DOCSLIB.ORG

New Medicines Committee Briefing March 2015 Simbrinza

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
New Medicines Committee Briefing March 2015 Simbrinza 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. 1 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: 2 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) 3 4 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. 5 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
Load more

Recommended publications
  • Brimonidine Tartrate; Brinzolamide
    Contains Nonbinding Recommendations Draft Guidance on Brimonidine Tartrate ; Brinzolamide This draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA, or the Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the Office of Generic Drugs. Active Ingredient: Brimonidine tartrate; Brinzolamide Dosage Form; Route: Suspension/drops; ophthalmic Strength: 0.2%; 1% Recommended Studies: One study Type of study: Bioequivalence (BE) study with clinical endpoint Design: Randomized (1:1), double-masked, parallel, two-arm, in vivo Strength: 0.2%; 1% Subjects: Males and females with chronic open angle glaucoma or ocular hypertension in both eyes. Additional comments: Specific recommendations are provided below. ______________________________________________________________________________ Analytes to measure (in appropriate biological fluid): Not applicable Bioequivalence based on (95% CI): Clinical endpoint Additional comments regarding the BE study with clinical endpoint: 1. The Office of Generic Drugs (OGD) recommends conducting a BE study with a clinical endpoint in the treatment of open angle glaucoma and ocular hypertension comparing the test product to the reference listed drug (RLD), each applied as one drop in both eyes three times daily at approximately 8:00 a.m., 4:00 p.m., and 10:00 p.m. for 42 days (6 weeks). 2. Inclusion criteria (the sponsor may add additional criteria): a. Male or nonpregnant females aged at least 18 years with chronic open angle glaucoma or ocular hypertension in both eyes b.
    [Show full text]
  • Table 1. Glaucoma Medications: Mechanisms, Dosing and Precautions Brand Generic Mechanism of Action Dosage/Avg
    OPTOMETRIC STUDY CENTER Table 1. Glaucoma Medications: Mechanisms, Dosing and Precautions Brand Generic Mechanism of Action Dosage/Avg. % Product Sizes Side Effects Warnings Reduction CHOLINERGIC AGENTS Direct Pilocarpine (generic) Pilocarpine 1%, 2%, 4% Increases trabecular outflow BID-QID/15-25% 15ml Headache, blurred vision, myopia, retinal detachment, bronchiole constriction, Angle closure, shortness of breath, retinal narrowing of angle detachment Indirect Phospholine Iodide (Pfizer) Echothiophate iodide 0.125% Increases trabecular outflow QD-BID/15-25% 5ml Same as above plus cataractogenic iris cysts in children, pupillary block, Same as above, plus avoid prior to any increased paralysis with succinylcholine general anesthetic procedure ALPHA-2 AGONISTS Alphagan P (Allergan) Brimonidine tartrate 0.1%, 0.15% with Purite Decreases aqueous production, increases BID-TID/up to 26% 5ml, 10ml, 15ml Dry mouth, hypotension, bradycardia, follicular conjunctivitis, ocular irritation, Monitor for shortness of breath, dizziness, preservative uveoscleral outflow pruritus, dermatitis, conjunctival blanching, eyelid retraction, mydriasis, drug ocular redness and itching, fatigue allergy Brimonidine tartrate Brimonidine tartrate 0.15%, 0.2% Same as above Same as above 5ml, 10ml Same as above Same as above (generic) Iopidine (Novartis) Apraclonidine 0.5% Decreases aqueous production BID-TID/up to 25% 5ml, 10ml Same as above but higher drug allergy (40%) Same as above BETA-BLOCKERS Non-selective Betagan (Allergan) Levobunolol 0.25%, 0.5% Decreases
    [Show full text]
  • ALPHAGAN® 0.2% Safely and Effectively
    NDA 20613/S-031 Page 4 HIGHLIGHTS OF PRESCRIBING INFORMATION ___________ ___________ ADVERSE REACTIONS Most common adverse reactions occurring in These highlights do not include all the information needed approximately 10 to 30% of patients receiving brimonidine to use ALPHAGAN® 0.2% safely and effectively. See full ophthalmic solution 0.2% included oral dryness, ocular prescribing information for ALPHAGAN® 0.2%. hyperemia, burning and stinging, headache, blurring, foreign body sensation, fatigue/drowsiness, conjunctival ALPHAGAN® (brimonidine tartrate ophthalmic solution) follicles, ocular allergic reactions, and ocular pruritus. (6.1) 0.2% For Topical Ophthalmic Use To report SUSPECTED ADVERSE REACTIONS, Initial U.S. Approval: 1996 contact Allergan at 1-800-433-8871 or the FDA at 1­ 800-FDA-1088 or www.fda.gov/medwatch. _________ _________ INDICATIONS AND USAGE ___________ ____________ DRUG INTERACTIONS ALPHAGAN® 0.2% is an alpha adrenergic agonist indicated Antihypertensives/cardiac glycosides may lower blood for lowering intraocular pressure (IOP) in patients with open- pressure. (7.1) angle glaucoma or ocular hypertension. (1) ________ ________ Use with CNS depressants may result in an additive or DOSAGE AND ADMINISTRATION potentiating effect. (7.2) One drop in the affected eye(s), three times daily, Tricyclic antidepressants may potentially blunt the approximately 8 hours apart. (2) hypotensive effect of systemic clonidine. (7.3) _______ _______ DOSAGE FORMS AND STRENGTHS Monoamine oxidase inhibitors may result in increased Solution containing 2 mg/mL brimonidine tartrate. (3) hypotension. (7.4) _________ _____________ _______ ______ CONTRAINDICATIONS USE IN SPECIFIC POPULATIONS Neonates and infants (under the age of 2 years). (4.1) Use with caution in children > 2 years of age.
    [Show full text]
  • View Board, Austin, Texas, As Well As the Ethics Com- Pendent Examiner in the Same Room with the Same Instru- Mittee of Eye Center and Research, Aseer, Saudi Arabia
    Abdelkader and Kaufman Eye and Vision (2016) 3:31 DOI 10.1186/s40662-016-0065-3 RESEARCH Open Access Clinical outcomes of combined versus separate carbachol and brimonidine drops in correcting presbyopia Almamoun Abdelkader1* and Herbert E. Kaufman2 Abstract Background: To test and compare in a masked fashion the efficacy of using a parasympathomimetic drug (3% carbachol) and an alpha-2 agonist (0.2% brimonidine) in both combined and separate forms to create optically beneficial miosis to pharmacologically improve vision in presbyopia. Methods: A prospective, double-masked, randomized, controlled clinical trial was conducted. Ten naturally emmetropic and presbyopic subjects between 42 and 58 years old with uncorrected distance visual acuity of at least 20/20 in both eyes without additional ocular pathology were eligible for inclusion. All subjects received 3% carbachol and 0.2% brimonidine in both combined and separate forms, 3% carbachol alone and 0.2% brimonidine (control) alone in their non-dominant eye in a crossover manner with one week washout between tests. The subjects’ pupil sizes and both near and distance visual acuities will be evaluated pre- and post-treatment at 1, 2, 4, and 8 h, by a masked examiner at the same room illumination. Results: Statistically significant improvement in mean near visual acuity (NVA) was achieved in all subjects who received combined 3% carbachol and 0.2% brimonidine in the same formula compared with those who received separate forms or carbachol alone or brimonidine alone (P < 0.0001). Conclusion: Based on the data, the combined solution demonstrated greater efficacy than the other solutions that were tested.
    [Show full text]
  • Generic Drugs and Trade Name Equivalents: Alphabetized by Generic Name
    GENERIC DRUGS AND TRADE NAME EQUIVALENTS: ALPHABETIZED BY GENERIC NAME Generic Trade Generic Trade Generic Trade acetaminophen Tylenol escitalopram Lexapro niacin, nicotinic acid Niaspan, Slo-Niacin acetaminophen-codeine Tylenol #3 estrogen Premarin nitroglycerin Nitro-bid acetazolamide Diamox eszopiclone Lunesta nystatin Mycostatin acyclovir Zovirax ethambutol Myambutol ofloxacin Ocuflox albuterol Proventil, Ventolin eye vitamin supplement Ocuvite PreserVision olopatadine Patanol alendronate Fosamax famciclovir Famvir omeprazole Prilosec allopurinol Zyloprim felodipine Plendil paraffin-mineral oil Lacri-Lube alprazolam Xanax fexofenadine Allegra paroxetine Paxil aminocaproic acid Amicar fexofenadine-pseudoephedrine Allegra-D pegaptanib Macugen amiodarone Cordarone finasteride Propecia, Proscar peginterferon alfa-2a Pegasys amitryptyline Elavil fluconazole Diflucan peginterferon alfa-2b PegIntron amlodipine Norvasc flunisolide AeroBid pemirolast potassium Alamast amoxicillin Amoxil, Dispermox fluorometholone FML phenytoin Dilantin amoxicillin-clavulanate Augmentin fluorouracil Efudex pilocarpine IsoptoCarpine, Pilocar apraclonidine Iopidine fluoxetine Prozac piroxicam Feldene AREDS formula PreserVision flutamide Eulexin polymyxin B-bacitracin Polysporin atenolol Tenormin fluticasone Flovent, Flonase polymyxin B-bacitracin-neomycin Neosporin (ointment) atorvastatin Lipitor folinic acid Folixor polymyxin B-neomycin-gramicidin Neosporin (suspension) azathioprine Imuran foscarnet Foscavir potassium chloride Micro-K, K-Dur, Klor-Com azelastine
    [Show full text]
  • COMBIGAN® EYE DROPS (Brimonidine Tartrate 2.0 Mg Per Ml and Timolol (As Maleate) 5.0 Mg Per Ml)
    COMBIGAN® EYE DROPS (brimonidine tartrate 2.0 mg per mL and timolol (as maleate) 5.0 mg per mL) Consumer Medicine Information What is in this leaflet aware of this gradual loss of sight. any of the ingredients listed at Sometimes even normal eye the end of this leaflet, some This leaflet answers some common pressure is associated with damage symptoms of an allergic reaction questions about COMBIGAN® eye to the back of the eye. include skin rash, itching, drops. It does not contain all the There are usually no symptoms of shortness of breath or swelling available information. It does not glaucoma. The only way of of the face, lips or tongue, which take the place of talking to your knowing that you have glaucoma is may cause difficulty in doctor or pharmacist. to have your eye pressure, optic swallowing or breathing All medicines have risks and nerve and visual field checked by an • you are taking monoamine benefits. Your doctor has weighed eye specialist or optometrist. If oxidase antidepressant the risks of you using glaucoma is not treated it can lead medication COMBIGAN® eye drops against to serious problems, including total • you have bronchospasm, the benefits they expect it will have blindness. In fact, untreated bronchial asthma or have a for you. glaucoma is one of the most history of bronchial asthma or common causes of blindness. other lung disease If you have any concerns about using this medicine, ask your doctor COMBIGAN® eye drops lower the • you have a severe or unstable or or pharmacist. pressure in the eye by decreasing uncontrolled heart condition Keep this leaflet with the the fluid produced and helping the • the seal around the cap is broken medicine.
    [Show full text]
  • Marrakesh Agreement Establishing the World Trade Organization
    No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX
    [Show full text]
  • Safety and Efficacy of SIMBRINZA BID As an Adjunctive to DUOTRAV
    Alcon - Business Use Only Protocol - Clinical Effective Date: 10-Apr-2017 Document: TDOC-0051572 Version: 2.0; Most-Recent; Effective; CURRENT Status: Effective Page 1 of 71 a Novartis company Short Title Safety and Efficacy of SIMBRINZA BID as an Adjunctive to DUOTRAV Long Title Safety and Efficacy with Twice Daily Brinzolamide 1% / Brimonidine 0.2% (SIMBRINZA) as an Adjunctive Therapy to Travoprost 0.004% / Timolol 0.5% (DUOTRAV) Protocol Number: GLJ576-P001/ NCT02730871 Study Phase: 4 Sponsor Name and Alcon Research, Ltd. Address: 6201 South Freeway Fort Worth, Texas 76134-2099 Investigational Product: SIMBRINZA Brinzolamide 1% (10 mg/mL)/Brimonidine 0.2% (2 mg/mL) eye drops suspension US IND# / EudraCT 2016-000176-20 Indication Studied: Ocular Hypertension Open Angle Glaucoma Printed By: Print Date: Alcon - Business Use Only Protocol - Clinical Effective Date: 10-Apr-2017 Document: TDOC-0051572 Version: 2.0; Most-Recent; Effective; CURRENT Status: Effective Page 2 of 71 Investigator Agreement: I have read the clinical study described herein, recognize its confidentiality, and agree to conduct the described trial in compliance with Good Clinical Practices (GCP), the ethical principles contained within the Declaration of Helsinki, this protocol, and all applicable regulatory requirements. Additionally, I will comply with all procedures for data recording and reporting, will permit monitoring, auditing, and inspection of my research center, and will retain all records until notified by the Sponsor. Principal Investigator: Signature Date Name: Address: Printed By: Print Date: Alcon - Business Use Only Protocol - Clinical Effective Date: 10-Apr-2017 Document: TDOC-0051572 Version: 2.0; Most-Recent; Effective; CURRENT Status: Effective Page 3 of 71 1 SYNOPSIS Sponsor: Alcon Research, Ltd.
    [Show full text]
  • Brimonidine Tartrate Ophthalmic Solution 0.025%) on Palpebral Fissure Height
    Protocol Title: The effect of LumifyTM (Brimonidine Tartrate Ophthalmic Solution 0.025%) on palpebral fissure height. Protocol Version: Version 1 27 September 2018 Principal Investigator: Wendy Lee, MD NCT Number: NCT03782701 1) Protocol Title The effect of LumifyTM (Brimonidine Tartrate Ophthalmic Solution 0.025%) on palpebral fissure height. 2) Objectives* Aim 1: To determine the in vivo effect of LumifyTM (Brimonidine Tartrate Ophthalmic Solution 0.025%) on palpebral fissure height. Hypothesis: We hypothesize application of LumifyTM Brimonidine Tartrate Ophthalmic Solution 0.025% will cause an increase in subjects’ palpebral fissure height. 3) Background* Eyelid ptosis most commonly results from malfunctioning levator palpebrae superior muscle or Müller’s muscle. Müller’s muscle, a smooth muscle with a predominance of - 1D adrenergic receptors, contracts in response to sympathetic stimulation or topical adrenergic agonists. (Skibell 2007) Therefore, topical ocular administration of compounds that agonize adrenergic receptors causes an increase in interpalpebral fissure height via contraction of Müller’s muscle, which helps mitigate ptosis effects as well as lending the cosmetically beneficial effect of an eye that is more open. (Munden 1991) Compounds such as apraclonidine, a medication with mixed and 1 properties, have been shown to reverse ptosis caused by Horner’s syndrome and botulinum injections, and to help assess blepharoptosis preoperatively. Although the primary mechanism of apraclonidine is 2 agonism, which inhibits norepinephrine release from sympathetic nerve terminals, it is also a weak agonist, and allows for direct stimulation of smooth muscle. Multiple studies have observed the abilty of topical apraclonidine to increase palpebral fissure height by elevating the upper lid. (Kirkpatrick 2018, Yazici 2008, Koc 2005) Brimonidine is a very similar medication; like apraclonidine, it is a selective adrenergic agonist with a much weaker affinity for the receptor.
    [Show full text]
  • Drug Class Review Ophthalmic Beta-Adrenergic Antagonists
    Drug Class Review Ophthalmic Beta-Adrenergic Antagonists 52:40.08 Beta-Adrenergic Blocking Agents Betaxolol (Betoptic®) Carteolol (Ocupress®) Levobunolol (Betagan®) Metipranolol (Optipranolol®) Timolol (Betimol®, Timoptic®, others) Timolol/Brimonidine (Combigan®) Timolol/Dorzolamide (Cosopt®; Cosopt PF®) Final Report November 2015 Review prepared by: Melissa Archer, PharmD, Clinical Pharmacist Carin Steinvoort, PharmD, Clinical Pharmacist Gary Oderda, PharmD, MPH, Professor University of Utah College of Pharmacy Copyright © 2015 by University of Utah College of Pharmacy Salt Lake City, Utah. All rights reserved. Table of Contents Executive Summary ......................................................................................................................... 3 Introduction .................................................................................................................................... 5 Table 1. Glaucoma Therapies ................................................................................................. 6 Table 2. Summary of Agents .................................................................................................. 7 Disease Overview ...................................................................................................................... 10 Table 3. Summary of Current Clinical Practice Guidelines .................................................. 11 Pharmacology ..............................................................................................................................
    [Show full text]
  • Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act
    Updated June 07, 2021 Bulk Drug Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act Three categories of bulk drug substances: • Category 1: Bulk Drug Substances Under Evaluation • Category 2: Bulk Drug Substances that Raise Significant Safety Risks • Category 3: Bulk Drug Substances Nominated Without Adequate Support Updates to Categories of Substances Nominated for the 503B Bulk Drug Substances List1 • Add the following entry to category 2 due to serious safety concerns of mutagenicity, cytotoxicity, and possible carcinogenicity when quinacrine hydrochloride is used for intrauterine administration for non- surgical female sterilization: 2,3 o Quinacrine Hydrochloride for intrauterine administration • Revision to category 1 for clarity: o Modify the entry for “Quinacrine Hydrochloride” to “Quinacrine Hydrochloride (except for intrauterine administration).” • Revision to category 1 to correct a substance name error: o Correct the error in the substance name “DHEA (dehydroepiandosterone)” to “DHEA (dehydroepiandrosterone).” 1 For the purposes of the substance names in the categories, hydrated forms of the substance are included in the scope of the substance name. 2 Quinacrine HCl was previously reviewed in 2016 as part of FDA’s consideration of this bulk drug substance for inclusion on the 503A Bulks List. As part of this review, the Division of Bone, Reproductive and Urologic Products (DBRUP), now the Division of Urology, Obstetrics and Gynecology (DUOG), evaluated the nomination of quinacrine for intrauterine administration for non-surgical female sterilization and recommended that quinacrine should not be included on the 503A Bulks List for this use. This recommendation was based on the lack of information on efficacy comparable to other available methods of female sterilization and serious safety concerns of mutagenicity, cytotoxicity and possible carcinogenicity in use of quinacrine for this indication and route of administration.
    [Show full text]
  • Examining Implementation of the Compounding Quality Act”
    Written Statement for the Record Energy and Commerce Subcommittee on Health “Examining Implementation of the Compounding Quality Act” American Society of Cataract and Refractive Surgery 4000 Legato Road, Suite 700 Fairfax, Virginia 22033-4055 Tuesday, January 30, 2018 Chairman Burgess, Ranking Member Green, and members of the Subcommittee, the American Society of Cataract and Refractive Surgery (ASCRS) would like to thank the Energy and Commerce Subcommittee on Health for the opportunity to provide written testimony for the January 30, 2018, hearing titled “Examining Implementation of the Compounding Quality Act.” ASCRS is a medical specialty society representing nearly 9,000 ophthalmologists in the United States and abroad who share a particular interest in cataract and refractive surgical care. ASCRS members annually perform the vast majority of cataract procedures in the United States. We are very concerned that the Food & Drug Administration (FDA) is implementing Title I of the Drug Quality and Security Act (DQSA), the Compounding Quality Act, in a way that severely impacts patient access to compounded medications and creates an unnecessary burden on physician practices to secure compounded drugs. The practice of ophthalmology relies heavily on compounded drugs, and it is vital that physicians have an immediate supply of compounded drugs available in their offices to treat patients who present with emergent conditions. However, through the use of guidance documents—mostly in draft form, the FDA is restricting physicians’ access to medications, which ultimately denies patients timely and effective treatment options. The FDA’s implementation of the DQSA and use of draft guidance documents has created an environment of uncertainty for stakeholders.
    [Show full text]