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Active substance(s): IOBENGUANE(131-I) CHLORIDE

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Read all of this leaflet carefully
before you are given MIBG
PackaGe LeaFLeT:
InFoRMaTIon FoR The UseR

(131I) for Therapeutic Use
Meta-lodobenzylguanidine (131I)
for Therapeutic Use
185-740 MBq/ml solution for
infusion or solution for injection
Meta-lodobenzylguanidine (131I) for
Therapeutic Use 185-740 MBq/ml
solution for infusion or solution for
injection is referred to as MIBG
Therapeutic in this leaflet.

– Keep this leaflet. You may need to
read it again.
– If you have any further questions,
ask your doctor.
– If any of the side effects gets
serious, or if you notice any side
effects not listed in this leaflet,
please tell your doctor or nurse.
In this leaflet:
1. What MIBG Therapeutic is and
what it is used for
2. Before you are given MIBG
3. How MIBG Therapeutic is given
4. Possible side effects
5. How to store MIBG Therapeutic
6. Further information


1. What MIBG Therapeutic is and
1. what it is used for
MIBG Therapeutic is a ‘radiopharmaceutical’ medicine.
• It contains an active ingredient
called ‘iobenguane’.
• It can be used to treat tumours
of the adrenal or thyroid glands.
Your doctor will tell you anything
else you need to know about how
MIBG Therapeutic works.
2. Before you are given MIBG
You should not be given MIBG
• If you are allergic
(hypersensitive) to the active
ingredient or any other
ingredient. (Listed in Section 6).

• If you are pregnant or think you
might be pregnant.
Do not have MIBG Therapeutic if
any of the above apply to you. If
you are not sure talk to your doctor
or nurse.
Premature babies or newborn
babies (neonates) must not be given
MIBG Therapeutic. (See “Important
information about some of the
ingredients of MIBG Therapeutic”).
Take special care with MIBG
Check with your doctor or nurse
before having MIBG Therapeutic:
• If you have missed your last
• If you are on a low sodium diet.


Taking other medicines
Please tell your doctor or nurse if
you are taking or have recently
taken any other medicines,
including medicines obtained
without a prescription. This includes
herbal medicines. This is because
some medicines can affect the way
MIBG Therapeutic works.
Before you are given MIBG
Therapeutic tell your doctor or
nurse if you are taking any of the
types of medicine below.
• Antihypertensive drugs (used to
treat high blood pressure) such as
reserpine, labetalol or calciumchannel blockers (which include
diltiazem, nifedipine, verapamil,
betanidine, debrisoquine,
bretylium and guanethidine).

• Antidepressants such as
amitriptyline, imipramine,
doxepin, amoxepine, loxapine,
maprotiline or trazolone.
• ‘Sympathomimetic agents’ (used
as decongestants in cough or
cold remedies) such as
phenylephrine, ephedrine or
• Cocaine.
If you are not sure if any of the
above apply to you, talk to your
doctor or nurse before having MIBG


Pregnancy and breast-feeding
You should not be given MIBG
Therapeutic if you are pregnant or
think that you may be pregnant.
This is because it may affect the
Do not breast-feed if you are given
MIBG Therapeutic. This is because
small amounts of ‘radio-activity’
may pass into the mother’s milk.
Your doctor may wait until you
have finished breast-feeding before
using MIBG Therapeutic. If it is not
possible to wait your doctor will ask
you to:
• stop breast-feeding, and
• use formula feed for your child,
• express (remove) breast milk
and throw away the milk.

Your doctor will let you know when
you can start breast-feeding again.
Driving and using machines
Ask your doctor if you can drive or
use machines after you have been
given MIBG Therapeutic.


Tests you will have with
MIBG Therapeutic
• Some people will have their blood
pressure and heart beat monitored
(using an ‘ECG’ machine) when they
are given MIBG Therapeutic.
• You will also be asked to give blood
samples for up to a month.
Important information about
some of the ingredients of MIBG
• MIBG Therapeutic contains
benzyl alcohol. Benzyl alcohol
may cause toxic reactions and
allergic reactions in infants and
children up to 3 years old.

Important information about MIBG
When MIBG Therapeutic is used you
are exposed to radioactivity.
• Your doctor will always consider
the possible risks and benefits
before you are given the
Ask your doctor if you have any


3. how MIBG Therapeutic is given
MIBG Therapeutic will be given to
you by a specially trained and
qualified person.
• MIBG Therapeutic will always be
used in a hospital or clinic.
• Your doctor will tell you to take
another medicine 24 to 48 hours
before you are given MIBG
Therapeutic. You will continue to
take this medicine for at least 5
days. This medicine is to stop
radioactivity building up in your
thyroid gland.
• You will be asked to drink plenty
of fluids for at least the first 24
• Scans may be taken after you
have been given MIBG

• The person giving you MIBG
Therapeutic will tell you anything
you need to know for its safe use.
Your doctor will decide the dose
that is best for you.
The usual dose is:
• single injection (as an infusion into
a vein over a period of one to four
If you are given more MIBG
Therapeutic than you should
MIBG Therapeutic is given in a hospital
or clinic by a specially trained and
qualified person. It is unlikely that you
will be given too much.
If you have any concerns talk to your
doctor or nurse.


4. Possible side effects

5. how to store MIBG Therapeutic

Like all medicines, MIBG Therapeutic
can cause side effects, although not
everybody gets them.

MIBG Therapeutic is kept out of the
reach and sight of children.

You may experience the following
side effects:
• nausea (feeling sick) and
vomiting (being sick) within the
first 24 hours
• suppression of the bone marrow.
This can include a decrease in
platelets in your blood. Signs of this
would be bleeding or bruising more
easily than usual.
If any of the side effects gets
serious, or if you notice any side
effects not listed in this leaflet,
please tell your doctor or nurse.

The product label includes the
correct storage conditions and the
expiry date for the batch. Hospital
staff will ensure that the product is
stored and disposed of correctly
and not used after the expiry date
stated on the label.


6. Further information
What MIBG Therapeutic contains
• The active ingredient is
[131I]iobenguane. Each vial of
MIBG Therapeutic contains
between 185-740 MBq/ml
(Megabecquerel – the unit in which
radioactivity is measured) of
iodine-131 at a fixed time.
• The other ingredients are
sodium chloride, benzyl alcohol
and water for injections.
What MIBG Therapeutic looks like
and contents of the pack
MIBG Therapeutic is supplied as a
single colourless glass vial
containing a solution for infusion or
solution for injection.

Marketing authorisation holder
GE Healthcare Limited
Amersham Place
Little Chalfont
Buckinghamshire HP7 9NA
United Kingdom
GE Healthcare Buchler GmbH & Co. KG
Gieselweg 1
38110 Braunschweig
This leaflet was last approved in
Marketing authorisation
UK: PL 00221/0125
Ireland: PA 240/8/1




EVS 220112 / 0212 / DD 800

GE and the GE Monogram are trademarks of General Electric Company.



PacKaGe leafleT:
InforMaTIon for HealTHcare ProfeSSIonal

HealTHcare ProfeSSIonal

(131I) for Therapeutic Use
185-740 MBq/ml solution
for infusion or solution for

1 naMe of THe MedIcInal ProdUcT
Meta-Iodobenzylguanidine (131I) for Therapeutic Use
185-740 MBq/ml solution for infusion or solution for injection
2 QUalITaTIve and QUanTITaTIve coMPoSITIon
[131I]iobenguane 0.185-0.740 GBq/ml
(Not more than 0.67 mg/ml)
Summary of the physical characteristics of the
radioactive isotope in the active substance:
iodine-131. Physical half-life 8.08 days.
The most important radiation emissions are as below:
Energy level
Abundance (%)
β-247 keV
β-334 keV
β-606 keV
β-806 keV
γ-364 keV



This medicinal product contains:
• Benzyl alcohol: 10 mg/ml
• Sodium: 3.54 mg/ml. This needs to be taken into
consideration for patients on a controlled sodium
For a full list of excipients, see section 6.1.
3 PHarMaceUTIcal forM
Solution for infusion or for solution for injection.
Clear, colourless solution.

clInIcal ParTIcUlarS

4.1 Therapeutic indications
Radiation therapy of tumour-tissue that is capable of
retaining iobenguane. These are tumours arising from
cells originating embryologically from the neural crest;
pheochromocytomas, neuro-blastomas, carcinoids
and medullary carcinomas of the thyroid gland (MCT).
4.2 Posology and method of administration
Therapeutic dose with an amount of [131I]iobenguane
individually tailored on the basis of a dosimetric study.
The size of the dose as well as the interval(s) between
possible multiple administrations are mainly
determined by haematological radio-toxicity and the
kind of tumour. The more rapid the rate of
progression of the tumour, the shorter the interval.

The “fixed” therapeutic dose is (3.7-7.4 GBq).
These recommended dosages are identical for
children (must not be given to premature babies or
neonates) and adults. No special dosage-scheme is
required for the elderly patient.
The therapeutic dose is administered intravenously,
generally as an infusion over a period of 1- 4 hours.
4.3 contraindications
Pregnancy is an absolute contraindication.
Hypersensitivity to the active substance or to any of
the excipients.
Must not be given to premature babies or neonates.
4.4 Special warnings and precautions for use
This medicinal product contains benzyl alcohol. Benzyl
alcohol may cause toxic reactions and anaphylactoid
reactions in infants and children up to 3 years old.
Normal tissue adjacent to the radiated cancer tissue
may become damaged (e.g. gonadal dysfunction in
patients with pelvic metastases).
Additive toxicity may occur in patients on chemotherapy (e.g. lung fibrosis, hypergonadotropic hypogonadism).
Children treated with [131I]iobenguane are at risk of
developing irreversible thyroid function loss, growth
retardation and hypergonadotropic hypogonadism.
During follow up it is therefore recommended that
special attention is paid to their endocrine status.

Drugs that may interfere with uptake and retention of
[131I]iobenguane should be stopped before treatment
(see section 4.5).
Several drugs used in the treatment of high blood
pressure and in psychiatry, interact with [131I]iobenguane. Concomitant use therefore may interfere with
the uptake and retention of [131I]iobenguane and thus
influence the radiation dose delivered both to normaland to tumour-tissue. These drugs should be stopped
before treatment (usually for four biological half-lives).
Thyroid blockade is started 24-48 hours before the
[131I]iobenguane is administered and continued for at
least 5 days. Blockade by potassium perchlorate is
achieved by administration of approximately 400
mg/day. Blockade by potassium iodide, potassiumiodate or Lugol solution must be performed with an
equivalent of 100 mg of iodine/day.
Patients are to be well hydrated for at least the first
24 hours.
[131I]iobenguane therapy should be considered only in
those patients where transplantation of autologous
bone marrow (containing little or no tumour cells) is
possible. The toxic effects on bone marrow (thrombocytopenia) must be monitored carefully and frequently.
Blood counts are to be controlled every 2 days during
the first week and later once a week for the month
following the last administration.
It is advisable but not mandatory to perform whole
body scintigram for about 1 week in order to study the
biodistribution of the agent and quantitate the uptake
in tumour foci.

Repeated treatments can be considered at 6-8
months intervals. Cumulative doses up to 29.6 GBq
have been reported; bone marrow toxicity is the
limiting factor.
Prior to administration, ensure emergency cardiac
antihypertensive treatments are readily available.
The uptake of iobenguane in the chromaffin granules
might, though rarely, cause rapid noradrenalin secretion which can induce a hypertensive crisis although
the likelihood of such an occurrence is believed to be
extremely low. This necessitates constant monitoring
of the patient during administration. Monitoring of
both ECG and blood pressure during administration
could be indicated in some patients.
In patients where the diagnostic evaluation shows diffuse bone marrow uptake of [131I]iobenguane, bone
marrow suppression may occur after administration
of a therapeutic dose.
[131I]iobenguane must be administered slowly (take at
least one minute for the administration of a patient
When the therapeutic administration for
pheochromocytoma is planned attention is to be
given to possible interference between the medication
for control of hypertension and the uptake of
[131I]iobenguane. Incompatible medication should be
stopped at least 2 weeks prior to the planned
therapeutic administration. If necessary propranolol
can be used instead.
The administration of high dose radioiodine may result
in significant environmental hazard. Suitable precautions should be taken concerning the activity elimina-

ted by the patients in order to avoid any contamination.
For radioprotection reasons following therapeutic doses, it is recommended to avoid close contact between mother and child for at least one week.
The therapeutic administration of the product in patients with significant renal impairment requires special attention with regards to administered activity.
Dosages for patients, who have undergone prior
treatment with cytostatic drugs (e.g. cisplatinum
compounds) resulting in reduced renal function, may
have to be adjusted accordingly.
The main adverse reactions in children are
thrombocytopenia (isolated) or bone marrow
suppression, the more so if there is tumour infiltration
in bone marrow. Adverse reactions related to the
function of the salivary glands or of the myocardium,
or toxic effects on the liver have not been described.
Women receiving [131I]iobenguane should be advised
not to become pregnant within at least 6-12 months
of administration.
For each patient, exposure to ionising radiation must
be justifiable on the basis of likely benefit. The activity
administered must be such that the resulting radiation
dose is as low as reasonably achievable bearing in
mind the need to obtain the intended diagnostic or
therapeutic result.
The radiation dose resulting from therapeutic exposure may results in higher incidences of cancer and mutations. In all cases it is necessary to ensure that the
risks of the radiation are less than from the disease itself.

This medicinal product contains sodium: 3.54 mg/ml.
This needs to be taken into consideration for patients
on a controlled sodium diet.
4.5 Interaction with other medicinal products and
other forms of interaction
The following drugs are known or may be expected to
prolong or to reduce the uptake of iobenguane in
neural crest tumours. There are additional drugs that
may interfere, but no formal proof exists.
• Nifedipine (a Ca-channel blocker) is reported to
prolong retention of iobenguane.
Decreased uptake was observed under therapeutic
regimens involving the administration of:
• Antihypertensive drugs as reserpine, labetalol,
calcium-channel blockers (diltiazem, nifedipine,
• Sympathomimetic agents (present in nasal
decongestants, such as phenylephrine, ephedrine
or phenylpropanolamine).
• Cocaine.
• Tricyclic antidepressants such as amitriptyline and
derivatives, imipramine and derivatives, doxepin,
amoxepine and loxapine.
For the following drugs inhibition of the uptake of
iobenguane is expected to occur, but no proof is yet
• Antihypertensives acting through adrenergic
neuron blockade (betanidine, debrisoquine,
bretylium and guanethidine).


Antidepressants such as maprotiline and
These drugs should be stopped before treatment
(usually for four biological half-lives).
Special care must be given to the selection of
anti-emetics that are often given to suppress the
nausea that generally accompanies the administration
of iobenguane in therapeutic quantities. Anti-emetics
that are dopamine/serotonin receptor antagonists do
not interfere with iobenguane uptake at
concentrations as are used in clinical practice.
4.6 fertility, pregnancy and lactation
The product is contraindicated during established or
suspected pregnancy or when pregnancy has not
been excluded (see section 4.3).
When it is necessary to administer radioactive
medicinal products to women of childbearing
potential, information should always be sought about
pregnancy. Any woman who has missed a period
should be assumed to be pregnant until proven
Before administering a radioactive medicinal product
to a mother who is breastfeeding, consideration
should be given as to whether the investigation could
be reasonably delayed until the mother has ceased

Breastfeeding should be discontinued after administration of the product.
4.7 effects on ability to drive and use machines
No studies on the effects on the ability to drive and
use machines have been performed.
4.8 Undesirable effects
Exposure to ionising radiation is linked with cancer
induction and a potential for development of
hereditary defects. For diagnostic nuclear medicine
investigations the current evidence suggests that
these adverse effects will occur with low frequency
because of the low radiation doses incurred.
The frequencies of undesirable effects 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), very rare (<1/10,000) and not known (cannot be estimated from the available data).
Infections and infestations
Not known: Infection susceptibility increased.
neoplasms benign, malignant and unspecified
(including cysts and polyps)
Not known: Leukaemias, malignant secondary cancers.
Blood and lymphatic system disorders
Not known: Bone marrow depression, anaemia,
thrombocytopenia, neutropenia.

endocrine disorders
Not known: Hypothyroidism, possibly leading to
growth retardation in children. Hyperthyroidism.
Gastrointestinal disorders
Very common: Nausea, vomiting.
Not known: Salivary gland conditions.
Injury, poisoning and procedural complications
Not known: Radiation injury (including radiation associated pain, interstitial lung disease, transient sialoadenitis, hypogonadism, ovarian failure).
4.9 overdose
The effect of an overdose of iobenguane is due to the
release of adrenaline. This effect is of short duration
and requires supportive measures aimed at lowering
the blood pressure. Prompt injection of a rapid acting
alpha-adrenergic blocking agent (phentolamine)
followed by a beta-blocker (propranolol). Because of
the renal elimination pathway maintaining the highest
possible urine flow is essential to reduce the influence
of radiation.
5 PHarMacoloGIcal ProPerTIeS
[131I]iobenguane is a radioiodinated aralkylguanidine.
Its structure contains the guanidine-group from
guanethidine linked to a benzyl-group into which
iodine is introduced. Like guanethidine, the
aralkylguanidines are adrenergic neuron blocking
agents. As consequence of a functional similarity
between adrenergic neurons and the chromaffin cells

of the adrenal medulla, iobenguane is able to localise
preferentially in the medulla of the adrenal glands. In
addition localisation in the myocardium occurs.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: therapeutic
radiopharmaceuticals, other therapeutic
radiopharmaceuticals, iobenguane (131I),
ATC code V10XAA02.
Of the various aralkylguanidines iobenguane is the
preferred substance because of its low liver uptake
and its best in vivo stability, resulting in the lowest
achievable uptake of liberated iodide by the thyroid.
Transport of iobenguane across the cell membranes
of cells originating from the neural crest is an active
process when the concentration of the drug is low (as
in diagnostic dosages). The uptake mechanism can be
inhibited by uptake of inhibitors such as cocaine or
desmethylimipramine. When the drug is administered
in higher concentrations (as in therapeutic dosages)
passive diffusion processes become also important.
The clinical implications towards dosimetry, if any, are
Subsequently, an active mechanism transfers at least
part of the intracellular iobenguane into the storage
granules within the cells.
5.2 Pharmacokinetic properties
Iobenguane is to a large extent excreted unaltered by
the kidneys. 70 to 90% of administered doses are
recovered in urine within 4 days. The following

metabolic breakdown products were recovered in
urine: iodide-131, [131I]-metaiodohippuric acid,
[131I]-hydroxy-iodobenzylguanidine and
[131I]-metaiodobenzoic acid. These substances
account for approximately 5 to 15% of the
administered dose.
The distribution pattern of iobenguane includes rapid
initial uptake in liver (33% of the administered dose)
and much less in lungs (3%), myocardium (0.8%),
spleen (0.6%) and salivary glands (0.4%). Uptake in
normal adrenals (adrenal medulla) is so low that these
can not be visualised with [131I]iobenguane.
Hyperplastic adrenals show a high uptake.
5.3 Preclinical safety data
In dogs 20 mg/kg is a lethal dose. Lower dose levels
(14mg/kg) cause transient clinical signs of toxic effect.
Repeated intravenous administrations in rats of 20 to
40 mg/kg induce signs of serious clinical toxicity.
Repeated intravenous administrations of 5 to 20
mg/kg do induce effects, including respiratory
distress, but long term effects are only a slight
increase in weight of liver and heart. Repeated
administration in dogs of 2.5 to 10 mg/kg do induce
clinical effects, including increased blood pressure and
abnormalities in heart rate and in cardiac pulse
propagation, but all signs were of a transient nature.
The margin of safety between administered amounts
of iobenguane (notably in therapeutic doses) and the
level at which unwanted secondary effects might
occur is not very wide, therefore patients should be
kept under close surveillance during and for at least
some hours after the infusion or injection of the drug.

In the test systems used no mutagenic effect could be
demonstrated. Studies of carcinogenic potential of
iobenguane have not been published.

PHarMaceUTIcal ParTIcUlarS

6.1 list of excipients
Benzyl alcohol
Sodium chloride
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal
product must not be mixed with other medicinal
6.3 Shelf life
The shelf-life is 2 days from the activity reference date
stated on the label.
diluted: Use within 2 hours of dilution.
6.4 Special precautions for storage
The product should be stored in dry ice (solid carbon
dioxide) until approximately one hour before use.
About 1 hour prior to administration the vial contained
within its lead shield should be thawed by placing it in
a water bath not exceeding 50°C.
Store in original lead container or in equivalent

6.5 nature and contents of container
The product is supplied in a clear neutral 10 ml glass
vial sealed with a PTFE-faced butyl rubber closure.
Pack sizes: single vials containing 0.37 to 3.7 GBq in
0.185 GBq steps
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other
Normal safety precautions for handling radioactive
materials should be observed. After use, all materials
associated with the preparation and administration of
radiopharmaceuticals, including any unused product
and its container, should be decontaminated or
treated as radioactive waste and disposed of in
accordance with the conditions specified by the local
competent authority. Contaminated material must be
disposed of as radioactive waste via an authorised
7 MarKeTInG aUTHorISaTIon Holder
GE Healthcare Limited
Amersham Place
Little Chalfont
Buckinghamshire HP7 9NA
United Kingdom
8 MarKeTInG aUTHorISaTIon nUMBer
PL 00221/0125



daTe of fIrST aUTHorISaTIon/renewal of
Date of first authorisation
14 February 1997

Date of last renewal
15 February 2002

10 daTe of revISIon of THe TexT

11 doSIMeTry
The table below shows the dosimetry as calculated
according to the publication 53 of the ICRP (International
Commission on Radiological Protection, Radiation
Dose to Patients from Radiopharmaceuticals,
Pergamon Press 1987).
Radiation dose to specific organs, which may not be
the target organ of therapy, can be influenced
significantly by pathophysiological changes induced
by the disease process. This should be taken into
consideration when using the following information.
With the exception of “uterus” the list includes only
those organs which are used in the calculation for the
effective (whole body) dose equivalent. These are the
seven standard organs and the additional five organs
with the highest absorbed dose (marked with *).


Bone surfaces
Red marrow
*Bladder wall
*Salivary glands
effective dose

absorbed dose
per unit activity administered (mGy/MBq)

15 year

10 year

5 year

1 year
















The above data are valid in normal pharmacokinetic
behaviour. Especially when renal function is impaired,
due to disease or due to previous therapy, the effective
dose equivalent and the radiation dose delivered to
organs (notably to bone, red marrow and lungs) might
be increased considerably.

12 InSTrUcTIonS for PreParaTIon of
This radiopharmaceutical may be received, used and
administered only by authorised persons in
designated clinical settings. Their receipt, storage, use,
transfer and disposal are subject to the regulations
and/or appropriate licences of the local competent
official organisations (see section 6.6).
The administration of radiopharmaceuticals creates
risks to other persons, from external radiation or
contamination from spills or urine, vomiting, etc.
Radiation protection precautions in accordance with
national regulations must therefore be taken.
Normal safety precautions for the handling of
radioactive materials should be observed in addition
to the use of septic technique to maintain sterility of
the vial contents.
radiochemical purity measurement
The radiochemical purity of [131I]iobenguane can be
determined by high performance liquid chromatography
on a silica gel (5 µm) column, 0.25 m x 4 mm,
eluted isocratically with a mixture of ammonium
nitrate solution (8%): dilute ammonia : methanol
(1:2:27). Peak detection is by the use of a suitable
radioactivity detector and by ultraviolet
spectrophotometry at 254 nm. Peaks are identified by
reference to standard solutions of sodium iodide
(1 mg/ml) and iobenguane sulphate (0.2 mg/ml).

13 oTHer InforMaTIon
GE Healthcare Buchler GmbH & Co. KG
Gieselweg 1


1178004-514 / 0113 /Oe1000

GE and the GE Monogram are trademarks of
General Electric Company.

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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.