1. Pharmaceutical Form
It is presented as turquoise cap
and turquoise body bearing the imprint of "ROCHE XENICAL 120"
2. Qualitative and
Active ingredient :
Excipients : Capsule filling :
microcrystalline cellulose, sodium starch glycollate, povidone, sodium
lauryl sulphate and talc.
Capsule shell : gelatine, indigo
carmine ( E132 ) and titamium dioxide ( E171 )
Xenical is indicated, in
conjunction with a mildly hypocaloric diet for the treatment of obese ( BMI ≥
30kg/m2 ) and overweight ( BMI ≥ 28kg/m2 )
patients, including patients with risk factors associated with obesity.
Xenical is effective in weight loss, weight maintenance and prevention of
weight regains. Treatment with Xenical results in an improvement of risk
factors and comorbidities associated with obesity, including
hypercholesterolemia, non-insulin dependent diabetes mellitus ( NIDDM ),
impaired glucose tolerance, hyperinsulinemia, hypertension and in a
reduction of visceral fat.
In type 2 diabetic patients who
are overweight ( BMI ≥ 28kg/m2 ) or obese ( BMI ≥
30kg/m2 ) Xenical, in conjunction with a mildly hypocaloric diet,
provides additional glycemic control when used in combination with
antidiabetic agents such as metformin, sulfonylurea and/or insulin.
Treatment with Xenical should
only be started if diet alone has previously produced a weight loss of at
least 2.5kg over a period of 4 consecutive weeks. Treatment with Orlistat
should be discontinued after 12 weeks if patients have been unable to lose
at least 5% of the body weight as measured at the start of drug therapy.
3.2 Dosage and
The recommended dose of Xenical
is one 120mg capsule with each main meal ( during or up to one hour after
the meal ). If a meal is missed or contains no fat, the dose of Xenical may
be omitted. The patient should be on a nutritionally balanced, mildly
hypocaloric diet that contains approximately 30% of calories from fat. The
daily intake of fat, carbohydrate and protein should be distributed over
three main meals.
Doses above 120mg three times
daily have not been shown to provide additional benefit.
Clinical investigation in
patients with hepatic and /or renal impairment and children under the age of
12 have not been undertaken.
Xenical is contraindicated in
patients with chronic malabsorption syndrome, cholestasis and in patients
with known hypersensitivity to orlistat or any of the other components
contained in the medicinal product.
3.4 Special Warnings and Special
Precautions For Use
The majority of patients in
longterm studies of up to four years of treatment had vitamin A, D, E and K
and beta-carotene levels within normal range. In order to ensure adequate
nutrition, the use of a multivitamin supplement could be considered.
Patients should be advised to
adhere to dietary guidelines ( see Dosage and administration ).
The possibility of experiencing
gastrointestinal events ( see Undesirable effects ) may increase when
Xenical is taken with a diet high in fat ( eg in a 2000 calorie/day diet,
>30% of calories from fat equates to >67g of fat ). The daily intake of fat
should be distributed over three main meals. If Xenical is taken with any
one meal very high in fat, the possibility of gastrointestinal effects may
Weight loss induced by Xenical is
accompanied by improved metabolic control in type 2 diabetics which might
allow or require reduction in the dose of oral hypoglycemic medication ( eg
A reduction in cyclosporin plasma
levels has been observed when Xenical is co-administered. Therefore it is
recommended to monitor more frequently than usual the cyclosporin plasma
levels when Xenical is co-administered ( see Interactions ).
Coagulation parameters should be
monitored in patients treated with concomitant oral anticoagulants.
In a PK study, oral
administration of amiodarone during orlistat treatment demonstrated a 25 -
30% reduction in the systemicexposure to amiodarone and desethylamiodarone.
Due to the complex pharmacokinetics of amiodarone, the clinical effect of
this is unclear. The effect of commencing orlistat treatment in patients on
stable amiodarone therapy has not been studied. A potential reduced
therapeutic efffect of amiodarone is possible.
Substantial weight loss can
increase the risk of cholelithiasis. In a clinical trial of Xenical for the
prevention of type 2 diabetes, the rates of cholelithiasis as an adverse
event were 2.9% ( 47/1649 ) for patients randomized to Xenical and 1.8% (
30/1655 ) for patients randomized to placebo. In this trail, the incidence
of cholelithiasis ( gallstones ) was similar for Xenical and placebo at
similar amounts of weight loss. No increase in cholelithiasis with xenical
was seen in trials that were not evaluating the prevention of type 2
3.5 Interactions With Other
Medicinal Products and Other Forms Of Interaction
No interactions based on specific drug-drug-interaction studies with
amitriptyline, atorvastatin, biguanides, digoxin, fibrates, fluoxetine,
losartan, phenytoin, oral contraceptives, phentermine, pravastatin, warfarin,
nifedipine Gastrointestinal Therapeutic System, nifedipine slow release,
sibutramine or alcohol have been observed.
However, when warfarin or other anticoagulants are given in combination with
orlistat, international normalized ratio (INR) values should be monitored.
Decreases in the absorption of vitamin D, E and G3-carotene have been
observed when co-administered with Xenical. If a multivitamin supplement is
recommended, it should be taken at least two hours after the administration
of Xenical or at bedtime. A reduction in cyclosporin plasma levels has been
observed when Xenical is co-administered. Therefore it is recommended to
monitor more frequently than usual the cyclosporin plasma levels when
Xenical is co-administered (see Special Warnings and Special Precautions For
In a PK study, oral administration of amiodarone during orlistat treatment
demonstrated a 25 - 30% reduction in the systemic exposure to amiodarone and
desethylamiodarone. Due to the complex pharmacokinetics of amiodarone, the
clinical effect of this is unclear. The effect of commencing orlistat
treatment in patients on stable amiodarone therapy has not been studied. A
reduced therapeutic effect of amiodarone is possible.
3.6 Pregnancy and
In animal reproductive studies, no embryotoxic or teratogenic effects were
observed with orlistat.
In absence of a teratogenic effect in animals, no malformative effect is
expected in human beings. However, Xenical is not rec
ommended for use during pregnancy in the absence of clinical data. The
secretion of orlistat in human breast milk has not been investigated.
Xenical should not be taken during breast-feeding.
3.7 Effects on Ability to
Drive and Use Machine
No information available
3.8 Undesirable effects
3.8.1 Experience from clinical trials
Adverse reactions to Xenical are largely gastrointestinal in nature and
related to the pharmacologic effect of the drug in preventing the absorption
of ingested fat. Commonly observed events are oily spotting, flatus with
discharge, fecal urgency, fatty/oily stool, oily evacuation, increased
defecation and fecal incontinence.
The incidence of these increases the
higher the fat content of the diet. Patients should be counseled as to the
possibility of gastrointestinal effects occurring and how best to handle
them such as reinforcing the diet, particularly the percentage of fat it
Consumption of a diet low in fat will decrease the likelihood of
experiencing adverse gastrointestinal events and this may help patients
monitor and regulate their fat intake. These adverse gastrointestinal
reactions are generally mild and transient. They occurred early in treatment
(within 3 months) and most patients experienced only one episode.
Treatment-emergent GI-adverse events that occurred commonly among patients
treated with Xenical were: abdominal pain/discomfort, flatulence, liquid
stools, soft stools, rectal pain/discomfort, tooth disorder, gingival
Other events observed were: upper respiratory infection, lower
respiratory infection; influenza; headache; menstrual irregularity; anxiety;
fatigue; urinary tract infection.
Unique treatment adverse events observed in obese type 2 diabetic patients
were hypoglycemia (very common) and abdominal distension (common). Weight
loss induced by Xenical is accompanied by improved metabolic control in type
2 diabetics which might allow or require reduction in the dose of
hypoglycemic medication (see Special Warnings and Special Precautions for
In a 4 year clinical trial, the general pattern of adverse events
distribution was similar to that reported for the 1 year 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.
In type 2 diabetic patients, adverse event reporting was comparable to that
reported in overweight and obese patients. The only unique treatment adverse
events that occurred at a frequency of >2% and with an incidence ? 1% above
placebo were hypoglycemia (which may occur as a result of improved glycaemic
control) and abdominal distention.
3.8.2 Post-marketing experience
Rare cases of hypersensitivity have been reported. Main clinical symptoms
are pruritus, rash, urticaria, angioedema, bronchospasm and anaphylaxis.
Very rare cases of bullous eruption, increase in liver transaminases and in
alkaline phosphatase and exceptional cases of hepatitis that may be serious
have been reported during the post marketing. No causal relationship or
physiopathological mechanism between hepatitis and orlistat therapy has been
Reports of decreased prothrombin, increased INR and unbalanced anticoagulant
treatment resulting in change of haemostatic parameters have been reported
in patients treated concomitantly with orlistat and anticoagulants during
Single doses of 800 mg Xenical and multiple doses of up to 400 mg t.i.d. for
15 days have been studied in normal weight and obese subjects without
significant adverse findings. In addition, doses of 240 mg t.i.d. have been
administered to obese patients for 6 months without significant increase of
adverse findings. Orlistat overdose cases received during post-marketing
reported either no adverse events or adverse events that are similar to
those reported with recommended dose. Should a significant overdose of
Xenical 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.