Topotecan Teva

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

  



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1. NAME OF THE MEDICINAL PRODUCT 
 
Topotecan Teva 1 mg/1 ml concentrate for solution for infusion 
Topotecan Teva 4 mg/4 ml concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Topotecan Teva 1 mg/1 ml concentrate for solution for infusion 
1 ml of concentrate for solution for infusion contains 1 mg topotecan (as hydrochloride). 
 
Topotecan Teva 4 mg/4 ml concentrate for solution for infusion 
1 ml of concentrate for solution for infusion contains 1 mg topotecan (as hydrochloride). 
One vial of 4 ml of concentrate for solution for infusion contains 4 mg topotecan (as hydrochloride). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Concentrate for solution for infusion. 
 
Clear pale yellow liquid. pH = 2.0-2.6. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Topotecan monotherapy is indicated for the treatment of: 
 patients with metastatic carcinoma of the ovary after failure of first line or subsequent therapy. 
 patients with relapsed small cell lung cancer (SCLC) for whom re-treatment with the 

first-line regimen is not considered appropriate (see section 5.1).  
 
Topotecan in combination with cisplatin is indicated for patients with carcinoma of the cervix 
recurrent after radiotherapy and for patients with Stage IVB disease. Patients with prior 
exposure to cisplatin require a sustained treatment free interval to justify treatment with the 
combination (see section 5.1).  
 
4.2 Posology and method of administration 
 
The use of topotecan should be confined to units specialised in the administration of cytotoxic 
chemotherapy and should only be administered under the supervision of a physician 
experienced in the use of chemotherapy (see section 6.6).  
 
Posology 
 
When topotecan is used in combination with cisplatin, the full prescribing information for 
cisplatin should be consulted.  
 
Prior to administration of the first course of topotecan, patients must have a baseline neutrophil 
count of ≥ 1.5 x 109/l, a platelet count of ≥ 100 x 109/l and a haemoglobin level of ≥ 9 g/dl (after 
transfusion if necessary).  
 
Ovarian and small cell lung carcinoma 
Initial dose 



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The recommended dose of topotecan is 1.5 mg/m2 body surface area per day administered by 
intravenous infusion over 30 minutes daily for five consecutive days with a three week interval 
between the start of each course. If well tolerated, treatment may continue until disease progression 
(see sections 4.8 and 5.1).  
 
Subsequent doses 
Topotecan should not be re-administered unless the neutrophil count is ≥ 1 x 109/l, the platelet 
count is ≥ 100 x 109/l, and the haemoglobin level is ≥ 9 g/dl (after transfusion if necessary).  
 
Standard oncology practice for the management of neutropenia is either to administer topotecan 
with other medicinal products (e.g. G-CSF) or to reduce the dose to maintain neutrophil counts. 
 
If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count 
< 0.5 x 109/l) for seven days or more, or severe neutropenia associated with fever or infection, 
or who have had treatment delayed due to neutropenia, the dose should be reduced by 
0.25 mg/m2/day to 1.25 mg/m2/day (or subsequently down to 1.0 mg/m2/day if necessary). 
 
Doses should be similarly reduced if the platelet count falls below 25 x 109/l. In clinical studies, 
topotecan was discontinued if the dose had been reduced to 1.0 mg/m2/day and a further dose 
reduction was required to manage adverse effects.  
 
Cervical carcinoma 
Initial dose 
The recommended dose of topotecan is 0.75 mg/m2/day administered as a 30-minute 
intravenous infusion on days 1, 2 and 3. Cisplatin is administered as an intravenous infusion on 
day 1 at a dose of 50 mg/m2/day and following the topotecan dose. This treatment schedule is 
repeated every 21 days for six courses or until progressive disease.  
 
Subsequent doses 
Topotecan should not be re-administered unless the neutrophil count is ≥ 1.5 x 109/l, the platelet 
count is ≥100 x 109/l, and the haemoglobin level is ≥ 9 g/dl (after transfusion if necessary).  
 
Standard oncology practice for the management of neutropenia is either to administer topotecan 
with other medicinal products (e.g. G-CSF) or to reduce the dose to maintain neutrophil counts.   
 
If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count 
< 0.5 x 109/l) for seven days or more, or severe neutropenia associated with fever or infection or 
who have had treatment delayed due to neutropenia, the dose should be reduced by 20% to 
0.60 mg/m2/day for subsequent courses (or subsequently down to 0.45 mg/m2/day if necessary). 
 
Doses should be similarly reduced if the platelet count falls below 25 x 109/l.  
 
Special populations 
Patients with renal impairment 
Monotherapy (ovarian and small cell lung carcinoma) 
There is insufficient experience with the use of topotecan in patients with severely impaired 
renal function (creatinine clearance <20 ml/min). Use of topotecan in this group of patients is 
not recommended (see section 4.4). 
Limited data indicate that the dose should be reduced in patients with moderate renal 
impairment. The recommended monotherapy dose of topotecan in patients with ovarian or small 
cell lung carcinoma and a creatinine clearance between 20 and 39 ml/min is 0.75 mg/m2/day for 
five consecutive days.  
 
Combination therapy (cervical carcinoma) 
In clinical studies with topotecan in combination with cisplatin for the treatment of cervical 
cancer, therapy was only initiated in patients with serum creatinine less than or equal to 
1.5 mg/dl. If, during topotecan/cisplatin combination therapy serum creatinine exceeds 



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1.5 mg/dl, it is recommended that the full prescribing information be consulted for any advice 
on cisplatin dose reduction/continuation. If cisplatin is discontinued, there are insufficient data 
regarding continuing monotherapy with topotecan in patients with cervical cancer.  
 
Patients with hepatic impairment 
A small number of hepatically impaired patients (serum bilirubin between 1.5 and 10 mg/dl) were 
given intravenous topotecan at 1.5 mg/m2/day for five days every three weeks. A reduction in 
topotecan clearance was observed. However, there are insufficient data available to make a dose 
recommendation for this patient group (see section 4.4). 
 
There is insufficient experience with the use of topotecan in patients with severely impaired hepatic 
function (serum bilirubin ≥ 10 mg/dl) due to cirrhosis. Topotecan is not recommended to be used in 
this patient group (see section 4.4). 
 
Paediatric population 
Currently available data are described in sections 5.1 and 5.2 but no recommendation on a posology 
can be made. 
 
 
Method of administration 
 
 
Topotecan must be further diluted before use (see section 6.6). 
 
4.3 Contraindications 
 
- Severe hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
- Breast-feeding (see section 4.6). 
- Severe bone marrow depression prior to starting first course, as evidenced by baseline 

neutrophils < 1.5 x 109/l and/or a platelet count of < 100 x 109/l.  
 
4.4 Special warnings and precautions for use 
 
Haematological toxicity is dose-related and full blood count including platelets should be determined 
regularly (see section 4.2). 
 
As with other cytotoxic medicinal products, topotecan can cause severe myelosuppression. 
Myelosuppression leading to sepsis and fatalities due to sepsis have been reported in patients 
treated with topotecan (see section 4.8). 
 
Topotecan-induced neutropenia can cause neutropenic colitis. Fatalities due to neutropenic 
colitis have been reported in clinical studies with topotecan. In patients presenting with fever, 
neutropenia, and a compatible pattern of abdominal pain, the possibility of neutropenic colitis 
should be considered.  
 
Topotecan has been associated with reports of interstitial lung disease (ILD), some of which 
have been fatal (see section 4.8). Underlying risk factors include history of ILD, pulmonary 
fibrosis, lung cancer, thoracic exposure to radiation and use of pneumotoxic substances and/or 
colony stimulating factors. Patients should be monitored for pulmonary symptoms indicative of 
ILD (e.g. cough, fever, dyspnoea and/or hypoxia), and topotecan should be discontinued if a 
new diagnosis of ILD is confirmed. 
 
Topotecan monotherapy and topotecan in combination with cisplatin are commonly associated 
with clinically relevant thrombocytopenia. This should be taken into account when prescribing 
Topotecan Teva, e.g. if patients at increased risk of tumour bleeds are considered for therapy.  
 



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As would be expected, patients with poor performance status (PS>1) have a lower response rate 
and an increased incidence of complications such as fever, infection and sepsis (see section 4.8). 
Accurate assessment of performance status at the time therapy is given is important, to ensure 
that patients have not deteriorated to PS 3.  
 
There is insufficient experience of the use of topotecan in patients with severely impaired renal 
function (creatinine clearance < 20 ml/min) or severely impaired hepatic function (serum 
bilirubin ≥ 10 mg/dl) due to cirrhosis. Use of topotecan in these patient groups is not 
recommended (see section 4.2). 
 
A small number of hepatically impaired patients (serum bilirubin between 1.5 and 10 mg/dl) 
were given intravenous topotecan at 1.5 mg/m2/day for five days every three weeks. A reduction 
in topotecan clearance was observed.  However there are insufficient data available to make a 
dose recommendation for this patient group (see section 4.2).  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No in vivo human pharmacokinetic interaction studies have been performed.  
 
Topotecan does not inhibit human P450 enzymes (see section 5.2). In a population study using 
the intravenous route, the co-administration of granisetron, ondansetron, morphine or 
corticosteroids did not appear to have a significant effect on the pharmacokinetics of total 
topotecan (active and inactive form). 
 
When combining topotecan with other chemotherapy agents, reduction of the doses of each 
medicinal product may be required to improve tolerability. However, when combining with 
platinum agents, there is a distinct sequence-dependent interaction depending on whether the 
platinum agent is given on day 1 or 5 of the topotecan dosing. If either cisplatin or carboplatin is 
given on day 1 of the topotecan dosing, a lower dose of each agent must be given to improve 
tolerability compared to the dose of each agent which can be given if the platinum agent is 
given on day 5 of the topotecan dosing.  
 
When topotecan (0.75 mg/m2/day for 5 consecutive days) and cisplatin (60 mg/m2/day on day 1) 
were administered in 13 patients with ovarian cancer, a slight increase in AUC (12%, n = 9) and 
Cmax (23%, n = 11) was noted on day 5. This increase is considered unlikely to be of clinical 
relevance.  
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential / Contraception in males and females 
 
Topotecan has been shown to cause embryo-foetal lethality and malformations in preclinical 
studies (see section 5.3). As with other cytotoxic medicinal products, topotecan may cause 
foetal harm and therefore women of childbearing potential should be advised to avoid becoming 
pregnant during therapy with topotecan.  
 
As with all cytotoxic chemotherapy, patients being treated with topotecan must be advised that 
they or their partner must use an effective method of contraception. 
 
Pregnancy 
 
If topotecan is used during pregnancy, or if the patient becomes pregnant during therapy with 
topotecan, the patient must be warned of the potential hazards to the foetus.  
 
Breast-feeding 
 



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Topotecan is contraindicated during breast-feeding (see section 4.3).  Although it is not known 
whether topotecan is excreted in human breast milk, breast-feeding should be discontinued at 
the start of therapy.  
 
Fertility 
 
No effects on male or female fertility have been observed in reproductive toxicity studies in rats 
(see section 5.3). However as with other cytotoxic medicinal products topotecan is genotoxic 
and effects on fertility, including male fertility, cannot be excluded. 
 
4.7 Effects on ability to drive and use machines 
 
No studies of the effects on the ability to drive and use machines have been performed. 
However, caution should be observed when driving or operating machines if fatigue and 
asthenia persist.  
 
4.8 Undesirable effects 
 
In dose-finding studies involving 523 patients with relapsed ovarian cancer and 631 patients 
with relapsed small cell lung cancer, the dose limiting toxicity of topotecan monotherapy was 
found to be haematological. Toxicity was predictable and reversible. There were no signs of 
cumulative haematological or non- haematological toxicity.  
 
The safety profile of topotecan when given in combination with cisplatin in the cervical cancer 
clinical studies is consistent with that seen with topotecan monotherapy. The overall 
haematological toxicity is lower in patients treated with topotecan in combination with cisplatin 
compared to topotecan monotherapy, but higher than with cisplatin alone.  
 
Additional adverse events were seen when topotecan was given in combination with cisplatin, 
however, these events were seen with cisplatin monotherapy and were not attributable to 
topotecan. The prescribing information for cisplatin should be consulted for a full list of adverse 
events associated with cisplatin use.  
 
The integrated safety data for topotecan monotherapy are presented below.  
 
Adverse reactions are listed below, by system organ class and absolute frequency (all reported 
events). Frequencies 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), not 
known (cannot be estimated from the available data).  
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.  
 
Infections and infestations 
Very common Infection 
Common Sepsis1 
Blood and lymphatic system disorders 
Very common Febrile neutropenia, neutropenia (see “Gastrointestinal disorders”), 

thrombocytopenia, anaemia, leucopenia 
Common Pancytopenia 
Not known Severe bleeding (associated with thrombocytopenia) 
Immune system disorders 
Common Hypersensitivity reaction including rash 
Rare Anaphylactic reaction, angioedema, urticaria 
Metabolism and nutrition disorders 
Very common Anorexia (which may be severe) 
Respiratory, thoracic and mediastinal disorders 
Rare Interstitial lung disease (some cases have been fatal) 



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Gastrointestinal disorders 
Very common Nausea, vomiting and diarrhoea (all of which may be severe), constipation, 

abdominal pain2, mucositis 
Not known Gastrointestinal perforation 
Hepatobiliary disorders 
Common Hyperbilirubinaemia 
Skin and subcutaneous tissue disorders 
Very common Alopecia 
Common Pruritus 
General disorders and administration site conditions 
Very common Pyrexia, asthenia, fatigue 
Common Malaise 
Very rare Extravasation3 
Not known Mucosal inflammation 
1 Fatalities due to sepsis have been reported in patients treated with topotecan (see section 4.4). 
2 Neutropenic colitis, including fatal neutropenic colitis, has been reported to occur as a complication 
of topotecan-induced neutropenia (see section 4.4). 
3 Reactions have been mild and have not generally required specific therapy. 
 
The adverse events listed above have the potential to occur with a higher frequency in patients 
who have a poor performance status (see section 4.4). 
 
The frequencies associated with the haematological and non-haematological adverse events 
listed below represent the adverse event reports considered to be related/possibly related to 
topotecan therapy.  
 
Haematological 
 
Neutropenia 
Severe (neutrophil count < 0.5 x 109/l) during course 1 in 55 % of patients, with duration 
≥ seven days in 20 % and overall in 77 % of patients (39 % of courses). In association with 
severe neutropenia, fever or infection occurred in 16 % of patients during course 1 and overall 
in 23 % of patients (6 % of courses). Median time to onset of severe neutropenia was nine days 
and the median duration was seven days. Severe neutropenia lasted beyond seven days in 11 % 
of courses overall. Among all patients treated in clinical studies (including both those with 
severe neutropenia and those who did not develop severe neutropenia), 11 % (4 % of courses) 
developed fever and 26 % (9 % of courses) developed infection. In addition, 5 % of all patients 
treated (1 % of courses) developed sepsis (see section 4.4).  
 
Thrombocytopenia 
Severe (platelets < 25 x 109/l) in 25 % of patients (8 % of courses); moderate (platelets between 
25.0 and 50.0 x 109/l) in 25 % of patients (15 % of courses). Median time to onset of severe 
thrombocytopenia was day 15 and the median duration was five days. Platelet transfusions were 
given in 4 % of courses. Reports of significant sequelae associated with thrombocytopenia 
including fatalities due to tumour bleeds have been infrequent.  
 
Anaemia 
Moderate to severe (Hb ≤ 8.0 g/dl) in 37 % of patients (14 % of courses). Red cell transfusions 
were given in 52 % of patients (21 % of courses).  
 
Non-haematological 
 
Frequently reported non-haematological effects were gastrointestinal, such as nausea (52 %), 
vomiting (32 %), diarrhoea (18 %), constipation (9 %) and mucositis (14 %). The incidence of 
severe (Grade 3 or 4) nausea, vomiting, diarrhoea and mucositis was 4, 3, 2 and 1 % 
respectively.  
 



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Mild abdominal pain was reported in 4 % of patients.  
 
Fatigue was observed in approximately 25 % and asthenia in 16 % of patients receiving 
topotecan. Severe (Grade 3 or 4) fatigue and asthenia both occurred with an incidence of 3 %.  
 
Total or pronounced alopecia was observed in 30 % of patients and partial alopecia in 15 % of 
patients.  
 
Other severe events that were recorded as related or possibly related to topotecan treatment were 
anorexia (12 %), malaise (3 %) and hyperbilirubinaemia (1 %).  
 
Hypersensitivity reactions including rash, urticaria, angioedema and anaphylactic reactions have been 
reported rarely. In clinical studies, rash was reported in 4 % of patients and pruritus in 1.5 % of 
patients.  
 
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 national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Overdoses have been reported in patients being treated with intravenous topotecan (up to 10 fold of 
the recommended dose) and topotecan capsules (up to 5 fold of the recommended dose). The signs and 
symptoms observed following overdose were consistent with the known undesirable events associated 
with topotecan (see section 4.8). The primary complications of overdose are bone marrow suppression 
and mucositis. In addition, elevated hepatic enzymes have been reported with intravenous topotecan 
overdose. 
 
There is no known antidote for topotecan overdose. Further management should be as clinically 
indicated or as recommended by the national poisons centre, where available. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: antineoplastic agents, other antineoplastic agents, ATC code: L01XX17. 
 
Mechanism of action 
 
The anti-tumour activity of topotecan involves the inhibition of topoisomerase-I, an enzyme 
intimately involved in DNA replication as it relieves the torsional strain introduced ahead of the 
moving replication fork. Topotecan inhibits topoisomerase-I by stabilising the covalent complex 
of enzyme and strand-cleaved DNA which is an intermediate of the catalytic mechanism. The 
cellular sequela of inhibition of topoisomerase-I by topotecan is the induction of protein-
associated DNA single-strand breaks.  
 
Clinical efficacy and safety 
 
Relapsed ovarian cancer 
In a comparative study of topotecan and paclitaxel in patients previously treated for ovarian 
carcinoma with platinum based chemotherapy (n = 112 and 114, respectively), the response rate 
(95 % CI) was 20.5 % (13 %, 28 %) versus 14 % (8 %, 20 %) and median time to progression 
19 weeks versus 15 weeks (hazard ratio 0.7 [0.6, 1.0]),  for topotecan and paclitaxel, 



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respectively. Median overall survival was 62 weeks for topotecan versus 53 weeks for paclitaxel 
(hazard ratio 0.9 [0.6, 1.3]).  
 
The response rate in the whole ovarian carcinoma programme (n = 392, all previously treated 
with cisplatin or cisplatin and paclitaxel) was 16 %. The median time to response in clinical 
studies was 7.6-11.6 weeks. In patients refractory to, or relapsing within 3 months after cisplatin 
therapy (n = 186), the response rate was 10%.  
 
These data should be evaluated in the context of the overall safety profile of the medicinal 
product, in particular of the significant haematological toxicity (see section 4.8).  
 
A supplementary retrospective analysis was conducted on data from 523 patients with relapsed 
ovarian cancer. Overall, 87 complete and partial responses were observed, with 13 of these 
occurring during cycles 5 and 6 and 3 occurring thereafter. Of the patients who received more 
than 6 cycles of therapy, 91 % completed the study as planned or were treated until disease 
progression with only 3 % withdrawn for adverse events.  
 
Relapsed SCLC 
A Phase III study (Study 478) compared oral topotecan plus best supportive care (BSC) (n=71) with 
BSC alone (n=70) in patients who had relapsed following first line therapy (median time to 
progression [TTP] from first-line therapy: 84 days for oral topotecan plus BSC, 90 days for BSC 
alone) and for whom re-treatment with intravenous chemotherapy was not considered appropriate. In 
the oral topotecan plus BSC group there was a statistically significant improvement in overall survival 
compared with the BSC alone group (Log- rank p = 0.0104). The unadjusted hazard ratio for the oral 
topotecan plus BSC group relative to the BSC alone group was 0.64 (95 % CI: 0.45, 0.90). Median 
survival in patients treated with oral topotecan plus BSC was 25.9 weeks (95 % CI 18.3, 31.6) 
compared to 13.9 weeks (95 % CI 11.1, 18.6) for patients receiving BSC alone (p = 0.0104). 
 
Patient self-reports of symptoms using an unblinded assessment showed a consistent trend for 
symptom benefit for oral topotecan plus BSC. 
 
One Phase II study (Study 065) and one Phase III study (Study 396) were conducted to evaluate the 
efficacy of oral topotecan versus intravenous topotecan in patients who had relapsed ≥ 90 days after 
completion of one prior regimen of chemotherapy (see Table 1). Oral and intravenous topotecan were 
associated with similar symptom palliation in patients with relapsed sensitive SCLC in patient self 
reports on an unblinded symptom scale assessment in each of these two studies. 
 
Table 1. Summary of survival, response rate, and time to progression in SCLC patients treated 
with oral or intravenous topotecan 
 
 Study 065 Study 396 

Oral 
topotecan 

Intravenous 
topotecan 

Oral topotecan Intravenous 
topotecan 

(N = 52) (N = 54) (N = 153) (N = 151) 
Median survival (weeks)  
      (95% CI) 

32.3 
(26.3, 40.9) 

25.1 
(21.1, 33.0) 

33.0 
(29.1, 42.4) 

35.0 
(31.0, 37.1) 

      Hazard ratio (95% CI) 0.88 (0.59, 1.31) 0.88 (0.7, 1.11) 
Response rate (%) 
      (95% CI) 

23.1 
(11.6, 34.5) 

14.8 
(5.3, 24.3) 

18.3 
(12.2, 24.4) 

21.9 
(15.3, 28.5) 

Difference in response 
rate 
(95% CI) 

8.3 (-6.6, 23.1) -3.6 (-12.6, 5.5) 

Median time to 
progression (weeks) 
      (95% CI) 

14.9 
 

(8.3, 21.3) 

13.1 
 

(11.6, 18.3) 

11.9 
 

(9.7, 14.1) 

14.6 
 

(13.3, 18.9) 
      Hazard ratio (95% CI) 0.90 (0.60, 1.35) 1.21 (0.96, 1.53) 



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N = total number of patients treated. 
CI = confidence interval. 
 
In another randomised Phase III study which compared intravenous (IV) topotecan to 
cyclophosphamide, doxorubicin and vincristine (CAV) in patients with relapsed, sensitive 
SCLC, the overall response rate was 24.3 % for topotecan compared to 18.3 % for the CAV 
group. Median time to progression was similar in the two  groups (13.3 weeks and 12.3 weeks 
respectively). Median survivals for the two groups were 25.0 and 24.7 weeks respectively. The 
hazard ratio for survival with IV topotecan relative to CAV was 1.04 (95 %   CI 0.78 – 1.40).  
 
The response rate to topotecan in the combined small cell lung cancer programme (n=480) for 
patients with relapsed disease sensitive to first-line therapy, was 20.2 %. Median survival was 
30.3 weeks (95 % CI: 27.6, 33.4). 
 
In a population of patients with refractory SCLC (those not responding to first line therapy), the 
response rate to topotecan was 4.0 %.  
 
Cervical carcinoma 
In a randomised, comparative Phase III study conducted by the Gynecologic Oncology Group 
(GOG 0179), topotecan plus cisplatin (n = 147) was compared with cisplatin alone (n = 146) for 
the treatment of histologically confirmed persistent, recurrent or Stage IVB carcinoma of the 
cervix where curative treatment with surgery and/or radiation was not considered appropriate. 
Topotecan plus cisplatin had a statistically significant benefit in overall survival relative to 
cisplatin monotherapy after adjusting for interim analyses (Log-rank p = 0.033). 
 
 

Study results Study GOG-0179 
 

ITT population 
 Cisplatin 

50 mg/m2 on 
day 1, every 

21 days 

Cisplatin 
50 mg/m2 on day 1 + 

Topotecan  
0.75 mg/m2 on 
days 1–3, every 

21 days 
Survival (months) (n = 146) (n = 147) 
Median (95% CI) 6.5 (5.8, 8.8) 9.4 (7.9, 11.9) 
Hazard ratio (95% CI) 0.76 (0.59, 0.98) 
Log rank p-value 0.033 
  

Patients without prior cisplatin chemoradiotherapy 
 Cisplatin Topotecan/Cisplatin 

Survival (months) (n = 46) (n = 44) 
Median (95% CI) 8.8 (6.4, 11.5) 15.7 (11.9, 17.7) 
Hazard ratio (95% CI) 0.51 (0.31, 0.82) 
  

Patients with prior cisplatin chemoradiotherapy 
 Cisplatin Topotecan/Cisplatin 

Survival (months) (n = 72) (n = 69) 
Median (95% CI) 5.9 (4.7, 8.8) 7.9 (5.5, 10.9) 
Hazard ratio (95% CI) 0.85 (0.59, 1.21) 

 
In patients (n = 39) with recurrence within 180 days after chemoradiotherapy with cisplatin, the 
median survival in the topotecan plus cisplatin arm was 4.6 months (95 % CI: 2,6, 6.1) versus 
4.5 months (95 % CI: 2.9, 9.6) for the cisplatin arm with a hazard ratio of 1.15 (0.59, 2.23). In those 



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patients (n = 102) with recurrence after 180 days, median survival in the topotecan plus cisplatin arm 
was 9.9 months (95 % CI: 7, 12.6) versus 6.3 months (95 % CI: 4.9, 9.5) for the cisplatin arm with a 
hazard ratio of 0.75 (0.49, 1.16).  
 
Paediatric population 
Topotecan was also evaluated in the paediatric population; however, only limited data on 
efficacy and safety are available.  
 
In an open-label study involving children (n = 108, age range: infant to 16 years) with recurrent 
or progressive solid tumours, topotecan, was administered at a starting dose of 2.0 mg/m2 given 
as a 30- minute infusion for 5 days repeated every 3 weeks for up to one year depending on 
response to therapy. Tumour types included were Ewing’s sarcoma/primitive neuroectodermal 
tumour, neuroblastoma, osteoblastoma, and rhabdomyosarcoma. Anti-tumour activity was 
demonstrated primarily in patients with neuroblastoma. Toxicities of topotecan in paediatric 
patients with recurrent and refractory solid tumours were similar to those historically seen in 
adult patients. In this study, forty-six (43 %) patients received G-CSF over 192 (42.1 %) 
courses; sixty-five (60 %) received transfusions of packed red blood cells and fifty (46 %) of 
platelets over 139 and 159 courses (30.5 % and 34.9 %), respectively. Based on the dose-
limiting toxicity of myelosuppression, the maximum tolerated dose (MTD) was established at 
2.0 mg/m2/day with G-CSF and 1.4 mg/m2/day without G-CSF in a pharmacokinetic study in 
paediatric patients with refractory solid tumours (see section 5.2).  
 
5.2 Pharmacokinetic properties 
 
Distribution 
 
Following intravenous administration of topotecan at doses of 0.5 to 1.5 mg/m2 as a 30 minute 
infusion daily for five days, topotecan demonstrated a high plasma clearance of 62 l/h (SD 22), 
corresponding to approximately 2/3 of liver blood flow. Topotecan also had a high volume of 
distribution, about 132 1 (SD 57), and a relatively short half-life of 2-3 hours. Comparison of 
pharmacokinetic parameters did not suggest any change in pharmacokinetics over the 5 days of  
dosing. Area under the curve increased approximately in proportion to the increase in dose. 
There is little or no accumulation of topotecan with repeated daily dosing and there is no 
evidence of a change in the pharmacokinetics after multiple doses. Preclinical studies indicate 
plasma protein binding of topotecan is low (35 %) and distribution between blood cells and 
plasma was fairly homogeneous. 
 
Biotransformation 
 
The elimination of topotecan has only been partly investigated in man. A major route of 
clearance of topotecan was by hydrolysis of the lactone ring to form the ring-opened 
carboxylate.  
 
Metabolism accounts for <10 % of the elimination of topotecan. An N-desmethyl metabolite, 
which was shown to have similar or less activity than the parent in a cell-based assay, was 
found in urine, plasma, and faeces. The mean metabolite: parent AUC ratio was < 10% for both 
total topotecan and topotecan lactone. An O-glucuronidation metabolite of topotecan and N-
desmethyl topotecan has been identified in the urine.  
 
Elimination 
 
Overall recovery of topotecan-related material following five daily doses of topotecan was 71 to 
76 % of the administered IV dose. Approximately 51 % was excreted as total topotecan and 3% 
was excreted as N-desmethyl topotecan in the urine. Faecal elimination of total topotecan 
accounted for 18% while faecal elimination of N-desmethyl topotecan was 1.7 %. Overall, the 
N-desmethyl metabolite contributed a mean of less than 7% (range 4-9%) of the total topotecan-



12 

related material accounted for in the urine and faeces. The topotecan-O-glucuronide and 
N-desmethyl topotecan-O-glucuronide in the urine were less than 2.0%.  
 
In vitro data using human liver microsomes indicate the formation of small amounts of 
N-demethylated topotecan. In vitro, topotecan did not inhibit human P450 enzymes CYP1A2, 
CYP2A6, CYP2C8/9, CYP2C19, CYP2D6, CYP2E, CYP3A or CYP4A, nor did it inhibit the 
human cytosolic enzymes dihydropyrimidine or xanthine oxidase.  
 
When given in combination with cisplatin (cisplatin day 1, topotecan days 1 to 5), the clearance 
of topotecan was reduced on day 5 compared to day 1 (19.1 l/h/m2 compared to 
21.3 l/h/m2 [n = 9]) (see section 4.5). 
 
Special populations 
 
Hepatic impairment 
Plasma clearance in patients with hepatic impairment (serum bilirubin between 1.5 and 
10 mg/dl) decreased to about 67 % when compared with a control group of patients. Topotecan 
half-life was increased by about 30% but no clear change in volume of distribution was 
observed. Plasma clearance of total topotecan (active and inactive form) in patients with hepatic 
impairment only decreased by about 10 % compared with the control group of patients.  
 
Renal impairment 
Plasma clearance in patients with renal impairment (creatinine clearance 41-60 ml/min.) 
decreased to about 67 % compared with control patients. Volume of distribution was slightly 
decreased and thus half-life only increased by 14 %. In patients with moderate renal impairment 
topotecan plasma clearance was reduced to 34 % of the value in control patients. Mean half-life 
increased from 1.9 hours to 4.9 hours.  
 
Age/weight 
In a population study, a number of factors including age, weight and ascites had no significant 
effect on clearance of total topotecan (active and inactive form).  
 
Paediatric population 
The pharmacokinetics of topotecan given as a 30-minute infusion for 5 days were evaluated in 
two studies. One study included a dose range of 1.4 to 2.4 mg/m2 in children (aged 2 up to 12 
years, n = 18), adolescents (aged 12 up to 16 years, n = 9) and young adults (aged 16 to 21 
years, n = 9) with refractory solid tumours. The second study included a dose range of 2.0 to 
5.2 mg/m2 in children (n = 8), adolescents (n = 3) and young adults (n = 3) with leukaemia. In 
these studies, there were no apparent differences in the pharmacokinetics of topotecan among 
children, adolescents, and young adult patients with solid tumours or leukaemia, but data are too 
limited to draw definite conclusions.  
 
5.3 Preclinical safety data 
 
Resulting from its mechanism of action, topotecan is genotoxic to mammalian cells (mouse lymphoma 
cells and human lymphocytes) in vitro and mouse bone marrow cells in vivo. Topotecan was also 
shown to cause embryo-foetal lethality when given to rats and rabbits.  
 
In reproductive toxicity studies with topotecan in rats there was no effect on male or female fertility; 
however, in females super-ovulation and slightly increased pre-implantation loss were observed. 
 
The carcinogenic potential of topotecan has not been studied.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 



13 

6.1 List of excipients 
 
Tartaric acid  (E334) 
Hydrochloric acid (E507) (for pH adjustment) 
Sodium hydroxide (E524) (for pH adjustment) 
Water for injections 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
Vial before opening 
30 months. 
 
Diluted solution 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user and 
would normally not be longer than 12 hours if stored below 25°C or 24 hours at 2-8°C, unless dilution 
has taken place in controlled and validated aseptic conditions.  
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C-8°C). Do not freeze. 
Keep the vial in the outer carton in order to protect from light.  
 
For storage conditions of the diluted medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Colourless, type I glass vial with bromobutyl rubber stopper, aluminium seal and polypropylene snap-
cap containing 1 ml or 4 ml of concentrate. 
 
Topotecan Teva is available in cartons containing 1 vial and 5 vials. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
General precautions 
The normal procedures for proper handling and disposal of anticancer medicinal products 
should be adopted, namely: 
- Personnel should be trained to dilute the medicinal product. 
- Pregnant staff should be excluded from working with this medicinal product.  
- Personnel handling this medicinal product during dilution should wear protective clothing 

including mask, goggles and gloves. 
- Accidental contact with the skin or eyes should be treated immediately with copious amounts of 

water.  
- All items for administration or cleaning, including gloves, should be placed in high-risk, 

waste disposal bags for high-temperature incineration. Liquid waste may be flushed with 
large amounts of water.  

 
Instructions for dilution 
The concentrate is pale yellow in colour and contains 1 mg per ml of topotecan. Futher dilution of the 
appropriate volume of the concentrate with either sodium chloride 9 mg/ml (0.9%) solution for 



14 

injection or glucose 50 mg/ml (5%) solution for injection to reach a final topotecan concentration of 
between 25 and 50 microgram/ml in the solution for infusion. 
 
Disposal 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
7. MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Topotecan Teva 1 mg/1 ml concentrate for solution for infusion 
EU/1/09/552/001- 1vial 
EU/1/09/552/002- 5 vials 
 
Topotecan Teva 4 mg/4 ml concentrate for solution for infusion 
EU/1/09/552/003- 1 vial 
EU/1/09/552/004- 5 vials 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21 September 2009 
Date of latest renewal: 19 June 2014 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMA) http://www.ema.europa.eu/. 
 
  



15 

 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



16 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
Pharmachemie B.V. 
Swensweg 5 
NL-2031 GA Haarlem 
The Netherlands 
 
TEVA Pharmaceutical Works Private Limited Company 
Táncsics Mihály út 82  
H-2100 Gödöllő 
Hungary 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 
Characteristics, Section 4.2). 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic Safety Update Reports 
  
The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 

 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 
 
Not applicable.  
 
  



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



19 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Topotecan Teva 1 mg/1 ml concentrate for solution for infusion 
topotecan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml of concentrate for solution for infusion contains 1 mg topotecan (as hydrochloride). 
Each vial contains 1 mg topotecan (as hydrochloride) in 1 ml concentrate. 
 
 
3. LIST OF EXCIPIENTS 
 
tartaric acid (E334), hydrochloric acid (E507) (for pH adjustment), sodium hydroxide (E524) (for pH 
adjustment) and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
 
1 vial of 1 ml (1 mg topotecan) 
5 vials of 1 ml (1 mg topotecan) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use, after dilution. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
CYTOTOXIC, special handling instructions (see package leaflet). 
 
 
8. EXPIRY DATE 
 
EXP 
Read the leaflet for the shelf life of the diluted product. 
 
 
9. SPECIAL STORAGE CONDITIONS 



20 

 
Store in a refrigerator. Do not freeze.  
Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/552/001 – 1 vial 
EU/1/09/552/002 – 5 vials  
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



21 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial Label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Topotecan Teva 1 mg/1 ml concentrate for solution for infusion 
topotecan 
IV use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml  
 
 
6. OTHER 
 
Cytotoxic  



22 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Topotecan Teva 4 mg/4 ml concentrate for solution for infusion 
topotecan 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml of concentrate for solution for infusion contains 1 mg topotecan (as hydrochloride). 
Each vial contains 4 mg topotecan (as hydrochloride) in 4 ml concentrate. 
 
 
3. LIST OF EXCIPIENTS 
 
tartaric acid (E334), hydrochloric acid (E507) (for pH adjustment), sodium hydroxide (E524) (for pH 
adjustment) and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Concentrate for solution for infusion 
 
1 vial of 4 ml (4 mg topotecan) 
5 vials of 4 ml (4 mg topotecan) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intravenous use, after dilution. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
CYTOTOXIC, special handling instructions (see package leaflet). 
 
 
8. EXPIRY DATE 
 
EXP 
Read the leaflet for the shelf life of the diluted product. 
 
 
9. SPECIAL STORAGE CONDITIONS 



23 

 
Store in a refrigerator. Do not freeze.  
Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
Any unused product or waste material should be disposed of in accordance with local requirements. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 
 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/552/003 – 1 vial 
EU/1/09/552/004 – 5 vials  
 
 
13. BATCH NUMBER 
 
Batch 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN:  



24 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial Label 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Topotecan Teva 4 mg/4 ml concentrate for solution for infusion 
topotecan 
IV use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Batch 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
4 ml  
 
 
6. OTHER 
 
Cytotoxic  



25 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



26 

Package leaflet: Information for the user 
 

Topotecan Teva 1 mg/1 ml concentrate for solution for infusion 
topotecan 

 
Read all of this leaflet carefully before you start using 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 nurse. 
- If  you get any side effects talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
1. What Topotecan Teva is and what it is used for 
2. What you need to know before you use Toptecan Teva 
3. How to use Topotecan Teva 
4. Possible side effects 
5. How to store Topotecan Teva 
6. Contents of the pack and other information 
 
 
1. What Topotecan Teva is and what it is used for 
 
Topotecan Teva helps to kill tumour cells.  
 
Topotecan Teva is used to treat: 
- ovarian cancer or small cell lung cancer that has come back after chemotherapy 
- advanced cervical cancer if surgery or radiotherapy treatment is not possible. When treating 

cervical cancer, Topotecan Teva is combined with another medicine called cisplatin. 
 
 
2. What you need to know before you use Topotecan Teva 
 
Do not use Topotecan Teva: 
- if you are allergic to topotecan or any of the other ingredients of this medicine (listed in section 

6);  
- if you are breast-feeding; 
- if your blood cells count is too low. Your doctor will tell you whether this is the case, based on 

the results of your last blood test;  
→Tell your doctor if you think any of these could apply to you.  
 
Warnings and precautions 
Talk to your doctor or nurse before using Topotecan Teva:  
- if you have any kidney problems. Your dose of Topotecan Teva may need to be adjusted. The 

use of Topotecan Teva is not recommended in patients with severe renal impairment; 
- if you have liver problems. Your dose of Topotecan Teva may need to be adjusted. The use of 

Topotecan Teva is not recommended in patients with severe liver impairment; 
- if you currently have lung problems, or if you have received previous radiation treatment or 

medicines that affected your lungs (also see section 4 ‘Possible side effects’); 
- if you suffer from unusual bruising or bleeding (also see section 4 ‘Possible side effects’); 
- if you are feeling very ill. 
 
Other medicines and Topotecan Teva 
Tell your doctor if you are taking, have recently taken or might take any other medicines.  
 
Pregnancy and breast-feeding 



27 

Topotecan Teva should not be used in pregnant women, unless clearly necessary. If you are or think 
you might be pregnant, tell your doctor immediately. 
 
Women of child-bearing potential should use effective contraception to avoid becoming pregnant 
while on treatment.  
 
Male patients who may wish to father a child should ask their doctor for family planning advice or 
treatment.  
 
You must not breast-feed while on treatment with Topotecan Teva.  
 
Driving and using machines 
Topotecan Teva can make you feel tired or weak.  
If you experience this, do not drive or use machines.  
 
Topotecan Teva contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-
free’. 
 
3. How to use Topotecan Teva 
 
Your dose of Topotecan Teva will depend on: 
- the disease being treated  
- your body surface area (m2) 
- the results of blood tests carried out before and during treatment 
- how well you tolerate treatment.  
 
Ovarian and small cell lung cancer 
The usual dose is 1.5 mg per m2 of body surface area once daily for 5 days. This treatment cycle will 
normally be repeated every three weeks. 
  
Cervical cancer 
The usual dose is 0.75 mg per m2 of body surface area once daily for 3 days. This treatment cycle will 
normally be repeated every three weeks. 
 
For cervical cancer it will be used together with another anticancer medicine containing cisplatin. For 
more information about cisplatin, please refer to the corresponding Package Leaflet.  
 
The experience in children is limited and treatment is therefore not recommended. 
 
How Topotecan Teva is prepared 
Topotecan Teva is supplied as a concentrate for solution for infusion. The concentrate must be diluted 
before administration. 
 
How Topotecan Teva is given 
A doctor or nurse will give you the diluted Topotecan Teva solution as an infusion (a drip) usually into 
your arm over about 30 minutes.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
You must tell your doctor immediately if you experience any of the following serious side effects. 
They may require hospitalisation and could even be life threatening. 
• Infections (very common (may affect more than 1 in 10 people)), with signs such as: 



28 

- fever 
- serious decline of your general condition 
- local symptoms such as sore throat or burning sensation when urinating 
- severe stomach pain, fever and possibly diarrhoea (rarely with blood) can be signs of 

bowel inflammation (neutropenic colitis). 
Topotecan Teva may reduce your ability to fight infections. 
 
• Lung inflammation (rare (may affect up to 1 in 1,000 people)), with signs such as: 

- difficulty breathing,  
- cough 
- fever. 

The risk of developing this severe condition (interstitial lung disease) is higher if you currently have 
lung problems, or if you have received previous radiation treatment or medicines that affected your 
lungs (also see section 2 ‘What you need to know before you use Topotecan Teva’). 
 
Other side effects with Topotecan Teva include:  
Very common (may affect more than 1 in 10 people) 
- Feeling generally weak and tired, which can be symptoms of a decrease in the number of red 

blood cells (anaemia). In some cases you may need a blood transfusion. 
- Unusual bruising or bleeding, sometimes severe, caused by a decrease in the number of blood 

clotting cells (platelets).  
- Abnormally low white blood cell count (leucopenia, neutropenia) which may be accompanied 

with fever and signs of infections (febrile neutropenia).  
- Weight loss and loss of appetite (anorexia), tiredness, weakness. 
- Feeling sick (nausea), vomiting, diarrhoea, stomach pain, constipation. 
- Inflammation and ulcers of the mouth, throat, tongue or gums (mucositis). 
- Fever. 
- Hair loss. 
 
Common (may affect up to 1 in 10 people) 
- Decrease in the number of all blood cells (pancytopenia) 
- Allergic or hypersensitivity reactions (including rash). 
- Yellow skin (jaundice) caused by abnormal liver function. 
- Itching (pruritus). 
- Severe infection (sepsis). 
- Feeling unwell (malaise). 
 
Rare (may affect up to 1 in 1,000 people) 
- Severe allergic (anaphylactic) reactions causing swelling of the lips, face or neck leading to 

severe difficulty in breathing, skin rash or hives, anaphylactic shock (a severe reduction in blood 
pressure, paleness, agitation, weak pulse, decreased consciousness). 

- Sudden swelling of the skin and mucosa (e.g. throat or tongue) caused by fluid build up 
(angioedema). 

- Itchy rash (or hives). 
 
Very rare (may affect up to 1 in 10,000 people) 
- Discharge of blood into tissues (extravasation).  
 
Not known (frequency cannot be estimated from the available data) 
- Severe stomach pain, nausea, vomiting of blood, black or bloody stools (possible symptoms of 

gastrointestinal perforation). 
- Mouth sores, difficulty swallowing, abdominal pain, nausea, vomiting, diarrhoea, bloody stools 

(possible signs and symptoms of inflammation of the inner lining of the mouth, stomach and/or 
gut [mucosal inflammation]). 

 
Tell a doctor if any of these becomes troublesome. 
 



29 

If you are being treated for cervical cancer, you may get side effects from the other medicine 
(cisplatin) that you will be given along with Topotecan Teva.  
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Topotecan Teva 
 
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 and vial after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. 
 
Keep the vial in the outer carton in order to protect from light.  
 
Diluted solution 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user and 
would normally not be longer than 12 hours if stored below 25°C or 24 hours at 2-8°C, unless dilution 
has taken place in controlled and validated aseptic conditions. 
 
Do not use Topotecan Teva if you notice any visible particles or if the solution is unclear. 
 
Any unused product or waste material should be disposed of in accordance with local requirements for 
cytotoxic material. 
 
 
6. Contents of the pack and other information 
 
What Topotecan Teva contains 
 
- The active substance is topotecan hydrochloride. One vial of 1 ml of concentrate contains 1 mg 

topotecan (as hydrochloride). 
- The other ingredients are: tartaric acid (E334), hydrochloric acid (E507), sodium hydroxide 

(E524) and water for injections. 
 
What Topotecan Teva looks like and contents of the pack 
 
Topotecan Teva is a clear pale yellow liquid in a colourless glass vial with bromobutyl rubber stopper, 
aluminium seal and snap-cap. 
Each vial contains 1 ml of the concentrate for solution for infusion. Topotecan Teva is supplied in 
cartons containing 1 vial or 5 vials. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 



30 

 
Manufacturer 
 
Pharmachemie B.V. 
Swensweg 5 
2031 GA Haarlem  
The Netherlands 
 
TEVA Pharmaceutical Works Private Limited Company 
Táncsics Mihály út 82  
H-2100 Gödöllő 
Hungary 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien  
Teva Pharma Belgium N.V./S.A./A.G. 
Tel/Tél: +32 3 820 73 73  

Lietuva 
UAB “Sicor Biotech” 
Tel: +370 5 266 02 03 

 
България  
Тева Фармасютикълс България ЕООД 
Teл: +359 2 489 95 82  

 
Luxembourg/Luxemburg  
Teva Pharma Belgium N.V./S.A./A.G.  
Tél: +32 3 820 73 73 
  

 
Česká republika  
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111  

 
Magyarország  
Teva Gyógyszergyár Zrt  
Tel.: +36 1 288 64 00 

 
Danmark  
Teva Denmark A/S  
Tlf: +45 44 98 55 11  

 
Malta  
Teva Pharmaceuticals Ireland 
L-Irlanda  
Tel: +353 51 321740 

 
Deutschland 
Teva GmbH 
Tel:  +49 731 402 08 

 
Nederland  
Teva Nederland B.V. 
Tel: +31 800 0228 400 

 
Eesti 
Teva Eesti esindus UAB Sicor Biotech 
Eesti filiaal 
Tel: +372 661 0801 

 
Norge 
Teva Norway AS 
Tlf: +47 6677 55 90 

 
Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

 
Österreich 
ratiopharm Arzneimittel Vertriebs GmbH 
Tel: +43 1 97007 0 

 
España 
Teva Pharma S.L.U. 
Tél: +34 91 387 32 80   

 
Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48 22 345 93 00 
 

 
France 
Teva Santé 
Tél: +33 1 55 91 7800 

Portugal 
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: +351 21 476 75 50 



31 

 
Hrvatska 
Pliva Hrvatska d.o.o 
Tel: + 385 1 37 20 000 

 
România 
Teva Pharmaceuticals S.R.L 
Tel: +4021 230 6524 

 
Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 51 321 740 

 
Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 

 
Ísland 
ratiopharm Oy 
Puh/Tel: +358 20 180 5900 

 
Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +421 2 5726 7911 

 
Italia 
Teva Italia S.r.l. 
Tel: +39 028 917 981 

 
Suomi/Finland 
ratiopharm Oy 
Puh/Tel: +358 20 180 5900 

 
Κύπρος 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

 
Sverige 
Teva Sweden AB 
Tel: +46 42 12 11 00 

 
Latvija 
UAB Sicor Biotech filiāle Latvijā  
Tel: +371 67 323 666 

 
United Kingdom 
Teva UK Limited 
Tel: +44 1977 628 500 
 

 
This leaflet was last revised in MM/YYYY. 
 
Detailed information on this medicine is available on the website of the European Medicines Agency 
(EMA) http://www.ema.europa.eu/. 
 
The following information is intended for healthcare professionals only: 
 
Instructions on how to dilute, store and dispose of Topotecan Teva 
 
Instructions for dilution 
The concentrate is pale yellow in colour and contains 1 mg per ml of topotecan. Futher dilution of the 
appropriate volume of the concentrate with either sodium chloride 9 mg/ml (0.9%) solution for 
injection or glucose 50 mg/ml (5%) solution for injection to reach a final topotecan concentration of 
between 25 and 50 microgram/ml in the solution for infusion. 
 
Storage of the diluted solution 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user and 
would normally not be longer than 12 hours if stored below 25°C or 24 hours at 2-8°C, unless dilution 
has taken place in controlled and validated aseptic conditions. 
 
Handling and disposal 
The normal procedures for proper handling and disposal of anticancer medicinal products should be 
adopted: 
- Staff should be trained to dilute the medicinal product. 
- Pregnant staff should be excluded from working with this medicinal product. 
- Staff handling this medicinal product during dilution should wear protective clothing including 

mask, goggles and gloves. 
- Accidental contact with the skin or eyes should be treated immediately with copious amounts of 

water. 



32 

- All items for administration or cleaning, including gloves, should be placed in high-risk, waste 
disposal bags for high-temperature incineration. 

  



33 

Package leaflet: Information for the user 
 

Topotecan Teva 4 mg/4 ml concentrate for solution for infusion 
topotecan 

 
Read all of this leaflet carefully before you start using 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 nurse. 
- If  you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
1. What Topotecan Teva is and what it is used for 
2. What you need to know before you use Toptecan Teva 
3. How to use Topotecan Teva 
4. Possible side effects 
5. How to store Topotecan Teva 
6. Contents of the pack and other information 
 
 
1. What Topotecan Teva is and what it is used for 
 
Topotecan Teva helps to kill tumour cells.  
 
Topotecan Teva is used to treat: 
- ovarian cancer or small cell lung cancer that has come back after chemotherapy 
- advanced cervical cancer if surgery or radiotherapy treatment is not possible.  When treating 

cervical cancer, Topotecan Teva is combined with another medicine called cisplatin. 
 
 
2. What you need to know before you use Topotecan Teva 
 
Do not use Topotecan Teva: 
- if you are allergic to topotecan or any of the other ingredients of  this medicine(listed in section 

6);  
- if you are breast feeding; 
- if your blood cells count is too low. Your doctor will tell you whether this is the case, based on 

the results of your last blood test; 
→Tell your doctor if you think any of these could apply to you.  
 
Warnings and precautions 
Talk to your doctor or nurse before using Topotecan Teva:  
- if you have any kidney problems. Your dose of Topotecan Teva may need to be adjusted. The 

use of Topotecan Teva is not recommended in patients with severe renal impairment; 
- if you have liver problems. Your dose of Topotecan Teva may need to be adjusted. The use of 

Topotecan Teva is not recommended in patients with severe liver impairment; 
- if you currently have lung problems, or if you have received previous radiation treatment or 

medicines that affected your lungs (also see section 4 ‘Possible side effects’); 
- if you suffer from unusual bruising or bleeding (also see section 4 ‘Possible side effects’); 
- if you are feeling very ill. 
 
Other medicines and Topotecan Teva 
Tell your doctor if you are taking, have recently taken or might take any other medicines.  
 
Pregnancy and breast-feeding 



34 

Topotecan Teva should not be used in pregnant women, unless clearly necessary. If you are or think 
you might be pregnant, tell your doctor immediately. 
 
Women of child-bearing potential should use effective contraception to avoid becoming pregnant 
while on treatment.  
 
Male patients who may wish to father a child should ask their doctor for family planning advice or 
treatment.  
 
You must not breast-feed while on treatment with Topotecan Teva.  
 
Driving and using machines 
Topotecan Teva can make you feel tired or weak.  
If you experience this, do not drive or use machines.  
 
Topotecan Teva contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-
free’. 
 
3. How to use Topotecan Teva 
 
Your dose of Topotecan Teva will depend on: 
- the disease being treated  
- your body surface area (m2) 
- the results of blood tests carried out before and during treatment 
- how well you tolerate treatment.  
 
Ovarian and small cell lung cancer 
The usual dose is 1.5 mg per m2 of body surface area once daily for 5 days. This treatment cycle will 
normally be repeated every three weeks. 
  
Cervical cancer 
The usual dose is 0.75 mg per m2 of body surface area once daily for 3 days. This treatment cycle will 
normally be repeated every three weeks. 
 
For cervical cancer it will be used together with another anticancer medicine containing cisplatin. For 
more information about cisplatin, please refer to the corresponding Package Leaflet.  
 
The experience in children is limited and treatment is therefore not recommended. 
 
How Topotecan Teva is prepared 
Topotecan Teva is supplied as a concentrate for solution for infusion. The concentrate must be diluted 
before administration. 
 
How Topotecan Teva is given 
A doctor or nurse will give you the diluted Topotecan Teva solution as an infusion (a drip) usually into 
your arm over about 30 minutes.  
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Serious side effects 
You must tell your doctor immediately if you experience any of the following serious side effects. 
They may require hospitalisation and could even be life threatening. 
 



35 

• Infections (very common (may affect more than 1 in 10 people)), with signs such as: 
- fever 
- serious decline of your general condition 
- local symptoms such as sore throat or burning sensation when urinating 
- severe stomach pain, fever and possibly diarrhoea (rarely with blood) can be signs of 

bowel inflammation (neutropenic colitis). 
Topotecan Teva may reduce your ability to fight infections. 
 
• Lung inflammation (rare (may affect up to 1 in 1,000 people)), with signs such as: 

- difficulty breathing,  
- cough 
- fever. 

The risk of developing this severe condition (interstitial lung disease) is higher if you currently have 
lung problems, or if you have received previous radiation treatment or medicines that affected your 
lungs (also see section 2 ‘What you need to know before you use Topotecan Teva’). 
 
Other side effects with Topotecan Teva include:  
Very common (may affect more than 1 in 10 people) 
- Feeling generally weak and tired, which can be symptoms of a decrease in the number of red 

blood cells (anaemia). In some cases you may need a blood transfusion. 
- Unusual bruising or bleeding, sometimes severe, caused by a decrease in the number of blood 

clotting cells (platelets).  
- Abnormally low white blood cell count (leucopenia, neutropenia) which may be accompanied 

with fever and signs of infections (febrile neutropenia). 
- Weight loss and loss of appetite (anorexia), tiredness, weakness. 
- Feeling sick (nausea), vomiting, diarrhoea, stomach pain, constipation. 
- Inflammation and ulcers of the mouth, throat, tongue or gums (mucositis). 
- Fever. 
- Hair loss. 
 
Common (may affect up to 1 in 10 people) 
- Decrease in the number of all blood cells (pancytopenia ) 
- Allergic or hypersensitivity reactions (including rash). 
- Yellow skin (jaundice) caused by abnormal liver function. 
- Itching (pruritus). 
- Severe infection (sepsis). 
- Feeling unwell (malaise). 
 
Rare (may affect up to 1 in 1,000 people) 
- Severe allergic (anaphylactic) reactions causing swelling of the lips, face or neck leading to 

severe difficulty in breathing, skin rash or hives,  anaphylactic shock (a severe reduction in 
blood pressure, paleness, agitation, weak pulse, decreased consciousness). 

- Sudden swelling of the skin and mucosa (e.g. throat or tongue) caused by fluid build up 
(angioedema). 

- Itchy rash (or hives). 
 
Very rare (may affect up to 1 in 10,000 people) 
- Discharge of blood into tissues (extravasation).  
 
Not known (frequency cannot be estimated from the available data) 
- Severe stomach pain, nausea, vomiting of blood, black or bloody stools (possible symptoms of 

gastrointestinal perforation). 
- Mouth sores, difficulty swallowing, abdominal pain, nausea, vomiting, diarrhoea, bloody stools 

(possible signs and symptoms of inflammation of the inner lining of the mouth, stomach and/or 
gut [mucosal inflammation]). 

 
Tell a doctor if any of these becomes troublesome. 



36 

 
If you are being treated for cervical cancer, you may get side effects from the other medicine 
(cisplatin) that you will be given along with Topotecan Teva.  
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V.  By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Topotecan Teva 
 
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 and vial after EXP. The 
expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. 
 
Keep the vial in the outer carton in order to protect from light.  
 
Diluted solution 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user and 
would normally not be longer than 12 hours if stored below 25°C or 24 hours at 2-8°C, unless dilution 
has taken place in controlled and validated aseptic conditions. 
 
Do not use Topotecan Teva if you notice any visible particles or if the solution is unclear. 
 
Any unused product or waste material should be disposed of in accordance with local requirements for 
cytotoxic material. 
 
6. Contents of the pack and other information 
 
What Topotecan Teva contains 
 
- The active substance is topotecan hydrochloride. One vial of 4 ml of concentrate contains 4 mg 

topotecan (as hydrochloride).  
- The other ingredients are: tartaric acid (E334), hydrochloric acid (E507), sodium hydroxide 

(E524) and water for injections. 
 
What Topotecan Teva looks like and contents of the pack 
 
Topotecan Teva is a clear pale yellow liquid in a colourless glass vial with bromobutyl rubber stopper, 
aluminium seal and snap-cap. 
Each vial contains  4 ml of the concentrate for solution for infusion. Topotecan Teva is supplied in 
cartons containing 1 vial or 5 vials. Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 



37 

 
Manufacturer 
 
Pharmachemie B.V. 
Swensweg 5 
2031 GA Haarlem  
The Netherlands 
 
TEVA Pharmaceutical Works Private Limited Company 
Táncsics Mihály út 82  
H-2100 Gödöllő 
Hungary 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien  
Teva Pharma Belgium N.V./S.A./A.G.  
Tel/Tél: +32 3 820 73 73  

Lietuva 
UAB “Sicor Biotech” 
Tel: +370 5 266 02 03 

 
България  
Тева Фармасютикълс България ЕООД 
Teл: +359 2 489 95 82  

 
Luxembourg/Luxemburg  
Teva Pharma Belgium N.V./S.A./A.G. 
Tél: +32 3 820 73 73 
  

 
Česká republika  
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111  

 
Magyarország  
Teva Gyógyszergyár Zrt  
Tel.: +36 1 288 64 00 

 
Danmark  
Teva Denmark A/S  
Tlf: +45 44 98 55 11  

 
Malta  
Teva Pharmaceuticals Ireland 
L-Irlanda  
Tel: +353 51 321740 

 
Deutschland 
Teva GmbH 
Tel: +49 731 402 08 

 
Nederland  
Teva Nederland B.V. 
Tel: +31 800 0228 400 

 
Eesti 
Teva Eesti esindus UAB Sicor Biotech 
Eesti filiaal 
Tel: +372 661 0801 

 
Norge 
Teva Norway AS 
Tlf: +47 6677 55 90 

 
Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

 
Österreich 
ratiopharm Arzneimittel Vertriebs GmbH 
Tel: +43 1 97007 0 

 
España 
Teva Pharma S.L.U. 
Tél: +34 91 387 32 80   

 
Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +48 22 345 93 00 

 
France 
Teva Santé 
Tél: +33 1 55 91 7800 

 
Portugal 
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: +351 21 476 75 50 

 
Hrvatska 

 
România 



38 

Pliva Hrvatska d.o.o 
Tel: + 385 1 37 20 000 

Teva Pharmaceuticals S.R.L 
Tel: +4021 230 6524 

 
Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 51 321 740 

 
Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 

 
Ísland 
ratiopharm Oy 
Puh/Tel: +358 20 180 5900 

 
Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +421 2 5726 7911 
 

Italia 
Teva Italia S.r.l. 
Tel: +39 028 917 981 

Suomi/Finland 
ratiopharm Oy 
Puh/Tel: +358 20 180 5900 

 
Κύπρος 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

 
Sverige 
Teva Sweden AB 
Tel: +46 42 12 11 00 

 
Latvija 
UAB Sicor Biotech filiāle Latvijā  
Tel: +371 67 323 666 

 
United Kingdom 
Teva UK Limited 
Tel: +44 1977 628 500 

 
This leaflet was last revised in MM/YYYY. 
 
Detailed information on this medicine is available on the website of the European Medicines Agency 
(EMA) http://www.ema.europa.eu/.The following information is intended for healthcare 
professionals only: 
 
Instructions on how to dilute, store and dispose of Topotecan Teva 
 
Instructions for dilution 
The concentrate is pale yellow in colour and contains 1 mg per ml of topotecan. Futher dilution of the 
appropriate volume of the concentrate with either sodium chloride 9 mg/ml (0.9%) solution for 
injection or glucose 50 mg/ml (5%) solution for injection to reach a final topotecan concentration of 
between 25 and 50 microgram/ml in the solution for infusion. 
 
Storage of the diluted solution 
From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are the responsibility of the user and 
would normally not be longer than 12 hours if stored below 25°C or 24 hours at 2-8°C, unless dilution 
has taken place in controlled and validated aseptic conditions. 
 
Handling and disposal 
The normal procedures for proper handling and disposal of anticancer medicinal products should be 
adopted: 
- Staff should be trained to dilute the medicinal product. 
- Pregnant staff should be excluded from working with this medicinal product. 
- Staff handling this medicinal product during dilution should wear protective clothing including 

mask, goggles and gloves. 
- Accidental contact with the skin or eyes should be treated immediately with copious amounts of 

water. 
- All items for administration or cleaning, including gloves, should be placed in high-risk, waste 

disposal bags for high-temperature incineration. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET