Each capsule contains Orlistat 120mg.
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.
The extent of absorption of orlistat was minimal. Plasma concentrations of
intact orlistat were non-measurable (< 5 ng/ml) following a single oral
administration 360mg of orlistat. In general, after long term treatment at
therapeutic doses, detection of intact orlistat in plasma was sporadic and
concentrations were extremely low (< 10 ng/ml or 0.02 Ámol), with no
evidence of accumulation, which is consistent with minimal absorption.
The volume of distribution cannot be determined because the drugs 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.
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 (1000 and 2500 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.
Faecal excretion of the unabsorbed drug 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, Ml and M3 are all
subject to biliary excretion.
Phormacokinetics in Special Populations
Plasma concentrations of orlistat and its metabolites Ml and M3 were similar
in paediatric patients compared to those found in adults at the same dose
level. Daily fecal fat excretions were 27% and 7% of dietary intake in
orlistat and placebo treatment groups, respectively.
Aslene is indicated in conjunction with a mildly hypocaloric diet for the
treatment of obese patients with a body mass index (BMI) greater or equal to
30 kg/m2, or overweight patients (BMI ≥ 28 kg/m2)
with risk factors associated with obesity.
Aslene is effective in weight loss, weight maintenance and prevention of
weight regains. Treatment with Aslene results in an improvement of risk
factors and comorbidities associated with obesity, including
hypercholesterolemia, noninsulin dependent diabetes mellitus (NIDDM),
impaired glucose tolerance, hyperinsulinemia, hypertension and in a
reduction of visceral fat.
The use of Aslene in type 2 diabetic patients who are overweight (BMI ≥
28 kg/m2) or obese (BMI ≥ 30 kg/m2), 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 Aslene 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 Aslene 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 therapy.
DOSAGE AND ADMINISTRATION
The recommended dose of Aslene 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 Aslene 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 120 mg three times daily have not been shown to provide
The effect of orlistat in patients with hepatic and/or renal impairment,
children under the age of 12, and elderly patents has not been studied.
Aslene is contraindicated in patients with chronic malabsorption syndrome,
cholestasis and in patients with known hypersensitivity to orlistat or any
component of this product.
WARNINGS AND PRECAUTIONS
In order to ensure adequate nutrition, the use of a multivitamin supplement
(Vitamin A, D, E and K, and beta-carotene) should be considered.
Patients should be advised to adhere to dietary guidelines (see Dosage and
A reduction in cyclosporin plasma levels has been observed when orlistat is
co-administered. Therefore it is recommended to monitor more frequently than
usual the cyclosporin plasma levels when orlistat is co-administered.
A potential reduced therapeutic effect of amiodarone is possible due to the
complex pharmacokinetics of amiodarone.
The possibility of experiencing gastrointestinal adverse reactions (see Side
Effects) may increase when orlistat is taken with a diet high in fat (e.g.
in a 2000 kcal/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
orlistat is taken with any one meal very high in fat, the possibility of
gastrointestinal effects may increase.
Weight loss induced by orlistat is accompanied by improved metabolic control
in type 2 diabetics which might allow or require reduction in the dose of
oral hypoglycemic medication (eg. sulfonylureas).
Substantial weight loss may increase the risk of cholelithiasis.
Coagulation parameters should be monitored in patients treated with
concomitant oral anticoagulants.
Cases of rectal bleeding have been reported with orlistat. Presenters should
investigate further in case of severe and/or persistent symptoms.