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4.2 Posology and method of administration
There is no relevant indication for use of Xenical
Xenical is not recommended for use in children below age due to a lack of data on safety and/or efficacy.
4.3 Contraindications
- Hypersensitivity to the active substance or to any of the excipients.
- Chronic malabsorption syndrome.
- Cholestasis.
- Breast-feeding.
- Hypersensitivity to the active substance or to any of the excipients
4.4 Special warnings and precautions for use
Coagulation parameters should be monitored in patients treated with concomitant oral anticoagulants (see section 4.5 and 4.8).
4.8 Undesirable effects
Adverse reactions to orlistat are largely gastrointestinal in nature. The incidence of adverse events decreased with prolonged use of orlistat.
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (³1/10), common (³1/100, to <1/10), uncommon (³1/1,000, to <1/100), rare (³1/10,000, to <1/1,000) and very rare (<1/10,000) including isolated reports.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
The following table of undesirable effects (first year of treatment) is based on adverse events that occurred at a frequency of > 2 % and with an incidence ³ 1 % above placebo in clinical trials of 1 and 2 years duration:
|
System organ class
|
Adverse reaction/event
|
|
Nervous system disorders
Very common:
|
Headache
|
|
Respiratory, thoracic and mediastinal disorders
Very common:
Common:
|
Upper respiratory infection
Lower respiratory infection
|
|
Gastrointestinal disorders
Very common:
Common:
|
Abdominal pain/discomfort
Oily spotting from the rectum
Flatus with discharge
Faecal urgency
Fatty/oily stool
Flatulence
Liquid stools
Oily evacuation
Increased defecation
Rectal pain/discomfort
Soft stools
Faecal incontinence
Abdominal distension*
Tooth disorder
Gingival disorder
|
|
Renal and urinary disorders
Common:
|
Urinary tract infection
|
|
Metabolism and nutrition disorders
Very common:
|
Hypoglycemia*
|
|
Infections and infestations
Very common:
|
Influenza
|
|
General disorders and administration site conditions
Common:
|
Fatigue
|
|
Reproductive system and breast disorders
Common:
|
Menstrual irregularity
|
|
Psychiatric disorders
Common:
|
Anxiety
|
|
System Organ Class
|
Adverse Event
|
XENICAL
|
Placebo
|
|
· Infections and Infestations
|
Very common (³ 10 %):
Influenza
|
39.7 %
|
36.2 %
|
|
· Metabolism and Nutrition
Disorders
|
Very common (³ 10 %):
Hypoglycemia*
|
13.0 %
|
10.0 %
|
|
· Psychiatric Disorders
|
Common (1 - < 10 %):
Anxiety
|
4.7 %
|
2.9 %
|
|
· Nervous System Disorders
|
Very common (³ 10 %):
Headache
|
30.6 %
|
27.6 %
|
|
· Respiratory, Thoracic and
Mediastinal Disorders
|
Very common (³ 10 %):
Upper respiratory infection
Common (1 -< 10 %):
Lower respiratory infection
|
38.1 %
7.8 %
|
32.8 %
6.6 %
|
|
· Gastrointestinal Disorders
|
Very common (³ 10 %):
Oily spotting from the rectum Abdominal pain/discomfort
Flatus with discharge
Faecal urgency
Fatty/oily stool
Flatulence
Liquid stools
Oily evacuation
Increased defecation
Common (1 - < 10 %):
Soft stools
Faecal incontinence
Abdominal distension*
Rectal pain/discomfort
Tooth disorder
Gingival disorder
|
26.6 %
25.5 %
23.9 %
22.1 %
20.0 %
16.0 %
15.8 %
11.9 %
10.8 %
8.8 %
7.7 %
6.0 %
5.2 %
4.3 %
4.1 %
|
1.3 %
21.4 %
1.4 %
6.7 %
2.9 %
13.1 %
11.4 %
0.8 %
4.1 %
6.8 %
0.9 %
4.0 %
4.0 %
3.1 %
2.9 %
|
|
· Renal and Urinary Disorders
|
Common (1 - < 10 %):
Urinary tract infection
|
7.5 %
|
7.3 %
|
|
· Reproductive System and
Breast Disorders
|
Common (1 - < 10 %):
Menstrual irregularity
|
9.8 %
|
7.4 %
|
|
· General Disorders and
Administration Site Conditions
|
Common (1 - < 10 %):
Fatigue
|
7.2 %
|
6.4 %
|
* only unique treatment adverse events that occurred at a frequency of > 2 % and with an incidence ³ 1 % above placebo in obese type 2 diabetic patients.
In a 4 year clinical trial, the general pattern of adverse event distribution was similar to that reported for the 1 and 2 year studies with the total incidence of gastrointestinal related adverse events occurring in year 1 decreasing year on year over the four year period.
The following table of undesirable effects is based on post-marketing spontaneous reports, and therefore the frequency remains unknown:
Increase in liver transaminases and in alkaline phosphatise, decreased prothrombin, increased INR (see section 4.4.) and unbalanced anticoagulant treatment resulting in variations of haemostatic parameters have been reported in patients treated with anticoagulants in association with orlistat, rectal bleeding, diverticulitis, pancreatitis, bullous eruptions, hypersensitivity (e.g. pruritus, rash, urticaria, angioedema, bronchospasm and anaphylaxis), cholelithiasis, hepatitis that may be serious.
|
System organ class
|
Adverse reaction
|
|
Investigations
|
Increase in liver transaminases and in alkaline
phosphatase.
Decreased prothrombin, increased INR and
unbalanced anticoagulant treatment resulting in
variations of haemostatic parameters have been
reported in patients treated with anticoagulants in
association with orlistat (see section 4.4 and 4.5)
|
|
Gastrointestinal disorders
|
Rectal bleeding
Diverticulitis
Pancreatitis
|
|
Skin and subcutaneous tissue disorders
|
Bullous eruptions
|
|
Immune system disorders
|
Hypersensitivity (e.g. pruritus, rash, urticaria,
angioedema, bronchospasm and anaphylaxis)
|
|
Hepatobiliary disorders
|
Cholelithiasis
Hepatitis that may be serious
|
|
· Immune System Disorders
Rare (0.01 - < 0.1 %): Hypersensitivity (e.g. pruritus, rash, urticaria, angioedema, bronchospasm and anaphylaxis)
|
|
· Gastrointestinal disorders
Very rare (< 0.01 %): Diverticulitis
|
|
· Hepato-Biliary Disorders
Very rare (< 0.01 %): Cholelithiasis
Hepatitis that may be serious
|
|
·Skin and subcutaneous tissue disorders
Very rare (< 0.01 %): Bullous eruptions
|
|
· Investigations
Very rare (< 0.01 %): Increase in liver transaminases and in alkaline phosphatase.
Decreased prothrombin, increased INR and unbalanced anticoagulant treatment resulting in variations of haemostatic parameters have been reported in patients treated with anticoagulants in association with orlistat
|
Rarely cases of rectal bleeding, generally of mild intensity have been reported.
6.1 List of excipients
Capsule shell:
Ggelatine,
indigo carmine (E132),
titanium dioxide (E171) and
edible printing ink (black iron oxide, ammonium hydroxide, potassium hydroxide, shellac)
6.5 Nature and contents of container
PVC/PE/PVDC blisters containing 21, 42 and 84 hard capsules.
and gGlass bottles with desiccant containing 21, 42 and 84 hard capsules.
containing 21, 42 and 84 hard capsules.
Not all pack sizes may be marketed.
