Hycamtin

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 

 

HYCAMTIN 1 mg powder for concentrate for solution for infusion 

HYCAMTIN 4 mg powder for concentrate for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

HYCAMTIN 1 mg powder for concentrate for solution for infusion 

Each vial contains 1 mg topotecan (as hydrochloride). 

 
The total content of active substance in the vial provides 1 mg per ml of active substance when 

reconstituted as recommended. 

 

HYCAMTIN 4 mg powder for concentrate for solution for infusion 

Each vial contains 4 mg topotecan (as hydrochloride). 
 

The total content of active substance in the vial provides 1 mg per ml of active substance when 

reconstituted as recommended. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Powder for concentrate for solution for infusion. 

 

Light yellow to greenish powder. 

 

 

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. 

 



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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 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. 



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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 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 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 

HYCAMTIN, 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 

 

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. 



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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) 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) 



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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, respectively. Median overall survival was 

62 weeks for topotecan versus 53 weeks for paclitaxel (hazard ratio 0.9 [0.6, 1.3]). 

 



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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) 32.3 25.1 33.0 35.0 

 (95% CI) (26.3, 40.9) (21.1, 33.0) (29.1, 42.4) (31.0, 37.1) 

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

Response rate (%) 23.1 14.8 18.3 21.9 

 (95% CI) (11.6, 34.5) (5.3, 24.3) (12.2, 24.4) (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) 

14.9 13.1 11.9 14.6 

 (95% CI) (8.3, 21.3) (11.6, 18.3) (9.7, 14.1) (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 

 



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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). 

 

Table 2 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 

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). 

 



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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 l (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-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. 

 



12 

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. 

 

 

  



13 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 
 

Tartaric acid (E334) 

Mannitol (E421) 

Hydrochloric acid (E507) 

Sodium hydroxide 

 

6.2 Incompatibilities 
 

None known. 

 

6.3 Shelf life 
 

Vials 

3 years. 

 

Reconstituted and diluted solutions 

The product should be used immediately after reconstitution as it contains no antibacterial 

preservative. If reconstitution and dilution is performed under strict aseptic conditions (e.g. an LAF 

bench) the product should be used (infusion completed) within 12 hours at room temperature or 

24 hours if stored at 2-8 0C after the first puncture of the vial. 

 

6.4 Special precautions for storage 
 

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

 

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 
 

HYCAMTIN 1 mg powder for concentrate for solution for infusion 

 

Type I flint glass vial with grey butyl rubber stopper and aluminium seal with plastic flip-off cap 

containing 1 mg of topotecan. 

 

HYCAMTIN 1 mg is available in packs containing 1 vial and 5 vials. 

 

HYCAMTIN 4 mg powder for concentrate for solution for infusion 

 

Type I flint glass vial, with grey butyl rubber stopper and aluminium seal with plastic flip-off cap 

containing 4 mg of topotecan. 

 

HYCAMTIN 4 mg is available in packs containing 1 vial and 5 vials. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal and other handling 

 

HYCAMTIN 1 mg powder for concentrate for solution for infusion 

 

The contents of HYCAMTIN 1 mg vials must be reconstituted with 1.1 ml water for injections. Since 

the vial contains a 10% overage, the clear, reconstituted solution is yellow to yellow-green in colour 

and provides 1 mg of topotecan per ml. Further dilution of the appropriate volume of the reconstituted 

solution with either sodium chloride 9 mg/ml (0.9%) or 5% w/v glucose is required to give a final 

concentration of between 25 and 50 microgram/ml. 



14 

 

HYCAMTIN 4 mg powder for concentrate for solution for infusion 

 

The contents of HYCAMTIN 4 mg vials must be reconstituted with 4 ml water for injections. The 

clear, reconstituted solution is yellow to yellow-green in colour and provides 1 mg of topotecan per 

ml. Further dilution of the appropriate volume of the reconstituted solution with either sodium chloride 

9 mg/ml (0.9%) or 5% w/v glucose is required to a final concentration of between 25 and 

50 microgram/ml. 

 

The normal procedures for proper handling and disposal of anticancer medicinal products should be 

adopted, namely: 

 Personnel should be trained to reconstitute the medicinal product. 

 Pregnant staff should be excluded from working with this medicinal product. 

 Personnel handling this medicinal product during reconstitution 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. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 
Ireland 

 

 

8. MARKETING AUTHORISATION NUMBERS 
 

HYCAMTIN 1 mg powder for concentrate for solution for infusion 

 

EU/1/96/027/004 

EU/1/96/027/005 

 

HYCAMTIN 4 mg powder for concentrate for solution for infusion 

 

EU/1/96/027/001 

EU/1/96/027/003 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 12 November 1996 

Date of latest renewal: 20 November 2006 

 

 

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 

1. NAME OF THE MEDICINAL PRODUCT 
 

HYCAMTIN 0.25 mg hard capsules 

HYCAMTIN 1 mg hard capsules 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

HYCAMTIN 0.25 mg hard capsules 

 

Each capsule contains 0.25 mg of topotecan (as hydrochloride). 

 

HYCAMTIN 1 mg hard capsules 

 

Each capsule contains 1 mg of topotecan (as hydrochloride). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Hard capsule. 

 

HYCAMTIN 0.25 mg hard capsules 

 

The capsules are opaque, white to yellowish white and imprinted with “HYCAMTIN” and “0.25 mg”. 

 

HYCAMTIN 1 mg hard capsules 

 

The capsules are opaque, pink and imprinted with “HYCAMTIN” and “1 mg”. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

HYCAMTIN capsules are indicated as monotherapy for the treatment of adult 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). 

 

4.2 Posology and method of administration 

 

HYCAMTIN capsules should only be prescribed and therapy supervised by a physician experienced in 

the use of chemotherapeutic agents. 

 

Posology 

 

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). 

 

Initial dose 

The recommended dose of HYCAMTIN capsules is 2.3 mg/m2 body surface area per day administered 

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). 

 



16 

The capsule(s) must be swallowed whole, and must not be chewed crushed or divided. 

Hycamtin capsules may be taken with or without food (see section 5.2). 

 

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 0.4 mg/m2/day to 

1.9 mg/m2/day (or subsequently down to 1.5 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 needed to be reduced below 1.5 mg/m2/day. 

 

For patients who experience Grade 3 or 4 diarrhoea, the dose should be reduced by 0.4 mg/m2/day for 

subsequent courses (see section 4.4). Patients with Grade 2 diarrhoea may need to follow the same 

dose modification guidelines. 

 

Proactive management of diarrhoea with anti-diarrhoeal agents is important. Severe cases of diarrhoea 

may require administration of oral or intravenous electrolytes and fluids, and interruption of topotecan 

therapy (see sections 4.4 and 4.8). 

 

Special populations 

Patients with renal impairment 

The recommended monotherapy dose of oral topotecan in patients with small cell lung carcinoma with 

creatinine clearance between 30 and 49 ml/min is 1.9 mg/m2/day for five consecutive days. If well 

tolerated, the dose may be increased to 2.3 mg/m2/day in subsequent cycles (see section 5.2). 

 

Limited data in Korean patients with creatinine clearance less than 50 ml/min suggest a further 

lowering of dose may be required (see section 5.2). 

 

Insufficient data are available to make a recommendation for patients with a creatinine clearance 

<30 ml/min. 

 

Patients with hepatic impairment 

Pharmacokinetics of HYCAMTIN capsules have not been specifically studied in patients with 

impaired hepatic function. There are insufficient data available with HYCAMTIN capsules to make a 

dose recommendation for 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. 

 

Elderly 

No overall differences in effectiveness were observed between patients aged over 65 years and 

younger adult patients. However in the two studies in which both oral and intravenous topotecan were 

administered, patients over 65 years old receiving oral topotecan experienced an increase in drug-

related diarrhoea compared to those younger than 65 years of age (see section 4.4 and 4.8). 

 



17 

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 

HYCAMTIN, 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. 

 

Topotecan is partly eliminated via renal excretion and renal impairment might lead to increased 

exposure to topotecan. Dosing recommendations for patients receiving oral topotecan with creatinine 

clearance less than 30 ml/min have not been established. Use of topotecan in these patients 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. There is insufficient experience of the use of topotecan in 

patients with severely impaired hepatic function (serum bilirubin 10 mg/dl). Use of topotecan in 

these patients is not recommended (see section 4.2). 

 

Diarrhoea, including severe diarrhoea requiring hospitalisation, has been reported during treatment 

with oral topotecan. Diarrhoea related to oral topotecan can occur at the same time as drug-related 

neutropenia and its sequelae. Communication with patients prior to drug administration regarding 

these side effects and proactive management of early and all signs and symptoms of diarrhoea is 

important. Cancer treatment-induced diarrhoea (CTID) is associated with significant morbidity and 

may be life-threatening. Should diarrhoea occur during treatment with oral topotecan, physicians are 

advised to aggressively manage diarrhoea. Clinical guidelines describing the aggressive management 

of CTID include specific recommendations on patient communication and awareness, recognition of 

early warning signs, use of anti-diarrhoeals and antibiotics, changes in fluid intake and diet, and need 

for hospitalisation (see sections 4.2 and 4.8). 



18 

 

Intravenous topotecan should be considered in the following clinical situations: uncontrolled emesis, 

swallowing disorders, uncontrolled diarrhoea, clinical conditions and medication that may alter 

gastrointestinal motility and drug absorption. 

 

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). 

 

Topotecan is a substrate for both ABCB1 (P-glycoprotein) and ABCG2 (BCRP). Inhibitors of ABCB1 

and ABCG2 administered with oral topotecan have been shown to increase topotecan exposure. 

 

Cyclosporin A (an inhibitor of ABCB1, ABCC1 [MRP-1], and CYP3A4) administered with oral 

topotecan increased topotecan AUC to approximately 2-2.5-fold of control. 

 

Patients should be carefully monitored for adverse reactions when oral topotecan is administered with 

a substance known to inhibit ABCB1 or ABCG2 (see section 5.2). 

 

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. Currently 

there is only limited experience in combining oral topotecan with other chemotherapy agents. 

 

The pharmacokinetics of topotecan were generally unchanged when co-administered with ranitidine. 

 

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. 

 



19 

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 clinical studies involving patients with relapsed small cell lung cancer, the dose-limiting toxicity of 

oral topotecan monotherapy was found to be haematological. Toxicity was predictable and reversible. 

There were no signs of cumulative haematological or non-haematological toxicity. 

 

The frequencies associated with the haematological and non-haematological adverse events presented 

are for adverse events considered to be related/possibly related to oral topotecan therapy. 

 

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), which may lead 

to dehydration (see sections 4.2 and 4.4) 

Common Abdominal pain2, constipation, mucositis, dyspepsia 

Not known Gastrointestinal perforation 

Hepatobiliary disorders 

Common Hyperbilirubinaemia 

Skin and subcutaneous tissue disorders 

Very common Alopecia 

Common Pruritus 



20 

General disorders and administration site conditions 

Very common Fatigue 

Common Asthenia, pyrexia, malaise 

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) 

 

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). 

 

Safety data are presented based on an integrated data set of 682 patients with relapsed lung cancer 

administered 2,536 courses of oral topotecan monotherapy (275 patients with relapsed SCLC and 407 

with relapsed non-SCLC). 

 

Haematological 

 

Neutropenia 

Severe neutropenia (Grade 4 - neutrophil count <0.5 x 109/l) occurred in 32% of patients in 13% of 

courses. Median time to onset of severe neutropenia was day 12 with a median duration of 7 days. In 

34% of courses with severe neutropenia, the duration was >7 days. In course 1 the incidence was 20%, 

by course 4 the incidence was 8%. Infection, sepsis and febrile neutropenia occurred in 17%, 2%, and 

4% of patients, respectively. Death due to sepsis occurred in 1% of patients. Pancytopenia has been 

reported. Growth factors were administered to 19% of patients in 8% of courses. 

 

Thrombocytopenia 

Severe thrombocytopenia (Grade 4 - platelets <10 x 109/l) occurred in 6% of patients in 2% of courses. 

Median time to onset of severe thrombocytopenia was day 15 with a median duration of 2.5 days. In 

18% of courses with severe thrombocytopenia the duration was >7 days. Moderate thrombocytopenia 

(Grade 3 - platelets between 10.0 and 50.0 x 109/l) occurred in 29% of patients in 14% of courses. 

Platelet transfusions were given to 10% of patients in 4% of courses. Reports of significant sequelae 

associated with thrombocytopenia including fatalities due to tumour bleeds have been infrequent. 

 

Anaemia 

Moderate to severe anaemia (Grade 3 and 4 – Hb 8.0 g/dl) occurred in 25% of patients (12% of 

courses). Median time to onset of moderate to severe anaemia was day 12 with a median duration of 

7 days. In 46% of courses with moderate to severe anaemia, the duration was >7 days. Red blood cell 

transfusions were given in 30% of patients (13% of courses). Erythropoietin was administered to 10% 

of patients in 8% of courses. 

 

Non-haematological 

 

The most frequently reported non-haematological effects were nausea (37%), diarrhoea (29%), fatigue 

(26%), vomiting (24%), alopecia (21%) and anorexia (18%). All cases were irrespective of associated 

causality. For severe cases (CTC Grade 3/4) reported as related/possibly related to topotecan 

administration the incidence was diarrhoea 5% (see section 4.4), fatigue 4%, vomiting 3%, nausea 3% 

and anorexia 2%. 

 

The overall incidence of drug-related diarrhoea was 22%, including 4% with Grade 3 and 0.4% with 

Grade 4. Drug-related diarrhoea was more frequent in patients 65 years of age (28%) compared to 

those less than 65 years of age (19%). 

 

Complete alopecia related/possibly related to topotecan administration was observed in 9% of patients 

and partial alopecia related/possibly related to topotecan administration in 11% of patients. 

 



21 

Therapeutic interventions associated with non-haematological effects included anti-emetic agents, 

given to 47% of patients in 38% of courses and anti-diarrhoeal agents, given to 15% of patients in 6% 

of courses. A 5-HT3 antagonist was administered to 30% of patients in 24% of courses. Loperamide 

was administered to 13% of patients in 5% of courses. The median time to onset of Grade 2 or worse 

diarrhoea was 9 days. 

 

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 topotecan capsules (up to 5 fold of the 

recommended dose) and intravenous topotecan (up to 10 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 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. 

 



22 

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) 32.3 25.1 33.0 35.0 

 (95% CI) (26.3, 40.9) (21.1, 33.0) (29.1, 42.4) (31.0, 37.1) 

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

Response rate (%) 23.1 14.8 18.3 21.9 

 (95% CI) (11.6, 34.5) (5.3, 24.3) (12.2, 24.4) (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) 

14.9 13.1 11.9 14.6 

 (95% CI) (8.3, 21.3) (11.6, 18.3) (9.7, 14.1) (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 

 

Paediatric population 

The safety and effectiveness of oral topotecan in paediatric patients have not been established. 

 

5.2 Pharmacokinetic properties 

 

Distribution 

 

The pharmacokinetics of topotecan after oral administration have been evaluated in cancer patients 

following doses of 1.2 to 3.1 mg/m2/day and 4 mg/m2/day administered daily for 5 days. The 

bioavailability of oral topotecan (total and lactone) in humans is approximately 40%. Plasma 

concentrations of total topotecan (i.e. lactone and carboxylate forms) and topotecan lactone (active 

moiety) peak at approximately 2.0 hours and 1.5 hours, respectively, and decline bi-exponentially with 

mean terminal half-life of approximately 3.0 to 6.0 hours. Total exposure (AUC) increases 

approximately proportionally with dose. There is little or no accumulation of topotecan with repeated 

daily dosing and there is no evidence of a change in 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 

 

A major route of clearance of topotecan is by hydrolysis of the lactone ring to form the ring-opened 

carboxylate. Other than hydrolysis, topotecan is cleared predominantly renally, with a minor 

component metabolised to the N-desmethyl metabolite (SB-209780) identified in plasma, urine and 

faeces. 

 



23 

Elimination 

 

Overall recovery of topotecan-related material following five daily doses of topotecan was 49 to 72% 

(mean 57%) of the administered oral dose. Approximately 20% was excreted as total topotecan and 

2% was excreted as N-desmethyl topotecan in the urine. Faecal elimination of total topotecan 

accounted for 33% while faecal elimination of N-desmethyl topotecan was 1.5%. Overall, the N-

desmethyl metabolite contributed a mean of less than 6% (range 4-8%) of the total topotecan-related 

material accounted for in the urine and faeces. O-glucuronides of both topotecan and N-desmethyl 

topotecan have been identified in the urine. The mean metabolite: parent plasma AUC ratio was less 

than 10% for both total topotecan and topotecan lactone. 

 

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. 

 

Following co-administration of the ABCB1 (P-gp) and ABCG2 (BCRP) inhibitor, elacridar 

(GF120918) at 100 to 1000 mg with oral topotecan, the AUC0-∞ of topotecan lactone and total 

topotecan increased approximately 2.5-fold (see section 4.5 for guidance). 

 

Administration of oral cyclosporine A (15 mg/kg), an inhibitor of transporters ABCB1 (P-gp) and 

ABCC1 (MRP-1) as well as the metabolising enzyme CYP3A4, within 4 hours of oral topotecan 

increased the dose normalised AUC0-24h of topotecan lactone and total topotecan approximately 

2.0- and 2.5-fold, respectively (see section 4.5). 

 

The extent of exposure was similar following a high-fat meal and in the fasted state, while tmax was 

delayed from 1.5 to 3 hours (topotecan lactone) and from 3 to 4 hours (total topotecan). 

 

Special populations 

 

Hepatic impairment 

The pharmacokinetics of oral topotecan have not been studied in patients with hepatic impairment (see 

section 4.2 and 4.4). 

 

Renal impairment 

Results of a cross-study analysis suggest that the exposure to topotecan lactone, the active moiety 

following topotecan administration, increases with decreased renal function. Geometric mean 

topotecan lactone dose-normalised AUC(0-) values were 9.4, 11.1 and 12.0 ng*h/ml in subjects with 

creatinine clearance values of more than 80 ml/min, 50 to 80 ml/min and 30 to 49 ml/min, 

respectively. In this analysis, creatinine clearance was calculated using the Cockcroft-Gault method. 

Similar results were obtained if glomerular filtration rate (ml/min) was estimated using the MDRD 

formula corrected for body weight. Patients with creatinine clearance >60 ml/min have been included 

in efficacy/safety studies of topotecan. Therefore, use of the normal starting dose in patients with a 

mild decrease in renal function is considered established (see section 4.2). 

 

Korean patients with renal impairment had generally higher exposure than non-Asian patients with the 

same degree of renal impairment. The clinical significance of this finding is unclear. Geometric mean 

topotecan lactone dose-normalised AUC(0-) values for Korean patients were 7.9, 12.9 and 

19.7 ng*h/ml in subjects with creatinine clearance values of more than 80 ml/min, 50 to 80 ml/min 

and 30 to 49 ml/min, respectively (see section 4.2 and 4.4). There are no data from Asian patients with 

renal impairment other than Koreans. 

 

Gender 

A cross-study analysis in 217 patients with advanced solid tumours indicated that gender did not affect 

the pharmacokinetics of HYCAMTIN capsules to a clinically relevant extent. 

 



24 

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 
 

HYCAMTIN 0.25 mg hard capsules 

 

Capsule contents 

Hydrogenated vegetable oil 

Glyceryl monostearate 

 

Capsule shell 

Gelatin 

Titanium dioxide (E171) 

 

Sealing band 

Gelatin 

 

Black ink 

Black iron oxide (E172) 

Shellac 

Anhydrous ethanol – see leaflet for further information 

Propylene glycol 

Isopropyl alcohol 

Butanol 

Concentrated ammonia solution 

Potassium hydroxide 

 

HYCAMTIN 1 mg hard capsules 

 

Capsule contents 

Hydrogenated vegetable oil 

Glyceryl monostearate 

 

Capsule shell 

Gelatin 

Titanium dioxide (E171) 

Red iron oxide (E172) 

 

Sealing band 

Gelatin 

 



25 

Black ink 

Black iron oxide (E172) 

Shellac 

Anhydrous ethanol – see leaflet for further information 

Propylene glycol 

Isopropyl alcohol 

Butanol 

Concentrated ammonia solution 

Potassium hydroxide 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

3 years. 

 

6.4 Special precautions for storage 
 

Store in a refrigerator (2ºC - 8ºC). 

 

Do not freeze. 

 

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

 

6.5 Nature and contents of container 
 

White polyvinyl chloride / polychlorotrifluoroethylene blister sealed with aluminium / 

Polyethylenterephtalate (PET) / paper foil lidding. The blisters are sealed with a peel-push child 

resistant opening feature. 

 

Each blister contains 10 capsules. 

 

6.6 Special precautions for disposal and other handling 

 

HYCAMTIN capsules should not be opened or crushed. 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 
Ireland 

 

 

  



26 

8. MARKETING AUTHORISATION NUMBERS 
 

HYCAMTIN 0.25 mg hard capsules 

 

EU/1/96/027/006 

 

HYCAMTIN 1 mg hard capsules 

 

EU/1/96/027/007 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 12 November 1996 

Date of latest renewal: 20 November 2006 

 

 

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/. 

  



27 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURERS 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 



28 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturers responsible for batch release 

 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 
Spain 

 

Novartis Pharma GmbH 

Roonstrasse 25 

90429 Nuremberg 

Germany 

 

Novartis Pharmaceuticals UK Limited 

Frimley Business Park 

Frimley 

Camberley, Surrey GU16 7SR 

United Kingdom 

 

GlaxoSmithKline Manufacturing S.p.A. 

Strada Provinciale Asolana 90 

43056 San Polo di Torrile 

Parma 

Italy 

 

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. 

 

 

  



29 

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; 

 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. 

  



30 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

 

  



31 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

  



32 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

HYCAMTIN 1 mg powder for concentrate for solution for infusion 

topotecan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

The total content of active substance in the vial provides 1 mg per ml of active substance when 

reconstituted as recommended (see Package Leaflet). 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: tartaric acid (E334), mannitol (E421), hydrochloric acid (E507), sodium hydroxide. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for concentrate for solution for infusion 

 

1 x 1 mg 

5 x 1 mg 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use. 

Reconstitute 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 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

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

 



33 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

WARNING: Cytotoxic agents, special handling instructions (see Package Leaflet). 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 
Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/96/027/005 1 x 1 mg vial 

EU/1/96/027/004 5 x 1 mg vials 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

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: 

  



34 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL 

 

 

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

 

HYCAMTIN 1 mg powder for concentrate for solution for infusion 

topotecan 

IV use 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

1 mg vial 

 

 

6. OTHER 

 

  



35 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

HYCAMTIN 4 mg powder for concentrate for solution for infusion 

topotecan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

The total content of active substance in the vial provides 1 mg per ml of active substance when 

reconstituted as recommended (see Package Leaflet). 

 

 

3. LIST OF EXCIPIENTS 

 

Also contains: tartaric acid (E334), mannitol (E421), hydrochloric acid (E507), sodium hydroxide. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for concentrate for solution for infusion 

 

1 x 4 mg 

5 x 4 mg 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use. 

Reconstitute 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 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

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

 



36 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

WARNING: Cytotoxic agents, special handling instructions (see Package Leaflet). 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 
Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/96/027/003 1 x 4 mg vial 

EU/1/96/027/001 5 x 4 mg vials 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

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: 

  



37 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL 

 

 

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

 

HYCAMTIN 4 mg powder for concentrate for solution for infusion 

topotecan 

IV use 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

4 mg vial 

 

 

6. OTHER 

 

 

  



38 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

HYCAMTIN 0.25 mg hard capsules 

topotecan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains topotecan hydrochloride equivalent to 0.25 mg of topotecan. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsules 

 

10 capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral 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 

 

HYCAMTIN capsules should not be broken or crushed. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

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

 

 



39 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

WARNING: Cytotoxic agent, special handling instructions (see Package Leaflet). 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/96/027/006 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16 INFORMATION IN BRAILLE 

 

hycamtin 0.25 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



40 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS BLISTERS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

HYCAMTIN 0.25 mg hard capsules 

topotecan 

 

 

2. NAME OF MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

  



41 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

HYCAMTIN 1 mg hard capsules 

topotecan 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each capsule contains topotecan hydrochloride equivalent to 1 mg of topotecan. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Hard capsules 

 

10 capsules 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Oral 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 

 

HYCAMTIN capsules should not be broken or crushed. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

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

 

 



42 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

WARNING: Cytotoxic agent, special handling instructions (see Package Leaflet). 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/96/027/007 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

hycamtin 1 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

  



43 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTERS 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

HYCAMTIN 1 mg hard capsules 

topotecan 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 

  



44 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



45 

Package leaflet: Information for the user 
 

Hycamtin 1 mg powder for concentrate for solution for infusion 

Hycamtin 4 mg powder for 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 Hycamtin is and what it is used for 

2. What you need to know before you are given Hycamtin 

3. How Hycamtin is used 

4. Possible side effects 

5. How to store Hycamtin 

6. Contents of the pack and other information 

 

 

1. What Hycamtin is and what it is used for 

 

Hycamtin helps to destroy tumours. A doctor or a nurse will give you the medicine as an infusion into 

a vein in hospital. 

 

Hycamtin 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, Hycamtin is combined with another medicine called cisplatin. 

 

Your doctor will decide with you whether Hycamtin therapy is better than further treatment with your 

initial chemotherapy. 

 

 

2. What you need to know before you are given Hycamtin 

 

You should not receive Hycamtin: 

 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 Hycamtin 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. 
Tell your doctor if any of these applies to you. 

 



46 

Other medicines and Hycamtin 

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 Hycamtin. 

 

Pregnancy and breast-feeding 
Hycamtin 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 Hycamtin. Do not restart breast-feeding until the 

doctor tells you it is safe to do so. 

 

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

 

 

3. How Hycamtin is used 

 

The dose of Hycamtin 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 mg per square metre 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 mg per square metre 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, Hycamtin 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 Hycamtin is given 

A doctor or nurse will administer Hycamtin as an infusion into your arm lasting about 30 minutes. 

 

 



47 

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 Hycamtin: 

 Signs of infections: Hycamtin 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). 

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

 

This rare side effect may affect up to 1 in 1,000 people treated with Hycamtin: 

 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 Hycamtin: 

 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 Hycamtin: 

 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 Hycamtin: 

 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). 
 



48 

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 Hycamtin. Those effects are described in the cisplatin 

patient leaflet. 

 

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 Hycamtin 

 

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. 

 

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, in-use storage times and conditions prior to use are the responsibility of the user. If 

reconstitution and dilution are performed under strict aseptic conditions (e.g. an LAF bench) the 

product should be used (infusion completed) within 24 hours if stored at 2ºC – 8ºC after the first 

puncture of the vial. 

 

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 Hycamtin contains 

 The active substance is topotecan. Each vial contains 1 mg or 4 mg of topotecan (as 
hydrochloride). 

 The other ingredients are: tartaric acid (E334), mannitol (E421), hydrochloric acid (E507) and 
sodium hydroxide. 

 

What Hycamtin looks like and contents of the pack 

Hycamtin comes as a powder for concentrate for solution for intravenous infusion. 

It is available in packs containing either 1 or 5 glass vials; each vial contains 1 mg or 4 mg of 

topotecan. 

The powder needs to be reconstituted and diluted before infusion. 

The powder in the vial provides 1 mg per ml of active substance when reconstituted as recommended. 

 



49 

Marketing Authorisation Holder 
Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 
Ireland 

 

Manufacturer 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Novartis Pharma GmbH 

Roonstrasse 25 

90429 Nuremberg 

Germany 

 

Novartis Pharmaceuticals UK Limited 

Frimley Business Park 

Frimley 

Camberley, Surrey GU16 7SR 

United Kingdom 

 

GlaxoSmithKline Manufacturing S.p.A. 

Strada Provinciale Asolana 90 

43056 San Polo di Torrile 

Parma 

Italy 

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

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 

SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел: +359 2 489 98 28 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 

Sandoz A/S 

Tlf: +45 63 95 10 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 88 04 52 555 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 

Sandoz A/S 

Tlf: +45 63 95 10 00 



50 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

BEXAL FARMACÉUTICA, S.A. 

Tel: +34 900 456 856 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Sandoz 

Tél: +33 800 45 57 99 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Sandoz S.R.L. 

Tel: +40 21 40751 60 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Sandoz A/S 

Tel: +45 63 95 10 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 

 

Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu/. 

 



51 

The following information is intended for healthcare professionals only: 

 

Instructions on how to reconstitute, store and dispose of Hycamtin 

 

Reconstitution 

Hycamtin 1 mg powder for concentrate for solution for infusion should be reconstituted with 1.1 ml 

of water for injections to provide 1 mg per ml of topotecan. 

Hycamtin 4 mg powder for concentrate for solution for infusion should be reconstituted with 4 ml of 

water for injections to provide 1 mg per ml of topotecan. 

 

Further dilution is required. The appropriate volume of the reconstituted solution should be diluted 

with either 0.9 % w/v sodium chloride intravenous infusion or 5 % w/v glucose intravenous infusion, 

to a final concentration of between 25 and 50 microgram per ml. 

 

Storage of the prepared solution 

The product should be used immediately after it is prepared for infusion. If reconstitution is performed 

under strict aseptic conditions Hycamtin infusion may be completed within 12 hours at room 

temperature (or 24 hours if stored at 2-8oC). 

 

Handling and disposal 

The normal procedures for proper handling and disposal of anti-tumour medicinal products should be 

adopted: 

 Staff should be trained to reconstitute the medicinal product. 

 Pregnant staff should be excluded from working with this medicinal product. 

 Staff handling this medicinal product during reconstitution 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. 

 Accidental contact with the skin or eyes should be treated immediately with copious amounts of 
water. 



52 

Package leaflet: Information for the user 
 

Hycamtin 0.25 mg hard capsules 

Hycamtin 1 mg hard capsules 

topotecan 

 

Read all of this leaflet carefully before you start taking this medicine because it contains 

important information for you. 

 Keep this leaflet. You may need to read it again. 

 If you have any further questions, ask your doctor or pharmacist. 

 This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even 
if their symptoms seem to be the same as yours. 

 If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. See section 4. 

 

What is in this leaflet: 

 

1. What Hycamtin is and what it is used for 

2. What you need to know before you take Hycamtin 

3. How to take Hycamtin 

4. Possible side effects 

5. How to store Hycamtin 

6. Contents of the pack and other information 

 

 

1. What Hycamtin is and what it is used for 

 

Hycamtin helps to destroy tumours. 

 

Hycamtin is used to treat small cell lung cancer that has come back after chemotherapy. 

 

Your doctor will decide with you whether Hycamtin therapy is better than further treatment with your 

initial chemotherapy. 

 

 

2. What you need to know before you take Hycamtin 

 

Do not take Hycamtin: 

 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 Hycamtin 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. 
Tell your doctor if any of these applies to you. 

 

  



53 

Other medicines and Hycamtin 

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. 

 

There may be a higher than usual chance of you getting side effects if you are also being treated with 

cyclosporin A. You will be monitored closely if you are taking both these medicines. 

 

Remember to tell your doctor if you start to take any other medicines while you are on Hycamtin. 

 

Pregnancy and breast-feeding 
Hycamtin 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 Hycamtin. Do not restart breast-feeding until the 

doctor tells you it is safe to do so. 

 

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

 

Hycamtin contains ethanol 

This medicine contains small amounts of ethanol (alcohol). 

 

 

3. How to take Hycamtin 

 

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 

if you are not sure. 

 

The capsule(s) must be swallowed whole, and must not be chewed, crushed or divided. 

 

The dose (and number of capsules) of Hycamtin 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 prescribed number of capsules should be swallowed whole, once a day for 5 days. 

 

Hycamtin capsules must not be opened or crushed. If the capsules are punctured or leaking, you 

should immediately wash your hands thoroughly with soap and water. If you get the capsule contents 

in your eyes, wash them immediately with gently flowing water for at least 15 minutes. Consult your 

doctor after eye contact or if you experience a skin reaction. 

 



54 

Taking out a capsule 

These capsules come in special packaging to prevent children removing them. 

 

1. Separate one capsule: tear along the perforated lines to separate one capsule “pocket” from the 

strip. 

 

 
 

2. Peel back the outer layer: starting at the coloured corner, lift and peel over the pocket. 

 

 
 

3. Push out the capsule: gently push one end of the capsule through the foil layer. 

 

 
 

If you take more Hycamtin than you should 

Contact a doctor or pharmacist immediately for advice if you have taken too many capsules or if a 

child has accidentally taken the medicine. 

 

If you forget to take Hycamtin 

Do not take a double dose to make up for a forgotten dose. Just take the next dose at the scheduled 

time. 

 

 



55 

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 Hycamtin: 

 Signs of infections: Hycamtin 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). 

 Diarrhoea. This can be serious. If you have more than 3 episodes of diarrhoea per day you 
should contact your doctor immediately. 

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

 
This rare side effect may affect up to 1 in 1,000 people treated with Hycamtin). 

 Lung inflammation (interstitial lung disease): You are most at risk if you have existing lung 

disease, had radiation treatment to your lungs, or have previously taken medicines that caused 

lung damage. Signs include: 

- difficulty in 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 Hycamtin: 

 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). 

 Hair loss. 
 

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

 Allergic or hypersensitivity reactions (including rash). 

 Inflammation and ulcers of the mouth, tongue or gums. 

 High body temperature (fever). 

 Stomach pain, constipation, indigestion. 

 Feeling unwell. 

 Itching sensation. 
 

Uncommon side effects 
These may affect up to 1 in 100 people treated with Hycamtin: 

 Yellow skin. 
 



56 

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

 Severe allergic or anaphylactic reactions. 

 Swelling caused by fluid build up (angioedema). 

 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]). 

 

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 Hycamtin 

 

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. 

 

Store in a refrigerator (2ºC - 8ºC). 

 

Do not freeze. 

 

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

 

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 

dispose of medicines no longer required. These measures will help to protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Hycamtin contains 

 The active substance is topotecan. Each capsule contains 0.25 mg or 1 mg of topotecan (as 
hydrochloride). 

 The other ingredients are: hydrogenated vegetable oil, glyceryl monostearate, gelatin, titanium 
dioxide (E171), and for 1 mg capsules only, red iron oxide (E172). The capsules are printed with 

black ink that contains black iron oxide (E172), shellac, anhydrous ethanol, propylene glycol, 

isopropyl alcohol, butanol, concentrated ammonia solution and potassium hydroxide. 

 

What Hycamtin looks like and contents of the pack 

Hycamtin 0.25 mg capsules are white to yellowish white and imprinted with “Hycamtin” and 

“0.25 mg”. 

 

Hycamtin 1 mg capsules are pink and imprinted with “Hycamtin” and “1 mg”. 

 

Hycamtin 0.25 mg and 1 mg capsules are available in packs containing 10 capsules. 

 



57 

Marketing Authorisation Holder 
Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 
Ireland 

 

Manufacturer 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Novartis Pharma GmbH 

Roonstrasse 25 

90429 Nuremberg 

Germany 

 

Novartis Pharmaceuticals UK Limited 

Frimley Business Park 

Frimley 

Camberley, Surrey GU16 7SR 

United Kingdom 

 

GlaxoSmithKline Manufacturing S.p.A. 

Strada Provinciale Asolana 90 

43056 San Polo di Torrile 

Parma 

Italy 

 

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

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 

SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел: +359 2 489 98 28 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 

Sandoz A/S 

Tlf: +45 63 95 10 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 88 04 52 555 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 

Sandoz A/S 

Tlf: +45 63 95 10 00 



58 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

BEXAL FARMACÉUTICA, S.A. 

Tel: +34 900 456 856 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Sandoz 

Tél: +33 800 45 57 99 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Sandoz S.R.L. 

Tel: +40 21 40751 60 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Sandoz A/S 

Tel: +45 63 95 10 00 

 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last revised in 

 

Other sources of information 
Detailed information on this medicine product is available on the European Medicines Agency web 

site: http://www.ema.europa.eu/. 

 


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