oedema .reticulocytopenia .rhabdomyolysis . seizure . tremor
l CONCEPTION AND CONTRACEPTION Contraceptive advice
required, see Pregnancy and reproductive function in
l PREGNANCY Avoid (teratogenic in animal studies). See
also Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Discontinue breast-feeding.
Dose adjustments Reduce dose—consult product literature.
▶ Haematological monitoring Cytarabine is a potent
myelosuppressant and requires careful haematological
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (July 2007)
that liposomal cytarabine suspension (DepoCyte ®) is not
recommended for use within NHS Scotland for the
intrathecal treatment of lymphomatous meningitis.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: solution for
▶ Cytarabine (Non-proprietary)
Cytarabine 20 mg per 1 ml Cytarabine 100mg/5ml solution for
injection Cytosafe vials | 5 vial P £20.48 (Hospital only)
Cytarabine 500mg/25ml solution for injection vials | 1 vial P £19.50
Cytarabine 500mg/25ml solution for injection Cytosafe vials | 1 vial P £19.50 (Hospital only)
Cytarabine 100 mg per 1 ml Cytarabine 1g/10ml solution for
injection Cytosafe vials | 1 vial P £39.00 (Hospital only)
Cytarabine 1g/10ml solution for injection vials | 1 vial P £40.00–
£49.78 (Hospital only) | 1 vial P £37.05–£39.00
Cytarabine 100mg/1ml solution for injection vials | 5 vial P £26.93
Cytarabine 2g/20ml solution for injection Cytosafe vials | 1 vial P £77.50 (Hospital only)
Cytarabine 2g/20ml solution for injection vials | 1 vial P £79.00–
£98.92 (Hospital only) | 1 vial P £73.63–£77.50
▶ DepoCyte (Napp Pharmaceuticals Ltd)
Cytarabine liposomal pegylated 10 mg per 1 ml DepoCyte
50mg/5ml suspension for injection vials | 1 vial P £1,223.75
Combinations available: Daunorubicin with cytarabine, p. 900
l DRUG ACTION Decitabine is a pyrimidine analogue.
Treatment of newly diagnosed acute myeloid leukaemia in
patients over 65 years of age who are not candidates for
standard induction chemotherapy
▶ Elderly: (consult local protocol)
l CAUTIONS History of severe congestive heart failure . history of unstable cardiac disease
l INTERACTIONS → Appendix 1: decitabine
infection . leucopenia . nausea . neutropenia . sepsis . stomatitis .thrombocytopenia . vomiting
▶ Uncommon Acute febrile neutrophilic dermatosis . pancytopenia
▶ Frequency not known Gastrointestinal disorders . interstitial lung disease
l CONCEPTION AND CONTRACEPTION Men must avoid
fathering a child during and for 3 months after treatment.
l PREGNANCY Avoid (teratogenic in animal studies). See
also Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises caution—no
l RENAL IMPAIRMENT Manufacturer advises caution if
creatinine clearance less than 30 mL/minute—no
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for infusion
ELECTROLYTES: May contain Potassium, sodium
Decitabine 50 mg Dacogen 50mg powder for concentrate for
solution for infusion vials | 1 vial P £970.86
Initial treatment of advanced B-cell chronic lymphocytic
leukaemia (CLL) or after first line treatment in patients
with sufficient bone-marrow reserves
▶ Adult: 40 mg/m2 for 5 days every 28 days, usually given
▶ BY INTRAVENOUS INJECTION, OR BY INTRAVENOUS INFUSION
▶ Adult: (consult product literature)
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
l CONTRA-INDICATIONS Haemolytic anaemia
l CAUTIONS Increased susceptibility to skin cancer. worsening of existing skin cancer
▶ Immunosuppression Fludarabine has a potent and prolonged
immunosuppresive effect. Patients treated with
fludarabine are more prone to serious bacterial,
opportunistic fungal, and viral infections, and prophylactic
therapy is recommended in those at risk. To prevent
potentially fatal transfusion-related graft-versus-host
reaction, only irradiated blood products should be
administered. Prescribers should consult specialist
literature when using highly immunosuppressive drugs.
Co-trimoxazole is used to prevent pneumocystis
l INTERACTIONS → Appendix 1: fludarabine
BNF 78 Cytotoxic responsive malignancy 909
Immune system and malignant disease
neutropenia . oedema . stomatitis .thrombocytopenia . vision disorders . vomiting
▶ Uncommon Autoimmune disorder. confusion . haemorrhage .tumour lysis syndrome
▶ Rare or very rare Agitation . arrhythmia . coma . heart
failure . seizure . severe cutaneous adverse reactions
▶ With oral use Progressive multifocal leukoencephalopathy
(PML). skin reactions . viral infection reactivation
▶ With parenteral use Pulmonary toxicity
▶ With parenteral use Encephalopathy . intracranial
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception during and for at least 6 months
after treatment in men or women.
l PREGNANCY Avoid (embryotoxic and teratogenic in animal
studies). See also Pregnancy and reproductive function in
l BREAST FEEDING Discontinue breast-feeding.
l RENAL IMPAIRMENT Avoid if creatinine clearance less than
Dose adjustments Reduce dose by up to 50% if creatinine
▶ Monitor for signs of haemolysis.
▶ Monitor for neurological toxicity.
▶ Assess creatinine clearance in patients over 65 years
l DIRECTIONS FOR ADMINISTRATION Concentrate for
intravenous injection or infusion must be diluted before
administration (consult product literature).
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Fludarabine monotherapy for the first-line treatment of
chronic lymphocytic leukaemia (February 2007) NICE TA119
Fludarabine monotherapy is not recommended for the
first-line treatment of chronic lymphocytic leukaemia.
▶ Fludarabine for the treatment of B-cell chronic lymphocytic
leukaemia (September 2001) NICE TA29
Oral fludarabine is recommended for the second-line
treatment of B-cell chronic lymphocytic leukaemia in
patients who have either failed, or are intolerant of, first
line chemotherapy, and who would otherwise have
received combination chemotherapy of either:
. cyclophosphamide, doxorubicin, vincristine and
. cyclophosphamide, doxorubicin and prednisolone (CAP)
. cyclophosphamide, vincristine and prednisolone (CVP)
Intravenous fludarabine should only be used when oral
fludarabine is contra-indicated.
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (October
2006) that fludarabine is accepted for restricted use for the
treatment of B-cell chronic lymphocytic leukaemia (CLL)
in patients with sufficient bone marrow reserves. First-line
treatment should only be initiated in patients with
advanced disease, Rai stages III/IV (Binet stage C), or Rai
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Fludarabine phosphate (Non-proprietary)
Fludarabine phosphate 25 mg per 1 ml Fludarabine phosphate
Powder for solution for injection
▶ Fludarabine phosphate (Non-proprietary)
Fludarabine phosphate 50 mg Fludarabine phosphate 50mg
powder for solution for injection vials | 1 vial P £155.00 (Hospital
Fludarabine phosphate 50 mg Fludara 50mg powder for solution
for injection vials | 5 vial P £735.34 (Hospital only)
Treatment of some solid tumours including gastrointestinal tract cancers and breast cancer | In
combination with folinic acid in advanced colorectal
▶ BY INTRAVENOUS INJECTION, OR BY INTRAVENOUS INFUSION,
▶ Adult: (consult product literature)
l CONTRA-INDICATIONS Bone marrow depression (after
treatment with radiotherapy or other antineoplastic
agents). complete or near complete absence of
dihydropyrimidine dehydrogenase activity (increased risk
of severe, life-threatening, or fatal toxicity)—consult
product literature . serious infections
l CAUTIONS History of heart disease . partial
dihydropyrimidine dehydrogenase deficiency—consult
l INTERACTIONS → Appendix 1: fluorouracil
▶ Rare or very rare Biliary sclerosis . cardiac arrest. cerebral
ischaemia . cholecystitis . coma . confusion . embolism and
impairment. sudden cardiac death
▶ Frequency not known Vein discolouration
910 Cytotoxic responsive malignancy BNF 78
Immune system and malignant disease
l CONCEPTION AND CONTRACEPTION Contraceptive advice
required, see Pregnancy and reproductive function in
l PREGNANCY Avoid (teratogenic). See also Pregnancy and
reproductive function in Cytotoxic drugs p. 888.
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises caution
(increased risk of hyperammonaemia and
hyperammonaemic encephalopathy).
Dose adjustments Manufacturer advises consider dose
l RENAL IMPAIRMENT Manufacturer advises caution
(increased risk of hyperammonaemia and
hyperammonaemic encephalopathy).
Dose adjustments Manufacturer advises consider dose
l PRE-TREATMENT SCREENING Manufacturer advises
genotyping of the DPYD gene to identify patients at
increased risk for severe toxicity—consult product
l MONITORING REQUIREMENTS Manufacturer advises
monitor cardiac function regularly
l HANDLING AND STORAGE Caution in handling—irritant to
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: solution for
▶ Fluorouracil (Non-proprietary)
Fluorouracil (as Fluorouracil sodium) 25 mg per 1 ml Fluorouracil
500mg/20ml solution for injection vials | 10 vial P £64.00
Fluorouracil 250mg/10ml solution for injection vials | 5 vial P £24.00 (Hospital only)
Fluorouracil (as Fluorouracil sodium) 50 mg per 1 ml Fluorouracil
1g/20ml solution for injection vials | 1 vial P £12.16–£12.80
▶ Fluorouracil (Non-proprietary)
Fluorouracil (as Fluorouracil sodium) 25 mg per 1 ml Fluorouracil
2.5g/100ml solution for infusion vials | 1 vial P £32.00 (Hospital
Fluorouracil (as Fluorouracil sodium) 50 mg per 1 ml Fluorouracil
5g/100ml solution for infusion vials | 1 vial P £64.00 (Hospital
only) | 1 vial P £60.80–£64.00
Fluorouracil 2.5g/50ml solution for infusion vials | 1 vial P £32.00
(Hospital only) | 1 vial P £30.40–£32.00
First-line treatment for locally advanced or metastatic
non-small cell lung cancer (as monotherapy in elderly
patients and in palliative treatment; otherwise in
combination with cisplatin)| Treatment of locally
advanced or metastatic pancreatic cancer | Treatment of
advanced or metastatic bladder cancer (in combination
with cisplatin)| Treatment of locally advanced or
metastatic epithelial ovarian cancer which has relapsed
after a recurrence-free interval of at least 6 months
following previous platinum-based therapy (in
combination with carboplatin)| Treatment of metastatic
breast cancer which has relapsed after previous
chemotherapy including an anthracycline (in
▶ Adult: (consult local protocol)
l INTERACTIONS → Appendix 1: gemcitabine
▶ Common or very common Alopecia . anaemia . appetite
▶ Uncommon Respiratory disorders
encephalopathy syndrome (PRES). severe cutaneous
adverse reactions (SCARs). skin ulcer.thrombocytosis
SIDE-EFFECTS, FURTHER INFORMATION Gemcitabine
should be discontinued if signs of microangiopathic
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception during treatment. Men must avoid
fathering a child during and for 6 months after treatment.
l PREGNANCY Avoid (teratogenic in animal studies). See
Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises caution
(limited information available).
l RENAL IMPAIRMENT Manufacturer advises caution.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Gemcitabine for the treatment of pancreatic cancer (May
Gemcitabine is an option for first-line chemotherapy for
patients with advanced or metastatic adenocarcinoma of
the pancreas and a Karnofsky score of at least 50
[Karnofsky score is a measure of the ability to perform
Gemcitabine is not recommended for patients who can
have potentially curative surgery. There is insufficient
evidence to support its use for second-line treatment of
▶ Gemcitabine for the treatment of metastatic breast cancer
Gemcitabine, in combination with paclitaxel, is an option
for the treatment of metastatic breast cancer only when
docetaxel monotherapy or docetaxel plus capecitabine are
www.nice.org.uk/guidance/TA116
▶ Bevacizumab in combination with gemcitabine and
carboplatin for the treatment of the first recurrence of
platinum-sensitive advanced ovarian cancer (May 2013)
Bevacizumab in combination with gemcitabine and
carboplatin is not recommended within its marketing
authorisation, that is, for the treatment of the first
recurrence of platinum-sensitive advanced ovarian cancer
(including fallopian tube and primary peritoneal cancer)
that has not been previously treated with bevacizumab or
other vascular endothelial growth factor (VEGF) inhibitors
or VEGF receptor-targeted agents.
www.nice.org.uk/guidance/TA285
▶ Topotecan, pegylated liposomal doxorubicin hydrochloride,
paclitaxel, trabectedin and gemcitabine for treating recurrent
ovarian cancer (April 2016) NICE TA389
Gemcitabine, in combination with carboplatin, is not
recommended for treating the first recurrence of
platinum-sensitive ovarian cancer.
BNF 78 Cytotoxic responsive malignancy 911
Immune system and malignant disease
Patients currently receiving gemcitabine in combination
with carboplatin should have the option to continue their
treatment until they and their clinician consider it
www.nice.org.uk/guidance/TA389
▶ Paclitaxel as albumin-bound nanoparticles with gemcitabine
for untreated metastatic pancreatic cancer (September 2017)
Gemcitabine with paclitaxel as albumin-bound
nanoparticles (nab-paclitaxel) is recommended as an
option for untreated metastatic adenocarcinoma of the
. other combination chemotherapies are unsuitable and
they would otherwise have gemcitabine monotherapy,
. the manufacturer provides nab-paclitaxel with the
discount agreed in the patient access scheme.
Patients whose treatment with nab-paclitaxel was started
before this guidance was published, should have the
option to continue treatment until they and their NHS
clinician consider it appropriate to stop.
www.nice.org.uk/guidance/TA476
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (December
2006) that gemcitabine (Gemzar ®) is accepted for
restricted use within NHS Scotland for the treatment of
metastatic breast cancer, which has relapsed following
previous chemotherapy including an anthracycline (unless
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Gemcitabine (Non-proprietary)
Gemcitabine (as Gemcitabine hydrochloride)
200 mg Gemcitabine 200mg/2ml concentrate for solution for
infusion vials | 1 vial P £6.40
Gemcitabine 200mg/5.26ml concentrate for solution for infusion vials
| 1 vial P £30.56 (Hospital only)
Gemcitabine (as Gemcitabine hydrochloride) 1 gram Gemcitabine
1g/26.3ml concentrate for solution for infusion vials | 1 vial P £152.67 (Hospital only)
Gemcitabine 1g/25ml concentrate for solution for infusion vials | 1 vial P £13.09
Gemcitabine 1g/10ml concentrate for solution for infusion vials | 1 vial P £13.09
Gemcitabine (as Gemcitabine hydrochloride) 2 gram Gemcitabine
2g/50ml concentrate for solution for infusion vials | 1 vial P £26.86
Gemcitabine 2g/20ml concentrate for solution for infusion vials | 1 vial P £26.86
Gemcitabine 2g/52.6ml concentrate for solution for infusion vials | 1 vial P £305.36 (Hospital only)
Gemcitabine (as Gemcitabine hydrochloride) 10 mg per
1 ml Gemcitabine 1.6g/160ml infusion bags | 1 bag P £140.00
Gemcitabine 2.2g/220ml infusion bags | 1 bag P £200.00
Gemcitabine 2g/200ml infusion bags | 1 bag P £180.00
Gemcitabine 1.2g/120ml infusion bags | 1 bag P £120.00
Gemcitabine 1.8g/180ml infusion bags | 1 bag P £160.00
Powder for solution for infusion
▶ Gemcitabine (Non-proprietary)
Gemcitabine (as Gemcitabine hydrochloride)
200 mg Gemcitabine 200mg powder for solution for infusion vials |
1 vial P £32.00–£32.55 (Hospital only) | 1 vial P £30.56–
Gemcitabine (as Gemcitabine hydrochloride) 1 gram Gemcitabine
1g powder for solution for infusion vials | 1 vial P £162.00–
£162.76 (Hospital only) | 1 vial P £148.26–£162.00
Gemcitabine (as Gemcitabine hydrochloride) 2 gram Gemcitabine
2g powder for solution for infusion vials | 1 vial P £324.00
(Hospital only) | 1 vial P £324.00–£393.82
Severe acute Crohn’s disease | Maintenance of remission of
Crohn’s disease | Ulcerative colitis
▶ Adult: 1–1.5 mg/kg daily, some patients may respond
Acute leukaemias | Chronic myeloid leukaemia
▶ Adult: Initially 2.5 mg/kg daily, adjusted according to
response, alternatively initially 50–75 mg/m2 daily,
adjusted according to response
▶ BY MOUTH USING ORAL SUSPENSION
▶ Adult: Initially 25–75 mg/m2 daily, adjusted according
DOSE ADJUSTMENTS DUE TO INTERACTIONS
▶ Manufacturer advises reduce dose to one-quarter of
the usual dose with concurrent use of allopurinol.
DOSE EQUIVALENCE AND CONVERSION
▶ Mercaptopurine tablets and Xaluprine ® oral
suspension are not bioequivalent, haematological
monitoring is advised when switching formulations.
l UNLICENSED USE Not licensed for use in severe ulcerative
Mercaptopurine has been confused with mercaptamine;
care must be taken to ensure the correct drug is
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
l CONTRA-INDICATIONS Absent thiopurine
l CAUTIONS Reduced thiopurine methyltransferase activity
▶ Thiopurine methyltransferase The enzyme thiopurine
methyltransferase (TPMT) metabolises thiopurine drugs
(azathioprine, mercaptopurine, tioguanine); the risk of
myelosuppression is increased in patients with reduced
activity of the enzyme, particularly for the few individuals
in whom TPMT activity is undetectable. Patients with
absent TPMT activity should not receive thiopurine drugs;
those with reduced TPMT activity may be treated under
l INTERACTIONS → Appendix 1: mercaptopurine
▶ Uncommon Arthralgia . fever. increased risk of infection . neutropenia . pancreatitis .rash
▶ Rare or very rare Alopecia . face oedema . intestinal ulcer. neoplasms . oligozoospermia
▶ Frequency not known Photosensitivity reaction
l CONCEPTION AND CONTRACEPTION Contraceptive advice
required, see Pregnancy and reproductive function in
l PREGNANCY Avoid (teratogenic). See also Pregnancy and
reproductive function in Cytotoxic drugs p. 888.
l BREAST FEEDING Discontinue breast-feeding.
912 Cytotoxic responsive malignancy BNF 78
Immune system and malignant disease
Dose adjustments May need dose reduction.
l PRE-TREATMENT SCREENING Consider measuring
thiopurine methyltransferase (TPMT) activity before
starting mercaptopurine therapy.
l MONITORING REQUIREMENTS Monitor liver function.
l PRESCRIBING AND DISPENSING INFORMATION Flavours of
oral liquid formulations may include raspberry.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: tablet, capsule, oral
EXCIPIENTS: May contain Aspartame
▶ Xaluprine (Nova Laboratories Ltd)
Mercaptopurine 20 mg per 1 ml Xaluprine 20mg/ml oral suspension
| 100 ml P £170.00 DT = £170.00
▶ Mercaptopurine (Non-proprietary)
Mercaptopurine 10 mg Mercaptopurine 10mg tablets | 100 tablet P s
Mercaptopurine 50 mg Mercaptopurine 50mg tablets | 25 tablet P £49.15 DT = £49.15
l DRUG ACTION Methotrexate inhibits the enzyme
dihydrofolate reductase, essential for the synthesis of
▶ Adult: Initially 25 mg once weekly until remission
induced; maintenance 15 mg once weekly
Maintenance of remission of severe Crohn’s disease
Moderate to severe active rheumatoid arthritis
▶ Adult: 7.5 mg once weekly, adjusted according to
response; maximum 20 mg per week
Severe active rheumatoid arthritis
▶ BY INTRAMUSCULAR INJECTION, OR BY SUBCUTANEOUS
▶ Adult: Initially 7.5 mg once weekly, then increased in
steps of 2.5 mg once weekly, adjusted according to
response; maximum 25 mg per week
▶ BY MOUTH, OR BY INTRAVENOUS INJECTION, OR BY
INTRAVENOUS INFUSION, OR BY INTRA-ARTERIAL INFUSION,
OR BY INTRAMUSCULAR INJECTION, OR BY INTRATHECAL
▶ Adult: (consult product literature)
Severe psoriasis unresponsive to conventional therapy
▶ BY MOUTH, OR BY INTRAMUSCULAR INJECTION, OR BY
INTRAVENOUS INJECTION, OR BY SUBCUTANEOUS INJECTION
▶ Adult: Initially 2.5–10 mg once weekly, then increased
in steps of 2.5–5 mg, adjusted according to response,
dose to be adjusted at intervals of at least 1 week; usual
dose 7.5–15 mg once weekly, stop treatment if
inadequate response after 3 months at the optimum
l UNLICENSED USE Not licensed for use in severe Crohn’s
Note that the dose is a weekly dose. To avoid error with
low-dose methotrexate, it is recommended that:
. the patient is carefully advised of the dose and
frequency and the reason for taking methotrexate and
any other prescribed medicine (e.g. folic acid);
. only one strength of methotrexate tablet (usually
2.5 mg) is prescribed and dispensed;
. the prescription and the dispensing label clearly show
the dose and frequency of methotrexate
. the patient is warned to report immediately the onset
of any feature of blood disorders (e.g. sore throat,
bruising, and mouth ulcers), liver toxicity (e.g. nausea,
vomiting, abdominal discomfort, and dark urine), and
respiratory effects (e.g. shortness of breath).
l CONTRA-INDICATIONS Active infection (in non-malignant
conditions). ascites . immunodeficiency syndromes (in
non-malignant conditions). significant pleural effusion
l CAUTIONS Photosensitivity—psoriasis lesions aggravated
ulceration .risk of accumulation in pleural effusion or
ascites— drain before treatment. ulcerative colitis . ulcerative stomatitis
▶ Blood count Bone marrow suppression can occur abruptly;
factors likely to increase toxicity include advanced age,
drop in white cell count or platelet count calls for
immediate withdrawal of methotrexate and introduction
▶ Gastro-intestinal toxicity Withdraw treatment if stomatitis
develops—may be first sign of gastro-intestinal toxicity.
▶ Liver toxicity Liver cirrhosis reported. Treatment should not
be started or should be discontinued if any abnormality of
liver function tests or liver biopsy is present or develops
during therapy. Abnormalities can return to normal within
2 weeks after which treatment may be recommenced if
▶ Pulmonary toxicity Pulmonary toxicity may be a special
problem in rheumatoid arthritis (patient to seek medical
attention if dyspnoea, cough or fever); monitor for
symptoms at each visit—discontinue if pneumonitis
l INTERACTIONS → Appendix 1: methotrexate
▶ With intrathecal use Necrotising demyelinating
leukoencephalopathy . neurotoxicity
▶ With parenteral use Anaemia . appetite decreased . chest
▶ With oral use Agranulocytosis . alopecia . arthralgia . bone
disorders . haemorrhage . healing impaired . hepatic
disorders . myalgia . neoplasms . nephropathy .
BNF 78 Cytotoxic responsive malignancy 913
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