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EPIVAL CR 500MG PROLONGED-RELEASE TABLETS

Active substance(s): SODIUM VALPROATE

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prolonged-release tablets
Active substance: sodium valproate



This medicine is subject to additional
monitoring. This will allow quick identification of
new safety information. You can help by reporting
any side effects you may get. See the end of
section 4 for how to report side effects.
WARNING
Valproate can cause birth defects and
problems with early development of the child if
it is taken during pregnancy. If you are a female
of childbearing age you should use an effective
method of contraception throughout your
treatment.
Your doctor will discuss this with you but you
should also follow the advice in section 2 of
this leaflet. Tell your doctor at once if you
become pregnant or think you might be
pregnant.

####++#++#

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 symptoms are the same as
yours.
– If you get any of the side effects, talk to your
doctor or pharmacist. This includes any
possible side effects not listed in this leaflet.
See section 4.
In this leaflet:
1. What Epival CR is and what it is used for
2.
What you need to know before you take
Epival CR
3. How to take Epival CR
4. Possible side effects
5. How to store Epival CR
6. Contents of the pack and other information
1. What Epival CR is and what it is used
for
This medicine is an anticonvulsant (medication
against epilepsy/fits). It is also used for the
treatment of mania.
Sodium valproate, the active substance in Epival
CR, is effective against certain types of
convulsions.
From the prolonged-release tablets, sodium
valproate is released slowly into your body, thus
acting over many hours.
Epival CR is used in the treatment of
– various forms of epilepsy (fits)
– mania, where you may feel very excited,
elated, agitated, enthusiastic or hyperactive.
Mania occurs in an illness called “bipolar
disorder”. Epival CR can be used when lithium
cannot be used.
– Epival CR must not be used by women who
are trying to become pregnant or are pregnant
as it can cause serious birth defects and
developmental problems in the child, unless
explicitly advised and agreed with your doctor
to do so. All female patients who are capable
of becoming pregnant will need to consider
this risk and follow the advice provided in
section 2. Your doctor will discuss this with
you.
2. What you need to know before you
take Epival CR
Do not take Epival CR
– if you are allergic (hypersensitive) to sodium
valproate or any of the other ingredients (see
section 6.1 What Epival CR contains)
– if you have an active liver disease
– if close family-members have severe liver
function disturbances or if there is a history of
such disturbances in your family
– if you have a severe disturbance of the
pancreas function
– if you suffer from hepatic porphyria (a rare
metabolic disease)
– if you have a genetic problem caused by
a mitochondrial disorder (e.g. Alpers-Hutten­
locher syndrome).
Warnings and precautions
Talk to your doctor or pharmacist before taking
Epival CR.

####++#++#

Special precautions are necessary
– you suffer from “systemic lupus
if
erythematosus” (a rare allergic condition
which causes joint pain, skin rashes and
fever): You should consult your doctor before
you start taking Epival CR.
– if you need to go in for surgery: Inform the
treating physician before any type of surgery
that you are taking Epival CR, because sodium
valproate may prolong the bleeding time.
Blood tests may have to be done.
– if there is a possibility that you suffer from
“urea cycle enzymatic deficiency” (a rare
metabolic disorder): You may have to undergo
tests before starting treatment with Epival CR
– if you know that there is a genetic problem
caused by a mitochondrial disorder in your
family.
A small number of people being treated with
anti-epileptics such as sodium valproate have
had thoughts of harming or killing themselves. If
at any time you have these thoughts, immediately
contact your doctor
Children and adolescents under 18 years of
age:
Epival CR should not be used in children and
adolescents under 18 years of age for the
treatment of mania.
Other important things you should know
before taking Epival CR:
– Liver damage
In rare cases severe liver damage resulting in
death has been reported. Patients most at risk
are children under the age of three years who
suffer from severe seizure disorders,
particularly in association with mental
retardation and/or congenital metabolic
disorders. The frequency of such liver diseases
generally decreases significantly in patients
older than 10 years. Liver damage mostly
occurred during the first 6 months of therapy,
particularly between weeks 2 and 12 of
treatment and usually when other antiepileptic drugs were given at the same time.
Especially during the first 6 months of
treatment, patients at risk should therefore
have their liver function checked regularly, and
their treatment must be closely monitored.
Signs of severe liver damage may include:
increase in seizures, feeling unwell, weakness,
loss of appetite, vomiting, pain in the upper
abdomen, oedema (swelling of the fingers,
legs and toes), lethargy, drowsiness, jaundice
(yellowing of the skin or whites of the eyes). If
you notice any such symptoms, please
consult a doctor immediately.
Similar symptoms may also occur in
connection with a disease of the pancreas.
The risk of liver failure may increase if
salicylates (e.g. aspirin) are taken at the
same time. This risk is particularly high in
infants and toddlers. Children under 12 years
should not be given Epival CR in combination
with acetylsalicylic acid at all. In adolescents,
this combination should only be used after
careful evaluation of the benefits and risks by
their doctor, because it could increase the
bleeding tendency and enhance the effects of
Epival CR.
– Patients who suffered from bone marrow
damage in the past may need special
monitoring by their doctor during treatment.

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GI25420GB_Epival_Tab_Fla_zE.indd 1

Other medicines and Epival CR
Tell your doctor or pharmacist if you are taking,
have recently taken or might take any other
medicines.
Epival CR and other medicines may
influence each other in their effects:
– The effect of certain medicines for depression,
medicines used to calm emotional and mental
conditions (so-called neuroleptics, MAOinhibitors, benzodiazepines such as lorazepam
and diazepam) may be enhanced by
Epival CR.
– The combination with clonazepam (for the
treatment of epilepsy) may induce absence
seizures: your doctor will adjust the dose of
your medication and monitor your treatment
carefully.
– Other medicines used to treat fits/epilepsy
(e.g. phenobarbital, primidone, phenytoin,
carbamazepine, lamotrigine, felbamate) and
Epival CR may increase or reduce each other’s
effects.
– The effect of fluoxetine (an antidepressant)
may be enhanced by Epival CR, whereas the
effect of Epival CR may be reduced.
– Certain antibiotics (e.g. erythromycin) may
increase the effect of Epival CR, others (e.g.
meropenem, panipenem, imipenem) may
reduce its effect.
– Cimetidine (used to treat stomach ulcers) may
enhance the effect of Epival CR.
– Cholestyramine (used to treat high blood fat
levels) may decrease the effect of Epival CR.
– The effect of certain anticoagulants (used to
thin the blood, e.g. warfarin) may be increased
by Epival CR.
– The effect of acetylsalicylic acid (e.g. aspirin)
may be enhanced by Epival CR and vice
versa.

Medicines against malaria (mefloquine,
chloroquine) may reduce the effect of Epival
CR.
– The effect of zidovudine (used to treat HIVinfections) may be enhanced by Epival CR.

The effect of temozolomide (for tumour
treatment) may be increased by Epival CR.

# # ++#++#

Epival ® CR

300 mg
Epival ® CR

500 mg


– A possible weight gain during therapy was
reported. Consult your doctor in order to
discuss a suitable strategy against this risk.
– Urine tests to diagnose diabetes may be
false-positive because of Epival CR. Please
inform your doctor before such tests that you
are taking Epival CR.
– If you require a blood test to have your
thyroid function checked, please inform
your doctor about this, because treatment
with Epival CR may lead to a false diagnosis
of hypothyroidism (insufficient production of
thyroid hormone).
– Occasionally tablet parts may appear in
the stools as a visible white residue. However,
this does not reduce the effect of the medicine,
as the active substance is completely released
from the tablet system (matrix) while the drug
passes through the intestine.

In particular, tell your doctor or nurse if you
are taking any of the following medicines:
Carbapenem agents (antibiotic used to treat
bacterial infections). The combination of valproic
acid and carbapenems should be avoided
because it may decrease the effect of sodium
valproate.
The potential liver-damaging effect of Epival CR
may be increased if you ingest alcohol or use
other treatments that could have a negative
effect on the liver.
Epival CR does not appear to influence the effect
of oral contraceptives.
Taking Epival CR with food, drink and alcohol
You can take Epival CR with or after food. During
treatment with Epival CR you should not drink
alcoholic beverages, as sodium valproate may
potentiate the effects of alcohol.
Pregnancy and breast-feeding and fertility

Important advice for women
– Valproate can be harmful to unborn children
when taken by a woman during pregnancy.

Valproate carries a risk if taken during
pregnancy. The higher the dose, the higher
the risks but all doses carry a risk.
– It can cause serious birth defects and can
affect the way in which the child develops as
it grows. Birth defects which have been
reported include spina bifida (where the bones
of the spine are not properly developed); facial
and skull malformations; heart, kidney, urinary
tract and sexual organ malformations; limb
defects.
– If you take valproate during pregnancy you
have a higher risk than other women of having
a child with birth defects that require medical
treatment. Because valproate has been used
for many years we know that in women who
take valproate around 10 babies in every
100 will have birth defects. This compares to
2–3 babies in ever 100 born to women who
don’t have epilepsy.
– It is estimated that up to 30–40% of preschool
children whose mothers took valproate during
pregnancy may have problems with early
childhood development. Children affected can
be slow to walk and talk, intellectually less
able than other children, and have difficulty
with language and memory.
– Autistic spectrum disorders are more often
diagnosed in children exposed to valproate
and there is some evidence children may be
more likely to develop symptoms of Attention
Deficit Hyperactivity Disorder (ADHD).
– If you are a woman capable of becoming
pregnant your doctor should only prescribe
valproate for you if nothing else works for you.
– Before prescribing this medicine to you, your
doctor will have explained what might happen
to your baby if you become pregnant whilst
taking valproate. If you decide later you want
to have a child you should not stop taking
your medicine until you have discussed this
with your doctor and agreed a plan for
switching you onto another product if this is
possible.
– Ask your doctor about taking folic acid when
trying for a baby. Folic acid can lower the
general risk of spina bifida and early
miscarriage that exists with all pregnancies.
However, it is unlikely that it will reduce the risk
of birth defects associated with valproate use.

# # ++#++#

PACKAGE LEAFLET:
INFORMATION FOR THE USER

FIRST PRESCRIPTION
If this is the first time you have been prescribed
valproate your doctor will have explained the
risks to an unborn child if you become pregnant.
Once you are of childbearing age, you will need
to make sure you use an effective method of
contraception throughout your treatment. Talk to
your doctor or family planning clinic if you need
advice on contraception.
Key messages:
– Make sure you are using an effective method
of contraception.
– Tell your doctor at once if you are pregnant or
think you might be pregnant.
CONTINUING TREATMENT AND NOT
TRYING FOR A BABY
If you are continuing treatment with valproate but
you don’t plan to have a baby make sure you are
using an effective method of contraception. Talk
to your doctor or family planning clinic if you
need advice on contraception.
Key messages:
– Make sure you are using an effective method
of contraception
– Tell your doctor at once if you are pregnant or
think you might be pregnant.
CONTINUING TREATMENT AND
CONSIDERING TRYING FOR A BABY
If you are continuing treatment with valproate
and you are now thinking of trying for a baby you
must not stop taking either your valproate or
your contraceptive medicine until you have
discussed this with your prescriber. You should
talk to your doctor well before you become
pregnant so that you can put several actions in
place so that your pregnancy goes as smoothly
as possible and any risks to you and your
unborn child are reduced as much as possible.
Your doctor may decide to change the dose of
valproate or switch you to another medicine
before you start trying for a baby.
If you do become pregnant you will be monitored
very closely both for the management of your
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14.09.15 13:58

underlying condition and to check how your
unborn child is developing.
Ask your doctor about taking folic acid when
trying for a baby. Folic acid can lower the general
risk of spina bifida and early miscarriage that
exists with all pregnancies. However, it is unlikely
that it will reduce the risk of birth defects
associated with valproate use.
Key messages:
– Do not stop using your contraception before
you have talked to your doctor and worked
together on a plan to ensure your epilepsy/
bipolar disorder is controlled and the risks to
your baby are reduced.
– Tell your doctor at once when you know or
think you might be pregnant.
UNPLANNED PREGNANCY WHILST
CONTINUING TREATMENT
Babies born to mothers who have been on
valproate are at serious risk of birth defects and
problems with development which can be
seriously debilitating. If you are taking valproate
and you think you are pregnant or might be
pregnant contact your doctor at once. Do not
stop taking your medicine until your doctor tells
you to.
Ask your doctor about taking folic acid. Folic
acid can lower the general risk of spina bifida
and early miscarriage that exists with all
pregnancies. However, it is unlikely that it will
reduce the risk of birth defects associated with
valproate use.
Key messages:
– Tell your doctor at once if you know you are
pregnant or think you might be pregnant.
– Do not stop taking valproate unless your
doctor tells you to.
BREASTFEEDING
Very little Epival CR gets into the breast milk.
However, talk to your doctor about whether you
should breast-feed your baby.
Ask your doctor or pharmacist for advice before
taking any medicine.
Make sure you read the patient booklet and
sign the Acknowledgement of Risk form
which should be given to you and discussed
with you by your doctor or pharmacist.
Driving and using machines
Use of this drug may affect reactivity and the
patient's ability to drive, particularly if other
medicines against epilepsy/fits or medicines with
a calming effect are taken and in combination
with alcohol.
Successful seizure control over a period of
several months may enable patients to actively
participate in road traffic. Your treating physician
will inform you whether you may drive a vehicle.
3. How to take Epival CR
Always take Epival CR exactly as your doctor
has told you. Check with your doctor or
pharmacist if you are not sure.
DOSAGE AND DURATION OF TREATMENT
Dosage and duration of treatment are individually
adjusted by your doctor.
In general, treatment is started with a lower
dose, which is then gradually increased by your
doctor until your optimal dose is reached.
The daily dose may be taken either once daily or
in two divided doses.
If you have the feeling that the effect of Epival CR
is too weak or too strong, please consult your
doctor or pharmacist.
The duration of treatment and the dose may vary
from one person to another; they will therefore
be decided by your doctor depending on the
course of your illness.
Epilepsy:
Epival CR treatment must be started and
supervised by a doctor specialised in the
treatment of epilepsy or bipolar disorders.
In general, the treatment of epilepsy is a longterm treatment.
Monotherapy
Adults
The recommended dose is between 1000 and
2000 mg daily; if necessary, a higher daily dose
(up to 2500 mg per day) may be prescribed by
your doctor.
Use in children and adolescents
Children over 20 kg body weight:
The dose is based on the child’s weight. In
general, 20 to 30 mg sodium valproate per kg
body weight per day are administered (for
example in case of 30 kg body weight and an
average dose of 25 mg/kg: 2½ tablets of
300 mg per day).
If necessary, the doctor may prescribe daily
doses higher than 30 mg per kg body weight.
For children under 20 kg body weight, other
presentations of Epival CR (for example an oral
solution or a syrup) are available and may be
prescribed instead of tablets.
The following table serves as a general dosage
guideline for orientation:
Age

Body Weight Average Dose
approx.
150
3 – 6 months
5.5 – 7.5 kg
mg per day
approx.
150 – 300
6 – 12 months
7.5 – 10 kg
mg per day
approx.
300 – 450
1 – 3 years
10 – 15 kg
mg per day
approx.
450 – 600
3 – 6 years
15 – 20 kg
mg per day
approx.
600 – 1200
7 – 11 years
20 – 40 kg
mg per day
approx.
1000 – 1500
12 – 17 years
40 – 60 kg
mg per day
Adults
(including
approx. 60 kg 1200 – 2100
elderly
and higher
mg per day
patients)

have a negative effect on your treatment and
might induce more seizures. Please discuss any
signs of intolerance or changes in the course of
your illness with your treating physician.
If you have any further questions on the use of
this product, ask your doctor or pharmacist.
4. Possible side effects
Like all medicines, this medicine can cause side
effects, although not everybody gets them.
Please note that the following list includes all
reported side effects – even those that occur
very rarely.
Tell your doctor straight away, if you notice
any of the following serious side effects –
you may need urgent medical treatment:
– Allergic reaction: Signs may include rash,
swallowing or breathing problems, swelling of
your lips, face, throat or tongue. In a very
small number of patients, serious skin
reactions may occur and may sometimes
even be life-threatening and may include
blistering or bleeding of the skin around the
lips, nose, eyes and genitals, or skin lesions
affecting also the palms or the soles of your
feet. These skin reactions may be
accompanied by a feeling of being generally
unwell, flu-like symptoms, fever and aching
muscles.
– Increased amount of ammonia in the blood:
Signs may be vomiting, problems with balance
and coordination and feeling lethargic or less
alert.
– Deep loss of consciousness (coma) may
occur in very few patients.
– Liver problems and problems of the pancreas:
These may show as a sudden illness with
signs including feeling sick, being sick
repeatedly, being very tired and weak,
stomach pain, jaundice (yellowing of the skin
or whites of the eyes), loss of appetite, or a
general feeling of being unwell.
– Increased tendency to bleed, or if you seem to
get bruises or infections more easily. This
could be due to certain conditions affecting
the blood cells, e.g. a severe reduction in the
number of white blood cells (possibly causing
frequent infections, fever, severe chills, sore
throat or mouth ulcers), reduction in the
number of red blood cells or in the total
number of blood cells (which can make you
feel tired, short of breath or look pale), or
conditions
inhibiting
blood
clotting
(coagulation) thus leading to more frequent
bruises or to bleeding more or longer than
usual.
Tell your doctor as soon as possible, if you
have any of the following side effects:
– Changes in mood (depression), confusion
(occasionally
followed
by
disturbed
consciousness or associated with hallucina­
tions or convulsions (fits)), lethargy, feeling less
responsive than normal, twitching of the eyes,
or loss of brain function (usually temporary)
– Disturbance or lack of coordination affecting
balance and manner of walking, limb or eye
movements and / or speech; dizziness/
spinning sensation
– Drowsiness: this is often experienced when
other medication used to treat epilepsy is
given at the same time.
– Dementia and memory loss (usually reversible)
– Trembling, particularly at higher dosages
– Pins and needles (tingling or numbness of the
hands and feet)
– Parkinson-like symptoms (such as reduced
capacity of movement, trembling, increased
muscular tension), or involuntary movements
– Increased alertness, hyperactivity, aggression
and inappropriate behaviour
– Porphyria (a rare metabolic disease which
may be associated with red coloration of the
urine, abdominal spasms and pain as well as
vomiting).
Tell your doctor or pharmacist, if any of the
following side effects get serious or last
longer than a few days, or if you notice any
side effects not listed in this leaflet:
– Vasculitis (inflammation of the blood vessels),
which may present as pain, reddening or
itching
– Menstruation disorders, e.g. irregular periods
or missed periods, cysts on the ovaries,
breast enlargement in men, increased growth
of face or body hair, acne
– Oedema (swelling of the hands, ankles and
feet)
– Nystagmus (rapid, uncontrollable movements
of the eyes)
– Tinnitus (buzzing, hissing, whistling, ringing or
other persistent noise in the ears), hearing loss
– Headache
– Increased appetite leading to weight gain
– Lack of appetite, weight loss, constipation,
increased saliva
– Feeling sick, stomach ache or diarrhoea,
especially at the beginning of treatment; this
can usually be helped by taking the tablets
with or after food (see under 3:
“Administration”).
– Temporary hair loss has been noted in some
patients. Regrowth normally begins within six
months, although the hair may become curlier
than before.
– Kidney problems leading to sugar/glucose in
the urine and other abnormalities, bedwetting
in children, or increased need to pass urine
– Skin changes, e.g. rash.
Other side effects:
– Changes in liver function may occur at the
beginning of treatment – detected by a blood
test.
There have been reports of bone disorders
including osteopenia and osteoporosis (thinning
of the bone) and fractures. Check with your
doctor or pharmacist if you are on long-term
antiepileptic medication, have a history of
osteoporosis, or take steroids.

Patients with disturbed kidney and/or liver
function:
Your doctor may prescribe a lower dose.

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:

Combination therapy
If you are also taking other medicinal products to
treat your illness, your doctor will adjust the dose
accordingly.

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.

Mania:
The daily dosage should be established and
controlled individually by your doctor.
Initial dose
The recommended initial daily dose is 750 mg.

5. How to store Epival CR
Keep out of the sight and reach of children.
Tightly close the container after each use.

Average recommended maintenance daily dose
The recommended daily doses usually range
between 1000 mg and 2000 mg.

Do not use Epival CR after the expiry date which
is stated on the container. The expiry date refers
to the last day of that month.

Use in children and adolescents
Epival CR is not recommended for the use in
children and adolescents for the treatment of
mania.

Do not throw away 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.

ADMINISTRATION
Take the tablets whole with sufficient amounts of
fluid. If gastro-intestinal side-effects (e.g. nausea)
occur at the beginning of treatment, you should
take the tablets during or after meals.
The tablets may be divided into halves, but must
not be chewed or crushed.
If you take more Epival CR
Symptoms of an acute overdose may include
nausea, vomiting, dizziness, sometimes also
serious, or even fatal, side-effects affecting the
central nervous system and breathing. If you
take more tablets than you should or if a child
has taken the medicine by accident, consult
your doctor or go to the nearest accident and
emergency department immediately. Take this
leaflet and any remaining tablets with you so the
doctor will know what you have taken.
If you forget to take Epival CR
If you forgot to take a dose at the right time, take
it as soon as you remember. However, if you are
already nearing the time for your next scheduled
dose, you should skip the forgotten dose and
then continue treatment as prescribed. Do not
take a double dose to make up for a forgotten
dose.

6. Contents of the pack and other
information
What Epival CR contains
– The active substance is sodium valproate.
1 prolonged-release tablet contains 300 /
500 mg sodium valproate.
– The other ingredients are:
Tablet core: citric acid monohydrate, ethyl­
cellulose, ammonio methacrylate copolymer
(type B) (contains sorbic acid), purified talc,
colloidal hydrated silica, magnesium stearate.

Film-coating:
ammonio
methacrylate
copolymer (type A & B) (contains sorbic acid),
purified talc, carmellose sodium, titanium
dioxide (E 171), triethyl citrate, vanillin.
What Epival CR looks like and contents of
the pack
White, oval-shaped prolonged-release tablets,
with score line and engraving “CC3” / “CC5” on
one side. The tablets can be divided into equal
halves.
Epival CR is available in tablet container of 50 or
100 tablets.
Marketing Authorisation Holder
manufacturer
G.L. Pharma GmbH
Schlossplatz 1, A-8502 Lannach

This leaflet was last updated on 04.08.2015.

If you stop taking Epival CR
Do not interrupt or stop the treatment with Epival
CR without consulting your doctor. This could

Reg.no.: PL 21597/0005 (300 mg)

PL 21597/0006 (500 mg)

50.2012/1077/GB

P r ä pa r at e n a m e n /S tä r k e :

A r t .-N r .:

GI25420GB, Epival CR 300/500 mg Tab.

E p i va l CR 300/500

GI25420GB



and

Produktion:

mg



50.2012/1077/GB ♦
intern
♦ F o r m at : 140 x 600

C o d e -N r .:

GI25420GB_Epival_Tab_Fla_zE.indd 2

Darreichungsform:

Land:

mm

Tabletten ♦

A b pa c k u n g s a r t :

F l a sc h e

S c h r i f t : H e lv e t i c a 8,0 / 8,6 P u n k t
G r o ss b r i ta n n i e n / GB ♦ P a c k m i t t e l a r t : G e b r a u c h s i n f o .
♦ D at u m /V e r s i o n : 14. 9. 2015 – 6 ♦ F a r b e :
Schwarz



14.09.15 13:58

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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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