Rebif 44micrograms/0.5ml (12million units) solution for injection
1.5ml cartridges | 4 cartridge P £813.21
Powder and solvent for solution for injection
Interferon beta-1b 300 microgram Betaferon 300microgram
powder and solvent for solution for injection vials | 15 vial P £596.63 (Hospital only)
▶ Extavia (Novartis Pharmaceuticals UK Ltd)
Interferon beta-1b 300 microgram Extavia 300microgram powder
and solvent for solution for injection vials | 15 vial P £596.63
l DRUG ACTION Peginterferon beta-1a is a polyethylene
glycol-conjugated (’pegylated’) derivative of interferon
beta; pegylation increases the persistence of interferon in
Treatment of relapsing, remitting multiple sclerosis
▶ Adult: (consult product literature)
l CONTRA-INDICATIONS Severe depression . suicidal ideation
l CAUTIONS History of cardiac disorders . history of
depressive disorders (avoid in severe depression or in
those with suicidal ideation). history of seizures . history
CAUTIONS, FURTHER INFORMATION Consult product
literature for further information about cautions.
l INTERACTIONS → Appendix 1: peginterferon beta-1a
illness . myalgia . nausea . pain . skin reactions . vomiting
▶ Uncommon Seizure .thrombocytopenia
▶ Rare or very rare Glomerulosclerosis . haemolytic uraemic
syndrome . injection site necrosis . nephrotic syndrome . thrombotic microangiopathy
▶ Frequency not known Pulmonary arterial hypertension
l CONCEPTION AND CONTRACEPTION Effective
contraception required during treatment—consult product
l PREGNANCY Do not initiate during pregnancy. Avoid
unless potential benefit outweighs risk.
l BREAST FEEDING Avoid—no information available.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
l RENAL IMPAIRMENT Caution in severe renal impairment.
▶ Monitor for signs of hepatic injury—hepatic failure has
▶ Thrombotic microangiopathy Patients should be monitored
for clinical features of thrombotic microangiopathy (TMA),
including thrombocytopenia, new onset hypertension,
fever, central nervous system symptoms (e.g. confusion
and paresis), and impaired renal function. Any signs of
TMA should be investigated fully and, if diagnosed,
interferon beta should be stopped immediately and
treatment for TMA promptly initiated (consult product
▶ Nephrotic syndrome Patients should also be monitored for
signs and symptoms of nephrotic syndrome, including
oedema, proteinuria, and impaired renal function—
monitor renal function periodically. If nephrotic syndrome
develops, treat promptly and consider stopping interferon
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Plegridy (Biogen Idec Ltd) A
Peginterferon beta-1a 126 microgram per 1 ml Plegridy
63micrograms/0.5ml solution for injection pre-filled pen | 1 pre-filled
Peginterferon beta-1a 188 microgram per 1 ml Plegridy
94micrograms/0.5ml solution for injection pre-filled pen | 1 pre-filled
Peginterferon beta-1a 250 microgram per 1 ml Plegridy
Glatiramer acetate 13-Jul-2018
l DRUG ACTION Glatiramer is an immunomodulating drug
comprising synthetic polypeptides.
Multiple sclerosis [relapsing-remitting] (initiated under
▶ Adult: 20 mg once daily, alternatively 40 mg 3 times a
week, doses to be separated by an interval of at least
occur within minutes of injection). ear disorder. eye
▶ Uncommon Abnormal dreams . abscess . alcohol
intolerance . angioedema . apnoea . arthritis . breast
nodule . splenomegaly . stupor. suicide attempt.testicular
disorder.thrombocytopenia . urinary tract disorder. urine
abnormal . varicose veins . vulvovaginal disorder
l PREGNANCY Manufacturer advises avoid—no information
l BREAST FEEDING Manufacturer advises caution—no
l RENAL IMPAIRMENT No information available—
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Beta interferons and glatiramer acetate for treating multiple
sclerosis (June 2018) NICE TA527
Glatiramer acetate (Copaxone ®) is recommended as an
option for treating multiple sclerosis, only if:
852 Immune system disorders and transplantation BNF 78
Immune system and malignant disease
. the patient has relapsing-remitting multiple sclerosis,
. the manufacturer provides it according to the
commercial arrangement.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 it appropriate to stop.
www.nice.org.uk/guidance/ta527
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (December
2015) that glatiramer acetate (Copaxone ®) is accepted for
use within NHS Scotland for the treatment of relapsing
NHS England Clinical Commissioning Policy NHS England
(May 2014) has provided guidance on the use of glatiramer
acetate for the treatment of multiple sclerosis in England.
An NHS England Clinical Commissioning Policy outlines
the funding arrangements and the criteria for initiating
and discontinuing this treatment option, see www.england.
nhs.uk/commissioning/spec-services/npc-crg/group-d/d04.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Glatiramer acetate 20 mg per 1 ml Brabio 20mg/1ml solution for
injection pre-filled syringes | 28 pre-filled disposable injection P £462.56
Glatiramer acetate 40 mg per 1 ml Brabio 40mg/1ml solution for
injection pre-filled syringes | 12 pre-filled disposable injection P £462.56
Glatiramer acetate 20 mg per 1 ml Copaxone 20mg/1ml solution
for injection pre-filled syringes | 28 pre-filled disposable
Glatiramer acetate 40 mg per 1 ml Copaxone 40mg/1ml solution
for injection pre-filled syringes | 12 pre-filled disposable
l DRUG ACTION Dimethyl fumarate has immunomodulatory
and anti-inflammatory properties.
Plaque psoriasis [moderate-to-severe] (under expert
▶ Adult: Initially 30 mg once daily for 1 week, dose to be
taken in the evening, then increased in steps of 30 mg
every week for 3 weeks, then increased in steps of
120 mg every week for 5 weeks, for further information
on the dose titration and administration schedule,
advice on establishing a maintenance dose, and for
dose adjustments due to side-effects, consult product
literature; maximum 720 mg per day
Multiple sclerosis [relapsing-remitting] (initiated by a
▶ Adult: Initially 120 mg twice daily for 7 days, then
increased to 240 mg twice daily, for dose adjustments
due to side effects—consult product literature
SKILARENCE ® Do not initiate if leucocyte count below
/litre . do not initiate if lymphocyte count below
/litre . do not initiate if pathological haematological
abnormalities identified . severe gastro-intestinal
l CAUTIONS Reduced lymphocyte count
TECFIDERA ® Serious infection (do not initiate until
infection resolved; consider suspending treatment if
infection develops). severe active gastro-intestinal disease
SKILARENCE ® Significant infection (consider avoiding
initiation until infection resolved and suspending
treatment if infection develops)
l INTERACTIONS → Appendix 1: dimethyl fumarate
▶ Uncommon Dizziness . proteinuria
▶ Rare or very rare Acute lymphocytic leukaemia . pancytopenia
▶ Frequency not known Progressive multifocal
leukoencephalopathy (PML).renal failure
SIDE-EFFECTS, FURTHER INFORMATION Severe prolonged
lymphopenia reported, and patients are exposed to a
potential risk of PML. Treatment should be stopped
immediately if PML is suspected.
TECFIDERA ® Manufacturer advises avoid unless essential
and potential benefit outweighs risk—toxicity in animal
SKILARENCE ® Manufacturer advises avoid—toxicity in
l BREAST FEEDING Manufacturer advises avoid.
TECFIDERA ® Manufacturer advises caution in severe
impairment (no information available).
SKILARENCE ® Manufacturer advises avoid in severe
impairment (no information available).
TECFIDERA ® Manufacturer advises caution in severe
impairment—no information available.
SKILARENCE ® Manufacturer advises avoid in severe
impairment—no information available.
▶ Manufacturer advises monitor full blood count before
treatment initiation then every 3 months thereafter—
consult product information for further information.
▶ Manufacturer advises monitor patient closely for features
of progressive multifocal leukoencephalopathy (PML) (e.g.
signs and symptoms of neurological dysfunction) and
other opportunistic infections.
▶ Manufacturer advises monitor renal and hepatic function
before treatment initiation and during treatment—consult
product literature for further information.
▶ Manufacturer of Tecfidera ® advises perform a baseline MRI
as a reference and repeat as required during treatment.
l PRESCRIBING AND DISPENSING INFORMATION
SKILARENCE ® The manufacturer of Skilarence ® has
provided a Healthcare Professional Guideline, which
includes important safety information on the risk of
l PATIENT AND CARER ADVICE Manufacturer advises
patients and their carers should be informed of the
possibility of experiencing symptoms of flushing; they
should also be advised to report symptoms of infection to
Immune system and malignant disease
their doctor. The MHRA recommends that patients and
their carers should be counselled on the risk of progressive
multifocal leukoencephalopathy and advised to seek
immediate medical attention if symptoms develop.
l NATIONAL FUNDING/ACCESS DECISIONS
Dimethyl fumarate (Tecfidera ®) is recommended for the
treatment of active relapsing-remitting multiple sclerosis,
. the patient does not have highly active or rapidly
evolving severe relapsing-remitting multiple sclerosis
. the manufacturer provides dimethyl fumarate with the
discount agreed in the patient access scheme
Patients currently receiving dimethyl fumarate whose
disease does not meet the above criteria should be able to
continue treatment until they and their clinician consider
www.nice.org.uk/guidance/TA320
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (April 2014)
that dimethyl fumarate (Tecfidera ®) is accepted for use
within NHS Scotland for the treatment of patients with
relapsing remitting multiple sclerosis. This advice is
contingent upon the continuing availability of the Patient
Access Scheme in NHS Scotland or a list price that is
▶ Dimethyl fumarate for treating moderate-to-severe plaque
psoriasis (September 2017) NICE TA475
Dimethyl fumarate is recommended as an option for
treating plaque psoriasis in adults, only if the disease:
. is severe, as defined by a total Psoriasis Area and
Severity Index (PASI) of 10 or more and a Dermatology
Life Quality Index (DLQI) of more than 10, and
. has not responded to other systemic therapies,
including, ciclosporin, methotrexate and PUVA
(psoralen and long-wave ultraviolet A radiation), or
these options are contra-indicated or not tolerated.
Stop dimethyl fumarate treatment at 16 weeks if the
psoriasis has not responded adequately. An adequate
. a 75% reduction in the PASI score (PASI 75) from when
. a 50% reduction in the PASI score (PASI 50) and a 5-
point reduction in DLQI from when treatment started.
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/ta475
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (April 2018)
that dimethyl fumarate (Skilarence ®) is accepted for
restricted use within NHS Scotland for the treatment of
moderate-to-severe plaque psoriasis in adults in need of
systemic medicinal therapy, whom other non-biologic
systemic treatments (methotrexate, ciclosporin and
acitretin) are not appropriate or have failed and who are
considered unsuitable for biologic therapy given their
current disease state or personal preference.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 21, 25
Dimethyl fumarate 120 mg Tecfidera 120mg gastro-resistant
capsules | 14 capsule P £343.00
Dimethyl fumarate 240 mg Tecfidera 240mg gastro-resistant
capsules | 56 capsule P £1,373.00
CAUTIONARY AND ADVISORY LABELS 21, 25
Dimethyl fumarate 30 mg Skilarence 30mg gastro-resistant tablets
| 42 tablet P £89.04 DT = £89.04
Dimethyl fumarate 120 mg Skilarence 120mg gastro-resistant
tablets | 90 tablet P £190.80 DT = £190.80 | 180 tablet P £381.60 DT = £381.60
l DRUG ACTION Fingolimod is an immunomodulating drug.
Treatment of highly active relapsing-remitting multiple
sclerosis in patients who have high disease activity
despite treatment with at least one disease modifying
therapy or in those with rapidly evolving severe
relapsing-remitting multiple sclerosis (initiated under
▶ Adult: 500 micrograms once daily
MHRA/CHM ADVICE: MULTIPLE SCLEROSIS THERAPIES: SIGNAL OF
REBOUND EFFECT AFTER STOPPING OR SWITCHING THERAPY
A signal of rebound syndrome in multiple sclerosis
patients whose treatment with fingolimod was stopped
or switched to other treatments has been reported in two
recently published articles. The MHRA advise to be
vigilant for such events and report any suspected
adverse effects relating to fingolimod, or other
treatments for multiple sclerosis, via the Yellow Card
Scheme, while this report is under investigation.
MHRA/CHM ADVICE: FINGOLIMOD—NOT RECOMMENDED FOR
PATIENTS AT KNOWN RISK OF CARDIOVASCULAR EVENTS. ADVICE
FOR EXTENDED MONITORING FOR THOSE WITH SIGNIFICANT
BRADYCARDIA OR HEART BLOCK AFTER THE FIRST DOSE AND
FOLLOWING TREATMENT INTERRUPTION (JANUARY 2013)
Fingolimod is known to cause transient bradycardias and
MHRA/CHM ADVICE: FINGOLIMOD: NEW CONTRA-INDICATIONS IN
RELATION TO CARDIAC RISK (DECEMBER 2017)
Fingolimod can cause persistent bradycardia, which can
increase the risk of serious cardiac arrhythmias. New
contra-indications have been introduced for patients
with pre-existing cardiac disorders—see Contraindications for further information.
MHRA/CHM ADVICE: FINGOLIMOD: UPDATED ADVICE ABOUT RISK
OF CANCERS AND SERIOUS INFECTIONS (DECEMBER 2017)
Fingolimod has an immunosuppressive effect and can
increase the risk of skin cancers and lymphoma.
Following a recent EU review, the MHRA has
recommended the following strengthened warnings:
. re-assess the benefit-risk balance of fingolimod
therapy in individual patients, particularly those with
additional risk factors for malignancy—either closely
monitor for skin cancers or consider discontinuation
. examine all patients for skin lesions before they start
fingolimod and then re-examine at least every 6 to
854 Immune system disorders and transplantation BNF 78
Immune system and malignant disease
. advise patients to protect themselves against UV
radiation exposure and seek urgent medical advice if
. refer patients with suspicious lesions to a
Fingolimod has also been associated with risk of fatal
fungal infections and reports of progressive multifocal
leukoencephalopathy (PML)—see Monitoring and Side
effects for further information.
l CONTRA-INDICATIONS Heart failure in the previous
6 months (New York Heart Association class III/IV). active
malignancies . baseline QTc interval 500 milliseconds or
greater. cerebrovascular disease (including transient
ischaemic attack). decompensated heart failure (requiring
inpatient treatment). increased risk for opportunistic
infections (including immunosuppression). myocardial
infarction . second-degree Mobitz type II atrioventricular
block or third-degree AV block, or sick-sinus syndrome, if
the patient does not have a pacemaker. severe active
infection . severe cardiac arrhythmias requiring treatment
with class Ia or class III anti-arrhythmic drugs . unstable
l CAUTIONS Check varicella zoster virus status—consult
product literature for further information . chronic
obstructive pulmonary disease . history of myocardial
infarction . history of symptomatic bradycardia or
recurrent syncope . patients receiving antiarrhythmic or
heart-rate lowering drugs including beta blockers, heart
rate-lowering calcium channel blockers (seek advice from
cardiologist regarding switching to alternative drugs, or if
appropriate monitoring if unable to switch). pulmonary
fibrosis .risk of bradycardia and cardiac rhythm
disturbance .risk of macular oedema . severe respiratory
disease . severe sleep apnoea . significant QT prolongation
(QTc greater than 470 milliseconds in women, or QTc
greater than 450 milliseconds in men); if QTc
prolongation (including electrolyte disturbances). uncontrolled hypertension
▶ Washout period A washout period is recommended when
switching treatment from some disease modifying
therapies—consult product literature for further
▶ Bradycardia and cardiac rhythm disturbance Fingolimod may
cause transient bradycardia, atrioventricular conduction
delays and heart block after the first dose. Fingolimod is
not recommended in patients with the cardiovascular risks
listed above unless the anticipated benefits outweigh the
potential risks, and advice from a cardiologist (including
monitoring advice) is sought before initiation.
l INTERACTIONS → Appendix 1: fingolimod
infection . neoplasms . skin reactions . vision blurred
▶ Uncommon Macular oedema . nausea .thrombocytopenia
▶ Rare or very rare Posterior reversible encephalopathy
▶ Frequency not known Peripheral oedema . progressive
multifocal leukoencephalopathy (PML)
SIDE-EFFECTS, FURTHER INFORMATION Basal-cell
carcinoma Patients should be advised to seek medical
advice if they have any signs of basal-cell carcinoma
including skin nodules, patches or open sores that do not
Progressive multifocal leukoencephalopathy (PML)
and other opportunistic infections Patients should be
advised to seek medical attention if they have any signs of
PML or any other infections. Suspension of treatment
should be considered if a patient develops a severe
infection, taking into consideration the risk-benefit.
l CONCEPTION AND CONTRACEPTION Exclude pregnancy
before treatment. Ensure effective contraception during
and for at least 2 months after treatment.
l PREGNANCY Avoid (toxicity in animal studies).
l HEPATIC IMPAIRMENT Manufacturer advises caution when
initiating treatment in mild to moderate impairment;
▶ All patients receiving fingolimod should be monitored at
treatment initiation, (first dose monitoring—before,
during and after dose), and after treatment interruption
(see note below); monitoring should include:
. an ECG and blood pressure measurement before starting
▶ During the first 6 hours of treatment
. continuous ECG monitoring for 6 hours
. blood pressure and heart rate measurement every hour
. a further ECG and blood pressure measurement
▶ If heart rate at the end of the 6 hour period is at its lowest
since fingolimod was first administered, monitoring
should be extended by at least 2 hours and until heart rate
▶ If post-dose bradyarrhythmia-related symptoms occur,
appropriate clinical management should be initiated and
monitoring should be continued until the symptoms have
resolved. If pharmacological intervention is required
during the first-dose monitoring, overnight monitoring
should follow, and the first-dose monitoring should then
be repeated after the second dose.
▶ If after 6 hours, the heart rate is less than 45 beats per
minute, or the ECG shows new onset second degree,
higher grade AV block, or a QTc interval of
500 milliseconds or greater, or if third degree AV block
occurs, monitoring should be extended (at least overnight,
until side-effect resolution).
▶ The occurrence at any time of third degree AV block
requires extended monitoring (at least overnight, until
▶ In case of T-wave inversion, ensure there are no associated
signs or symptoms of myocardial ischaemia—if suspected
seek advice from a cardiologist.
▶ First dose monitoring as above should be repeated in all
patients whose treatment is interrupted for:
. 1 day or more during the first 2 weeks of treatment
. more than 7 days during weeks 3 and 4 of treatment
. more than 2 weeks after one month of treatment
▶ If the treatment interruption is of shorter duration than
the above, treatment should be continued with the next
▶ Manufacturer advises eye examination recommended
3–4 months after initiation of treatment (and before
initiation of treatment in patients with diabetes or history
▶ Manufacturer advises skin examination for skin lesions
before starting treatment and then every 6 to 12 months
thereafter or as clinically indicated.
▶ Monitor hepatic transaminases before treatment, then
every 3 months for 1 year, then periodically thereafter.
▶ Monitor full blood count before treatment, at 3 months,
then at least yearly thereafter and if signs of infection
(interrupt treatment if lymphocyte count reduced)—
Immune system and malignant disease
▶ Monitor for signs and symptoms of haemophagocytic
syndrome (including pyrexia, asthenia, hepatosplenomegaly and adenopathy—may be associated with
hepatic failure and respiratory distress; also progressive
cytopenia, elevated serum-ferritin concentrations,
hypertriglyceridaemia, hypofibrinogenaemia,
coagulopathy, hepatic cytolysis, hyponatraemia)—initiate
▶ Manufacturer advises to monitor routine MRI for lesions
suggestive of progressive multifocal leukoencephalopathy
(PML), particularly in patients considered at increased
risk; monitor for signs and symptoms of new neurological
l NATIONAL FUNDING/ACCESS DECISIONS
Fingolimod is recommended as an option for the
treatment of highly active relapsing-remitting multiple
. they have an unchanged or increased relapse rate or
ongoing severe relapses compared with the previous
year despite treatment with interferon beta, and
. the manufacturer provides fingolimod with the discount
agreed as part of the patient access scheme
Patients currently receiving fingolimod whose disease
does not meet the above criteria should be able to
continue treatment until they and their clinician consider
www.nice.org.uk/guidance/ta254
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (September
2012) that fingolimod (Gilenya ®) is accepted for restricted
use within NHS Scotland as single disease modifying
therapy in highly active relapsing-remitting multiple
sclerosis despite treatment with interferon beta, with an
unchanged or increased relapse rate or ongoing severe
relapses, as compared to the previous year. This advice is
contingent upon the continuing availability of the patient
access scheme in NHS Scotland.
The Scottish Medicines Consortium has advised (October
2014) that fingolimod (Gilenya ®) is accepted for restricted
use within NHS Scotland as a single disease modifying
therapy in highly active relapsing remitting multiple
sclerosis for adults with rapidly evolving severe relapsing
remitting multiple sclerosis. This advice is contingent
upon the continuing availability of the patient access
scheme in NHS Scotland, or a list price that is equivalent
The Scottish Medicines Consortium has advised (April
2015) that fingolimod (Gilenya ®) is accepted for use within
NHS Scotland as a single disease modifying therapy in
highly active relapsing remitting multiple sclerosis for
adults with high disease activity despite treatment with at
least one disease modifying therapy. This advice is
contingent upon the continuing availability of the patient
access scheme in NHS Scotland, or a list price that is
All Wales Medicines Strategy Group (AWMSG) decisions
The All Wales Medicines Strategy Group has advised
(January 2017) that fingolimod (Gilenya ®) is recommended
multiple sclerosis only in patients with rapidly evolving
severe relapsing-remitting multiple sclerosis defined by 2
or more disabling relapses in 1 year and with 1 or more
gadolinium-enhancing lesions on brain magnetic
resonance imaging (MRI) or a significant increase in T2
lesion load compared with a previous recent MRI, only if
the manufacturer provides fingolimod with the discount
agreed as part of the patient access scheme or where the
list price is equivalent or lower.
NHS England Clinical Commissioning Policy NHS England
(May 2014) has provided guidance on the use of fingolimod
for the treatment of multiple sclerosis in England. An NHS
England Clinical Commissioning Policy outlines the
funding arrangements and the criteria for initiating and
discontinuing this treatment option, see www.england.nhs.
uk/commissioning/spec-services/npc-crg/group-d/d04/.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Gilenya (Novartis Pharmaceuticals UK Ltd) A
Fingolimod (as Fingolimod hydrochloride)
500 microgram Gilenya 0.5mg capsules | 7 capsule P £367.50
(Hospital only) | 28 capsule P £1,470.00 (Hospital only)
IMMUNOSUPPRESSANTS › MONOCLONAL
l DRUG ACTION The anti-lymphocyte monoclonal
antibodies cause lysis of B lymphocytes.
All anti-lymphocyte monoclonal antibodies should be
given under the supervision of an experienced specialist,
in an environment where full resuscitation facilities are
infarction . neutropenia . night sweats .thrombocytopenia . vomiting
▶ Uncommon Progressive multifocal leukoencephalopathy
▶ Frequency not known Anaphylactic reaction
SIDE-EFFECTS, FURTHER INFORMATION Infusion-related
side-effects In rare cases infusion reactions may be fatal.
Infusion-related side-effects occur predominantly during
the first infusion. Patients should receive premedication
before administration of anti-lymphocyte monoclonal
antibodies to reduce these effects—consult product
literature for details of individual regimens. The infusion
Cytokine release syndrome Fatalities following severe
cytokine release syndrome (characterised by severe
dyspnoea) and associated with features of tumour lysis
syndrome have occurred after infusions of antilymphocyte monoclonal antibodies. Patients with a high
tumour burden as well as those with pulmonary
insufficiency or infiltration are at increased risk and should
be monitored very closely (and a slower rate of infusion
l PRE-TREATMENT SCREENING All patients should be
screened for hepatitis B before treatment.
l MONITORING REQUIREMENTS Patients should also be
monitored for cytopenias—consult product literature for
856 Immune system disorders and transplantation BNF 78
Immune system and malignant disease
Treatment of adults with relapsing-remitting multiple
sclerosis with active disease defined by clinical or
▶ Adult: (consult product literature)
l UNLICENSED USE Although no longer licensed for
oncological and transplant indications, alemtuzumab is
also available through a patient access programme for
Alemtuzumab should be given under the care of a
specialist with facilities for the management of
hypersenstivity and anaphylactic reactions.
MHRA/CHM ADVICE: ALEMTUZUMAB (LEMTRADA ®): RESTRICTION
OF USE DUE TO SERIOUS SAFETY CONCERNS (APRIL 2019)
There have been reports of serious cardiovascular
reactions, autoimmune hepatitis, and haemophagocytic
lymphohistiocytosis with the use of Lemtrada ®. Whilst a
review by the European Medicines Agency is ongoing,
healthcare professionals are advised to only initiate
treatment in new patients with relapsing-remitting
multiple sclerosis (RRMS) that is highly active despite a
full and adequate course of treatment with at least two
other disease-modifying treatments, or in patients with
highly active RRMS where all other disease-modifying
treatments are contra-indicated or unsuitable.
Healthcare professionals should monitor liver function
and vital signs, including blood pressure before and
during treatment. Stop infusions if clinically significant
changes in vital functions are observed and consider
additional monitoring, including ECG. Readministration should be carefully considered if
seek immediate medical attention if they experience
symptoms within a few days of the infusion or if
symptoms of hepatic injury occur.
l CONTRA-INDICATIONS Human immunodeficiency virus
l CAUTIONS Hepatitis B carriers . hepatitis C carriers . in
patients with active infection, a delay in initiation of
alemtuzumab treatment should be considered until the
infection is fully controlled . not recommended for inactive
disease . not recommended for stable disease . patients
should receive oral prophylaxis for herpes infection
starting on the first day of treatment and continuing for at
least a month following each treatment course . patients
with previous autoimmune conditions other than multiple
sclerosis . pretreatment before administration is required
CAUTIONS, FURTHER INFORMATION For full details of
cautions, consult product literature.
▶ Autoimmune mediated conditions The risk of autoimmune
mediated conditions may increase during treatment,
including immune thrombocytopenic purpura, thyroid
disorders, nephropathies, and cytopenias, and should be
monitored for throughout the course of treatment (consult
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Common or very common Abdominal pain . anxiety . autoimmune thyroiditis . cough . cytokine release
cycle irregularities . multiple sclerosis exacerbated . muscle
abnormal . skin reactions . stomatitis .tremor. vertigo . vision blurred
▶ Rare or very rare Haemophagocytic lymphohistiocytosis
▶ Frequency not known Artery dissection . cerebrovascular
insufficiency .Goodpasture’s syndrome . hepatitis
autoimmune (including fatal cases). liver injury . meningitis listeria . nephropathy
l CONCEPTION AND CONTRACEPTION Women of
childbearing potential should use effective contraception
during and for 4 months after treatment.
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—toxicity in animal studies.
Autoimmune thyroid disease during treatment may affect
fetus (consult product literature).
l BREAST FEEDING Manufacturer advises avoid during and
for 4 months after each treatment course unless potential
l PRE-TREATMENT SCREENING Screening patients at high
risk of hepatitis B or C is recommended before treatment.
All patients should be evaluated for active or latent
tuberculosis before starting treatment.
l MONITORING REQUIREMENTS For further information on
monitoring, see Important safety information.
▶ HPV screening should be carried out annually in female
l PRESCRIBING AND DISPENSING INFORMATION All patients
should receive oral prophylaxis for herpes infection
starting on the first day of treatment and continuing for at
least a month following each treatment course.
l PATIENT AND CARER ADVICE Patients should be provided
with a patient alert card and patient guide.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Alemtuzumab for treating relapsing-remitting multiple
sclerosis (May 2014) NICE TA312
Alemtuzumab (Lemtrada ®) is recommended as an option,
within its marketing authorisation, for treating adults with
active relapsing-remitting multiple sclerosis.
www.nice.org.uk/guidance/ta312
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Lemtrada (Genzyme Therapeutics Ltd)
Alemtuzumab 10 mg per 1 ml Lemtrada 12mg/1.2ml concentrate
for solution for infusion vials | 1 vial P £7,045.00 (Hospital only)
▶ MabCampath (Genzyme Therapeutics Ltd)
Alemtuzumab 30 mg per 1 ml MabCampath 30mg/1ml concentrate
for solution for infusion vials | 3 vial P £792.34 (Hospital only)
Highly active relapsing-remitting multiple sclerosis
despite treatment with interferon beta or glatiramer
acetate, or those patients with rapidly evolving severe
relapsing-remitting multiple sclerosis (initiated under
▶ Adult 18–65 years: 300 mg every 4 weeks, treatment
should be discontinued if no response after 6 months
l CONTRA-INDICATIONS Active infection . active
malignancies (except cutaneous basal cell carcinoma).
Immune system and malignant disease
immunosuppression . progressive multifocal
▶ Progressive Multifocal Leucoencephalopathy Natalizumab is
associated with an increased risk of opportunistic infection
and progressive multifocal leucoencephalopathy (PML)
caused by JC virus. The risk of developing PML increases
with the presence of anti-JCV antibodies, previous use of
immunosuppressant therapy, and treatment duration
(especially beyond 2 years of treatment); the risk beyond
4 years of treatment is not known. Patients with all three
risk factors should only be treated with natalizumab if the
benefits of treatment outweigh the risks. Treatment
should be suspended until PML has been excluded. If a
patient develops an opportunistic infection or PML,
natalizumab should be permanently discontinued.
For information on cautions consult product literature.
l INTERACTIONS → Appendix 1: monoclonal antibodies
l SIDE-EFFECTS Acute retinal necrosis . basophil count
SIDE-EFFECTS, FURTHER INFORMATION Progressive
Multifocal Leukoencephalopathy (PML) If suspected,
treatment should be suspended until PML has been
excluded. If a patient develops an opportunistic infection
or PML, natalizumab should be permanently discontinued.
Liver injury Discontinue treatment if significant liver
Infusion-related reactions Infusion-related reactions
including dizziness, nausea, urticaria, chills, vomiting and
flushing have been reported either during infusion or
within 1 hour after completion of infusion.
l PREGNANCY Avoid unless essential—toxicity in animal
l BREAST FEEDING Present in milk in animal studies—avoid.
Progressive Multifocal Leucoencephalopathy A magnetic
resonance image (MRI) scan is recommended before
starting treatment with natalizumab.
Testing for serum anti-JCV antibodies before starting
treatment or in those with unknown antibody status
already receiving natalizumab is recommended and should
be repeated every 6 months (consult product literature for
▶ Progressive Multifocal Leucoencephalopathy A magnetic
resonance image (MRI) scan is recommended annually.
Patients should be monitored for new or worsening
neurological symptoms, and for cognitive and psychiatric
All patients should continue to be monitored for signs and
▶ Hypersensitivity reactions Patients should be observed for
hypersensitivity reactions, including anaphylaxis, during
the infusion and for 1 hour after completion of the
l DIRECTIONS FOR ADMINISTRATION For intravenous infusion
(Tysabri ®), give intermittently in Sodium chloride 0.9%;
dilute 300 mg in 100 mL infusion fluid; gently invert to
mix, do not shake. Use within 8 hours of dilution and give
Hypersensitivity reactions Patients should be told the
importance of uninterrupted dosing, particularly in the
early months of treatment (intermittent therapy may
increase risk of sensitisation).
Progressive Multifocal Leucoencephalopathy Patients should be
informed about the risks of PML before starting treatment
with natalizumab and again after 2 years; they should be
given an alert card which includes information about the
Liver toxicity Advise patients to seek immediate medical
attention if symptoms such as jaundice or dark urine
Alert card A patient alert card should be provided.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Natalizumab for the treatment of adults with highly active
relapsing-remitting multiple sclerosis (August 2007)
Natalizumab is an option for the treatment only of rapidly
evolving severe relapsing-remitting multiple sclerosis
(RES). RES is defined by 2 or more disabling relapses in
1 year, and 1 or more gadolinium-enhancing lesions on
brain magnetic resonance imaging (MRI) or a significant
increase in T2 lesion load compared with a previous MRI.
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (August
2007) that natalizumab is accepted for restricted use as
single disease-modifying therapy in highly active
relapsing-remitting multiple sclerosis only in patients with
rapidly evolving severe relapsing-remitting multiple
sclerosis defined by 2 or more disabling relapses in 1 year
and with 1 or more gadolinium-enhancing lesions on brain
magnetic resonance imaging (MRI) or a significant
increase in T2 lesion load compared with a previous MRI.
NHS England Clinical Commissioning Policy NHS England
(May 2014) has provided guidance on the use of
natalizumab for the treatment of multiple sclerosis in
England. An NHS England Clinical Commissioning Policy
outlines the funding arrangements and the criteria for
initiating and discontinuing this treatment option, see
www.england.nhs.uk/commissioning/spec-services/npc-crg/
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
ELECTROLYTES: May contain Sodium
Natalizumab 20 mg per 1 ml Tysabri 300mg/15ml concentrate for
solution for infusion vials | 1 vial P £1,130.00 (Hospital only)
Multiple sclerosis (specialist use only)
▶ Adult: Initially 300 mg, then 300 mg after 2 weeks;
maintenance 600 mg every 6 months, the first
maintenance dose should be given 6 months after the
first initial dose; a minimum interval of 5 months
should be maintained between each maintenance dose,
for dose interruption, adjustment of infusion rate or
discontinuation of treatment due to infusion-related
reactions or side-effects—consult product literature
l CONTRA-INDICATIONS Active infection . active
malignancies . severely immunocompromised patients
l CAUTIONS Complete required vaccinations at least 6 weeks
before treatment initiation . hepatitis B reactivation
l INTERACTIONS → Appendix 1: monoclonal antibodies
l CONCEPTION AND CONTRACEPTION Manufacturer advises
women of childbearing potential should use contraception
during treatment and for 12 months after the last dose.
858 Immune system disorders and transplantation BNF 78
Immune system and malignant disease
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—limited information available;
monitor infants for B-cell depletion.
l BREAST FEEDING Manufacturer advises avoid—present in
▶ Manufacturer advises monitor for signs and symptoms of
progressive multifocal leucoencephalopathy (PML)
(including any new onset or worsening of neurological
symptoms)—if PML is suspected, interrupt treatment;
discontinue treatment permanently if PML is confirmed.
▶ Manufacturer advises monitor for infusion-related
reactions during the infusion and observe patients for
1 hour after completion of the infusion—if severe
pulmonary symptoms occur, permanently discontinue
l PRESCRIBING AND DISPENSING INFORMATION
Manufacturer advises to record the batch number after
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8°C)—consult product literature for further
information regarding storage conditions after preparation
l PATIENT AND CARER ADVICE Manufacturer advises
patients and carers should be advised that infusion-related
reactions can occur within 24 hours of infusion.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Ocrelizumab for treating relapsing–remitting multiple
sclerosis (July 2018) NICE TA533
Ocrelizumab (Ocrevus ®) is recommended as an option for
treating relapsing–remitting multiple sclerosis in adults
with active disease defined by clinical or imaging features,
. alemtuzumab is contra-indicated or otherwise
. the manufacturer provides ocrelizumab according to the
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/ta533
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (December
2018) that ocrelizumab (Ocrevus ®) is accepted for
restricted use within NHS Scotland for the treatment of
relapsing remitting multiple sclerosis in adults with active
disease defined by clinical or imaging features who are
contra-indicated or otherwise unsuitable for
alemtuzumab. 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.
▶ Ocrevus (Roche Products Ltd) A
Ocrelizumab 30 mg per 1 ml Ocrevus 300mg/10ml concentrate for
solution for infusion vials | 1 vial P £4,790.00
IMMUNOSUPPRESSANTS › PYRIMIDINE
l DRUG ACTION Teriflunomide is a metabolite of
leflunomide which has immunomodulating and antiinflammatory properties.
Treatment of relapsing-remitting multiple sclerosis
(initiated under specialist supervision)
immunodeficiency . significantly impaired bone-marrow
l CAUTIONS Adult over 65 years . anaemia . dyspnoea—
assess for interstitial lung disease and consider suspending
treatment. hypoproteinaemia (avoid if severe). impaired
bone-marrow function (avoid if severe). latent
tuberculosis . leucopenia . persistent cough—assess for
interstitial lung disease and consider suspending
treatment. severe infection—delay or suspend treatment
until resolved . significant alcohol consumption . signs or
symptoms of serious skin reactions (including ulcerative
stomatitis, Stevens-Johnson syndrome, and toxic
epidermal necrolysis)—discontinue treatment. switching
between other immunomodulating drugs . thrombocytopenia
l INTERACTIONS → Appendix 1: teriflunomide
of infection . menorrhagia . myalgia . nausea . nerve
increased . vomiting . weight decreased
▶ Frequency not known Asthenia . hepatitis acute . interstitial
lung disease . nail disorder. pancreatitis . sepsis
SIDE-EFFECTS, FURTHER INFORMATION Hepatic injury
Discontinue treatment if signs or symptoms of hepatic
injury, or if liver enzymes exceed 3 times the upper limit of
Important: accelerated elimination procedure
recommended following discontinuation due to serious
adverse effects (consult product literature).
l CONCEPTION AND CONTRACEPTION Effective
contraception essential for women of child-bearing
potential during treatment and for up to 2 years after
treatment. In patients undergoing treatment with
teriflunomide that are planning to conceive, the
accelerated elimination procedure should be used prior to
conception. Use of non-oral contraception is
recommended during the accelerated elimination
procedure—consult product literature.
l PREGNANCY Avoid—toxicity in animal studies.
l BREAST FEEDING Present in milk in animal studies—
l HEPATIC IMPAIRMENT Manufacturer advises avoid in
▶ Monitor full blood count (including differential white cell
count and platelet count) before treatment and as
clinically indicated during treatment.
▶ Monitor blood pressure before treatment and periodically
Immune system and malignant disease
▶ Hepatic monitoring Monitor liver function before treatment
and every 2 weeks for first 6 months then every 8 weeks
thereafter or as clinically indicated (pre-existing liver
disease may increase risk). Increase to weekly monitoring
if alanine aminotransferase (ALT) is 2–3 times the upper
limit of reference range; discontinue treatment if signs or
symptoms of hepatic injury, or if liver enzymes exceed
3 times the upper limit of reference range.
Accelerated elimination procedures To aid drug elimination in
case of serious adverse effect or before conception, stop
treatment and give either colestyramine p. 197 or charcoal,
activated p. 1366. After the accelerated elimination
procedure a plasma concentration of less than
20 micrograms/litre (measured on 2 occasions at least
14 days apart) and a waiting period of one and a half
months are necessary before conception.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Teriflunomide for treating relapsing-remitting multiple
sclerosis (January 2014) NICE TA303
Teriflunomide is recommended for the treatment of adults
with active relapsing-remitting multiple sclerosis
(normally defined as 2 clinically significant relapses in the
previous 2 years), in adults who:
. do not have highly active or rapidly evolving severe
relapsing-remitting multiple sclerosis and
. the manufacturer provides teriflunomide with the
discount agreed in the patient access scheme
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (February
2014) that the use of teriflunomide (Aubagio) ® in NHS
disease, and only as an alternative to treatment with
interferon beta or glatiramer acetate.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Aubagio (Genzyme Therapeutics Ltd)
Teriflunomide 14 mg Aubagio 14mg tablets | 28 tablet P £1,037.84
ANTINEOPLASTIC DRUGS › MONOCLONAL
l DRUG ACTION Atezolizumab is a monoclonal antibody,
which binds to the programmed death-ligand 1 (PD-L1),
thereby reactivating the immune response to tumour cells.
Urothelial carcinoma [as monotherapy] (specialist use
only)| Non-small cell lung cancer [as monotherapy]
▶ Adult: 1200 mg every 3 weeks, for dose interruption,
adjustment of infusion rate or discontinuation of
treatment due to side-effects or infusion-related
reactions—consult product literature
Non-small cell lung cancer [as combination therapy]
▶ Adult: (consult product literature)
l CAUTIONS Abnormal thyroid function—manufacturer
advises to consider appropriate treatment. patients may
need pre-medication to minimise the development of
infusion-related reactions—consult product literature
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Common or very common Abdominal pain . appetite
▶ Rare or very rare Encephalitis non-infective . hypophysitis
SIDE-EFFECTS, FURTHER INFORMATION Immune-related
reactions Manufacturer advises most immune-related
adverse reactions are reversible and managed by
temporarily stopping treatment and administration of a
corticosteroid—consult product literature.
Infusion-related reactions Manufacturer advises
permanently discontinue treatment in patients with severe
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception in women of childbearing
potential, during treatment and for 5 months after
stopping treatment. See also Pregnancy and reproductive
function in Cytotoxic drugs p. 888.
l PREGNANCY Manufacturer advises avoid unless
essential—no information available. See also Pregnancy
and reproductive function in Cytotoxic drugs p. 888.
l BREAST FEEDING Manufacturer advises avoid—no
l MONITORING REQUIREMENTS Manufacturer advises
monitor for signs and symptoms of infusion- and immunerelated reactions—consult product literature.
l PRESCRIBING AND DISPENSING INFORMATION
Manufacturer advises to record the brand name and batch
number after each administration.
All prescribers should be familiar with the Physician
Information and Management Guidelines provided by the
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8°C); consult product literature for storage
l PATIENT AND CARER ADVICE An alert card should be
Missed doses Manufacturer advises if a dose is missed, it
should be administered as soon as possible—
administration schedule should be adjusted to maintain a
3-week interval between doses.
Driving and skilled tasks Manufacturer advises patients
should be counselled on the effects on driving and
performance of skilled tasks—increased risk of drowsiness.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Atezolizumab for untreated PD-L1-positive locally advanced
or metastatic urothelial cancer when cisplatin is unsuitable
(updated July 2018) NICE TA492
Atezolizumab (Tecentriq ®) is recommended for use within
the Cancer Drugs Fund as an option for untreated locally
advanced or metastatic urothelial carcinoma in adults, for
whom cisplatin-based chemotherapy is unsuitable, only if:
Immune system and malignant disease
. their tumours express PD-L1 at a level of 5% or more,
. 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/ta492
▶ Atezolizumab for treating locally advanced or metastatic
urothelial carcinoma after platinum-containing chemotherapy
Atezolizumab is recommended as an option for treating
locally advanced or metastatic urothelial carcinoma in
adults who have had platinum-containing chemotherapy,
. atezolizumab is stopped at 2 years of uninterrupted
treatment or earlier if the disease progresses, and
. the company provides atezolizumab 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/ta525
Atezolizumab is recommended as an option for treating
locally advanced or metastatic non-small-cell lung cancer
(NSCLC) in adults who have had chemotherapy (and
targeted treatment if they have an EGFR- or ALK-positive
. atezolizumab is stopped at 2 years of uninterrupted
treatment or earlier if the disease progresses, and
. the manufacturer provides atezolizumab 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/ta520
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (July 2018)
that atezolizumab (Tecentriq ®) is accepted for restricted
use within NHS Scotland for the treatment of adults with
locally advanced or metastatic non-small cell lung cancer
after prior chemotherapy, 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.
The Scottish Medicines Consortium has advised
(November 2018) that atezolizumab (Tecentriq ®) is not
recommended for use within NHS Scotland as
monotherapy for the treatment of adults with locally
advanced or metastatic urothelial carcinoma after prior
platinum-containing chemotherapy, or who are
considered cisplatin ineligible, as the clinical and
economic case was not demonstrated.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Tecentriq (Roche Products Ltd) A
Atezolizumab 60 mg per 1 ml Tecentriq 1200mg/20ml concentrate
for solution for infusion vials | 1 vial P £3,807.69
l DRUG ACTION Avelumab is a monoclonal antibody, which
binds to the programmed death-1 (PD-1) receptor, thereby
potentiating an immune response to tumour cells.
Metastatic Merkel cell carcinoma (specialist use only)
▶ Adult: 10 mg/kg every 2 weeks, for information on dose
delay or interruption due to side-effects and infusionrelated reactions—consult product literature
l CAUTIONS Patients should receive pre-medication to
minimise the development of adverse reactions (consult
l INTERACTIONS → Appendix 1: monoclonal antibodies
reactions . vomiting . weight decreased
disorders . hypopituitarism . myositis . nephritis
tubulointerstitial . systemic inflammatory response
syndrome .thrombocytopenia . uveitis
▶ Rare or very rare Myocarditis
SIDE-EFFECTS, FURTHER INFORMATION Infusion-related
reactions For treatment modifications in patients with
grade 1 or 2 infusion-related reactions, consult product
literature. Manufacturer advises permanently discontinue
treatment in patients with grade 3 or 4 infusion-related
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
l CONCEPTION AND CONTRACEPTION Manufacturer advises
women of child-bearing potential should use effective
contraception during treatment and for at least 1 month
l PREGNANCY Manufacturer advises avoid unless
essential—no information available. See also Pregnancy
and reproductive function in Cytotoxic drugs p. 888.
l BREAST FEEDING Manufacturer advises avoid during
treatment and for at least 1 month after stopping
treatment—no information available.
l MONITORING REQUIREMENTS Manufacturer advises
monitor for signs and symptoms of infusion- and immunerelated reactions.
l DIRECTIONS FOR ADMINISTRATION Manufacturer advises
for intermittent intravenous infusion (Bavencio ®), dilute
requisite dose with Sodium Chloride 0.9%; give over
60 minutes via a separate line using a low-protein binding
l HANDLING AND STORAGE Manufacturer advises store in a
refrigerator (2–8 °C)—consult product literature for
storage conditions after preparation of the infusion.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Avelumab for treating metastatic Merkel cell carcinoma (April
Avelumab is recommended as an option for treating
metastatic Merkel cell carcinoma in adults, only if they
BNF 78 Antibody responsive malignancy 861
Immune system and malignant disease
have had 1 or more lines of chemotherapy for metastatic
Avelumab is recommended for use within the Cancer
Drugs Fund as an option for treating metastatic Merkel cell
. they have not had chemotherapy for metastatic disease,
. 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/ta517
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (May 2018)
that avelumab (Bavencio ®) is accepted for use within NHS
Scotland as monotherapy for treating adults with
metastatic Merkel cell carcinoma.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Bavencio (Merck Serono Ltd) A
Avelumab 20 mg per 1 ml Bavencio 200mg/10ml concentrate for
solution for infusion vials | 1 vial P £768.00
l DRUG ACTION Bevacizumab is a monoclonal antibody that
inhibits vascular endothelial growth factor.
Treatment of metastatic colorectal cancer in combination
with fluoropyrimidine-based chemotherapy | First-line
treatment of metastatic breast cancer in combination
with paclitaxel when treatment with other
chemotherapy, including taxanes or anthracyclines is
not appropriate | First-line treatment of metastatic
breast cancer in combination with capecitabine when
treatment with other chemotherapy, including taxanes
or anthracyclines is not appropriate (patients who have
received adjuvant taxane or anthracycline-containing
regimens in the previous 12 months should not be
treated with bevacizumab in combination with
capecitabine)| Advanced or metastatic renal cell
recurrent non-small cell lung cancer other than
predominantly squamous cell histology (In combination
with platinum-based chemotherapy)| First-line
treatment of advanced (FIGO stages IIIB, IIIC and IV)
epithelial ovarian, fallopian tube, or primary peritoneal
cancer (in combination with carboplatin and paclitaxel)|
First recurrence of platinum-sensitive epithelial ovarian,
fallopian tube, or primary peritoneal cancer in patients
who have not been treated previously with bevacizumab
or other drugs that target vascular endothelial growth
factor (in combination with carboplatin and
▶ Adult: (consult local protocol)
MHRA/CHM ADVICE: BEVACIZUMAB AND SUNITINIB: RISK OF
OSTEONECROSIS OF THE JAW (JANUARY 2011)
Treatment with bevacizumab or sunitinib may be a risk
factor for the development of osteonecrosis of the jaw.
Patients treated with bevacizumab or sunitinib, who
have previously received bisphosphonates, or are treated
concurrently with bisphosphonates, may be particularly
Dental examination and appropriate preventive
dentistry should be considered before treatment with
If possible, invasive dental procedures should be
avoided in patients treated with bevacizumab or
sunitinib who have previously received, or who are
currently receiving, intravenous bisphosphonates.
l CAUTIONS Elective surgery (withhold treatment and avoid
for at least 28 days after major surgery or until wound fully
healed). history of arterial thromboembolism . history of
cardiovascular disease (increased risk of cardiovascular
events, especially in the elderly). history of hypertension
(increased risk of proteinuria—discontinue if nephrotic
syndrome). increased risk of fistulas (discontinue
permanently if tracheo-oesophageal or grade 4 fistula
develops). increased risk of haemorrhage . increased risk
of tumour-associated haemorrhage . intra-abdominal
inflammation (risk of gastro-intestinal perforation and gall
bladder perforation . uncontrolled hypertension . untreated CNS metastases
l INTERACTIONS → Appendix 1: monoclonal antibodies
▶ Common or very common Abscess . anaemia . appetite
neuropathy . proteinuria .rectovaginal fistula . sepsis . skin
▶ Rare or very rare Encephalopathy . necrotising fasciitis
(discontinue and initiate treatment promptly)
l CONCEPTION AND CONTRACEPTION Effective
contraception required during and for at least 6 months
l PREGNANCY Avoid—toxicity in animal studies. See also
Pregnancy and reproductive function in Cytotoxic drugs
▶ Monitor for necrotising fasciitis (usually secondary to
wound healing complications, gastro-intestinal
perforation or fistula formation)—discontinue and initiate
▶ Monitor for congestive heart failure.
▶ Monitor for posterior reversible encephalopathy syndrome
(presenting as seizures, headache, altered mental status,
visual disturbance or cortical blindness, with or without
▶ Consider dental check-up before initiating treatment (risk
862 Antibody responsive malignancy BNF 78
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