PURINETHOL 50 mg Coated Tablet

Зміст інструкції

1. PURINETHOL 50 mg tablets
   1. What is PURINETHOL and what is it used for
   2. What you need to know before taking PURINETHOL
   3. How to take PURINETHOL
   4. Possible side effects
   5. How to store PURINETHOL
   6. Contents of the pack and other information

PURINETHOL 50 mg tablets

mercaptopurine monohydrate

Read this leaflet carefully before you start to use this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

• 1. What PURINETHOL is and what it is used for
• 2. What you need to know before you take PURINETHOL
• 3. How to take PURINETHOL
• 4. Possible side effects
• 5. How to store PURINETHOL
• 6. Contents of the pack and other information

1. What is PURINETHOL and what is it used for

PURINETHOL contains the active substance mercaptopurine monohydrate. Mercaptopurine monohydrate
belongs to a group of medicines called chemotherapeutic agents (also called cytotoxic, meaning toxic
to cells).
PURINETHOL is used in the treatment of some types of blood cancers (acute lymphoblastic leukemia and acute promyelocytic leukemia/acute myeloid leukemia) in adults, adolescents and children.
These are diseases characterized by a rapid progression, which leads to an increase in the number of
new white blood cells. These new leukocytes are immature (not fully
formed) and unable to grow and function properly. They are therefore unable to fight
infections and can cause bleeding. Please consult your doctor if you would like more information on
this disease.

2. What you need to know before taking PURINETHOL

Do not take PURINETHOL

• If you are allergic to the active ingredient or to any of the other ingredients of this medicine (see section 6).
• Do not get vaccinated against yellow fever while taking PURINETHOL as it could be fatal.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using PURINETHOL if:
you have been vaccinated with a yellow fever vaccine or have recently had, or are planning
to have, a vaccination (vaccine).
You are taking PURINETHOL, you must avoid vaccines containing live organisms (e.g. the vaccine
against influenza, the vaccine for measles, the vaccine for tuberculosis, etc.) until your
doctor tells you it is safe to get vaccinated. This is because some vaccines can
cause an infection if they are given to you while you are taking PURINETHOL.
you have kidney or liver problems, as your doctor will need to check the function of these organs
you have a condition in which your body produces insufficient of the TPMT enzyme
(thiopurine methyltransferase), as your doctor may need to adjust the dose.
you are planning to have a child. This applies to both men and women. PURINETHOL
can damage sperm or eggs (see "Pregnancy, breastfeeding and fertility" below).
you have an allergy to a medicine called azathioprine (also used for the treatment of
cancer);
you have had or have not had chickenpox, shingles or hepatitis B (a liver disease
caused by a virus)
you have a genetic condition called Lesch-Nyhan syndrome.
If you are receiving immunosuppressive therapy, taking PURINETHOL may increase
the risk of developing:
tumors, including skin cancer. Therefore, if you are taking PURINETHOL you should avoid
excessive exposure to sunlight, wear protective clothing and use sunscreen with a high
protection factor.
lymphoproliferative disorders
or treatment with PURINETHOL increases the risk of developing a type of cancer
called a lymphoproliferative disorder. A treatment regimen based on
multiple immunosuppressants (including thiopurines) can lead to death.
or the simultaneous administration of a combination of multiple immunosuppressants
increases the risk of developing disorders of the lymphatic system caused by a viral
infection (Epstein-Barr virus (EBV)-associated lymphoproliferative disorders).
Taking PURINETHOL may increase the risk of:

• developing a serious condition called Macrophage Activation Syndrome (excessive activation of white blood cells associated with inflammation) which usually occurs in people with certain types of arthritis.
• Some patients with inflammatory bowel disease who have received mercaptopurine monohydrate have developed a rare and aggressive type of cancer called T-cell hepatosplenic lymphoma (see section 4, Possible side effects). The use of PURINETHOL for the treatment of inflammatory bowel disease (IBD) is an unauthorized indication.

Blood tests
Treatment with PURINETHOL affects the bone marrow. This means that a
reduction in the number of white blood cells, platelets and (less frequently) red blood cells may occur.
Your doctor will have blood tests done to check the levels of these cells
daily when you are at the beginning of therapy (induction), at least weekly when
therapy is advanced (maintenance). If the therapy is stopped promptly, your blood
cells will return to normal levels.

Liver function
PURINETHOL is toxic to the liver. Therefore, while taking PURINETHOL your doctor will
have tests done to check your liver function weekly. If you already have a
liver disease or if you are taking other medicines that can affect the liver, your doctor
will have these tests done more often. If you notice yellowing of the whites of your eyes or skin, tell
your doctor immediately as you may need to stop treatment immediately.

Vitamin B3 (pellagra) deficiency
Tell your doctor immediately if you experience diarrhea, pigmented skin rash
(dermatitis) or deterioration of memory, reasoning and thinking skills
(dementia) as these symptoms may indicate a vitamin B3 deficiency. Your doctor will prescribe
vitamin supplements (niacin/nicotinamide) to improve your condition.

Infections
During treatment with PURINETHOL the risk of viral, fungal and bacterial infections is
increased and infections may be more severe. See also section 4.
Before starting treatment, tell your doctor if you have had chickenpox, shingles or
hepatitis B (a liver disease caused by a virus). If you think you have an infection, tell
your doctor immediately.

Sun and ultraviolet (UV) rays
While taking PURINETHOL, the sensitivity of your skin to the sun and UV rays increases.
Therefore you must limit exposure to the sun and UV rays, wear covering clothes and use
sunscreen with a high protection factor.

NUDT15 gene mutation
If you have an inherited mutation of the NUDT15 gene (a gene involved in the transformation of
PURINETHOL in the body), you are at higher risk of infections and hair loss, and in
this case your doctor may give you a lower dose.

Children and adolescents
A low level of sugars in the blood has sometimes been observed in children (sweating more than usual, nausea,
dizziness, confusion, etc.), mainly in children under six years of age or with
low body mass index. Talk to your child's pediatrician if this happens.
If you are not sure if the above applies to you, ask your doctor or pharmacist before taking
PURINETHOL.

Other medicines and PURINETHOL
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
In particular, tell your doctor or pharmacist if you are taking any of the following
medicines:
ribavirin (used to treat viruses)
other cytotoxic medicines (chemotherapy – used to treat tumors)
allopurinol, thiopurinol, oxipurinol and febuxostat (used to treat gout)
olsalazine or mesalazine (used to treat Crohn's disease and an intestinal condition
called ulcerative colitis)
sulfasalazine (used to treat rheumatoid arthritis or ulcerative colitis)
methotrexate (used to treat cancer, rheumatoid arthritis or skin conditions
(severe psoriasis))
infliximab (used to treat certain intestinal diseases (Crohn's disease and
ulcerative colitis), rheumatoid arthritis, ankylosing spondylitis or skin conditions (severe psoriasis))
warfarin or acenocoumarol (used to thin the blood)
antiepileptic medicines such as phenytoin, carbamazepine. It may be necessary to
monitor blood levels of antiepileptic medicines and adjust doses accordingly.

Vaccination during treatment with PURINETHOL
You must tell your doctor or nurse before having a vaccination (vaccine). If you are
taking PURINETHOL, vaccination with live vaccines (such as those against polio, measles,
mumps and rubella) is not recommended without your doctor's advice, as these vaccines can
cause an infection if given while you are taking PURINETHOL.

PURINETHOL with food and drink
You can take PURINETHOL with or without food; however, you should maintain the same way of
taking it every day. You should take this medicine at least one hour before, or two hours after
ingesting milk or dairy products.

Pregnancy, breastfeeding and fertility
Do not take PURINETHOL if you are planning to have a child without first asking your
doctor. This applies to both men and women. PURINETHOL may damage sperm or
eggs. An effective method of contraception must be used to avoid pregnancy while one
of the partners is taking PURINETHOL. Men and women must continue to use effective
contraceptive methods for at least three months after stopping the last dose.
If you are already pregnant, you should consult your doctor before taking PURINETHOL. PURINETHOL
should not be handled by pregnant women, breastfeeding women or women planning a
pregnancy.
Do not breastfeed while taking PURINETHOL. Ask your doctor, pharmacist or midwife for advice.
If you are pregnant, suspect you are pregnant, or are planning to become pregnant, or if you are
breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Taking PURINETHOL during pregnancy can cause severe and excessive itching without
rash. Nausea and loss of appetite may also occur at the same time, which
may indicate a condition called intrahepatic cholestasis of pregnancy (a liver disease during
pregnancy). See your doctor immediately, as this condition can cause damage to the fetus.

Driving and using machines
PURINETHOL is not expected to affect the ability to drive and operate machines,
however, studies to confirm this have not been conducted.

PURINETHOL tablets contains lactose
If your doctor has diagnosed you with lactose intolerance, contact him before taking
this medicine.

3. How to take PURINETHOL

Take this medicine following always exactly the instructions of a specialist with
experience in the treatment of blood cancers.

• While taking PURINETHOL, your doctor will have you undergo regular blood tests to check the number and type of blood cells and to ensure that your liver is functioning correctly.
• The doctor may also ask you for blood and urine tests to monitor kidney function and measure uric acid levels. Uric acid is a natural substance produced by the body, the levels of which may increase while taking PURINETHOL. High levels of uric acid can damage the kidneys.
• Sometimes the doctor may modify the dose of PURINETHOL following the results of these tests.

Take this medicine following always exactly the instructions of the doctor or pharmacist.
If you have doubts, consult your doctor or pharmacist. It is important that you take the medicine at the right times.
The label on the package will tell you how many tablets to take and how often. If the label
does not contain this information or if you have any doubts, contact your doctor, nurse or pharmacist.
The recommended dose for adults and children is 2.5 mg per kilogram of your body weight per day
(or alternatively 50 to 75 mg per m of body surface area per day).
The dose of PURINETHOL that is prescribed to you is calculated and adjusted by your doctor based on weight,
test results, taking other chemotherapeutic drugs and kidney and
liver function.

Swallow the tablet whole. The tablets must not be broken or crushed. People who
come into contact with broken tablets should wash their hands immediately.
PURINETHOL with food and drinks
You can take PURINETHOL with or without food; however, you must maintain the same
method of taking it every day. You should take this medicine at least one hour before, or two
hours after ingesting milk or dairy products.
It is important to take PURINETHOL in the evening hours to enhance its effectiveness

If you take more PURINETHOL than you should
If you take more PURINETHOL than you should, you may feel unwell, vomit or have diarrhea. Report this immediately to your doctor or go directly to the hospital.

If you forget to take PURINETHOL
Report this to your doctor. Do not take a double dose to make up for the forgotten
tablet.

If you stop taking PURINETHOL
Do not stop taking the medicine unless your doctor tells you to, because
you may have a relapse of your condition.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you notice any of the following side effects, tell your specialist doctor or go to hospital immediately:
Allergic reaction, the signs of which may include:
o skin rashes
o high fever
o joint pain
o facial swelling
o skin nodules (erythema nodosum) (frequency is unknown).
Any sign of fever or infection (sore/inflamed throat or urinary problems)
Any unexpected bruising or bleeding, as this could mean there is insufficient production of a particular type of blood cells
Any sudden feeling of unwellness (even with a normal temperature) accompanied by abdominal pain and nausea/vomiting, as this could be a sign of inflammation of the pancreas.

• Any yellowing of the whites of the eyes or skin (jaundice).

Contact your doctor if you experience any of the following side effects, listed in order of frequency, which may also occur with this medicine:

Very common (affects more than 1 in 10 people)
Decrease in the number of white blood cells and platelets (can be revealed by blood tests)

Common (affects less than 1 in 10 people)
nausea or vomiting
liver damage (which can be revealed by blood tests)
decrease in red blood cells, which can cause fatigue, weakness or shortness of breath (called anemia)
loss of appetite
inflammation of the pancreas (pancreatitis) in patients with inflammatory bowel disease

Uncommon (affects less than 1 in 100 people)
inflammation of the pancreas (pancreatitis)
joint pain
skin rashes
fever
permanent liver damage (necrosis)
bacterial and viral infections, infections associated with neutropenia

Rare (affects less than 1 in 1,000 people)
hair loss
mouth ulcers
in men: temporary decrease in the number of sperm
facial swelling caused by allergic reaction
various types of cancer including blood cancers, lymphomas and skin cancers
inflammation of the pancreas (pancreatitis) in patients with leukemia (a blood cancer)

Very rare (affects less than 1 in 10,000 people)
a type of leukemia different from the one being treated
intestinal ulcers; symptoms may include abdominal pain and bleeding

Not known (frequency cannot be estimated from the available data)
a rare type of cancer (T-cell hepatosplenic lymphoma) in patients with a condition called
Inflammatory Bowel Disease) (see section 2, Warnings and precautions)
increased sensitivity to sunlight and UV rays causing skin reactions
decrease in blood sugar levels
burning or tingling sensation in the mouth or lips (inflammation of the mucous membrane, stomatitis)
chapped or swollen lips (cheilitis)
vitamin B3 deficiency (pellagra) associated with localized pigmented rash, diarrhea or decreased memory, reasoning or other cognitive abilities
decreased clotting factors.

Additional side effects in children
Low blood sugar levels (excessive sweating, nausea, dizziness, confusion, etc.) have been reported in some children receiving PURINETHOL, the frequency of which is not known.
However, most children were under six years of age and had a low body weight.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store PURINETHOL

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 of the bottle and on the
box after Expiry. This is printed with month, and year and refers to the last day of that month.
Do not store at a temperature above 25°C. Store in the original bottle and in the box to
protect the medicine from light and moisture. Keep the bottle tightly closed to protect the
medicine from moisture.
If your doctor tells you to stop taking the tablets, it is important to return the
remaining tablets to the pharmacist who will destroy them according to the guidelines for the disposal of
hazardous substances. Keep the tablets only if your doctor tells you to do so.

6. Contents of the pack and other information

What PURINETHOL contains

• The active ingredient is mercaptopurine monohydrate. Each tablet contains 50 mg of mercaptopurine monohydrate.
• The other ingredients are: lactose monohydrate, corn starch, modified corn starch, stearic acid, magnesium stearate.

Description of the appearance of PURINETHOL and contents of the pack
Pale yellow, biconvex, round tablets with a score line on one side. The tablets are
engraved with PT and 50 above and below the score line and are smooth on the other side.
PURINETHOL is available in bottles containing 25 tablets.

Marketing Authorisation Holder
Aspen Pharma Trading Limited
3016 Lake Drive,
Citywest Business Campus,
Dublin 24, Ireland
Tel: +39 0687 502 429

Manufacturer
Excella GmbH & Co. KG, Nürnberger Strasse 12, 90537 Feucht, Germany
Aspen Bad Oldesloe GmbH, Industriestrasse 32-36, 23843 Bad Oldesloe, Germany