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BOSENTAN MILPHARM 62.5 MG FILM-COATED TABLET

Active substance(s): BOSENTAN MONOHYDRATE / BOSENTAN MONOHYDRATE / BOSENTAN MONOHYDRATE

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arrange for regular blood tests to check for changes in
your liver function and haemoglobin level.

Package leaflet: Information for the user

Bosentan 62.5 mg film-coated
tablets
Bosentan 125 mg film-coated
tablets
bosentan
Read all of this leaflet carefully before you start
taking this medicine because it contains important
information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor
or pharmacist.
- This medicine has been prescribed for you only. Do
not pass it on to others. It may harm them, even if
their signs of illness are the same as yours.
- If you get any side effects, talk to your doctor or
pharmacist. This includes any possible side effects
not listed in this leaflet. See section 4.
What is in this leaflet
1. What Bosentan is and what it is used for
2. What you need to know before you take Bosentan
3. How to take Bosentan
4. Possible side effects
5. How to store Bosentan
6. Contents of the the pack and other information
1. What Bosentan is and what it is used for
Bosentan tablets contain bosentan, which blocks a
naturally occurring hormone called endothelin-1 (ET1), which causes blood vessels to narrow. Bosentan
therefore causes blood vessels to expand and belongs
to the class of medicines called “endothelin receptor
antagonists”.
Bosentan is used to treat:
• Pulmonary arterial hypertension (PAH): PAH is
a disease of severe narrowing of the blood vessels
in the lungs resulting in high blood pressure in the
blood vessels (the pulmonary arteries) that carry
blood from the heart to the lungs. This pressure
reduces the amount of oxygen that can get into the
blood in the lungs, making physical activity more
difficult. Bosentan widens the pulmonary arteries,
making it easier for the heart to pump blood through
them. This lowers the blood pressure and relieves
the symptoms.
Bosentan is used to treat patients with class III
pulmonary arterial hypertension (PAH) to improve
exercise capacity (the ability to carry out physical
activity) and symptoms. The ‘class’ reflects the
seriousness of the disease: ‘class III’ involves marked
limitation of physical activity. Some improvements have
also been shown in patients with class II PAH. ‘Class
II’ involves slight limitation of physical activity. The PAH
for which Bosentan is indicated can be:






primary (with no identified cause or familial);
caused by scleroderma (also called systemic
sclerosis, a disease where there is abnormal growth
of the connective tissue that supports the skin and
other organs);
caused by congenital (inborn) heart defects with
shunts (abnormal passageways) causing abnormal
flow of blood through the heart and lungs.
Digital ulcers: (sores on the fingers and toes) in
adult patients with a condition called scleroderma.
Bosentan reduces the number of new finger and
toe ulcers that appear.

2. What you need to know before you take
Bosentan
Do not take Bosentan:
• if you are allergic to bosentan or any of the other
ingredients of this medicine (listed in section 6)
• if you have liver problems (ask your doctor)
• if you are pregnant, or could get pregnant
because you are not using reliable contraceptive
methods. Please read the information under
“Contraceptives” and “Other medicines and
Bosentan”
• if you are taking cyclosporine A (a medicine used
after a transplant or to treat psoriasis)
If any of these apply to you, tell your doctor.
Warnings and precautions
Talk to your doctor or pharmacist before taking
Bosentan.
Tests your doctor will do before treatment
• a blood test to check your liver function
• a blood test to check for anaemia (low
haemoglobin)
• a pregnancy test if you are a woman of childbearing potential

For all these tests please refer also to the Patient
Alert Card (inside your pack of Bosentan tablets). It is
important that you have these regular blood tests as
long as you are taking Bosentan. We suggest you write
the date of your most recent test and also of your next
test (ask your doctor for the date) on the Patient Alert
Card, to help you remember when your next test is
due.
Blood tests for liver function
These will be done every month for the duration of
treatment with Bosentan. After an increase in dose an
additional test will be done after 2 weeks.
Blood tests for anaemia
These will be done every month for the first 4 months
of treatment, then every 3 months after that, as patients
taking Bosentan may get anaemia.
If these results are abnormal, your doctor may decide
to reduce your dose or stop treatment with Bosentan
and to perform further tests to investigate the cause.
Children and adolescents
Bosentan is not recommended in paediatric patients
with systemic sclerosis and ongoing digital ulcer
disease. Please see also section 3. How to take
Bosentan.
Other medicines and Bosentan
Tell your doctor or pharmacist if you are taking, have
recently taken or might take any other medicines. It is
especially important to tell your doctor if you are taking:
• cyclosporine A (a medicine used after transplants
and to treat psoriasis), which must not be used
together with Bosentan
• sirolimus or tacrolimus, which are medicines used
after transplants, as these are not recommended to
be used together with Bosentan
• glibenclamide (a diabetes medicine), rifampicin
(a tuberculosis medicine) or fluconazole (a
medicine against fungal infections), nevirapine
(an HIV medicine) as these medicines are not
recommended to be used together with Bosentan
• other medicines for the treatment of HIV infection,
which may require special monitoring if used
together with Bosentan
• hormonal contraceptives, which are not effective
as the sole method of contraception when you take
Bosentan. Inside your pack of Bosentan tablets
you will find a Patient Alert Card which you should
read carefully. Your doctor and/or gynaecologist will
establish the contraception which is appropriate for
you.
Bosentan with food, drink and alcohol
Bosentan can be taken with or without food.
Pregnancy, breast-feeding and fertility
If you are pregnant or breast-feeding, think you may
be pregnant or are planning to have a baby, ask your
doctor or pharmacist for advice before taking this
medicine.
Women of child-bearing age
Do NOT take Bosentan if you are pregnant or planning
to become pregnant.
Pregnancy tests
Bosentan may harm unborn babies conceived before
starting or during treatment. If you are a woman who
could become pregnant, your doctor will ask you to
take a pregnancy test before you start taking Bosentan,
and regularly while you are taking Bosentan.
Contraceptives
If it is possible that you could become pregnant, use
a reliable form of birth control (contraception) while
you are taking Bosentan. Your doctor or gynaecologist
will advise you about reliable contraceptive methods
while taking Bosentan. Because Bosentan may make
hormonal contraception (e.g., oral, injection, implant, or
skin patches) ineffective, this method on its own is not
reliable. Therefore, if you use hormonal contraceptives
you must also use a barrier method (e.g., female
condom, diaphragm, contraceptive sponge, or your
partner must also use a condom). Inside your pack of
Bosentan tablets you will find a Patient Alert Card. You
should complete this card and take it to your doctor
at your next visit so that your doctor or gynaecologist
can assess whether you need additional or alternative
reliable contraceptive methods. Monthly pregnancy
tests are recommended while you are taking Bosentan
and are of child-bearing age.
Breast-feeding
Tell your doctor immediately if you are breast-feeding.
You are advised to stop breast-feeding if Bosentan is
prescribed for you, because it is not known whether
this medicine passes into breast milk.
Fertility
If you are a man taking Bosentan, it is possible that
this medicine may lower your sperm count. It cannot
be excluded that this may affect your ability to father a
child. Talk to your doctor if you have any questions or
concerns about this.
Driving and using machines
Bosentan has no or negligible influence on the ability to
drive and use machines.

Tests your doctor will do during treatment

However, Bosentan can induce hypotension
(decrease of your blood pressure) which can make

During treatment with Bosentan, your doctor will

Black

P15xxxxx

Some patients taking Bosentan have been found to
have abnormal liver function tests and anaemia (low
haemoglobin).

Therefore, if you feel dizzy or that your vision
is blurred while taking Bosentan, do not drive
or operate any tools or machines.
3. How to take Bosentan
Treatment with Bosentan should only be
started and monitored by a doctor who
has experience in the treatment of PAH or
systemic sclerosis. Always take this medicine
exactly as your doctor has told you. Check
with your doctor or pharmacist if you are not
sure.
Bosentan with food and drink
Bosentan can be taken with or without food.
Recommended dose
Adult
The treatment in adults is usually started for the first 4
weeks with 62.5 mg twice daily (morning and evening),
from then your doctor will usually advise you to take a
125 mg tablet twice daily, depending on how you react
to Bosentan.
Children and adolescents
The dose recommendation in children is only for PAH.
For children 1 year and older, treatment with Bosentan
is usually started with 2 mg per kg bodyweight twice
daily (morning and evening). Your doctor will advise
you on your dosing.
Please note that other formulations of bosentan are
also available which may make correct dosing easier
for children and patients with low body weight or
difficulties to swallow film-coated tablets.
If you have the impression that the effect of Bosentan
is too strong or too weak, talk to your doctor in order to
find out whether your
dose needs to be changed.
How to take Bosentan
Tablets should be taken (morning and evening),
swallowed with water. The tablets can be taken with or
without food
If you take more Bosentan than you should
If you take more tablets than you have been told to
take, contact your doctor immediately.
If you forget to take Bosentan
If you forget to take Bosentan, take a dose as soon as
you remember, then continue to take your tablets at the
usual times. Do not take a double dose to make up for
forgotten tablets.

Uncommon (may affect up to one in 100 people):
• Thrombocytopenia (low number of blood platelets)
• Neutropenia/leukopenia (low number of white blood
cells)
• Elevated liver function tests with hepatitis
(inflammation of the liver) including possible
exacerbation of underlying hepatitis and/or jaundice
(yellowing of the skin or the whites of the eyes)
Rare (may affect up to one in 1000 people):
• Anaphylaxis (general allergic reaction), angioedema
(swelling, most commonly around the eyes, lips,
tongue or throat)
• Cirrhosis (scarring) of the liver, liver failure (serious
disturbance of liver function)
Blurred vision have also been reported at an unknown
frequency (frequency cannot be estimated from the
available data).
Side effects in children and adolescents
The side effects that have been reported in children
treated with bosentan are the same as those in adults.
Reporting of side effects
If you get any side effects, talk to your doctor or
pharmacist. This includes any possible side effects
not listed in this leaflet. You can also report side
effects directly via the national reporting system listed
in Yellow Card Scheme Website: www.mhra.gov.uk/
yellowcard. By reporting side effects you can help
provide more information on the safety of this medicine.
5. How to store Bosentan
Keep this medicine out of the sight and reach of
children.
Do not use this medicine after the expiry date which is
stated on the label, carton after EXP. The expiry date
refers to the last day of that month.
This medicinal product does not require any special
storage conditions.
Do not throw away any medicines via wastewater or
household waste. Ask your pharmacist how to throw
away medicines you no longer use. These measures
will help protect the environment.
6. Contents of the pack and other information
What Bosentan contains
- The active substance is bosentan as monohydrate.
Each film-coated tablet contains 62.5 mg bosentan
(as monohydrate).
Each film-coated tablet contains 125 mg bosentan
(as monohydrate).
-

If you stop taking Bosentan
Suddenly stopping your treatment with Bosentan may
lead to your symptoms getting worse. Do not stop
taking Bosentan unless your doctor tells you to. Your
doctor may tell you to reduce the dose over a few days
before stopping completely.
If you have any further questions on the use of this
medicine, ask your doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can cause side
effects, although not everybody gets them.
The most serious side effects with bosentan are
• Abnormal liver function which may affect more than
1 in 10 people
• Anaemia (low blood value) which may affect up to
1 in 10 people. Anaemia may occasionally require
blood transfusion.
Your liver and blood values will be monitored during
treatment with bosentan (see section 2). It is important
that you have these tests as ordered by your doctor.
Signs that your liver may not be working properly
include:
• nausea (urge to vomit)
• vomiting
• fever (high temperature)
• pain in your stomach (abdomen)
• jaundice (yellowing of your skin or the whites of
your eyes)
• dark-coloured urine
• itching of your skin
• lethargy or fatigue (unusual tiredness or exhaustion)
• flu-like syndrome (joint and muscle pain with fever)
If you notice any of these signs tell your doctor
immediately
Other side effects:
Very common (may affect more than one in 10
people):
• Headache
• Oedema (swelling of the legs and ankles or other
signs of fluid retention)
Common (may affect up to one in 10 people):
• Flushed appearance or redness of skin
• Hypersensitivity reactions (including skin
inflammation, itching and rash)
• Gastrooesophageal reflux disease (acid reflux)
• Diarrhoea
• Syncope (fainting)
• Palpitations (fast or irregular heart beats)
• Low blood pressure
• Nasal congestion

The other ingredients are:
Tablet core: Pregelatinised starch, maize starch,
sodium starch glycolate (type-A), crospovidone
(type-B), povidone (K-90) glycerol dibehenate and
magnesium stearate.
Film coating: Hypromellose (E464), ethyl cellulose,
triacetin, talc, titanium dioxide (E171), iron oxide
yellow, iron oxide red.

What Bosentan looks like and contents of the pack
Film- coated tablet.
Bosentan 62.5 mg film-coated tablets
Orange-white coloured, round [Diameter: 6.1mm],
biconvex, film-coated tablets debossed with ‘K’ on one
side and ‘21’ on other side.
Bosentan 125 mg film-coated tablets
Orange-white coloured, oval, biconvex, film-coated
tablets debossed with ‘K’ on one side and ‘22’ on other
side, separated by breakline. The tablet can be divided
into equal doses. The size is: 11.2 mm x 5.2 mm
Bosentan film-coated tablets are available in triple
laminated white opaque PVC/PE/PVdC–Aluminium
foil blister pack and HDPE bottle with polypropylene
closures.
Blister pack:
For 62.5 mg: 14, 28, 30, 50, 56, 60, 90, 98 and 112
film-coated tablets.
For 125 mg: 10, 14, 28, 30, 50, 56, 60, 90, 98, 100 and
112 film-coated tablets.
Bottle pack:
30,100 and 1000 film-coated tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Milpharm Limited
Ares Block, Odyssey Business Park
West End Road
Ruislip HA4 6QD
United Kingdom
Manufacturer
APL Swift Services (Malta) Limited
Hf26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta
or
Milpharm Limited
Ares Block, Odyssey Business Park
West End Road
Ruislip HA4 6QD
United Kingdom
This leaflet was last revised in 07/2016.

P15xxxxx

you feel dizzy, affect your vision and affect
your ability to drive and use machines.

((Front cover))

((Inside 1))

Important Safety Alerts for Patients taking Bosentan

This card contains important information about Bosentan. Please read
this card carefully before starting your treatment with Bosentan.

Your name:

Prescribing doctor:
If you have questions about Bosentan ask your doctor.

Milpharm Limited
Contraception

Blood Test for Liver Function
Some patients taking Bosentan were found to have abnormal liver
function tests. During treatment with Bosentan, your doctor will
arrange for regular blood tests to check for changes in your liver
function.

Do you currently use or take contraceptives?

Remember to have your liver blood test every month.
After an increase in dose, an additional test will be done after
2 weeks.

No

Yes

If you are a woman of child bearing age read this page
carefully
Pregnancy: Bosentan may harm the development of the foetus.
Therefore, you must not take Bosentan if you are pregnant and you
must also not become pregnant while taking Bosentan.
Moreover, if you are suffering from pulmonary hypertension disease,
the occurrence of a pregnancy can severely deteriorate the symptoms
of your disease. If you suspect you may be pregnant, tell your doctor
or gynaecologist.
Contraception: Birth control based on hormones – such as oral
contraceptives or birth control pills, hormone injections, implants, or
birth control skin patches don’t reliably prevent pregnancy in women
who are taking Bosentan. You need to use a barrier form of birth
control – like a condom, diaphragm or vaginal sponge – in addition to
any of these kinds of hormonal birth control. Be sure to discuss
anyquestions you may have with your doctor or your gynaecologist –
complete the details on the back of this card and take it to your doctor
or gynaecologist at your next visit.
You should have a pregnancy test before initiation of Bosentan
and every month during the treatment even if you think that you
are not pregnant.
Date of first monthly test:

Date of first monthly test:

((Back cover))

P14XXXXX

Take this card to your doctor or your gynaecologist at your next visit
and he/she will be able to advise you on whether you need to use
additional or alternative contraceptive methods.

Jan

May

Sep

Feb

Jun

Okt

Mar

Jul

Nov

Apr

Aug

Dec

((Inside 2))

P14XXXXX

Your monthly liver blood test schedule:

If Yes, write the names of these here:

Expand Transcript

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.

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