Cytotoxic elimination via Haemodialysis
Dialysed or likely to be dialysed
Not dialysed or thought unlikely
Unknown
Carboplatin
Cisplatin
Cyclophosphamide
5-Fluorouracil
Ifosfamide
Gemcitabine
Mercaptopurine
Bleomycin
Carmustine
Chlorambucil
Cytarabine
Daunorubicin
Docetaxel
Doxorubicin
Epiruicin
Etoposide
Irinotecan
Lomustine
Melphalan
Methotrexate
Oxaliplatin
Paclitaxel
Raltitrexed
Vinblastine
Cladribine
Fludarabine
Mitomycin C
Topotecan
Vincristine
Vinorelbine
Adapted from The Renal Handbook (2004)
Leucovorin dosing schedule depending on methotrexate levels
Leucovorin dose
1000mg/m 2 6 hourly IV
Methotrexate drug level – Molar
50 micromol/L (>5 x 10 -5 M)
5 - 50 micromol/L (5 x 10 -5 M to 10 -6 M)
0.5 - 5 micromol/L (5 x 10 -6 M to 5 x 10 -7 M)
< 0.5 micromol/L (<5 x 10 -7 M)
100mg/m
30mg/m
10mg/m
2
2
2 3 hourly IV
6 hourly IV/PO
6 hourly PO/IV
Toxbase (Poisons Information) 2007
Doses >50mg to be given intravenously (as oral absorption saturable)
Intravenous injections by slow IV bolus, max rate 160mg/min
Larger doses usually as infusion in sodium chloride 0.9% or glucose 5%
See chemotherapy protocol for leucovorin rescue following intentional high dose methotrexate treatment.

Specific Chemotherapy Rescue Treatments
Methotrexate urine alkalisation
Regimen used for high dose methotrexate treatment (in haematology)
1 litre dextrose/saline + 50mmol sodium bicarbonate + 20mmol potassium chloride
Infused at a rate of 125ml/m 2 /hr
(50mmol sodium bicarbonate = 50ml 8.4% solution)
Concentration of sodium bicarbonate is adjusted to maintain urinary pH between 7-8
Alternative schedule as suggested by Toxbase

225ml 8.4% sodium bicarbonate over 2 hours

1.5 litres of 1.26% sodium bicarbonate over 2 hours
Ifosfamide encephalopathy – stop ifosfamide
Methylene blue 50mg IV every 4 hours
Give as slow intravenous bolus over at least 5 minutes
Or in 250ml Glucose 5% over 30 minutes
Correct any low serum albumin levels
Hydration
Give mesna 1 gram IV if any signs of protein in urine repeat if necessary
Oxaliplatin
Neurotoxicity or diarrhoea

1 gram (10ml 10% injection) calcium gluconate 1000ml sodium chloride 0.9% infusion
1 gram (4mmol) magnesium sulphate in 500ml sodium chloride 0.9% infusion.
Mucositis
Especially haematology patients - Palifermin
60 micrograms/kg/day IV bolus for three days prior to chemotherapy and for three days after
Palifermin should not be administered within 24 hours of chemotherapy
Tumour lysis
Allopurinol not effective
Rasburicase 0.2mg/kg/day up to 7 days 50ml sodium chloride 0.9% infusion over 30 min
Chemoprotectants that will not reverse acute toxicities
Dexrazoxane
Amifostine
Little information is available regarding anecdotal and experimental agents, please contact senior staff if other rescue therapies are suggested.

USE OF ANTIDOTES AND SPECIFIC RESCUE THERAPIES IN
CHEMOTHERAPY - INFORMATION SUPPORT FOR MEDICAL STAFF AND
PHARMACISTS AT UNIVERSITY HOSPITAL OF NORTH STAFFORDSHIRE NHS
TRUST
Isabel Breeze, Nicola Stringer, Pharmacy Directorate
University Hospitals of North Staffordshire NHS Trust
Stoke-on-Trent
Introduction
Treatment following drug overdose can be difficult to manage, especially due to the toxicity of chemotherapy. Overdose may be accidental; due to high dose therapy or as a result of reduced elimination. Unexpected or severe adverse events warrant the use of antidotes where available. However, there is very little evidence to support rescue treatment or no available antidote means that haematological support with
GCSF, platelet, blood transfusions and symptomatic control of side effects is the mainstay of treatment.
Objective
To provide the Cancer team and the on-call pharmacists with a summary of information for which rescue therapies are available and selective antidotes to particular toxicity or agent.
Method
A literature review was carried out include Toxbase, ASCO guidelines and case reports.
Results
Toxbase 1 is a database that provides guidance on limiting oral absorption of chemotherapy agents. However, treatment options are limited to a small number of drugs
–methotrexate; chlorambucil; cyclophosphamide; imatinib and procarbazine.
Elimination – this can be enhanced by haemodiaylsis in a limited number of agents 2 ;

Carboplatin

Cisplatin

Cyclophosphamide

5-Fluorouracil

Ifosfamide

Gemcitabine

Mercaptopurine
Use of chemoprotectants has been studied, but as this requires planned treatment with the chemotherapy they were not considered as salvage therapies.

Specific agents
Folinic acid rescue +/- hydration is recognised as standard treatment post methotrexate. Dosage is dependent on plasma levels following drug overdose or intentional high dose treatment.
There have been reports of methylene blue being used for ifosfamide induced encephalopathy. However, its usefulness is unclear as many patients have recovered spontaneously without any antidote 3 .
Conclusion
There is little information available regarding specific salvage therapies following a chemotherapy overdose. Case reports offer some advice on methods or agents used to reverse toxicity but there have been no large studies regarding their use.
A summary of recognised treatment options has been produced in the form of an information sheet available for medical staff and pharmacy. This is to be available on the oncology/haematology ward and with the on-call pharmacist.
Reference
1. Toxbase [online] Available from: http://www.spib.axl.co.uk/toxbaseindex.htm
2. Ashley, C. & Currie, A. eds. (2004) The Renal Drug Handbook . 2 nd edn.
Oxford: UK Renal Pharmacy Group Radcliffe Medical Press.
3. Patel, P.N. (2006) Methylene Blue for Management of Ifosfamide-induced
Encephalopathy. The Annuals of Pharmacotherapy 40 (2): 299-303

USE OF ANTIDOTES AND SPECIFIC RESCUE THERAPIES IN CHEMOTHERAPY
- INFORMATION SUPPORT FOR MEDICAL STAFF AND PHARMACISTS AT
UNIVERSITY HOSPITAL OF NORTH STAFFORDSHIRE NHS TRUST
Isabel Breeze, Nicola Stringer, Pharmacy Directorate
University Hospitals North Staffordshire NHS Trust (UHNS), Stoke-on-Trent
Contact details:
Isabel Breeze
Senior Pharmacist, Oncology
University Hospital of North Staffordshire
The Cancer Centre
Pharmacy
City General
Newcastle Road
Stoke-on-Trent
ST4 6QG
Telephone 01782 552254
Fax
E-mail
01782 552784 isabel.breeze@uhns.nhs.uk