Doxorubin 10 mg, 50mg powder for solution for Injection.

SMPC, Taj Pharma ceuti cals

DOXORUBIN Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, D OXORU BIN D osage & Rx Info | DOX ORUBI N Use s, Side Effe ct s -: I ndicati ons, Side E ffects, Warnings, DOXO RUBI N - Drug Infor mation - Taj Phar ma, DOXORU BIN dose Taj pharma ceuti cals DOXORU BIN intera ctions, Taj P ha rmace utical DOXORU BIN contraindi cations, DOXORUBIN price, DOX ORUBIN Taj Phar ma Cancer, oncologyDoxorubin 10 mg, 50mg powder for solution for Injection. SMPC- Taj Phar ma . Stay connecte d to all update d on D OX ORUBI N Taj Phar mace uticals Taj pharma ceutical s Hyderaba d.

RX The vial contents must be reconstituted before

use with water for injection or normal saline (see
DOXORUBICIN POWDER Section 6.6 Instructions for Use/Handling).

FOR SOLTION FOR Doxorubicin should not be administered

intramuscularly or subcutaneously.
INJECTION
INTRAVENOUS ADMINISTRATION
10MG, 50 MG Doxorubicin may be given by intravenous bolus
injection, or as continuous infusion. Bolus
1.NAME OF THE MEDICINAL injection causes higher peak plasma
PRODUCT concentration and therefore is probably more
Doxorubin 10 mg, 50mg powder for solution for cardiotoxic. Intravenous administration occurs
Injection. preferably through a running, recently applied
intravenous infusion, of sodium chloride
2. QUALITATIVE AND injection, dextrose injection 5% or sodium
QUANTITATIVE COMPOSITION chloride and dextrose injection over 3 to 5
minutes.
Doxorubin 10 mg: Doxorubin, powder for
solution for injection contains 10 mg of Patients with an increased risk for cardiotoxicity
doxorubicin hydrochloride (see section 4.4 Special warnings and
precautions for use) should be considered for
Doxorubin 50 mg: Doxorubin, powder for treatment with a 24 hours continuous infusion,
solution for injection contains 50 mg of rather than bolus injection. In this way,
doxorubicin hydrochloride cardiotoxicity may be less frequent, without a
3. PHARMACEUTICAL FORM reduction in therapeutic efficacy. In these
patients, the ejection fraction should be
Powder for solution for injection. measured before each course.
4. CLINICAL PARTICULARS ADULTS
4.1 Therapeutic indications Dosage depends on tumour type, hepatic
In combination with other antineoplastic drugs, function, and concurrent chemotherapy.
doxorubicin is intended for the treatment of
The commonly recommended dosage schedule
acute lymphocytic leukaemia, (except acute
lymphatic leukaemia of low risk in children), as single agent is 60-75 mg/m2 by intravenous
acute myeloid leukaemia, Hodgkin- and non- injection, once every 3 weeks. An alternative
Hodgkin lymphomas, osteosarcoma, Ewing dose schedule is 20 mg/m2 intravenously, during
3 consecutive days, once every 3 weeks.
sarcoma, adult soft tissue sarcoma, metastatic
breast carcinoma, gastric carcinoma, small-cell Lower doses may be required in patients with
lung cancer, neuroblastoma, Wilms tumour and inadequate marrow reserves and in patients who
bladder carcinoma. have had prior treatment with other cytotoxic
agents. When used in combination with other
Doxorubicin may be used intravesically as
single agent for treatment and prophylaxis of chemotherapeutic agents the dosage of 30-60
superficial bladder carcinoma. mg/m2 are administered. Myelosuppression may
be more pronounced because of the additive
4.2 Posology and method of administration effect of the drugs.
The route of administration is by intravenous The risk of development of cardiomyopathy
injection. gradually increases with the dosage. The
maximum cumulative dose of 450 mg/m2should
not be exceeded. The administration of
doxorubicin should be monitored by
Doxorubin 10 mg, 50mg powder for solution for Injection. SMPC, Taj Pharma ceuti cals
DOXORUBIN Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, D OXORU BIN D osage & Rx Info | DOX ORUBI N Use s, Side Effe ct s -: I ndicati ons, Side E ffects, Warnings, DOXO RUBI N - Drug Infor mation - Taj Phar ma, DOXORU BIN dose Taj pharma ceuti cals DOXORU BIN intera ctions, Taj P ha rmace utical DOXORU BIN contraindi cations, DOXORUBIN price, DOX ORUBIN Taj Phar ma Cancer, oncologyDoxorubin 10 mg, 50mg powder for solution for Injection. SMPC- Taj Phar ma . Stay connecte d to all update d on D OX ORUBI N Taj Phar mace uticals Taj pharma ceutical s Hyderaba d.

electrocardiography, echocardiography and 3. Previous treatment with complete cumulative

carotid pulse curve: When the voltage of the doses of doxorubicin or other anthracyclines.
QRS wave decreases by 30% or at a fractional
shortening of 5% it is recommended to stop 4. Doxorubicin should not be used intravesically
treatment. for the treatment of bladder carcinoma in
patients with urethral stenosis who can not be
If a patient receives mediastinal irradiation, has catheterised.
concomitant heart disease, or is also treated with
other cardiotoxic, non-anthracycline oncolytics, 4.4 Special Warnings and precautions for
a maximal cumulative dose of 400 mg/m2 is use
recommended. General precautions
Doxorubicin dosage should be reduced if the Doxorubicin should only be used under
bilirubin is elevated. When bilirubin is 12 to 30 supervision of a physician who is experienced in
mg/l - half the dosage should be given; when cytotoxic therapy. Nausea, vomiting and
bilirubin concentrations> 30 mg/l, one quarter of mucositis are often severe and should be treated
the dosage should be given. appropriately.
In general, impaired renal function does not Doxorubicin should not be administered
require dose reduction. intramuscularly or subcutaneously.
CHILDREN The total dose of doxorubicin administered to
Dosage for children may be lowered, since they the individual patient should take into account
have an increased risk for late cardiotoxicity. any previous or concomitant therapy with
Myelotoxicity should be anticipated, with nadirs related compounds such as daunorubicin.
at 10 to 14 days after start of treatment, but is Extravasation
usually followed by a rapid recovery due to the
large bone marrow reserve of children as Extravasation results in a severe and progressive
compared to adults. tissue necrosis. If extravasation occurs, the
injection should be terminated immediately and
SUPERFICIAL BLADDER CARCINOMA restarted in another vein. Flooding with normal
AND BLADDER CARCINOMA IN SITU: saline, local infiltration with corticosteroids with
The recommended dosage is 50 mg in 50 ml or without sodium hydrogen carbonate solution
normal saline, administered via a sterile catheter. (8.4%), and application of dimethylsulfoxide
Initially, this dose is given weekly, later on have been reported with varying success. The
monthly. The optimal duration of treatment has advice of a plastic surgeon should be sought, and
not yet been determined; it ranges from 6 to 12 wide excision of the involved area should be
months. considered.

Restrictions regarding the maximal cumulative Cardiotoxicity

dose, as with intravenous administration, do not Congestive heart failure and/or cardiomyopathy
apply to intravesical administration, because may be encountered several weeks after
systemic absorption of doxorubicin is negligible. discontinuation of doxorubicin therapy. Severe
4.3 Contraindications cardiac failure may occur precipitously without
Doxorubicin therapy should not be started in the antecedent ECG change.
following cases: The risk of severe, irreversible and therapy-
1. Marked myelosuppression induced by resistant cardiomyopathy and resulting
previous chemotherapy or by radiotherapy. congestive heart failure gradually increases with
increasing dosages. A cumulative dose of 450
2. Pre-existing heart disease. mg/m2 should not be exceeded.
Doxorubin 10 mg, 50mg powder for solution for Injection. SMPC, Taj Pharma ceuti cals
DOXORUBIN Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, D OXORU BIN D osage & Rx Info | DOX ORUBI N Use s, Side Effe ct s -: I ndicati ons, Side E ffects, Warnings, DOXO RUBI N - Drug Infor mation - Taj Phar ma, DOXORU BIN dose Taj pharma ceuti cals DOXORU BIN intera ctions, Taj P ha rmace utical DOXORU BIN contraindi cations, DOXORUBIN price, DOX ORUBIN Taj Phar ma Cancer, oncologyDoxorubin 10 mg, 50mg powder for solution for Injection. SMPC- Taj Phar ma . Stay connecte d to all update d on D OX ORUBI N Taj Phar mace uticals Taj pharma ceutical s Hyderaba d.

Age over 70 or below 15 years and female Hepatic function (SGOT, SGPT, alkaline
gender in children should be considered a risk phosphatase and bilirubin) should be evaluated
factor, as well as concomitant heart disease. In before and during therapy.
addition, ECG changes may occur including a
Hyperuricaemia
reduction in the voltage of the QRS wave, and a
prolongation of the systolic time interval, and Doxorubicin may induce hyperuricemia. The
the ejection fraction may be reduced. blood uric acid level should be monitored.
In patients previously treated with other Sufficient fluid intake should be ascertained
(with a daily minimum of 3 l/m2). If necessary, a
anthracyclines or cyclophosphamide, mitomycin
xanthine-oxidase inhibitor (allopurinol) may be
C or dacarbazine, and patients who received
administered.
radiotherapy to the mediastinal area,
cardiotoxicity may occur at doses lower than the Discoloration of urine
recommended cumulative limit. The concurrent
use of trastuzumab and anthracyclines (like Doxorubicin may impart a red coloration to the
doxorubicin) is not recommended (see section urine.
4.5). 4.5 Interaction with other medicinal
Acute severe arrhythmias have been reported to products and other forms of interaction
occur during or within a few hours after
Doxorubicin cardiotoxicity is enhanced by
doxorubicin administration.
previous or concurrent use of other
Heart function should be assessed before, during anthracyclines, mitomycin C, dacarbazine,
and after doxorubicin therapy, e.g., by ECG, dactinomycin and, possibly, cyclophosphamide.
echocardiography or determination of the Also the risk of cardiotoxicity is increased if
ejection fraction. If test results indicate change trastuzumab is given with or after doxorubicin.
in cardiac function associated with doxorubicin Trastuzumab and anthracyclines should not be
the benefit of continued therapy must be used concurrently in combination except in a
carefully evaluated against the risk of producing well-controlled clinical trial setting with cardiac
irreversible cardiac damage. monitoring. Furthermore, paclitaxel decreases
the elimination of doxorubicin. Care should be
Myelosuppression taken in case of co- administration of both drugs,
The high incidence of bone marrow depression because of an increased risk of cardiotoxic
requires careful haematologic monitoring. The effects of doxorubicin. The severity of
nadir is reached between 10-14 days after neutropenia or stomatitis may also be increased.
administration. Blood values usually return to Doxorubicin may cause exacerbations of
normal within 21 days after administration. haemorrhagic cystitis caused by previous
Doxorubicin therapy should not be started or cyclophosphamide therapy.
continued when polynuclear granulocyte counts
are below 2000/mm3, except in the treatment of Doxorubicin may enhance the hepatotoxicity of
acute leukaemia, where lower limits may be 6-mercaptopurine.
applied, depending on the circumstances.
The effects of radiation may be enhanced, and
Careful haematologic monitoring is also recall of these reactions may occur with
required because of the risk of secondary doxorubicin therapy, even some time after
leukaemias after treatment with cytotoxic agents termination of radiotherapy.
(see section 4.8 Undesirable effects). A
Inducers of the enzyme cytochrome P-450 (e.g.
remission of acute leukaemia can be achieved rifampicin and barbiturates) may stimulate the
when detected at an early stage.
metabolism of doxorubicin, with a possible
Hepatic impairment decrease in efficacy.
Doxorubin 10 mg, 50mg powder for solution for Injection. SMPC, Taj Pharma ceuti cals
DOXORUBIN Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, D OXORU BIN D osage & Rx Info | DOX ORUBI N Use s, Side Effe ct s -: I ndicati ons, Side E ffects, Warnings, DOXO RUBI N - Drug Infor mation - Taj Phar ma, DOXORU BIN dose Taj pharma ceuti cals DOXORU BIN intera ctions, Taj P ha rmace utical DOXORU BIN contraindi cations, DOXORUBIN price, DOX ORUBIN Taj Phar ma Cancer, oncologyDoxorubin 10 mg, 50mg powder for solution for Injection. SMPC- Taj Phar ma . Stay connecte d to all update d on D OX ORUBI N Taj Phar mace uticals Taj pharma ceutical s Hyderaba d.

Inhibitors of cytochrome P-450 (e.g. cimetidine) Hypersensitivity reactions, such as fever,

may decrease the metabolism of doxorubicin, urticaria and anaphylaxis occur rarely.
with a possible increase in toxic effects. Doxorubicin influences and potentiates normal
tissue reactions to radiation. Also, late (recall)
4.6 pregnancy and lactation reactions may occur when doxorubicin is
Clinical evidence suggests a possible adverse administered some time after irradiation. Facial
effect on the foetus. In animals doxorubicin has flushing may occur if the injection is given too
embryotoxic and teratogenic effects. rapidly.

Doxorubicin is excreted into breast milk. Usage Cardiac Disorder

during pregnancy and lactation is therefore not Cardiotoxicity may occur as arrhythmia directly
recommended. following drug administration; ECG changes,
Men as well as women should take effective including T-wave flattening and S-T depression,
contraceptive measures during and for at least may last up to 2 weeks after administration.
three months after doxorubicin therapy. The risk of cardiomyopathy increases with an
4.7 Effects on ability to drive and use increasing dosage. Severe cardiotoxicity is more
machines likely after high cumulative doses of
doxorubicin (see section 4.4 Special Warnings
and Precautions for Use) and may occur months
Due to the frequent occurrence of nausea and
or years after administration.
vomiting, driving cars and operation of
machinery should be discouraged. Gastrointestinal Disorder
4.8 Undesirable Effects Nausea and vomiting are very common and
diarrhoea occurs occasionally.
Dose limiting toxicities of therapy are
Mucositis (stomatitis or oesophagitis) may occur
myelosuppression and cardiotoxicity.
5 to 10 days after administration.
Blood and Lymphatic System Disorder
Hepato-biliary Disorder
Myelosuppression includes a transient
Slight transient increases of liver enzymes have
leucopenia very commonly. Anaemia and
been reported. Concomitant irradiation of the
thrombocytopenia are less common.
liver may cause severe hepatotoxicity,
Myelosuppression reaches its nadir at 10 to 14
sometimes progressing to cirrhosis.
days after treatment. Blood levels usually return
to normal within 21 days after administration. Other adverse reactions:
Myelodysplastic syndrome and acute myeloid A generally reversible alopecia is very common.
leukaemia have been observed after treatment
with combination therapy including doxorubicin. A red colouration of the urine, imparted by
With topoisomerase II inhibitors, secondary doxorubicin, is very common.
leukaemias have been reported more frequently Thrombophlebitis and conjunctivitis have been
than expected in the form of acute myeloid reported.
leukaemia classification 2, 3, and 4. These forms
of leukaemia can have a short period of latency Doxorubicin may induce hyperuricemia.
(1 to 3 years) but much longer periods have been Intravesical Administration
reported. They can be cured when detected at an
early stage and with an appropriate curative Intravesical administration may cause the
treatment (see section 4.4 Special warnings and following adverse reactions: haematuria, vesical
special precautions for use). and urethral irritation, dysuria, stranguria and
pollakisuria. These reactions are usually of
Immune Disorder moderate severity and of short duration.
Doxorubin 10 mg, 50mg powder for solution for Injection. SMPC, Taj Pharma ceuti cals
DOXORUBIN Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, D OXORU BIN D osage & Rx Info | DOX ORUBI N Use s, Side Effe ct s -: I ndicati ons, Side E ffects, Warnings, DOXO RUBI N - Drug Infor mation - Taj Phar ma, DOXORU BIN dose Taj pharma ceuti cals DOXORU BIN intera ctions, Taj P ha rmace utical DOXORU BIN contraindi cations, DOXORUBIN price, DOX ORUBIN Taj Phar ma Cancer, oncologyDoxorubin 10 mg, 50mg powder for solution for Injection. SMPC- Taj Phar ma . Stay connecte d to all update d on D OX ORUBI N Taj Phar mace uticals Taj pharma ceutical s Hyderaba d.

Intravesical administration of doxorubicin may The intravenous administration of doxorubicin is

sometimes cause a haemorrhagic cystitis; this followed by a rapid plasma clearance (t1/2 ~ 10
may cause a decrease in bladder capacity. min.) and significant tissue binding. The
terminal half-life is approximately 30 hours.
4.9 Overdose
Acute overdose of doxorubicin enhances the Doxorubicin is partly metabolised, mainly to
toxic effects, particularly-mucositis, leucopenia doxorubicinol and to a lesser extent, to the
and thrombocytopenia. Overdose of intravesical aglycone, and is conjugated to the glucuronide
administration may result in more severe and sulphate. Biliary and faecal excretion
cystitis. Treatment of acute overdose consists of represents the major excretion route. About 10%
treatment of the severely myelosuppressed of the dose is eliminated by renal excretion.
patient with hospitalisation, antibiotics and Plasma protein binding of doxorubicin ranges
transfusions after consultation of an oncologist. from 50-85%. The volume of distribution is 800-
3500 1/m2.
Chronic overdosage with cumulative doses
exceeding 450 mg/m2 increases the risk of Doxorubicin is not absorbed after oral
cardiomyopathy and resultant congestive heart administration; it does not cross the blood-brain
failure. Treatment consists of vigorous barrier.
management of congestive heart failure with
Impairment of liver function may decrease the
digitalis preparations and diuretics. Single doses
clearance of doxorubicin and its metabolites.
of 250 mg and 500 mg of doxorubicin have
proved fatal. Such doses may cause acute 5.3 Preclinical safety data
myocardial degeneration within 24 hours and
severe myelosuppression, the effects of which There are no preclinical safety data of relevance
are greatest between 10 and 15 days after to the prescriber which are additional to those
administration. Treatment should be already stated in other sections of the SPC.
symptomatic and supportive. Delayed cardiac 6. PHARMACEUTICAL
failure may occur up to six months after the
PARTICULARS
overdose.
5. PHARMACOLOGICAL 6.1 List of excipients
PROPERTIES Lactose

5.1 Pharmacodynamic properties 6.2 Incompatibilities

Doxorubicin should not be mixed with other
Doxorubicin is an oncolytic drug of the drugs. Alkaline solutions may hydrolyse
anthracycline group. It is isolated from cultures doxorubicin. Doxorubicin should not be mixed
of Streptomyces peucetius var. caesius. Animal with heparin or 5-fluorouracil. Contact with
studies have shown an oncolytic action in aluminium should be avoided.
several solid and haematologic tumours. The
mechanism of action is not completely
elucidated. A major mechanism is probably
6.3 Shelf life
inhibition of topoisomerase II, resulting in DNA
Following the special precautions for storage
breakage. Intercalation and free-radical
(see below) the shelf life for the powder for
formation is probably of minor importance.
solution for injection is 5 years. The expiration
Drug resistance, due to increased expression of
date is printed on the label.
the MDR-1 gene encoding for a multidrug efflux
pump, has been reported regularly. Chemical and physical in-use stability of the
reconstituted solution in 0.9% sodium chloride
5.2 Pharmacokinetic properties solution has been demonstrated for 7 days at 15-
25 C and for 14 days under refrigeration (2-8 C).
Doxorubin 10 mg, 50mg powder for solution for Injection. SMPC, Taj Pharma ceuti cals
DOXORUBIN Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, D OXORU BIN D osage & Rx Info | DOX ORUBI N Use s, Side Effe ct s -: I ndicati ons, Side E ffects, Warnings, DOXO RUBI N - Drug Infor mation - Taj Phar ma, DOXORU BIN dose Taj pharma ceuti cals DOXORU BIN intera ctions, Taj P ha rmace utical DOXORU BIN contraindi cations, DOXORUBIN price, DOX ORUBIN Taj Phar ma Cancer, oncologyDoxorubin 10 mg, 50mg powder for solution for Injection. SMPC- Taj Phar ma . Stay connecte d to all update d on D OX ORUBI N Taj Phar mace uticals Taj pharma ceutical s Hyderaba d.

Chemical and physical in-use stability of a 0.5 again. Should the fragments still be visible,
mg/ml solution in water for injections has been discard the solution.
demonstrated for 24 hours at temperatures below
25 C. When water for injections is used, immediate
dilution to a concentration of less than 0.4mg/ml
Chemical and physical in-use stability of doxorubicin with 0.9% sodium chloride solution
solutions in the range 0.05 mg/ml to 5 mg/ml in or 5% glucose solution is needed in order to
0.9% sodium chloride solution has been obtain an isotonic solution.
demonstrated for 7 days at room temperature
(15-25 C). Due to the toxic nature of doxorubicin it is
recommended that the following protective
From a microbiological point of view, the measures be taken:
product should be used immediately. If not used
-General instructions for safe use of cytotoxics:
immediately, in-use storage times and conditions
prior to use are the responsibility of the user and - Training in good techniques for reconstitution
would normally not be longer than 24 hours at 2 and handling should be given to relevant
to 8 C, unless reconstitution has taken place in personnel.
controlled and validated aseptic conditions.
- Pregnant staff should be excluded from
6.4 Special precautions for storage working with this drug

Doxorubin, powder for solution for injection, 10 - Protective clothing should be worn while
mg (50 mg) should be stored at 15-25 C, administering, handling or reconstituting
protected from light. doxorubicin
- Contact with skin or eyes should be avoided. If
6.5 Nature and contents of container
it occurs, the affected area should be washed
Doxorubin, powder for solution for injection, 10 immediately with water, soap and water or
mg (50 mg) is supplied as a red-orange, sterile, sodium bicarbonate solution.
lyophilized powder, in glass injection vials with
- Any spillages should be cleaned with dilute
aluminium seal. The package size is 1 or 10
sodium hypochlorite solution.
vials.
- All equipment used for the handling,
6.6 Special precautions for disposal and preparation and administration of doxorubicin
other handling should be incinerated.
Instructions for reconstitution: Unused products should be disposed of in a
For intravenous injection, Doxorubicin powder suitable labelled container, marked as hazardous
for solution for injection should be reconstituted waste.
to a concentration of 2 mg/ml in water for 7. MANUFACTURER:
injections immediately before use. Alternatively,
sodium chloride for injections may be used as a
solvent, however, the product may take longer to
dissolve.
Manufactured in India by:
In order to reconstitute the product, ensure the
TAJ PHARMACEUTICALS LTD.
powder, solutions and equipment are at room
Mumbai, India
temperature, add 5 (25) ml to the 10 (50) mg vial Survey No.188/1 to 189/1,190/1 to 4,
and shake for at least 60 seconds and leave to Athiyawad, Dabhel,
stand at room temperature for at least 5 minutes Daman- 396210 (INDIA)
before administration to get a clear red mobile
liquid. If gelatinous fragments are seen, leave
the solution to stand for 5 minutes and shake
Doxorubin 10 mg, 50mg powder for solution for Injection. SMPC, Taj Pharma ceuti cals
DOXORUBIN Taj P harma : Uses, Side E ffects, I nteractions, Pict ures, War nings, D OXORU BIN D osage & Rx Info | DOX ORUBI N Use s, Side Effe ct s -: I ndicati ons, Side E ffects, Warnings, DOXO RUBI N - Drug Infor mation - Taj Phar ma, DOXORU BIN dose Taj pharma ceuti cals DOXORU BIN intera ctions, Taj P ha rmace utical DOXORU BIN contraindi cations, DOXORUBIN price, DOX ORUBIN Taj Phar ma Cancer, oncologyDoxorubin 10 mg, 50mg powder for solution for Injection. SMPC- Taj Phar ma . Stay connecte d to all update d on D OX ORUBI N Taj Phar mace uticals Taj pharma ceutical s Hyderaba d.