New Medicines Committee Briefing March 2015 Simbrinza

Home , Brimonidine

New Medicines Committee Briefing March 2015 Simbrinza® (Brinzolamide 10mg + Brimonidine tartrate 2mg/ml) for treatment of elevated intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension.

Simbrinza® is to be reviewed for use within: Primary Care  Secondary Care  Summary:

 Simbrinza® is a combination of brinzolamide which is a carbonic anhydrase (CA-II) inhibitor and brimonidine which is an alpha-2 adrenergic agonist.

 Simbrinza® is licensed for the treatment of elevated IOP in adult patients with open-angle glaucoma or ocular hypertension whom failed on mono-therapy.

 Simbrinza® is administered twice daily in the affected eye(s).

 Simbrinza® is the first combination therapy which does not contain a beta-blocker.

 SMC has accepted Simbrinza® for use within NHS Scotland, as there is no significant additional cost associated with the combination product compared with its individual components.

 One trial indicated that fixed combination of Simbrinza® administered BD had a significantly greater IOP lowering effect compared to either brinzolamide 1% or brimonidine 0.2% alone and displayed a safety profile consistent with its individual components.

 Another trial noted Simbrinza® to be non-inferior to separate administration of brimonidine and brinzolamide less than 10 min apart to prevent wash out.

Formulary application:

Opthamology department:

Consultant submitting application: Mr Lynval Jones (Consultant Ophthalmologist, Glaucoma)

Clinical Director supporting application: Gareth Rowland (Clinical Director of Specialised Surgery)

Mr Jones has requested for Simbrinza® to be considered for inclusion in the North Staffordshire Joint Formulary for the treatment of elevated intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension who have not responded to monotherapy.

Mr Jones stated in his application that the evidence showed brinzolamide 1% and brimonidine 0.2% fixed combination administered BD had a significantly greater IOP-lowering effect than either brinzolamide or brimonidine alone and displayed a safety profile consistent with its individual components.

Mr Jones estimates that 100 new patients will be treated per year with Simbrinza® at a cost of £110.76 per patient. This cost he stated in his application will be met by reducing the expenditure for prescribing of Alphagan® (brimonidine) and brinzolamide separately.

Background:

Glaucoma is one of the most common ophthalmic conditions encountered in primary and secondary care. The World Health Organization estimated that in 2010 glaucoma accounted for 2% of visual impairment and 8% of global blindness. Disability adjusted life years attributable to glaucoma more than double between 1990 and 2010 due to the worldwide increase in the elderly population.

In the UK glaucoma accounts for up to 23% of the workload for Ophthalmologists’, and in the UK it accounts for 9-12% of registration of visual impairment in people over 65 years.1 With chronic open-angle glaucoma (COAG) being the most common, affecting an estimated 500,000 people in England.2

Glaucoma refers to a group of conditions with heterogeneous causes that result in damage to the optic nerve head and loss of visual field. It is usually associated with an increase in IOP above the normal value usually estimated at 21mmHg (mean15.5 +/- 2 standard deviations range 10-21).

Glaucoma can be split into subcategories based upon its aetiology:3

Angle closure glaucoma, the angle between the iris and the cornea is at least partially closed. This blocks the trabecular meshwork and prevents it from draining the intraocular fluid. As intraocular fluid continues to be produced, the pressure within the eye increases and the optic nerve is damaged. The onset may be acute or chronic, and there may be intermittent, prodromal attacks. Open angle glaucoma, the angle between the iris and the cornea is open. The onset is usually insidious, and the course chronic. It usually affects both eyes, but the signs of damage may be worse in one eye. The intraocular pressure is usually increased but can be within the normal range (normal tension glaucoma). Secondary glaucoma is classified as chronic open angle glaucoma caused by:

o Pseudoexfoliative glaucoma, Pigmentary glaucoma, Neovascular glaucoma, Uveitic glaucoma, Steroid-induced glaucoma, Angle-recession glaucoma and Childhood secondary glaucoma.

Ocular hypertension is a condition defined by consistently or recurrently elevated intraocular pressure (greater than 21 mmHg) and no signs of glaucoma.

Angle closure glaucoma is treated in an emergency setting however open-angle glaucoma and ocular hypertension require chronic management. The main aims of treatment is to reduce the IOP, by at least 20% or to a level below 18mmHg, via surgical, pharmacological or laser treatments.

This can be done pharmacologically using agents such as:

Prostoglandin analogues Beta-blockers Sympathomimetics (alpha agonists) Carbonic anhydrase inhibitors

Initial treatment should be started with a single agent normally a prostaglandin analogue if this fails to reduce the IOP sufficiently NICE recommend trial another single agent, if this also fails to reduce IOP multiple agents can be used or consideration for surgical intervention. 4

Current formulary status:

Glaucoma Treatment Algorithm APC Review: June 2011 11.6 TREATMENT OF GLAUCOMA  & November 2013 (Approved Prescribing Guidelines folder)

Miotics Pilocarpine 2 Sympathomimetics Brimonidine 2

Beta-blockers Betaxolol hydrochloride 2 Carteolol hydrochloride 2 Timolol maleate 2 Carbonic anhydrase inhibitors and systemic drugs Acetazolamide 2 Brinzolamide 2 Azarga® 2 Restriction: Initiation by Consultant Ophthalmologist only (Brinzolamide & Timolol) Dorzolamide 2 Prostaglandin analogues and prostamides Latanoprost 2 1st line prostaglandin analogue  MTRAC Bimatoprost 2 2nd line prostaglandin analogue after latanoprost  MTRAC Travoprost 2  MTRAC Xalacom® 2 (Latanoprost & Timolol) Ganfort® 2 2nd line after Xalacom® eye drops (Bimatoprost & Timolol)

Therapeutic class and mode of action:5

Simbrinza contains two active substances: brinzolamide and brimonidine tartrate. These two components lower intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT) by suppressing the formation of aqueous humour from the ciliary process in the eye. Although both brinzolamide and brimonidine lower IOP by suppressing aqueous humour formation, their mechanisms of action are different.

Brinzolamide acts by inhibiting the enzyme carbonic anhydrase (CA-II) in the ciliary epithelium that reduces the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport across the ciliary epithelium, resulting in decreased aqueous humour formation.

Brimonidine, an alpha-2 adrenergic agonist, inhibits the enzyme adenylate cyclase and suppresses the cAMP-dependent formation of aqueous humour. Additionally, administration of brimonidine results in an increase in uveoscleral outflow.

Licensed indication: 5

Decrease of elevated intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension for whom mono-therapy provides insufficient IOP reduction.

Dosage and administration:5

One drop twice daily to the affected eye(s)

Safety and adverse effects:5

Contraindications: Hypersensitivity to the active substance or to any of the excipients or to sulphonamides. Patients receiving monoamine oxidase (MOA) inhibitor therapy. Patents on antidepressants which affect noradrenergic transmission (e.g. tricyclic antidepressants and mianserin). Patients with severe renal impairment. Patients with hyperchloraemic acisdosis. Neonates and infants under the age of 2 years.

Caution:

Paediatric population

The safety and efficacy of Simbrinza® in children and adolescents aged 2 to 17 years has not been established. Symptoms of brimonidine overdose (including loss of consciousness, hypotension, hypotonia, bradycardia, hypothermia, cyanosis and apnoea) have been reported in neonates and infants receiving brimonidine eye drops as part of medical treatment of congenital glaucoma. Simbrinza® is therefore contraindicated in children below 2 years of age.

Treatment of children 2 years and above (especially in those in the 2-7 age range and/or weighing < 20 kg) is not recommended because of the potential for central nervous system-related side effects.

Cardiac disorders Following administration of Simbrinza®, small decreases in blood pressure were observed in some patients. Caution is advised when using medicinal products such as antihypertensives and/or cardiac glycosides concomitantly with Simbrinza® or in patients with severe or unstable and uncontrolled cardiovascular disease.

Simbrinza® should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension or thromboangiitis obliterans.

Mental alertness Oral carbonic anhydrase inhibitors may impair the ability to perform tasks requiring mental alertness and/or physical coordination in elderly patients. Simbrinza® is absorbed systemically and therefore this may occur with topical administration.

Systemic effects Simbrinza® contains brinzolamide, a sulphonamide inhibitor of carbonic anhydrase and, although administered topically, is absorbed systemically. The same types of adverse reactions that are attributable to sulphonamides may occur with topical administration. If signs of serious reactions or hypersensitivity occur, the use of this medicinal product should be discontinued.

Renal and hepatic impairment: Use with caution in patients with risk of renal impairment because of the possible risk of metabolic acidosis. Simbrinza® is contraindicated in patients with severe renal impairment

Simbrinza® has not been studied in patients with hepatic impairment; caution should be used in treating such patients

Effects on ability to drive and use machines

Simbrinza® may cause dizziness, fatigue and/or drowsiness, which may impair the ability to drive or use machines. Temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs at instillation the patient must wait until the vision clears before driving or using machines

Pregnancy There are no or limited amount of data from the use of Simbrinza® in pregnant women. Brinzolamide was teratogenic in rats, but not rabbits, following systemic administration. Animal studies with oral brimonidine do not indicate direct harmful effects with respect to reproductive toxicity. In animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent. Simbrinza® is not recommended during pregnancy and in women of child bearing potential not using contraception.

Breast-feeding It is unknown whether topical Simbrinza® is excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown that following oral administration, minimal levels of brinzolamide are excreted in breast milk. Brimonidine administered orally is excreted in breast milk. Simbrinza® should not be used by women nursing infants.

Fertility Nonclinical data do not show any effects of brinzolamide or brimonidine on fertility. There are no data on the effect of topical ocular administration of Simbrinza® on human fertility.

Undesirable effects:

The most common adverse reactions were ocular hyperaemia and ocular allergic type reactions occurring in approximately 6-7% of patients, and dysgeusia occurring in approximately 3% of patients.

Simbrinza® contains brinzolamide which is a sulphonamide inhibitor of carbonic anhydrase with systemic absorption. Gastrointestinal, nervous system, haematological, renal and metabolic effects are generally

6 associated with systemic carbonic anhydrase inhibitors. The same type of adverse reactions attributable to oral carbonic anhydrase inhibitors may occur with topical administration.

Adverse reactions commonly associated with the brimonidine component of Simbrinza® include the development of ocular allergic type reactions, fatigue and/or drowsiness, and dry mouth. The use of brimonidine has been associated with minimal decreases in blood pressure. Some patients who dosed with Simbrinza® experienced decreases in blood pressure similar to those observed with the use of brimonidine as monotherapy.

For additional information refer to the Summaries of Product Characteristics.

Drug Interactions:5

No specific drug interaction studies have been performed with Simbrinza®.

Simbrinza® is contraindicated in patients receiving monoamine oxidase inhibitors and patients on antidepressants which affect noradrenagic transmission (e.g. tricyclic antidepressants and mianserin), (see section 4.3). Tricyclic antidepressants may blunt the ocular hypotensive response of Simbrinza®.

Caution is advised due to the possibility of an additive or potentiating effect with CNS depressants (e.g. alcohol, barbiturates, opiates, sedatives, or anaesthetics).

No data on the level of circulating catecholamines after Simbrinza® administration are available. Caution, however, is advised in patients taking medicinal products which can affect the metabolism and uptake of circulating amines (e.g. chlorpromazine, methylphenidate, reserpine, serotonin-norepinephrine reuptake inhibitors).

Alpha adrenergic agonists (e.g. brimonidine tartrate), as a class, may reduce pulse and blood pressure. Caution is advised when using medicinal products such as antihypertensives and/or cardiac glycosides concomitantly with Simbrinza®.

Caution is advised when initiating (or changing the dose of) a concomitant systemic medicinal products (irrespective of pharmaceutical form) which may interact with α-adrenergic agonists or interfere with their activity i.e. agonists or antagonists of the adrenergic receptor (e.g. isoprenaline, prazosin). Brinzolamide is a carbonic anhydrase inhibitor and, although administered topically, is absorbed systemically. Acid-base disturbances have been reported with oral carbonic anhydrase inhibitors. The potential for interactions must be considered in patients receiving Simbrinza®.

There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and topical brinzolamide. The concomitant administration of Simbrinza® and oral carbonic anhydrase inhibitors is not recommended.

The cytochrome P-450 isozymes responsible for metabolism of brinzolamide include CYP3A4 (main), CYP2A6, CYP2B6, CYP2C8 and CYP2C9. It is expected that inhibitors of CYP3A4 such as ketoconazole, itraconazole, clotrimazole, ritonavir and troleandomycin will inhibit the metabolism of brinzolamide by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly. However, accumulation of brinzolamide is unlikely as renal elimination is the major route. Brinzolamide is not an inhibitor of cytochrome P-450 isozymes.

Presentation:5

8 mL round opaque low density polyethylene (LDPE) bottles with a LDPE dropper tip and white polypropylene screw cap (Drop-Tainer) containing 5 mL suspension.

Special precautions for storage:

This medicinal product does not require any special storage conditions.

Guidance:

Nice Guidance published:4 YES Nice CG 85, Glaucoma, Diagnosis and management of chronic open angle glaucoma and ocular hypertension, April 2009.

Treatment for people with ocular hypertension (OHT) or suspected COAG: Initially treatment is either a beta-blocker or a prostaglandin analogue depending on measurements of IOP, corneal thickness and age. If insufficient reductions in IOP offer alternative pharmacological treatment to prevent the risk of progression to sight loss (more than one medicine may be needed concurrently to achieve target IOP)

Offer a preservative-free preparation to people with an allergy to preservatives only if they are at a high risk of conversion to COAG. Also ensure their technique is sufficient to use the eye drops prescribed.

Treatment for people with COAG: Newly diagnosed patients with early or moderate COAG, and at risk of significant visual loss in their lifetime, initial treatment with a prostaglandin analogue is recommended. If fails to sufficiently reduce IOP offer alternative pharmacological treatment such as; beta-blocker, carbonic anhydrase inhibitor or sympathomimetic. Combination therapy may be required at this stage of management.

Consider offering people with COAG who are intolerant to a prescribed medication alternative pharmacological treatment or a preservative-free preparation if there is evidence that the person is allergic to the preservative. Also ensure their technique is sufficient to use the eye drops prescribed.

After offering treatment with two pharmacological agents, consider offering surgery with pharmacological augmentation (MMC or 5-FU) as indicated or laser trabeculoplasty.

SMC recommended use within NHS Scotland:6 YES

SMC stated that Simbrinza® is accepted for use within NHS Scotland following an abbreviated submission.

They also stated there is no significant additional cost associated with the combination product compared with the individual components and it allows patients to administer fewer drops.

All Wales Medicines Strategy Group (AWSG) NO

Regional Drug and Therapeutic Centre (RDTC): NO

European Glaucoma Society (EGS) guidelines:7 YES

The current European Glaucoma Society (EGS) guidelines recommend several classes of IOP-lowering agents as first-choice mono-therapy for glaucoma. This choice depends on the management strategy (taking into account the efficacy, safety, costs, adherence, quality of life and tolerability in the patient).

The EGS also recommends where treatment is insufficient, mono-therapy should be considered by the use of prostaglandin analogue as first line treatment. If at this stage in treatment it is ineffective at controlling the IOP then adjunctive treatment should be added to the therapy.

If more than two topical treatments are being tried and patients are still not achieving control of their disease, the EGS recommend other forms of therapy such as laser trabeculoplasty or surgery be considered.

MTRAC: NO

Cochrane Review: NO

Efficacy:

Twice- daily brinzolamide/brimonidine fixed combination versus brinzolamide or brimonidine in open angle glaucoma or ocular hypertension. 8

Summary: Brinzolamide 10mg (1%) and brimonidine 2mg(0.2%)/ ml fixed combination (BBFC) administered BD had a significantly greater IOP lowering effect than either brinzolamide 1% or brimonidine 0.2% alone and displayed a safety profile consistent with its individual components.

A multi-centre, randomized, double masked, six month phase 3 trail. A total of 560 patients with primary open angle glaucoma (POAG) or ocular hypertension (OH) who had insufficient IOP reduction with their current therapeutic regime or who were receiving ≥2 IOP lowering medications. The purpose of this trial was to compare the IOP lowering efficacy and safety of brinzolamide 1% and brimonidine 0.2% fixed combination with that of brinzolamide 1% and brimonidine 0.2% monotherapy all at BD dosing.

The primary end point was mean change in diunal IOP from baseline to month 3. Supportive endpoints included mean diurnal IOP change from baseline at week 2, week 6, and month 6: and mean IOP, mean IOP change from baseline, mean percentage IOP change from baseline, and percentage of patients with IOP < 18mmHg at week 2, week 6, month 3, and month 6 at each assessment time point ( 9am, 11 am, and 4pm). With one eye (the worse eye) been designated the “study eye”, if there was only one eye been treated this was designated the “study eye”.

The patients were all asked to discontinue their previous treatments and were asked to complete a wash out period. Then the eligible patients were randomized 1:1:1 at each investigational centre using an interactive web response system to receive BBFC or monotherapy for up to 6 months. This was conducted over 63 centres over the Asia-Pacific region.

The intention-to-treat (ITT) population compromised of 559 patients, 193 in the BBFC group, 191 in the brinzolamide 1% group and 175 in the brimonidine 0.2% group. The numbers of patients to complete the study were 160, 178, and 145 respectively, with a discontinuation rate of n=33, n=13, and n=30 respectively.

The IOP lowering efficacy of BBFC was superior to both brinzolamide and brimonidine alone on the basis of LS mean diurnal IOP change from baseline at the month 3; primary end point. The mean change from baseline for BBFC minus brinzolamide was -1.4mmHg; P<0.0001 and brimonidine was -1.5mmHg; P<0.0001. Overall, the results of the last observation carried forward sensitivity analysis were similar to those of the observed case evaluation. This also showed a LS mean difference with BBFC minus brinzolamide, - 1.5mmHg; p<0.0001 and brimonidine was -1.3mmhg; P < 0.0001.

The mean IOP values of BBFC vs brimonidine or brinzolamide was shown at all study visits and measurement points to be superior. The mean percentages of IOP reduction from baseline were 26.7% - 36.0% with BBFC, 22.4% - 29.7% for brinzolamide and 20.6% - 31.3% for brimonidine.

Saftey:

The safety profile of BBFC was consistent with the known safety profile of its individual components; BBFC did not pose any additional risk to patients relative to the individual components. The majority of adverse drug reactions were ocular side effects with a known association with brinzolamide or brimonidine. There were greater eyelid/conjunctiva changes in the BBFC and brimonidine groups (14% and 13.8%) than in the brinzolamide group (6.8%). The overall incidence of serious adverse events were numerically similar among treatment groups, BBFC n=5; brinzolamide n=2 and brimonidine n=3. The investigator reported that they were unrelated to the study medication.

Limitations The trial cannot compare the efficacy of BBFC with that of other fixed combination therapies or concomitant but separate administration of these individual IOP lowering agents. There is no direct comparison between BBFC and another dual combination IOP lowering therapy.

Randomised trial of brinzolamide/brimonidine versus brinzolamide plus brimonidine for open-angle glaucoma or ocular hypertension. 9

This was a prospective, phase 3 multicentre, double-masked, parallel group, non-inferiority trail conducted at 102 sites in Europe, central/south America, Australasia, India, Canada and USA over 6-months. The study evaluated the safety and efficacy of BD BBFC compared with BD Brinz+Brim in reducing IOP in patients with open-angle glaucoma or ocular hypertension who, in the medical opinion of the investigator examining the patient were insufficiently controlled on monotherapy or who were receiving multiple IOP lowering medications.

Inclusion criteria for the trial was, aged ≥ 18 years, diagnosed with open-angle glaucoma or ocular hypertension that was insufficiently controlled on monotherapy or being treated with multiple IOP lowering medications, mean IOP for ≥ 1 eye (same eye) were 24-36 mmHg at 9 a.m. and 21-36mmHg at 11a.m. during both eligibility visits post washout period.

Exclusion criteria included, pregnant/ nursing mothers, Schaffer angle grade <2 in either eye, cup-to-disc ratio >0.80 in either eye, sever central visual field loss, unable to safely discontinue IOP medication for washout period, chronic / recurrent severe inflammatory eye disease, ocular trauma ≤6 months prior to study, significant or progressive retinal disease, BCVA score worse than 55, intraocular surgery ≤ 6 months before study or laser treatment ≤ 3 months before, use of high dose (>1g daily) salicylate therapy ≤ 4 months before study, any other investigational agent ≤ 30 days before screening visit any contraindication to use of brimonidine or brinzolamide.

1190 patients were enrolled onto the trail and 890 were randomised post screening. BBFC n=451 and Brinz+Brim n=439. 85.4% (n=385) completed the trial for BBFC and 82.2% (n=361) for Brinz+Brim group. In the PP population, LS mean ± standard error (SE) diurnal IOP change from baseline at month 3 was - 8.5±0.16mmHg for patients receiving BBFC and -8.3±0.16mmHg for patients receiving Brinz+Brim. Mean between group difference, -0.1mmHG; 95% CI -0.5 to 0.2mmHg. Because the upper limit of the 95% CI of the between group difference was less than the pre-specified margin of 1.5mmHg, BBFC was demonstrated to be non-inferior to Brinz+Brim. The results were similar in the ITT population.

Decreases from baseline of over 8 mmHg were observed for LS mean diurnal IOP in both groups as early as week 2 and continued to the end of the study. The upper limits of the 95% CIs at all points were <1.5mmHg therefore BBFC was non-inferior to Brinz+Brim throughout the study. At all study visits and time points the mean IOP were similar in the BBFC and Brinz+Brim groups and ranged from 19.1 to 19.7 mmHg at 9 a.m. measurments and from 16.0 to 16.5 mmHg at 11 a.m. The patients achieving IOP <18mmHg was also similar with both treatments, at the time of peak morning efficacy 11 a.m., the percentage of patients with

IOP <18mmHg across study visits was 68.9-71.6% for those receiving BBFC and 65.8-71.6% for those receiving Brinz+Brim.

Safety profile of BBFC was consistent with that known for the safety profile of the individual components. Adverse drug reactions assessed as related to treatment were reported in a similar percentage of patients receiving BBFC 23.5% and Brinz+Brim 26.8%, of these reported the majority of them were local ocular side effects with known causal association with the individual components. The most common were hyperemia of the eye, visual disturbances, ocular allergic type reactions and ocular discomfort. Systemic ADRs reported in the study included dysgeusia, oral dryness and fatigue/drowsiness. Treatment was discontinued because of an AE in 13.3% of patients in the Brinz+Brim group and 10.6% in the BBFC group. No clinically meaningful alteration in other ocular or cardiovascular assessments was observed.

This study also showed that IOP reductions achieved with BD BBFC administration from baseline at 3 months (28.6-37.6%) was similar to that previously observed with TDS BBFC administration over similar morning time points at 3 months in a previous trial (approximately 24%-35%). Long term IOP reductions at 6 months were also similar with BD vs. TDS dosing of BBFC.

Twice daily BBFC was non-inferior to Brinz+Brim twice daily application for reducing elevated IOP in patients with open-angular glaucoma or ocular hypertension, and was not associated with any additional safety risks.

This study was funded by Alcon laboratories whom manufacture Simbrinza and 2 of the authors have received grants or personal fees from Alcon laboratories Inc.

Cost analysis:

Cost at UHNS per pack Cost in primary care Drug Strength Dose Pack Size (exc VAT) per pack* (exc VAT)

(Brinzolamide 10mg + Simbrinza® 1 drop BD 5ml £8.58 £9.23 Brimonidine 2mg /ml)

Azopt® (Brinzolamide 10mg/ml) 1 drop BD 5ml £5.00 £6.92 (Max TDS) Alphagan® (Brimonidine 2mg/ml) 1 drop BD 5ml £1.10 £2.26

Current spend for brinzolamide and brimonidine:

Expenditure for Dec13-Nov14:

NORTH UHNM Acute STOKE ON TRENT Medicine Medicine Description STAFFORDSHIRE CCG Trust CCG

BRIMONIDINE BRIMONIDINE 0.2% (2mg/ml) EYE DROPS (5mL) £213.54 £6,353.09 £4,751.19 BRINZOLAMIDE BRINZOLAMIDE 10mg/mL EYE DROPS (5mL) £4,152.64 £40,364.21 £41,380.78 SIMBRINZA BRINZOLAMIDE 10mg/mL + BRINMONIDINE 2mg/mL £25.70 £68.21 £25.58 TOTAL £4,391.88 £46,785.51 £46,157.55

References

1 King, Anthony. Azuara-Blanco, Augusto. Tuulonen, Anja. Glaucoma. British Medical Journal (BMJ), Clinical Review. 2013;346, 1-9.

2 Elain Mann. Treatment of open-angle glaucoma. The Pharmaceutical Journal. Clinical pharmacist, 1 Jan 2010.

3 Clinical Knowledge Summaries (CKS). Glaucoma; revised September 2010. Available at http://cks.nice.org.uk/glaucoma.

4 National Institute for Health and Care Excellence (NICE). Glaucoma: Diagnosis and management of chronic open angle glaucoma and ocular hypertension. April 2009, CG 85.

5 Summary of Product Charateristics (SPC). Simbrinza 10mg/ml+ 2mg/ml eye drops, suspension. Alcon Laboratories Ltd. Updated 7/8/14. Available at https://www.medicines.org.uk/emc/medicine/29083.

6 Scottish Medicines Consortium (SMC). Product update: Brinzolamide 10mg/ml and brimonidine tartrate 2mg/ml eye drops, suspension (simbrinza). Issued 10/10/14.

7 European Glaucoma Society (EGS). Terminology and guidelines for Glaucoma. 3rd edition 2008. Available at; www .eugs.org.

8 Aung, Tina. Et al. Twice daily brinzolamide/brimonidine fixed combination versus brinzolamide or brimonidine in open angle glaucoma or ocular hypertension. American Academy of Ophthalmology. Ophthalmology 2014 accepted article:10.1016/j optha 2014.06.22

9 Gandolfi, Sefano. Et al. Randomised trial of brinzolamide/brimonidine versus brinzolamide plus brimonidine for open angle glaucoma or ocular hypertension. Advances in Therapy, 2014, 31:1213-1227.

Produced by Richard Lewis Specialist Rotational Pharmacist Medicines Management University Hospital of North Midlands Royal Stoke Hospital Telephone: 01782 674542 e-mail: [email protected] Produced for use within the NHS. Not to be reproduced for commercial purposes.