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9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 29 July 1998
Date of latest renewal: 29 July 2008
6.1 List of excipients
Capsule filling:
microcrystalline cellulose (E460)
sodium starch glycollate (type A)
povidone (E1201)
sodium lauriyl sulfphate
talc
Capsule shell:
gelatine
indigo carmine (E132)
titanium dioxide (E171)
edible printing ink (black iron oxide, ammoniaum hydroxide solution concentrated, potassium hydroxide, shellac, propylene glycol)
Underlined text has been added, text with strike through deleted:
4.4 Special warnings and precautions for use
The use of orlistat may be associated with hyperoxaluria and oxalate nephropathy in patients with underlying chronic kidney disease and/or volume depletion a (see section 4.8).
Rare occurrence of hypothyroidism and/or reduced control of hypothyroidism may occur. The mechanism, although not proven, may involve a decreased absorption of iodine salts and/or levothyroxine (see section 4.5).
Antiepileptics patient: Orlistat may unbalance anticonvulsivant treatment by decreasing the absorption of antiepileptic drugs, leading to convulsions (see section 4.5).
4.5 Interaction with other medicinal products and other forms of interaction
Amiodarone
A slight small 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.; Iin patients receiving amiodarone treatment, the clinical relevance of this effect remains unknown but may become clinically relevant in some cases. However, iIn patients receiving concomitant amiodarone treatment, reinforcement of clinical and ECG monitoring is warranted.
Convulsions have been reported in patients treated concomitantly with orlistat and antiepileptic drugs e.g. valproate, lamotrigine, for which a causal relationship to an interaction cannot be excluded. Therefore, these patients should be monitored for possible changes in the frequency and/or severity of convulsions.
Rare occurrence of hypothyroidism and/or reduced control of hypothyroidism may occur. The mechanism, although not proven, may involve a decreased absorption of iodine salts and/or levothyroxine (see section 4.4).
4.8 Undesirable effects
Nervous system disorders
Convulsions have been reported in patients treated concomitantly with orlistat and antiepileptic drugs (see section 4.5)
Renal and urinary disorders
Oxalate nephropathy
4.2 Posology and method of administration
There is no relevant indication for use of Xenical in children.
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
Coagulation parameters should be monitored in patients treated with concomitant oral anticoagulants (see section 4.5 and 4.8).
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
Very common:
Headache
Respiratory, thoracic and mediastinal disorders
Common:
Upper respiratory infection
Lower respiratory infection
Gastrointestinal disorders
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
Urinary tract infection
Metabolism and nutrition disorders
Hypoglycemia*
Infections and infestations
Influenza
General disorders and administration site conditions
Fatigue
Reproductive system and breast disorders
Menstrual irregularity
Psychiatric disorders
Anxiety
* 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.
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)
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
·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.
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.