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  • Hycamtin IV
    / Novartis


    Active Ingredient

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    1 X 4 mg

    partial basket chart 75309 8349

    Dosage

    Prior to administration of the first course of topotecan, patients must have a baseline neutrophil count of ≥ 1.5 x 10^9/l, a platelet count of ≥ 100 x 10^9/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/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.
    Subsequent doses: Topotecan should not be re-administered unless the neutrophil count is ≥ 1 x 10^9/l, the platelet count is ≥ 100 x 10^9/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 medications (e.g. G-CSF) or to dose reduce to maintain neutrophil counts. If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count < 0.5 x 10^9/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 10^9/l. In clinical trials, topotecan was discontinued if the dose had been reduced to 1.0 mg/m2 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 30 minute intravenous infusion daily on days 1, 2 and 3. Cisplatin is administered as an intravenous infusion on day 1 at a dose of 50 mg/m²/day and following the topotecan dose. This treatment schedule is repeated every 21 days for six courses or until progressive disease.
    Subsequent doses: Topotecan should not be re-administered unless the neutrophil count is more than or equal to 1.5 x 10^9/l, the platelet count is more than or equal to 100 x 10^9/l, and the haemoglobin level is more than or equal to 9 g/dl (after transfusion if necessary). Standard oncology practice for the management of neutropenia is either to administer topotecan with other medications (e.g. G-CSF) or to dose reduce to maintain neutrophil counts. If dose reduction is chosen for patients who experience severe neutropenia (neutrophil count less than 0.5 x 10^9/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 10^9/l.
    Dosage in renally impaired patients
    Monotherapy (Ovarian and Small cell lung carcinoma): Insufficient data are available to make a recommendation for patients with a creatinine clearance < 20 ml/min. Limited data indicate that the dose should be reduced in patients with moderate renal impairment. The recommended monotherapy dose of topotecan in patients with ovarian or small cell lung carcinoma and a creatinine clearance between 20 and 39 ml/min is 0.75 mg/m² /day for five consecutive days.
    Combination therapy (Cervical carcinoma): In clinical studies with topotecan in combination with cisplatin for the treatment of cervical cancer, therapy was only initiated in patients with serum creatinine less than or equal to 1.5 mg/dl. If, during topotecan/cisplatin combination therapy serum creatinine exceeds 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.
    Paediatric population: The experience in children is limited, therefore no recommendation for treatment of paediatric patients with HYCAMTIN can be given.


    Indications

    Small cell lung cancer sensitive disease after failure of first line chemotherapy. Metastatic carcinoma of the ovary after failure of first-line or subsequent therapy. In combination with cisplatin for the treatment of stage IV-B, recurrent, or persistent carcinoma of the cervix, which is not amenable to curative treatment with surgery and/or radiation therapy.


    Contra-Indications

    Topotecan is contra-indicated in patients who
    – have a history of severe hypersensitivity to the active substance or to any of the excipients.
    – are breast-feeding
    – already have severe bone marrow depression prior to starting first course, as evidenced by baseline neutrophils < 1.5 x 10^9/l and/or a platelet count of < 100 x 10^9/l.


    Special Precautions

    Haematological toxicity is dose-related and full blood count including platelets should be monitored regularly. 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. Topotecan-induced neutropenia can cause neutropenic colitis. Fatalities due to neutropenic colitis have been reported in clinical trials 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. Underlying risk factors include history of ILD, pulmonary fibrosis, lung cancer, thoracic exposure to radiation and use of pneumotoxic drugs 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. in case patients at increased risk of tumour bleeds are considered for therapy.
    As 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. Accurate assessment of performance status at the time therapy is given is important, to ensure that patients have not deteriorated to performance status 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. Topotecan is not recommended to be used in these patient groups.
    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 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.


    Side Effects

    Very common: febrile neutropenia, neutropenia, thrombocytopenia, anaemia, leucopenia, nausea, vomiting and diarrhoea (all of which may be severe), constipation, abdominal pain, mucositis, alopecia, anorexia (which may be severe), infection, pyrexia, asthenia, fatigue.
    Common: pancytopenia, pruritus, sepsis, malaise, hypersensitivity reaction including rash, hyperbilirubinaemia.
    For full details see prescribing information.


    Drug interactions

    No in vivo human pharmacokinetic interaction studies have been performed. Topotecan does not inhibit human P450 enzymes. In an intravenous population study, 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).
    In combining topotecan with other chemotherapy agents, reduction of the doses of each medicinal product may be required to improve tolerability. However, in 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.


    Pregnancy and Lactation

    Pregnancy: Topotecan has been shown to cause embryo-foetal lethality and malformations in preclinical studies. 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 and to inform the treating physician immediately should this occur. 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.
    Lactation: Topotecan is contra-indicated during breast-feeding. Although it is not known whether topotecan is excreted in human breast milk, breast-feeding should be discontinued at the start of therapy.


    Overdose

    Overdoses (up to 10-fold of the prescribed dose) occurred in patients treated with intravenous topotecan. The primary complication of overdosage is bone marrow suppression. The observed signs and symptoms of overdose are consistent with the known adverse reactions associated with HYCAMTIN for intravenous use. In addition, elevated hepatic enzymes and mucositis have been reported following overdose. One patient received a single dose of 40 mg/m² of intravenous topotecan and developed gastrointestinal toxicity, skin toxicity, and myelosuppression leading to septic shock. Another patient received a single dose of 35 mg/m² and experienced severe, reversible neutropenia. There is no known antidote for overdosage with HYCAMTIN. If an overdose is suspected, monitor the patient for bone marrow suppression and institute supportive-care measures (such as prophylactic G-CSF and antibiotic therapy) as appropriate.


    Important notes

    Reconstituted and diluted solutions: The product should be used immediately after reconstitution as it contains no antibacterial preservative. If reconstitution and dilution are 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 breakage.
    Storage: Keep the vial in the outer carton in order to protect from light. Store below 30°C.


    Manufacturer
    GlaxoSmithKline Manufacturing S.p.A, Parma, Italy
    Licence holder
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