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ANTINEOPLASTIC DRUGS › ANTI-ANDROGENS

Abiraterone acetate 27-Apr-2019

l INDICATIONS AND DOSE

Metastatic castration-resistant prostate cancer in

patients whose disease has progressed during or after

treatment with a docetaxel-containing chemotherapy

regimen (in combination with prednisone or

prednisolone)| Metastatic castration-resistant prostate

cancer in patients who are asymptomatic or mildly

symptomatic after failure of androgen deprivation

therapy in whom chemotherapy is not yet clinically

indicated (in combination with prednisone or

prednisolone)

▶ BY MOUTH

▶ Adult: 1 g once daily, for dose of concurrent prednisone

or prednisolone—consult product literature

l CAUTIONS Diabetes (increased risk of hyperglycaemia—

monitor blood sugar frequently). history of cardiovascular

disease

CAUTIONS, FURTHER INFORMATION

▶ Cardiovascular disease Correct hypertension and

hypokalaemia before treatment (if significant risk of

congestive heart failure, such as history of cardiac failure,

uncontrolled hypertension or cardiac events, consult

product literature for management and increased

monitoring).

l INTERACTIONS → Appendix 1: abiraterone

l SIDE-EFFECTS

▶ Common or very common Angina pectoris . arrhythmias . bone fracture . diarrhoea . dyspepsia . haematuria . heart

failure . hepatic disorders . hypertension . hypertriglyceridaemia . hypokalaemia . left ventricular

dysfunction . osteoporosis . peripheral oedema .rash . sepsis . urinary tract infection

▶ Uncommon Adrenal insufficiency . myopathy

▶ Rare or very rare Alveolitis allergic

▶ Frequency not known Myocardial infarction . QT interval

prolongation

l CONCEPTION AND CONTRACEPTION Men should use

condoms if their partner is pregnant, and use condoms in

combination with another effective contraceptive method

if their partner is of child-bearing potential—toxicity in

animal studies.

l HEPATIC IMPAIRMENT Manufacturer advises use with

caution in moderate impairment and only if benefit clearly

outweighs risk; avoid in severe impairment.

l RENAL IMPAIRMENT Use with caution in severe

impairment—no information available.

l MONITORING REQUIREMENTS

▶ Monitor blood pressure, serum potassium concentration,

and fluid balance before treatment, and at least monthly

during treatment—consult product literature for

management of hypertension, hypokalaemia and oedema.

▶ Monitor liver function before treatment, then every

2 weeks for the first 3 months of treatment, then monthly

thereafter—interrupt treatment if serum alanine

aminotransferase or aspartate aminotransferase greater

than 5 times the upper limit (consult product literature for

details of restarting treatment at a lower dose) and

discontinue permanently if 20 times the upper limit.

l NATIONAL FUNDING/ACCESS DECISIONS

NICE decisions

▶ Abiraterone for castration-resistant metastatic prostate

cancer previously treated with a docetaxel-containing

regimen (updated July 2016) NICE TA259

Abiraterone in combination with prednisone or

prednisolone is recommended as an option for the

treatment of castration-resistant metastatic prostate

cancer only if:

. their disease has progressed on or after one docetaxelcontaining chemotherapy regimen, and

. the manufacturer provides abiraterone in accordance

with the commercial access arrangement as agreed with

NHS England.

Patients currently receiving abiraterone in combination

with prednisone or prednisolone whose disease does not

meet the first criteria should be able to continue therapy

until they and their clinician consider it appropriate to

stop.

www.nice.org.uk/guidance/ta259

▶ Abiraterone for treating metastatic hormone-relapsed

prostate cancer before chemotherapy is indicated (updated

July 2016) NICE TA387

Abiraterone, in combination with prednisone or

prednisolone, is recommended, within its marketing

authorisation, as an option for treating metastatic

hormone-relapsed prostate cancer:

. in people who have no or mild symptoms after androgen

deprivation therapy has failed, and before chemotherapy

is indicated

. only when the manufacturer provides abiraterone in

accordance with the commercial access arrangement as

agreed with NHS England.

www.nice.org.uk/guidance/ta387

Scottish Medicines Consortium (SMC) decisions

SMC No. 764/12

The Scottish Medicines Consortium has advised (August

2012) that abiraterone acetate (Zytiga ®), in combination

with prednisone or prednisolone, is accepted for restricted

use within NHS Scotland for the treatment of metastatic

castration-resistant prostate cancer in patients whose

disease has progressed during or after treatment with

docetaxel-containing chemotherapy regimen, and have

received only one prior chemotherapy regimen. This

advice is contingent upon the continuing availability of

the patient access scheme in NHS Scotland.

SMC No. 873/13

The Scottish Medicines Consortium has advised (October

2015) that abiraterone acetate (Zytiga ®) in combination

with prednisone or prednisolone, is accepted for use

within NHS Scotland for the treatment of metastatic

castration-resistant prostate cancer in patients who are

asymptomatic or mildly symptomatic, after failure of

androgen deprivation therapy in whom chemotherapy is

not yet clinically 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.

Tablet

CAUTIONARY AND ADVISORY LABELS 23

▶ Zytiga (Janssen-Cilag Ltd)

Abiraterone acetate 500 mg Zytiga 500mg tablets | 56 tablet P £2,735.00

Apalutamide 23-Apr-2019

l DRUG ACTION Apalutamide is an androgen receptor

inhibitor that decreases tumour cell proliferation and

increases apoptosis.

l INDICATIONS AND DOSE

Prostate cancer (specialist use only)

▶ BY MOUTH

▶ Adult: 240 mg once daily, for dose adjustments due to

side-effects—consult product literature

l CONTRA-INDICATIONS History or risk of seizures

946 Hormone responsive malignancy BNF 78

Immune system and malignant disease

8

l CAUTIONS History or risk of QT-interval prolongation . recent cardiovascular disease

l INTERACTIONS → Appendix 1: apalutamide

l SIDE-EFFECTS

▶ Common or very common Arthralgia . autoimmune

thyroiditis . bone fractures . conjunctivitis . costal cartilage

fracture . dyslipidaemia . fall . fatigue . genital rash . hypothyroidism . oral disorders .rash pustular. sacrum

fracture . skin reactions . weight decreased

▶ Uncommon Seizure (discontinue permanently)

▶ Frequency not known QT interval prolongation

l CONCEPTION AND CONTRACEPTION Manufacturer advises

men should use condoms in combination with another

highly effective contraceptive method during treatment

and for 3 months after stopping treatment if their partner

is of childbearing potential.

l HEPATIC IMPAIRMENT Manufacturer advises avoid in

severe impairment (no information available).

l RENAL IMPAIRMENT Manufacturer advises caution in

severe impairment (no information available).

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

▶ Erleada (Janssen-Cilag Ltd) A

Apalutamide 60 mg Erleada 60mg tablets | 112 tablet P £2,735.00

Bicalutamide 07-Jun-2018

l INDICATIONS AND DOSE

Locally advanced prostate cancer at high risk of disease

progression either alone or as adjuvant treatment to

prostatectomy or radiotherapy | Locally advanced, nonmetastatic prostate cancer when surgical castration or

other medical intervention inappropriate

▶ BY MOUTH

▶ Adult: 150 mg once daily

Advanced prostate cancer, in combination with

gonadorelin analogue or surgical castration

▶ BY MOUTH

▶ Adult: 50 mg once daily, to be started at the same time

as surgical castration or at least 3 days before

gonadorelin therapy

Prostate cancer (metastatic) with the aim of retaining

sexual function.

▶ BY MOUTH

▶ Adult: 150 mg once daily

l UNLICENSED USE g Bicalutamide is used in prostate

cancer (metastatic) with the aim of retaining sexual

function, hbut it is not licensed for this indication.

l CAUTIONS Risk of photosensitivity—avoid excessive

exposure to UV light and sunlight

l INTERACTIONS → Appendix 1: bicalutamide

l SIDE-EFFECTS

▶ Common or very common Alopecia . anaemia . appetite

decreased . asthenia . breast tenderness . chest pain . constipation . depression . dizziness . drowsiness . flatulence . gastrointestinal discomfort. gynaecomastia . haematuria . hair changes . hepatic disorders . hot flush . hypertransaminasaemia . nausea . oedema . sexual

dysfunction . skin reactions . weight increased

▶ Uncommon Angioedema . interstitial lung disease

▶ Rare or very rare Photosensitivity reaction

▶ Frequency not known QT interval prolongation

l HEPATIC IMPAIRMENT Manufacturer advises caution in

moderate to severe impairment (increased risk of

accumulation).

l MONITORING REQUIREMENTS Consider periodic liver

function tests.

l PATIENT AND CARER ADVICE

Risk of photosensitivity Patients should be advised to

consider the use of sunscreen.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: oral suspension

Tablet

▶ Bicalutamide (Non-proprietary)

Bicalutamide 50 mg Bicalutamide 50mg tablets | 28 tablet P £128.00 DT = £5.55

Bicalutamide 150 mg Bicalutamide 150mg tablets | 28 tablet P £240.00 DT = £9.60

▶ Casodex (AstraZeneca UK Ltd)

Bicalutamide 50 mg Casodex 50mg tablets | 28 tablet P £119.79 DT = £5.55

Bicalutamide 150 mg Casodex 150mg tablets | 28 tablet P £240.00 DT = £9.60

Enzalutamide 14-Jul-2018

l INDICATIONS AND DOSE

Metastatic castration-resistant prostate cancer in

patients whose disease has progressed during or after

docetaxel therapy

▶ BY MOUTH

▶ Adult: 160 mg once daily, for dose adjustments due to

side-effects, consult product literature

DOSE ADJUSTMENTS DUE TO INTERACTIONS

▶ Manufacturer advises if concurrent use of potent

inhibitors of CYP2C8 is unavoidable, reduce dose to

80 mg daily.

l CAUTIONS Alcoholism . bradycardia . brain injury . brain

metastases . brain tumours . history of QT-interval

prolongation . history or risk of seizure .recent

cardiovascular disease .risk factors for QT-interval

prolongation . stroke . uncontrolled hypertension

l INTERACTIONS → Appendix 1: enzalutamide

l SIDE-EFFECTS

▶ Common or very common Anxiety . asthenia . bone fracture . concentration impaired . fall . gynaecomastia . headache . hot flush . hypertension . memory loss .restless legs . skin

reactions

▶ Uncommon Cognitive disorder. leucopenia . neutropenia . seizure . visual hallucinations

▶ Frequency not known Back pain . diarrhoea . muscle

complaints . muscle weakness . nausea . oral disorders . posterior reversible encephalopathy syndrome (PRES). QT

interval prolongation .throat oedema .thrombocytopenia . vomiting

l CONCEPTION AND CONTRACEPTION Men should use

condoms during treatment and for 3 months after

stopping treatment if their partner is pregnant, and use

condoms in combination with another effective

contraceptive method if their partner is of child-bearing

potential—toxicity in animal studies.

l RENAL IMPAIRMENT Caution in severe impairment—no

information available.

l NATIONAL FUNDING/ACCESS DECISIONS

NICE decisions

▶ Enzalutamide for treating metastatic hormone-relapsed

prostate cancer before chemotherapy is indicated (January

2016) NICE TA377

Enzalutamide is recommended as an option for treating

metastatic hormone-relapsed prostate cancer in patients

who have mild or no symptoms after androgen deprivation

therapy has failed, and before chemotherapy is indicated,

BNF 78 Hormone responsive malignancy 947

Immune system and malignant disease

8

and only if the manufacturer provides enzalutamide with

the discount agreed in the patient access scheme.

www.nice.org.uk/TA377

▶ Enzalutamide for metastatic hormone-relapsed prostate

cancer previously treated with a docetaxel-containing

regimen (July 2014) NICE TA316

Enzalutamide is recommended, within its marketing

authorisation, as an option for treating metastatic

hormone-relapsed prostate cancer in adults only if, their

disease has progressed during or after docetaxelcontaining chemotherapy, and the manufacturer provides

enzalutamide with the discount agreed in the patient

access scheme. This guidance does not cover the use of

enzalutamide for metastatic hormone-relapsed prostate

cancer previously treated with abiraterone.

www.nice.org.uk/TA316

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Capsule

CAUTIONARY AND ADVISORY LABELS 25

▶ Xtandi (Astellas Pharma Ltd)

Enzalutamide 40 mg Xtandi 40mg capsules | 112 capsule P £2,734.67 DT = £2,734.67

Flutamide 28-Mar-2017

l INDICATIONS AND DOSE

Advanced prostate cancer | Metastatic prostate cancer

refractory to gonadorelin analogue therapy

(monotherapy)

▶ BY MOUTH

▶ Adult: 250 mg 3 times a day

l CAUTIONS Avoid excessive alcohol consumption . avoid in

Acute porphyrias p. 1058 . cardiac disease (oedema

reported)

l SIDE-EFFECTS

▶ Common or very common Appetite abnormal . asthenia . breast abnormalities . diarrhoea . drowsiness . galactorrhoea . gynaecomastia . hepatic function abnormal

(sometimes fatal). hepatitis (sometimes fatal). insomnia . nausea . vomiting

▶ Rare or very rare Alopecia . anxiety . breast neoplasm . cardiovascular disorder. chest pain . constipation . cough . depression . dizziness . dyspnoea . gastrointestinal

discomfort. gastrointestinal disorders . hair growth

abnormal . headache . herpes zoster. hot flush . hypertension . interstitial pneumonitis . libido decreased . lupus-like syndrome . lymphoedema . malaise . muscle

cramps . oedema . photosensitivity reaction . skin reactions .thirst. vision blurred

▶ Frequency not known QT interval prolongation

l HEPATIC IMPAIRMENT Manufacturer advises caution.

l MONITORING REQUIREMENTS Liver function tests,

monthly for first 4 months, periodically thereafter and at

the first sign or symptom of liver disorder (e.g. pruritus,

dark urine, persistent anorexia, jaundice, abdominal pain,

unexplained influenza-like symptoms).

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

▶ Flutamide (Non-proprietary)

Flutamide 250 mg Flutamide 250mg tablets | 84 tablet P £106.24 DT = £106.24

OESTROGENS

Diethylstilbestrol 06-Aug-2018

(Stilboestrol)

l INDICATIONS AND DOSE

Breast cancer in postmenopausal women

▶ BY MOUTH

▶ Adult: 10–20 mg daily

Prostate cancer

▶ BY MOUTH

▶ Adult: 1–3 mg daily

l CAUTIONS Cardiovascular disease

l SIDE-EFFECTS Bone pain (in breast cancer). breast

abnormalities . cervical mucus increased . cholelithiasis . contact lens intolerance . depression . erectile dysfunction . erythema nodosum .feminisation . fluid retention . gynaecomastia . headaches . hypercalcaemia (in breast

cancer). hypertension . increased risk of thrombosis . jaundice cholestatic . mood altered . nausea . neoplasms . skin reactions . sodium retention .testicular atrophy . uterine disorders . vomiting . weight changes . withdrawal

bleed

l PREGNANCY In first trimester, high doses associated with

vaginal carcinoma, urogenital abnormalities, and reduced

fertility in female offspring. Increased risk of hypospadias

in male offspring.

l HEPATIC IMPAIRMENT Manufacturer advises caution in

mild to moderate impairment; avoid in severe or active

impairment.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

▶ Diethylstilbestrol (Non-proprietary)

Diethylstilbestrol 1 mg Diethylstilbestrol 1mg tablets |

28 tablet P £117.85 DT = £117.61

Diethylstilbestrol 5 mg Diethylstilbestrol 5mg tablets | 28 tablet P £185.00–£208.00 DT = £208.00

PITUITARY AND HYPOTHALAMIC HORMONES

AND ANALOGUES › ANTI-GONADOTROPHINRELEASING HORMONES

Degarelix 08-Feb-2019

l INDICATIONS AND DOSE

Advanced hormone-dependent prostate cancer

▶ BY SUBCUTANEOUS INJECTION

▶ Adult: Initially 240 mg, to be administered as

2 injections of 120 mg, then 80 mg every 28 days, dose

to be administered into the abdominal region

l CAUTIONS Diabetes . susceptibility to QT-interval

prolongation

l SIDE-EFFECTS

▶ Common or very common Anaemia . chills . diarrhoea . dizziness . fatigue . fever. gynaecomastia . headache . hot

flush . influenza like illness . insomnia . musculoskeletal

discomfort. musculoskeletal pain . nausea . sexual

dysfunction . skin reactions . sweat changes .testicular

disorders . weight changes

▶ Uncommon Alopecia . appetite decreased . arrhythmias . bone disorders . breast pain . cognitive impairment. constipation . depression . diabetes mellitus . dry mouth . dyspnoea . gastrointestinal discomfort. genital discomfort . hyperglycaemia . hypertension . hypotension . joint

disorders . malaise . muscle spasms . muscle weakness . numbness . palpitations . pelvic pain . peripheral oedema .

948 Hormone responsive malignancy BNF 78

Immune system and malignant disease

8

QT interval prolongation .renal impairment. urinary

disorders . vision blurred . vomiting

▶ Rare or very rare Febrile neutropenia . heart failure . injection site necrosis . myocardial infarction

l HEPATIC IMPAIRMENT Manufacturer advises caution

(limited information available)—monitor liver function.

l RENAL IMPAIRMENT Manufacturer advises caution in

severe impairment—no information available.

l MONITORING REQUIREMENTS Monitor bone density.

l NATIONAL FUNDING/ACCESS DECISIONS

NICE decisions

▶ Degarelix for treating advanced hormone-dependent prostate

cancer (August 2016) NICE TA404

Degarelix (Firmagon ®) is recommended as an option for

treating advanced hormone-dependent prostate cancer in

patients with spinal metastases, only if at least the same

discounted drug cost which was available to the NHS in

June 2016 is achieved by the commissioner.

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/ta404

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Powder and solvent for solution for injection

▶ Firmagon (Ferring Pharmaceuticals Ltd)

Degarelix (as Degarelix acetate) 80 mg Firmagon 80mg powder

and solvent for solution for injection vials | 1 vial P £129.37 DT =

£129.37

Degarelix (as Degarelix acetate) 120 mg Firmagon 120mg powder

and solvent for solution for injection vials | 2 vial P £260.00 DT =

£260.00

PITUITARY AND HYPOTHALAMIC HORMONES

AND ANALOGUES › SOMATOSTATIN ANALOGUES

Somatostatin analogues, malignant

disease

Overview

Lanreotide below, octreotide p. 950 and pasireotide p. 951

are analogues of the hypothalamic release-inhibiting

hormone somatostatin. Lanreotide and octreotide are

indicated for the relief of symptoms associated with

neuroendocrine (particularly carcinoid) tumours and

acromegaly. Additionally, lanreotide is licensed for the

treatment of thyroid tumours and octreotide is also licensed

for the prevention of complications following pancreatic

surgery. Lanreotide (Somatuline Autogel ®) is also licensed for

the treatment of unresectable locally advanced or metastatic

gastroenteropancreatic neuroendocrine tumours of midgut,

pancreatic or unknown origin where hindgut sites of origin

have been excluded. Octreotide long-acting depot injection

is licensed for treatment of advanced neuroendocrine

tumours of the midgut, or treatment where primary origin is

not known but non-midgut sites of origin have been

excluded. Octreotide may also be valuable in reducing

vomiting in palliative care and in stopping variceal bleeding

[unlicensed indication]—see also vasopressin p. 669 and

terlipressin acetate p. 90. Pasireotide is licensed for the

treatment of Cushing’s disease when surgery has failed or is

inappropriate.

Somatostatin analogues f

l CAUTIONS Diabetes mellitus (antidiabetic requirements

may be reduced). insulinoma (increased depth and

duration of hypoglycaemia may occur—observe patients

and monitor blood glucose levels when initiating

treatment and changing doses). may cause growth

hormone-secreting pituitary tumour expansion during

treatment (causing serious complications)

l SIDE-EFFECTS

▶ Common or very common Alopecia . appetite decreased . asthenia . cholecystitis . cholelithiasis (following long term

use). cholestasis . constipation . diabetes mellitus . diarrhoea . dizziness . gastrointestinal discomfort. gastrointestinal disorders . glucose tolerance impaired

(following long term use). headache . hyperglycaemia

(long term use). hypoglycaemia . myalgia . nausea . pruritus . sinus bradycardia . vomiting

l MONITORING REQUIREMENTS

▶ Monitor for signs of tumour expansion (e.g. visual field

defects).

▶ Ultrasound examination of the gallbladder is

recommended before treatment and at intervals of

6–12 months during treatment.

l DIRECTIONS FOR ADMINISTRATION Injection sites should

be rotated.

eiii F abovei

Lanreotide 04-Oct-2018

l INDICATIONS AND DOSE

SOMATULINE AUTOGEL ®

Acromegaly (if somatostatin analogue not given

previously)

▶ BY DEEP SUBCUTANEOUS INJECTION

▶ Adult: Initially 60 mg every 28 days, adjusted according

to response, (consult product literature), for patients

treated previously with somatostatin analogue, consult

product literature for initial dose, dose to be given in

the gluteal region

Neuroendocrine (particularly carcinoid) tumours

▶ BY DEEP SUBCUTANEOUS INJECTION

▶ Adult: Initially 60–120 mg every 28 days, adjusted

according to response, dose to be given in the gluteal

region

Unresectable locally advanced or metastatic

gastroenteropancreatic neuroendocrine tumours of

midgut, pancreatic or unknown origin where hindgut

sites of origin have been excluded

▶ BY DEEP SUBCUTANEOUS INJECTION

▶ Adult: 120 mg every 28 days

SOMATULINE LA ®

Acromegaly and neuroendocrine (particularly carcinoid)

tumours

▶ BY INTRAMUSCULAR INJECTION

▶ Adult: Initially 30 mg every 14 days, increased to 30 mg

every 7–10 days, adjusted according to response

Thyroid tumours

▶ BY INTRAMUSCULAR INJECTION

▶ Adult: Initially 30 mg every 14 days, increased to 30 mg

every 10 days, adjusted according to response

l CAUTIONS Cardiac disorders (including bradycardia). patients with carcinoid tumours—exclude the presence of

an obstructive intestinal tumour before treatment

l INTERACTIONS → Appendix 1: lanreotide

l SIDE-EFFECTS

▶ Common or very common Biliary dilatation . lethargy . musculoskeletal pain . weight decreased

▶ Uncommon Hot flush . insomnia

▶ Frequency not known Pancreatitis

l PREGNANCY Manufacturer advises use only if potential

benefit outweighs risk.

BNF 78 Hormone responsive malignancy 949

Immune system and malignant disease

8

l BREAST FEEDING Manufacturer advises caution—no

information available.

l MONITORING REQUIREMENTS Monitor for hypothyroidism

when clinically indicated.

l NATIONAL FUNDING/ACCESS DECISIONS

All Wales Medicines Strategy Group (AWMSG) decisions

AWMSG No. 1988

The All Wales Medicines Strategy Group has advised

(September 2018) that lanreotide (Somatuline ® Autogel ®)

is recommended as an option for use within NHS Wales for

the treatment of grade 1 and a subset of grade 2 (Ki67

index up to 10%) gastroenteropancreatic neuroendocrine

tumours of midgut, pancreatic or unknown origin where

hindgut sites of origin have been excluded, in adults with

unresectable locally advanced or metastatic disease.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Solution for injection

▶ Somatuline Autogel (Ipsen Ltd)

Lanreotide (as Lanreotide acetate) 120 mg per 1 ml Somatuline

Autogel 60mg/0.5ml solution for injection pre-filled syringes with

safety system | 1 pre-filled disposable injection P £551.00 DT =

£551.00

Lanreotide (as Lanreotide acetate) 180 mg per 1 ml Somatuline

Autogel 90mg/0.5ml solution for injection pre-filled syringes with

safety system | 1 pre-filled disposable injection P £736.00 DT =

£736.00

Lanreotide (as Lanreotide acetate) 240 mg per 1 ml Somatuline

Autogel 120mg/0.5ml solution for injection pre-filled syringes with

safety system | 1 pre-filled disposable injection P £937.00 DT =

£937.00

Powder and solvent for suspension for injection

▶ Somatuline LA (Ipsen Ltd)

Lanreotide (as Lanreotide acetate) 30 mg Somatuline LA 30mg

powder and solvent for suspension for injection vials | 1 vial P £323.00 DT = £323.00

eiiiF 949i

Octreotide 04-Oct-2018

l INDICATIONS AND DOSE

Symptoms associated with carcinoid tumours with

features of carcinoid syndrome, VIPomas, glucagonomas

▶ BY SUBCUTANEOUS INJECTION

▶ Adult: Initially 50 micrograms 1–2 times a day,

adjusted according to response; increased to

200 micrograms 3 times a day, higher doses may be

required exceptionally; maintenance doses are

variable; in carcinoid tumours, discontinue after

1 week if no effect, if rapid response required, initial

dose may be given by intravenous injection (with ECG

monitoring and after dilution)

Acromegaly, short-term treatment before pituitary

surgery or long-term treatment in those inadequately

controlled by other treatment or until radiotherapy

becomes fully effective

▶ BY SUBCUTANEOUS INJECTION

▶ Adult: 100–200 micrograms 3 times a day, discontinue

if no improvement within 3 months

Prevention of complications following pancreatic surgery

▶ BY SUBCUTANEOUS INJECTION

▶ Adult: (consult product literature)

Test dose before use of depot preparation

▶ BY SUBCUTANEOUS INJECTION

▶ Adult: Test dose 50–100 micrograms for 1 dose, test

dose should be given if subcutanous octreotide not

previously given

Acromegaly | Neuroendocrine (particularly carcinoid)

tumour adequately controlled by subcutaneous

octreotide

▶ BY DEEP INTRAMUSCULAR INJECTION USING DEPOT INJECTION

▶ Adult: Initially 20 mg every 4 weeks for 3 months then

adjusted according to response, increased if necessary

up to 30 mg every 4 weeks, to be administered into the

gluteal muscle, for acromegaly, start depot 1 day after

the last dose of subcutaneous octreotide, for

neuroendocrine tumours, continue subcutaneous

octreotide for 2 weeks after first dose of depot

octreotide

Advanced neuroendocrine tumours of the midgut, or

tumours of unknown primary origin where non-midgut

sites of origin have been excluded

▶ BY DEEP INTRAMUSCULAR INJECTION USING DEPOT INJECTION

▶ Adult: 30 mg every 4 weeks

Reduce intestinal secretions in palliative care | Reduce

vomiting due to bowel obstruction in palliative care

▶ BY CONTINUOUS SUBCUTANEOUS INFUSION

▶ Adult: 0.25–0.5 mg/24 hours (max. per dose

0.75 mg/24 hours), occasionally doses higher than the

maximum are sometimes required

l INTERACTIONS → Appendix 1: octreotide

l SIDE-EFFECTS

▶ Common or very common Arrhythmias . biliary sludge . dyspnoea . hyperbilirubinaemia . hypothyroidism . skin

reactions .thyroid disorder

▶ Uncommon Dehydration

▶ Frequency not known Hepatic disorders . pancreatitis acute

(after administration).thrombocytopenia

SIDE-EFFECTS, FURTHER INFORMATION Administering nondepot injections of octreotide between meals and at

bedtime may reduce gastrointestinal side-effects.

l CONCEPTION AND CONTRACEPTION Effective

contraception required during treatment.

l PREGNANCY Possible effect on fetal growth; manufacturer

advises use only if potential benefit outweighs risk.

l BREAST FEEDING Manufacturer advises avoid—present in

milk in animal studies.

l HEPATIC IMPAIRMENT Manufacturer advises caution (risk

of increased half-life in cirrhosis).

Dose adjustments Manufacturer advises consider dose

reduction—consult product literature.

l MONITORING REQUIREMENTS

▶ Monitor thyroid function on long-term therapy.

▶ Monitor liver function.

▶ With intravenous use ECG monitoring required with

intravenous administration.

l TREATMENT CESSATION Avoid abrupt withdrawal of shortacting subcutaneous octreotide (associated with biliary

colic and pancreatitis).

l DIRECTIONS FOR ADMINISTRATION For intravenous

injection or intravenous infusion, dilute with Sodium

Chloride 0.9% to a concentration of 10–50%.

l PRESCRIBING AND DISPENSING INFORMATION

Palliative care For further information on the use of

octreotide in palliative care, see www.medicinescomplete.

com/#/content/palliative/octreotide.

l NATIONAL FUNDING/ACCESS DECISIONS

All Wales Medicines Strategy Group (AWMSG) decisions

AWMSG No. 3732

The All Wales Medicines Strategy Group has advised

(September 2018) that octreotide (Sandostatin ® LAR ®) is

recommended as an option for use within NHS Wales for

the treatment of patients with advanced neuroendocrine

tumours of the midgut or of unknown primary origin

where non-midgut sites of origin have been excluded.

950 Hormone responsive malignancy BNF 78

Immune system and malignant disease

8

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Solution for injection

▶ Octreotide (Non-proprietary)

Octreotide (as Octreotide acetate) 50 microgram per

1 ml Octreotide 50micrograms/1ml solution for injection pre-filled

syringes | 5 pre-filled disposable injection P £18.85 DT = £18.85

Octreotide 50micrograms/1ml solution for injection vials | 5 vial P £22.00 DT = £22.00

Octreotide 50micrograms/1ml solution for injection ampoules | 5 ampoule P £14.85–£18.60 DT = £14.87

Octreotide (as Octreotide acetate) 100 microgram per

1 ml Octreotide 100micrograms/1ml solution for injection ampoules

| 5 ampoule P £32.65 DT = £27.97

Octreotide 100micrograms/1ml solution for injection pre-filled

syringes | 5 pre-filled disposable injection P £30.34–£32.90 DT =

£30.34

Octreotide 100micrograms/1ml solution for injection vials | 5 vial P £32.65 DT = £32.65

Octreotide (as Octreotide acetate) 200 microgram per

1 ml Octreotide 1mg/5ml solution for injection vials | 1 vial P £65.00 DT = £65.00

Octreotide (as Octreotide acetate) 500 microgram per

1 ml Octreotide 500micrograms/1ml solution for injection vials | 5 vial P £158.25

Octreotide 500micrograms/1ml solution for injection ampoules |

5 ampoule P £135.47–£169.35 DT = £135.47

Octreotide 500micrograms/1ml solution for injection pre-filled

syringes | 5 pre-filled disposable injection P £154.22–£169.00 DT

= £154.22

▶ Sandostatin (Novartis Pharmaceuticals UK Ltd)

Octreotide (as Octreotide acetate) 50 microgram per

1 ml Sandostatin 50micrograms/1ml solution for injection ampoules

| 5 ampoule P £14.87 DT = £14.87

Octreotide (as Octreotide acetate) 100 microgram per

1 ml Sandostatin 100micrograms/1ml solution for injection ampoules

| 5 ampoule P £27.97 DT = £27.97

Octreotide (as Octreotide acetate) 500 microgram per

1 ml Sandostatin 500micrograms/1ml solution for injection ampoules

| 5 ampoule P £135.47 DT = £135.47

Powder and solvent for suspension for injection

▶ Sandostatin LAR (Novartis Pharmaceuticals UK Ltd)

Octreotide (as Octreotide acetate) 10 mg Sandostatin LAR 10mg

powder and solvent for suspension for injection vials | 1 vial P £549.71 DT = £549.71

Octreotide (as Octreotide acetate) 20 mg Sandostatin LAR 20mg

powder and solvent for suspension for injection vials | 1 vial P £799.33 DT = £799.33

Octreotide (as Octreotide acetate) 30 mg Sandostatin LAR 30mg

powder and solvent for suspension for injection vials | 1 vial P £998.41 DT = £998.41

eiiiF 949i

Pasireotide 02-Mar-2018

l INDICATIONS AND DOSE

Cushing’s disease [when surgery has failed or is

inappropriate]

▶ BY SUBCUTANEOUS INJECTION

▶ Adult: Initially 600 micrograms twice daily for

2 months, then increased if necessary to

900 micrograms twice daily, consider discontinuation if

no response after 2 months of treatment, for dose

adjustment due to side-effects—consult product

literature

▶ BY DEEP INTRAMUSCULAR INJECTION

▶ Adult: Initially 10 mg every 4 weeks, increased if

necessary up to 40 mg every 4 weeks, dose may be

titrated every 2–4 months based on response and

tolerability, consider discontinuation if no clinical

benefit observed, for dose adjustment due to sideeffects—consult product literature

Acromegaly [when surgery has failed or is inappropriate,

and control with another somatostatin analogue is

inadequate]

▶ BY DEEP INTRAMUSCULAR INJECTION

▶ Adult: Initially 40 mg every 4 weeks, increased if

necessary up to 60 mg every 4 weeks, dose may be

increased if levels of growth hormone and/or insulinlike growth factor-1 are not fully controlled after

3 months of initial dosing, for dose adjustment due to

side-effects—consult product literature

l CAUTIONS Cardiac disorders (including bradycardia). susceptibility to QT-interval prolongation (including

electrolyte disturbances)

l INTERACTIONS → Appendix 1: pasireotide

l SIDE-EFFECTS

▶ Common or very common Adrenal insufficiency . arthralgia . hypotension . QT interval prolongation

▶ Uncommon Anaemia

l PREGNANCY Manufacturer advises avoid—toxicity in

animal studies.

l BREAST FEEDING Manufacturer advises avoid—present in

milk in animal studies.

l HEPATIC IMPAIRMENT Manufacturer advises caution in

moderate impairment (risk of increased exposure); avoid

in severe impairment.

Dose adjustments ▶ With subcutaneous use for Cushing’s

disease Manufacturer advises reduce initial dose to

300 micrograms twice daily (max. dose 600 micrograms

twice daily) in moderate impairment.

▶ With intramuscular use for Cushing’s disease Manufacturer

advises max. dose 20 mg every four weeks in moderate

impairment.

▶ When used for Acromegaly Manufacturer advises reduce

initial dose to 20 mg every four weeks (max. dose 40 mg

every four weeks) in moderate impairment.

l RENAL IMPAIRMENT Manufacturer advises caution in

severe impairment—increased plasma-pasireotide

exposure.

l MONITORING REQUIREMENTS

▶ Manufacturer advises consider monitoring pituitary

function before treatment initiation and periodically

thereafter.

▶ With subcutaneous use Manufacturer advises monitor liver

function before treatment initiation, after 1, 2, 4, 8, and

12 weeks of treatment, and thereafter as clinically

indicated. Manufacturer advises assess glycaemic status

before treatment initiation, weekly for the first

2–3 months of treatment, over the first 2–4 weeks after

any dose increase, periodically thereafter, and 3 months

after treatment is complete—if glycaemic control is poor,

diabetes management and monitoring should be

intensified before and during treatment. Manufacturer

advises monitor ECG and electrolytes before treatment

initiation, after one week of treatment, and periodically

thereafter.

▶ With intramuscular use Manufacturer advises monitor liver

function before treatment initiation, after the first

2–3 weeks of treatment, then monthly for 3 months, and

thereafter as clinically indicated. Manufacturer advises

assess glycaemic status before treatment initiation, weekly

for the first 3 months of treatment, over the first

4–6 weeks after any dose increase, periodically thereafter,

and 3 months after treatment is complete—if glycaemic

control is poor, diabetes management and monitoring

should be intensified before and during treatment.

Manufacturer advises monitor ECG and electrolytes before

treatment initiation, after 3 weeks of treatment, and

periodically thereafter.

BNF 78 Hormone responsive malignancy 951

Immune system and malignant disease

8

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