Topotecan oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of topotecan
Drugs List
Therapeutic Indications
Uses
Relapsed small cell lung cancer if first-line retreatment isn't appropriate
Treatment of adult patients with relapsed small cell lung cancer for whom re-treatment with the first line regimen is not considered appropriate.
Dosage
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Adults
Initial dose :
The recommended dose is 2.3 mg/metre square of body surface area per day for 5 consecutive days with a 3 week interval between the start of each course. If well tolerated, treatment may continue until disease progression.
Prior to administration of the first course of topotecan, patients must have a baseline neutrophil count greater than or equal to 1.5 x 10 to the power of 9 per litre. A platelet count greater than or equal to 100 x 10 to the power of 9 per litre and a haemoglobin level equal to or greater than 9 g per dl (after transfusion if necessary).
Subsequent doses :
Topotecan should not be re-administered unless:
The neutrophil count is greater than or equal to 1 x 10 to the power of 9 per litre, the platelet count is greater than or equal to 100 x 10 to the power of 9 per litre and the haemoglobin level is greater than or equal to 9 g per dl (after transfusion if necessary).
Patients with severe neutropenia (neutrophil count less than 0.5 x 10 to the power of 9 per litre) for 7 days or more, or severe neutropenia associated with fever or infection or where treatment has been delayed due to neutropenia should be given a dose reduced by 0.4 mg per metre square per day to 1.9 mg per metre square per day (or subsequently down to 1.5 mg per metre square per day if necessary).
A similar reduction should be made if platelet count falls below 25 x 10 to the power of 9 per litre. Where a dose reduction below 1.5 mg per metre square per day was required in clinical trials, topotecan was discontinued.
Elderly
Initial dose :
The recommended dose is 2.3 mg/metre square of body surface area per day for 5 consecutive days with a 3 week interval between the start of each course. If well tolerated, treatment may continue until disease progression.
Prior to administration of the first course of topotecan, patients must have a baseline neutrophil count greater than or equal to 1.5 x 10 to the power of 9 per litre. a platelet count greater than or equal to 100 x 10 to the power of 9 per litre and a haemoglobin level equal to or greater than 9 g per dl (after transfusion if necessary).
Subsequent doses :
Topotecan should not be re-administered unless:
The neutrophil count is greater than or equal to 1 x 10 to the power of 9 per litre, the platelet count is greater than or equal to 100 x 10 to the power of 9 per litre and the haemoglobin level is greater than or equal to 9 g per dl (after transfusion if necessary).
Patients with severe neutropenia (neutrophil count less than 0.5 x 10 to the power of 9 per litre) for 7 days or more, or severe neutropenia associated with fever or infection or where treatment has been delayed due to neutropenia should be given a dose reduced by 0.4 mg per metre square per day to 1.9 mg per metre square per day (or subsequently down to 1.5 mg per metre square per day if necessary).
A similar reduction should be made if platelet count falls below 25 x 10 to the power of 9 per litre. Where a dose reduction below 1.5 mg per metre square per day was required in clinical trials, topotecan was discontinued.
Patients with Renal Impairment
Creatinine clearance greater than 49 ml/minute: Dose as normal.
Creatinine clearance between 30 and 49 ml/minute: 1.9 mg/metre squared per day for 5 consecutive days. If well tolerated increase dose to 2.3 mg/metre squared per day in subsequent cycles.
Creatinine clearance less than 30 ml/minute: Not recommended.
Limited data in korean patients with creatinine clearance less than 50 ml/minute suggest a further lowering of dose may be required.
Note that the different recommendation apply to parenteral topotecan due to different dose regimens
Additional Dosage Information
For patients who experience Grade 3 or 4 diarrhoea, the dose should be reduced by 0.4 mg/metre square per day for subsequent doses. Patients with Grade 2 diarrhoea may need to follow the same dose modification guidelines.
Diarrhoea is more common in elderly patients.
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
Hepatic impairment
Pregnancy
Renal impairment - creatinine clearance below or equal to 30ml/minute
Severe myelosuppression
Precautions and Warnings
History of thoracic radiotherapy
Performance status of ECOG 1 or greater
History of pulmonary disease
Interstitial lung disease
Neoplasm with increased bleeding risk
Pulmonary fibrosis
Renal impairment - creatinine clearance 30-50ml/minute
Advise ability to drive/operate machinery may be affected by side effects
Anti-diarrhoeals may be required during treatment
Treatment to be prescribed under the supervision of a specialist
Consult local policy on the safe use of oral anti-cancer drugs
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
Patients with new pulmonary symptoms should be investigated
Advise patient to report any new or worsening respiratory symptoms
Advise patient to report symptoms of infection immediately
Consider dose reduction for subsequent doses if severe diarrhoea occurs
Discontinue treatment if interstitial lung disease develops
Male & female: Ensure adequate contraception during treatment
Advise on measures to take if diarrhoea occurs
Patients with poor Eastern Co-operative Oncology Group (ECOG) performance status (greater than 1) have a lower response rate and an increased risk of complications such as fever, infection, sepsis. Patients should be assessed at the time of therapy to ensure they have not deteriorated to performance status 3.
Patients should be advised prior to treatment of the possibility of severe or life threatening diarrhoea occurring. Advice on the management of early and all signs and symptoms of diarrhoea is important. In two studies administering both oral and intravenous topotecan, patients older than 65 years old receiving oral topotecan experienced an increase in drug related diarrhoea compared to those younger than 65 years of age.
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.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Lactation
Topotecan is contraindicated in 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.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Side Effects
Abdominal pain
Alopecia
Anaemia
Anaphylactic reaction
Angioedema
Anorexia
Asthenia
Bleeding
Constipation
Dehydration
Diarrhoea
Dyspepsia
Fatigue
Febrile neutropenia
Fever
Hyperbilirubinaemia
Hypersensitivity reactions
Infections
Interstitial lung disease
Leukopenia
Malaise
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: July 2016
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 5th July 2016.
Summary of Product Characteristics: Hycamtin 0.25 and 1mg hard capsule. GlaxoSmithKline UK. Revised April 2015.
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