Medication Guide App

ZAVEDOS CAPSULES 5MG

Active substance: IDARUBICIN HYDROCHLORIDE

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Page 3

Zavedos® 5 mg and 10 mg Capsules
idarubicin hydrochloride




severe renal impairment
- 
- uncontrolled infections
- severe cardiomyopathy
- 
recent myocardial infarction
- severe arrhythmias
- persistent myelosuppression
- 
previous treatment with maximum cumulative doses of idarubicin
and/or other anthracyclines and anthracenediones (See warning
section)
breast-feeding should be stopped during drug therapy (See section
- 
“use for pregnancy & lactation”)
Warnings and precautions
General
Idarubicin should be administered only under the supervision of
physicians experienced in the use of cytotoxic chemotherapy.
This ensures that immediate and effective treatment of severe
complications of the disease and/or its treatment (e.g. haemorrhage,
overwhelming infections) may be carried out.
Patients should recover from acute toxicities of prior cytotoxic treatment
(such as stomatitis, neutropenia, thrombocytopenia, and generalized
infections) before beginning treatment with idarubicin.
Cardiac Function
Cardiotoxicity is a risk of anthracycline treatment that may be manifested
by early (i.e. acute) or late (i.e. delayed) events.
Early (i.e. Acute) Events
Early cardiotoxicity of idarubicin consists mainly of sinus tachycardia
and/or electrocardiogram (ECG) abnormalities, such as non-specific
ST-T wave changes. Tachyarrhythmias, including premature ventricular
contractions and ventricular tachycardia, bradycardia, as well as
atrioventricular and bundle-branch block have also been reported.
These effects do not usually predict subsequent development of delayed
cardiotoxicity, are rarely of clinical importance, and are generally not a
reason for the discontinuation of idarubicin treatment.
Late (i.e. Delayed) Events
Delayed cardiotoxicity usually develops late in the course of therapy or
within 2 to 3 months after treatment termination, but later events, several
months to years after completion of treatment have also been reported.
Delayed cardiomyopathy is manifested by reduced left ventricular
ejection fraction (LVEF) and/or signs and symptoms of congestive heart
failure (CHF) such as dyspnoea, pulmonary oedema, dependent oedema,
cardiomegaly, hepatomegaly, oliguria, ascites, pleural effusion, and gallop
rhythm. Subacute effects such as pericarditis/myocarditis have also been
reported. Life-threatening CHF is the most severe form of anthracycline-

induced cardiomyopathy and represents the cumulative dose-limiting
toxicity of the drug. Cumulative dose limits for IV or oral idarubicin have
not been defined. However, idarubicin-related cardiomyopathy was
reported in 5% of patients who received cumulative IV doses of 150 to
290 mg/m2. Available data on patients treated with oral idarubicin
total cumulative doses up to 400 mg/m2 suggest a low probability of
cardiotoxicity.
Cardiac function should be assessed before patients undergo treatment
with idarubicin and must be monitored throughout therapy to minimize
the risk of incurring severe cardiac impairment. The risk may be
decreased through regular monitoring of LVEF during the course of
treatment with prompt discontinuation of idarubicin at the first sign of
impaired function. The appropriate quantitative method for repeated
assessment of cardiac function (evaluation of LVEF) includes Multiple
Gated Acquisition (MUGA) scan or echocardiography (ECHO). A baseline
cardiac evaluation with an ECG and either a MUGA scan or an ECHO
is recommended, especially in patients with risk factors for increased
cardiotoxicity. Repeated MUGA or ECHO determinations of LVEF should
be performed, particularly with higher, cumulative anthracycline doses.
The technique used for assessment should be consistent throughout
follow-up.
Risk factors for cardiac toxicity include active or dormant cardiovascular
disease, prior or concomitant radiotherapy to the mediastinal/pericardial
area, previous therapy with other anthracyclines or anthracenediones,
and concomitant use of drugs with the ability to suppress cardiac
contractility or cardiotoxic drugs (e.g. trastuzumab). Anthracyclines
including idarubicin should not be administered in combination with
other cardiotoxic agents unless the patient’s cardiac function is closely
monitored (see section 4.5). Patients receiving anthracyclines after
stopping treatment with other cardiotoxic agents, especially those with
long half-lives such as trastuzumab, may also be at an increased risk
of developing cardiotoxicity. The reported half-life of trastuzumab is
approximately 28-38 days and may persist in the circulation for up
to 27 weeks. Therefore, physicians should avoid anthracycline-based
therapy for up to 27 weeks after stopping trastuzumab when possible.
If anthracyclines are used before this time, careful monitoring of cardiac
function is recommended.
Cardiac function monitoring must be particularly strict in patients
receiving high cumulative doses and in those with risk factors. However,
cardiotoxicity with idarubicin may occur at lower cumulative doses
whether or not cardiac risk factors are present.
In infants and children there appears to be a greater susceptibility
to anthracycline induced cardiac toxicity, and a long-term periodic

evaluation of cardiac function has to be performed. It is probable that
the toxicity of idarubicin and other anthracyclines or anthracenediones
is additive.
Haematologic Toxicity
Idarubicin is a potent bone marrow suppressant. Severe
myelosuppression will occur in all patients given a therapeutic dose of
this agent.
Haematologic profiles should be assessed before and during each cycle
of therapy with idarubicin, including differential white blood cell (WBC)
counts.
A dose-dependent, reversible leukopaenia and/or granulocytopenia
(neutropenia) is the predominant manifestation of idarubicin hematologic
toxicity and is the most common acute doselimiting toxicity of this drug.
Leukopenia and neutropenia are usually severe; thrombocytopenia
and anaemia may also occur. Neutrophil and platelet counts usually
reach their nadir 10 to 14 days after drug administration; however, cell
counts generally return to normal levels during the third week. During
the phase of severe myelosuppression, deaths due to infections and/or
haemorrhages have been reported.
Clinical consequences of severe myelosuppression include fever,
infections, sepsis/septicaemia, septic shock, haemorrhage, tissue
hypoxia, or death. If febrile neutropenia occurs, treatment with an
IV antibiotic is recommended.
Secondary Leukaemia
Secondary leukaemia, with or without a preleukemic phase, has been
reported in patients treated with anthracyclines, including idarubicin.
Secondary leukaemia is more common when such drugs are given in
combination with DNA damaging antineoplastic agents, when patients
have been heavily pretreated with cytotoxic drugs, or when doses of the
anthracyclines have been escalated. These leukaemias can have a 1- to
3-year latency period.
Gastrointestinal
Idarubicin is emetigenic. Mucositis (mainly stomatitis, less often
oesophagitis) generally appears early after drug administration and,
if severe, may progress over a few days to mucosal ulcerations. Most
patients recover from this adverse event by the third week of therapy.
Occasionally, episodes of serious gastrointestinal events (such as
perforation or bleeding) have been observed in patients receiving oral
idarubicin who had acute leukaemia or a history of other pathologies or
had received medications known to lead to gastrointestinal complications.

N. ZAVCPS10

Page 1

Package leaflet: Information for the
patient

Zavedos® 5 mg and 10 mg Capsules


FPO

Idarubicin is an antimitotic and cytotoxic anthracycline.
Description
Zavedos capsules are supplied as hard gelatin capsules containing an
orange powder:
5 mg capsules:
Opaque, red cap and body, size No. 4 capsules
10 mg capsules:
Opaque, red cap and white body, size No. 4 capsules
Pharmacology
Idarubicin intercalates with DNA and interacts with topoisomerase II and
has an inhibitory effect on nucleic acid synthesis.
The compound has a high lipophilicity which results in an increased rate
of cellular uptake compared with doxorubicin and daunorubicin.
Idarubicin has been shown to have a higher potency with respect to
daunorubicin and to be an effective agent against murine leukaemia and
lymphomas both by iv. and oral routes.
Studies in vitro on human and murine anthracycline-resistant cells have
shown a lower degree of cross-resistance for idarubicin compared with
doxorubicin and daunorubicin. Cardiotoxicity studies in animals have
indicated that idarubicin has a better therapeutic index than daunorubicin
and doxorubicin. The main metabolite, idarubicinol, has shown, in vitro
and in vivo, antitumoral activity in experimental models. In the rat,
idarubicinol, administered at the same doses as the parent drug, is
clearly less cardiotoxic than idarubicin.
Pharmacokinetics
After oral administration to patients with normal renal and hepatic
function, idarubicin is rapidly absorbed, with a peak time of 2-4 hours, is
eliminated from systemic circulation with a terminal plasma t½ ranging
between 10-35 hours and is extensively metabolized to an active
metabolite, idarubicinol, which is more slowly eliminated with a plasma
t½ ranging between 33 and 60 hours. The drug is mostly eliminated
by biliary excretion, mainly in the form of idarubicinol, urinary excretion
accounting for 1-2% of the dose as unchanged drug and for up to 4.6%
as idarubicinol.

Average values of absolute bioavailability have been shown to range
between 18 and 39% (individual values observed in the studies ranged
between 3 and 77%), whereas the average values calculated on the data
from the active metabolite, idarubicinol, are somewhat higher (29-58%;
extremes 12 - 153%).
Studies on cellular (nucleated blood and bone marrow cells) drug
concentrations in leukemic patients have shown that uptake is rapid and
almost parallels the appearance of the drug in plasma. Idarubicin and
idarubicinol concentrations in nucleated blood and bone marrow cells
are more than two hundred times the plasma concentrations. Idarubicin
and idarubicinol disappearance rates in plasma and cells were almost
comparable.
Indications
Whenever intravenous idarubicin cannot be employed e.g. for medical,
psychological or social reasons, oral idarubicin can be used for remission
induction in patients with previously untreated, relapsed or refractory
acute non-lymphocytic leukaemia.
Zavedos capsules may be used in combination chemotherapy regimens
involving other cytotoxic agents.
Zavedos capsules are indicated as a single agent in the treatment of
advanced breast cancer after failure of front line chemotherapy not
including anthracyclines.
Dosage and administration
Dosage is usually calculated on the basis of body surface area.
In adult ANLL the recommended dose schedule is 30 mg/m² orally given
daily for 3 days as a single agent, or between 15 and 30 mg/m² orally
daily for 3 days in combination with other antileukemic agents.
In advanced breast cancer the recommended dose schedule as a single
agent is 45 mg/m² orally given either on a single day or divided over
3 consecutive days (15 mg/m²/day, to be repeated every 3 or 4 weeks
based on haematological recovery.
A maximum cumulative dose of 400 mg/m² is recommended.
These dosage schedules should, however, take into account the
haematological status of the patient and the dosages of other cytotoxic
drugs when used in combination. In patients with hepatic impairment a
dose reduction of Zavedos should be considered (see warnings). Before
administration it should be ensured that the capsules are intact. They
should be swallowed whole with some water and should not be sucked,
bitten or chewed. Zavedos capsules may also be taken with a light meal.
Contraindications
- 
hypersensitivity to idarubicin or to any of the excipients, other
anthracyclines or anthracenediones
severe hepatic impairment
- 

FPO

PHYSICIANS LEAFLET

idarubicin hydrochloride




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
• 
•  you have any questions ask your doctor or
If
pharmacist
This medicine has been prescribed for you
• 
only. Do not pass it 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 Zavedos is and what it is used for
2.  hat you need to know before you take
W
Zavedos
3. How to take Zavedos
4. Possible side effects
5. How to store Zavedos
6. Contents of the pack and other

information
1. What Zavedos is and what it is used for
• 
Zavedos contains an active ingredient called
idarubicin, which belongs to a group of
medicines called anthracyclines. Zavedos

interferes with ways in which the cells of your
body grow and increase in number and is used
in the treatment of cancers (chemotherapy).
• 
Zavedos is used for the treatment of acute
non-lymphoblastic leukaemia (ANLL) also
referred to as acute myelogenous leukaemia
(AML), or advanced breast cancer.
You must talk to a doctor if you do not feel better
or if you feel worse.
W
2.  hat you need to know before you take
Zavedos
Do not take Zavedos if:
You
•  have ever had an allergic (hypersensitivity)
reaction to idarubicin or any of the other
ingredients of this medicine (listed in section 6)
or other anthracyclines.
•  have an infection which is not under
You
control.
Your liver or kidneys are not working properly.
• 
You
•  have had previous or current history of
bone marrow depression caused by previous
therapy.
You
•  have had a previous or current history of
heart disease.
You
•  have had a previous or current history of
abnormal heart rhythms.
You
•  have previously been treated with
high doses of idarubicin and/ or other
anthracyclines or anthracenediones.
•  are breast-feeding.
You
Warnings and precautions
Talk to your doctor or pharmacist before taking
Zavedos:
•  you suffer from bone marrow depression
If
caused by previous therapy.

If
•  you have suffered from heart trouble in the
past or are presently receiving treatment for
this.
•  you have had a previous or current history of
If
stomach problems (e.g. ulcer) or any problem
with your bowels.
Your doctor will assess your health and discuss
the risk and benefits of your treatment carefully
before prescribing Zavedos capsules to you.
Zavedos might not be a suitable treatment for
you, or a reduced dose might have to be used.
Zavedos might not be a suitable treatment for
infants or children as they are more at risk of
heart trouble.
Other medicines and Zavedos
Tell your doctor or pharmacist if you are taking,
have recently taken or might take any other
medicines:
If
•  you are given medicines or were previously
given medicines such as anthracyclines or
anthracenediones that have a similar action
to Zavedos. They can make the effects of
Zavedos stronger.
If
•  you are using Zavedos with medicines like
calcium channel blockers or chemotherapies
that have cardiac toxicity.
•  you are receiving radiotherapy.
If
If
•  you are taking oral drugs that prevent blood
clots as it will require close monitoring.
If
•  you are taking a medicine called
Cyclosporin A.

You should not take live or live-attenuated
vaccines (e.g. yellow fever) because of the
risk of serious infection after treatment with
chemotherapy.
Zavedos with food and drink
Zavedos capsules may be taken with a light meal.
Pregnancy
If you are pregnant, think you may be pregnant
or are planning to have a baby, ask your doctor
or pharmacist for advice before taking this
medicine. Avoid becoming pregnant while you
or your partner is being treated with Zavedos. If
you are sexually active, you are advised to use
effective birth control to prevent pregnancy during
treatment, whether you are male or female. Males
should continue to use effective contraception up
to 3 months after treatment. Zavedos may harm
an unborn child, so it is important to tell your
doctor if you think you are pregnant.
Breast-feeding
You should not breast-feed whilst receiving
Zavedos, as some of the medicine may get into
your milk and possibly harm your child.
Ask your doctor or pharmacist for advice before
taking any medicine.
Driving and using machines
Special care should be taken if it is essential that
you drive or operate machinery while undergoing
treatment especially if you are lacking strength or
are in a debilitated condition.
3. How to take Zavedos
Always take this medicine exactly as your doctor
or pharmacist has told you. Check with your
doctor or pharmacist if you are not sure.

N. ZAVCPS10

Page 2

If you take more Zavedos than you should
The single-dose packaging is designed to
minimise the risk of overdose.
Intestinal bleeding can occur with high doses
of Zavedos. This may need to be observed for
patients treated with oral idarubicin.
However if you take more Zavedos than you
should, then seek medical attention.
If you forget to take Zavedos
If you forget to take Zavedos take it as soon as
you can. Take your next dose at the right time. Do
not take a double dose to make up for a forgotten
dose.
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.
Tell your doctor immediately if you experience
any of the following symptoms after taking
this medicine. Although they are very rare the
symptoms can be severe.
•  may have allergic reactions such as feel
You
dizzy, feverish, short of breath with a tight
chest, with or without an itchy rash.
•  have an inflammation of the pericardium
You
(the fibrous sac surrounding the heart),
inflammation of the heart muscle, a disease of
the electrical system of the heart.
•  condition in which a blood clot that has
A
formed inside a blood vessel or inside the heart,
redness of the skin, typically over the cheeks or
neck.
N. ZAVCPS10

Zavedos capsules are taken by mouth.
• 
Your doctor will prescribe the required amount
(the dose). The dose is decided by taking into
account your condition being treated, your
height and weight.
From your height and weight the doctor will
• 
work out your body surface area (in square
metres); this is necessary because the dose is
usually calculated as ‘…milligrams per square
metre’ (mg/m2).
•  dose will be given daily for three days (or
The
on one day only for breast cancer).
• 
However, your doctor may alter the dose and
number of days depending on your condition
and any other treatment you may receive.
•  capsules should be swallowed whole with
The
some water and should not be sucked, bitten
or chewed.
Regular checks by your doctor during
Zavedos treatment
During treatment your doctor will be making
regular checks of:
• 
Your blood, to check for low blood cell counts
that may need treatment.
• 
Your heart function, as Zavedos can have
effects upon this.
• 
Your liver - again using blood tests - to
check that Zavedos is not affecting the way it
functions in a harmful way.
• 
Blood uric acid levels - Zavedos may increase
uric acid levels in the blood, which might cause
gout. Another medicine may be given if your
uric acid levels are too high.
You will find more information on some of these
effects in Section 4.

• 
Stomach ulcer (abdominal pain or burning
sensation).
• 
Hand foot syndrome (tingling, redness, flaking,
swelling or small sores on the palms of the
hands or soles of the feet).
• 
Anaemia (low red cells) that can leave you
feeling tired and lethargic.
• 
Leukopenia (low white cells) leading to
increased chance of infections with symptoms
of raised temperature or fever and chills
(like flu).
• 
Thrombocytopenia (low platelets, these help
the blood to clot). You may bruise more easily
or bleed more than usual if you hurt yourself.
• 
Tumour lysis syndrome (severe infections can
occur after treatment with idarubicin alone or in
combination with other medicines, and may be
fatal).
Very common (may affect more than 1 in
10 people)
• Infections.
• 
Decrease in number of red blood cells, reduced
numbers of white blood cells, abnormally low
amount of platelets.
•  lack or loss of appetite for food.
A
• 
Feeling sick or being sick, the painful
inflammation and ulceration of the mucous
membranes lining the digestive tract, diarrhoea,
stomach ache.
• Hair loss.
• 
Red colouration of urine.
• 
Fever (rise in temperature).
• Headache.
• Chills.

Common (may affect up to 1 in 10 people)
• 
Increase or decrease in heart rate, irregular
heart beat/pulse, heart failure, heart attack.
• 
Inflammation of the vein, swelling (inflammation)
of a vein caused by a blood clot.
Bleeding from the intestines, bellyache.
• 
• 
Liver enzyme elevation.
• Rash, itch.
• Haemorrhages.
• 
Increased sensitivity of irradiated skin ‘radiation
recall reaction’.
Uncommon side effects (may affect up to 1 in
100 people)
• 
Blood infection, bacteria in the blood.
• 
Cancers of blood such as secondary leukaemia
or unfavourable leukaemia (acute myeloid
leukaemia (AML) or myelodysplastic syndrome
(MDS)).
• 
Painful joints due to increased uric acid levels in
your blood (gouty arthritis).
• ECG changes.
• Shock.
• 
Inflammation of the oesophagus, inflammation
of the colon.
• 
Darkening of the skin and nails.
Excessive loss of body fluid.
• 
• 
Spreading of bacterial infection below the skin
surface and tissue damage.
• Heart attack.
• Hives.
Rare side effects (may affect up to 1 in
1,000 people)
• Stroke

Very Rare side effects (may affect up to 1 in
10,000 people)
• 
Serious allergic reaction.
• 
Inflammation of the pericardium (the fibrous
sac surrounding the heart), defect in the heart’s
electrical system.
• 
Minor ulceration of the gastric mucosa.
• 
Hand foot syndrome.
• 
Inflammation of covering of the heart and heart
muscle.
Not known (frequency cannot be estimated from
the available data
• 
Change in certain chemicals in the blood.
• 
Abnormally low levels of all blood cells
produced by the bone marrow.
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 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 Zavedos
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 carton after EXP. The expiry
date refers to the last day of that month.
Store in a dry place.
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 Zavedos contains
The active substance is idarubicin hydrochloride.
The other ingredients are microcrystalline cellulose
and glyceryl palmito-stearate.
Capsule shell: red iron oxide (E172), titanium
dioxide (E171), sodium dodecyl sulphate and
gelatin.
Printing ink: shellac, propylene glycol and black
iron oxide (E172).
What Zavedos looks like and the contents of
the pack
Zavedos are capsules containing 5 mg or 10 mg
of the active substance idarubicin hydrochloride
and are packaged singly in amber glass bottles.
5 mg capsules: Opaque, red cap and red body
10 mg capsules: Opaque, red cap and white body
The capsules are packed in amber glass bottles.
Marketing Authorisation Holder and
Manufacturer
Marketing Authorisation Holder:
Pfizer Limited, Ramsgate Road, Sandwich, Kent,
CT13 9NJ, UK.
Manufacturer:
Actavis Italy S.p.A., 10 Viale Pasteur,
20014 Nerviano (MI), Italy.
Company Contact address:
If you have any comments on the way this leaflet
is written, please contact Medical Information at
Pfizer Ltd., Walton Oaks, Tadworth, Surrey, UK.
Telephone: 01304 616161.
This leaflet was last revised in 06/2014
Ref: ZD 10_1

Page 4

In patients with active gastrointestinal disease with increased risk of
bleeding and/or perforation, the physician must balance the benefit of oral
idarubicin therapy against the risk.
Hepatic and/or Renal Function
Since hepatic and/or renal function impairment can affect the disposition of
idarubicin, liver and kidney function should be evaluated with conventional
clinical laboratory tests (using serum bilirubin and serum creatinine as
indicators) prior to, and during, treatment. In a number of Phase III clinical
trials, treatment was contraindicated if bilirubin and/or creatinine serum
levels exceeded 2.0-mg %. With other anthracyclines a 50% dose reduction
is generally used if bilirubin levels are in the range 1.2 to 2.0-mg %.
Tumour Lysis Syndrome
Idarubicin may induce hyperuricaemia as a consequence of the extensive
purine catabolism that accompanies rapid drug-induced lysis of neoplastic
cells (‘tumour lysis syndrome’). Blood uric acid levels, potassium, calcium
phosphate, and creatinine should be evaluated after initial treatment.
Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent
hyperuricaemia may minimize potential complications of tumour lysis
syndrome.
Immunosuppressant Effects/Increased Susceptibility to Infections
Administration of live or live-attenuated vaccines (like yellow fever) in
patients immunocompromised by chemotherapeutic agents including
idarubicin, may result in serious or fatal infections. Vaccination with a
live vaccine should be avoided in patients receiving idarubicin. Killed or
inactivated vaccines may be administered; however, the response to such
vaccines may be diminished.
Reproductive system
Men treated with idarubicin hydrochloride are advised to adopt contraceptive
measures during therapy and, if appropriate and available, to seek advice on
sperm preservation due to the possibility of irreversible infertility caused by
the therapy (See section “Impairment of Fertility”).
Other
As with other cytotoxic agents, thrombophlebitis and thromboembolic
phenomena, including pulmonary embolism have been coincidentally
reported with the use of idarubicin.
The product may cause a red colouration of the urine for 1 - 2 days after
administration and patients should be advised of this fact.
Use during pregnancy and lactation
Fertility
Idarubicin can induce chromosomal damage in human spermatozoa.
For this reason, males undergoing treatment with idarubicin should use
effective contraceptive methods up to 3 months after treatment (See section
“warnings & precautions”).
N. ZAVCPS10

Pregnancy
The embryotoxic potential of idarubicin has been demonstrated in both in
vitro and in vivo studies. However, there are no adequate and well-controlled
studies in pregnant women. Women of childbearing potential should be
advised not to become pregnant during treatment and adopt adequate
contraceptive measures during therapy as suggested by a physician.
Idarubicin should be used during pregnancy only if the potential benefit
justifies the potential risk to the foetus. The patient should be informed of
the potential hazard to the foetus. Patients desiring to have children after
completion of therapy should be advised to obtain genetic counselling first if
appropriate and available.
Breast-feeding
It is not known whether idarubicin or its metabolites are excreted in human
milk. Mothers should not breast-feed during treatment with idarubicin
hydrochloride.
Effects on ability to drive and use machines
The effect of idarubicin on the ability to drive or use machinery has not been
systematically evaluated.
Adverse reactions
The frequencies of undesirable effects are based on the following
categories:
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)
Not known (cannot be estimated from the available data)
Infections and infestations
Very common
Infections
Uncommon
Sepsis, septicaemia
Neoplasms benign, malignant and unspecified (including cysts
and polyps)
Uncommon
Secondary leukaemia (acute myeloid leukaemia and
myelodysplastic syndrome)
Blood and lymphatic system disorders
Very common
Anaemia, severe leukopenia and neutropenia,
thrombocytopenia
Not known
Pancytopenia
Immune system disorders
Very rare
Anaphylaxis
Endocrine disorders
Very common
Anorexia
Uncommon
Dehydration

Metabolism and nutrition disorders
Uncommon
Hyperuricaemia
Not known
Tumour Lysis Syndrome
Nervous system disorders
Rare
Cerebral haemorrhages
Cardiac disorders
Common
Bradycardia, sinus tachycardia, tachyarrhythmia,
asymptomatic reduction of left ventricular ejection
fraction, congestive heart failure, cardiomyopathies
(see section “Warnings & Precautions for associated
signs and symptoms)
Uncommon
ECG abnormalities (e.g. nonspecific ST segment
changes), myocardial infarction
Very rare
Pericarditis, myocarditis, atrioventricular and bundle
branch block
Vascular disorders
Common
Local phlebitis, thrombophlebitis, haemorrhages
Uncommon
Shock
Very rare
Thromboembolism, flush
Gastrointestinal disorders
Very common
Nausea, vomiting, mucositis/stomatitis, diarrhoea,
abdominal pain or burning sensation
Common
Gastrointestinal tract bleeding, bellyache
Uncommon
Oesophagitis, colitis (including severe enterocolitis /
neutropenic enterocolitis with perforation)
Very rare
Gastric erosions or ulcerations
Hepatobiliary disorders
Common
Elevation of the liver enzymes and bilirubin
Skin and subcutaneous tissue disorders
Very common
Alopecia
Common
Rash, itch, hypersensitivity of irradiated skin
(‘radiation recall reaction’)
Uncommon
Skin and nail hyperpigmentation, urticaria, cellulitis
(this event can be severe), tissue necrosis
Very rare
Acral erythema
Renal and urinary disorders
Very common
Red colouration of the urine for 1 – 2 days after
the treatment.
General disorders and administration site conditions
Very common
Fever, headache, chills

Description of selected adverse reactions
Haematopoietic system
Pronounced myelosuppression is the most severe adverse effect of
idarubicin treatment. However, this is necessary for the eradication of
leukemic cells (See section “warnings and precautions”).
Cardiotoxicity
Life-threatening CHF is the most severe form of anthracycline-induced
cardiomyopathy and represents the cumulative dose-limiting toxicity of the
drug (See section “warnings and precautions”).
Gastrointestinal
Stomatitis and in severe cases ulceration of mucosa, dehydration caused by
severe vomiting and diarrhoea; risk of perforation of colon etc.
Other adverse reactions: hyperuricaemia
Prevention of symptoms by hydration, urine alkalinisation, and prophylaxis
with allopurinol may minimise potential complications of tumour lysis
syndrome.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/risk
balance of the medicinal product. Healthcare professionals are asked to
report any suspected adverse reactions via the Yellow Card Scheme at
www.mhra.gov.uk/yellowcard.
Interactions
Idarubicin is a potent myelosuppressant and combination chemotherapy
regimens including other agents with similar action may be expected to
induce additive myelosuppressant effects (See Section “warnings and
precautions”). The use of idarubicin in combination chemotherapy with
other potentially cardiotoxic drugs, as well as the concomitant use of
other cardioactive compounds (e.g. calcium channel blockers), requires
monitoring of cardiac function throughout treatment.
Changes in hepatic or renal function induced by concomitant therapies may
affect idarubicin metabolism, pharmacokinetics, and therapeutic efficacy
and/or toxicity (See section “warnings and precautions”).
An additive myelosuppressant effect may occur when radiotherapy is given
concomitantly or within 2-3 weeks prior to treatment with idarubicin.
Concomitant use of live attenuated vaccines (e.g. yellow fever) is not
recommended, due to a risk of possibly fatal systemic disease. The risk
is increased in subjects who are already immunosuppressed by their
underlying disease. An inactivated vaccine should be used if available.
At combination of oral anticoagulants and anticancer chemotherapy,
increased frequency of the INR (International Normalised Ratio) monitoring is
recommended, since the risk for an interaction cannot be excluded.

Cyclosporin A: The coadminstration of cyclosporin A as a single
chemosensitizer significantly increased idarubicin AUC (1.78-fold) and
idarubicinol AUC (2.46-fold) in patients with acute leukaemia.  The clinical
significance of this interaction is unknown.
A dosage adjustment may be necessary in some patients.
Overdose
Very high doses of idarubicin may be expected to cause acute myocardial
toxicity within 24 hours and severe myelosuppression within one to two
weeks.
Delayed cardiac failure has been seen with anthracyclines for up to several
months after the overdose.
Patients treated with oral idarubicin should be observed for possible
gastrointestinal haemorrhage and severe mucosal damage.
Pharmaceutical precautions
In case of accidental contact of the powder from the capsule with the eye,
skin, or mucosa, the area should be immediately and thoroughly rinsed with
water: medical attention should be sought.
Presentation
5 or 10 mg capsules in amber glass bottles.
Package quantities
Individual capsule of 5 or 10 mg in amber glass bottles.
Legal category
POM
Product licenses
Zavedos Capsules 5 mg: PL 00057/1064
Zavedos Capsules 10 mg: PL 00057/1062
Further information is available to the medical and allied professions on
request from:
Medical Information Department, Pfizer Limited, Walton Oaks, Dorking Road,
Tadworth, KT20 7NS. Tel: 01304 616161.
Product licence holder
Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK.

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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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