
Nonclinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to fertility,
reproduction and development.
6.
6.1 List of excipients
Capsule filling
Microcrystalline cellulose (E460)
Sodium starch glycolate
Povidone (E1201)
8
Sodium laurilsulfate
Talc
Capsule shell
Gelatin
Indigo carmine (E132)
Titanium dioxide (E171)
Sodium laurilsulfate
Sorbitan monolaurate
Capsule printing ink
Shellac
Iron oxide black (E172)
Propylene glycol
Band
Gelatin
Polysorbate 80
Indigo carmine (E132)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years.
Discard any capsules stored in the carry case for more than one month.
6.4 Special precautions for storage
Do not store above 25°C.
Keep the container tightly closed in order to protect from moisture.
6.5 Nature and contents of container
HDPE bottle with child resistant closure containing 42, 60, 84, 90 or 120 hard capsules. The bottle
also contains two sealed canisters containing silica gel desiccant.
A polystyrene resin / polyurethane carry case (Shuttle) which can hold 3 capsules is included in each
pack.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7.
Glaxo Group Limited
Glaxo Wellcome House
Berkeley Avenue
Greenford
Middlesex
9
UB6 0NN
United Kingdom
8.
EU/1/07/401/007-011
9.
Date of first authorisation: 23 July 2007
Renewal of the authorisation:
Detailed information on this medicinal product is available on the European Medicines Agency
website: http://www.ema.europa.eu
10
1.
alli 27 mg chewable tablets
2.
Each chewable tablet contains 27 mg orlistat.
Excipients
Each chewable tablet contains 86.79 mg of lactose and 6.48 mg of sucrose (as monopalmitate).
For a full list of excipients, see section 6.1.
3.
Chewable tablet.
White to off-white, faceted, triangular shaped tablets of 12 mm, debossed with “alli”.
4.
alli is indicated for weight loss in adults who are overweight (body mass index, BMI, ≥28 kg/m
2
) and
should be taken in conjunction with a mildly hypocaloric, lower-fat diet.
Posology
Adults
The recommended dose of alli is one 27 mg tablet to be taken three times daily. No more than three
27 mg tablets should be taken in 24 hours.
It is possible that the systemic absorption from 27 mg chewable tablets may be higher than that from
60 mg hard capsules. It is therefore recommended not to take two tablets at the same time.
Diet and exercise are important parts of a weight loss programme. It is recommended that a diet and
exercise programme is started before beginning treatment with alli.
While taking orlistat, the patient should be on a nutritionally balanced, mildly hypocaloric diet that
contains approximately 30% of calories from fat (e.g. in a 2,000 kcal/day diet, this equates to <67 g of
fat). The daily intake of fat, carbohydrate and protein should be distributed over three main meals.
The diet and exercise programme should continue to be followed when treatment with alli is stopped.
Treatment should not exceed 6 months.
If patients have been unable to lose weight after 12 weeks of treatment with alli, they should consult
their doctor or a pharmacist. It may be necessary to discontinue treatment.
Special populations
11
Elderly (
>
65 years old)
There are limited data on the use of orlistat in the elderly. However, as orlistat is minimally absorbed,
no dose adjustment is necessary in the elderly.
Hepatic and renal impairment
The effect of orlistat in individuals with hepatic and/or renal impairment has not been studied.
However, as orlistat is minimally absorbed, no dose adjustment is necessary in individuals with
hepatic and/or renal impairment.
Paediatric population
The safety and efficacy of alli in children below 18 years of age has not been established. No data are
available.
Method of administration
The tablet should be chewed immediately before, during or up to 1 hour after each main meal. If a
meal is missed or contains no fat, the dose of orlistat should be omitted.
•
Hypersensitivity to the active substance or to any of the excipients
•
Concurrent treatment with ciclosporin (see section 4.5)
•
Chronic malabsorption syndrome
•
Cholestasis
•
Pregnancy (see section 4.6)
•
Breast-feeding (see section 4.6)
•
Concurrent treatment with warfarin or other oral anticoagulants (see sections 4.5 and 4.8)
Patients should be advised to adhere to the dietary recommendations they are given (see section 4.2).
The possibility of experiencing gastrointestinal symptoms (see section 4.8) may increase when orlistat
is taken with an individual meal or a diet high in fat.
Treatment with orlistat may potentially impair the absorption of fat-soluble vitamins (A, D, E and K)
(see section 4.5). For this reason, a multivitamin supplement should be taken at bedtime.
As weight loss may be accompanied by improved metabolic control in diabetes, patients who are
taking a medicinal product for diabetes should consult a doctor or pharmacist before starting treatment
with alli, in case it is necessary to adjust the dose of the antidiabetic medicinal product.
Weight loss may be accompanied by an improvement in blood pressure and cholesterol levels. Patients
who are taking a medicinal product for hypertension or hypercholesterolaemia should consult a doctor
or pharmacist when taking alli, in case it is necessary to adjust the dose of these medicinal products.
Patients who are taking amiodarone should consult a doctor before starting treatment with alli (see
section 4.5).
Cases of rectal bleeding have been reported in patients taking orlistat. If this occurs, the patient should
consult a doctor.
The use of an additional contraceptive method is recommended to prevent possible failure of oral
contraception that could occur in case of severe diarrhoea (see section 4.5).
Patients with kidney disease should consult a doctor before starting treatment with alli, as the use of
orlistat may rarely be associated with hyperoxaluria and oxalate nephropathy.
12
Hypothyroidism and/or reduced control of hypothyroidism may occur when orlistat and levothyroxine
are co-administered (see section 4.5). Patients taking levothyroxine should consult a doctor before
starting treatment with alli, as orlistat and levothyroxine may need to be taken at different times and
the dose of levothyroxine may need to be adjusted.
Patients taking an antiepileptic medicinal product should consult a doctor before starting treatment
with alli, as they should be monitored for possible changes in the frequency and severity of
convulsions. If this occurs, consideration could be given to administering orlistat and antiepileptic
medicinal products at different times (see section 4.5).
The chewable tablets contain lactose. Patients with rare hereditary problems of galactose intolerance,
the Lapp lactase deficiency, glucose-galactose malabsorption should not take this medicinal product.
The chewable tablets also contain sucrose. Patients with rare hereditary problems of fructose
intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this
medicinal product.
Ciclosporin
A decrease in ciclosporin plasma levels has been observed in a drug-drug interaction study and also
reported in several cases, when orlistat was administered concomitantly. This could potentially lead to
a decrease of immunosuppressive efficacy. Concurrent use of alli and ciclosporin is contraindicated
(see section 4.3).
Oral anticoagulants
When warfarin or other oral anticoagulants are given in combination with orlistat, international
normalised ratio (INR) values could be affected (see section 4.8). Concurrent use of alli and warfarin
or other oral anticoagulants is contraindicated (see section 4.3).
Oral contraceptives
The absence of an interaction between oral contraceptives and orlistat has been demonstrated in
specific drug-drug interaction studies. However, orlistat may indirectly reduce the availability of oral
contraceptives and lead to unexpected pregnancies in some individual cases. An additional
contraceptive method is recommended in case of severe diarrhoea (see section 4.4).
Levothyroxine
Hypothyroidism and/or reduced control of hypothyroidism may occur when orlistat and levothyroxine
are taken at the same time (see section 4.4). This could be due to a decreased absorption of iodine salts
and/or levothyroxine.
Antiepileptic medicinal products
Convulsions have been reported in patients treated concomitantly with orlistat and antiepileptic
medicinal products e.g. valproate, lamotrigine, for which a causal relationship to an interaction cannot
be excluded. Orlistat may decrease the absorption of antiepileptic medicinal products, leading to
convulsions.
Fat soluble vitamins
Treatment with orlistat may potentially impair the absorption of fat-soluble vitamins (A, D, E and K).
13
The vast majority of subjects receiving up to 4 full years of treatment with orlistat in clinical studies
had vitamin A, D, E and K and beta-carotene levels that stayed within normal range. However,
patients should be advised to use a multivitamin supplement at bedtime to help ensure adequate
vitamin intake (see section 4.4).
Acarbose
In the absence of pharmacokinetic interaction studies, alli is not recommended to be used by patients
receiving acarbose.
Amiodarone
A decrease in plasma levels of amiodarone, when given as a single dose, has been observed in a
limited number of healthy volunteers who received orlistat concomitantly. The clinical relevance of
this effect in patients receiving amiodarone treatment remains unknown. Patients who are taking
amiodarone should consult a doctor before starting treatment with alli. The dose of amiodarone may
need to be adjusted during treatment with alli.
Women of childbearing potential / Contraception in males and females
The use of an additional contraceptive method is recommended to prevent possible failure of oral
contraception that could occur in case of severe diarrhoea (see sections 4.4 and 4.5).
Pregnancy
For orlistat, no clinical data on exposed pregnancies are available. Animal studies do not indicate
direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition
or postnatal development (see section 5.3).
alli is contraindicated in pregnancy (see section 4.3).
Breast-feeding
As it is not known whether orlistat is secreted into human milk, alli is contraindicated during breast-
feeding (see section 4.3).
Fertility
Animal studies do not indicate harmful effects with respect to fertility.
Orlistat has no or negligible influence on the ability to drive and use machines.
Adverse reactions to orlistat are largely gastrointestinal in nature and related to the pharmacologic
effect of the medicinal product on preventing the absorption of ingested fat.
The gastrointestinal adverse reactions identified from clinical trials with orlistat 60 mg of 18 months to
2 years duration were generally mild and transient. They generally occurred early in treatment (within
3 months) and most patients experienced only one episode. Consumption of a diet low in fat will
decrease the likelihood of experiencing adverse gastrointestinal reactions (see section 4.4).
14
Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as:
very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000
to <1/1,000) and very rare (<1/10,000), not known (cannot be estimated from the available data).
The frequencies of adverse reactions identified during post-marketing use of orlistat are not known as
these reactions were reported voluntarily from a population of uncertain size.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
System organ class and frequency
Adverse reaction
Blood and lymphatic system disorders
Not known
Decreased prothrombin and increased INR (see
sections 4.3 and 4.5)
Immune system disorders
Not known
Hypersensitivity reactions including anaphylaxis,
bronchospasm, angioedema, pruritus, rash, and
urticaria
Psychiatric disorders
Common
Anxiety†
Gastrointestinal disorders
Very common
Oily spotting
Flatus with discharge
Faecal urgency
Fatty oily stool
Oily evacuation
Flatulence
Soft stools
Common
Abdominal pain
Faecal incontinence
Liquid stools
Increased defaecation
Not known
Diverticulitis
Pancreatitis
Mild rectal bleeding (see section 4.4)
Renal and urinary disorders
Not known
Oxalate nephropathy
Hepatobiliary disorders
Not known
Hepatitis
Cholelithiasis
Increase in transaminases and in alkaline
phosphatase
Skin and subcutaneous tissue disorders
Not known
Bullous eruption
†It is plausible that treatment with orlistat can lead to anxiety in anticipation of or secondary to
gastrointestinal adverse reactions.
15
Single doses of 800 mg orlistat and multiple doses of up to 400 mg three times daily for 15 days have
been studied in normal weight and obese subjects without significant clinical findings. In addition,
doses of 240 mg three times daily have been administered to obese patients for 6 months. The majority
of orlistat overdose cases received during post-marketing reported either no adverse reactions or
adverse reactions that are similar to those reported with recommended doses of orlistat.
In the event of an overdose, medical advice should be sought. Should a significant overdose of orlistat
occur, it is recommended that the patient be observed for 24 hours. Based on human and animal
studies, any systemic effects attributable to the lipase-inhibiting properties of orlistat should be rapidly
reversible.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antiobesity preparations, excl. diet products, peripherally acting
antiobesity products, ATC code A08AB01.
Orlistat is a potent, specific and long-acting inhibitor of gastrointestinal lipases. It exerts its therapeutic
activity in the lumen of the stomach and small intestine by forming a covalent bond with the active
serine site of the gastric and pancreatic lipases. The inactivated enzyme is thus unavailable to
hydrolyse dietary fat, in the form of triglycerides, into absorbable free fatty acids and monoglycerides.
Pharmacodynamic equivalence of alli 27 mg chewable tablets and alli 60 mg hard capsules has been
established using a faecal fat excretion model.
From clinical studies, it has been estimated that orlistat 60 mg taken three times daily blocks the
absorption of approximately 25% of dietary fat. The effect of orlistat results in an increase in faecal fat
as early as 24 to 48 hours after dosing. Upon discontinuation of therapy, faecal fat content returns to
pre-treatment levels, usually within 48 to 72 hours.
Two double-blind, randomised, placebo-controlled studies in adults with a BMI ≥28 kg/m
2
support the
efficacy of orlistat 60 mg taken three times daily in conjunction with a hypocaloric, lower-fat diet.
The primary parameter, change in body weight from baseline (time of randomisation), was assessed
for body weight over time (Table 1) and the percentage of subjects who lost ≥5% or ≥10% of body
weight (Table 2). Although weight loss was assessed during 12 months of treatment in both studies,
most weight loss occurred within the first 6 months.
Table 1: Effect of 6 months treatment on body weight measured at baseline
Treatment
group
N
Relative mean change
(%)
Mean change
(kg)
Study 1
Placebo
Orlistat 60 mg
204
216
-3.24
-5.55
-3.11
-5.20
a
Study 2
Placebo
Orlistat 60 mg
183
191
-1.17
-3.66
-1.05
-3.59
a
Pooled data
Placebo
Orlistat 60 mg
387
407
-2.20
-4.60
-2.09
-4.40
a
a
p<0.001 versus placebo
16
Table 2: Responder analysis at 6 months
Lost
≥
5% of baseline body weight
(%)
Lost
≥
10% of baseline body weight
(%)
Placebo
Orlistat 60 mg
Placebo
Orlistat 60 mg
Study 1
30.9
54.6
a
10.3
21.3
b
Study 2
21.3
37.7
a
2.2
10.5
b
Pooled data
26.4
46.7
a
6.5
16.2
a
Comparison versus placebo:
a
p<0.001;
b
p<0.01
The weight loss induced by orlistat 60 mg conferred other important health benefits after 6 months of
treatment in addition to weight loss. The mean relative change in total cholesterol was -2.4% for
orlistat 60 mg (baseline 5.20 mmol/l) and +2.8% for placebo (baseline 5.26 mmol/l). The mean
relative change in LDL cholesterol was -3.5% for orlistat 60 mg (baseline 3.30 mmol/l) and +3.8% for
placebo (baseline 3.41 mmol/l). For waist circumference, the mean change was -4.5 cm for orlistat
60 mg (baseline 103.7 cm) and -3.6 cm for placebo (baseline 103.5 cm). All comparisons against
placebo were statistically significant.
5.2 Pharmacokinetic properties
Absorption
Studies in normal weight and obese volunteers have shown that the extent of absorption of orlistat was
minimal. Plasma concentrations of intact orlistat were non-measurable (<5 ng/ml) 8 hours following
oral administration of orlistat 360 mg.
In general, at therapeutic doses, detection of intact orlistat in plasma was sporadic and concentrations
were extremely low (<10 ng/ml or 0.02 µmol), with no evidence of accumulation, which is consistent
with minimal absorption.
Distribution
The volume of distribution cannot be determined because the active substance is minimally absorbed
and has no defined systemic pharmacokinetics. In vitro, orlistat is >99% bound to plasma proteins
(lipoproteins and albumin were the major binding proteins). Orlistat minimally partitions into
erythrocytes.
Biotransformation
Based on animal data, it is likely that the metabolism of orlistat occurs mainly within the
gastrointestinal wall. Based on a study in obese patients, of the minimal fraction of the dose that was
absorbed systemically, two major metabolites, M1 (4-member lactone ring hydrolysed) and M3 (M1
with N-formyl leucine moiety cleaved), accounted for approximately 42% of the total plasma
concentration.
M1 and M3 have an open beta-lactone ring and extremely weak lipase inhibitory activity (1,000- and
2,500-fold less than orlistat, respectively). In view of this low inhibitory activity and the low plasma
levels at therapeutic doses (average of 26 ng/ml and 108 ng/ml, respectively), these metabolites are
considered to be pharmacologically inconsequential.
Elimination
Studies in normal weight and obese subjects have shown that faecal excretion of the unabsorbed active
substance was the major route of elimination. Approximately 97% of the administered dose was
excreted in faeces and 83% of that as unchanged orlistat.
17
The cumulative renal excretion of total orlistat-related materials was <2% of the given dose. The time
to reach complete excretion (faecal plus urinary) was 3 to 5 days. The disposition of orlistat appeared
to be similar between normal weight and obese volunteers. Orlistat, M1 and M3 are all subject to
biliary excretion.
5.3 Preclinical safety data
Nonclinical data reveal no special hazard for humans based on conventional studies of safety
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to fertility,
reproduction and development.
6.
6.1 List of excipients
Mannitol (E421)
Xylitol (E967)
Anhydrous lactose
Sodium starch glycolate
Microcrystalline cellulose (E460)
Povidone (E1201)
Glycerol dibehenate (E471)
Sucrose monopalmitate (E473)
Sodium stearyl fumarate
Macrogol stearate (E431)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years.
Discard any tablets stored in the carry case for more than one month.
6.4 Special precautions for storage
Do not store above 25°C.
Keep the container tightly closed in order to protect from moisture.
6.5 Nature and contents of container
HDPE bottle with child resistant closure containing 42, 60, 84, 90 or 120 tablets. The bottle also
contains two sealed canisters containing silica gel desiccant.
A polystyrene resin/polyurethane carry case (Shuttle) which can hold 3 tablets is included in each
pack.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
18
7.
Glaxo Group Limited
Glaxo Wellcome House
Berkeley Avenue
Greenford
Middlesex
UB6 0NN
United Kingdom
8.
EU/1/07/401/012-016
9.
Date of first authorisation: 23
rd
July 2007.
Detailed information on this medicinal product is available on the European Medicines Agency
website: http://www.ema.europa.eu
19
ANNEX II
A. MANUFACTURING AUTHORISATION HOLDER
RESPONSIBLE FOR BATCH RELEASE
B. CONDITIONS OF THE MARKETING AUTHORISATION
20
A. MANUFACTURING AUTHORISATION HOLDERS RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturers responsible for batch release
alli 60 mg hard capsules/alli 27 mg chewable tablets:
Famar S.A., 49 KM Athens-Lamia, 190 11 Avlona, Greece
Catalent UK Packaging Limited, Sedge Close, Headway, Great Oakley, Corby, Northamptonshire
NN18 8HS, UK.
The printed package leaflet of the medicinal product must state the name and address of the
manufacturer responsible for the release of the concerned batch.
B. CONDITIONS OF THE MARKETING AUTHORISATION
•
alli 60 mg hard capsules: Medicinal product not subject to medical prescription.
alli 27 mg chewable tablets: Medicinal product not subject to medical prescription.
•
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
•
OTHER CONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, presented in Module 1.8.1. of the
Marketing Authorisation, is in place and functioning before and whilst the product is on the market.
Risk Management Plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in
the Pharmacovigilance Plan, as agreed in version 5.0 of the Risk Management Plan (RMP) presented
in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP
agreed by the CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, any
updated RMP should be submitted at the same time as the following Periodic Safety Update Report
(PSUR).
In addition, an updated RMP should be submitted:
•
When new information is received that may impact on the current Safety Specification,
Pharmacovigilance Plan or risk minimisation activities
•
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being
reached
•
At the request of the European Medicines Agency
21
PSURs
The PSUR cycle for alli will be restarted after the Commission Decision on the extension application
for alli 27 mg chewable tablet. Therefore, the Marketing Authorisation Holder will submit 6 monthly
PSURs for two years. Then yearly for 2 years and every three years thereafter.
22
ANNEX III
LABELLING AND PACKAGE LEAFLET
23
A. LABELLING
24
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON SLEEVE, 42, 60, 84, 90 or 120 CAPSULES
1.
alli 60 mg hard capsules
Orlistat
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each hard capsule contains 60 mg orlistat.
3.
LIST OF EXCIPIENTS
4.
This pack includes:
1 bottle containing 42 hard capsules
1 bottle containing 60 hard capsules
1 bottle containing 84 hard capsules
1 bottle containing 90 hard capsules
1 bottle containing 120 hard capsules
1 carry case
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
25
Do not store above 25°C.
Keep the container tightly closed in order to protect from moisture.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Glaxo Group Limited
Glaxo Wellcome House
Berkeley Avenue
Greenford
Middlesex
UB6 0NN
United Kingdom
EU/1/07/401/007-011
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product not subject to medical prescription.
15. INSTRUCTIONS ON USE
Weight loss aid
Can help you lose more weight than dieting alone.
alli is used for weight loss alongside reduced calorie, lower-fat meals in overweight adults, aged 18 or
over.
alli is clinically proven to help you lose more weight than dieting alone. The capsules work only in
your digestive system to stop about a quarter of the fat in your meals from being absorbed. This fat
passes out of your body and may cause changes to your bowel movements. Eat lower-fat meals to
help manage these effects.
To see if alli is right for you, find your height on the chart. If you weigh less than the weight shown
for your height, do not use alli.
26
Height
Weight
Height Weight
1.50 m
63 kg
4' 10''
9 st 8 lbs
1.55 m
67.25 kg
5' 0''
10 st 3 lbs
1.60 m
71.75 kg
5' 2''
10 st 13 lbs
1.65 m
76.25 kg
5' 4''
11 st 9 lbs
1.70 m
81 kg
5' 6''
12 st 5 lbs
1.75 m
85.75 kg
5' 8''
13 st 2 lbs
1.80 m
90.75 kg
5' 10''
13 st 13 lbs
1.85 m
95.75 kg
6' 0''
14 st 10 lbs
1.90 m
101 kg
6' 2''
15 st 8 lbs
Being overweight increases your risk of developing several serious health problems such as diabetes
and heart disease. You should see your doctor for a check-up.
Do not use
•
if you are under 18.
•
if you are pregnant or breast-feeding.
•
if you are taking ciclosporin.
•
if you are taking warfarin or any other medicines used to thin the blood.
•
if you are allergic to orlistat or any of the ingredients.
•
if you have cholestasis (condition where the flow of bile from the liver is blocked).
•
if you have problems absorbing food (chronic malabsorption syndrome).
Talk to your doctor before taking alli
•
if you are taking amiodarone for heart rhythm problems.
•
if you are taking a medicine for diabetes.
•
if you are taking a medicine for epilepsy.
•
if you have kidney disease.
•
if you are taking a thyroid medicine (levothyroxine).
Talk to your doctor or pharmacist when taking alli
•
if you are taking a medicine for high blood pressure.
•
if you are taking a medicine for high cholesterol.
How to use
•
take one capsule whole with water, three times a day with each main meal containing fat.
•
do not take more than three capsules a day.
•
you should take a multivitamin (containing vitamins A, D, E and K) once a day, at bedtime.
•
you should not take alli for more than six months.
<www.xxx.xxx>
16. INFORMATION IN BRAILLE
alli 60 mg hard capsules
27
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
INNER CARTON SLEEVE, 42, 60, 84, 90 or 120 CAPSULES
1.
alli 60 mg hard capsules
Orlistat
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each hard capsule contains 60 mg orlistat.
3.
LIST OF EXCIPIENTS
4.
This pack includes:
1 bottle containing 42 hard capsules
1 bottle containing 60 hard capsules
1 bottle containing 84 hard capsules
1 bottle containing 90 hard capsules
1 bottle containing 120 hard capsules
1 carry case
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the container tightly closed in order to protect from moisture.
28
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Glaxo Group Limited
Glaxo Wellcome House
Berkeley Avenue
Greenford
Middlesex
UB6 0NN
United Kingdom
EU/1/07/401/007-011
13. BATCH NUMBER
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product not subject to medical prescription.
15. INSTRUCTIONS ON USE
Weight loss aid
Can help you lose more weight than dieting alone.
alli is used for weight loss alongside reduced calorie, lower-fat meals in overweight adults, aged 18 or
over.
alli is clinically proven to help you lose more weight than dieting alone. The capsules work only in
your digestive system to stop about a quarter of the fat in your meals from being absorbed. This fat
passes out of your body and may cause changes to your bowel movements. Eat lower-fat meals to
help manage these effects.
How to use
•
take one capsule whole with water, three times a day with each main meal containing fat.
•
do not take more than three capsules a day.
•
you should take a multivitamin (containing vitamins A, D, E and K) once a day, at bedtime.
•
you should not take alli for more than six months.
For further information about the alli weight loss programme visit <www.xxx.xxx>.
16. INFORMATION IN BRAILLE
29
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
BOTTLE LABEL, 42, 60, 84, 90 or 120 CAPSULES
1.
alli 60 mg hard capsules
Orlistat
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each hard capsule contains 60 mg orlistat.
3.
LIST OF EXCIPIENTS
4.
42 hard capsules
60 hard capsules
84 hard capsules
90 hard capsules
120 hard capsules
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the container tightly closed in order to protect from moisture.
30
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Glaxo Group Limited
Glaxo Wellcome House
Berkeley Avenue
Greenford
Middlesex
UB6 0NN
United Kingdom
EU/1/07/401/007-011
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product not subject to medical prescription.
15. INSTRUCTIONS ON USE
Weight loss aid
Adults, aged 18 or over, who are overweight.
16. INFORMATION IN BRAILLE
31
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
CARRY CASE (SHUTTLE)
1.
alli 60 mg hard capsules
Orlistat
Oral use
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
4.
BATCH NUMBER
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
Holds 3 capsules.
6.
OTHER
Read the package leaflet before use.
Do not store above 25°C.
Discard any capsules stored in this case for more than one month.
32
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON SLEEVE, 42, 60, 84, 90 or 120 TABLETS
1.
alli 27 mg chewable tablets
Orlistat
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each chewable tablet contains 27 mg orlistat.
3.
LIST OF EXCIPIENTS
Contains lactose and sucrose. See leaflet for further information.
4.
This pack includes:
1 bottle containing 42 chewable tablets
1 bottle containing 60 chewable tablets
1 bottle containing 84 chewable tablets
1 bottle containing 90 chewable tablets
1 bottle containing 120 chewable tablets
1 carry case
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
33
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the container tightly closed in order to protect from moisture.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Glaxo Group Limited
Glaxo Wellcome House
Berkeley Avenue
Greenford
Middlesex
UB6 0NN
United Kingdom
EU/1/07/401/012-016
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product not subject to medical prescription.
15. INSTRUCTIONS ON USE
Weight loss aid.
Can help you lose more weight than dieting alone.
Chew one tablet three times a day.
alli is used for weight loss alongside reduced calorie, lower-fat meals in overweight adults, aged 18 or
over.
alli is clinically proven to help you lose more weight than dieting alone. The tablets work only in your
digestive system to stop about a quarter of the fat in your meals from being absorbed. This fat passes
out of your body and may cause changes to your bowel movements. Eat lower-fat meals to help
manage these effects.
To see if alli is right for you, find your height on the chart. If you weigh less than the weight shown for
your height, do not use alli.
34
Height
Weight
Height Weight
1.50 m
63 kg
4 ' 10 '' 9 st 8 lbs
1.55 m
67.25 kg
5 ' 0 ''
10 st 3 lbs
1.60 m
71.75 kg
5 ' 2 ''
10 st 13 lbs
1.65 m
76.25 kg
5 ' 4 ''
11 st 9 lbs
1.70 m
81 kg
5 ' 6 ''
12 st 5 lbs
1.75 m
85.75 kg
5 ' 8 ''
13 st 2 lbs
1.80 m
90.75 kg
5 ' 10 '' 13 st 13 lbs
1.85 m
95.75 kg
6 ' 0 ''
14 st 10 lbs
1.90 m
101 kg
6 ' 2 ''
15 st 8 lbs
Being overweight increases your risk of developing several serious health problems such as diabetes
and heart disease. You should see your doctor for a check-up.
Do not use
-
if you are under 18.
-
if you are pregnant or breast-feeding.
-
if you are taking warfarin or any other medicines used to thin the blood.
-
if you are allergic to orlistat or any of the ingredients.
-
if you have cholestasis (condition where the flow of bile from the liver is blocked).
-
if you have problems absorbing food (chronic malabsorption syndrome).
Talk to your doctor before taking alli
-
if you are taking amiodarone for heart rhythm problems.
-
if you are taking a medicine for epilepsy.
-
if you have kidney disease.
-
if you are taking a thyroid medicine (levothyroxine).
Talk to your doctor or pharmacist when taking alli
-
if you are taking a medicine for high blood pressure.
How to use
-
chew one tablet, three times a day with each main meal containing fat.
-
you should take a multivitamin (containing vitamins A, D, E and K) once a day, at bedtime.
-
you should not take alli for more than six months.
<www.xxx.xxx>
16. INFORMATION IN BRAILLE
alli 27 mg chewable tablets
35
-
if you are taking ciclosporin.
-
if you are taking a medicine for diabetes.
-
if you are taking a medicine for high cholesterol.
-
do not take more than three tablets a day.
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
INNER CARTON SLEEVE, 42, 60, 84, 90 or 120 TABLETS
1.
alli 27 mg chewable tablets
Orlistat
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each chewable tablet contains 27 mg orlistat.
3.
LIST OF EXCIPIENTS
Contains lactose and sucrose. See leaflet for further information.
4.
This pack includes:
1 bottle containing 42 chewable tablets
1 bottle containing 60 chewable tablets
1 bottle containing 84 chewable tablets
1 bottle containing 90 chewable tablets
1 bottle containing 120 chewable tablets
1 carry case
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
9.
SPECIAL STORAGE CONDITIONS
36
Do not store above 25°C.
Keep the container tightly closed in order to protect from moisture.
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Glaxo Group Limited
Glaxo Wellcome House
Berkeley Avenue
Greenford
Middlesex
UB6 0NN
United Kingdom
EU/1/07/401/012-016
13. BATCH NUMBER
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product not subject to medical prescription.
15. INSTRUCTIONS ON USE
Weight loss aid
Can help you lose more weight than dieting alone.
Chew one tablet three times a day.
alli is used for weight loss alongside reduced calorie, lower-fat meals in overweight adults, aged 18 or
over.
alli is clinically proven to help you lose more weight than dieting alone. The tablets work only in your
digestive system to stop about a quarter of the fat in your meals from being absorbed. This fat passes
out of your body and may cause changes to your bowel movements. Eat lower-fat meals to help
manage these effects.
How to use
-
chew one tablet, three times a day with each main meal containing fat.
-
you should take a multivitamin (containing vitamins A, D, E and K) once a day, at bedtime.
-
you should not take alli for more than six months.
For further information about the alli weight loss programme visit <www.xxx.xxx>.
37
-
do not take more than three tablets a day.
16. INFORMATION IN BRAILLE
38
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING
BOTTLE LABEL, 42, 60, 84, 90 or 120 TABLETS
1.
alli 27 mg chewable tablets
Orlistat
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
Each chewable tablet contains 27 mg orlistat.
3.
LIST OF EXCIPIENTS
Contains lactose and sucrose.
4.
42 chewable tablets
60 chewable tablets
84 chewable tablets
90 chewable tablets
120 chewable tablets
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
Read the package leaflet before use.
Oral use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF
THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP
9.
SPECIAL STORAGE CONDITIONS
Do not store above 25°C.
Keep the container tightly closed in order to protect from moisture.
39
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Glaxo Group Limited
Glaxo Wellcome House
Berkeley Avenue
Greenford
Middlesex
UB6 0NN
United Kingdom
EU/1/07/401/012-016
13. BATCH NUMBER
Lot
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product not subject to medical prescription.
15. INSTRUCTIONS ON USE
Weight loss aid
Adults, aged 18 or over, who are overweight.
16. INFORMATION IN BRAILLE
40
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
CARRY CASE (SHUTTLE)
1.
alli 27 mg chewable tablets
Orlistat
Oral use
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
4.
BATCH NUMBER
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
Holds 3 tablets.
6.
OTHER
Read the package leaflet before use.
Do not store above 25°C.
Discard any tablets stored in this case for more than one month.
41
B. PACKAGE LEAFLET
42
PACKAGE LEAFLET: INFORMATION FOR THE USER
alli 60 mg hard capsules
Orlistat
Read all of this leaflet carefully because it contains important information for you.
This medicine is available without a prescription. However, you still need to use it carefully to get the
best results from it.
•
Keep this leaflet. You may need to read it again.
•
Ask your doctor or pharmacist if you need more information or advice.
•
If you do not lose weight after taking alli for 12 weeks, see your doctor or pharmacist for advice.
You may need to stop taking alli.
•
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, tell
your doctor or pharmacist.
In this leaflet:
1.
What alli is and what it is used for
•
Risk of being overweight
•
How alli works
2.
Before you take alli
•
Do not take alli
•
Take special care with alli
•
Taking other medicines
•
Taking alli with food and drink
•
Pregnancy and breast-feeding
•
Driving and using machines
3.
How to take alli
•
Preparing to lose weight
o
Choose your start date
o
Decide on your weight loss goal
o
Set your calorie and fat targets
•
Taking alli
o
Adults 18 and over
o
How long should I take alli for?
o
If you take too much alli
o
If you forget to take alli
4.
Possible side effects
•
Serious side effects
•
Very common side effects
•
Common side effects
•
Effects seen in blood tests
•
Learn to deal with diet-related treatment effects
5.
Further information
•
What alli contains
•
What alli looks like and contents of the pack
•
Marketing authorisation holder and manufacturer
•
Further helpful information
1.
WHAT alli IS AND WHAT IT IS USED FOR
alli is used for weight loss in adults aged 18 and over who are overweight, and have a body mass index
(BMI) of 28 or above. alli should be used along with a reduced calorie, lower-fat diet.
43
6.
How to store alli
BMI is a way to find out if you have a healthy weight, or are overweight, for your height. The chart
below will help you find out whether you are overweight and whether alli is right for you.
Find your height on the chart. If you weigh less than the weight shown for your height, do not take
alli
.
Height
Weight Height
Weight
1.50 m
63 kg
4' 10''
9 st 8 lbs
1.55 m
67.25 kg
5' 0''
10 st 3 lbs
1.60 m
71.75 kg
5' 2''
10 st 13 lbs
1.65 m
76.25 kg
5' 4''
11 st 9 lbs
1.70 m
81 kg
5' 6''
12 st 5 lbs
1.75 m
85.75 kg
5' 8''
13 st 2 lbs
1.80 m
90.75 kg 5' 10''
13 st 13 lbs
1.85 m
95.75 kg
6' 0''
14 st 10 lbs
1.90 m
101 kg
6' 2''
15 st 8 lbs
Risk of being overweight
Being overweight increases your risk of developing several serious health problems such as diabetes
and heart disease. These conditions may not cause you to feel unwell so you should see your doctor
for a general health check.
How alli works
The active ingredient (orlistat) in alli is designed to target fat in your digestive system. It stops about a
quarter of the fat in your meals from being absorbed. This fat will pass out of the body in your stools.
You may experience diet-related treatment effects (see Chapter 4). It is therefore important that you
commit to a lower-fat diet to manage these effects. If you do, the action of the capsules will assist
your efforts by helping you to lose more weight compared to dieting alone. For every 2 kg (4 lb) you
lose from dieting alone, alli can help you lose 1 kg (2 lb) more.
2.
BEFORE YOU TAKE alli
Do not take alli
•
If you are under 18.
•
If you are pregnant or breast-feeding.
•
If you are taking ciclosporin, used after organ transplants, for severe rheumatoid arthritis and
some severe skin conditions.
•
If you are taking warfarin or other medicines used to thin the blood.
•
If you are allergic (hypersensitive) to orlistat or any of the ingredients of alli: see Chapter 6 for
further information.
•
If you have cholestasis (condition where the flow of bile from the liver is blocked).
•
If you have problems absorbing food (chronic malabsorption syndrome) diagnosed by a doctor.
Take special care with alli
If you have diabetes. Tell your doctor who may need to adjust your anti-diabetic medicine.
44
If you have kidney disease. Talk to your doctor before taking alli if you have problems with your
kidneys. The use of orlistat may be associated with kidney stones in patients suffering from chronic
kidney disease.
Taking other medicines
alli may affect some medicines you have to take.
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Do not take alli with these medicines
•
Ciclosporin: ciclosporin is used after organ transplants, for severe rheumatoid arthritis and some
severe skin conditions.
•
Warfarin or other medicines used to thin the blood.
The oral contraceptive pill and alli
•
The oral contraceptive pill may be less effective if you get severe diarrhoea. Use an extra method
of contraception if you get severe diarrhoea.
Multivitamins and alli
•
You should take a multivitamin, every day. alli can lower the levels of some vitamins absorbed by
your body. The multivitamin should contain vitamins A, D, E and K. You should take the
multivitamin at bedtime, when you will not be taking alli, to help ensure that the vitamins are
absorbed.
Talk to your doctor before taking alli if you are taking
•
amiodarone, used for heart rhythm problems.
•
acarbose, used for diabetes.
•
a thyroid medicine (levothyroxine) as it may be necessary to adjust your dose and take your
medicines at different times of the day.
•
a medicine for epilepsy as any changes in the frequency and severity of your convulsions should
be discussed with your doctor.
Talk to your doctor or pharmacist when taking alli
•
If you are taking a medicine for high blood pressure as it may be necessary to adjust your dose.
•
If you are taking a medicine for high cholesterol as it may be necessary to adjust your dose.
Taking alli
with food and drink
alli should be used along with a reduced calorie, lower-fat diet. Try to start this diet before beginning
treatment. For information on how to set your calorie and fat targets, see
Further helpful information
in the blue pages in Chapter 6.
Take alli just before, during or up to one hour after meals. This usually means one capsule at
breakfast, lunch and dinner. If you miss a meal, or your meal contains no fat, do not take a capsule.
alli does not work unless there is some fat in the meal.
If you eat a high-fat meal, do not take more than the recommended dose. Taking the capsule with a
meal containing too much fat may increase your chance of getting diet-related treatment effects (see
Chapter 4). Make every effort to avoid any high-fat meals while taking alli.
Pregnancy and breast-feeding
Do not take alli if you are pregnant or breast-feeding.
Driving and using machines
45
alli is unlikely to affect your ability to drive and use machines.
3.
HOW TO TAKE alli
Preparing to lose weight
1. Choose your start date
Choose the day you will start taking the capsules ahead of time. Before you start taking the capsules,
begin your reduced calorie, lower-fat diet and give your body a few days to adjust to your new eating
habits. Keep a record of what you are eating in a food diary. Food diaries are effective, because they
make you aware of what you are eating, how much you eat, and give you the basis to make changes.
2. Decide on your weight loss goal
Think about how much weight you want to lose and then set a target weight. A realistic goal is to lose
between 5% to 10% of your starting weight. The amount of weight you lose may vary from week to
week. You should aim to lose weight at a gradual, steady pace of about 0.5 kg (1 lb) per week.
3. Set your calorie and fat targets
To help you reach your weight-loss goal you need to set two daily targets, one for calories and one for
fat. For further advice see
Further helpful information
in the blue pages in Chapter 6.
Taking alli
Adults 18 and over
•
Take one capsule, three times a day.
•
Take alli just before, during or up to one hour after meals. This usually means one capsule at
breakfast, lunch and dinner. Make sure your three main meals are well balanced, reduced calorie,
and lower-fat.
•
If you miss a meal, or your meal contains no fat, do not take a capsule. alli does not work unless
there is some fat in the meal.
•
Swallow the capsule whole with water.
•
Do not take more than 3 capsules a day.
•
You can keep your daily dose of alli in the blue carry case (Shuttle) included in this pack.
•
Eat lower-fat meals to reduce the chance of diet-related treatment effects (see Chapter 4).
•
Try to be more physically active before you start taking the capsules. Physical activity is an
important part of a weight loss programme. Remember to check with your doctor first if you have
not exercised before.
•
Continue to be active while taking alli and after you stop taking it.
How long should I take alli for?
•
alli should not be taken for more than six months.
•
If you do not lose weight after taking alli for 12 weeks, see your doctor or pharmacist for advice.
You may need to stop taking alli.
•
Successful weight loss is not just about eating differently for a short period of time before
reverting to your old habits. People who lose weight and maintain the loss make lifestyle changes,
which include changes to what they eat and how active they are.
46
If you take too much alli
Do not take more than 3 capsules a day.
Î
If you take too many capsules, contact a doctor as soon as possible.
If you forget to take alli
If you miss taking a capsule:
•
If it is less than an hour since your last main meal, take the missed capsule.
•
If it is more than an hour since your last main meal, do not take the missed capsule. Wait and take
the next capsule around your next main meal as usual.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, alli can cause side effects, although not everybody gets them.
Most of the common side effects related to alli (for example, wind with or without oily spotting,
sudden or more frequent bowel motions and soft stools) are caused by the way it works (see Chapter
1). Eat lower-fat meals to help manage these diet-related treatment effects.
Serious side effects
It is not known how frequently these side effects occur
Severe allergic reactions
•
Signs of a severe allergic reaction include: severe breathing difficulties, sweating, rash, itching,
swollen face, rapid heart beat, collapse.
Î
Stop taking the capsules. Get medical help immediately.
Other serious side effects
•
Bleeding from the back passage (rectum)
•
Diverticulitis (inflammation of the large intestine). Symptoms may include lower stomach
(abdominal) pain, particularly on the left side, possibly with fever and constipation
•
Pancreatitis (inflammation of the pancreas). Symptoms may include severe abdominal pain
sometimes radiating towards the back, possibly with fever, nausea and vomiting
•
Skin blistering (including blisters that burst)
•
Severe stomach pain caused by gallstones.
•
Hepatitis (inflammation of the liver). Symptoms can include yellow skin and eyes, itching,
stomach pain and liver tenderness.
Î
Stop taking the capsules. Tell your doctor if you get any of these.
Very common side effects
These may affect more than 1 in 10 people taking alli
•
Wind (flatulence), with or without oily spotting
•
Sudden bowel motions
•
Fatty or oily stools
•
Soft stools
Î
Tell your doctor or pharmacist if any of these side effects gets severe or troublesome.
Common side effects
These may affect up to 1 in 10 people taking alli
•
Stomach (abdominal) pain
•
Incontinence (stools)
•
Runny/liquid stools
47
•
More frequent bowel motions
•
Anxiety
Î
Tell your doctor or pharmacist if any of these side effects gets severe or troublesome.
Effects seen in blood tests
It is not known how frequently these effects occur
•
Increases in the levels of some liver enzymes
•
Effects on blood clotting in people taking warfarin or other blood-thinning (anti-coagulant)
medicines
Î
Tell your doctor that you are taking alli when you have a blood test.
If any of the side effects become serious, or if you notice any side effects not listed in this leaflet, tell
your doctor or pharmacist.
Learn to deal with diet-related treatment effects
The most common side effects are caused by the way the capsules work and result from some of the
fat being passed out of your body. Such effects typically occur within the first few weeks of using the
capsules, before you may have learnt to limit the amount of fat in your diet. Such diet-related
treatment effects may be a signal that you have eaten more fat than you should have done.
You can learn to minimise the impact of diet-related treatment effects by following these guidelines:
•
Start your lower-fat diet a few days, or even a week, before you begin taking the capsules.
•
Find out more about how much fat your favourite foods typically contain, and the size of your
portions. By familiarising yourself with portions you will be less likely to accidentally exceed
your fat target.
•
Distribute your fat allowance evenly across your meals for the day. Do not “save up” fat and
calorie allowances and then splurge on a high-fat meal or dessert, as you may have done on other
weight loss programmes.
•
Most users who experience these effects find that they can manage and control them by adjusting
their diet.
Do not be concerned if you do not experience any of these problems. This does not mean that the
capsules are not working.
5.
HOW TO STORE alli
•
Keep out of the reach and sight of children.
•
Do not use alli after the expiry date which is stated on the carton and bottle after “EXP”. The
expiry date refers to the last day of that month.
•
Do not store above 25°C.
•
Keep the container tightly closed to protect from moisture.
•
The bottle contains two sealed canisters containing silica gel to keep the capsules dry. Keep the
canisters in the bottle. Do not swallow them.
•
You can also keep your daily dose of alli in the blue carry case (Shuttle) included in this pack.
Discard any capsules stored in the carry case for more than one month.
6.
FURTHER INFORMATION
What alli contains
The active substance is orlistat. Each hard capsule contains 60 mg of orlistat.
The other ingredients are:
•
Capsule filling: microcrystalline cellulose (E460), sodium starch glycolate, povidone (E1201),
sodium laurilsulfate, talc.
48
•
Capsule shell: gelatin, indigo carmine (E132), titanium dioxide (E171), sodium laurilsulfate,
sorbitan monolaurate, black ink (shellac, iron oxide black (E172), propylene glycol).
•
Capsule band: gelatin, polysorbate 80, indigo carmine (E132).
What alli looks like and contents of the pack
alli capsules have a turquoise cap and body, with a dark blue band round the middle, imprinted with
"alli".
alli is available in pack sizes of 42, 60, 84, 90 and 120 capsules. Not all pack sizes may be available in
all countries.
A blue carry case (Shuttle) is included in this pack for carrying your daily dose of alli.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Glaxo Group Limited, Glaxo Wellcome House, Berkeley
Avenue, Greenford, Middlesex UB6 0NN, United Kingdom.
Manufacturer:
Famar, 190 11 Avlona, Greece
Catalent UK Packaging Limited, Sedge Close, Headway, Great Oakley, Corby,
Northamptonshire NN18 8HS, United Kingdom.
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder.
You can also visit your country specific alli website for further information about the alli weight loss
programme.
België/Belgique/Belgien
GlaxoSmithKline s.a./n.v.
Tél/Tel: + 32 2656 2900
Luxembourg/Luxemburg
GlaxoSmithKline s.a./n.v.
Belgique/Belgien
Tél/Tel: + 32 2656 2900
www.alli.be
България
ГлаксоСмитКлайн Консюмър Хелткеър
Teл.: + 359 2 953 10 34
Magyarország
GlaxoSmithKline Kft.
Consumer Healthcare
Tel.: + 36 1 225 5800
Malta
GlaxoSmithKline (Malta) Limited
Tel: + 356 21 238131
Deutschland
Norge
49
GlaxoSmithKline Consumer Healthcare GmbH
& Co. KG,
Tel: 0049 (0) 180 3 63462554
www.alliplan.no
Österreich
GlaxoSmithKline Markenartikel GmbH
Tel: 0043 (0) 512 / 390 11040
Ελλάδα
GlaxoSmithKline A.E.B.E.
Λ. Κηφισίας 266, 152 32 Χαλάνδρι
Τηλ: + 30 210 68 82 100
Polska
GlaxoSmithKline Consumer Healthcare Sp. z o.o.
Tel.: + 48 (0)22 576 96 00
España
GlaxoSmithKline Consumer Healthcare, S.A.
Tel: + 34 902 014 400
Portugal
GlaxoSmithKline Consumer Healthcare – Produtos
para a Saúde e Higiene, Lda.
Tel: 800201343
France
GlaxoSmithKline Santé Grand Public
Tél.: + 33 (0)1 39 17 80 00
România
GlaxoSmithKline Consumer Healthcare S.R.L.
Tel: + 40 21 302 8 208
Ireland
GlaxoSmithKline Consumer Healthcare
(Ireland) Limited
Tel: + 353 (0)1 495 5000
Slovenija
GlaxoSmithKline d.o.o.
Tel: + 386 (0)1 280 25 66
Ísland
Icepharma hf.
Sími: + 354 540 8000
Slovenská republika
GlaxoSmithKline Slovakia s. r. o.
Tel: + 421 (0)2 48 26 11 11
Italia
GlaxoSmithKline Consumer Healthcare S.p.A.
Tel: + 39 02 38062020
Suomi/Finland
GlaxoSmithKline Oy
Consumer Healthcare
Puh/Tel: +358 (0)10 30 30 100
50
Κύπρος
Χ.Α.Παπαέλληνας & Σία Λτδ,
Τ.Θ. 24018, 1700 Λευκωσία
Tηλ. +357 22 741 741
www.alli.com.cy
United Kingdom
GlaxoSmithKline Consumer Healthcare
Tel: + 44 (0)500 888 878 (Freephone)
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
---------------------------------------------------------------------------------------------------------------------------
FURTHER HELPFUL INFORMATION
Risk of being overweight
Being overweight will affect your health and increase your risk of developing serious health problems
such as:
•
High blood pressure
•
Diabetes
•
Heart disease
•
Stroke
•
Certain forms of cancer
•
Osteoarthritis
Talk to your doctor about your risk of developing these conditions.
Importance of losing weight
Losing weight and maintaining weight loss, for example by improving your diet and increasing your
physical activity, can help reduce the risk of serious health problems and help improve your health.
Helpful tips on your diet and your calorie and fat targets while taking alli
alli should be used along with a reduced calorie, lower-fat diet. The capsules work by preventing
some of the fat you eat from being absorbed but you can still eat foods from all the main food groups.
Although you should focus on the calories and fat that you eat, it is important to eat a balanced diet.
You should choose meals which contain a range of different nutrients and learn to eat healthily for the
long term.
Understanding the importance of calorie and fat targets
51
Calories are a measurement of the energy your body needs. They are sometimes called kilocalories or
kcal. Energy may also be measured in kilojoules, which you may also see on food labels.
•
The calorie target is the maximum number of calories you will eat each day. See the chart
further on in this section.
•
Your fat gram target is the maximum number of grams of fat you will eat in each meal. The fat
gram target chart follows the information below on setting your calorie target.
•
Controlling your fat target is essential because of the way the capsules work. Taking alli means
your body will pass more fat through, and therefore may struggle to cope with eating as much
fat as before. So by meeting your fat target, you will maximise weight loss results while
minimising the risk of diet-related treatment effects.
•
You should aim to lose weight gradually and steadily. Losing around 0.5 kg (1 lb) per week is
ideal.
How to set your calorie target
The following table has been worked out so that it gives you a calorie target that is about 500 calories
fewer per day than your body needs to maintain your current weight. That adds up to 3500 fewer
calories per week, about the number of calories in 0.5 kg (1 lb) of fat.
Your calorie target alone should allow you to lose weight at a gradual, steady pace of about 0.5 kg
(1 lb) per week, without feeling frustrated or deprived.
Eating fewer than 1200 calories per day is not recommended.
You will need to know your activity level to set your calorie targets. The more active you are, the
higher your calorie target.
•
Low activity means you do little or no walking, climbing stairs, gardening, or other physical
activity on a daily basis.
•
Moderate activity means you burn around 150 calories per day in physical activity, for
example, walking three kilometres (2 miles), gardening for 30 to 45 minutes, or running two
kilometres (1.25 miles) in 15 minutes. Choose the level that most closely fits your daily
routine. If you are unsure which level you are, choose Low activity.
Women
Low activity
Below 68.1 kg
Below 10 st 10 lb
1200 calories
68.1 kg to 74.7 kg
10 st 10 lb to 11 st 11 lb
1400 calories
74.8 kg to 83.9 kg
11 st 12 lb to 13 st 2 lb
1600 calories
84.0 kg and over
13 st 3 lb and over
1800 calories
Moderate
activity
Below 61.2 kg
Below 9 st 9 lb
1400 calories
61.3 kg to 65.7 kg
9 st 9 lb to 10 st 4 lb
1600 calories
65.8 kg and over
10 st 5 lb and over
1800 calories
Men
Low activity
Below 65.7 kg
Below 10 st 4 lb
1400 calories
65.8 kg to 70.2 kg
10 st 5 lb to 11 st
1600 calories
70.3 kg and over
11 st 1 lb and over
1800 calories
Moderate
activity
59.0 kg and over
9 st 4 lb and over
1800 calories
How to set your fat target
The following chart shows how to set your fat target based on the amount of calories you are allowed
per day. You should plan to have three meals per day. If you have set a target of 1400 calories per
day, for example, the maximum amount of fat allowed per meal would be 15 g. To stay within your
daily allowance for fat, snacks should contain no more than 3 g of fat.
52
Amount of calories
you can eat per day
Maximum amount
of fat allowed per
meal
Maximum
amount of fat
allowed from
snacks per day
1200
12 g
3 g
1400
15 g
3 g
1600
17 g
3 g
1800
19 g
3 g
Remember
•
Stick to realistic calorie and fat targets as this is a good way of maintaining your weight loss
achievements in the long-term.
•
Write down what you eat in a food diary, including the calorie and fat content.
•
Try to be more physically active before you start taking the capsules. Physical activity is an
important part of a weight loss programme. Remember to check with your doctor first if you have
not exercised before.
•
Continue to be active while taking alli and after you stop taking it.
The alli weight loss programme combines the capsules with an eating plan and a wide range of
resources to help you understand how to eat a reduced calorie, lower-fat diet and guidelines for
becoming more active.
The alli website (please refer to your country specific website included in the list of local
representatives above) provides you with a range of interactive tools, lower-fat recipes, physical
activity tips and other useful information to help you lead a healthy life and to support you in meeting
your weight loss goals, together with details of a weight loss programme which is individually tailored
for you.
Visit <www.xxx.xxx>
53
PACKAGE LEAFLET: INFORMATION FOR THE USER
alli 27 mg chewable tablets
Orlistat
Read all of this leaflet carefully because it contains important information for you.
This medicine is available without a prescription. However, you still need to use it carefully to get the
best results from it.
-
Keep this leaflet. You may need to read it again.
-
If you do not lose weight after taking alli for 12 weeks, see your doctor or pharmacist for
advice. You may need to stop taking alli.
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
tell your doctor or pharmacist.
In this leaflet:
1.
What alli is and what it is used for
-
Risk of being overweight
2.
Before you take alli
-
How alli works
Do not take alli
-
Take special care with alli
-
Taking other medicines
-
Taking alli with food and drink
-
Pregnancy and breast-feeding
-
Driving and using machines
-
Important information about some of the ingredients of alli
3.
How to take alli
-
Preparing to lose weight
-
Choose your start date
-
Decide on your weight loss goal
-
Set your calorie and fat targets
-
Taking alli
-
Adults 18 and over
-
How long should I take alli for?
-
If you take too much alli
-
If you forget to take alli
4.
Possible side effects
-
Serious side effects
-
Very common side effects
-
Common side effects
-
Effects seen in blood tests
-
Learn to deal with diet-related treatment effects
5.
How to store alli
6.
Further information
-
What alli contains
-
What alli looks like and contents of the pack
-
Marketing Authorisation Holder and Manufacturer
-
Further helpful information
1.
WHAT alli IS AND WHAT IT IS USED FOR
alli is used for weight loss in adults aged 18 and over who are overweight, and have a body mass index
(BMI) of 28 or above. alli should be used along with a reduced calorie, lower-fat diet.
54
-
Ask your doctor or pharmacist if you need more information or advice.
-
BMI is a way to find out if you have a healthy weight, or are overweight, for your height. The chart
below will help you find out whether you are overweight and whether alli is right for you.
Find your height on the chart. If you weigh less than the weight shown for your height, do not take
alli
.
Height
Weight Height
Weight
1.50 m
63 kg
4 ' 10 ''
9 st 8 lbs
1.55 m
67.25 kg 5 ' 0 ''
10 st 3 lbs
1.60 m
71.75 kg 5 ' 2 ''
10 st 13 lbs
1.65 m
76.25 kg 5 ' 4 ''
11 st 9 lbs
1.70 m
81 kg
5 ' 6 ''
12 st 5 lbs
1.75 m
85.75 kg 5 ' 8 ''
13 st 2 lbs
1.80 m
90.75 kg 5 ' 10 ''
13 st 13 lbs
1.85 m
95.75 kg 6 ' 0 ''
14 st 10 lbs
1.90 m
101 kg
6 ' 2 ''
15 st 8 lbs
Risk of being overweight
Being overweight increases your risk of developing several serious health problems such as diabetes
and heart disease. These conditions may not cause you to feel unwell so you should see your doctor
for a general health check.
How alli works
The active ingredient (orlistat) in alli is designed to target fat in your digestive system. It stops about a
quarter of the fat in your meals from being absorbed. This fat will pass out of the body in your stools.
You may experience diet-related treatment effects (see Chapter 4). It is therefore important that you
commit to a lower-fat diet to manage these effects. If you do, the action of the tablets will assist your
efforts by helping you to lose more weight compared to dieting alone.
Each tablet contains ingredients that help alli work efficiently in your digestive system and chewing
the tablet releases these substances quickly. So for every 2 kg (4 lb) you lose from dieting alone, alli
chewable tablets can help you lose 1 kg (2 lb) more. Chew one tablet, three times a day.
2.
BEFORE YOU TAKE alli
Do not take alli
-
If you are under 18.
-
If you are taking ciclosporin, used after organ transplants, for severe rheumatoid arthritis and
some severe skin conditions.
-
If you are allergic (hypersensitive) to orlistat or any of the ingredients of alli: see Chapter 6 for
further information.
-
If you have problems absorbing food (chronic malabsorption syndrome) diagnosed by a doctor.
Take special care with alli
55
-
If you are pregnant or breast-feeding.
-
If you are taking warfarin or other medicines used to thin the blood.
-
If you have cholestasis (condition where the flow of bile from the liver is blocked).
-
If you have kidney disease. Talk to your doctor before taking alli if you have problems with
your kidneys. The use of orlistat may be associated with kidney stones in patients suffering
from chronic kidney disease.
Taking other medicines
alli may affect some medicines you have to take.
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
Do not take alli with these medicines
-
Ciclosporin: ciclosporin is used after organ transplants, for severe rheumatoid arthritis and some
-
Warfarin or other medicines used to thin the blood.
The oral contraceptive pill and alli
-
The oral contraceptive pill may be less effective if you get severe diarrhoea. Use an extra
method of contraception if you get severe diarrhoea.
Multivitamins and alli
-
You should take a multivitamin, every day. alli can lower the levels of some vitamins absorbed
by your body. The multivitamin should contain vitamins A, D, E and K. You should take the
multivitamin at bedtime, when you will not be taking alli, to help ensure that the vitamins are
absorbed.
Talk to your doctor before taking alli if you are taking
-
amiodarone, used for heart rhythm problems.
-
acarbose, used for diabetes.
-
a thyroid medicine (levothyroxine) as it may be necessary to adjust your dose and take your
medicines at different times of the day.
-
a medicine for epilepsy as any changes in the frequency and severity of your convulsions should
be discussed with your doctor.
Talk to your doctor or pharmacist when taking alli
-
If you are taking a medicine for high blood pressure as it may be necessary to adjust your dose.
Taking alli
with food and drink
alli should be used along with a reduced calorie, lower-fat diet. Try to start this diet before beginning
treatment. For information on how to set your calorie and fat targets, see
Further helpful information
in the blue pages in Chapter 6.
Take alli just before, during or up to one hour after meals. This usually means one tablet at breakfast,
lunch and dinner. If you miss a meal, or your meal contains no fat, do not take a tablet. alli does not
work unless there is some fat in the meal.
If you eat a high-fat meal, do not take more than the recommended dose. Taking the tablet with a meal
containing too much fat may increase your chance of getting diet-related treatment effects (see
Chapter 4). Make every effort to avoid any high-fat meals while taking alli.
Pregnancy and breast-feeding
Do not take alli if you are pregnant or breast-feeding.
Driving and using machines
alli is unlikely to affect your ability to drive and use machines.
56
-
If you have diabetes. Tell your doctor who may need to adjust your anti-diabetic medicine.
severe skin conditions.
-
If you are taking a medicine for high cholesterol as it may be necessary to adjust your dose.
Important information about some of the ingredients of alli
This medicine contains lactose and sucrose. If you have been told by your doctor that you have an
intolerance to some sugars, contact your doctor before taking this medicine.
3.
HOW TO TAKE alli
Preparing to lose weight
1. Choose your start date
Choose the day you will start taking the tablets ahead of time. Before you start taking the tablets, begin
your reduced calorie, lower-fat diet and give your body a few days to adjust to your new eating habits.
Keep a record of what you are eating in a food diary. Food diaries are effective, because they make
you aware of what you are eating, how much you eat, and give you the basis to make changes.
2. Decide on your weight loss goal
Think about how much weight you want to lose and then set a target weight. A realistic goal is to lose
between 5 % to 10 % of your starting weight. The amount of weight you lose may vary from week to
week. You should aim to lose weight at a gradual, steady pace of about 0.5 kg (1 lb) per week.
3. Set your calorie and fat targets
To help you reach your weight-loss goal you need to set two daily targets, one for calories and one for
fat. For further advice see
Further helpful information
in the blue pages in Chapter 6.
Taking alli
Adults 18 and over
-
Take alli just before, during or up to one hour after meals. This usually means one tablet at
breakfast, lunch and dinner. Make sure your three main meals are well balanced, reduced
calorie, and lower-fat.
-
If you miss a meal, or your meal contains no fat, do not take a tablet. alli does not work unless
there is some fat in the meal.
-
Do not take more than 3 tablets a day.
-
You can keep your daily dose of alli in the blue carry case (Shuttle) included in this pack.
-
Eat lower-fat meals to reduce the chance of diet-related treatment effects (see Chapter 4).
-
Try to be more physically active before you start taking the tablets. Physical activity is an
important part of a weight loss programme. Remember to check with your doctor first if you
have not exercised before.
-
Continue to be active while taking alli and after you stop taking it.
How long should I take alli for?
-
alli should not be taken for more than six months.
-
If you do not lose weight after taking alli for 12 weeks, see your doctor or pharmacist for
advice. You may need to stop taking alli.
-
Successful weight loss is not just about eating differently for a short period of time before
reverting to your old habits. People who lose weight and maintain the loss make lifestyle
changes, which include changes to what they eat and how active they are.
57
-
Chew one tablet, three times a day.
If you take too much alli
Do not take more than 3 tablets a day.
Î
If you take too many tablets, contact a doctor as soon as possible.
If you forget to take alli
If you miss taking a tablet:
-
If it is more than an hour since your last main meal, do not take the missed tablet. Wait and take
the next tablet around your next main meal as usual.
-
Do not take 2 tablets at the same time to make up for a forgotten tablet.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, alli can cause side effects, although not everybody gets them.
Most of the common side effects related to alli (for example, wind with or without oily spotting,
sudden or more frequent bowel motions and soft stools) are caused by the way it works (see
Chapter 1). Eat lower-fat meals to help manage these diet-related treatment effects.
Serious side effects
It is not known how frequently these side effects occur
Severe allergic reactions
- Signs of a severe allergic reaction include: severe breathing difficulties, sweating, rash, itching,
swollen face, rapid heart beat, collapse.
Î
Stop taking the tablets. Get medical help immediately.
Other serious side effects
- Bleeding from the back passage (rectum).
- Diverticulitis (inflammation of the large intestine). Symptoms may include lower stomach
(abdominal) pain, particularly on the left side, possibly with fever and constipation.
- Pancreatitis (inflammation of the pancreas). Symptoms may include severe abdominal pain
sometimes radiating towards the back, possibly with fever, nausea and vomiting.
- Skin blistering (including blisters that burst).
- Severe stomach pain caused by gallstones.
- Hepatitis (inflammation of the liver). Symptoms can include yellow skin and eyes, itching,
stomach pain and liver tenderness.
Î
Stop taking the tablets. Tell your doctor if you get any of these.
Very common side effects
These may affect more than 1 in 10 people taking alli
- Wind (flatulence), with or without oily spotting.
- Sudden bowel motions.
- Fatty or oily stools.
- Soft stools.
Î
Tell your doctor or pharmacist if any of these side effects gets severe or troublesome.
Common side effects
These may affect up to 1 in 10 people taking alli
-
Stomach (abdominal) pain.
-
Incontinence (stools).
58
-
If it is less than an hour since your last main meal, take the missed tablet.
-
Runny/liquid stools.
- More frequent bowel motions.
- Anxiety.
Î
Tell your doctor or pharmacist if any of these side effects gets severe or troublesome.
Effects seen in blood tests
It is not known how frequently these effects occur
- Increases in the levels of some liver enzymes.
- Effects on blood clotting in people taking warfarin or other blood-thinning (anti-coagulant)
medicines.
Î
Tell your doctor that you are taking alli when you have a blood test.
If any of the side effects become serious, or if you notice any side effects not listed in this leaflet, tell
your doctor or pharmacist.
Learn to deal with diet-related treatment effects
The most common side effects are caused by the way the tablets work and result from some of the fat
being passed out of your body. Such effects typically occur within the first few weeks of using the
tablets, before you may have learnt to limit the amount of fat in your diet. Such diet-related treatment
effects may be a signal that you have eaten more fat than you should have done.
You can learn to minimise the impact of diet-related treatment effects by following these guidelines:
- Start your lower-fat diet a few days, or even a week, before you begin taking the tablets.
- Find out more about how much fat your favourite foods typically contain, and the size of your
portions. By familiarising yourself with portions you will be less likely to accidentally exceed
your fat target.
- Distribute your fat allowance evenly across your meals for the day. Do not “save up” fat and
calorie allowances and then splurge on a high-fat meal or dessert, as you may have done on
other weight loss programmes.
- Most users who experience these effects find that they can manage and control them by
adjusting their diet.
Do not be concerned if you do not experience any of these problems. This does not mean that the
tablets are not working.
5.
HOW TO STORE alli
-
Do not use alli after the expiry date which is stated on the carton and bottle after “EXP”. The
expiry date refers to the last day of that month.
-
Keep the container tightly closed to protect from moisture.
-
The bottle contains two sealed canisters containing silica gel to keep the tablets dry. Keep the
canisters in the bottle. Do not swallow them.
-
You can also keep your daily dose of alli in the blue carry case (Shuttle) included in this pack.
Discard any tablets stored in the carry case for more than one month.
6.
FURTHER INFORMATION
What alli contains
-
The active substance is orlistat. Each chewable tablet contains 27 mg of orlistat.
-
glycolate, microcrystalline cellulose (E460), povidone (E1201), glycerol dibehenate (E471),
sucrose monopalmitate (E473), sodium stearyl fumarate, macrogol stearate (E431).
59
-
Keep out of the reach and sight of children.
-
Do not store above 25°C.
The other ingredients are mannitol (E421), xylitol (E967), anhydrous lactose, sodium starch
What alli looks like and contents of the pack
The chewable tablets are white to off-white, faceted and triangular in shape, debossed with ‘alli’.
alli is available in pack sizes of 42, 60, 84, 90 and 120 tablets. Not all pack sizes may be available in
all countries.
A blue carry case (Shuttle) is included in this pack for carrying your daily dose of alli.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
:
Glaxo Group Limited,
Glaxo Wellcome House,
Berkeley Avenue,
Greenford,
Middlesex UB6 0NN,
United Kingdom.
Manufacturer:
Famar,
190 11 Avlona,
Greece.
Catalent UK Packaging Limited,
Sedge Close, Headway,
Great Oakley,
Corby,
Northamptonshire NN18 8HS,
United Kingdom.
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder.
You can also visit your country specific alli website for further information about the alli weight loss
programme.
België/Belgique/Belgien
GlaxoSmithKline s.a./n.v.
Tél/Tel: + 32 2656 2900
Luxembourg/Luxemburg
GlaxoSmithKline s.a./n.v.
Belgique/Belgien
Tél/Tel: + 32 2656 2900
www.alli.be
България
ГлаксоСмитКлайн Консюмър Хелткеър
Teл.: + 359 2 953 10 34
Magyarország
GlaxoSmithKline Kft.
Consumer Healthcare
Tel.: + 36 1 225 5800
Malta
GlaxoSmithKline (Malta) Limited
Tel: + 356 21 238131
60
Deutschland
GlaxoSmithKline Consumer Healthcare GmbH
& Co. KG,
Tel: 0049 (0) 180 3 63462554
www.alliplan.no
Österreich
GlaxoSmithKline Markenartikel GmbH
Tel: 0043 (0) 512 / 390 11040
Ελλάδα
GlaxoSmithKline A.E.B.E.
Λ. Κηφισίας 266, 152 32 Χαλάνδρι
Τηλ: + 30 210 68 82 100
Polska
GlaxoSmithKline Consumer Healthcare Sp. z o.o.
Tel.: + 48 (0)22 576 96 00
España
GlaxoSmithKline Consumer Healthcare, S.A.
Tel: + 34 902 014 400
Portugal
GlaxoSmithKline Consumer Healthcare – Produtos
para a Saúde e Higiene, Lda.
Tel: 800201343
France
GlaxoSmithKline Santé Grand Public
Tél.: + 33 (0)1 39 17 80 00
România
GlaxoSmithKline Consumer Healthcare S.R.L.
Tel: + 40 21 302 8 208
Ireland
GlaxoSmithKline Consumer Healthcare
(Ireland) Limited
Tel: + 353 (0)1 495 5000
Slovenija
GlaxoSmithKline d.o.o.
Tel: + 386 (0)1 280 25 66
Ísland
Icepharma hf.
Sími: + 354 540 8000
Slovenská republika
GlaxoSmithKline Slovakia s. r. o.
Tel: + 421 (0)2 48 26 11 11
61
Italia
GlaxoSmithKline Consumer Healthcare S.p.A.
Tel: + 39 02 38062020
Suomi/Finland
GlaxoSmithKline Oy
Consumer Healthcare
Puh/Tel: +358 (0) 10 30 30 100
Κύπρος
Χ.Α.Παπαέλληνας & Σία Λτδ,
Τ.Θ. 24018, 1700 Λευκωσία
Tηλ. +357 22 741 741
www.alli.com.cy
United Kingdom
GlaxoSmithKline Consumer Healthcare
Tel: + 44 (0)500 888 878 (Freephone)
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency web site:
---------------------------------------------------------------------------------------------------------------------------
FURTHER HELPFUL INFORMATION
Risk of being overweight
Being overweight will affect your health and increase your risk of developing serious health problems
such as
- High blood pressure
- Diabetes
- Heart disease
- Stroke
- Certain forms of cancer
- Osteoarthritis
Talk to your doctor about your risk of developing these conditions.
Importance of losing weight
Losing weight and maintaining weight loss, for example by improving your diet and increasing your
physical activity, can help reduce the risk of serious health problems and help improve your health.
Helpful tips on your diet and your calorie and fat targets while taking alli
62
alli should be used along with a reduced calorie, lower-fat diet. The tablets work by preventing some
of the fat you eat from being absorbed but you can still eat foods from all the main food groups.
Although you should focus on the calories and fat that you eat, it is important to eat a balanced diet.
You should choose meals which contain a range of different nutrients and learn to eat healthily for the
long term.
Understanding the importance of calorie and fat targets
Calories are a measurement of the energy your body needs. They are sometimes called kilocalories or
kcal. Energy may also be measured in kilojoules, which you may also see on food labels.
-
The calorie target is the maximum number of calories you will eat each day. See the chart
further on in this section.
-
Your fat gram target is the maximum number of grams of fat you will eat in each meal. The fat
gram target chart follows the information below on setting your calorie target.
-
Controlling your fat target is essential because of the way the tablets work. Taking alli means
your body will pass more fat through, and therefore may struggle to cope with eating as much
fat as before. So by meeting your fat target, you will maximise weight loss results while
minimising the risk of diet-related treatment effects.
-
You should aim to lose weight gradually and steadily. Losing around 0.5 kg (1 lb) per week is
ideal.
How to set your calorie target
The following table has been worked out so that it gives you a calorie target that is about 500 calories
fewer per day than your body needs to maintain your current weight. That adds up to 3500 fewer
calories per week, about the number of calories in 0.5 kg (1 lb) of fat.
Your calorie target alone should allow you to lose weight at a gradual, steady pace of about 0.5 kg
(1 lb) per week, without feeling frustrated or deprived.
Eating fewer than 1200 calories per day is not recommended.
You will need to know your activity level to set your calorie targets. The more active you are, the
higher your calorie target.
-
Low activity means you do little or no walking, climbing stairs, gardening, or other physical
-
example, walking three kilometres (2 miles), gardening for 30 to 45 minutes, or running two
kilometres (1.25 miles) in 15 minutes. Choose the level that most closely fits your daily routine.
If you are unsure which level you are, choose Low activity.
63
activity on a daily basis.
Moderate activity means you burn around 150 calories per day in physical activity, for
Women
Low activity
Below 68.1 kg
Below 10 st 10 lbs
1200 calories
68.1 kg to 74.7 kg
10 st 10 lbs to 11 st 11 lbs 1400 calories
74.8 kg to 83.9 kg
11 st 12 lbs to 13 st 2 lbs 1600 calories
84.0 kg and over
13 st 3 lbs and over
1800 calories
Moderate
activity
Below 61.2 kg
Below 9 st 9 lbs
1400 calories
61.3 kg to 65.7 kg
9 st 9 lbs to 10 st 4 lbs
1600 calories
65.8 kg and over
10 st 5 lbs and over
1800 calories
Men
Low activity
Below 65.7 kg
Below 10 st 4 lbs
1400 calories
65.8 kg to 70.2 kg
10 st 5 lbs to 11 st
1600 calories
70.3 kg and over
11 st 1 lb and over
1800 calories
Moderate
activity
59.0 kg and over
9 st 4 lbs and over
1800 calories
How to set your fat target
The following chart shows how to set your fat target based on the amount of calories you are allowed
per day. You should plan to have three meals per day. If you have set a target of 1400 calories per day,
for example, the maximum amount of fat allowed per meal would be 15 g. To stay within your daily
allowance for fat, snacks should contain no more than 3 g of fat.
Amount of calories
you can eat per day
Maximum amount
of fat allowed per
meal
Maximum
amount of fat
allowed from
snacks per day
1200
12 g
3 g
1400
15 g
3 g
1600
17 g
3 g
1800
19 g
3 g
Remember
-
Stick to realistic calorie and fat targets as this is a good way of maintaining your weight loss
achievements in the long-term.
-
Write down what you eat in a food diary, including the calorie and fat content.
-
Try to be more physically active before you start taking the tablets. Physical activity is an
important part of a weight loss programme. Remember to check with your doctor first if you
have not exercised before.
-
Continue to be active while taking alli and after you stop taking it.
The alli weight loss programme combines the tablets with an eating plan and a wide range of resources
to help you understand how to eat a reduced calorie, lower-fat diet and guidelines for becoming more
active.
The alli website (please refer to your country specific website included in the list of local
representatives above) provides you with a range of interactive tools, lower-fat recipes, physical
activity tips and other useful information to help you lead a healthy life and to support you in meeting
your weight loss goals, together with details of a weight loss programme which is individually tailored
for you.
Visit <www.xxx.xxx>
64
Source: European Medicines Agency
- Please bookmark this page (add it to your favorites).
- If you wish to link to this page, you can do so by referring to the URL address below this line.
https://theodora.com/drugs/eu/alli.html
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