Topotecan Hospira

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



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1. NAME OF THE MEDICINAL PRODUCT

Topotecan Hospira 4 mg/4 ml concentrate for solution for infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml of concentrate for solution for infusion contains 1 mg topotecan (as hydrochloride).
Each 4 ml vial of concentrate contains 4 mg topotecan (as hydrochloride).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Concentrate for solution for infusion (sterile concentrate).

A clear yellow to yellow-green solution.

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. Topotecan 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
The recommended dose of topotecan is 1.5 mg/m2 body surface area perday 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).



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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 1.5mg/dl. If, during 
topotecan/cisplatin combination therapy, serum creatinine exceeds 1.5mg/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.



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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 reconstituted and further diluted before use (see section 6.6).

4.3 Contraindications

− Severe hypersensitivity to the active substance or to any of the excipients.
− 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
Hospira, e.g. if patients at increased risk of tumour bleeds are considered for therapy.

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 



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≥ 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

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.



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

be severe), constipation, abdominal pain2, 
mucositis 

Not known Gastrointestinal perforation 
Hepatobiliary disorders 



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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 
1Fatalities due to sepsis have been reported in patients treated with topotecan (see section 4.4). 
2Neutropenic colitis, including fatal neutropenic colitis, has been reported to occur as a complication 
of topotecan-induced neutropenia (see section 4.4). 
3Reactions 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.

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 %). 



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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, 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).



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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 % C.I. 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 topotecan 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)

N = total number of patients treated.
CI = Confidence interval.

In another randomised Phase III trial 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).



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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).

Table 2. Study results Study GOG-0179

ITT population
Cisplatin

50 mg/m2 on 
day 1, every 

2l days.

Cisplatin
50 mg/m2 on day 1 +

Topotecan 
0.75 mg/m2 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% C.I.: 2.9, 9.6) for the cisplatin arm, with an hazard ratio of 1.15 (0.59, 2.23). In those patients 
(n=102) with recurrence after 180 days, the 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.



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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/m2day 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 132l (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 < 7% (range 4-9 %) of the total topotecan-related material accounted 
for in the urine and faeces. The topotecan-O-glucuronide and N-desmethyl topotecan-O-glucuronide in 
the urine were < 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.



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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

6.1 List of excipients

Tartaric acid (E334)
Hydrochloric acid (E507) (for pH adjustment)
Sodium hydroxide (for pH adjustment)
Water for injections



13

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

Unopened vial 
3 years

After first opening
Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C under normal light 
conditions and at 2°C-8°C when protected from light.  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 24 hours at 
2°C to 8°C, unless reconstitution/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

Topotecan Hospira 4 mg/4 ml is supplied in Type I clear glass vials, each sealed with a chlorobutyl 
rubber stopper, aluminium seal and plastic flip-off closure.   

Each vial contains 4 ml of concentrate.  

Topotecan Hospira is available in pack sizes of 1 vial and 5 vials. Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Topotecan Hospira is provided as a sterile concentrate containing 4 mg topotecan in 4 ml solution
(1 mg/ml). 

Parenteral products should be visually inspected for particulate matter and discolouration prior to 
administration. Topotecan Hospira is a yellow/yellow green solution. If visible particles are observed, 
the product should not be administered.

Further dilution with either sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 
50 mg/ml (5%) solution for injection is required, to obtain a final concentration of between 25 and 
50 micrograms/ml prior to administration to the patient.

The normal procedures for proper handling and disposal of anticancer medicinal products should be 
adopted, namely:
− Personnel should be trained to prepare and administer the medicinal product.
− Pregnant staff should be excluded from working with this medicinal product.
− Personnel handling this medicinal product should wear protective clothing including mask, goggles 
and gloves.
− 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.



14

− Accidental contact with the skin or eyes should be treated immediately with copious amounts of 
water. If there is lasting irritation, a doctor should be consulted.
- Any unused product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/633/001 – Single pack
EU/1/10/633/002 – 5 pack

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 10 June 2010
Date of latest renewal: 28 May 2015

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.



15

ANNEX II

A. MANUFACTURER(S) 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(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release

Hospira UK Limited
Horizon
Honey Lane
Hurley
Maidenhead
SL6 6RJ
UK

Or

Hospira Enterprises B.V.
Randstad 22-11
1316 BN, Almere
The Netherlands

Or

Pfizer Service Company BVBA 
Hoge Wei 10 
1930 Zaventem 
Belgium

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) 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2. of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 

An updated RMP should be submitted: 
 At the request of the European Medicines Agency; 



17

 Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of an 
important (pharmacovigilance or risk minimisation) milestone being reached. 



18

ANNEX III

LABELLING AND PACKAGE LEAFLET



19

A. LABELLING



20

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON 

1. NAME OF THE MEDICINAL PRODUCT

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

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each ml of concentrate contains 1 mg topotecan (as hydrochloride).  
Each 4 ml vial contains 4 mg topotecan (as hydrochloride).

3. LIST OF EXCIPIENTS

Also contains: tartaric acid (E334), water for injections, and hydrochloric acid
(E507) or sodium hydroxide (for pH adjustment).

4. PHARMACEUTICAL FORM AND CONTENTS

Concentrate for solution for infusion
4 mg/4 ml 
1 vial
5 vials

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For intravenous use.
Dilute before use.
Read the package leaflet before use.

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

8. EXPIRY DATE

EXP: 
Use immediately after opening.



21

9. SPECIAL STORAGE CONDITIONS

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

WARNING: This is a cytotoxic agent. Special handling and disposal instructions apply (see package 
leaflet).

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/10/633/001  (x1)
EU/1/10/633/002  (x5)

13. BATCH NUMBER

BN: 

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.



22

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC: 
SN: 
NN: 



23

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

VIAL LABEL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Topotecan Hospira 4 mg/4 ml sterile concentrate
topotecan
Intravenous use

2. METHOD OF ADMINISTRATION

Dilute before use.

3. EXPIRY DATE

EXP: 

4. BATCH NUMBER

BN: 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

4 mg/ 4ml 

6. OTHER

Pfizer Europe MA EEIG



24

B. PACKAGE LEAFLET



25

Package leaflet: Information for the user

Topotecan Hospira 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.
• If you get any side effects, talk to your doctor. This includes any possible side effects not listed in 
this leaflet. See section 4.

What is in this leaflet:

1. What Topotecan Hospira is and what it is used for
2. What you need to know before you are given Topotecan Hospira
3. How to use Topotecan Hospira
4. Possible side effects
5. How to store Topotecan Hospira
6. Contents of the pack and other information

1. What Topotecan Hospira is and what it is used for

Topotecan Hospira helps to destroy tumours. A doctor or a nurse will give you the medicine as an 
infusion into a vein in hospital.

Topotecan Hospira 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 Hospira is combined with another medicine called 
cisplatin. 

Your doctor will decide with you whether Topotecan Hospira therapy is better than further treatment 
with your initial chemotherapy.

2. What you need to know before you are given Topotecan Hospira

You should not receive Topotecan Hospira:
• 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 cell counts are 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 any of these applies to you.

Warnings and precautions 
Before you are given this medicine 
your doctor needs to know :
• if you have any kidney or liver problems. Your dose of Topotecan Hospira may need to be 

adjusted.
• if you are pregnant or plan to become pregnant. See section “Pregnancy and breast-feeding” 

below.
• if you plan to father a child. See section “Pregnancy and breast-feeding” below.



26

Tell your doctor if any of these applies to you.

Other medicines and Topotecan Hospira
Tell your doctor if you are taking, have recently taken, or might take any other medicines, including 
any herbal products or medicines obtained without a prescription. Remember to tell your doctor if you 
start to take any other medicines while you are on Topotecan Hospira.

Pregnancy and breast-feeding
Topotecan is not recommended for pregnant women. It may harm a baby conceived before, during or 
soon after treatment. You should use an effective method of contraception. Ask your doctor for advice. 
Do not try to become pregnant until a doctor advises you it is safe to do so. 

Male patients who wish to father a child should ask their doctor for family planning advice or 
treatment. If your partner becomes pregnant during your treatment, tell your doctor immediately.

Do not breast-feed if you are being treated with topotecan. Do not restart breast-feeding until the 
doctor tells you it is safe to do so.

Driving and using machines
Topotecan can make people feel tired. If you feel tired or weak, do not drive or use machines.

3. How Topotecan Hospira is used
The dose of topotecan you are given will be worked out by your doctor, based on:
• your body size (surface area measured in square metres)
• the results of blood tests carried out before treatment 
• the disease being treated.

The usual dose
• Ovarian and small cell lung cancer: 1.5 milligrams per m2 of body surface area per day.
You will have treatment once a day for 5 days. This pattern of treatment will normally be repeated 
every 3 weeks.
• Cervical cancer: 0.75 milligrams per m2 of body surface area per day. You will have treatment once 
a day for 3 days. This pattern of treatment will normally be repeated every 3 weeks.

When treating cervical cancer, Topotecan Hospira is combined with another medicine, called 
cisplatin. Your doctor will determine the correct dose of cisplatin. 

The treatment may vary, depending on the results of your regular blood tests.

How topotecan is given
A doctor or nurse will administer topotecan as an infusion into your arm lasting  about 30 minutes.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects: tell your doctor

These very common side effects may affect more than 1 in 10 people treated with Topotecan 
Hospira: 
• Signs of infection: Topotecan may reduce the number of white blood cells and lower your resistance 
to infection. This can even be life threatening. Signs include:

 fever
 serious deterioration of your general condition
 local symptoms such as sore throat or urinary problems (for example, a burning sensation 

when urinating, which may be a urinary infection).



27

• Occasionally severe stomach pain, fever and possibly diarrhoea (rarely with blood) can be signs of 
bowel inflammation (colitis) can be signs of bowel inflammation (colitis).

This rare side effect may affect up to 1 in 1,000 people treated with Topotecan Hospira:
• Lung inflammation (interstitial lung disease): You are most at risk if you have existing lung 
disease, have had radiation treatment to your lungs, or have previously taken medicines that caused 
lung damage. Signs include:

 difficulty breathing
 cough
 fever

Tell your doctor immediately if you get any symptoms of these conditions, as hospitalisation may be 
necessary.

Very common side effects
These may affect more than 1 in 10 people treated with Topotecan Hospira:
• Feeling generally weak and tired (temporary anaemia). In some cases you may need a blood 
transfusion.
• Unusual bruising or bleeding, caused by a decrease in the number of clotting cells in the blood. This 
can lead to severe bleeding from relatively small injuries such as a small cut. Rarely, it can lead to 
more severe bleeding (haemorrhage). Talk to your doctor for advice on how to minimise the risk of 
bleeding.
• Weight loss and loss of appetite (anorexia); tiredness; weakness.
• Feeling sick (nausea), being sick (vomiting); diarrhoea; stomach pain; constipation.
• Inflammation and ulcers of the mouth, tongue or gums.
• High body temperature (fever).
• Hair loss.

Common side effects
These may affect up to 1 in 10 people treated with Topotecan Hospira:

• Allergic or hypersensitivity reactions (including rash).
• Yellow skin.
• Feeling unwell.
• Itching sensation.

Rare side effects
These may affect up to 1 in 1,000 people treated with Topotecan Hospira:

• Severe allergic or anaphylactic reactions.
• Swelling caused by fluid build up (angioedema).
• Mild pain and inflammation at the site of injection.
• Itchy rash (or hives).

Side effects with frequency not known 
The frequency of some side effects is not known (events from spontaneous reports and the 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]). 

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 Hospira. Those effects are described in the 
cisplatin patient leaflet. 



28

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
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 Hospira

Keep this medicine out of the sight and reach of children.

Do not use Topotecan Hospira after the expiry date stated on the vial and carton after EXP.

Store in a refrigerator (2°C-8°C). Do not freeze.

Keep the vial in the outer carton in order to protect from light.

This medicine is for single use only. After opening, the product should be used immediately.  If not 
used immediately, Topotecan Hospira can be used for up to 24 hours when stored in the fridge 
(protected from light) or at room temperature (in normal daylight conditions).

If visible particles are observed, the medicine should not be administered.

Do not throw away any medicines via wastewater. Ask your pharmacist how to throw away medicines 
you no longer use. These measures will help protect the environment.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Topotecan Hospira contains
The active substance in Topotecan Hospira is topotecan (as hydrochloride). 1 ml of concentrate for 
solution for infusion contains 1 mg topotecan (as hydrochloride). Each 4 ml vial of concentrate 
contains 4 mg topotecan (as hydrochloride).  

The other ingredients are: tartaric acid (E334), water for injections and hydrochloric acid (E507) or 
sodium hydroxide (to adjust the pH of the solution).

What Topotecan Hospira looks like and the contents of the pack
Topotecan Hospira is a clear, yellow or yellow-green concentrate for solution for infusion supplied in 
clear glass vials, each containing 4 ml concentrate. Topotecan Hospira is available in two pack sizes, 
containing either 1 vial or 5 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium

Manufacturer
Hospira UK Limited
Horizon
Honey Lane
Hurley
Maidenhead
SL6 6RJ
UK



29

Or

Hospira Enterprises B.V.
Randstad 22-11
1316 BN, Almere
The Netherlands

Or

Pfizer Service Company BVBA 
Hoge Wei 10 
1930 Zaventem 
Belgium

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 

BE
Pfizer SA/NV
Tél/Tel: +32 2 554 62 11

LT
Pfizer Luxembourg SARL filialas Lietuvoje
Tel. + 370 52 51 4000

BG
Пфайзер Люксембург САРЛ, Клон България
Тел.: +359 2 970 4333

LU
Pfizer SA/NV
Tél/Tel: +32 2 554 62 11

CZ
Pfizer, spol. s r.o.
Tel: +420-283-004-111

HU
Pfizer Kft.
Tel.: + 36 1 488 37 00

DK
Pfizer ApS
Tlf: + 45 44 20 11 00

MT
Drugsales Ltd
Tel: + 356 21 419 070/1/2

DE 
Pfizer Pharma PFE GmbH
Tel: + 49 (0)800 8535555

NL
Pfizer bv
Tel: +31 (0)10 406 43 01

EE
Pfizer Luxembourg SARL Eesti filiaal
Tel: +372 666 7500

NO
Pfizer AS
Tlf: +47 67 52 61 00

EL
Aenorasis S.A.
Τel: + 30 210 6136332

AT
Pfizer Corporation Austria Ges.m.b.H.
Tel: +43 (0)1 521 15-0

ES
Pfizer, S.L. 
Tel: +34 91 490 99 00

PL
Pfizer Polska Sp. z o.o.
Tel.: +48 22 335 61 00

FR
Pfizer
Tél: + 33 (0)1 58 07 34 40

PT
Laboratórios Pfizer, Lda.
Tel: +351 21 423 55 00



30

HR
Pfizer Croatia d.o.o.
Tel: +385 1 3908 777

RO
Pfizer România S.R.L.
Tel: +40 (0)21 207 28 00

IE
Pfizer Healthcare Ireland
Tel: 1800 633 363 (toll free)
+44 (0) 1304 616161

SI
Pfizer Luxembourg SARL
Pfizer, podružnica za svetovanje s področja 
farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

IS
Icepharma hf.
Sími: +354 540 8000

SK
Pfizer Luxembourg SARL, organizačná zložka
Tel: +421–2–3355 5500

IT
Pfizer Italia Srl
Tel: +39 06 33 18 21

FI
Pfizer PFE Finland Oy
Puh/Tel: +358 (0)9 430 040

CY
Pharmaceutical Trading Co Ltd
Τηλ: 24656165

SE
Pfizer AB
Tel: +46 (0)8 550 520 00

LV
Pfizer Luxembourg SARL filiāle Latvijā
Tel.: + 371 670 35 775

UK
Hospira UK Limited
Tel: + 44 (0) 1628 515500

This leaflet was last revised in 

Other sources of information
DDetailed information on this medicine is available on the website of the European Medicines Agency 
http://www.ema.europa.eu.

The following information is intended for medical or healthcare professionals only.

Storage, Use, Handling & Disposal of Topotecan Hospira

Storage
Unopened vial: Store in a refrigerator (2°C-8°C). Do not freeze. Keep the vial in the outer carton in 
order to protect from light.

Use
Refer to the SmPC for full details.

Topotecan Hospira 4 mg/4 ml concentrate for solution for infusion requires dilution to a final 
concentration of 25-50 micrograms/ml, prior to administration to the patient. The approved diluents 
for the concentrate are sodium chloride 9 mg/ml (0.9%) solution for injection and glucose 50 mg/ml 
(5%) solution for injection. Use the aseptic technique during any further dilution of the solution for 
infusion. 

Parenteral products should be visually inspected for particulate matter and discolouration prior to 
administration. Topotecan Hospira is a yellow/yellow green solution.

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 ≥ 9g/dl (after transfusion if 



31

necessary).  Neutropenia and thrombocytopenia should be managed.  For further details, refer to the 
SPC.

Dosage: Ovarian and Small Cell Lung Carcinoma 
Initial dose: 1.5 mg/ m2 body surface area/day, administered by intravenous infusion over 30 minutes 
for 5 consecutive days, with a 3 week interval between the start of each course. 

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). 

Dosage: Cervical Carcinoma
Initial dose: 0.75 mg/m2/day administered as 30 minute intravenous infusion daily, 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 6 courses or until 
progressive disease.

Subsequent doses: Topotecan should not be re-administered unless the neutrophil count is more than 
or equal to 1.5 x 109/l, the platelet count is more than or equal to 100 x 109/l, and the haemoglobin 
level is more than or equal to 9g/dl (after transfusion if necessary). 

Dosage: Renally impaired patients
Limited data indicate that the dose should be reduced in patients with moderate renal impairment. 
Please refer to the SPC for further details.

Dosage: Paediatric population
Limited data available.  Use not recommended.

Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C under normal light
conditions and at 2°C -8°C when protected from light.  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 24 hours at 
2°C to 8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic 
conditions.

Handling and disposal
The normal procedures for proper handling and disposal of anti-tumour medicinal products should be 
adopted:
• Staff should be adequately trained in the preparation, administration and disposal of cytotoxics
• Pregnant staff should be excluded from working with this medicinal product.
• Staff handling this medicinal product should wear adequate protective clothing including mask, 
goggles and gloves.
• All items used in the preparation, administration, and cleaning of the medicinal product, 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.
• Accidental contact with the skin or eyes should be treated immediately with copious amounts of 
water. If there is lasting irritation, a doctor should be consulted.
• Any unused product or waste material should be disposed of in accordance with local requirements.



Document Approval Record

Document Name:

Document Title:

Signed By: Date(GMT) Signing Capacity


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) 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