Topotecan infusion
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of topotecan
Drugs List
Therapeutic Indications
Uses
Carcinoma - cervix
Metastatic carcinoma of ovary (after previous therapy failure)
Relapsed small cell lung cancer if first-line retreatment isn't appropriate
Metastatic carcinoma of ovary where first line or subsequent therapy has failed.
Relapsed small cell lung cancer where re-treatment with the first-line regimen is not considered appropriate.
Cervical cancer in combination with cisplatin in patients with stage IVB disease or for recurrent disease following radiotherapy. Patients with prior exposure to cisplatin require a sustained treatment free interval to justify treatment with this combination.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
When used in combination with cisplatin, the prescribing information for cisplatin should be consulted.
Adults
Ovarian and small cell lung carcinoma
Initial dose:
1.5 mg/metre squared of body surface area (BSA) daily by intravenous infusion over 30 minutes for 5 consecutive days followed by a 3 week interval before the next cycle.
Treatment should continue until disease progression or unacceptable toxicity.
Subsequent doses:
Topotecan should not be re-administered unless:
Neutrophil count is greater than or equal to 1 x 10 to the power of 9/L, the platelet count is greater than or equal to 100 x 10 to the power of 9/L and the haemoglobin level is greater than or equal to 9 g/dL (after transfusion if necessary).
Combination therapy for cervical carcinoma
Initial dose:
0.75 mg/metre squared as a 30 minute intravenous infusion on days 1, 2 and 3 of a 21-day cycle. Repeated for 6 courses or until disease progression.
See prescribing information for cisplatin.
Subsequent doses:
Topotecan should not be re-administered unless:
The neutrophil count is greater than or equal to 1.5 x 10 to the power of 9/L, the platelet count is greater than or equal to 100 x 10 to the power of 9/L and the haemoglobin level is greater than or equal to 9 g/dL (after transfusion if necessary).
Elderly
(See Dosage; Adult)
Patients with Renal Impairment
Monotherapy for ovarian and small cell lung carcinoma
Creatinine clearance greater than 39 ml/minute: Dose as normal.
Creatinine clearance between 20 and 39 ml/minute: 0.75 mg/metre squared per day for 5 consecutive days.
Creatinine clearance less than 20 ml/minute: Not recommended.
Combination therapy for cervical carcinoma
In clinical studies, combination therapy was only initiated in patients with serum creatinine less than or equal to 1.5 mg/dL.
If during therapy serum creatinine exceeds 1.5 mg/dL, it is recommended that the prescribing information for cisplatin is consulted for advice on dose reduction/discontinuation. If cisplatin is discontinued, there are insufficient data regarding continuation of topotecan monotherapy in patients with cervical cancer.
The Renal Drug Handbook recommends the following dose reductions:
Glomerular filtration rate greater than 40 ml/minute: Dose as normal.
Glomerular filtration rate between 20 and 39 ml/minute: 50% of dose.
Glomerular filtration rate less than 20 ml/minute: 25% of dose.
Additional Dosage Information
Ovarian and small cell lung carcinoma
Reduce dose if any of the following occur:
Neutrophil count less than 0.5 x 10 to the power of 9/L for 7 days or more.
Severe neutropenia associated with fever or infection.
If treatment has been delayed due to neutropenia.
Platelet count falls below 25 x 10 to the power of 9/L.
Reduce dose to 1.25 mg/metre squared per day (or subsequently down to 1 mg/metre squared per day if necessary).
Consider discontinuing if the dose has been reduced to 1 mg/metre squared and a further dose reduction is required.
Combination therapy for cervical carcinoma
Reduce dose if any of the following occur:
Neutrophil count less than 0.5 x 10 to the power of 9/L for 7 days or more.
Severe neutropenia associated with fever or infection.
If treatment has been delayed due to neutropenia.
Platelet count falls below 25 x 10 to the power of 9/L.
Reduce dose to 0.6 mg/metre squared per day (or subsequently down to 0.45 mg/metre squared per day if necessary).
Administration
For intravenous infusion only over 30 minutes.
Contraindications
Children under 18 years
Haemoglobin concentration below 9g/dl
Neutrophil count below 1.0 x 10 to the power of 9 / L
Neutrophil count below 1.5 x 10 to the power of 9 / L at baseline
Platelet count below 100 x 10 to the power of 9/ L
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 20ml/minute
Renal impairment - serum creatinine > 133 micromol/L - Rxed for cervical Ca
Severe hepatic impairment - serum bilirubin equal to or more than 10mg/dl
Severe myelosuppression
Precautions and Warnings
History of thoracic radiotherapy
Performance status of ECOG 1 or greater
Hepatic impairment
History of pulmonary disease
Lung cancer
Neoplasm with increased bleeding risk
Pulmonary fibrosis
Renal impairment - creatinine clearance 20 - 39ml/minute
Advise ability to drive/operate machinery may be affected by side effects
Not all presentations are licensed for all indications
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of anti-cancer drugs
Dilute and use as an infusion
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Monitor haematological parameters before and during treatment
Consider neutropenic colitis if abdominal pain, fever and neutropenia occur
Monitor for signs and symptoms of interstitial lung disease
Reduce dose if neutrophil count < 500 cells/cubic mm for more than 7 days
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report symptoms of infection immediately
Advise patient to report unexplained fever, sore throat, bruising, bleeding
Consider G-CSF in severe neutropenia / agranulocytosis
Discontinue treatment if interstitial lung disease develops
Advise patient to seek advice at first indications of pregnancy
Reduce dose if neutrophils < 0.5 x 10 to the power 9/L with fever/infection
Reduce dose if platelets <25 x 10 to the power of 9/L
May cause impaired fertility
Male & female: Contraception required during & for 6 months after treatment
Pregnancy and Lactation
Pregnancy
Topotecan is contraindicated during pregnancy.
At the time of writing there is limited data on the use of topotecan in human pregnancy. Studies in rats and rabbits have shown embryo-foetal lethality and malformations.
The effect of concurrent therapies must also be considered.
Lactation
Topotecan is contraindicated during breastfeeding.
At the time of writing its is unknown whether topotecan is excreted in human breast milk, however the molecular weight suggests that it will be. Therefore a risk to neonates cannot be excluded.
The effect of concurrent therapies must also be considered.
Side Effects
Abdominal pain
Alopecia
Anaemia
Anaphylactic reaction
Angioedema
Anorexia
Asthenia
Bleeding
Constipation
Diarrhoea
Extravasation
Fatigue
Febrile neutropenia
Fever
Gastro-intestinal perforation
Hyperbilirubinaemia
Hypersensitivity reactions
Infections
Interstitial lung disease
Leukopenia
Malaise
Mucosal inflammation
Mucositis
Nausea
Neutropenia
Neutropenic colitis
Pancytopenia
Pruritus
Rash
Sepsis
Thrombocytopenia
Tumour haemorrhage
Urticaria
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: September 2015
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 6 May 2022.
Summary of Product Characteristics: Hycamtin 1mg and 4mg powder for concentrate for solution for infusion. Novartis Pharmaceuticals UK Ltd. Revised April 2015.
Summary of Product Characteristics: Potactasol 1mg powder for concentrate for solution for infusion. Actavis UK Ltd. Revised April 2015.
Summary of Product Characteristics: Potactasol 4mg powder for concentrate for solution for infusion. Actavis UK Ltd. Revised April 2015.
Summary of Product Characteristics: Topotecan 1mg/ml concentrate for solution for infusion. Accord Healthcare Ltd. Revised May 2021.
Summary of Product Characteristics: Topotecan 4mg powder for concentrate for solution for infusion. Accord Healthcare Ltd. Revised March 2015.
Summary of Product Characteristics: Topotecan 1mg powder for concentrate for solution for infusion. Actavis UK Ltd. Revised September 2011.
Summary of Product Characteristics: Topotecan 4mg powder for concentrate for solution for infusion. Actavis UK Ltd. Revised September 2011.
Summary of Product Characteristics: Topotecan 4mg/4ml concentrate for solution for infusion. Hospira UK Ltd. Revised May 2015.
Summary of Product Characteristics: Topotecan 1mg/ml concentrate for solution for infusion. Medac. Revised October 2014.
Summary of Product Characteristics: Topotecan 1mg/ml concentrate for solution for infusion. Teva. Revised November 2014.
Summary of Product Characteristics: Topotecan 4mg/4ml concentrate for solution for infusion. Teva. Revised November 2014.
The Renal Drug Handbook. 5th Edition (2019) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.
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