Skip to Content

ORLISTAT 60 MG HARD CAPSULES

Active substance(s): ORLISTAT / ORLISTAT

View full screen / Print PDF » Download PDF ⇩
Transcript
SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Orlos 60mg hard capsules
Orlistat 60mg hard capsules

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each hard capsule contains 60 mg orlistat.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Hard capsule
The capsule has a brightly blue body.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Orlistat is indicated for weight loss in adults who are overweight (body mass index,
BMI, ≥28 kg/m2) and should be taken in conjunction with a mildly hypocaloric,
lower-fat diet.

4.2

Posology and method of administration
Adults
The recommended dose of Orlistat 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 Orlistat.
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
Orlistat is stopped.
Treatment should not exceed 6 months.
If patients have been unable to lose weight after 12 weeks of treatment with Orlistat,
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.
Hepatic and renal impairment
The effect of orlistat in individuals with hepatic and/or renal impairment has not been
studied (see section 4.4). 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 Orlistat 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.

4.3

Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section
6.1.
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).

4.4

Special warnings and precautions for use
Gastrointestinal symptoms
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.
Fat-soluble vitamins
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.
Antidiabetic medicinal products
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 Orlistat, in case it is necessary to adjust the dose of the
antidiabetic medicinal product.
Medicinal products for hypertension or hypercholesterolaemia
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 Orlistat ,
in case it is necessary to adjust the dose of these medicinal products.
Amiodarone
Patients who are taking amiodarone should consult a doctor before starting treatment
with Orlistat (see section 4.5).
Rectal bleeding
Cases of rectal bleeding have been reported in patients taking orlistat. If this occurs,
the patient should consult a doctor.
Oral contraceptives
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).
Kidney disease
Patients with kidney disease should consult a doctor before starting treatment with
Orlistat, as the use of orlistat may rarely be associated with hyperoxaluria and oxalate
nephropathy (see section 4.8).
Levothyroxine
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
Orlistat, as orlistat and levothyroxine may need to be taken at different times and the
dose of levothyroxine may need to be adjusted.

Antiepileptic medicinal products

Patients taking an antiepileptic medicinal product should consult a doctor before
starting treatment with Orlistat, 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).
Antiretrovirals for HIV
Patients should consult a physician before taking Orlistat concomitantly with
antiretroviral medications. Orlistat may potentially reduce the absorption of
antiretroviral medicines for HIV and could negatively affect the efficacy of
antiretroviral medications for HIV (see section 4.5).

4.5

Interaction with other medicinal products and other forms of interaction
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 Orlistat 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 Orlistat 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.
Antiretroviral medications
Based on reports from literature and post-marketing experience orlistat may
potentially reduce the absorption of antiretroviral medicines for HIV and could
negatively affect the efficacy of antiretroviral medications for HIV (see section 4.4).

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, Orlistat 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 Orlistat. The dose of amiodarone may need to be
adjusted during treatment with Orlistat.
Antidepressants and Antipsychotic medicinal products
There are some case reports of reduced efficacy of antidepressants and antipsychotics
coincidental to the initiation of orlistat treatment in previously well-controlled
patients. Therefore orlistat treatment should only be initiated after careful
consideration of the possible impact in these patients.

4.6

Fertility, pregnancy and lactation
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).
Orlistat is contraindicated in pregnancy (see section 4.3).

Breast-feeding
As it is not known whether orlistat is secreted into human milk, Orlistat is
contraindicated during breast-feeding (see section 4.3).
Fertility
Animal studies do not indicate harmful effects with respect to fertility.

4.7

Effects on ability to drive and use machines
Orlistat has no or negligible influence on the ability to drive and use machines.

4.8

Undesirable effects
Summary of the safety profile
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).
Tabulated list of adverse reactions
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), and
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
Adverse reaction
frequency
Blood and lymphatic system disorders

Decreased prothrombin and increased

Not known:

INR (see sections 4.3 and 4.5).

Not known:

Hypersensitivity reactions including
anaphylaxis, bronchospasm,
angioedema, pruritus, rash, and urticaria.

Immune system disorders

Psychiatricdisorders
Common:

Anxiety†

Gastrointestinal disorders
Oily spotting

Very
common:

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 that may be serious
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.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via the national reporting system listed in https://yellowcard.mhra.gov.uk

4.9

Overdose
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

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmaco-therapeutic group: antiobesity preparations, excl.
peripherally acting antiobesity products, ATC code A08AB01.

diet

products;

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/m2 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

Study 1

Placebo
Orlistat 60 mg
Study 2
Placebo
Orlistat 60 mg
Pooled data
Placebo
Orlistat 60 mg
* p<0.001 versus placebo

N

Relative
mean change
(%)

Mean change
(kg)

204
216
183
191
387
407

-3.24
-5.55
-1.17
-3.66
-2.20
-4.60

-3.11
-5.20*
-1.05
-3.59*
-2.09
-4.40*

Table 2: Responder analysis at 6 months
Lost ≥5% of baseline body
weight
(%)
Placebo
Orlistat 60mg
Study 1
30.9
54.6 a
Study 2
21.3
37.7a
Pooled data
26.4
46.7 a
Comparison versus placebo: a p<0.001; b p<0.01

Lost ≥10% of baseline body
weight
(%)
Placebo
Orlistat 60mg
10.3
21.3b
2.2
10.5 b
6.5
16.2 a

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 nonmeasurable (<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.
The medicinal use of orlistat is unlikely to represent a risk to the aquatic or terrestrial
environment. However, any possible risk should be avoided (see section 6.6).

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Capsule filling:
Microcrystalline cellulose (E460)
Sodium starch glycolate (type A)
Sillica, colloidal anhydrous
Sodium lauryl sulphate
Capsule shell:
Gelatine
Indigo carmine (E132)
Titanium dioxide (E171)

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
24 months

6.4

Special precautions for storage
Do not store above 25°C. Store in original package in order to protect from light and
moisture.

6.5

Nature and contents of container
Al/PVC/PVDC blisters with PVC\PVDC heat seal foil containing 42, 60, 84 and 90
hard capsules.
HDPE bottles with Polyethylene caps and desiccant containing 42, 60, 84, 90 and 120
capsules.
Not all pack types and sizes may be marketed.

6.6

Special precautions for disposal
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.

7

MARKETING AUTHORISATION HOLDER
Crescent Pharma Limited, Units 3 & 4,
Quidhampton Business Units,
Polhampton Lane, Overton,
Hants, RG25 3ED

8

MARKETING AUTHORISATION NUMBER(S)
PL 20416/0269

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
13/07/2016

10

DATE OF REVISION OF THE TEXT
03/02/2017

Expand view ⇕

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

Hide