ulcer. syncope .thrombocytopenia . urinary disorders . vertigo . vision disorders
cutaneous adverse reactions (SCARs). vasospasm
▶ Frequency not known Cardiomyopathy . heart failure . sudden death
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.
l HEPATIC IMPAIRMENT Manufacturer advises monitor liver
function in mild-to-moderate dysfunction—consult
product literature for guidance on treatment interruption;
l RENAL IMPAIRMENT Avoid if creatinine clearance less than
Dose adjustments Reduce starting dose of 1.25 g/m2 to 75%
if creatinine clearance 30–50 mL/minute.
▶ Monitor plasma-calcium concentration.
▶ Monitor for eye disorders (including keratitis and corneal
▶ Severe skin reactions Monitor for symptoms of severe skin
reactions (including Stevens-Johnson syndrome and toxic
epidermal necrolysis)—permanently discontinue
treatment immediately if symptoms occur.
▶ Hand-foot syndrome Monitor for symptoms of hand-foot
syndrome—interrupt treatment if significant syndrome
occurs and refer to product literature.
l NATIONAL FUNDING/ACCESS DECISIONS
Bevacizumab in combinations with capecitabine is not
recommended within its marketing authorisation for the
first-line treatment of metastatic breast cancer, that is,
when treatment with other chemotherapy options
including taxanes or anthracyclines is not considered
appropriate, or when taxanes or anthracyclines have been
used as part of adjuvant treatment in the previous
▶ Bevacizumab in combination with oxaliplatin and either
fluorouracil plus folinic acid or capecitabine for the treatment
of metastatic colorectal cancer (December 2010) NICE TA212
Bevacizumab in combination with oxaliplatin and either
fluorouracil plus folinic acid or capecitabine is not
recommended for the treatment of metastatic colorectal
▶ Capecitabine for the treatment of advanced gastric cancer
Capecitabine in combination with a platinum-based
regimen is recommended for the first-line treatment of
inoperable advanced gastric cancer.
▶ Capecitabine and tegafur with uracil for metastatic colorectal
Capecitabine or tegafur with uracil [now discontinued] (in
combination with folinic acid) is an option for the first-line
treatment of metastatic colorectal cancer.
▶ Capecitabine and oxaliplatin in the adjuvant treatment of
stage III (Dukes’ C) colon cancer (April 2006) NICE TA100
Capecitabine alone or oxaliplatin combined with
fluorouracil and folinic acid are options for adjuvant
treatment following surgery for stage III (Dukes’ C) colon
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 21
▶ Capecitabine (Non-proprietary)
Capecitabine 150 mg Capecitabine 150mg tablets | 60 tablet P £40.02 DT = £30.00
Capecitabine 300 mg Capecitabine 300mg tablets | 60 tablet P £76.04
Capecitabine 150 mg Xeloda 150mg tablets | 60 tablet P £40.02 DT = £30.00
Capecitabine 500 mg Xeloda 500mg tablets | 120 tablet P £265.55 DT = £225.72
l DRUG ACTION Cladribine is a nucleoside analogue that is
cytotoxic particularly to lymphocytes and monocytes,
immune events central to multiple sclerosis.
Hairy cell leukaemia (specialist use only)
▶ BY SUBCUTANEOUS INJECTION, OR BY INTRAVENOUS INFUSION
▶ Adult: (consult product literature or local protocols)
B-cell chronic lymphocytic leukaemia (specialist use only)
▶ Adult: (consult product literature or local protocols)
Highly active relapsing-remitting multiple sclerosis
▶ Adult: (consult product literature or local protocols)
MHRA/CHM ADVICE: CLADRIBINE FOR LEUKAEMIA: REPORTS OF
PROGRESSIVE MULTIFOCAL ENCEPHALOPATHY (PML); STOP
TREATMENT IF PML SUSPECTED (DECEMBER 2017)
The MHRA is aware of 3 confirmed cases of progressive
multifocal encephalopathy (PML) that developed
6 months to several years after cladribine treatment for
haematological conditions. An association between
cladribine and prolonged lymphopenia has been
PML should be considered in the differential diagnosis
for patients with new or worsening neurological signs or
symptoms. Patients should be monitored for signs and
symptoms of new neurological dysfunction, and advised
to seek urgent medical attention if they experience
symptoms—stop treatment immediately if PML is
suspected and ensure specialist investigation is received.
▶ With oral use Active chronic hepatitis . active chronic
tuberculosis . active malignancy . HIV infection . immunocompromised patients
GENERAL CAUTIONS Acute infection . use irradiated blood
only (haematology consultation advised)
906 Cytotoxic responsive malignancy BNF 78
Immune system and malignant disease
▶ With intravenous use or subcutaneous use High tumour
burden—consult product literature . symptomatic or
▶ Immunosuppressive effect of cladribine
▶ With intravenous use or subcutaneous use Cladribine has
potent and prolonged myelosuppressive and
immunosuppressive effects. Patients treated with
cladribine are more prone to serious bacterial,
opportunistic fungal, and viral infections, and prophylactic
therapy should be considered in those at risk. Acute
infections should be treated before initiating cladribine.
should be administered. Prescribers should consult
specialist literature when using highly immunosuppressive
▶ With oral use Manufacturer advises vaccination prior to
initiation of therapy in patients who have no history of
exposure to varicella zoster virus; delay treatment for
l INTERACTIONS → Appendix 1: cladribine
▶ Common or very common Increased risk of infection
▶ With oral use Alopecia . lymphopenia .rash
▶ With subcutaneous use Anaemia . anxiety . appetite
▶ With intravenous use Heart failure
adverse reactions (SCARs). speech disorder.tumour lysis
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception during treatment and for at least
6 months after the last dose in men and women of
▶ With oral use Manufacturer advises exclude pregnancy
before each treatment course; if using a hormonal
contraceptive, a barrier method should also be used for at
least 4 weeks after the last dose of each course.
l PREGNANCY Manufacturer advises avoid—teratogenic in
animal studies. See also Pregnancy and reproductive
function in Cytotoxic drugs p. 888.
▶ With intravenous use or subcutaneous use Manufacturer
advises avoid during treatment and for 6 months after the
last dose—no information available.
▶ With oral use Manufacturer advises avoid during treatment
and for 1 week after the last dose—no information
▶ With intravenous use Manufacturer advises caution (limited
▶ With subcutaneous use Manufacturer advises caution in mild
impairment; avoid in moderate to severe impairment (no
▶ With oral use Manufacturer advises avoid in moderate to
severe impairment (no information available).
▶ With subcutaneous use Manufacturer advises caution in mild
impairment; avoid in moderate-to-severe impairment.
▶ With oral use Manufacturer advises avoid in moderate-tosevere impairment—no information available.
▶ With intravenous use Manufacturer advises caution—limited
▶ With oral use Manufacturer advises exclude HIV infection,
active or latent tuberculosis and active or latent hepatitis
before starting each treatment course—delay treatment
until infection adequately treated.
▶ Manufacturer advises monitor for malignancy—follow
routine cancer screening guidelines.
▶ Manufacturer advises monitor for progressive multifocal
leucoencephalopathy—perform a baseline MRI.
▶ Manufacturer advises monitor for haemolysis in patients
who are or who become Coombs’ positive.
▶ Manufacturer advises haematological monitoring
required—consult product literature.
▶ With intravenous use or subcutaneous use Renal and hepatic
function should be monitored periodically as clinically
l DIRECTIONS FOR ADMINISTRATION Litak ® for
subcutaneous use only—no dilution required;
manufacturer advises patients may self-administer, after
Leustat ® for infusion use only.
LITAK ® Manufacturer advises store in a refrigerator
LEUSTAT ® Manufacturer advises store in a refrigerator
▶ With intravenous use or subcutaneous use Manufacturer
advises patients and carers should be counselled on the
effects on driving and performance of skilled tasks—
increased risk of dizziness and drowsiness.
BNF 78 Cytotoxic responsive malignancy 907
Immune system and malignant disease
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Cladribine tablets for treating relapsing–remitting multiple
sclerosis (December 2017) NICE TA493
Cladribine tablets are recommended as an option for
treating highly active multiple sclerosis in adults, only if
. rapidly evolving severe relapsing–remitting multiple
sclerosis, that is, at least 2 relapses in the previous year
and at least 1 T1 gadolinium-enhancing lesion at
. relapsing–remitting multiple sclerosis that has
year and MRI evidence of disease activity.
Patients whose treatment was started within the NHS
before this guidance was published should have the option
to continue treatment, without change to their funding
arrangements, until they and their NHS clinician consider
www.nice.org.uk/guidance/ta493
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (February
2018) that cladribine (Mavenclad ®) is accepted for
restricted use within NHS Scotland for the treatment of
. rapidly evolving severe relapsing-remitting multiple
sclerosis: patients with two or more relapses in the prior
year whether on treatment or not, and at least one T1
gadolinium-enhancing lesion, or
. sub-optimal therapy relapsing-remitting multiple
sclerosis: patients with one or more relapses in the
previous year while on disease modifying therapy, and at
least one T1 gadolinium-enhancing lesion or nine T2
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Cladribine 2 mg per 1 ml Litak 10mg/5ml solution for injection vials
| 1 vial P £165.00 (Hospital only)
ELECTROLYTES: May contain Sodium
Cladribine 1 mg per 1 ml Leustat 10mg/10ml solution for infusion
▶ Mavenclad (Merck Serono Ltd)
Relapsed or refractory acute lymphoblastic leukaemia in
patients who have received at least two previous
▶ Adult 18–20 years: (consult local protocol)
l INTERACTIONS → Appendix 1: clofarabine
▶ Common or very common Alopecia . anxiety . appetite
l CONCEPTION AND CONTRACEPTION Contraceptive advice
required, see Pregnancy and reproductive function in
l PREGNANCY Manufacturer advises avoid (teratogenic in
animal studies). See also Pregnancy and reproductive
function in Cytotoxic drugs p. 888.
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises use with
caution in mild-to-moderate impairment; avoid in severe
impairment—no information available.
l RENAL IMPAIRMENT Manufacturer advises caution in mild
to moderate impairment. Avoid in severe impairment.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
ELECTROLYTES: May contain Sodium
▶ Clofarabine (Non-proprietary)
Clofarabine 1 mg per 1 ml Clofarabine 20mg/20ml concentrate for
solution for infusion vials | 1 vial P £1,259.87–£1,326.18 (Hospital
Clofarabine 1 mg per 1 ml Evoltra 20mg/20ml concentrate for
solution for infusion vials | 1 vial P £1,326.18 (Hospital only)
l DRUG ACTION Cytarabine acts by interfering with
Induction of remission of acute myeloblastic leukaemia
▶ BY INTRAVENOUS INFUSION, OR BY INTRAVENOUS INJECTION,
▶ Adult: (consult local protocol)
▶ Adult: (consult local protocol)
Not all cytarabine preparations can be given by
intrathecal injection—consult product literature.
l INTERACTIONS → Appendix 1: cytarabine
▶ Common or very common Alopecia . anaemia . appetite
disorders . haemorrhagic conjunctivitis (consider
▶ Uncommon Arthralgia . dyspnoea . headache . increased
▶ Rare or very rare Arrhythmias
▶ Frequency not known Acute respiratory distress syndrome
(ARDS). amenorrhoea . ataxia . azoospermia . bone marrow
disorders . cardiomyopathy . cerebellar dysfunction . chest
908 Cytotoxic responsive malignancy BNF 78
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