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l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Solution for infusion

▶ Trisenox (Teva UK Ltd)

Arsenic trioxide 1 mg per 1 ml Trisenox 10mg/10ml concentrate for

solution for infusion ampoules | 10 ampoule P £2,920.00

(Hospital only)

Asparaginase 11-Sep-2018

l DRUG ACTION Asparaginase is an enzyme which acts by

breaking down L-asparagine to aspartic acid and ammonia,

this disrupts protein synthesis of tumour cells.

l INDICATIONS AND DOSE

Acute lymphoblastic leukaemia (in combination with

other antineoplastic drugs) (specialist use only)

▶ BY INTRAVENOUS INFUSION

▶ Adult: 5000 units/m2 every 3 days

l CONTRA-INDICATIONS History of pancreatitis related to

asparaginase therapy . history of serious haemorrhage

related to asparaginase therapy . history of serious

thrombosis related to asparaginase therapy . pancreatitis . pre-existing known coagulopathy

l CAUTIONS Diabetes (may raise blood glucose). hypersensitivity reactions . hypertriglyceridaemia

(severe)—increased risk of acute pancreatitis

CAUTIONS, FURTHER INFORMATION

▶ Hypersensitivity reactions Serious hypersensitivity reactions,

including life-threatening anaphylaxis, can occur—

asparaginase should only be administered when

appropriately trained staff and resuscitation facilities are

immediately available; in the event of a hypersensitivity

reaction, treatment should be stopped immediately and

appropriate management initiated. Manufacturer advises

an intracutaneous or small intravenous test dose can be

used but is of limited value for predicting which patients

will experience an allergic reaction.

l INTERACTIONS → Appendix 1: asparaginase

l SIDE-EFFECTS

▶ Common or very common Abdominal pain . agitation . anaemia . angioedema . appetite decreased . arthralgia . back pain . bronchospasm . confusion . depression . diarrhoea . disseminated intravascular coagulation . dizziness . drowsiness . dyspnoea . embolism and

thrombosis . fatigue . flushing . haemorrhage . hallucination . hyperglycaemia . hypersensitivity . hypoalbuminaemia . hypoglycaemia . hypotension . increased risk of infection . leucopenia . nausea . neurological effects . oedema . pancreatitis . skin reactions .thrombocytopenia . vomiting . weight decreased

▶ Uncommon Headache . hyperammonaemia . hyperuricaemia

▶ Rare or very rare Coma . consciousness impaired . diabetic

ketoacidosis . hepatic disorders . hyperparathyroidism . hypoparathyroidism . ischaemic stroke . necrotising

pancreatitis . pancreatic pseudocyst. posterior reversible

encephalopathy syndrome (PRES). seizure .tremor

SIDE-EFFECTS, FURTHER INFORMATION There have been

rare reports of cholestasis, icterus, hepatic cell necrosis

and hepatic failure with fatal outcome; manufacturer

advises interrupt treatment if these symptoms develop.

l CONCEPTION AND CONTRACEPTION Manufacturer advises

effective contraception in men and women of childbearing potential during treatment and for at least

3 months after last dose; asparaginase may reduce

effectiveness of oral contraceptives—additional

precautions (e.g. barrier method) are required, see also

Pregnancy and reproductive function in Cytotoxic drugs

p. 888.

l PREGNANCY Manufacturer advises avoid unless

essential—toxicity in animal studies. See also Pregnancy

and reproductive function in Cytotoxic drugs p. 888.

l BREAST FEEDING Manufacturer advises avoid—no

information available.

l HEPATIC IMPAIRMENT Manufacturer advises avoid in

severe impairment—no information available.

l MONITORING REQUIREMENTS

▶ Manufacturer advises monitor trough serum asparaginase

levels 3 days after administration; consider switching to a

different asparaginase preparation if target levels not

reached—seek expert advice.

▶ Manufacturer advises monitor bilirubin, hepatic

transaminases, and coagulation parameters before and

during treatment; in addition, monitor plasma and urinary

glucose, amylase, lipase, triglycerides, cholesterol and

serum protein levels during treatment.

l HANDLING AND STORAGE Manufacturer advises store in a

refrigerator (2–8°C)—consult product literature for storage

conditions after reconstitution and dilution.

l PATIENT AND CARER ADVICE

Driving and skilled tasks Manufacturer advises

asparaginase has moderate influence on driving and

performance of skilled tasks—increased risk of dizziness

and somnolence.

l NATIONAL FUNDING/ACCESS DECISIONS

Scottish Medicines Consortium (SMC) decisions

SMC No. 1319/18

The Scottish Medicines Consortium has advised (April 2018)

that asparaginase (Spectrila ®) is accepted for use within

NHS Scotland when used as a component of antineoplastic

combination therapy for the treatment of acute

lymphoblastic leukaemia in paediatric patients from birth

to 18 years and adults.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Powder for solution for infusion

▶ Spectrila (medac UK) A

Asparaginase 10000 unit Spectrila 10,000unit powder for

concentrate for solution for infusion vials | 1 vial P £450.00

(Hospital only)

Crisantaspase 16-Mar-2017

l DRUG ACTION Crisantaspase is the enzyme asparaginase

produced by Erwinia chrysanthemi.

l INDICATIONS AND DOSE

Acute lymphoblastic leukaemia

▶ BY INTRAMUSCULAR INJECTION, OR BY SUBCUTANEOUS

INJECTION, OR BY INTRAVENOUS INJECTION

▶ Adult: (consult product literature)

l CONTRA-INDICATIONS History of pancreatitis related to

asparaginase therapy

l CAUTIONS Diabetes (may raise blood glucose)

l INTERACTIONS → Appendix 1: crisantaspase

l SIDE-EFFECTS

▶ Common or very common Chills . coagulation disorders . confusion . diarrhoea . dizziness . drowsiness . dyspnoea . face oedema .fever. headache . hepatic disorders . hypersensitivity . limb swelling . lip swelling . neurotoxicity . pain . pallor. pancreatitis . seizures . skin

reactions .thrombosis

▶ Uncommon Hyperglycaemia . hyperlipidaemia . hypoxia . increased risk of infection .respiratory disorders

▶ Rare or very rare Arthritis reactive . coma . diabetic

ketoacidosis . dysphagia . dysphasia . encephalopathy . haemorrhage . level of consciousness decreased . myalgia .

BNF 78 Cytotoxic responsive malignancy 933

Immune system and malignant disease

8

myocardial infarction . necrotising pancreatitis . neutropenia . paresis . sepsis .thrombocytopenia

▶ Frequency not known Abdominal pain . flushing . hyperammonaemia . hypertension . hypotension . nausea . pseudocyst. vomiting

l CONCEPTION AND CONTRACEPTION Contraceptive advice

required, see Pregnancy and reproductive function in

Cytotoxic drugs p. 888.

l PREGNANCY Avoid. See also, Pregnancy and reproductive

function in Cytotoxic drugs p. 888.

l BREAST FEEDING Discontinue breast-feeding.

l DIRECTIONS FOR ADMINISTRATION Facilities for the

management of anaphylaxis should be available.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Powder for solution for injection

▶ Erwinase (Jazz Pharmaceuticals UK)

Crisantaspase 10000 unit Erwinase 10,000unit powder for solution

for injection vials | 5 vial P £3,065.00

Eribulin 08-Feb-2019

l INDICATIONS AND DOSE

Treatment of locally advanced or metastatic breast cancer

when the disease has progressed after treatment with at

least 1 chemotherapy regimen for advanced disease

▶ BY INTRAVENOUS INJECTION

▶ Adult: Give on day 1 and day 8 of a 21-day cycle,

previous therapy should have included an

anthracycline and a taxane in either the adjuvant or

metastatic setting unless the patient is unsuitable for

these treatments (consult local protocol)

l CONTRA-INDICATIONS Congenital long QT syndrome

l CAUTIONS Bradyarrhythmias (increased susceptibility to

QT-interval prolongation). congestive heart failure

(increased susceptibility to QT-interval prolongation). electrolyte disturbances (increased susceptibility to QTinterval prolongation). susceptibility to QT-interval

prolongation

l INTERACTIONS → Appendix 1: eribulin

l SIDE-EFFECTS

▶ Common or very common Alopecia . anaemia . appetite

decreased . arthralgia . asthenia . chest pain . chills . conjunctivitis . constipation . cough . decreased leucocytes . dehydration . depression . diarrhoea . dizziness . dry

mouth . dyspnoea . dysuria . electrolyte imbalance . embolism and thrombosis . excessive tearing .fever. gastrointestinal discomfort. gastrooesophageal reflux

disease . haemorrhage . headache . hot flush . hyperbilirubinaemia . hyperglycaemia . increased risk of

infection . influenza like illness . insomnia . lethargy . mucositis . muscle complaints . muscle weakness . nail

disorder. nausea . nerve disorders . neurotoxicity . neutropenia . oral disorders . oropharyngeal pain . pain . peripheral oedema .rhinorrhoea . sensation abnormal . skin reactions . sweat changes .tachycardia .taste altered . thrombocytopenia .tinnitus . vertigo . vomiting . weight

decreased

▶ Uncommon Angioedema . hepatotoxicity . interstitial lung

disease . pancreatitis . proteinuria .renal failure . sepsis

▶ Rare or very rare Disseminated intravascular coagulation

▶ Frequency not known QT interval prolongation . severe

cutaneous adverse reactions (SCARs)

l CONCEPTION AND CONTRACEPTION Ensure effective

contraception during and for up to 3 months after

treatment in men or women.

l PREGNANCY Avoid unless essential (teratogenic in animal

studies). See also Pregnancy and reproductive function in

Cytotoxic drugs p. 888.

l BREAST FEEDING Discontinue breast-feeding.

l HEPATIC IMPAIRMENT Manufacturer advises caution

(increased risk of neutropenia).

Dose adjustments Manufacturer advises dose reduction—

consult product literature.

l RENAL IMPAIRMENT

Dose adjustments Consider dose reduction if creatinine

clearance less than 40 mL/minute.

l MONITORING REQUIREMENTS

▶ Monitor for signs of peripheral neuropathy—severe

peripheral neurotoxicity requires treatment delay or dose

reduction (consult product literature).

▶ ECG monitoring recommended in patients prescribed

concomitant use of drugs that prolong the QT-interval or

who are susceptible to QT-interval prolongation.

▶ Monitor electrolytes periodically.

l NATIONAL FUNDING/ACCESS DECISIONS

NICE decisions

▶ Eribulin for treating locally advanced or metastatic breast

cancer after 2 or more chemotherapy regimens (December

2016) NICE TA423

Eribulin (Halaven ®) is recommended for the treatment of

locally advanced or metastatic breast cancer, only if:

. the condition has progressed after at least 2

chemotherapy regimens (which may include an

anthracycline or a taxane, and capecitabine), and

. the manufacturer provides eribulin with the discount

agreed in the patient access scheme.

Patients whose treatment was started within the NHS

before this guidance was published should continue

treatment, without change to their funding arrangements,

until they and their NHS clinician consider it appropriate

to stop.

www.nice.org.uk/guidance/ta423

▶ Eribulin for treating locally advanced or metastatic breast

cancer after 1 chemotherapy regimen (March 2018)

NICE TA515

Eribulin (Halaven ®) is not recommended for treating

locally advanced or metastatic breast cancer in adults who

have had only 1 chemotherapy regimen.

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/ta515

Scottish Medicines Consortium (SMC) decisions

SMC No. 1065/15

The Scottish Medicines Consortium has advised (March

2016) that eribulin (Halaven ®) is accepted for restricted

use within NHS Scotland for the treatment of patients with

locally advanced or metastatic breast cancer that has

progressed after at least two prior chemotherapy regimens

for advanced disease, which includes capecitabine if

indicated. 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.

Solution for injection

EXCIPIENTS: May contain Ethanol

▶ Halaven (Eisai Ltd)

Eribulin.44 mg per 1 ml Halaven 0.88mg/2ml solution for injection

vials | 1 vial P £361.00 (Hospital only)

934 Cytotoxic responsive malignancy BNF 78

Immune system and malignant disease

8

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