Liposomal formulations Liposomal formulations of
doxorubicin may reduce the incidence of cardiotoxicity
and lower the potential for local necrosis, but infusion
reactions, sometimes severe, may occur. Hand-foot
syndrome (painful, macular reddening skin eruptions)
occurs commonly with liposomal doxorubicin and may be
dose limiting. It can occur after 2–3 treatment cycles and
may be prevented by cooling hands and feet and avoiding
socks, gloves, or tight-fitting footwear. It may also occur
with non-liposomal formulations.
Elevated bilirubin concentrations Doxorubicin is
largely excreted in the bile and an elevated bilirubin
concentration is an indication for reducing the dose.
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception during and for at least 6 months
after treatment in men or women.
l PREGNANCY Avoid (teratogenic and toxic in animal
studies). See also Pregnancy and reproductive function in
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT For liposomal formulation,
manufacturer advises caution. For solution for injection or
infusion, manufacturer advises caution in mild to moderate
impairment; avoid in severe impairment.
Dose adjustments Manufacturer advises dose reduction
according to bilirubin concentration.
l RENAL IMPAIRMENT Consult product literature in severe
l MONITORING REQUIREMENTS Patients should be assessed
before treatment, by echocardiography. Cardiac
monitoring during treatment may assist in determining
l DIRECTIONS FOR ADMINISTRATION Conventional
doxorubicin is given by injection into a fast-running
infusion, commonly at 21-day intervals.
l PRESCRIBING AND DISPENSING INFORMATION Doxorubicin
is available as both conventional and liposomal
formulations. The different formulations vary in their
licensed indications, pharmacokinetics, dosage and
administration, and are not interchangeable.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Topotecan, pegylated liposomal doxorubicin hydrochloride,
paclitaxel, trabectedin and gemcitabine for treating recurrent
ovarian cancer (April 2016) NICE TA389
Pegylated liposomal doxorubicin hydrochloride (PLDH)
monotherapy or in combination with platinum, is
recommended as an option for treating recurrent ovarian
PLDH, in combination with trabectedin, is not
recommended for treating the first recurrence of
platinum-sensitive ovarian cancer.
Patients currently receiving PLDH in combination with
trabectedin should have the option to continue their
treatment until they and their clinician consider it
www.nice.org.uk/guidance/TA389
▶ Olaratumab in combination with doxorubicin for treating
advanced soft tissue sarcoma (August 2017) NICE TA465
Doxorubicin, in combination with olaratumab, is
recommended for use within the Cancer Drugs Fund as an
option for advanced soft tissue sarcoma in patients, only
BNF 78 Cytotoxic responsive malignancy 901
Immune system and malignant disease
. they have not had any previous systemic chemotherapy
for advanced soft tissue sarcoma;
. they cannot have curative treatment with surgery or
their disease does not respond to radiotherapy;
. the conditions in the managed access agreement for
www.nice.org.uk/guidance/TA465
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
injection, solution for infusion
▶ Doxorubicin hydrochloride (Non-proprietary)
Doxorubicin hydrochloride 2 mg per 1 ml Doxorubicin 10mg/5ml
solution for injection vials | 1 vial P £18.54 (Hospital only)
Doxorubicin 50mg/25ml solution for injection Cytosafe vials |
1 vial P £103.00 (Hospital only)
Doxorubicin 50mg/25ml solution for infusion vials | 1 vial P £103.00 (Hospital only)
Doxorubicin 10mg/5ml solution for injection Cytosafe vials |
1 vial P £20.60 (Hospital only)
Doxorubicin 10mg/5ml solution for infusion vials | 1 vial P £20.60
Doxorubicin 50mg/25ml solution for injection vials | 1 vial P £92.70 (Hospital only)
▶ Doxorubicin hydrochloride (Non-proprietary)
Doxorubicin hydrochloride 2 mg per 1 ml Doxorubicin
200mg/100ml solution for infusion vials | 1 vial P £412.00
Doxorubicin 20mg/10ml concentrate for solution for infusion vials | 1 vial P s (Hospital only)
Doxorubicin 100mg/50ml concentrate for solution for infusion vials | 1 vial P s (Hospital only)
Doxorubicin 200mg/100ml solution for injection Cytosafe vials |
1 vial P £412.00 (Hospital only)
Doxorubicin 200mg/100ml concentrate for solution for infusion vials
Doxorubicin hydrochloride (as Doxorubicin hydrochloride
liposomal pegylated) 2 mg per 1 ml Caelyx 50mg/25ml concentrate
for solution for infusion vials | 1 vial P £712.49
Caelyx 20mg/10ml concentrate for solution for infusion vials | 1 vial P £360.23
Powder and solvent for suspension for infusion
ELECTROLYTES: May contain Sodium
Doxorubicin hydrochloride liposomal pegylated 50 mg Myocet
50mg powder and solvent for suspension for infusion vials | 2 vial P £912.26 (Hospital only)
Epirubicin hydrochloride 05-May-2017
Treatment of breast cancer | Treatment and prophylaxis of
certain forms of superficial bladder cancer
▶ BY INTRAVENOUS INFUSION, OR BY INTRAVESICAL
▶ Adult: (consult product literature or local protocols)
l CONTRA-INDICATIONS Bladder inflammation or
instillation). haematuria (when used as a bladder
instillation). invasive tumours penetrating the bladder
epirubicin or other anthracycline .recent myocardial
infarction . severe arrhythmia . severe myocardial
insufficiency . unstable angina . urinary tract infections
(when used as a bladder instillation)
l CAUTIONS Caution in handling—irritant to tissues
l INTERACTIONS → Appendix 1: anthracyclines
▶ Common or very common Paraesthesia . urinary frequency
▶ With intravesical use Chemical cystitis
▶ With parenteral use Embolism and thrombosis . thrombocytopenia
effusion . pulmonary oedema . skin reactions
▶ With intravesical use Cystitis bacterial
SIDE-EFFECTS, FURTHER INFORMATION Manufactuer
advises extreme caution with cumulative doses exceeding
—risk of congestive heart failure increased.
l CONCEPTION AND CONTRACEPTION Contraceptive advice
required, see Pregnancy and reproductive function in
l PREGNANCY Avoid (carcinogenic in animal studies). See
also Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
mild to moderate impairment; avoid in severe impairment.
Dose adjustments Manufacturer advises dose reduction
Dose adjustments Dose reduction may be necessary in
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
injection, solution for infusion
▶ Epirubicin hydrochloride (Non-proprietary)
Epirubicin hydrochloride 2 mg per 1 ml Epirubicin 10mg/5ml
solution for injection vials | 1 vial P £17.38–£20.18
Epirubicin 50mg/25ml solution for injection vials | 1 vial P £86.89–£100.88
Epirubicin hydrochloride 2 mg per 1 ml Pharmorubicin 50mg/25ml
solution for injection Cytosafe vials | 1 vial P £106.19 (Hospital
Pharmorubicin 10mg/5ml solution for injection Cytosafe vials | 1 vial P £21.24 (Hospital only)
▶ Epirubicin hydrochloride (Non-proprietary)
Epirubicin hydrochloride 2 mg per 1 ml Epirubicin 200mg/100ml
solution for infusion vials | 1 vial P £306.20–£366.85
Epirubicin 100mg/50ml solution for infusion vials | 1 vial P £201.76
Epirubicin hydrochloride 2 mg per 1 ml Pharmorubicin
200mg/100ml solution for infusion Cytosafe vials | 1 vial P £386.16 (Hospital only)
902 Cytotoxic responsive malignancy BNF 78
Immune system and malignant disease
Idarubicin hydrochloride 04-May-2017
Acute non-lymphocytic leukaemias monotherapy
▶ Adult: 30 mg/m2 daily for 3 days; maximum 400 mg/m2
Acute non-lymphocytic leukaemia in combination therapy
▶ Adult: 15–30 mg/m2 daily for 3 days; maximum
Advanced breast cancer after failure of first-line
chemotherapy (not including anthracyclines)—
▶ Adult: 45 mg/m2 for 1 dose, repeat treatment every
3–4 weeks, alternatively 15 mg/m2 daily for
3 consecutive days, repeat treatment every 3–4 weeks;
Acute leukaemias | Advanced breast cancer after failure of
first-line chemotherapy (not including anthracyclines)
▶ Adult: (consult product literature)
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
l CONTRA-INDICATIONS Previous treatment with maximum
l CAUTIONS Caution in handling—irritant to tissues
l INTERACTIONS → Appendix 1: anthracyclines
▶ Common or very common Alopecia . anaemia . appetite
thrombosis . fever. haemorrhage . headache . increased
risk of infection . leucopenia . nausea . neutropenia . skin
reactions . stomatitis .thrombocytopenia . urine red . vomiting
infarction . nail discolouration . sepsis . shock . soft tissue
▶ Rare or very rare Cardiac conduction disorders . cardiac
inflammation . flushing . intracranial haemorrhage
▶ Frequency not known Bone marrow disorders .tumour lysis
▶ With intravenous use Abdominal pain . mucosal
abnormalities . paraesthesia .radiation injuries
▶ With oral use Gastrointestinal discomfort. mucositis . radiation skin sensitivity
l CONCEPTION AND CONTRACEPTION Contraceptive advice
required, see Pregnancy and reproductive function in
l PREGNANCY Avoid (teratogenic and toxic in animal
studies). See also Pregnancy and reproductive function in
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
mild to moderate impairment; avoid in severe impairment.
Dose adjustments Manufacturer advises consider dose
reduction in mild to moderate impairment—consult
l RENAL IMPAIRMENT Avoid in severe impairment.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 25
Idarubicin hydrochloride 5 mg Zavedos 5mg capsules | 1 capsule P £41.47
Idarubicin hydrochloride 10 mg Zavedos 10mg capsules | 1 capsule P £69.12
Powder for solution for injection
Idarubicin hydrochloride 5 mg Zavedos 5mg powder for solution
for injection vials | 1 vial P £87.36 (Hospital only)
Idarubicin hydrochloride 10 mg Zavedos 10mg powder for solution
for injection vials | 1 vial P £174.72 (Hospital only)
Metastatic breast cancer | Non-Hodgkin’s lymphoma |
Adult acute non-lymphocytic leukaemia | Non-resectable
primary hepatocellular carcinoma
▶ Adult: (consult local protocol)
l CAUTIONS Intrathecal administration not recommended
l INTERACTIONS → Appendix 1: anthracyclines
effects . paraesthesia . scleral discolouration . skin
discolouration . stomatitis .thrombocytopenia . urine blue . vomiting
SIDE-EFFECTS, FURTHER INFORMATION Cardiac
examinations are recommended after a cumulative dose of
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception during and for at least 6 months
after treatment in men or women.
l PREGNANCY Avoid. See also Pregnancy and reproductive
function in Cytotoxic drugs p. 888.
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises caution
(limited information available).
Dose adjustments Manufacturer advises consider dose
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Mitoxantrone (Non-proprietary)
Mitoxantrone (as Mitoxantrone hydrochloride) 2 mg per
1 ml Mitoxantrone 20mg/10ml concentrate for solution for infusion
vials | 1 vial P £121.85 (Hospital only) | 1 vial P £51.43
▶ Onkotrone (Baxter Healthcare Ltd)
Mitoxantrone (as Mitoxantrone hydrochloride) 2 mg per
1 ml Onkotrone 20mg/10ml solution for infusion vials | 1 vial P £103.57
Onkotrone 25mg/12.5ml solution for infusion vials | 1 vial P £129.48
BNF 78 Cytotoxic responsive malignancy 903
Immune system and malignant disease
Treatment of refractory or multiply relapsed aggressive
non-Hodgkin B-cell lymphomas (monotherapy)
▶ Adult: (consult product literature)
l CONTRA-INDICATIONS Active severe infection .risk factors
l CAUTIONS Active cardiovascular disease . cardiac risk
of cardiovascular disease . previous radiotherapy to the
mediastinal area . previous therapy with anthracenediones . previous therapy with anthracyclines
l INTERACTIONS → Appendix 1: anthracyclines
▶ Common or very common Alopecia . anaemia . appetite
decreased . arrhythmias . asthenia . blood disorder. bundle
branch block . cancer progression . cardiac disorder (during
or following treatment). chest pain . congestive heart
imbalance . eye inflammation .fever. gastrointestinal
malignancy . skin reactions .taste altered . thrombocytopenia . urine discolouration . vascular
▶ Uncommon Anxiety . arthralgia . arthritis . bone marrow
l CONCEPTION AND CONTRACEPTION Ensure effective
contraception during and for at least 6 months after
l PREGNANCY Manufacturer advises avoid—toxicity in
animal studies. See also Pregnancy and reproductive
function in Cytotoxic drugs p. 888.
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises caution in
mild to moderate impairment; avoid in severe impairment
l RENAL IMPAIRMENT No information available—
▶ Baseline investigations should include a full blood count,
assessment of cardiac function measured by left
ventricular ejection fraction, and measurement of serum
concentrations of total bilirubin and total creatinine.
▶ Full blood count and cardiac function should be monitored
Photosensitivity Photosensitivity is a theoretical risk and
patients should be advised to follow sun protection
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Pixantrone monotherapy for treating multiply relapsed or
refractory aggressive non-Hodgkin’s B-cell lymphoma
Pixantrone (Pixuvri ®) monotherapy is recommended as an
option for treating adults with multiply relapsed or
refractory aggressive non-Hodgkin’s B-cell lymphoma in
. who have previously been treated with rituximab, and
. who are receiving third- or fourth-line treatment, and
. if the manufacturer provides pixantrone with the
discount agreed in the patient access scheme.
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/ta306
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 Sodium
▶ Pixuvri (Servier Laboratories Ltd) A
Pixantrone (as Pixantrone dimaleate) 29 mg Pixuvri 29mg powder
for concentrate for solution for infusion vials | 1 vial P £553.50
ANTINEOPLASTIC DRUGS › ANTIMETABOLITES
l DRUG ACTION Azacitidine is a pyrimidine analogue.
Treatment of intermediate-2 and high-risk
myelodysplastic syndromes, chronic myelomonocytic
leukaemia, and acute myeloid leukaemia, in adults who
are not eligible for haemotopoietic stem cell
▶ Adult: (consult local protocol)
l CONTRA-INDICATIONS Advanced malignant hepatic
assessment before and during treatment). unstable
pulmonary disease (consider cardiopulmonary assessment
l INTERACTIONS → Appendix 1: azacitidine
▶ Uncommon Hepatic coma . hepatic failure . pyoderma
gangrenosum .renal tubular acidosis
▶ Rare or very rare Injection site necrosis .tumour lysis
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception during and for 3 months after
l PREGNANCY Avoid (toxicity in animal studies). See also
Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
severe impairment (no information available)—monitor
904 Cytotoxic responsive malignancy BNF 78
Immune system and malignant disease
Dose adjustments Manufacturer advises consider dose
reduction—consult local protocol.
baseline value and above the upper level of normal until
values return to normal or baseline, and then reduce dose
by 50% on the next treatment cycle.
Reduce dose by 50% on the next treatment cycle if
serum-bicarbonate concentration less than 20 mmol/litre.
▶ Monitor liver function tests, serum creatinine, and serum
bicarbonate before initiation of treatment and before each
▶ Monitor full blood count before initiation of treatment,
before each treatment cycle, and as clinically indicated.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Azactidine for treating acute myeloid leukaemia with more
than 30% bone marrow blasts (July 2016) NICE TA399
Azacitidine (Vidaza ®) is not recommended, within its
marketing authorisation, for treating acute myeloid
leukaemia with greater than 30% bone marrow blasts in
patients aged 65 years or above who are not eligible for
haematopoietic stem cell transplant.
Patients whose treatment was started before this
guidance was published should continue treatment until
they and their NHS clinician consider it appropriate to
www.nice.org.uk/guidance/ta399
▶ Azacitidine for the treatment of myelodysplastic syndromes,
chronic myelomonocytic leukaemia and acute myeloid
leukaemia (March 2011) NICE TA218
Azacitidine (Vidaza ®) is recommended in adults who are
not eligible for haematopoietic stem cell transplantation
. intermediate-2 and high-risk myelodysplastic
syndromes according to the International Prognostic
. chronic myelomonocytic leukaemia with 10–29%
marrow blasts without myeloproliferative disorder, or
. acute myeloid leukaemia with 20–30% blasts and
multilineage dysplasia, according to the World Health
Organization classification, and
. if the manufacturer provides azacitidine with the
discount agreed as part of the patient access scheme.
www.nice.org.uk/guidance/ta218
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for suspension for injection
Azacitidine 100 mg Vidaza 100mg powder for suspension for
injection vials | 1 vial P £321.00
l DRUG ACTION Capecitabine is metabolised to fluorouracil.
Stage III colon cancer, adjuvant following surgery
▶ Adult: 1.25 g/m2 twice daily for 14 days, subsequent
courses repeated after a 7-day interval, recommended
duration of treatment is 6 months, adjust dose
according to tolerability—consult product literature
Stage III colon cancer, adjuvant following surgery
▶ Adult: 0.8–1 g/m2 twice daily for 14 days, subsequent
courses repeated after a 7-day interval, recommended
duration of treatment is 6 months, adjust dose
according to tolerability—consult product literature
Metastatic colorectal cancer (monotherapy)
▶ Adult: 1.25 g/m2 twice daily for 14 days, subsequent
courses repeated after a 7-day interval, adjust dose
according to tolerability—consult product literature
Metastatic colorectal cancer (combination therapy)
▶ Adult: 0.8–1 g/m2 twice daily for 14 days, subsequent
courses repeated after a 7-day interval, adjust dose
according to tolerability—consult product literature
Advanced gastric cancer (first-line treatment in
combination with a platinum based regimen)
▶ Adult: 0.8–1 g/m2 twice daily for 14 days, subsequent
courses repeated after a 7-day interval, alternatively
625 mg/m2 twice daily given continuously, adjust dose
according to tolerability—consult product literature
Locally advanced or metastatic breast cancer (second-line
treatment as monotherapy after failure of a taxane and
anthracycline regimen or where further anthracycline
treatment is not indicated)| Locally advanced or
metastatic breast cancer (second-line treatment, in
combination with docetaxel, where previous therapy
▶ Adult: 1.25 g/m2 twice daily for 14 days, subsequent
courses repeated after a 7-day interval, adjust dose
according to tolerability—consult product literature
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
l CONTRA-INDICATIONS Dihydropyrimidine dehydrogenase
l CAUTIONS Diabetes mellitus . diarrhoea or dehydration—
consult product literature for guidance on dose
modification and treatment interruption . electrolyte
disturbances . history of angina pectoris . history of
arrhythmias . history of significant cardiovascular disease . nervous system disease
l INTERACTIONS → Appendix 1: capecitabine
▶ Common or very common Alopecia . anaemia . appetite
inflammation . eye irritation .fever. gastrointestinal
mellitus . dysphagia . ear pain .facial swelling . haemolytic
weakness . musculoskeletal stiffness . palpitations .
BNF 78 Cytotoxic responsive malignancy 905
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