ups, and immediately report any oral symptoms such as
dental mobility, pain, or swelling to a doctor and dentist.
Hypocalcaemia All patients should be advised to report
symptoms of hypocalcaemia to their doctor (e.g. muscle
spasms, twitches, cramps, numbness or tingling in the
fingers, toes, or around the mouth).
Patient reminder card A patient reminder card should be
provided (risk of osteonecrosis of the jaw).
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Denosumab for the prevention of osteoporotic fractures in
postmenopausal women (October 2010) NICE TA204
Denosumab (Prolia ®) is recommended as a treatment
option for the primary prevention of osteoporotic fragility
fractures in postmenopausal women at increased risk of
. who are unable to comply with the special instructions
for administering alendronate and risedronate, or have
an intolerance of, or a contra-indication to, those
. who comply with particular combinations of bone
mineral density measurement, age, and independent
risk factors for fracture, as indicated in the full NICE
Denosumab (Prolia ®) is recommended as a treatment
option for the secondary prevention of osteoporotic fragility
fractures only in postmenopausal women at increased risk
of fractures who are unable to comply with the special
instructions for administering alendronate and
risedronate, or have an intolerance of, or a contraindication to, those treatments.
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/ta204
▶ Denosumab for the prevention of skeletal-related events in
adults with bone metastases from solid tumours (October
Denosumab (Xgeva ®) is recommended for the prevention
of skeletal-related events in adults with bone metastases
from breast cancer and from solid tumours other than
. bisphosphonates would otherwise be prescribed, and
. the manufacturer provides denosumab with the discount
agreed in the patient access scheme.
Patients with bone metastases from solid tumours
currently receiving denosumab whose disease does not
meet the above criteria can continue treatment until they
and their clinician consider it appropriate to stop.
www.nice.org.uk/guidance/ta265
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (December
2010) that denosumab (Prolia ®) is accepted for restricted
use within NHS Scotland for the treatment of osteoporosis
in postmenopausal women at increased risk of fractures
who have a bone mineral density T-score <–2.5 and –4.0
and for whom oral bisphosphonates are unsuitable.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 10
EXCIPIENTS: May contain Sorbitol
Denosumab 60 mg per 1 ml Prolia 60mg/1ml solution for injection
pre-filled syringes | 1 pre-filled disposable injection P £183.00 DT
Denosumab 70 mg per 1 ml Xgeva 120mg/1.7ml solution for
injection vials | 1 vial P £309.86 DT = £309.86
DOPAMINERGIC DRUGS › DOPAMINE RECEPTOR
Bromocriptine p. 419 is used for the treatment of
galactorrhoea, and for the treatment of prolactinomas (when
it reduces both plasma prolactin concentration and tumour
size). Bromocriptine also inhibits the release of growth
hormone and is sometimes used in the treatment of
acromegaly, but somatostatin analogues (such as octreotide
Cabergoline p. 421 has similar side-effects to
bromocriptine, however patients intolerant of bromocriptine
may be able to tolerate cabergoline (and vice versa).
Quinagolide below has actions and uses similar to those of
ergot-derived dopamine agonists, but its side-effects differ
Although bromocriptine and cabergoline are licensed to
suppress lactation, they are not recommended for routine
suppression (or for the relief of symptoms of postpartum
pain and engorgement) that can be adequately treated with
simple analgesics and breast support. If a dopamine-receptor
agonist is required, cabergoline is preferred. Quinagolide is
not licensed for the suppression of lactation.
l DRUG ACTION Quinagolide is a non-ergot dopamine D2
▶ Adult: Initially 25 micrograms once daily for 3 days,
dose to be taken at bedtime, increased in steps of
25 micrograms every 3 days; usual dose
75–150 micrograms daily, for doses higher than
300 micrograms daily increase in steps of
75–150 micrograms at intervals of not less than
l UNLICENSED USE Not licensed for the suppression of
l CAUTIONS Acute porphyrias p. 1058 . history of psychotic
illness . history of serious mental disorders
▶ Hyperprolactinemic patients In hyperprolactinaemic patients,
the source of the hyperprolactinaemia should be
established (i.e. exclude pituitary tumour before
l INTERACTIONS → Appendix 1: dopamine receptor agonists
▶ Common or very common Abdominal pain . appetite
congestion . nausea . oedema . syncope . vomiting
▶ Rare or very rare Acute psychosis . drowsiness
736 Dopamine responsive conditions BNF 78
l ALLERGY AND CROSS-SENSITIVITY Quinagolide should not
be used in patients with hypersensitivity to quinagolide
(does not apply to hypersensitivity to ergot alkaloids).
l CONCEPTION AND CONTRACEPTION Advise non-hormonal
contraception if pregnancy not desired.
l PREGNANCY Discontinue when pregnancy confirmed
unless medical reason for continuing (specialist advice
l BREAST FEEDING Suppresses lactation.
l HEPATIC IMPAIRMENT Manufacturer advises avoid (no
l RENAL IMPAIRMENT Avoid—no information available.
l MONITORING REQUIREMENTS Monitor blood pressure for a
few days after starting treatment and following dosage
Sudden onset of sleep Excessive daytime sleepiness and
sudden onset of sleep can occur with dopamine-receptor
Patients starting treatment with these drugs should be
warned of the risk and of the need to exercise caution
when driving or operating machinery. Those who have
experienced excessive sedation or sudden onset of sleep
should refrain from driving or operating machines until
these effects have stopped occurring.
Management of excessive daytime sleepiness should
focus on the identification of an underlying cause, such as
depression or concomitant medication. Patients should be
counselled on improving sleep behaviour.
Hypotensive reactions Hypotensive reactions can be
disturbing in some patients during the first few days of
treatment with dopamine-receptor agonists, particular
care should be exercised when driving or operating
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 10, 21
▶ Quinagolide (Non-proprietary)
Quinagolide 50microgram tablets and Quinagolide 25microgram
tablets | 6 tablet P £30.00–£37.50 DT = £37.49
Quinagolide (as Quinagolide hydrochloride)
25 microgram Quinagolide 25microgram tablets | 3 tablet P s
Quinagolide (as Quinagolide hydrochloride)
50 microgram Quinagolide 50microgram tablets | 3 tablet P s
Quinagolide (as Quinagolide hydrochloride)
75 microgram Quinagolide 75microgram tablets | 30 tablet P £75.00 DT = £75.00
▶ Norprolac (Ferring Pharmaceuticals Ltd)
Quinagolide (as Quinagolide hydrochloride)
25 microgram Norprolac 25microgram tablets | 3 tablet P s
Quinagolide (as Quinagolide hydrochloride)
50 microgram Norprolac 50microgram tablets | 3 tablet P s
Danazol p. 742 is licensed for the treatment of endometriosis
and for the relief of severe pain and tenderness in benign
fibrocystic breast disease where other measures have proved
unsatisfactory. It may also be effective in the long-term
management of hereditary angioedema[unlicensed
Cetrorelix below and ganirelix p. 738 are luteinising
hormone releasing hormone antagonists, which inhibit the
release of gonadotrophins (luteinising hormone and follicle
stimulating hormone). They are used in the treatment of
infertility by assisted reproductive techniques.
Gonadorelin analogues are used in the treatment of
endometriosis, precocious puberty, infertility, male
hypersexuality with severe sexual deviation, anaemia due to
uterine fibroids (together with iron supplementation), breast
cancer, prostate cancer and before intra-uterine surgery. Use
of leuprorelin acetate and triptorelin for 3 to 4 months
before surgery reduces the uterine volume, fibroid size and
Once any serious underlying cause for breast pain has been
ruled out, most women will respond to reassurance and
reduction in dietary fat; withdrawal of an oral contraceptive
or of hormone replacement therapy may help to resolve the
Mild, non-cyclical breast pain is treated with simple
analgesics; moderate to severe pain, cyclical pain or
symptoms that persist for longer than 6 months may require
Danazol is licensed for the relief of severe pain and
tenderness in benign fibrocystic breast disease which has not
Tamoxifen p. 953 may be a useful adjunct in the treatment
of mastalgia [unlicensed indication] especially when
symptoms can definitely be related to cyclic oestrogen
production; it may be given on the days of the cycle when
Treatment for breast pain should be reviewed after
6 months and continued if necessary. Symptoms recur in
about 50% of women within 2 years of withdrawal of therapy
PITUITARY AND HYPOTHALAMIC HORMONES
AND ANALOGUES › ANTI-GONADOTROPHINRELEASING HORMONES
Adjunct in the treatment of female infertility (initiated
▶ Adult (female): 250 micrograms once daily, dose to be
administered in the morning, starting on day 5 or 6 of
ovarian stimulation with gonadotrophins (or each
evening starting on day 5 of ovarian stimulation),
continue throughout administration of gonadotrophin
including day of ovulation induction (or evening before
ovulation induction), dose to be injected into the lower
▶ Common or very common Ovarian hyperstimulation
▶ Uncommon Headache . hypersensitivity . nausea
l PREGNANCY Avoid in confirmed pregnancy.
l HEPATIC IMPAIRMENT Manufacturer advises use with
caution—no information available.
l RENAL IMPAIRMENT Avoid in moderate or severe renal
BNF 78 Gonadotrophin responsive conditions 737
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder and solvent for solution for injection
▶ Cetrotide (Merck Serono Ltd)
Cetrorelix (as Cetrorelix acetate) 250 microgram Cetrotide
250microgram powder and solvent for solution for injection vials |
Adjunct in the treatment of female infertility (initiated
▶ Adult: 250 micrograms once daily, dose to be
administered in the morning (or each afternoon)
starting on day 5 or day 6 of ovarian stimulation with
gonadotrophins, continue throughout administration
of gonadotrophins including day of ovulation
induction (if administering in afternoon, give last dose
in afternoon before ovulation induction), dose to be
injected preferably into the upper leg (rotate injection
▶ Common or very common Skin reactions
▶ Uncommon Headache . malaise . nausea
▶ Rare or very rare Dyspnoea . facial swelling . hypersensitivity
▶ Frequency not known Abdominal distension . ovarian
hyperstimulation syndrome . pelvic pain
l PREGNANCY Avoid in confirmed pregnancy—toxicity in
l BREAST FEEDING Avoid—no information available.
l HEPATIC IMPAIRMENT Manufacturer advises avoid in
moderate to severe impairment (no information available).
l RENAL IMPAIRMENT Avoid in moderate to severe renal
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Fyremadel (Ferring Pharmaceuticals Ltd)
Ganirelix 500 microgram per 1 ml Fyremadel
PITUITARY AND HYPOTHALAMIC HORMONES
AND ANALOGUES › GONADOTROPIN-RELEASING
l DRUG ACTION Administration of gonadorelin analogues
produces an initial phase of stimulation; continued
administration is followed by down-regulation of
gonadotrophin-releasing hormone receptors, thereby
reducing the release of gonadotrophins (follicle
stimulating hormone and luteinising hormone) which in
turn leads to inhibition of androgen and oestrogen
▶ BY INTRANASAL ADMINISTRATION
▶ Adult: 300 micrograms 3 times a day maximum
duration of treatment 6 months (do not repeat), to be
started on days 1 or 2 of menstruation; administer one
150 microgram spray into each nostril
Pituitary desensitisation before induction of ovulation by
gonadotrophins for in vitro fertilisation (under expert
▶ Adult: 200–500 micrograms once daily, increased if
necessary up to 500 micrograms twice daily, starting in
early follicular phase (day 1) or, after exclusion of
pregnancy, in midluteal phase (day 21) and continued
until down-regulation achieved (usually 1–3 weeks)
then maintained during gonadotrophin administration
(stopping gonadotrophin and buserelin on
administration of chorionic gonadotrophin at
appropriate stage of follicular development)
▶ BY INTRANASAL ADMINISTRATION
▶ Adult: 150–300 micrograms 4 times a day,
(150 micrograms equivalent to one spray), to be
administered during waking hours. Start in early
follicular phase (day 1) or, after exclusion of
pregnancy, in the midluteal phase (day 21) and
continued until down-regulation achieved (usually
about 2–3 weeks) then maintained during
gonadotrophin administration (stopping
gonadotrophin and buserelin on administration of
chorionic gonadotrophin at appropriate stage of
▶ INITIALLY BY SUBCUTANEOUS INJECTION
▶ Adult: 500 micrograms every 8 hours for 7 days, then
(by intranasal administration) 200 micrograms 6 times
a day, (a single 100 microgram spray to be administered
▶ When used for pituitary desensitisation Hormone dependent
tumours . undiagnosed vaginal bleeding
l CAUTIONS Depression . diabetes . hypertension . patients
with metabolic bone disease (decrease in bone mineral
density can occur). polycystic ovarian disease
▶ Common or very common Depression . mood altered
interval prolongation . sexual dysfunction . shock . skin
degeneration . vision disorders . vomiting . vulvovaginal
SIDE-EFFECTS, FURTHER INFORMATION During the initial
stage (1–2 weeks) increased production of testosterone
may be associated with progression of prostate cancer. In
738 Gonadotrophin responsive conditions BNF 78
susceptible patients this tumour ‘flare’ may cause spinal
cord compression, ureteric obstruction or increased bone
l CONCEPTION AND CONTRACEPTION Non-hormonal, barrier
methods of contraception should be used during entire
treatment period. Pregnancy should be excluded before
treatment, the first injection should be given during
menstruation or shortly afterwards or use barrier
contraception for 1 month beforehand.
l DIRECTIONS FOR ADMINISTRATION
▶ With intranasal use Avoid use of nasal decongestants before
and for at least 30 minutes after treatment.
▶ With subcutaneous use Rotate injection site to prevent
l PATIENT AND CARER ADVICE Patients or carers should be
given advice on how to administer buserelin nasal spray.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Buserelin (as Buserelin acetate) 1 mg per 1 ml Suprecur
5.5mg/5.5ml solution for injection vials | 2 vial P £33.02
Buserelin (as Buserelin acetate) 1 mg per 1 ml Suprefact
5.5mg/5.5ml solution for injection vials | 2 vial P £34.37
Buserelin (as Buserelin acetate) 150 microgram per
1 dose Suprecur 150micrograms/dose nasal spray | 168 dose P £105.16
Buserelin (as Buserelin acetate) 100 microgram per
1 dose Suprefact 100micrograms/dose nasal spray | 336 dose P £122.24
l DRUG ACTION Administration of gonadorelin analogues
produces an initial phase of stimulation; continued
administration is followed by down-regulation of
gonadotrophin-releasing hormone receptors, thereby
reducing the release of gonadotrophins (follicle
stimulating hormone and luteinising hormone) which in
turn leads to inhibition of androgen and oestrogen
Locally advanced prostate cancer as an alternative to
surgical castration | Adjuvant treatment to radiotherapy
or radical prostatectomy in patients with high-risk
localised or locally advanced prostate cancer |
Neoadjuvant treatment prior to radiotherapy in patients
with high-risk localised or locally advanced prostate
cancer | Metastatic prostate cancer
▶ Adult: 10.8 mg every 12 weeks, to be administered into
Locally advanced prostate cancer as an alternative to
surgical castration | Adjuvant treatment to radiotherapy
or radical prostatectomy in patients with high-risk
localised or locally advanced prostate cancer |
Neoadjuvant treatment prior to radiotherapy in patients
with high-risk localised or locally advanced prostate
cancer | Metastatic prostate cancer | Advanced breast
cancer | Oestrogen-receptor-positive early breast cancer
▶ Adult: 3.6 mg every 28 days, to be administered into
▶ Adult: 3.6 mg every 28 days maximum duration of
treatment 6 months (do not repeat), to be administered
into the anterior abdominal wall
Endometrial thinning before intra-uterine surgery
▶ Adult: 3.6 mg, dose may be repeated after 28 days if
uterus is large or to allow flexible surgical timing, to be
administered into the anterior abdominal wall
Before surgery in women who have anaemia due to
▶ Adult: 3.6 mg every 28 days maximum duration of
treatment 3 months, to be given with supplementary
iron, to be administered into the anterior abdominal
Pituitary desensitisation before induction of ovulation by
gonadotrophins for in vitro fertilisation (after exclusion
of pregnancy) (under expert supervision)
administered (stopping gonadotrophin on
administration of chorionic gonadotrophin at
appropriate stage of follicular development), to be
administered into the anterior abdominal wall
l CONTRA-INDICATIONS Undiagnosed vaginal bleeding . use
longer than 6 months in endometriosis (do not repeat)
l CAUTIONS Depression . diabetes . hypertension . patients
with metabolic bone disease (decrease in bone mineral
density can occur). polycystic ovarian disease .risk of
spinal cord compression in men .risk of ureteric
impaired . gynaecomastia . headache . heart failure . hot
dysfunction . skin reactions . spinal cord compression . vulvovaginal disorders . weight increased
▶ Uncommon Hypercalcaemia (in women). ureteral
disorder. uterine leiomyoma degeneration . voice
alteration . vomiting . vulvovaginal infection . withdrawal
SIDE-EFFECTS, FURTHER INFORMATION Tumour flare can
occur when androgen deprivation therapy is initiated.
BNF 78 Gonadotrophin responsive conditions 739
l CONCEPTION AND CONTRACEPTION Non-hormonal, barrier
methods of contraception should be used during entire
treatment period. Pregnancy should be excluded before
treatment, the first injection should be given during
menstruation or shortly afterwards or use barrier
contraception for 1 month beforehand.
l MONITORING REQUIREMENTS Men at risk of tumour ‘flare’
should be monitored closely during the first month of
l DIRECTIONS FOR ADMINISTRATION Rotate injection site to
prevent atrophy and nodule formation.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Zoladex (AstraZeneca UK Ltd)
Goserelin (as Goserelin acetate) 3.6 mg Zoladex 3.6mg implant
SafeSystem pre-filled syringes | 1 pre-filled disposable injection P £70.00 DT = £70.00
▶ Zoladex LA (AstraZeneca UK Ltd)
Goserelin (as Goserelin acetate) 10.8 mg Zoladex LA 10.8mg
implant SafeSystem pre-filled syringes | 1 pre-filled disposable
injection P £235.00 DT = £235.00
l DRUG ACTION Administration of gonadorelin analogues
produces an initial phase of stimulation; continued
administration is followed by down-regulation of
gonadotrophin-releasing hormone receptors, thereby
reducing the release of gonadotrophins (follicle
stimulating hormone and luteinising hormone) which in
turn leads to inhibition of androgen and oestrogen
Locally advanced prostate cancer as an alternative to
surgical castration | Adjuvant treatment to radiotherapy
or radical prostatectomy in patients with high-risk
localised or locally advanced prostate cancer | Metastatic
▶ Adult: 11.25 mg every 3 months
▶ Adult: Initially 11.25 mg for 1 dose, dose to be given as
a single dose in first 5 days of menstrual cycle, then
11.25 mg every 3 months for maximum 6 months
Locally advanced prostate cancer as an alternative to
surgical castration | Adjuvant treatment to radiotherapy
or radical prostatectomy in patients with high-risk
localised or locally advanced prostate cancer | Metastatic
▶ BY SUBCUTANEOUS INJECTION, OR BY INTRAMUSCULAR
▶ BY SUBCUTANEOUS INJECTION, OR BY INTRAMUSCULAR
▶ Adult: Initially 3.75 mg for 1 dose, dose to be given as a
single dose in first 5 days of menstrual cycle, then
3.75 mg every month for maximum 6 months (course
Endometrial thinning before intra-uterine surgery
▶ BY SUBCUTANEOUS INJECTION, OR BY INTRAMUSCULAR
▶ Adult: Initially 3.75 mg for 1 dose, dose to be given as a
single dose between day 3 and 5 of menstrual cycle,
Reduction of size of uterine fibroids and of associated
▶ BY SUBCUTANEOUS INJECTION, OR BY INTRAMUSCULAR
▶ Adult: Initially 3.75 mg every month usually for
▶ When used for endometriosis use longer than 6 months (do
mineral density can occur).risk of spinal cord
compression in men with prostate cancer.risk of ureteric
obstruction in men with prostate cancer
▶ Uncommon Alopecia . diarrhoea . fever. myalgia . palpitations . visual impairment. vomiting
▶ Rare or very rare Haemorrhage
SIDE-EFFECTS, FURTHER INFORMATION In prostate cancer,
during the initial stage (1–2 weeks) increased production
of testosterone may be associated with progression of
prostate cancer. In susceptible patients this tumour ‘flare’
may cause spinal cord compression, ureteric obstruction or
l CONCEPTION AND CONTRACEPTION Non-hormonal, barrier
methods of contraception should be used during entire
treatment period. Pregnancy should be excluded before
treatment, the first injection should be given during
menstruation or shortly afterwards or use barrier
contraception for 1 month beforehand.
l PREGNANCY Avoid—teratogenic in animal studies.
▶ Men at risk of tumour ‘flare’ should be monitored closely
during the first month of therapy.
l DIRECTIONS FOR ADMINISTRATION Rotate injection site to
prevent atrophy and nodule formation.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Powder and solvent for suspension for injection
▶ Prostap 3 DCS (Takeda UK Ltd)
Leuprorelin acetate 11.25 mg Prostap 3 DCS 11.25mg powder and
solvent for suspension for injection pre-filled syringes | 1 pre-filled
disposable injection P £225.72 DT = £225.72
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