l BREAST FEEDING Manufacturer advises avoid
breastfeeding during and for 2 months after treatment.
l PRE-TREATMENT SCREENING Evidence of non-mutated
RAS status (at exons 2, 3 and 4 of KRAS and NRAS) is
required before panitumumab treatment is initiated, and
should be determined by an experienced laboratory using a
▶ Monitor for hypomagnesaemia.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Cetuximab, bevacizumab and panitumumab for the treatment
of metastatic colorectal cancer after first-line chemotherapy
Panitinumab monotherapy is not recommended for the
treatment of patients with metastatic colorectal cancer
that has progressed after first-line chemotherapy.
www.nice.org.uk/guidance/TA242
▶ Cetuximab and panitumumab for previously untreated
metastatic colorectal cancer (updated September 2017)
Panitumumab is recommended, within its marketing
authorisation, as an option for previously untreated RAS
wild-type metastatic colorectal cancer in adults in
. 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX), or
. 5-fluorouracil, folinic acid and irinotecan (FOLFIRI).
This advice is contingent upon the manufacturer providing
panitumumab with the discount agreed in the patient
www.nice.org.uk/guidance/TA439
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
ELECTROLYTES: May contain Sodium
Panitumumab 20 mg per 1 ml Vectibix 400mg/20ml concentrate for
solution for infusion vials | 1 vial P £1,517.16 (Hospital only)
Vectibix 100mg/5ml concentrate for solution for infusion vials | 1 vial P £379.29 (Hospital only)
l DRUG ACTION Pembrolizumab is a monoclonal antibody,
which binds to the programmed death-1 (PD-1) receptor,
thereby potentiating an immune response to tumour cells.
Melanoma (specialist use only)| Non-small cell lung cancer
(specialist use only)| Urothelial carcinoma (specialist
use only)| Classical Hodgkin lymphoma (specialist use
only)| Head and neck squamous cell carcinoma
▶ Adult: 200 mg every 3 weeks, for dose adjustments due
to side-effects or infusion-related reactions—consult
MHRA/CHM ADVICE: PEMBROLIZUMAB (KEYTRUDA ®): REPORTS
OF ORGAN TRANSPLANT REJECTION (JULY 2017)
A European review of worldwide data concluded that
pembrolizumab may increase the risk of rejection in
organ transplant recipients. The MHRA recommends
considering the benefit of treatment with
pembrolizumab versus the risk of possible organ
transplant rejection for each patient.
l CAUTIONS Patients may need pretreatment to minimise
the development of adverse reactions (consult product
l INTERACTIONS → Appendix 1: monoclonal antibodies
(SCARs). skin reactions .taste altered . vomiting
▶ Uncommon Adrenal insufficiency . alopecia . decreased
▶ Rare or very rare Erythema nodosum . haemolytic anaemia . myasthenic syndrome . sarcoidosis
▶ Frequency not known Solid organ transplant rejection
SIDE-EFFECTS, FURTHER INFORMATION Immune-related
reactions Most immune-related adverse reactions are
reversible and managed by temporarily stopping treatment
and administration of a corticosteroid—consult product
literature for further information.
Infusion-related reactions Manufacturer advises to
permanently discontinue treatment in patients with severe
l CONCEPTION AND CONTRACEPTION Manufacturer
recommends effective contraception during treatment and
for at least 4 months after treatment in women of
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—no information available
l BREAST FEEDING Manufacturer advises avoid—no
l MONITORING REQUIREMENTS Manufacturer advises
monitor for signs and symptoms of infusion- and immunerelated reactions.
878 Antibody responsive malignancy BNF 78
Immune system and malignant disease
l HANDLING AND STORAGE Manufacturer advises store in a
l PATIENT AND CARER ADVICE Patients should be provided
with an alert card and advised to keep it with them at all
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Pembrolizumab for treating advanced melanoma after
disease progression with ipilimumab (updated September
Pembrolizumab (Keytruda ®) is recommended as an option
for treating advanced (unresectable or metastatic)
. after the disease has progressed with ipilimumab and,
for BRAF V600 mutation-positive disease, a BRAF or
. the manufacturer provides pembrolizumab in line with
the commercial access agreement with NHS England.
www.nice.org.uk/guidance/ta357
▶ Pembrolizumab for advanced melanoma not previously
treated with ipilimumab (updated September 2017)
Pembrolizumab (Keytruda ®) is recommended as an option
for treating advanced (unresectable or metastatic)
melanoma that has not been previously treated with
ipilimumab, in adults, only when the manufacturer
provides pembrolizumab in line with the commercial
access agreement with NHS England.
www.nice.org.uk/guidance/ta366
▶ Pembrolizumab for adjuvant treatment of resected melanoma
with high risk of recurrence (December 2018) NICE TA553
Pembrolizumab (Keytruda ®) is recommended for use
within the Cancer Drugs Fund as an option for the
adjuvant treatment of stage III melanoma with lymph
node involvement in adults who have had complete
resection. It is recommended only if the conditions in the
managed access agreement for pembrolizumab are
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/ta553
▶ Pembrolizumab for treating PD-L1-positive non-small-cell
lung cancer after chemotherapy (updated September 2017)
Pembrolizumab (Keytruda ®) is recommended as an option
for treating locally advanced or metastatic PD-L1-positive
non-small-cell lung cancer in adults who have had at least
one chemotherapy (and targeted treatment if they have an
epidermal growth factor receptor (EGFR)- or anaplastic
lymphoma kinase (ALK)-positive tumour), only if:
. pembrolizumab is stopped at 2 years of uninterrupted
treatment and no documented disease progression, and
. the manufacturer provides pembrolizumab in line with
the commercial access agreement with NHS England.
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 or their NHS clinician consider it
www.nice.org.uk/guidance/ta428
Pembrolizumab (Keytruda ®) is recommended as an option
for untreated PD-L1-positive metastatic non-small-cell
lung cancer in adults whose tumours express PD-L1 (with
at least a 50% tumour proportion score) and have no
epidermal growth factor receptor- or anaplastic lymphoma
kinase-positive mutations, only if:
. pembrolizumab is stopped at 2 years of uninterrupted
treatment or earlier in the event of disease progression,
. the manufacturer provides pembrolizumab according to
the commercial access agreement.
www.nice.org.uk/guidance/ta531
▶ Pembrolizumab with pemetrexed and platinum chemotherapy
for untreated, metastatic, non-squamous non-small-cell lung
cancer (January 2019) NICE TA557
Pembrolizumab (Keytruda ®), with pemetrexed and
platinum chemotherapy is recommended for use within
the Cancer Drugs Fund, as an option for untreated,
metastatic, non-squamous non-small-cell lung cancer in
adults whose tumours have no epidermal growth factor
receptor- or anaplastic lymphoma kinase-positive
mutations. It is only recommended if:
. pembrolizumab is stopped at 2 years of uninterrupted
treatment or earlier if disease progresses, and
. the manufacturer provides pembrolizumab according to
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/ta557
▶ Pembrolizumab for treating locally advanced or metastatic
urothelial carcinoma after platinum-containing chemotherapy
Pembrolizumab (Keytruda ®) is recommended for use
within the Cancer Drugs Fund as an option for treating
locally advanced or metastatic urothelial carcinoma in
adults who have had platinum-containing chemotherapy,
. pembrolizumab is stopped at 2 years of uninterrupted
treatment or earlier in the event of disease progression,
. the conditions in the managed access agreement for
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/ta519
▶ Pembrolizumab for untreated PD-L1-positive locally advanced
or metastatic urothelial cancer when cisplatin is unsuitable
(updated July 2018) NICE TA522
Pembrolizumab (Keytruda ®) is recommended for use
within the Cancer Drugs Fund as an option for untreated
locally advanced or metastatic urothelial carcinoma in
adults when cisplatin-containing chemotherapy is
. their tumours express PD-L1 with a combined positive
. pembrolizumab is stopped at 2 years of uninterrupted
treatment or earlier if the disease progresses, and
. the conditions of the managed access agreement for
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/ta522
▶ Pembrolizumab for treating relapsed or refractory classical
Hodgkin lymphoma (September 2018) NICE TA540
Pembrolizumab (Keytruda ®) is not recommended for
treating relapsed or refractory classical Hodgkin
lymphoma in adults who have had autologous stem cell
transplant and brentuximab vedotin.
BNF 78 Antibody responsive malignancy 879
Immune system and malignant disease
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/ta540
▶ Pembrolizumab for treating relapsed or refractory classical
Hodgkin lymphoma (September 2018) NICE TA540
Pembrolizumab (Keytruda ®) is recommended for use
within the Cancer Drugs Fund as an option for treating
relapsed or refractory classical Hodgkin lymphoma in
adults who have had brentuximab vedotin and cannot
have autologous stem cell transplant, only if:
. pembrolizumab is stopped after 2 years of treatment or
earlier if the person has a stem cell transplant or the
. the conditions in the managed access agreement for
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/ta540
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (November
2015) that pembrolizumab (Keytruda ®) is accepted for use
within NHS Scotland as monotherapy for the treatment of
advanced (unresectable or metastatic) melanoma in adults
previously untreated with ipilimumab. The advice is
contingent upon the continuing availability of the patient
access scheme in NHS Scotland or a list price that is
The Scottish Medicines Consortium has advised
(December 2016) that pembrolizumab (Keytruda ®) is not
recommended for use within NHS Scotland as
monotherapy for the treatment of advanced (unresectable
or metastatic) melanoma in adults previously treated with
ipilimumab as the economic case was not demonstrated.
The Scottish Medicines Consortium has advised (January
2017) that pembrolizumab (Keytruda ®) is accepted for
restricted use within NHS Scotland for the treatment of
locally advanced or metastatic non-small cell lung
carcinoma (NSCLC) in adults whose tumours express
programmed death ligand 1 (PD-L1) and who have
received at least one prior chemotherapy regimen, subject
to a two-year clinical stopping rule. The advice is
contingent upon the continuing availability of
pembrolizumab at the price agreed in the patient access
scheme in NHS Scotland or a list price that is equivalent or
The Scottish Medicines Consortium has advised (July
2017) that pembrolizumab (Keytruda ®) is accepted for
restricted use within NHS Scotland as monotherapy for the
first-line treatment of metastatic non-small cell lung
carcinoma (NSCLC) in adults whose tumours express
programmed death ligand 1 (PD-L1) with a 50% tumour
proportion score with no epidermal growth factor receptor
or anaplastic lymphoma kinase positive tumour
mutations, subject to a two-year clinical stopping rule. The
advice is contingent upon the continuing availability of
the patient access scheme in NHS Scotland or a list price
The Scottish Medicines Consortium has advised (February
2019) that pembrolizumab (Keytruda ®) is not
recommended for use within NHS Scotland when used in
combination with pemetrexed and platinum
chemotherapy, for the first-line treatment of metastatic
non-squamous non-small cell lung carcinoma in adults
economic case was not demonstrated.
The Scottish Medicines Consortium has advised (February
2018) that pembrolizumab (Keytruda ®) is accepted for
restricted use within NHS Scotland as monotherapy for the
treatment of locally advanced or metastatic urothelial
is subject to a two-year clinical stopping rule. This advice
is contingent upon the continuing availability of the
patient access scheme in NHS Scotland or a list price that
The Scottish Medicines Consortium has advised
(September 2018) that pembrolizumab (Keytruda ®) is not
recommended for use within NHS Scotland as
monotherapy, for the treatment of locally advanced or
metastatic urothelial carcinoma in adults who are not
eligible for cisplatin-containing chemotherapy and whose
tumours express PD-L1 with a combined positive score
(CPS)10, as the economic case was not demonstrated.
The Scottish Medicines Consortium has advised (March
2018) that pembrolizumab (Keytruda ®) is accepted for
restricted use within NHS Scotland as monotherapy for the
treatment of adults with relapsed or refractory classical
Hodgkin lymphoma who have failed autologous stem cell
transplant and brentuximab vedotin, or who are
transplant-ineligible and have failed brentuximab vedotin.
Treatment with pembrolizumab is subject to a two-year
clinical stopping rule. This advice is contingent upon the
continuing availability of the patient access scheme in
NHS Scotland or a list price that is equivalent or lower.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 3
▶ Keytruda (Merck Sharp & Dohme Ltd) A
Pembrolizumab 25 mg per 1 ml Keytruda 100mg/4ml concentrate
for solution for infusion vials | 1 vial P £2,630.00 (Hospital only)
Powder for solution for infusion
CAUTIONARY AND ADVISORY LABELS 3
▶ Keytruda (Merck Sharp & Dohme Ltd) A
Pembrolizumab 50 mg Keytruda 50mg powder for concentrate for
solution for infusion vials | 1 vial P £1,315.00 (Hospital only)
l DRUG ACTION Pertuzumab is a recombinant humanised
monoclonal antibody, and acts by inhibiting human
epidermal growth factor receptor 2 protein (HER2)
HER2-positive early stage breast cancer (in combination
with trastuzumab and chemotherapy)| HER2-positive
metastatic or locally recurrent unresectable breast
cancer (in combination with trastuzumab and docetaxel)
▶ Adult: (consult product literature or local protocols)
l CAUTIONS Conditions that could impair left ventricular
function . history of congestive heart failure . impaired left
infarction . serious cardiac arrhythmia . uncontrolled
880 Antibody responsive malignancy BNF 78
Immune system and malignant disease
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Common or very common Alopecia . anaemia . appetite
decreased . arthralgia . asthenia . chills . congestive heart
tearing .fever. headache . hypersensitivity . increased risk
of infection . infusion related reaction . insomnia . left
reactions . stomatitis .taste altered . vomiting
SIDE-EFFECTS, FURTHER INFORMATION Side effects mostly
described for pertuzumab in combination with
l CONCEPTION AND CONTRACEPTION Ensure effective
contraception during and for six months after treatment in
women of childbearing potential.
l PREGNANCY Avoid (toxicity in animal studies). Most
cytotoxic drugs are teratogenic and should not be
administered during pregnancy, especially during the first
trimester. Considerable caution is necessary if a pregnant
woman presents with cancer requiring chemotherapy, and
specialist advice should always be sought.
l BREAST FEEDING Avoid—no information available.
l HEPATIC IMPAIRMENT Manufacturer advises caution (no
l RENAL IMPAIRMENT Caution in severe impairment—no
▶ Assess for signs and symptoms of congestive heart failure
(including left ventricular ejection fraction) before and
during treatment—consult product literature, and
withhold treatment if necessary.
▶ Monitor for febrile neutropenia.
l DIRECTIONS FOR ADMINISTRATION Resuscitation facilities
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Pertuzumab for the neoadjuvant treatment of HER2-positive
breast cancer (December 2016) NICE TA424
Pertuzumab (Perjeta ®), in combination with trastuzumab
and chemotherapy, is recommended, within its marketing
authorisation, as an option for neoadjuvant treatment in
adults with human epidermal growth factor receptor 2
manufacturer provides it with the discount agreed in the
www.nice.org.uk/guidance/ta424
▶ Pertuzumab with trastuzumab and docetaxel for treating
HER2-positive breast cancer (March 2018) NICE TA509
Pertuzumab (Perjeta ®), in combination with trastuzumab
and docetaxel, is recommended, within its marketing
authorisation, for treating HER2-positive metastatic or
locally recurrent unresectable breast cancer, in adults who
have not had previous anti-HER2 therapy or chemotherapy
for their metastatic disease, only if the manufacturer
provides pertuzumab within the agreed commercial access
www.nice.org.uk/guidance/ta509
▶ Pertuzumab for adjuvant treatment of HER2-positive early
stage breast cancer (March 2019) NICE TA569
Pertuzumab (Perjeta ®), with intravenous trastuzumab and
chemotherapy, is recommended for the adjuvant
treatment of human epidermal growth factor receptor 2
(HER2)-positive early stage breast cancer in adults, only if
they have lymph node-positive disease and the
manufacturer provides it according to the commercial
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/ta569
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (June 2017)
that pertuzumab (Perjeta ®) is not recommended for use
within NHS Scotland for the treatment of HER2-positive
metastatic or locally recurrent unresectable breast cancer
in combination with trastuzumab and docetaxel, in adults
who have not received previous anti-HER2 therapy or
chemotherapy as the economic case was not sufficient to
The Scottish Medicines Consortium has advised
(December 2018) that pertuzumab (Perjeta ®) is accepted
for use within NHS Scotland in combination with
trastuzumab and chemotherapy for the neoadjuvant
treatment of adults with HER2-positive, locally advanced,
inflammatory, or early stage breast cancer at high risk of
recurrence. This advice is contingent upon the continuing
availability of the patient access scheme in NHS Scotland
or a list price that is equivalent or lower.
The Scottish Medicines Consortium has advised (January
2019) that pertuzumab (Perjeta ®) is accepted for use
within NHS Scotland in combination with trastuzumab
and docetaxel, in adults with HER2-positive metastatic or
locally recurrent unresectable breast cancer, who have not
received previous anti-HER2 therapy or chemotherapy for
their metastatic disease. This advice is contingent upon
the continuing availability of the patient access scheme in
NHS Scotland or a list price that is equivalent or lower.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Perjeta (Roche Products Ltd)
Pertuzumab 30 mg per 1 ml Perjeta 420mg/14ml concentrate for
solution for infusion vials | 1 vial P £2,395.00 (Hospital only)
l DRUG ACTION Ramucirumab is a human monoclonal
antibody that binds to the vascular endothelial growth
factor receptor-2 (VEGFR-2), inhibiting VEGF-induced
Treatment of advanced gastric cancer or gastrooesophageal junction adenocarcinoma, in combination
with paclitaxel, in patients with disease progression
after prior platinum and fluoropyrimidine
▶ Adult: 8 mg/kg on days 1 and 15 of a 28 day cycle, dose
to be administered prior to paclitaxel infusion, consult
product literature for dose adjustments due to sideeffects and infusion-related reactions continued→
BNF 78 Antibody responsive malignancy 881
Immune system and malignant disease
Treatment of advanced gastric cancer or gastrooesophageal junction adenocarcinoma, as monotherapy,
in patients with disease progression after prior platinum
or fluoropyrimidine chemotherapy, and for whom
treatment in combination with paclitaxel is not
▶ Adult: 8 mg/kg every 2 weeks, consult product
literature for dose adjustments due to side-effects and
Treatment of metastatic colorectal cancer, in combination
with FOLFIRI (irinotecan, fluorouracil and folinic acid),
in patients with disease progression on, or after, prior
therapy with bevacizumab, oxaliplatin and a
▶ Adult: 8 mg/kg every 2 weeks, dose to be administered
prior to FOLFIRI administration, consult product
literature for dose adjustments due to side-effects and
Treatment of locally advanced or metastatic non-small
cell lung cancer, in combination with docetaxel, in
patients with disease progression after platinum-based
▶ Adult: 10 mg/kg on day 1 of a 21 day cycle, dose to be
administered prior to docetaxel infusion, consult
product literature for dose adjustments due to sideeffects and infusion-related reactions
l CAUTIONS Elective surgery—discontinue treatment for at
least 4 weeks prior to surgery . hypertension—must be
controlled before initiation . impaired wound healing—
discontinue treatment until wound fully healed . pretreatment is recommended to minimise the
development of adverse reactions (consult product
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Common or very common Asthenia . diarrhoea . electrolyte
imbalance . gastrointestinal discomfort. gastrointestinal
▶ Frequency not known Arterial thrombosis . back pain . back
reaction . myocardial infarction . paraesthesia .respiratory
disorders . supraventricular tachycardia .tremor
SIDE-EFFECTS, FURTHER INFORMATION Infusion-related
hypersensitivity reactions have been reported with
ramucirumab, particularly during or following the first or
second infusion; if the patient experiences a grade 1 or 2
infusion-related reaction, the manufacturer advises to
reduce rate of infusion by 50% and give premedication for
all subsequent infusions—consult product literature.
Manufacturer advises to permanently discontinue
treatment in the event of a grade 3 or 4 infusion-related
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception during treatment and for up to
3 months after treatment in women of childbearing
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—no information available.
l BREAST FEEDING Manufacturer advises discontinue
breast-feeding during treatment and for at least 3 months
after treatment—no information available.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
severe cirrhosis, cirrhosis with hepatic encephalopathy,
cirrhosis with clinically significant ascites, or hepatorenal
syndrome (risk of progressive hepatic failure, no
l MONITORING REQUIREMENTS Manufacturer advises
monitor for signs of infusion-related hypersensitivity
reactions; monitor blood pressure prior to each infusion;
monitor for development or worsening of proteinuria
during treatment—consult product literature; monitor
blood counts and coagulation parameters in patients at
l DIRECTIONS FOR ADMINISTRATION For intravenous infusion
(Cyramza ®), give intermittently in Sodium chloride 0.9%;
dilute requisite dose with infusion fluid to final volume of
250 mL and invert gently to mix. Do not exceed a rate of
25 mg/minute, and give over approximately 60 minutes via
an infusion pump using a separate infusion line with a
protein sparing 0.22 micron filter.
l PRESCRIBING AND DISPENSING INFORMATION For
Cyramza ®, each 10 mL vial contains sodium 17 mg
(equivalent to Na+ 0.74 mmol).
l NATIONAL FUNDING/ACCESS DECISIONS
chemotherapy (January 2016) NICE TA378
Ramucirumab alone or in combination with paclitaxel is
not recommended for the treatment of advanced gastric
cancer or gastro-oesophageal junction adenocarcinoma
previously treated with chemotherapy.
Patients whose treatment was started before this
guidance was published, should have the option to
continue treatment until they and their clinician consider
▶ Ramucirumab for previously treated locally advanced or
metastatic non-small-cell lung cancer (August 2016)
Ramucirumab, in combination with docetaxel, is not
recommended for treating locally advanced or metastatic
non-small-cell lung cancer in patients whose disease has
progressed after platinum-based chemotherapy.
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 clinicians consider it
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
ELECTROLYTES: May contain Sodium
▶ Cyramza (Eli Lilly and Company Ltd) A
Ramucirumab 10 mg per 1 ml Cyramza 100mg/10ml concentrate
for solution for infusion vials | 1 vial P £500.00 (Hospital only)
Cyramza 500mg/50ml concentrate for solution for infusion vials |
1 vial P £2,500.00 (Hospital only)
Rheumatoid arthritis (specialist use only)
▶ Adult: 1 g, then 1 g after 2 weeks, consult product
literature for information on retreatment
882 Antibody responsive malignancy BNF 78
Immune system and malignant disease
Non-Hodgkin’s lymphoma (specialist use only)| Chronic
lymphocytic leukaemia (specialist use only)|
Granulomatosis with polyangiitis and microscopic
polyangiitis (specialist use only)
▶ Adult: (consult product literature)
Non-Hodgkin’s lymphoma (specialist use only)
▶ Adult: (consult product literature)
Pemphigus vulgaris (specialist use only)
▶ Adult: 1 g, then 1 g after 2 weeks; maintenance 0.5 g, at
months 12 and 18, and then every 6 months thereafter
if needed, consult product literature for the treatment
▶ When used for pemphigus vulgaris, rheumatoid arthritis and
granulomatosis with polyangiitis and microscopic
polyangiitis Severe heart failure . severe, uncontrolled heart
CONTRA-INDICATIONS, FURTHER INFORMATION
For full details on contra-indications, consult product
GENERAL CAUTIONS History of cardiovascular disease;
exacerbation of angina, arrhythmia, and heart failure have
been reported . patients receiving cardiotoxic
chemotherapy; exacerbation of angina, arrhythmia, and
heart failure have been reported . pre-medication
recommended to minimise adverse reactions (consult
product literature). predisposition to infection .transient
▶ When used for pemphigus vulgaris, granulomatosis with
polyangiitis and microscopic polyangiitis Pneumocystis jirovecii
pneumonia—consult product literature for prophylaxis
CAUTIONS, FURTHER INFORMATION For full details on
cautions, consult product literature or local treatment
▶ Hepatitis B infection and reactivation Hepatitis B infection and
reactivation (including fatal cases) have been reported in
patients taking rituximab. Patients with positive hepatitis
B serology should be referred to a liver specialist for
monitoring and initiation of antiviral therapy before
treatment initiation; treatment should not be initiated in
patients with evidence of current hepatitis B infection
until the infection has been adequately treated. Patients
should be closely monitored for clinical and laboratory
signs of active hepatitis B infection during treatment and
for up to a year following the last infusion (consult product
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Common or very common Angioedema . anxiety . appetite
disorder. malaise . migraine . multi organ failure . muscle
tone increased . myalgia . nausea . nerve disorders .
abnormal . sepsis . skin reactions .throat irritation . tinnitus . vasodilation . weight decreased
▶ Uncommon Asthma . coagulation disorder. haemolytic
anaemia . heart failure . hypoxia . ischaemic heart disease . lymphadenopathy .taste altered
▶ Rare or very rare Cytokine release syndrome . facial
necrolysis (discontinue).tumour lysis syndrome . vasculitis . vision disorders
(PRES). psychiatric disorder. seizure . skin papilloma
SIDE-EFFECTS, FURTHER INFORMATION Associated with
infections, sometimes severe, including tuberculosis,
septicaemia, and hepatitis B reactivation.
Progressive multifocal leucoencephalopathy has been
reported in association with rituximab; patients should be
monitored for cognitive, neurological, or psychiatric signs
and symptoms. If progressive multifocal
leucoencephalopathy is suspected, suspend treatment
l CONCEPTION AND CONTRACEPTION Effective
contraception (in both sexes) required during and for
l PREGNANCY Avoid unless potential benefit to mother
outweighs risk of B-lymphocyte depletion in fetus.
l BREAST FEEDING Avoid breast-feeding during and for
l MONITORING REQUIREMENTS For full details on
monitoring requirements consult product literature.
l DIRECTIONS FOR ADMINISTRATION
▶ With intravenous use For intravenous infusion, give
intermittently in Glucose 5% or Sodium chloride 0.9%;
dilute to 1–4 mg/mL and gently invert bag to avoid
foaming; for further information, consult product
l PRESCRIBING AND DISPENSING INFORMATION Rituximab is
a biological medicine. Biological medicines must be
prescribed and dispensed by brand name, see Biological
medicines and Biosimilar medicines, under Guidance on
Alert card Patients should be provided with a patient alert
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Rituximab in combination with glucocorticoids for treating
anti-neutrophil cytoplasmic antibody-associated vasculitis
▶ With intravenous use This NICE guidance was issued for
rituximab by intravenous infusion. Rituximab, in
combination with glucocorticoids, is recommended as an
option for inducing remission in adults with antineutrophil cytoplasmic antibody [ANCA]-associated
vasculitis (severely active granulomatosis with polyangiitis
[Wegener’s] and microscopic polyangiitis), only if:
. further cyclophosphamide treatment would exceed the
maximum cumulative cyclophosphamide dose, or
. cyclophosphamide is contra-indicated or not tolerated,
. the patient has not completed their family, and
treatment with cyclophosphamide may materially affect
. the disease has remained active or progressed despite a
course of cyclophosphamide lasting 3–6 months or
. the patient has had uroepithelial malignancy.
BNF 78 Antibody responsive malignancy 883
Immune system and malignant disease
www.nice.org.uk/guidance/ta308
▶ Adalimumab, etanercept, infliximab, rituximab, and
abatacept for the treatment of rheumatoid arthritis after the
failure of a TNF inhibitor (August 2010) NICE TA195
▶ With intravenous use This NICE guidance was issued for
rituximab by intravenous infusion. Rituximab, in
combination with methotrexate, is recommended as an
option for the treatment of severe active rheumatoid
arthritis in adults who have had an inadequate response
to, or are intolerant of, other disease-modifying
antirheumatic drugs (DMARDs), including at least 1
tumour necrosis factor (TNF) inhibitor. Repeat courses of
rituximab should be given no more frequently than every
6 months, and should only be continued if an adequate
response is achieved and maintained.
www.nice.org.uk/guidance/ta195
▶ Rituximab for the first-line treatment of stage III-IV follicular
lymphoma (January 2012) NICE TA243
▶ With intravenous use This NICE guidance was issued for
rituximab by intravenous infusion. Rituximab, in
. cyclophosphamide, vincristine and prednisolone (CVP);
. cyclophosphamide, doxorubicin, vincristine and
. mitoxantrone, chlorambucil and prednisolone (MCP);
. cyclophosphamide, doxorubicin, etoposide,
prednisolone and interferon-alfa (CHVPi); or
is recommended as an option for the treatment of
symptomatic stage III and IV follicular lymphoma in
previously untreated patients.
www.nice.org.uk/guidance/ta243
▶ Rituximab for the treatment of relapsed or refractory stage III
or IV follicular non-Hodgkin’s lymphoma (February 2008)
▶ With intravenous use This NICE guidance was issued for
rituximab by intravenous infusion. Rituximab, in
combination with chemotherapy, is recommended as an
option for the induction of remission in patients with
relapsed stage III or IV follicular non-Hodgkin’s
lymphoma. Rituximab monotherapy, as maintenance
therapy, is recommended as an option for the treatment of
patients with relapsed stage III or IV follicular nonHodgkin’s lymphoma in remission induced with
chemotherapy (with or without rituximab). Rituximab
monotherapy is recommended as an option for the
treatment of patients with relapsed or refractory stage III
or IV follicular non-Hodgkin’s lymphoma, when all
alternative treatment options have been exhausted (that
is, if there is resistance to or intolerance of chemotherapy).
www.nice.org.uk/guidance/ta137
▶ Rituximab for the treatment of relapsed or refractory chronic
lymphocytic leukaemia (July 2010) NICE TA193
▶ With intravenous use This NICE guidance was issued for
rituximab by intravenous infusion. Rituximab in
combination with fludarabine and cyclophosphamide is
recommended as a treatment option for patients with
relapsed or refractory chronic lymphocytic leukaemia
. is refractory to fludarabine (that is, it has not responded
to fludarabine, or has relapsed within 6 months of
. has previously been treated with rituximab, unless it was
in the context of a clinical trial, at a dose lower than the
dose currently licensed for chronic lymphocytic
leukaemia or with chemotherapy other than fludarabine
Rituximab in combination with fludarabine and
cyclophosphamide is recommended only in the context of
research for patients with relapsed or refractory chronic
lymphocytic leukaemia that has previously been treated
with rituximab, unless rituximab has been given as
www.nice.org.uk/guidance/ta193
▶ Rituximab for the first-line maintenance treatment of
follicular non-Hodgkin’s lymphoma (June 2011) NICE TA226
▶ With intravenous use This NICE guidance was issued for
rituximab by intravenous infusion. Rituximab
maintenance therapy is recommended as an option for the
treatment of patients with follicular non-Hodgkin’s
lymphoma that has responded to first-line induction
therapy with rituximab in combination with
www.nice.org.uk/guidance/ta226
▶ Rituximab for the first-line treatment of chronic lymphocytic
leukaemia (July 2009) NICE TA174
▶ With intravenous use This NICE guidance was issued for
rituximab by intravenous infusion. Rituximab, in
combination with fludarabine and cyclophosphamide, is
recommended as an option for the first-line treatment of
chronic lymphocytic leukaemia.
www.nice.org.uk/guidance/ta174
▶ Idelalisib for treating chronic lymphocytic leukaemia (October
Rituximab, in combination with idelalisib, is
recommended as an option for treatment in adults:
. who have untreated chronic lymphocytic leukaemia or
. who have chronic lymphocytic leukaemia when the
disease has been treated but has relapsed within
. if the manufacturer provides idelalisib with the discount
agreed in the simple discount agreement.
Patients who are already receiving idelalisib should
continue treatment until they or their clinician consider it
www.nice.org.uk/guidance/ta359
▶ Venetoclax with rituximab for previously treated chronic
lymphocytic leukaemia (February 2019) NICE TA561
Venetoclax (Venclyxto ®) with rituximab is recommended,
within its marketing authorisation, as an option for
treating chronic lymphocytic leukaemia in adults who
have had at least 1 previous therapy. It is recommended
only if the manufacturer provides it according to the
www.nice.org.uk/guidance/ta561
Scottish Medicines Consortium (SMC) decisions
▶ With intravenous use The Scottish Medicines Consortium has
advised (August 2013) that Rituximab (MabThera ®) is
accepted for restricted use within NHS Scotland, in
combination with glucocorticoids for the induction of
remission in adult patients with severe, active
granulomatosis with polyangiitis (Wegener’s) and
microscopic polyangiitis. It is restricted to use in patients
who have relapsed following treatment with
cyclophosphamide or who are intolerant to or unable to
▶ With subcutaneous use The Scottish Medicines Consortium
has advised (June 2014) that subcutaneous rituximab
(MabThera) ® is accepted for restricted use within NHS
Scotland, in accordance with UK licensing, except in the
maintenance setting, where use is restricted to patients
who have responded to induction therapy with rituximab
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ MabThera (Roche Products Ltd)
Rituximab 119.66 mg per 1 ml MabThera 1400mg/11.7ml solution
for injection vials | 1 vial P £1,344.65 (Hospital only)
884 Antibody responsive malignancy BNF 78
Immune system and malignant disease
EXCIPIENTS: May contain Polysorbates
ELECTROLYTES: May contain Sodium
▶ MabThera (Roche Products Ltd)
Rituximab 10 mg per 1 ml MabThera 100mg/10ml concentrate for
solution for infusion vials | 2 vial P £349.25
MabThera 500mg/50ml concentrate for solution for infusion vials | 1 vial P £873.15
Rituximab 10 mg per 1 ml Rixathon 100mg/10ml concentrate for
solution for infusion vials | 2 vial P £314.33 (Hospital only)
Rixathon 500mg/50ml concentrate for solution for infusion vials |
1 vial P £785.84 (Hospital only) | 2 vial P £1,571.67 (Hospital
▶ Truxima (Napp Pharmaceuticals Ltd) A
Rituximab 10 mg per 1 ml Truxima 100mg/10ml concentrate for
solution for infusion vials | 2 vial P £314.33
Truxima 500mg/50ml concentrate for solution for infusion vials |
l DRUG ACTION Siltuximab is a monoclonal antibody that
inhibits interleukin-6 receptor binding.
Treatment of multicentric Castleman’s disease (MCD) in
patients who are human immunodeficiency virus (HIV)
negative and human herpesvirus-8 (HHV-8) negative
▶ Adult: 11 mg/kg every 3 weeks
l CAUTIONS Patients at increased risk of gastrointestinal
perforation—promptly investigate those presenting with
Consult product literature for further information about
▶ Hypersensitivity reactions Infusion-related side-effects are
reported commonly with siltuximab; resuscitation
facilities should be available during treatment.
l INTERACTIONS → Appendix 1: monoclonal antibodies
reactions .thrombocytopenia . weight increased
SIDE-EFFECTS, FURTHER INFORMATION Siltuximab therapy
should be discontinued permanently in the event of a
severe infusion-related reaction, anaphylaxis, a severe
allergic reaction, or the occurrence of cytokine-release
syndrome. Mild to moderate infusion-related reactions
may improve by temporarily reducing the rate or stopping
the infusion. When restarting treatment, a reduced
infusion rate and the administration of antihistamines,
paracetamol, and corticosteroids may be considered.
Consider discontinuation of siltuximab if more than
2 doses are delayed due to treatment-related toxicities
during the first 48 weeks—for full details consult product
l CONCEPTION AND CONTRACEPTION Women of
childbearing potential should use effective contraception
during and for 3 months after treatment.
l PREGNANCY Manufacturer advises avoid unless potential
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises caution (no
▶ Monitor neutrophil and platelet count, and haemoglobin
levels prior to each dose of siltuximab treatment for the
first 12 months and thereafter prior to every third dosing
cycle. Consider delaying treatment if required neutrophil,
platelet, and haemoglobin levels not achieved—consult
product literature for details.
▶ Monitor for infection during treatment.
l DIRECTIONS FOR ADMINISTRATION For intravenous infusion
(Sylvant ®), give intermittently in Glucose 5%. Allow vials
to reach room temperature over approximately
30 minutes, then reconstitute each 100 mg vial with 5.2 mL
of water for injection, and each 400 mg vial with 20 mL of
water for injection, to produce a 20 mg/mL solution.
Gently swirl without shaking to dissolve. Further dilute to
250 mL with glucose 5% and gently mix. Use within 6 hours
of dilution and give over 60 minutes using an
administration set lined with polyvinyl chloride or
polyurethane, through a low-protein binding in-line
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for infusion
▶ Sylvant (Janssen-Cilag Ltd) A
Siltuximab 100 mg Sylvant 100mg powder for concentrate for
solution for infusion vials | 1 vial P £415.00 (Hospital only)
Siltuximab 400 mg Sylvant 400mg powder for concentrate for
solution for infusion vials | 1 vial P £1,661.00 (Hospital only)
Treatment of early breast cancer which overexpresses
human epidermal growth factor receptor-2 (HER2)
(initiated by a specialist)| Treatment of metastatic
breast cancer in patients with HER2-positive tumours
who have not received chemotherapy for metastatic
breast cancer and in whom anthracycline treatment is
inappropriate (in combination with paclitaxel or
docetaxel) (initiated by a specialist)| Treatment of
metastatic breast cancer in postmenopausal patients
with hormone-receptor positive HER2-positive tumours
not previously treated with trastuzumab (in
combination with an aromatase inhibitor) (initiated by a
▶ BY INTRAVENOUS INFUSION, OR BY SUBCUTANEOUS INJECTION
▶ Adult: (consult product literature or local protocols)
Monotherapy for metastatic breast cancer in patients
with tumours that overexpress HER2 who have received
at least 2 chemotherapy regimens including, where
appropriate, an anthracycline and a taxane (initiated by
▶ BY INTRAVENOUS INFUSION, OR BY SUBCUTANEOUS INJECTION
▶ Adult: Women with oestrogen-receptor-positive breast
cancer should also have received hormonal therapy
(consult product literature or local protocols)
Treatment of metastatic gastric cancer in patients with
HER2-positive tumours who have not received treatment
for metastatic gastric cancer (in combination with
capecitabine or fluorouracil and cisplatin) (initiated by a
▶ Adult: (consult product literature or local protocols)
l CONTRA-INDICATIONS Severe dyspnoea at rest
l CAUTIONS Coronary artery disease . history of
hypertension . symptomatic heart failure . uncontrolled
l INTERACTIONS → Appendix 1: monoclonal antibodies
BNF 78 Antibody responsive malignancy 885
Immune system and malignant disease
eye . dry mouth . dyspnoea . excessive tearing . eye
disorder.respiratory disorders .rhinorrhoea . sepsis . skin
▶ Uncommon Deafness . pericardial effusion
fibrosis (may be delayed). pulmonary oedema (may be
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception in women of childbearing potential
during and for 7 months after treatment. See also
Pregnancy and reproductive function in Cytotoxic drugs
l PREGNANCY Manufacturer advises avoid—
oligohydramnios reported. See also Pregnancy and
reproductive function in Cytotoxic drugs p. 888.
l BREAST FEEDING Avoid breast-feeding during treatment
▶ Cardiotoxicity Monitor cardiac function before and during
treatment—for details of monitoring and managing
cardiotoxicity, consult product literature.
l DIRECTIONS FOR ADMINISTRATION Resuscitation facilities
should be available during administration of trastuzumab.
l PRESCRIBING AND DISPENSING INFORMATION When
prescribing, dispensing or administering, check that this is
the correct preparation—trastuzumab is not
interchangeable with trastuzumab emtansine.
Trastuzumab is a biological medicine. Biological
medicines must be prescribed and dispensed by brand
name, see Biological medicines and Biosimilar medicines,
under Guidance on prescribing p. 1.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Guidance on the use of trastuzumab for the treatment of
advanced breast cancer (March 2002) NICE TA34
Trastuzumab in combination with paclitaxel is
recommended as an option for patients with tumours
expressing human epidermal growth factor receptor 2
(HER2) scored at levels of 3+ who have not received
chemotherapy for metastatic breast cancer, and in whom
anthracycline treatment is inappropriate.
Trastuzumab monotherapy is recommended as an
option for patients with tumours expressing HER2 scored
at levels of 3+ who have received at least two
chemotherapy regimens for metastatic breast cancer. Prior
chemotherapy must have included at least an
anthracycline and a taxane where these treatments are
appropriate. It should also have included hormonal
therapy in suitable oestrogen-receptor-positive patients.
▶ Trastuzumab for the adjuvant treatment of early-stage
HER2-positive breast cancer (August 2006) NICE TA107
Trastuzumab, given at 3-week intervals for 1 year or until
disease recurrence (whichever is the shorter period), is
recommended as an option for women with early-stage
HER2-positive breast cancer following surgery,
chemotherapy (neoadjuvant or adjuvant) and radiotherapy
www.nice.org.uk/guidance/ta107
▶ Lapatinib or trastuzumab in combination with an aromatase
Lapatinib or trastuzumab in combination with an
aromatase inhibitor is not recommended for first-line
treatment in postmenopausal women of metastatic
hormone-receptor-positive breast cancer that
overexpresses human epidermal growth factor receptor 2
Postmenopausal women currently receiving lapatinib or
trastuzumab in combination with an aromatase inhibitor
for this indication should have the option to continue
treatment until they and their clinician consider it
www.nice.org.uk/guidance/ta257
▶ Pertuzumab with trastuzumab and docetaxel for treating
HER2-positive breast cancer (March 2018) NICE TA509
Pertuzumab, in combination with trastuzumab and
docetaxel, is recommended, within its marketing
authorisation, for treating HER2-positive metastatic or
locally recurrent unresectable breast cancer, in adults who
have not had previous anti-HER2 therapy or chemotherapy
for their metastatic disease, only if the manufacturer
provides pertuzumab within the agreed commercial access
www.nice.org.uk/guidance/ta509
▶ Trastuzumab for the treatment of HER2-positive metastatic
gastric cancer (November 2010) NICE TA208
Trastuzumab in combination with cisplatin and
capecitabine or fluorouracil is recommended for human
epidermal growth factor receptor-2-positive metastatic
adenocarcinoma of the stomach or gastro-oesophageal
. have not received treatment for metastatic disease and
. have tumours expressing high levels of HER2 as defined
by a positive immunohistochemistry score of 3.
www.nice.org.uk/guidance/ta208
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (January
2014) that subcutaneous trastuzumab injection
(Herceptin ®) is accepted for restricted use within NHS
Scotland for the treatment of adults with HER2 positive
metastatic breast cancer and early breast cancer, when
used within licensed indications excluding use in
combination with an aromatase inhibitor for the treatment
of postmenopausal patients with hormone-receptor
positive metastatic breast cancer, not previously treated
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