l PREGNANCY Manufacturer advises avoid unless potential
benefit outweighs risk—toxicity in animal studies.
l BREAST FEEDING Present in milk in animal studies;
Changes to eye colour Before initiating treatment, patients
should be warned of a possible change in eye colour as an
increase in the brown pigment in the iris can occur, which
may be permanent; particular care is required in those
with mixed coloured irides and those receiving treatment
to one eye only. Changes in eyelashes and vellus hair can
also occur, and patients should also be advised to avoid
repeated contact of the eye drop solution with skin as this
can lead to hair growth or skin pigmentation.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Propylene glycol
▶ Travoprost (Non-proprietary)
Travoprost 40 microgram per 1 ml Travoprost 40micrograms/ml
eye drops | 2.5 ml P £3.24–£10.95 DT = £3.24
Travoprost 40 microgram per 1 ml Bondulc 40micrograms/ml eye
drops | 2.5 ml P £10.94 DT = £3.24
▶ Travatan (Novartis Pharmaceuticals UK Ltd)
Travoprost 40 microgram per 1 ml Travatan 40micrograms/ml eye
drops | 2.5 ml P £10.95 DT = £3.24
1186 Glaucoma and ocular hypertension BNF 78
The properties listed below are those particular to the
combination only. For the properties of the components
please consider, travoprost p. 1186, timolol maleate p. 1180.
Raised intra-ocular pressure in patients with open-angle
glaucoma or ocular hypertension when beta-blocker or
prostaglandin analogue alone not adequate
l INTERACTIONS → Appendix 1: beta blockers, non-selective
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Propylene glycol
▶ Travoprost with timolol (Non-proprietary)
Travoprost 40 microgram per 1 ml, Timolol (as Timolol maleate)
5 mg per 1 ml Travoprost 40micrograms/ml / Timolol 5mg/ml eye
drops | 2.5 ml P £13.95 DT = £13.95
▶ DuoTrav (Novartis Pharmaceuticals UK Ltd)
Travoprost 40 microgram per 1 ml, Timolol (as Timolol maleate)
5 mg per 1 ml DuoTrav 40micrograms/ml / 5mg/ml eye drops |
2.5 ml P £13.95 DT = £13.95 | 7.5 ml P £39.68
SYMPATHOMIMETICS › ALPHA2-ADRENOCEPTOR
l DRUG ACTION Apraclonidine is an alpha2-adrenoceptor
agonist that lowers intra-ocular pressure by reducing
aqueous humour formation. It is a derivative of clonidine.
▶ Adult: Apply 1 drop, 1 hour before laser procedure,
then 1 drop, immediately after completion of
procedure, 1% eye drops to be administered
Short-term adjunctive treatment of chronic glaucoma in
patients not adequately controlled by another drug
▶ Adult: Apply 1 drop 3 times a day usually for maximum
1 month, 0.5% eye drops to be administered, may not
provide additional benefit if patient already using two
drugs that suppress the production of aqueous humour
l CONTRA-INDICATIONS History of severe or unstable and
uncontrolled cardiovascular disease
l CAUTIONS Cerebrovascular disease . depression . heart
failure . history of angina . hypertension. loss of effect may
occur over time . Parkinson’s syndrome . Raynaud’s
syndrome .recent myocardial infarction .reduction in
vision in end-stage glaucoma (suspend treatment). severe
coronary insufficiency .thromboangiitis obliterans . vasovagal attack
l INTERACTIONS → Appendix 1: apraclonidine
▶ Common or very common Eye disorders
SIDE-EFFECTS, FURTHER INFORMATION Since absorption
may follow topical application, systemic effects may
occur– see clonidine hydrochloride p. 145.
Ocular intolerance Manufacturer advises withdrawal if
eye pruritus, ocular hyperaemia, increased lacrimation, or
oedema of the eyelids and conjunctiva occur.
l PREGNANCY Manufacturer advises avoid—no information
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises use with
caution and monitor, including close monitoring of
cardiovascular parameters—no information available.
l RENAL IMPAIRMENT Use with caution in chronic renal
▶ Monitor intra-ocular pressure and visual fields.
▶ Monitor for excessive reduction in intra-ocular pressure
Driving and skilled tasks Drowsiness may affect
performance of skilled tasks (e.g. driving).
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Benzalkonium chloride
▶ Iopidine (Novartis Pharmaceuticals UK Ltd)
Apraclonidine (as Apraclonidine hydrochloride) 5 mg per
1 ml Iopidine 5mg/ml eye drops | 5 ml P £10.88 DT = £10.88
Apraclonidine (as Apraclonidine hydrochloride) 10 mg per
1 ml Iopidine 1% eye drops 0.25ml unit dose | 24 unit dose P £77.85 DT = £77.85
Brimonidine tartrate 12-Jul-2017
l DRUG ACTION Brimonidine, an alpha2-adrenoceptor
agonist, is thought to lower intra-ocular pressure by
reducing aqueous humour formation and increasing
Raised intra-ocular pressure in open-angle glaucoma in
patients for whom beta-blockers are inappropriate |
Ocular hypertension in patients for whom beta-blockers
are inappropriate | Adjunctive therapy when intra-ocular
pressure is inadequately controlled by other
l INTERACTIONS → Appendix 1: brimonidine
▶ Uncommon Arrhythmias . nasal dryness . palpitations
▶ Rare or very rare Dyspnoea . hypertension. hypotension . insomnia . syncope
▶ Frequency not known Face oedema . vasodilation
l PREGNANCY Manufacturer advises use only if benefit
outweighs risk—limited information available.
l BREAST FEEDING Manufacturer advises avoid—no
BNF 78 Glaucoma and ocular hypertension 1187
l HEPATIC IMPAIRMENT Manufacturer advises caution (no
l RENAL IMPAIRMENT Manufacturer advises use with
Driving and skilled tasks Drowsiness may affect
performance of skilled tasks (e.g. driving).
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Benzalkonium chloride
▶ Brimonidine tartrate (Non-proprietary)
Brimonidine tartrate 2 mg per 1 ml Brimonidine 2mg/ml eye drops
Brimonidine 0.2% eye drops | 5 ml P £3.98 DT = £3.04
Brimonidine tartrate 2 mg per 1 ml Alphagan 0.2% eye drops | 5 ml P £6.85 DT = £3.04
▶ Brymont (Blumont Pharma Ltd)
Brimonidine tartrate 2 mg per 1 ml Brymont 2mg/ml eye drops | 5 ml P £1.50 DT = £3.04
Combinations available: Brinzolamide with brimonidine,
The properties listed below are those particular to the
combination only. For the properties of the components
please consider, brimonidine tartrate p. 1187, timolol
Raised intra-ocular pressure in open-angle glaucoma and
for ocular hypertension when beta-blocker alone not
l INTERACTIONS → Appendix 1: beta blockers, non-selective . brimonidine
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
EXCIPIENTS: May contain Benzalkonium chloride
Brimonidine tartrate 2 mg per 1 ml, Timolol (as Timolol maleate)
5 mg per 1 ml Combigan eye drops | 5 ml P £10.00 DT = £10.00
Age-related macular degeneration
Age-related macular degeneration is a progressive eye
condition that affects the central area of the retina (macula).
It occurs mainly in people aged 55 years and over and is a
common cause of vision loss. The progressive loss of central
vision affects the patient’s ability to see well enough to
recognise faces, drive, and to read and write. Although the
exact cause is unknown, known risk factors in addition to
increasing age include smoking and a family history of agerelated macular degeneration.
There are two types of age-related macular degeneration—
dry and wet. Dry (non-neovascular) age-related macular
degeneration progresses slowly as extensive wasting of
beneath and within the retina, and can lead to a rapid
deterioration of vision. Wet age-related macular
degeneration is further classified as wet-active (neovascular
lesions that may benefit from treatment) and wet-inactive
(neovascular disease with irreversible structural change).
treatment is initiated under specialist care.
Treatment is dependent on the stage and type of age-related
macular degeneration, with drug treatment only
recommended in patients with wet-active age-related
macular degeneration. Counselling and support, advice on
Smoking cessation p. 497, and use of visual aids is
recommended in all patients with age related macular
g An intravitreal anti-vascular endothelial growth
factor (anti-VEGF), such as aflibercept p. 1008, ranibizumab
p. 1190, or bevacizumab p. 862 [unlicensed use], is first-line
treatment for patients with wet-active age-related macular
degeneration who have a visual acuity between 6/12 and
6/96. If visual acuity is less than 6/96, anti-VEGF treatment
should only be given if the patient’s overall visual function is
likely to improve (e.g. if the affected eye is the patient’s
better-seeing eye). Anti-VEGF treatment should only be
administered by healthcare professionals experienced in the
use of intravitreal injections. See also National
funding/access decisions for aflibercept p. 1008 and
Treatment should be stopped if the patient develops
severe, progressive loss of visual acuity despite treatment, or
if the patient’s age-related macular degeneration develops
into wet-inactive with no prospect of visual function
improvement. A treatment-free period can be considered in
patients whose age-related macular degeneration appears to
Photodynamic therapy alone should not be given to
patients with wet-active age-related macular degeneration. It
can be given as an adjunct to anti-VEGF treatment as a
second-line option in the context of a randomised controlled
trial. Intravitreal corticosteroids are not recommended in
combination with anti-VEGF treatment because there is
limited evidence of benefit to a patient’s visual acuity.
Patients should be advised to attend routine sight tests,
self-monitor, and to report any changes in vision such as
appearance of grey patches or blurred vision, straight lines
appearing distorted, and objects appearing smaller than
Age-related macular degeneration. National Institute for
Health and Care Excellence. NICE guideline 82. January
ANTINEOVASCULARISATION DRUGS ›
VASCULAR ENDOTHELIAL GROWTH FACTOR
l DRUG ACTION Aflibercept is a recombinant fusion protein
that acts as a soluble decoy receptor and binds to vascular
endothelial growth factors A and B (VEGF-A, VEGF-B) and
placental growth factor (PlGF). Aflibercept inhibits the
activation of VEGF receptors and the proliferation of
endothelial cells, thereby inhibiting the growth of new
Neovascular (wet) age-related macular degeneration
▶ Adult: Initially 2 mg once a month for 3 months, then
2 mg every 2 months, review treatment frequency after
Macular oedema secondary to retinal vein occlusion
▶ Adult: Initially 2 mg once a month until maximum
visual acuity is achieved or there are no signs of disease
activity (discontinue treatment if no improvement in
Diabetic macular oedema (specialist use only)
▶ Adult: Initially 2 mg once a month for 5 months, then
maintenance 2 mg every 2 months, review treatment
frequency after 12 months (discontinue treatment if no
improvement in visual and anatomic outcomes)
Myopic choroidal neovascularisation (specialist use only)
▶ Adult: 2 mg for 1 dose, if visual or anatomic outcomes
indicate that disease persists, additional doses may be
administered; the interval between 2 doses should be
l CONTRA-INDICATIONS Clinical signs of irreversible
ischaemic visual function loss . ocular or periocular
infection . severe intra-ocular inflammation
l CAUTIONS Active systemic infection . diabetic patients
with uncontrolled hypertension . discontinue treatment if
stage 3 or 4 macular holes develop—consult product
literature for full details . discontinue treatment in the
event of a retinal break—consult product literature for full
details . discontinue treatment in the event of
rhegmatogenous retinal detachment—consult product
literature for full details . patients at risk of retinal pigment
epithelial tear. poorly controlled glaucoma .recent history
of myocardial infarction .recent history of stroke .recent
history of transient ischaemic attack
CAUTIONS, FURTHER INFORMATION Aflibercept is given by
intravitreal injection by specialists experienced in the
management of this condition. There is a potential risk of
arterial thromboembolic events and non-ocular
haemorrhage following the intravitreal injection of
vascular endothelial growth factor inhibitors.
Endophthalmitis can occur after intravitreal injections—
patients should be advised to report any signs of infection
l INTERACTIONS → Appendix 1: aflibercept
▶ Common or very common Cataract. eye discomfort. eye
disorders . eye inflammation . haemorrhage .retinal
pigment epithelial tear. vision disorders
l CONCEPTION AND CONTRACEPTION Manufacturer
recommends women use effective contraception during
and for at least 3 months after treatment.
l PREGNANCY Manufacturer advises avoid unless potential
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises caution in
severe impairment (no information available).
l MONITORING REQUIREMENTS Monitor intra-ocular
l DIRECTIONS FOR ADMINISTRATION For further information
on administration, consult product literature.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Aflibercept solution for injection for treating wet age-related
macular degeneration (July 2013) NICE TA294
Aflibercept solution for injection is recommended as an
option for treating wet age-related macular degeneration
. it is used in accordance with the recommendations for
ranibizumab in NICE TA 155 and
. the manufacturer provides aflibercept solution for
injection with the discount agreed in the patient access
www.nice.org.uk/guidance/TA294
▶ Aflibercept for treating visual impairment caused by macular
oedema secondary to central retinal vein occlusion (February
Aflibercept solution for injection is recommended as an
option for treating visual impairment caused by macular
oedema secondary to central retinal vein occlusion only if
the manufacturer provides aflibercept solution for
injection with the discount agreed in the patient access
www.nice.org.uk/guidance/TA305
▶ Aflibercept for treating diabetic macular oedema (July 2015)
Aflibercept solution for injection is recommended as an
option for treating visual impairment caused by diabetic
. the eye has a central retinal thickness of
400 micrometres or more at the start of treatment and
. the manufacturer provides aflibercept with the discount
agreed in the patient access scheme.
www.nice.org.uk/guidance/TA346
▶ Aflibercept for treating visual impairment caused by macular
oedema after branch retinal vein occlusion (September 2016)
Aflibercept is recommended, within its marketing
authorisation, as an option for treating visual impairment
in adults caused by macular oedema after branch retinal
vein occlusion, only if the manufacturer provides
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