IMMUNOSTIMULANTS › INTERLEUKINS
l DRUG ACTION Aldesleukin produces tumour shrinkage in a
small proportion of patients, but it has not been shown to
Metastatic renal cell carcinoma (specialist use only)
▶ BY SUBCUTANEOUS INJECTION, OR BY INTRAVENOUS INFUSION
▶ Adult: (consult product literature)
l UNLICENSED USE Aldesleukin is not licensed for use in
patients in whom all three of the following prognostic
organ with metastatic disease sites, and a period of less
than 24 months between initial diagnosis of primary
tumour and date of evaluation of treatment.
l CONTRA-INDICATIONS Consult product literature for
information about aldesleukin contra-indications.
l CAUTIONS Consult product literature for information
congestion . nausea . nerve disorders . oedema . oral
disorders . pain . palpitations . paraesthesia . pulmonary
▶ Uncommon Angioedema . cardiac arrest. cardiac
inflammation . cardiomyopathy . coma . embolism and
▶ Frequency not known Capillary leak syndrome . immune
complex RPGN . inflammatory arthritis . intracranial
haemorrhage . leukoencephalopathy . myocardial
infarction . oculo-bulbar myasthenia gravis . psychiatric
disorder. stroke .thyroiditis . vasculitis cerebral
l CONCEPTION AND CONTRACEPTION Ensure effective
contraception during treatment in men and women.
l PREGNANCY Use only if potential benefit outweighs risk
(toxicity in animal studies). See also Pregnancy and
reproductive function in Cytotoxic drugs p. 888.
l BREAST FEEDING Discontinue breast-feeding.
l DIRECTIONS FOR ADMINISTRATION Aldesleukin is now
rarely given by intravenous infusion because of an
increased risk of capillary leak syndrome, which can cause
pulmonary oedema and hypotension.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for injection
▶ Proleukin (Novartis Pharmaceuticals UK Ltd)
Aldesleukin 18 mega u Proleukin 18million unit powder for solution
for injection vials | 1 vial P £112.00 | 10 vial P £1,036.00
l DRUG ACTION Bacillus Calmette-Guérin is a live
attenuated strain derived from Mycobacterium bovis.
Bladder instillation for the treatment of primary or
recurrent bladder carcinoma and for the prevention of
recurrence following transurethral resection
▶ BY INTRAVESICAL INSTILLATION
▶ Adult: (consult product literature)
l CONTRA-INDICATIONS Fever of unknown origin . HIV
infection . impaired immune response . severe haematuria .tuberculosis . urinary-tract infection
l CAUTIONS Bladder injury (delay administration until
mucosal damage healed).traumatic catheterisation (delay
administration until mucosal damage healed). urethral
injury (delay administration until mucosal damage healed)
disorders . malaise . myalgia . nausea . pain . skin reactions . urinary disorders . vomiting
▶ Uncommon Abdominal pain . anaemia . coagulation
illness . interstitial lung disease . nephritis .renal abscess . renal failure
l PRE-TREATMENT SCREENING Screen for active tuberculosis
(contra-indicated if tuberculosis confirmed).
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for reconstitution for instillation
▶ OncoTICE (Merck Sharp & Dohme Ltd)
TICE strain Bacillus of Calmette-Guerin 12.5 mg OncoTICE 12.5mg
powder for reconstitution for instillation vials | 1 vial P £71.61
Treatment of high-grade, resectable, non-metastatic
osteosarcoma after complete surgical resection (in
combination with chemotherapy)
▶ Adult: Infusion to be given over 1 hour (consult
product literature or local protocols)
l UNLICENSED USE Not licensed for use in patients over
30 years of age at initial diagnosis.
l CAUTIONS Asthma—consider prophylactic bronchodilator
therapy . chronic obstructive pulmonary disease—consider
958 Immunotherapy responsive malignancy BNF 78
Immune system and malignant disease
prophylactic bronchodilator therapy . history of
autoimmune disease . history of collagen disease . history
l INTERACTIONS → Appendix 1: mifamurtide
l CONCEPTION AND CONTRACEPTION Effective
l BREAST FEEDING Avoid—no information available.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
moderate impairment (risk of increased half-life and
exposure); avoid in severe impairment (no information
l RENAL IMPAIRMENT Use with caution—no information
▶ Monitor renal function, hepatic function and clotting
▶ Monitor patients with history of venous thrombosis,
vasculitis, or unstable cardiovascular disorders for
persistent or worsening symptoms during
administration—consult product literature.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Mifamurtide for the treatment of osteosarcoma (October
indication), as an option for the treatment of high-grade
resectable non-metastatic osteosarcoma after
macroscopically complete surgical resection in children,
adolescents and young adults and when mifamurtide is
made available at a reduced cost to the NHS under the
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for suspension for infusion
Mifamurtide 4 mg Mepact 4mg powder for suspension for infusion
IMMUNOSUPPRESSANTS › THALIDOMIDE AND
l DRUG ACTION Lenalidomide is an immunomodulating
drug with anti-neoplastic, anti-angiogenic, and proerythropoietic properties.
Multiple myeloma (newly diagnosed) in patients not
eligible for transplant, given in combination with
dexamethasone until disease progression
▶ Adult: 25 mg once daily for 21 consecutive days of
repeated 28-day cycles, for doses of dexamethasone,
and dose adjustments due to side-effects, consult
Multiple myeloma (newly diagnosed) in patients not
eligible for transplant, given in combination with
melphalan and prednisone followed by maintenance
▶ Adult: 10 mg once daily for 21 consecutive days of
repeated 28-day cycles for up to 9 cycles, for doses of
melphalan and prednisone, and dose adjustments due
to side- effects, consult product literature
Multiple myeloma in patients who have received at least
one prior therapy, given in combination with
▶ Adult: 25 mg once daily for 21 consecutive days of
repeated 28-day cycles, for doses of dexamethasone,
and dose adjustments due to side-effects, consult
(MDS) associated with an isolated deletion 5q
cytogenetic abnormality when other treatment options
are insufficient or inadequate
▶ Adult: 10 mg once daily for 21 consecutive days of
repeated 28-day cycles, for dose adjustments due to
side-effects, consult product literature
l CAUTIONS High tumour burden—risk of tumour lysis
syndrome . patients with risk factors for myocardial
▶ Thromboembolism Risk factors for thromboembolism (such
as smoking, hypertension, hyperlipidaemia) should be
minimised and thromboprophylaxis should be considered
in patients with multiple risk factors.
▶ Second primary malignancy Patients should be carefully
evaluated before and during treatment with lenalidomide
using routine cancer screening for occurrence of second
primary malignancy and treatment should be instituted as
l INTERACTIONS → Appendix 1: lenalidomide
complaints . muscle weakness . myocardial infarction .
BNF 78 Immunotherapy responsive malignancy 959
Immune system and malignant disease
▶ Rare or very rare Severe cutaneous adverse reactions
pneumonitis . pancreatitis .reactivation of infections
SIDE-EFFECTS, FURTHER INFORMATION If rash occurs,
treatment should be discontinued and only restarted
following appropriate clinical evaluation.
Discontinue permanently if angioedema, exfoliative or
bullous rash, or if Stevens-Johnson syndrome or toxic
epidermal necrolysis is suspected.
starting treatment with lenalidomide (perform pregnancy
test on initiation or within 3 days prior to initiation).
Women must practise effective contraception at least
1 month before, during, and for at least 1 month after
treatment, including during dose interruptions (oral
combined hormonal contraceptives and copper-releasing
intra-uterine devices not recommended) and men should
use condoms during treatment, during dose interruption,
and for at least 1 week after stopping if their partner is
pregnant or is of childbearing potential and not using
effective contraception. Patients, prescribers and
pharmacists must comply with pregnancy prevention
measures as specified in the manufacturer’s Pregnancy
l PREGNANCY Important: teratogenic risk. Lenalidomide
is structurally related to thalidomide and there is a risk of
l BREAST FEEDING Discontinue breast-feeding—no
Dose adjustments Reduce dose in moderate to severe
impairment—consult product literature.
▶ Monitor full blood count (including differential white cell
count, platelet count, haemoglobin, and haematocrit) and
liver function before treatment, then every week for the
first 8 weeks, then monthly thereafter (reduce dose or
interrupt treatment if neutropenia, thrombocytopenia or
impaired liver function develop—consult product
▶ Monitor for arterial or venous thromboembolism (if
thromboembolic event occurs, discontinue lenalidomide
and treat with standard anticoagulation therapy;
lenalidomide may be restarted with continued
anticoagulation therapy once thromboembolic event
resolved—consult product literature).
▶ Monitor for signs and symptoms of peripheral neuropathy.
▶ Monitor visual ability regularly (risk of cataract).
▶ Hepatic disorders Liver function should be monitored
particularly when there is history of, or concurrent viral
liver infection, or when lenalidomide is combined with
drugs known to be associated with liver dysfunction (e.g.
l PRESCRIBING AND DISPENSING INFORMATION Patient,
prescriber, and supplying pharmacy must comply with a
pregnancy prevention programme. Every prescription
must be accompanied by a completed Prescription
Thromboembolism Patients and their carers should be made
aware of the symptoms of thromboembolism and advised
to report sudden breathlessness, chest pain, or swelling of
Neutropenia and thrombocytopenia Patients and their carers
should be made aware of the symptoms of neutropenia and
advised to seek medical advice if symptoms suggestive of
neutropenia (such as fever, sore throat) or of
thrombocytopenia (such as bleeding) develop.
Conception and contraception Patient counselling is
advised for lenalidomide capsules (pregnancy and
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Lenalidomide for treating myelodysplastic syndromes
associated with an isolated deletion 5q cytogenetic
abnormality (September 2014) NICE TA322
Lenalidomide is recommended as an option, within its
myelodysplastic syndromes associated with an isolated
deletion 5q cytogenetic abnormality when other
therapeutic options are insufficient or inadequate, with
. the drug cost of lenalidomide (excluding any related
costs) for people who remain on treatment for more than
26 cycles (each of 28 days; normally a period of 2 years)
www.nice.org.uk/guidance/ta322
▶ Lenalidomide for the treatment of multiple myeloma (updated
Lenalidomide in combination with dexamethasone is an
option for the treatment of multiple myeloma in patients
who have received two or more prior therapies. The drug
cost of lenalidomide will be met by the manufacturer for
patients who remain on treatment for more than 26 cycles.
www.nice.org.uk/guidance/ta171
▶ Ixazomib with lenalidomide and dexamethasone for treating
relapsed or refractory multiple myeloma (February 2018)
Ixazomib, with lenalidomide and dexamethasone, is
recommended for use within the Cancer Drugs Fund as an
option for treating multiple myeloma in adults only if:
. they have already had 2 or 3 lines of therapy, and
. 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/ta505
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (May 2010)
that lenalidomide, in combination with dexamethasone, is
accepted for restricted use within NHS Scotland for
patients with multiple myeloma who have received at least
The Scottish Medicines Consortium has advised (April
2014) that lenalidomide, in combination with
dexamethasone, is accepted for restricted use within NHS
Scotland for treatment of multiple myeloma in adults to
use at first relapse in those who have received prior
therapy with bortezomib and for whom thalidomide has
not been tolerated or is contra-indicated.
The Scottish Medicines Consortium has advised
(December 2015) that lenalidomide is accepted for
restricted use within NHS Scotland for patients with
previously untreated multiple myeloma who are not
eligible for transplant and when thalidomide-containing
960 Immunotherapy responsive malignancy BNF 78
Immune system and malignant disease
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 25
Lenalidomide 2.5 mg Revlimid 2.5mg capsules | 21 capsule P £3,426.00 DT = £3,426.00
Lenalidomide 5 mg Revlimid 5mg capsules | 21 capsule P £3,570.00 DT = £3,570.00
Lenalidomide 7.5 mg Revlimid 7.5mg capsules | 21 capsule P £3,675.00 DT = £3,675.00
Lenalidomide 10 mg Revlimid 10mg capsules | 21 capsule P £3,780.00 DT = £3,780.00
Lenalidomide 15 mg Revlimid 15mg capsules | 21 capsule P £3,969.00 DT = £3,969.00
Lenalidomide 20 mg Revlimid 20mg capsules | 21 capsule P £4,168.50 DT = £4,168.50
Lenalidomide 25 mg Revlimid 25mg capsules | 21 capsule P £4,368.00 DT = £4,368.00
l DRUG ACTION Pomalidomide is structurally related to
thalidomide and has immunomodulatory properties and
direct anti-myeloma tumoricidal activity.
Treatment of relapsed and refractory multiple myeloma
in patients who have received at least two prior
treatment regimens, including both lenalidomide and
bortezomib, and who have had disease progression
during the last treatment (in combination with
▶ Adult: 4 mg once daily for 21 consecutive days of
repeated 28–day cycles, for doses of dexamethasone
and dose adjustment due to side effects—consult
DOSE ADJUSTMENTS DUE TO INTERACTIONS
▶ Manufacturer advises halve dose with concurrent use
of potent inhibitors of CYP1A2 and ciprofloxacin.
MHRA/CHM ADVICE (MAY 2016): RISK OF HEPATITIS B
An EU wide review has concluded that pomalidomide can
cause hepatitis B reactivation; the MHRA recommends
to establish hepatitis B virus status in all patients before
l CAUTIONS Cardiac disease . cardiac risk factors . hepatitis
B infection . high tumour burden—risk of tumour lysis
syndrome . interstitial lung disease—discontinue if
suspected . peripheral neuropathy
▶ Thromboembolism Risk factors for thromboembolism (such
as smoking, hypertension, hyperlipidaemia) should be
minimised. Thromboprophylaxis should be considered,
particularly in patients with additional risk factors.
▶ Second primary malignancy Patients should be carefully
evaluated before and during treatment with pomalidomide
using routine cancer screening for occurrence of second
primary malignancy and treatment should be instituted as
▶ Hepatitis B infection The MHRA advises that those with a
history of hepatitis B infection should be closely
monitored for signs and symptoms of active infection
throughout treatment; expert advice should be sought for
patients who test positive for active infection.
l INTERACTIONS → Appendix 1: pomalidomide
▶ Common or very common Anaemia . angioedema . appetite
consciousness decreased . muscle spasms . myocardial
▶ Uncommon Hepatitis . hyperbilirubinaemia . neoplasms . stroke .tumour lysis syndrome
▶ Frequency not known Hepatitis B reactivation
starting treatment with pomalidomide (perform pregnancy
test on initiation or within 3 days prior to initiation).
Women must practise effective contraception at least
1 month before, during, and for at least 1 month after
treatment, including during dose interruptions (oral
combined hormonal contraceptives and copper-releasing
intra-uterine devices not recommended) and men should
use condoms during treatment, during dose interruption,
and for at least 1 week after stopping if their partner is
pregnant or is of childbearing potential and not using
effective contraception. Patients, prescribers and
pharmacists must comply with pregnancy prevention
measures as specified in the manufacturer’s Pregnancy
l PREGNANCY Important: teratogenic risk.
l BREAST FEEDING Avoid—present in milk in animal studies.
l HEPATIC IMPAIRMENT Manufacturer advises caution (risk
l RENAL IMPAIRMENT Manufacturer advises caution—no
▶ Maufacturer advises monitor full blood count before
treatment, then every week for the first 8 weeks, then
monthly thereafter (reduce dose or interrupt treatment if
neutropenia or thrombocytopenia develop—consult
▶ Manufacturer advises monitor for arterial or venous
▶ Manufacturer advises monitor for signs and symptoms of
▶ Manufacturer advises monitor for acute onset or
unexplained worsening of respiratory symptoms.
▶ Manufacturer advises monitor liver function for 6 months
after initiation, then as clinically indicated.
l PRESCRIBING AND DISPENSING INFORMATION Patient,
prescriber, and supplying pharmacy must comply with a
pregnancy prevention programme. Every prescription
must be accompanied by a completed Prescription
l PATIENT AND CARER ADVICE Patients and their carers
should be made aware of the symptoms of
thromboembolism and advised to report sudden
breathlessness, chest pain, or swelling of a limb.
Patients and their carers should be made aware of the
symptoms of neutropenia and advised to seek medical
advice if symptoms suggestive of neutropenia (such as
fever, sore throat) or of thrombocytopenia (such as
Conception and contraception Patient counselling is
advised for pomalidomide capsules (pregnancy and
BNF 78 Immunotherapy responsive malignancy 961
Immune system and malignant disease
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Pomalidomide for multiple myeloma previously treated with
lenalidomide and bortezomib (January 2017) NICE TA427
Pomalidomide (Imnovid ®), in combination with low-dose
dexamethasone, is recommended as an option for treating
multiple myeloma in adults at third or subsequent relapse
(that is, after three previous treatments including both
lenalidomide and bortezomib), only when the
manufacturer provides pomalidomide 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/ta427
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 3, 25
EXCIPIENTS: May contain Propylene glycol
Pomalidomide 1 mg Imnovid 1mg capsules | 21 capsule P £8,884.00
Pomalidomide 2 mg Imnovid 2mg capsules | 21 capsule P £8,884.00
Pomalidomide 3 mg Imnovid 3mg capsules | 21 capsule P £8,884.00
Pomalidomide 4 mg Imnovid 4mg capsules | 21 capsule P £8,884.00
l DRUG ACTION Thalidomide has immunomodulatory and
First-line treatment for untreated multiple myeloma, in
patients aged 65 years and over, or for those not eligible
for high-dose chemotherapy (for example, patients with
significant co-morbidity such as cardiac risk factors) in
combination with melphalan and prednisolone
▶ Adult 18–75 years: 200 mg once daily for 6–week cycle
for a maximum of 12 cycles, dose to be taken at
▶ Adult 76 years and over: 100 mg once daily for 6–week
cycle for a maximum of 12 cycles, dose to be taken at
l CAUTIONS High tumour burden—risk of tumour lysis
syndrome . patients aged 76 years and over—increased risk
▶ Thromboembolism Risk factors for thromboembolism (such
as smoking, hypertension, hyperlipidaemia) should be
minimised. Thromboprophylaxis is recommended for at
least the first 5 months of treatment, especially in patients
with additional thrombotic risk factors.
▶ Second primary malignancy Patients should be carefully
evaluated before and during treatment with thalidomide
using routine cancer screening for occurrence of second
primary malignancy and treatment should be instituted as
▶ Peripheral neuropathy Patients with pre-existing peripheral
neuropathy should not be treated with thalidomide unless
the potential clinical benefits outweigh the risk.
l INTERACTIONS → Appendix 1: thalidomide
reversible encephalopathy syndrome (PRES). pulmonary
SIDE-EFFECTS, FURTHER INFORMATION Rash If rash
occurs, treatment should be discontinued and only
restarted following appropriate clinical evaluation.
Peripheral neuropathy If symptoms suggestive of
peripheral neuropathy develop (such as paraesthesia,
abnormal coordination, or weakness) dose reduction, dose
interruption, or treatment discontinuation may be
necessary—consult product literature.
starting treatment with thalidomide (perform pregnancy
test on initiation or within 3 days prior to initiation).
Women must practise effective contraception at least
1 month before, during, and for at least 1 month after
treatment, including during dose interruptions (oral
combined hormonal contraceptives and copper-releasing
intra-uterine devices not recommended) and men should
use condoms during treatment, during dose interruption,
and for at least 1 week after stopping if their partner is
pregnant or is of childbearing potential and not using
effective contraception. Patients, prescribers and
pharmacists must comply with pregnancy prevention
measures as specified in the manufacturer’s Pregnancy
l PREGNANCY Important: teratogenic risk.
l BREAST FEEDING Avoid—present in milk in animal studies.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
severe impairment (no information available).
l RENAL IMPAIRMENT Caution in severe impairment—no
▶ Monitor white blood cell count (including differential
count) and platelet count (reduce dose or interrupt
treatment if neutropenia or thrombocytopenia develop—
▶ Monitor for arterial or venous thromboembolism.
▶ Monitor patients for signs and symptoms of peripheral
▶ Hepatic disorder Liver function should be monitored,
particularly when there is history of, or concurrent viral
liver infection, or when thalidomide is combined with
drugs known to be associated with liver dysfunction (e.g.
l PRESCRIBING AND DISPENSING INFORMATION Patient,
prescriber, and supplying pharmacy must comply with a
pregnancy prevention programme. Every prescription
must be accompanied by a complete Prescription
l PATIENT AND CARER ADVICE Patients and their carers
should be made aware of the symptoms of
thromboembolism and advised to report sudden
breathlessness, chest pain, or swelling of a limb.
Patients and their carers should be made aware of the
symptoms of neutropenia and advised to seek medical
advice if symptoms suggestive of neutropenia (such as
962 Immunotherapy responsive malignancy BNF 78
Immune system and malignant disease
fever, sore throat) or of thrombocytopenia (such as
Patients and their carers should be advised to seek
medical advice if symptoms of peripheral neuropathy such
as paraesthesia, abnormal coordination, or weakness
Conception and contraception Patient counselling advised
for thalidomide capsules (pregnancy and contraception).
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Bortezomib and thalidomide for the first-line treatment of
multiple myeloma (July 2011) NICE TA228
Thalidomide (Thalidomide Celgene ®) in combination with
an alkylating drug and a corticosteroid is recommended as
an option for the first-line treatment of multiple myeloma
in people for whom high-dose chemotherapy with stem
cell transplantation is considered inappropriate.
www.nice.org.uk/guidance/ta228
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: tablet, oral
▶ Talidex (Alan Pharmaceuticals)
Thalidomide 25 mg Talidex 25mg tablets | 30 tablet £1,075.00
CAUTIONARY AND ADVISORY LABELS 2
▶ Thalidomide (Non-proprietary)
Thalidomide 50 mg Thalidomide Celgene 50mg capsules | 28 capsule P £298.48
l DRUG ACTION Porfimer sodium accumulates in malignant
tissue and is activated by laser light to produce a cytotoxic
Photodynamic therapy of non-small cell lung cancer and
obstructing oesophageal cancer
▶ BY SLOW INTRAVENOUS INJECTION
▶ Adult: (consult product literature)
reaction (sunscreens ineffective). stomatitis . thromboembolism .tumour lysis syndrome . vomiting
l PREGNANCY Manufacturer advises avoid unless essential.
l BREAST FEEDING No information available—manufacturer
l HEPATIC IMPAIRMENT Manufacturer advises caution in
mild to moderate impairment (may increase duration of
photosensitivity); avoid in severe impairment (no
Photosensitivity Avoid exposure of skin and eyes to direct
sunlight or bright indoor light for at least 30 days.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for injection
▶ Photofrin (Axcan Pharma Inc, Pinnacle Biologics BV)
Porfimer sodium 15 mg Photofrin 15mg powder for solution for
injection vials | 1 vial P s (Hospital only)
Porfimer sodium 75 mg Photofrin 75mg powder for solution for
injection vials | 1 vial P £1,011.00 (Hospital only)
l DRUG ACTION Temoporfin accumulates in malignant
tissue and is activated by laser light to produce a cytotoxic
Photodynamic therapy of advanced head and neck
squamous cell carcinoma refractory to, or unsuitable for,
▶ BY SLOW INTRAVENOUS INJECTION
▶ Adult: (consult product literature)
l CONTRA-INDICATIONS Acute porphyrias p. 1058 . concomitant photosensitising treatment. diseases
l CONCEPTION AND CONTRACEPTION Manufacturer advises
avoid pregnancy for at least 3 months after treatment.
l PREGNANCY Toxicity in animal studies. See also
Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Manufacturer advises avoid
breastfeeding for at least 1 month after treatment—no
Photosensitivity Avoid exposure of skin and eyes to direct
sunlight or bright indoor light for at least 15 days after
Avoid prolonged exposure of injection site arm to direct
sunlight for 6 months after administration.
If extravasation occurs protect area from light for at
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Foscan (Biolitec Pharma Ltd)
Temoporfin 1 mg per 1 ml Foscan 3mg/3ml solution for injection
vials | 1 vial P £1,800.00 (Hospital only)
Foscan 6mg/6ml solution for injection vials | 1 vial P £3,400.00
BNF 78 Photodynamic therapy responsive malignancy 963
Immune system and malignant disease
ANTINEOPLASTIC DRUGS › PROTEASOME
l DRUG ACTION Bortezomib is a proteasome inhibitor.
Treatment of multiple myeloma that has progressed
despite the use of at least one therapy, and where the
patient has already had, or is unable to have,
haematopoietic stem cell transplantation (either as
monotherapy, or in combination with pegylated
liposomal doxorubicin or dexamethasone)| Treatment of
previously untreated multiple myeloma in patients who
are not eligible for high-dose chemotherapy with
haematopoietic stem cell transplantation (in
combination with melphalan and prednisolone)|
Induction treatment of previously untreated multiple
myeloma in patients who are eligible for high-dose
chemotherapy with haematopoietic stem cell
transplantation (in combination with dexamethasone, or
with dexamethasone and thalidomide)
▶ BY INTRAVENOUS INJECTION, OR BY SUBCUTANEOUS INJECTION
▶ Adult: (consult local protocol)
Bortezomib injection is for intravenous or
subcutaneous administration only. Inadvertent
intrathecal administration with fatal outcome has been
l CONTRA-INDICATIONS Acute diffuse infiltrative pulmonary
l CAUTIONS Amyloidosis . cardiovascular disease . consider
of syncope . pulmonary disease (discontinue if interstitial
lung disease develops).risk factors for seizures .risk of
neuropathy—consult product literature
l INTERACTIONS → Appendix 1: bortezomib
▶ Common or very common Anaemia . anxiety . appetite
weakness . nausea . nerve disorders . neuromuscular
disorders . concentration impaired . confusion . Cushing’s
syndrome . dry eye . dysphonia . ear discomfort. embolism
and thrombosis . eye discomfort. eye disorders .failure to
thrive . gait abnormal . gas exchange abnormal . genital
syndrome (PRES) (discontinue). proteinuria . psychiatric
disorders . vasculitis . vasodilation
disorder. cardiac valve disorder. cholelithiasis . CNS
haemorrhage . cognitive disorder. coma . coronary artery
disorder. multi organ failure . nail disorder. neoplasm
▶ Frequency not known Herpes zoster reactivation .JC virus
infection . progressive multifocal leukoencephalopathy
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception during and for 3 months after
l PREGNANCY Toxicity in animal studies. See also Pregnancy
and reproductive function in Cytotoxic drugs p. 888.
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
moderate to severe impairment–monitor for toxicity.
Dose adjustments Manufacturer advises reduce dose in
moderate to severe impairment—consult product
l RENAL IMPAIRMENT No information available for
creatinine clearance less than 20 mL/minute/1.73 m2
▶ Monitor blood-glucose concentration in patients on oral
▶ Monitor for symptoms of progressive multifocal
leucoencephalopathy (presenting as new or worsening
neurological signs or symptoms)—discontinue treatment if
▶ Chest x-ray recommended before treatment to monitor for
pulmonary disease—discontinue if interstitial lung disease
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Bortezomib for previously untreated mantle cell lymphoma
Bortezomib is recommended as an option for the
treatment of previously untreated mantle cell lymphoma
964 Targeted therapy responsive malignancy BNF 78
Immune system and malignant disease
in adults for whom haematopoietic stem cell
transplantation is unsuitable.
▶ Bortezomib for induction therapy in multiple myeloma before
high-dose chemotherapy and autologous stem cell
transplantation (April 2014) NICE TA311
Bortezomib is recommended as an option within its
marketing authorisation, in combination with
dexamethasone, or with dexamethasone and thalidomide,
for the induction treatment of adults with previously
untreated multiple myeloma, who are eligible for highdose chemotherapy with haematopoietic stem cell
▶ Bortezomib and thalidomide for the first-line treatment of
multiple myeloma (July 2011) NICE TA228
Bortezomib in combination with an alkylating drug and a
corticosteroid is recommended as an option for the firstline treatment of multiple myeloma if:
. high-dose chemotherapy with stem cell transplantation
is considered inappropriate and
. the person is unable to tolerate or has contraindications to thalidomide.
▶ Bortezomib monotherapy for relapsed multiple myeloma
Bortezomib monotherapy is an option for the treatment of
progressive multiple myeloma in patients who are at first
relapse having received one prior therapy and who have
undergone, or are unsuitable for, bone-marrow
transplantation, under the following circumstances:
. the response to bortezomib is measured using serum M
protein after a maximum of four cycles of treatment, and
treatment is continued only in patients who have a
reduction in serum M protein of 50% or more (where
serum M protein is not measurable, an appropriate
alternative biochemical measure of response should be
. the manufacturer rebates the full cost of bortezomib if
there is an inadequate response (as defined above) after
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium, has advised (December
2013) that bortezomib (Velcade ®) is accepted for restricted
use within NHS Scotland in combination with
dexamethasone and thalidomide for the induction
treatment of adults with previously untreated multiple
myeloma who are eligible for high-dose chemotherapy
with haematopoietic stem cell transplantation.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for injection
Bortezomib 3.5 mg Velcade 3.5mg powder for solution for injection
vials | 1 vial P £762.38 (Hospital only)
l DRUG ACTION Carfilzomib is an irreversible selective
proteasome inhibitor that disrupts tumour cell turnover
Treatment of multiple myeloma in patients who have
received at least one prior therapy (in combination with
dexamethasone, or with dexamethasone and
lenalidomide) (specialist use only)
▶ Adult: (consult product literature or local protocols)
l CAUTIONS Elderly (over 75 years)—higher incidence of
▶ Infusion-related reactions Manufacturer advises
premedication with dexamethasone to reduce incidence
and severity of infusion-related reactions.
▶ Risk of herpes zoster reactivation Manufacturer advises
consider antiviral prophylaxis for herpes zoster infection.
l INTERACTIONS → Appendix 1: carfilzomib
▶ Common or very common Anaemia . anxiety . appetite
▶ Rare or very rare Posterior reversible encephalopathy
syndrome (PRES).thrombotic microangiopathy
l CONCEPTION AND CONTRACEPTION Manufacturer
recommends effective contraception during and for
1 month after treatment in women of childbearing
potential; efficacy of oral contraceptives may be reduced,
and hormonal contraceptives associated with a risk of
thrombosis should be avoided. Male patients should use
effective contraception during and for 3 months after
treatment if their partner is pregnant or of childbearing
potential. See also Pregnancy and reproductive function in
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—toxicity in animal studies. See also
Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Manufacturer advises avoid during and
for at least 2 days after treatment—no information
l HEPATIC IMPAIRMENT Manufacturer advises caution
(increased risk of side-effects), particularly in moderate to
severe impairment (limited information available).
l RENAL IMPAIRMENT Manufacturer advises caution—
increased incidence of adverse effects.
l MONITORING REQUIREMENTS Manufacturer advises
monitoring of the following patient parameters: serum
potassium concentration at least monthly; signs and
symptoms of fluid overload, especially in those at risk of
cardiac failure; renal function at treatment initiation and
at least monthly during treatment—consider dose
modification; hepatic function at treatment initiation and
monthly during treatment—consider dose modification;
platelet count and blood pressure. Also monitor for signs
and symptoms of thrombotic microangiopathy.
BNF 78 Targeted therapy responsive malignancy 965
Immune system and malignant disease
l HANDLING AND STORAGE Manufacturer advises store in a
l PATIENT AND CARER ADVICE Manufacturer advises that
patients and carers are warned to report signs and
symptoms of thromboembolism (such as dyspnoea, chest
pain, arm or leg swelling or pain).
Driving and skilled tasks Patients and their carers should be
counselled on the effects on driving and skilled tasks—
increased risk of dizziness, hypotension and blurred
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Carfilzomib for previously treated multiple myeloma (July
Carfilzomib (Kyprolis ®) in combination with
dexamethasone is recommended as an option for treating
multiple myeloma in adults, only if:
. they have had only 1 previous therapy, which did not
. the manufacturer provides carfilzomib with the discount
agreed in the patient access scheme.
Patients currently receiving carfilzomib whose disease
does not meet the above criteria should have the option to
continue their treatment until they and their NHS clinician
consider it appropriate to stop.
www.nice.org.uk/guidance/ta457
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (January
2017) that carfilzomib (Kyprolis ®) in combination with
lenalidomide and dexamethasone is not recommended for
use within NHS Scotland for the treatment of adults with
multiple myeloma who have received at least one prior
therapy as the economic case was not demonstrated.
The Scottish Medicines Consortium has advised (August
2017) that carfilzomib (Kyprolis ®) is accepted for use
within NHS Scotland, in combination with dexamethasone
alone for the treatment of adults with multiple myeloma
who have received at least one prior therapy. This advice is
contingent upon the continuing availability of the patient
access scheme in NHS Scotland or a list price that is
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder for solution for infusion
ELECTROLYTES: May contain Sodium
Carfilzomib 10 mg Kyprolis 10mg powder for solution for infusion
Carfilzomib 30 mg Kyprolis 30mg powder for solution for infusion
Carfilzomib 60 mg Kyprolis 60mg powder for solution for infusion
l DRUG ACTION Ixazomib is a proteasome inhibitor.
Multiple myeloma in patients who have received at least
one prior therapy, in combination with lenalidomide and
dexamethasone (specialist use only)
▶ Adult: 4 mg once weekly on days 1, 8, and 15 of a
28-day treatment cycle, for dose adjustments due to
side-effects, consult product literature
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
l CAUTIONS Risk of herpes zoster reactivation
▶ Herpes zoster reactivation Manufacturer advises consider
concomitant antiviral prophylaxis to decrease the risk of
l INTERACTIONS → Appendix 1: ixazomib
symptoms). peripheral oedema .rash .thrombocytopenia . vomiting
▶ Frequency not known Posterior reversible encephalopathy
l CONCEPTION AND CONTRACEPTION Manufacturer advises
effective contraception in women of child-bearing
potential and in men with a partner of child-bearing
potential, during treatment and for at least 90 days after
stopping treatment; additional barrier method
recommended in women using hormonal contraceptives.
l PREGNANCY Manufacturer advises avoid—toxicity in
animal studies. See also Pregnancy and reproductive
function in Cytotoxic drugs p. 888.
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises caution in
moderate to severe impairment (risk of increased
Dose adjustments Manufacturer advises dose reduction to
3 mg in moderate to severe impairment.
Dose adjustments Manufacturer advises reduce dose to
3 mg in severe impairment (creatinine clearance less than
l MONITORING REQUIREMENTS Manufacturer advises to
monitor hepatic function regularly and adjust dose
accordingly—consult product literature.
Missed doses Manufacturer advises if less than 72 hours
remain before the next scheduled dose, the missed dose
should not be taken and the next dose should be taken at
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Ixazomib with lenalidomide and dexamethasone for treating
relapsed or refractory multiple myeloma (February 2018)
Ixazomib, with lenalidomide and dexamethasone, is
recommended for use within the Cancer Drugs Fund as an
option for treating multiple myeloma in adults only if:
. they have already had 2 or 3 lines of therapy, and
. the conditions in the managed access agreement for
966 Targeted therapy responsive malignancy BNF 78
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/ta505
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 23, 25
Ixazomib (as Ixazomib citrate) 2.3 mg Ninlaro 2.3mg capsules | 3 capsule P £6,336.00
Ixazomib (as Ixazomib citrate) 3 mg Ninlaro 3mg capsules | 3 capsule P £6,336.00
Ixazomib (as Ixazomib citrate) 4 mg Ninlaro 4mg capsules | 3 capsule P £6,336.00
ANTINEOPLASTIC DRUGS › PROTEIN KINASE
l DRUG ACTION Abemaciclib is a selective inhibitor of
cyclin-dependent kinases 4 and 6, which leads to
disruption of cancer cell proliferation.
Locally advanced or metastatic breast cancer (initiated by
▶ Adult: 150 mg twice daily, for dose adjustments due to
side-effects—consult product literature
DOSE ADJUSTMENTS DUE TO INTERACTIONS
▶ Manufacturer advises if concomitant use with potent
CYP3A4 inhibitors is unavoidable, reduce abemaciclib
dose to 100 mg twice daily; in those already taking a
reduced dose, consult product literature. If the CYP3A4
inhibitor is stopped, increase the abemaciclib dose
(after 3–5 half lives of the inhibitor) to the dose used
before starting the CYP3A4 inhibitor.
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
l INTERACTIONS → Appendix 1: abemaciclib
▶ Common or very common Alopecia . anaemia . appetite
l CONCEPTION AND CONTRACEPTION Manufacturer advises
highly effective contraception in women of childbearing
potential during treatment and for at least 3 weeks after
completing treatment. See also Pregnancy and reproductive
function in Cytotoxic drugs p. 888.
l PREGNANCY Manufacturer advises avoid—toxicity in
animal studies. See also Pregnancy and reproductive
function in Cytotoxic drugs p. 888.
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises caution in
severe impairment. Temporary or permanent withdrawal
may be needed following increases in aminotransferases—
Dose adjustments Manufacturer advises dose reduction to
150 mg once daily in severe impairment.
l RENAL IMPAIRMENT Manufacturer advises caution in
severe impairment—monitor for signs of toxicity.
l MONITORING REQUIREMENTS Manufacturer advises
monitor full blood count, and alanine and aspartate
aminotransferases before starting treatment, every
2 weeks for the first 2 months, monthly for the following
2 months, and as clinically indicated thereafter.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Abemaciclib with an aromatase inhibitor for previously
untreated, hormone receptor-positive, HER2-negative, locally
advanced or metastatic breast cancer (February 2019)
Abemaciclib (Verzenios ®) with an aromatase inhibitor is
recommended, within its marketing authorisation, as an
option for treating locally advanced or metastatic,
hormone receptor-positive, human epidermal growth
factor receptor 2 (HER2)-negative breast cancer as first
endocrine-based therapy in adults. Abemaciclib is
recommended only if the manufacturer provides it
according to the commercial arrangement.
www.nice.org.uk/guidance/ta563
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 3, 25
▶ Verzenios (Eli Lilly and Company Ltd) A
l DRUG ACTION Afatinib is a protein kinase inhibitor.
Treatment of locally advanced or metastatic non-small
cell lung cancer with activating epidermal growth factor
receptor (EGFR) mutations, in patients who have not
previously been treated with EGFR tyrosine kinase
▶ Adult: 40 mg once daily; increased if tolerated to up to
50 mg once daily, dose increase may be considered
after 3 weeks at initial dose; consult product literature
for details on dosing and dose adjustment due to side
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
l CAUTIONS Cardiac risk factors . conditions which may
affect left ventricular ejection fraction—consider cardiac
monitoring, including assessment of left ventricular
product literature). exposure to sun (protect skin from
exposure to sun). history of keratitis . new pulmonary
symptoms (including dyspnoea, cough, fever)—interrupt
treatment until interstitial lung disease is excluded . severe
dry eyes . signs and symptoms of keratitis— promptly refer
to ophthalmologist for assessment. signs and symptoms of
skin reaction—treat promptly and interrupt afatinib
treatment if severe or if Stevens-Johnson syndrome
BNF 78 Targeted therapy responsive malignancy 967
Immune system and malignant disease
(including dyspnoea, cough, fever)—interrupt treatment
until interstitial lung disease is excluded
l INTERACTIONS → Appendix 1: afatinib
▶ Uncommon Interstitial lung disease . pancreatitis
▶ Rare or very rare Severe cutaneous adverse reactions
l CONCEPTION AND CONTRACEPTION Ensure effective
contraception during and for at least one month after
treatment in women of childbearing potential.
l PREGNANCY Manufacturer advises avoid. See also
Pregnancy and reproductive function in Cytotoxic drugs
l BREAST FEEDING Manufacturer advises avoid—present in
l HEPATIC IMPAIRMENT Manufacturer advises caution in
mild to moderate impairment; avoid in severe impairment
Dose adjustments Manufacturer advises consider dose
interruption if hepatic function worsens in mild to
moderate impairment—consult product literature.
l RENAL IMPAIRMENT Manufacturer advises avoid in severe
l DIRECTIONS FOR ADMINISTRATION Tablets should be
taken whole on an empty stomach. Food should not be
consumed for at least 3 hours before and at least 1 hour
Giotrif ® tablets may be dispersed in approximately
100 mL of noncarbonated water by stirring occasionally for
up to 15 minutes (must not be crushed). The dispersion
should be swallowed immediately, and the glass rinsed
with the same volume of water which should also be
swallowed. The dispersion can also be administered via a
l PATIENT AND CARER ADVICE Patient counselling advised
Driving and skilled tasks Ocular adverse reactions may
affect performance of skilled tasks e.g. driving.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Afatinib for treating epidermal growth factor receptor
mutation-positive locally advanced or metastatic non-smallcell lung cancer (April 2014) NICE TA310
Afatinib is recommended as an option, within its
marketing authorisation, for treating locally advanced or
metastatic non-small-cell lung cancer in adults:
. whose tumour tests positive for the epidermal growth
factor receptor tyrosine kinase (EGFR-TK) mutation,
. who have not previously had an EGFR-TK inhibitor, and
. if the manufacturer provides afatinib with the discount
agreed in the patient access scheme.
www.nice.org.uk/guidance/ta310
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 25
▶ Giotrif (Boehringer Ingelheim Ltd)
Afatinib (as Afatinib dimaleate) 20 mg Giotrif 20mg tablets | 28 tablet P £2,023.28
Afatinib (as Afatinib dimaleate) 30 mg Giotrif 30mg tablets | 28 tablet P £2,023.28
Afatinib (as Afatinib dimaleate) 40 mg Giotrif 40mg tablets | 28 tablet P £2,023.28
Afatinib (as Afatinib dimaleate) 50 mg Giotrif 50mg tablets | 28 tablet P £2,023.28
l DRUG ACTION Alectinib is a tyrosine kinase inhibitor.
Anaplastic lymphoma kinase (ALK)-positive advanced
non-small cell lung cancer (specialist use only)
▶ Adult: 600 mg twice daily, for dose adjustments due to
side-effects—consult product literature
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
l INTERACTIONS → Appendix 1: alectinib
▶ Uncommon Drug-induced liver injury .respiratory
l CONCEPTION AND CONTRACEPTION Manufacturer advises
women of child-bearing potential should use effective
contraception during and for at least 3 months after
l PREGNANCY Manufacturer advises avoid—toxicity in
animal studies. See also Pregnancy and reproductive
function in Cytotoxic drugs p. 888.
l BREAST FEEDING Manufacturer advises avoid—no
Dose adjustments Manufacturer advises reduce dose to
450 mg twice daily in severe impairment.
▶ Manufacturer advises monitor creatine phosphokinase
every 2 weeks for the first month and as clinically indicated
thereafter in patients reporting symptoms of myalgia.
▶ Manufacturer advises monitor heart rate and blood
pressure as clinically indicated.
▶ Manufacturer advises monitor liver function at baseline
then every 2 weeks during the first 3 months of treatment
and periodically thereafter as clinically indicated; more
frequent monitoring should be performed in patients who
develop aminotransferase and bilirubin elevations.
▶ Manufacturer advises monitor for symptoms of interstitial
Photosensitivity Manufacturer advises patients should use a
broad spectrum sunscreen and lip balm and be advised to
avoid prolonged sun exposure during treatment, and for
Myalgia Manufacturer advises patients should advised to
report any unexplained muscle pain, tenderness or
Vomiting Manufacturer advises if vomiting occurs after
taking tablets, no additional dose should be taken on that
day and the next dose should be taken at the usual time.
Missed doses Manufacturer advises if a dose is more than
6 hours late, the missed dose should not be taken and the
next dose should be taken at the normal time.
Driving and skilled tasks Manufacturer advises patients and
carers should be counselled on the effects on driving and
performance of skilled tasks—increased risk of
symptomatic bradycardia and vision disorders.
968 Targeted therapy responsive malignancy BNF 78
Immune system and malignant disease
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Alectinib for untreated ALK-positive advanced non-small-cell
lung cancer (August 2018) NICE TA536
Alectinib (Alecensa ®) is recommended, within its
marketing authorisation, as an option for untreated
anaplastic lymphoma kinase (ALK)-positive advanced
non-small cell lung cancer in adults. It is recommended
only if the manufacturer provides alectinib according to
www.nice.org.uk/guidance/ta536
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (August
2018) that alectinib (Alecensa ®) is accepted for use within
NHS Scotland as monotherapy for the first-line treatment
of adults with anaplastic lymphoma kinase (ALK)-positive
advanced non-small cell lung cancer. This advice is
contingent upon the continuing availability of the patient
access scheme in NHS Scotland or a list price that is
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 11, 21
ELECTROLYTES: May contain Sodium
▶ Alecensa (Roche Products Ltd) A
Alectinib (as Alectinib hydrochloride) 150 mg Alecensa 150mg
capsules | 224 capsule P £5,032.00
l DRUG ACTION Axitinib is a tyrosine kinase inhibitor.
Treatment of advanced renal cell carcinoma following
failure of previous treatment with sunitinib or a
cytokine (aldesleukin or interferon alfa)
▶ Adult: (consult product literature)
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
l CONTRA-INDICATIONS Recent active gastro-intestinal
bleeding . untreated brain metastases
l INTERACTIONS → Appendix 1: axitinib
▶ Common or very common Alopecia . anaemia . appetite
▶ Uncommon Leucopenia . neutropenia . posterior reversible
encephalopathy syndrome (PRES)
l CONCEPTION AND CONTRACEPTION Effective
contraception required during and for up to 1 week after
l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk (toxicity in animal studies). See also
Pregnancy and reproductive function in Cytotoxic drugs
l HEPATIC IMPAIRMENT Manufacturer advises avoid in
severe impairment—no information available.
Dose adjustments Manufacturer advises reduce dose in
▶ Monitor for thyroid dysfunction.
▶ Monitor haemoglobin or haematocrit before and during
▶ Monitor for symptoms of gastro-intestinal perforation.
▶ Monitor for symptoms of fistula.
▶ Monitor for proteinuria before and during treatment.
▶ Monitor liver function before and during treatment.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Axitinib for treating advanced renal cell carcinoma after
failure of prior systemic treatment (February 2015)
Axitinib (Inlyta ®) is recommended as an option for
treating adults with advanced renal cell carcinoma after
failure of treatment with a first-line tyrosine kinase
inhibitor or a cytokine, only if the manufacturer provides
axitinib with the discount agreed in the patient access
www.nice.org.uk/guidance/ta333
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 25
Axitinib 1 mg Inlyta 1mg tablets | 56 tablet P £703.40 (Hospital
Axitinib 3 mg Inlyta 3mg tablets | 56 tablet P £2,110.20
Axitinib 5 mg Inlyta 5mg tablets | 56 tablet P £3,517.00
Axitinib 7 mg Inlyta 7mg tablets | 56 tablet P £4,923.80
l DRUG ACTION Binimetinib inhibits the mitogen-activated
inhibiting BRAF V600 mutation-positive cell growth.
Unresectable or metastatic melanoma with a BRAF V600
mutation (in combination with encorafenib) (specialist
▶ Adult: 45 mg twice daily, for dose adjustments due to
side-effects, consult product literature
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
l CONTRA-INDICATIONS History of retinal vein occlusion
l CAUTIONS Left ventricular dysfunction (ejection fraction
below 50%, or below the institutional lower limits of
normal). neuromuscular conditions associated with
elevated creatine kinase and rhabdomyolysis .risk factors
for retinal vein occlusion .risk factors for venous
BNF 78 Targeted therapy responsive malignancy 969
Immune system and malignant disease
epithelium . diarrhoea . dizziness . embolism and
thrombosis . eye inflammation . fatigue . fever. fluid
retention . gastrointestinal discomfort. gastrointestinal
colitis . vision disorders . vomiting
▶ Uncommon Facial paralysis . pancreatitis . paresis
▶ Frequency not known Respiratory disorders .retinal
occlusion (discontinue permanently)
l CONCEPTION AND CONTRACEPTION Manufacturer advises
women of child-bearing potential should use effective
contraception during and for at least one month after
l PREGNANCY Manufacturer advises avoid—toxicity in
animal studies. See also Pregnancy and reproductive
function in Cytotoxic drugs p. 888.
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises avoid in
moderate or severe impairment (increased exposure).
▶ Manufacturer advises monitor liver function before
treatment, at least monthly during the first 6 months, and
thereafter as clinically indicated.
▶ Manufacturer advises assess left ventricular ejection
fraction before treatment, one month after starting
treatment, then every 3 months or more frequently as
▶ Manufacturer advises monitor for visual disturbances.
▶ Manufacturer advises monitor blood pressure before and
▶ Manufacturer advises monitor creatine kinase and
creatinine levels monthly during the first 6 months of
treatment, and as clinically indicated.
Missed doses Manufacturer advises if a dose is more than
6 hours late, the missed dose should not be taken and the
next dose should be taken at the normal time.
Driving and skilled tasks Manufacturer advises patients and
carers should be counselled on the effects on driving and
performance of skilled tasks—increased risk of visual
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Encorafenib with binimetinib for unresectable or metastatic
BRAF V600 mutation-positive melanoma (February 2019)
Encorafenib with binimetinib (Mektovi ®) is recommended,
within its marketing authorisation, as an option for
manufacturer provides binimetinib according to the
www.nice.org.uk/guidance/ta562
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 3, 25
▶ Mektovi (Pierre Fabre Ltd) A
Binimetinib 15 mg Mektovi 15mg tablets | 84 tablet P £2,240.00 (Hospital only)
Previously treated chronic, accelerated and blast phase
Philadelphia chromosome-positive chronic myeloid
leukaemia (specialist use only)
▶ Adult: 500 mg once daily, consult product literature for
dose adjustment due to side-effects, or incomplete
haematologic response by week 8, or incomplete
cytogenetic response by week 12
Newly-diagnosed chronic phase Philadelphia
chromosome-positive chronic myeloid leukaemia
▶ Adult: 400 mg once daily, consult product literature for
dose adjustment due to side-effects, or failure to
demonstrate breakpoint cluster region-Abelson (BCRABL) transcripts 10% by month 3
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
MHRA/CHM ADVICE (MAY 2016): RISK OF HEPATITIS B VIRUS
REACTIVATION WITH BCR-ABL TYROSINE KINASE INHIBITORS
An EU wide review has concluded that bosutinib can
cause hepatitis B reactivation; the MHRA recommends
establishing hepatitis B virus status in all patients before
l CAUTIONS Cardiac disease . hepatitis B infection . history
of pancreatitis—withhold treatment if lipase elevated and
abdominal symptoms occur. history of QT prolongation—
monitor ECG and correct hypokalaemia and
hypomagnesaemia before and during treatment.recent
cardiac event—monitor ECG and correct hypokalaemia and
hypomagnesaemia before and during treatment.risk
factors for QT prolongation—monitor ECG and correct
hypokalaemia and hypomagnesaemia before and during
treatment. significant gastrointestinal disorder
▶ Hepatitis B infection The MHRA advises that patients who
are carriers of hepatitis B virus should be closely
monitored for signs and symptoms of active infection
throughout treatment and for several months after
stopping treatment; expert advice should be sought for
patients who test positive for hepatitis B virus and in those
l INTERACTIONS → Appendix 1: bosutinib
interval prolongation .renal impairment.respiratory
disorders . skin reactions .taste altered .thrombocytopenia . vomiting
▶ Frequency not known Severe cutaneous adverse reactions
l CONCEPTION AND CONTRACEPTION Effective
contraception required during treatment in women.
970 Targeted therapy responsive malignancy BNF 78
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