Data from the recent therapeutic

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1 Getting started in therapeutics Part 8a What drugs will I prescribe and supply? Continuing our series on therapeutics in practice, Lucy Titcomb and Professor John Lawrenson review the range of ophthalmic drugs currently available to at all levels and those that may be used by future independent prescribers. C7749, two CET points suitable for, additional supply and supplementary prescribers Data from the recent therapeutic practice survey carried out by City University showed that community routinely managed a range of common non-sight-threatening ocular conditions using therapeutic agents available through the Medicines Act exemptions (Optician, July 27, 2007). Recent changes to medicines legislation have provided opportunities for to train for extended prescribing roles. For example, additional supply (AS) are able to use and supply further prescription-only medicines (POMs) from an additional supply list that includes the antimicrobial mixture, Polyfax (polymyxin B and bacitracin), anti-allergy drugs, a mucolytic and the non-steroidal anti-inflammatory drug (NSAID) diclofenac sodium. Optometrist supplementary prescribers are theoretically able to prescribe any licensed medicine, provided that the drug is listed in the patient s clinical management plan. While this prescribing model works for practitioners working in a hospital environment, it has limited scope in community optometric practice as a diagnosis has to be made by an independent prescriber and a clinical management plan has to be drawn up before treatment can begin. This limitation has been recognised by the Department of Health which recently announced that will soon be able to train as independent prescribers of any licensed medicine for ocular conditions affecting the eye and the surrounding tissues, within their recognised area of expertise and competence. Before prescribing any medication it is important that the prescriber is aware of the licensed indications of the particular drug, its contraindications, dosage and potential side-effects. This article provides an overview of the major classes of therapeutic agent used in ophthalmic practice: Antimicrobials Corticosteroids and other This monthly series is designed to provide with a practical, step-by-step guide to getting started in therapeutic practice and will seek to answer the following questions: How should I plan my strategy? What training will I need? What equipment will I need? What conditions should I manage and treat initially? What conditions can I manage and treat with training? How do therapeutics fit in to contact lens practice? What drugs will I prescribe and treat? What are the legal and ethical considerations? How should I market my therapeutics business? The series is compiled by Alison Ewbank with input from Bill Harvey, John Lawrenson and Nick Rumney. anti-inflammatories. Emphasis will be placed on those drugs currently available to (entry level and AS) as well as drugs that can be appropriately used by supplementary prescribers or future independent prescribers. Antimicrobials Antimicrobials include agents active against bacteria, fungi, viruses, protozoa and other parasites. The aim of antimicrobial therapy is to kill (for a microbicidal agent) or stop the growth of (for a microbistatic agent) the pathogen, known as the prokaryote, with minimal adverse effects on the host, the eukaryote. Choice of a drug delivery system to administer the drug is dependent upon the concentration of the antimicrobial required at the site of the infection. Thus eye drops are suitable for the treatment of, while intravitreal injections are necessary for endophthalmitis and systemically administered agents for the treatment of ocular toxoplasmosis. This article will concentrate on commercially available topical antimicrobials (Table 1) with special reference to those available to the optometrist. Antibacterials This group, covered in section of the British National Formulary (BNF), contains the following drugs: Aminoglycosides (gentamicin and neomycin) Bacitracin Chloramphenicol Fluoroquinolones (ciprofloxacin, levofloxacin and ofloxacin) Fusidic acid Gramicidin Polymyxin B Propamidine and Dibrompropamidine. Aminoglycosides The aminoglycosides are bactericidal antibiotics derived from fungal isolates. They inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit. Their antibacterial spectrum varies, with gentamicin possessing a wide spectrum of activity being effective against both Gram-positive and Gram-negative organisms, including Peudomonas aeruginosa, while neomycin is active against Gram-negative bacteria but not P aeruginosa. Neomycin, therefore, is rarely used alone but is found in combination with agents active against Gram-positive bacteria such as gramicidin and those with activity against P aeruginosa such as polymyxin B. Neomycin is widely used as the antibiotic in antibiotic-corticosteroid combinations employed post-operatively in products such as betamethasone and neomycin and prednisolone and neomycin and with polymyxin B in Maxitrol, although there is a reported allergy rate of about 4 per cent. Two other aminoglycoside antibiotics, framycetin and tobramycin, are not used alone in the UK but are available in the antibiotic-steroid combinations Sofradex and Tobradex respectively. Although gentamicin eye drops are licensed for the treatment and prophylaxis of bacterial infections, with the wide range of antibacterial preparations now available, this antibiotic is no longer the drug of choice for patients intolerant of, or unresponsive 22 Optician

2 Table 1 Commercially available topical ophthalmic preparations containing antimicrobials Antibacterials Antibacterial Formulation(s) Trade name(s) Combination antibiotic POM P preparations Bacitracin Polyfax eye ointment** Chloramphenicol Eye drops 0.5% * ^ Eye ointment 1% *^ Unit dose eye drops 0.5% * Ciprofloxacin Eye drops 0.3% Eye ointment 0.3% Dibrompropamidine isetionate Eye ointment 0.15 % ^ Chloromycetin Chloromycetin Minims Chloramphenicol Ciloxan Brochlor Optrex Infected Eyes Galpharm Chloramphenicol Boots Pharmacy Antibiotic Eye Drops Brolene Golden eye Other combinations Framycetin Sofradex eye drops Fusidic acid Eye drops 1% * Fucithalmic Gentamicin Eye drops 0.3% Unit dose eye drops 0.3% Genticin Minims Gentamicin Sulphate Gramicidin Neosporin eye drops Levofloxacin Eye drops 0.5% Oftaquix Neomycin Eye drops 0.5% (3500 units/ml) Eye ointment 0.5% (3500 units/g) Ofloxacin Eye drops 0.3% Exocin Neosporin eye drops Polymyxin B Neosporin eye drops Polyfax eye ointment ** Propamidine isetionate Tobramycin Antivirals Eye drops 0.1% ^ Brolene Golden eye Antiviral Formulation(s) Trade name(s) Combination antiviral POM P preparations Aciclovir Eye ointment 3% Zovirax *Available to at registration **Available only to additional supply ^Available as pharmacy medicine Betnesol-N eye drops Vistamethasone-N eye drops Maxitrol eye drops and ointment Neo-Cortef eye ointment Predsol-N eye drops Maxitrol eye drops and ointment Tobradex eye drops Other combinations to chloramphenicol. However, fortified preparations of gentamicin eye drops, containing five times the concentration of the aminoglycoside in the commercially available product and available from special order manufacturers, still have a place in the treatment of bacterial keratitis. Neomycin has activity against Acanthamoeba but being a poor cysticide is used in combination with a diamidine although Acanthamoeba infections are generally treated with chlorhexidine or polyhexamethylbiguanide which have been shown to be more effective. It can be seen that while there is still a place for the aminoglycosides in the treatment of ophthalmic infection, their use has declined with the introduction of newer agents. All aminoglycosidecontaining preparations are POMs and none are available to. Bacitracin Bacitracin is an antibiotic derived from Bacillus subtilis which interferes with Optician 23

3 Continuing education CET Table 2 Commercially available topical ocular corticosteroids Corticosteroid Formulation(s) Trade name(s) Combination products Betamethasone 10ml eye drops 0.1%, 3g eye ointment 0.1% 10ml eye drops 0.1% Betnesol Vista-Methasone Betnesol N Dexamethasone 5ml eye drops 0.1% Maxidex Maxitrol Dexamethasone sodium phosphate Dexamethasone sodium metasulphobenzoate Single dose eye drops 0.1% Minims Dexamethasone Vista-Methasone N Tobradex Sofradex Formulation of combination products 10ml eye drops containing betamethasone 0.1% and neomycin 0.5% 5ml and 10ml eye drops containing betamethasone 0.1% and neomycin 0.5% 5ml eye drops containing dexamethasone 0.1%, hypromellose 0.5%, neomycin 0.35% and polymyxin B 6,000 units/ml 3.5g eye ointment containing dexamethasone 0.1%, neomycin 0.35% and polymyxin B 6,000 units/g 5ml eye drops containing dexamethasone 0.1% and tobramycin 0.3% 10ml eye/ear drops containing dexamethasone sodium metasulphobenzoate 0.05%, framycetin 0.5% and gramicidin 0.005% Fluorometholone 5ml and 10ml eye drops 0.1% Hydrocortisone acetate 10ml eye drops 1% 3g eye ointment 0.5%, 1%, 2.5% Prednisolone acetate Prednisolone sodium phosphate 5ml and 10ml eye drops 1% 10ml eye drops Single dose eye drops 0.5% FML Pred-Forte Rimexolone 5ml eye drops 1% Vexol Predsol Minims Prednisolone sodium phosphate Neo-cortef Predsol N 3.9g eye ointment containing hydrocortisone acetate 1.5% and neomycin 0.5% 10ml eye drops containing prednisolone sodium phosphate 0.5% and neomycin 0.5% bacterial cell wall synthesis and is primarily active against Gram-positive bacteria. It is not, therefore, used alone but in combination with antibacterials active against Gram-negative bacteria such as polymyxin B in Polyfax. Polyfax eye ointment, which is licensed for the treatment and prevention of bacterial infection of the eye, is a suitable alternative to chloramphenicol eye ointment for patients intolerant of or unresponsive to chloramphenicol and is available to AS. Chloramphenicol Chloramphenicol is an antibiotic which is mainly bacteriostatic in action, but exerts a bactericidal effect against some strains of Gram-positive cocci and against Haemophilus influenzae and neisseria. It has a broad spectrum of action against both Gram-positive and Gram-negative bacteria (excluding P aeruginosa), rickettsiae and chlamydia. Chloramphenicol is the drug of choice for the treatment of bacterial and is the gold standard treatment against which other antibacterials for this condition are compared. It is well tolerated, exhibits good ocular penetration and is available in a range of formulations. The eye drop form of chloramphenicol (0.5 per cent) and the eye ointment (1 per cent) classed as POMs have been available for sale or supply by all registered, provided this is in the course of their professional practice and in an emergency, since However, in June 2005 the eye drops, and in June 2007 the eye ointment, were granted pharmacy (P) licences for the treatment of acute bacterial in patients older than two years and may now be sold or supplied by without the emergency restriction. The BNF describes the recommendation that chloramphenicol eye drops should be avoided because of an increased risk of aplastic anaemia as not well founded although topical chloramphenicol should be avoided in those with a known personal or family history of blood dyscrasias. Fluoroquinolones The three fluoroquinolones ciprofloxacin, levofloxacin and ofloxacin while licensed for the treatment of, are generally reserved for more serious bacterial infections such as bacterial keratitis. In countries where they are widely used, there are concerns about fluoroquinolone resistance. The fluoroquinolones inhibit DNA gyrase, an enzyme needed by the bacterium for the synthesis of DNA. Thus, vital information from the bacterial chromosomes cannot be transcribed, which causes a breakdown of bacterial metabolism. They are active against almost all Gram-negative microorganisms including P aeruginosa but less active against Gram-positive bacteria and are not the drugs of choice for streptococcal infections. Each fluoroquinolone has its own advantages and disadvantages. Ciprofloxacin is available in drop and ointment forms and has greater in vitro antibacterial activity than ofloxacin. However, it does not penetrate the eye 26 Optician

4 as well as ofloxacin and has an unfortunate side-effect of precipitation of the drug on the cornea in a small percentage of patients. Levofloxacin, the most expensive topical quinolone, penetrates the eye better than ciprofloxacin or ofloxacin but this has not yet been shown to result in an increase in clinical efficacy. While it is more active against Gram-positive organisms than ciprofloxacin, it is less active against certain Gram-negatives including P aeruginosa. A marketing authorisation has been granted for unitdose (preservative-free) levofloxacin eye drops 0.5 per cent but at the time of writing these were not commercially available in the UK. Neither ciprofloxacin nor levofloxacin are licensed for use in children under one year-old. Ofloxacin is the least expensive topical quinolone and is not contraindicated in babies, although its duration of use is restricted to 10 days. All the topical fluoroquinolones are POMs and none are available to. Fusidic acid This antibiotic, which was first isolated in 1962 from the fungus Fusidium coccineum, exerts its bacteriostatic activity by inhibition of protein synthesis. Fusidic acid eye drops are presented as a carbomer-containing gel which has a long ocular retention time (tear fluid concentrations of fusidic acid exceed 10 micrograms/ml six hours after instillation) allowing twice daily dosage. Since April 2005 it has been available to all registered for sale and supply, provided this is in the course of their professional practice and in an emergency. Fusidic acid has a limited bacterial spectrum and is recommended in the BNF for staphylococcal infections. The eye drops are licensed for the treatment of bacterial where the organism is known to be sensitive to the antibiotic and this is unlikely for infections caused by Streptococcus or Haemophilus species. One advantage of fusidic acid eye drops over other commercially available eye drops is that the preparation is not contraindicated in pregnancy or lactation. Gramicidin Gramicidin is a polypeptide antibiotic produced by the growth of Bacillus brevis. It is effective against many Grampositive organisms and is therefore used in combination with antibacterials with activity against Gram-negative bacteria. Gramicidin increases the permeability of cell membranes and uncouples oxidative phosphorylation in the bacterial cell wall with a temporary stimulation of oxygen consumption. It is an ingredient of neosporin eye drops which also contains neomycin and polymyxin B. Neosporin is a POM and is not available to. Polymyxin B Polymyxin B is one of a family of polypeptide antibiotics produced by various Bacillus polymyxa strains. It is bactericidal for a variety of Gramnegative bacteria, including P aeruginosa, Enterobacter and Escherichia coli, by disrupting the integrity of the bacterial cell membrane and increasing bacterial cell permeability. However, as it is not active against Gram-positive bacteria it is used in combination with antibiotics with activity against these organisms. Unfortunately, the combination of polymyxin B and trimethoprim (Polytrim) which is included in the 2005 legislation, allowing the use of topical ocular polymyxin B preparations by AS, was discontinued before the legislation reached the statute book. However, Polyfax, the combination of polymyxin B and bacitracin, an antibiotic active against Gram-positive bacteria, is available to AS. Propamidine isetionate and dibrompropamidine isetionate These bacteriostatic antimicrobials, present in eye drop and eye ointment formulations respectively, are aromatic diamidines active against Gram-positive bacteria, particularly staphylococci, but less active against Gram-negative bacteria. They also have antifungal activity. They are licensed for the treatment of minor eye infections such as and blepharitis at a dose of four times a day for the eye drops and once or twice daily for the eye ointment. The activity of the diamidines is retained in the presence of organic matter such as tissue fluids, pus and serum. Ophthalmic preparations of these drugs are classified as P medicines and so are available to all registered. One advantage of the diamidines over chloramphenicol is that there is no restriction on the age of the patient in whom the P medicine can be used. Although these drugs are also active against Acanthamoeba species, this is not a licensed use of these preparations. Oral antibiotics Although are not permitted to sell or supply oral preparations, the looking after London eyes Renowned expertise at 147 Harley Street For a full list of our sub-specialists, to make an appointment, or to speak with our ophthalmic nurse specialist please contact us on: eyecentre@thelondonclinic.co.uk Please visit The London Clinic Eye Centre under specialties at: The London Clinic s new dedicated Eye Centre consolidates the latest diagnostics and treatment for eye disorders with our outstanding consultant expertise in a single location. We invite you to refer your patients to the Eye Centre for unrivalled excellence and individual care regardless of the level or change to your patients eye condition Optician 27

5 Continuing education CET Table 3 Pharmacy and general sales list oral and nasal preparations for allergic rhinitis Class Drug Products available nasal spray Azelastine 140 micrograms/spray POM Rhinolast nasal spray (22ml) P Rhinolast Hayfever (36 doses) tablets Cetirizine Benadryl Allergy Oral Syrup; Galpharm hayfever and allergy relief tablets (30); Piriteze Allergy tablets (30); Pollenshield Hayfever(30); Zirtek Allergy tablets; Zirtek Allergy Solution Loratadine Clarityn Allergy tablets (30), Clarityn Allergy Syrup Corticosteroid nasal spray Beclometasone dipropionate 50 micrograms/spray Beconase nasal spray (aqueous) Nasobec aqueous spray Beconase allergy nasal spray (100, 180 doses) Hayfever relief nasal spray (200 doses) Nasobec Hayfever (200 doses) Fluticasone propionate 50 micrograms/spray Flixonase aqueous nasal spray (150 doses), Nasofan aqueous nasal sparay (150 doses) Flixonase Allergy Nasal Spray (60 doses) Triamcinolone acetonide 55 micrograms/ spray Nasacort (120 doses) Decongestant nasal drops and spray Ephedrine 0.5%, 1% Ephedrine nasal drops 0.5%, 1% Oxymetazoline 0.05% Phenylephrine 0.5% Fenox nasal drops, Fenox nasal spray Xylometazoline 0.05% Xylometazoline 0.1% treatment of blepharitis, and particularly that associated with acne rosacea, may involve the use of a tetracycline antibiotic such as oxytetracycline or doxycycline or erythromycin. A referral to the patient s general practitioner recommending a three-month course of one of these treatments may be appropriate. Antivirals The only topical ophthalmic antiviral commercially available in the UK, covered in section of the BNF is aciclovir. Aciclovir Aciclovir is an antiviral agent which is highly active in vitro against herpes simplex (HSV) types I and II, but its toxicity to mammalian cells is low. This is because the drug is phosphorylated to the active compound aciclovir triphosphate after entry into cells infected by the herpes virus. The first step in this process requires the presence of the HSV-coded enzyme thymidine kinase. Aciclovir triphosphate acts as an inhibitor of, and substrate for, herpes-specified DNA polymerase, preventing further viral DNA synthesis without affecting normal cellular processes. Aciclovir is rapidly absorbed from the ophthalmic ointment through the corneal epithelium and superficial ocular tissues, achieving antiviral concentrations in the aqueous humour. Aciclovir 3 per cent eye ointment (Zovirax) is used at a frequency of five times a day at approximately four hourly intervals. Treatment should continue for at least three days after healing is complete. Aciclovir eye ointment is a POM and is not available to. 28 Optician

6 Restrictions on dose and pack size GSL P GSL N/A Maximum dose 140 micrograms per nostril, maximum daily dose 280 micrograms per nostril, package contains not more than 5.04mg azelastine (36 doses) N/A Restrictions on age Adults and children over 5 years Galpharm hayfever and allergy relief tablets (7)and syrup; Benadryl One A Day Relief; Benadryl for Children Allergy Solution; Piriteze Allergy tablets (7); Pollenshield Hayfever (7); Zirtek Allergy relief (7); Zirtek Allergy relief for children (70ml) Maximum daily dose = 10mg Maximum daily dose = 10mg, maximum strength 10mg, not > 14 tablets in pack or maximum strength 1mg/ml, not > 70ml in pack Adults and children over 6 years Clarityn Allergy tablets (7) Maximum daily dose = 10mg Maximum daily dose = 10mg, maximum strength 10mg, not > 7 tablets in pack Beconase Hayfever Relief for Adults 0.05% Nasal Spray (100 doses) N/A Maximum dose 100 micrograms per nostril, maximum daily dose 200 micrograms per nostril, maximum period of 3 months, package contains not more than 20mg beclometasone (200 doses) Maximum dose 100 micrograms per nostril, maximum daily dose 200 micrograms per nostril, maximum period of 3 months and pack size of 3mg fluticasone Maximum dose and daily dose 110 micrograms per nostril, maximum period of 3 months and pack size of 3.575mg triamcinolone N/A Adults and children over 2 years and weighing 30Kg or more Adults, 18 years and over POM - adults and children over 12 years, P - adults, 18 years and over Adults, 18 years and over Maximum strength 2% 0.5% child over 3 months Afrazine nasal spray, Boots nasal spray, Vicks Sinex decongestant Non-oily nasal spray, maximum strength 0.05% Adults and children over 5/6 years (product dependent) Nasal drops, nasal sprays and nasal inhalations All preparations except nasal drops, nasal sprays and nasal inhalations equivalent to maximum dose 10mg Adults and children over 5 years Otrivine child nasal drops, Otradrops child formula Otrivine adult nasal spray and drops, Otradrops, Otraspray Non-oily nasal spray or drops maximum strength 0.1%, maximum period 7 days Child over 3 months Adults and children over 12 years Other antimicrobials A number of other antimicrobials are used in secondary care for the treatment of resistant infections or in cases where there are no commercially available preparations or those that are available are not suitable or not tolerated. Such special eye drops include the antibacterials amikacin, benzylpenicillin, cefuroxime and ceftazidime, the antifungals clotrimazole, econazole, miconazole and natamycin, and the antiviral trifluorothymidine. Corticosteroids This group, covered in section of the BNF, contains the following drugs: Betamethasone Dexamethasone Fluorometholone Hydrocortisone Prednisolone Rimexolone. When used alone, they are licensed for the short-term treatment of steroidresponsive inflammatory conditions of the eye, after clinical exclusion of bacterial, viral and fungal infections, while combination with antibacterials allows use when prophylactic antibiotic treatment is also required. The choice of steroid (Table 2) is dependent on the potency of anti-inflammatory action required, the susceptibility of the patient to a corticosteroid-induced rise in intraocular pressure (IOP) and the drug delivery system best suited to the patient s needs. Hydrocortisone, prednisolone sodium phosphate and betamethasone These corticosteroids are used where Optician 29

7 Continuing education CET Table 4 Commercially available topical antihistamines Drug and formulation Antazoline 0.5% with xylometazoline 0.05% eye drops Drug properties with sympathomimetic Trade name and volume Otrivine-Antistin 10ml Licensed indications Age restrictions and dosages Comments Temporary relief of redness and itching of the eye due to seasonal and perennial allergies such as hay fever or house dust allergy Adults and children over five years old. One drop in each eye two to three times daily Available as a P medicine therefore available to at registration Azelastine 0.05% eye drops and mast cell stabiliser Optilast 8ml (Aller-eze eye drops, the P version of azelastine, have been discontinued) Treatment and prevention of the symptoms of seasonal allergic Treatment of the symptoms of non-seasonal (perennial) allergic Adults and children over 4 years old. One drop in each eye twice a day. This may be increased to four times a day Adults and children over 12 years old. One drop in each eye twice a day increased if necessary to four times a day. It is licensed for a period of up to 6 weeks as longer periods have not been studied POM but available to additional supply Emedastine 0.05% eye drops Emadine 5ml Symptomatic treatment of seasonal allergic Age 3-65 years old. One drop in the affected eyes twice a day. Due to lack of data they are only licensed for 6 weeks continuous use POM but available to additional supply Epinastine 0.05% eye drops and mast cell stabiliser Relestat 5ml Treatment of the symptoms of seasonal allergic Adults and children over 12. One drop in the affected eye/s twice daily. Due to lack of data it is only licensed for 8 weeks continuous use POM Not available to Ketotifen 0.025% eye drops and mast cell stabiliser Zaditen 5ml Symptomatic treatment of seasonal allergic Adults and children over 3 years. One drop in affected eye/s twice a day POM but available to additional supply Olopatadine 0.1% eye drops and mast cell stabiliser Opatanol 5ml Treatment of ocular signs and symptoms of seasonal allergic Adults and children over 3 years. One drop in the affected eye/s twice a day. Treatment may be continued for up to 4 months POM but available to additional supply a mild to medium anti-inflammatory potency drug is required with hydrocortisone being at the lower end of the potency scale and betamethasone being more potent than prednisolone sodium phosphate. However, the potency of an individual product is also dependent on concentration of the active ingredient and hydrocortisone 2.5 per cent eye ointment is seen as a suitable alternative to betamethasone 0.1 per cent eye ointment. Strengths of prednisolone sodium phosphate lower than that commercially available (for example, 0.05 per cent, 0.1 per cent) are produced by special order manufacturers for use by ophthalmologists in conditions where there is a contraindication to use of the full-strength preparation, for example in viral infection of the eye. Severe cases of allergic or vernal may also necessitate use of one of the less potent corticosteroids. All these drugs are available in combination with neomycin in either eye drop or eye ointment form. Fluoromethalone and rimexolone These drugs are more expensive than prednisolone sodium phosphate and betamethasone and are generally reserved for patients who have experienced an increase in IOP with other topical corticosteroids as both fluoromethalone and rimexolone have a lower propensity to cause this adverse effect. However, increased intraocular pressure with these drugs does still occur in certain individuals and patients should be regularly monitored while on these treatments. While both drugs are licensed for the treatment of anterior uveitis, and for the treatment of corticosteroid responsive inflammation of the palpebral and bulbar conjunctiva, 32 Optician

8 Table 5 Commercially available topical mast cell stabilisers Drug and formulation Trade name(s) Licensed indications Dosages Available to? POM P POM P POM P POM P Lodoxamide 0.1% eye drops Alomide (10ml) Alomide Allergy (5ml) The treatment of allergic-atopic, vernal and giant papillary The treatment of ocular signs and symptoms of allergic Adult and child over 4 years one drop in each eye four times a day Adult and child over 4 years one drop in each eye four times a day Available to additional supply P medicine available to at registration Nedocromil 2% eye drops Rapitil (5ml) Rapitil Allergy (3ml) P medicine marketing authorisation granted to Aventis Pharma Ltd (now Sanofi Aventis) in 2004 but no P product currently available Prevention, relief and treatment of allergic, including seasonal allergic, allergic and vernal kerato- Prevention, relief and treatment of seasonal and perennial allergic Allergic, adult and child over 6 years and vernal kerato in adults one drop in each eye twice a day, increased if necessary to four times a day Adult and child over 6 years One drop into each eye twice daily, increasing if necessary to four times daily. Maximum period of use 12 weeks without consulting doctor Available to additional supply P medicine available to at registration when P medicine becomes available Sodium cromoglicate 2% eye drops Hay-Crom Aqueous, Opticrom Aqueous, Vividrin (13.5ml) Clariteyes, Galpharm Allergy, Numark Allergy, Opticrom Allergy, Optrex Allergy Eyes, Pollenase, Vivicrom (10ml) Allergic, vernal kerato Acute seasonal and perennial allergic Adult and child one drop in each eye four times a day Adult and child one drop in each eye four times a day Available to additional supply P medicine available to at registration cornea, and anterior segment of the globe, rimexolone is also licensed for the treatment of postoperative inflammation following ocular surgery. Dexamethasone, dexamethasone sodium phosphate and prednisolone acetate These corticosteroids are at the most potent end of the anti-inflammatory spectrum with prednisolone acetate being the most and dexamethasone sodium phosphate the least potent. They are used in the treatment of conditions such as anterior uveitis, iritis, cyclitis, herpes zoster keratitis, superficial punctate keratitis and non-specific superficial keratitis. They are also used postoperatively in cases in which betamethasone is considered to have insufficient anti-inflammatory activity, for example in diabetic patients or those with pre-existing inflammatory disease. All topical corticosteroids can cause a secondary glaucoma with optic nerve damage, visual acuity or field defects, Optician 33

9 Continuing education CET secondary ocular infection from pathogens liberated from ocular tissues, exacerbation of viral and fungal infections, and perforation of the globe, particularly in diseases which cause thinning of the cornea or sclera. Intensive or prolonged use of topical corticosteroids may lead to the formation of posterior subcapsular cataract. Local side-effects of steroid therapy, such as skin atrophy, striae and telangiectasia, may affect facial skin. The systemic effects of corticosteroids are possible with excessive use of steroid eye drops, particularly when administered concomitantly with other forms of the drugs. All these corticosteroid-containing preparations are POMs and none are available to. Other anti-inflammatory preparations These groups of drugs which are used in the treatment of allergic eye disorders are covered in section of the BNF and include topical antihistamines and mast cell stabilisers. Diclofenac, which is licensed for the treatment of allergic in addition to a number of other indications, is included in section with the other topical NSAIDs. There are three commercially available eye preparations of non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac (Voltarol Ophtha), flurbiprofen (Ocufen) and ketorolac (Acular). Flurbiprofen is available in a single dose form, ketorolac in a multidose form and diclofenac, the only one of these preparations available to additional supply, is available in both forms. These drugs have anti-inflammatory and analgesic properties due to their inhibition of the biosynthesis of prostaglandins, chemical mediators which play a major role in the causation of inflammation and pain. Prostaglandins in the eye cause vasodilation, increased vascular permeability, disruption of ocular blood barriers and miosis so these drugs are used to control pain and inflammation post laser and postoperatively, for allergic and to prevent miosis during cataract surgery. Non-steroidal anti-inflammatory drugs have no intrinsic mydriatic properties and are used preoperatively in conjunction with mydriatic and mydriatic-cycloplegic drugs. Diclofenac eye drops, in addition to being available in more than one topical ocular presentation have the widest range of indications. None of these drugs are licensed for use in children. If nasal symptoms predominate in a case of allergic rhino, the optometrist should recommend one of the antihistamine or corticosteroid nasal sprays available as P and as General Sale List (GSL) medicines (see BNF, section ) for intermittent or continual symptoms respectively. Several topical nasal decongestants are also available as P and GSL medicines but should only be recommended for short-term use because of the danger of rebound vasodilatation. Oral antihistamines are an alternative therapy for those who prefer this route and the optometrist can recommend cetirizine or loratadine tablets, non-sedating antihistamines which are also available as P and GSL medicines (Table 3). However, for the control of ocular symptoms, oral therapy is not the preferred route because oral antihistamines, even the non-sedating ones, can cause drowsiness in certain individuals; they are not as fast-acting as topically administered drugs and may give rise to anticholinergic side-effects such as blurred vision and a reduction in tear secretion. The latter is particularly unwanted in allergic where the effect of tears washing out the allergen is protective. The preferred route of administration of an antihistamine for allergic is topical. Topical antihistamines This group of drugs includes: Antazoline Azelastine Emedastine Epinastine Ketotifen Olopatadine. The group may be subdivided into pure antihistamines and those with antihistamine and mast cell-stabilising activity (Table 4). Pure antihistamines Antazoline is not available alone but in combination with the sympathomimetic vasoconstrictor xylometazoline. It has been available for many years as a P medicine and is therefore available to all registered. The inclusion of a sympathomimetic in the formulation means that it is contraindicated in patients receiving monoamine oxidase inhibitors, or who have stopped such treatment in the previous 14 days, and in those with narrow angle-glaucoma, and with caution in patients susceptible to angle-closure glaucoma. The preparation is not recommended for long-term use because of the potential for systemic side-effects from the sympathomimetic component and because of the occurrence of rebound hyperaemia when the eye drops are stopped.emedastine is a potent selective and topically effective histamine H1 antagonist. In vitro examinations of emedastine s affinity for histamine receptors (H1, H2, and H3) demonstrate 10,000-fold selectivity for the H1 receptor. In vivo topical ocular administration of emedastine produces a concentration-dependent inhibition of histamine-stimulated conjunctival vascular permeability. Studies with emedastine have not shown effects on adrenergic, dopaminergic or serotonin receptors. The overall incidence of ocular adverse events in the clinical trials was per cent. s with mast cellstabilising activity Azelastine is a well tolerated dual-action antihistamine which may give rise to a bitter taste in some patients. The P medicine form of the product, Allereze eye drops, was discontinued by the manufacturer in Epinastine, while not as specific for H1 receptors as emedastine, having affinity for adrenergic and serotonin receptors and affinity for cholinergic and dopaminergic receptors, is well tolerated and has an adverse drug reaction rate less than 10 per cent. Epinastine ameliorates ocular symptoms following ocular antigen challenge for at least eight hours allowing a twice daily dosage. Epinastine was not commercially available while the 2005 legislation was being considered and is not therefore available to. It is the most expensive preparation in this class. Ketotifen is another well tolerated, twice daily, dual-action antihistamine shown to be as effective as but faster acting than emedastine in allergic and superior to olopatadine in vernal kerato. It is faster acting than the mast cell stabiliser nedocromil and superior to a two-week, four times daily regimen of sodium cromoglicate in alleviating symptoms of allergic in the conjunctival allergen-challenge model. Olopatadine is the least expensive of the topical antihistamines (excluding Otrivine-Antistin) and its use is supported by a very large number of clinical trials as the drug was available for many years as Patanol in the US before the launch of Opatanol in the UK. Olopatadine has been shown to be more effective than the antihistamines 34 Optician

10 azelastine and epinastine, the mast cellstabilisers sodium cromoglicate and nedocromil, the corticosteroid loteprednol and the non-steroidal anti-inflammatory drug ketorolac in the treatment of seasonal allergic. However, nedocromil has been shown to be superior in the treatment of perennial allergic and ketotifen in vernal kerato. Although ketotifen and olopatadine appear to be equally efficacious in the treatment of seasonal allergic, olopatadine seems to be better tolerated and preferred by patients. Mast cell stabilisers Topical mast cell stabilisers prevent the release of histamine and other inflammatory mediators from mast cells. They have been proven to be more effective than placebo in several randomised controlled trials but may take up to 14 days to relieve symptoms if used alone. All three mast cell stabilisers (Table 5) are available to AS and, where a P medicine product is available, to all registered. Sodium cromoglicate is the original topical ocular mast cell-stabiliser. It is inexpensive, widely available and there are no restrictions on the age of the patients. A preservative-free preparation is available on a named patient basis. However, sodium cromoglicate needs to be used four times a day which is a disadvantage. Lodoxamide and nedocromil are newer, more expensive topical agents available as alternatives to sodium cromoglicate. Nedocromil has the advantage of a twice daily dosage and could be sold as a P medicine if such a preparation becomes available. Although lodoxamide must be administered four times a day, it is available as a P medicine. Diclofenac The other topical preparation licensed for the treatment of seasonal allergic is diclofenac 0.1 per cent (Voltarol Ophtha) eye drops for which it has been shown to be superior to ketorolac, another NSAID, but not antihistamines or mast cell-stabilisers. It is a POM but available to AS in multidose and unit-dose (preservative-free) forms, an advantage over other treatments. It is used at a frequency of four times a day for as long as required. Diclofenac is also licensed for the control of ocular pain and discomfort associated with corneal epithelial defects after excimer PRK surgery or accidental non-penetrating trauma. Multiple-choice questions take part at The antibiotic chloramphenicol: 1 A May be used by all registered B Is available in eye drop and eye ointment form as a P medicine C Is available as preservative-free eye drops D All of the above Which of the following statements 2 relating to fusidic acid eye drops is false? A It is available to all registered B It is a prescription-only medicine C It is a broad-spectrum antibacterial D It requires twice daily instillation Which of the following antimicrobial 3 agents are available as eye drops as a P medicine? A Ciprofloxacin B Propamidine isetionate C Gentamicin D Polymyxin B Which of the following drugs requires 4 phosphorylation before it can exert its antimicrobial activity? A Aciclovir B Bacitracin C Polymyxin B D Neomycin Which of the following corticosteroids 5 would be preferred in a patient with a history of a steroid-induced rise in IOP? A Betamethasone 0.1% B Dexamethasone 0.1% C Prednisolone 1% D Rimexolone 1% Which of the following corticosteroid eye 6 drops may be prescribed by an additional supply optometrist? A Hydrocortisone 1% B Fluoromethalone 0.1% C Prednisolone 0.5% D None of the above Part 8b will cover anti-glaucoma medication and artificial tears/ lubricants. Bibliography 1 British National Formulary (September 2007) (available at: 2 Competency Framework for Prescribing Optometrists (can be downloaded from: files/pdf/optometrist_document_final.pdf). 3 Clinical Knowledge Summaries (available at: knowledge/clinical_topics/by_clinical_ specialty/eyes). Which of the following drugs is an 7 antihistamine with mast cell-stabilising activity? A Emedastine B Azelastine C Nedocromil D Antazoline Which of the following anti-inflammatory 8 preparations may be used in children under three years of age? A Ketotifen eye drops B Olopatadine eye drops C Lodoxamide eye drops D Sodium cromoglicate eye drops Which of the following statements on 9 aminoglycosides is false? A They are derived from fungi B They bind to the 30S ribosomal subunit C They all have a wide spectrum of antibacterial activity D They include neomycin and gentamicin Which of the following is an 10 antihistamine? A Xylometazoline B Oxymetazoline C Antazoline D Phenylephrine Which of the following is unavailable 11 to entry level? A Diclofenac B Fusidic acid C Chloramphenicol D Propamidine isetionate Against which of the following will 12 polymixin B be ineffective? A Pseudomonas aeruginosa B Staphylococcus aureus C Enterobacter D Escherichia coli Successful participation counts as two credits towards the GOC CET scheme and one towards the Association of Optometrists Ireland s scheme. Deadline for response is November 22 4 Doughty MJ, Dutton GN. Fusidic acid viscous eyedrops an evaluation of pharmacodynamics, pharmacokinetics and clinical use for UK Ophthalmic Physiol Opt, 2006;26: The electronic medicines compendium (available at ) Lucy Titcomb is lead ophthalmic pharmacist at the Birmingham and Midland Eye Centre. John Lawrenson is professor of clinical visual science in the Department of Optometry and Visual Science, City University, London Optician 35

11 Continuing education CET Table 6 Drug Bimatoprost Latanoprost Travoprost Drug class Prostamide Prostaglandin analogue Prostaglandin analogue Manufacturer Allergan Pharmacia Alcon Trade name Lumigan Xalatan Travatan Strength 300 micrograms/ml (0.03%) 50 micrograms/ml (0.005%) 40 micrograms/ml (0.004%) Preservative Benzalkonium chloride 0.005% Benzalkonium chloride 0.02% Benzalkonium chloride 0.01% Combination product (with 0.5% timolol ) Dose Ganfort Xalacom Duotrav One drop at night (Lumigan) One drop in the morning (Ganfort) One drop at night (Xalatan) One drop in the morning (Xalacom) Once drop at night (Travatan) One drop in the morning or night (Duotrav) Table 7 Drug Betaxolol Hydrochloride Carteolol Hydrochloride Levobunolol Metipranolol Timolol Maleate Drug class Selective beta blocker Non-selective beta blocker Non-selective beta blocker Non-selective beta blocker Non-selective beta blocker Trade names Betoptic Tetoptic Betagan Minims Metipranolol Timoptol Long-acting Nyogel Timolol LA For combination products see Tables 6, 8 and 9 Available formulations 0.5% eyedrops 0.25% suspension 0.25% SDU 1% eyedrops 2% eyedrops 0.5% eyedrops 0.5% SDU 0.1% SDU 0.25% eyedrops 0.25% SDU 0.1% gel (Nyogel) 0.25% gel forming solution (Timolol LA) Dose One drop twice a day One drop twice a day One drop once or twice a day One drop twice a day One drop twice a day Nyogel and Timolol LA ( once a day) Table 8 Drug Brand name Available as Dose Acetazolamide Diamox Diamox sodium parenteral Diamox SR Tablets 250mg Injection 500mg Modified-release capsules 250mg 250mg to 1 gram daily in divided doses 250mg to 1 gram daily in divided doses mg daily Brinzolamide Azopt Eye drop suspension 1% As monotherapy or as adjunctive therapy with an ophthalmic beta-blocker twice a day., some patients may have a better response with a three times a day. dosage Dorzolamide Trusopt Trusopt preservative-free Cosopt Cosopt preservative-free Eye drop solution 2% 2% SDU Combination product with timolol 0.5% Eye drop solution Unit dose eye drops As monotherapy, three times per day; as adjunctive therapy with an ophthalmic beta-blocker, twice a day. Twice a day 36 Optician

12 Table 9 Drug Trade name Preparations available Dosage Therapeutic indication Apraclonidine Iopidine Eye drops 0.5% Unit dose eye drops 1% Brimonidine Alphagan Eye drops 0.2% One drop tds One drop one hour before and one drop on completion of procedure One drop bd Short-term adjunctive therapy of chronic glaucoma in patients on maximally tolerated medical therapy who require additional intraocular pressure (IOP) reduction to delay laser treatment or glaucoma surgery Control or prevention of postsurgical elevations in intraocular pressure that occur in patients after anterior segment laser surgery Reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension. As monotherapy in patients in whom topical beta-blocker therapy is contraindicated. As adjunctive therapy to other intraocular pressure lowering medications when the target IOP is not achieved with a single agent Combigan Eye drops containing Brimonidine 0.2% Timolol 0.5% One drop bd Chronic open-angle glaucoma or ocular hypertension in patients who are insufficiently responsive to topical beta-blockers Optician 37

13 Continuing education CET Table 10 Generic name Trade name Formulation Dosage Therapeutic indication Acetylcysteine Ilube 5% acetylcysteine, 0.35% hypromellose Adults & children (1 month and over). Instill 1 or 2 drops into the affected eye three or four times daily. Carbomers GelTears Liposic 0.2% carbomer % carbomer 980 Adults & children (12 years and over, except GelTears and Liposic which are licensed Liquivisc 0.25% carbomer 974P from 1 month). Apply 1or 2 drops 3-4 times per day or as Viscotear 0.2% carbomer 980 required. Viscotears (SDU) 0.2% carbomer 980 Relief of dry eye syndromes associated with deficient tear secretion and impaired or abnormal mucus production. Carbomers are synthetic high molecular weight polymers of acrylic acid used for the treatment of dry eye or an unstable tear film. Hydroxyethycellulose Minims Artifiical Tears (SDU) 0.44% hydroxyethylcellulose Adults & children (1 month and over). Apply 1 or 2 drops 3-4 times per day or as required. Hypromellose Artelac (SDU) 0.32% hypromellose Adults & children (1 month Isopto Alkaline 1% hypromellose and over). Apply 1 or 2 drops 3-4 times per day or as required. Isopto Plain Tears Naturale 0.5% hypromellose 0.3% hypromellose with dextran % Liquid paraffin Lacrilube 57.3% white soft paraffin, 42.5% liquid paraffin, 0.2% wool alcohols Lubritears 60% white soft paraffin, 30% liquid paraffin, 10% wool fat Adults & children (1 month and over). Apply a small amount to the affected eye(s) as required. Polyvinyl Alcohol Liquifilm Tears 1.4% polyvinyl alcohol Adults & children (1 month and over). Apply 1 or 2 drops Liquifilm Tears (SDU) 3-4 times per day or as required. Tear substitute for the treatment of dry eye Tear substitute for the treatment of dry eye. Lubrication and protection of the eye in conditions such as exposure keratitis, decreased corneal sensitivity, recurrent corneal erosions and kerato sicca. Treatment of dry eye or an unstable tear film Sno Tears Povidone Oculotect (SDU) 5% povidone Adults & children (1 month and over). Apply 1or 2 drops 4 times per day or as required. Carmellose Sodium Celluvisc 0.5%, 1% carmellose sodium Adults & children (1 month and over). Apply 1 or 2 drops 3-4 times per day or as required. Polyethylene glycol 400 Systane (Alcon) 0.4% polyethylene glycol 400 and 0.3% propylene glycol Systane (SDU) demulcents with HP-Guar (Alcon) (hydroxypropylguar) as a gelling agent Adults & children (from 1 month). Apply 1or 2 drops 3-4 times per day or as required. Treatment of dry eye or an unstable tear film Tear substitute for the treatment of dry eye. Treatment of dry eye or an unstable tear film. SDU= Single dose unit (preservative-free) 38 Optician

14 Optician 39

15 second part Anti-glaucoma medication The principal aim of glaucoma therapy is to reduce IOP to a level that prevents further visual loss. Modern glaucoma management advocates the use of target pressures. Target pressures will vary depending on risk factors and disease severity, but typically involve an IOP reduction of between per cent from the pressure at which damage first occurred. This is usually achieved by topical agents that decrease aqueous secretion or increase outflow (achieved either by improving flow through the conventional (trabecular) pathway or increasing uveoscleral drainage). Drugs used in the treatment of glaucoma are covered in section 11.6 of the BNF and include: Prostaglandin analogues/prostamide Beta-blockers Carbonic anhydrase inhibitors Sympathomimetics/alpha2-agonists Cholinergic agonists/miotics. Systemic therapy is sometimes used for short-term treatment of acutely elevated IOP, consisting of oral or intravenous (IV) acetazolamide (Diamox) or the osmotic diuretics IV mannitol or oral glycerol. This section will deal with the most commonly prescribed first-line and second-line anti-glaucoma drugs (Tables 6-9). Initial glaucoma therapy is almost always with a single agent (monotherapy) which may be substituted if unresponsive or a second drug added as adjunctive therapy. Prostaglandin analogues Prostaglandin analogues (PGAs) are thought to reduce IOP by increasing the rate of uveoscleral aqueous outflow. There is evidence that PGAs reduce IOP more effectively than the beta-blockers and they are commonly the first drug of choice (Table 6). Latanoprost (Xalatan) is preferred since it has a better safety profile than other members of the class; although there is some evidence that travoprost (Travatan) is more effective in patients of African origin. The most common side-effect of PGAs is conjunctival hyperaemia, particular during the early weeks of treatment. Hyperaemia is most pronounced in patients taking travoprost (35 per cent of patients in clinical trials), although it rarely leads to a discontinuation of therapy. PGAs may also cause darkening of the iris and lengthening of the eyelashes. Bimatoprost (Lumigan) is a prostamide, a synthetic structural analogue of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower IOP in humans by increasing outflow of aqueous humour through both the trabecular meshwork and uveoscleral routes. Side-effects of bimatoprost are similar to PGAs. Beta-blockers Beta-blockers reduce IOP principally by reducing the rate of aqueous secretion. The non-selective beta-blocker timolol remains the gold standard against which all new therapies are compared and topical beta-blockers remain an effective therapy for selected patients. For example, beta-blockers are the drug of choice in pregnant women and children and several members of this class of drugs are available in preservative-free formulations (Table 7). Particular caution needs to be exercised when prescribing topical beta-blockers as there have been several reports of serious systemic adverse reactions, particularly with non-selective receptor blockers (beta-1 and beta-2). At least 80 per cent of the administered drop drains through the nasolacrimal canal from where it can be absorbed across the nasal mucosa. Since the systemically-absorbed drug bypasses hepatic first-pass metabolism, the drug behaves like an intravenous dose, increasing the propensity to cause prolonged and severe side-effects. Several cardiovascular adverse events that have been reported, including arrhythmias, hypotension, angina pectoris, myocardial infarction, heart failure, and syncope (fainting). Topical beta-blockers can also exacerbate bronchospasm in asthmatics and patients with chronic obstructive pulmonary disease. Carbonic anhydrase inhibitors Carbonic anhydrase is a key enzyme involved in aqueous production. Carbonic anhydrase inhibitors (CAIs) include both oral and topical agents (Table 8). Acetazolamide (Diamox) can be given by mouth or intravenous (IV) injection and is typically used in the treatment of angle closure (500mg IV stat dose followed by 250mg orally four times daily). Topical CAIs, dorzolamide and brinzolamide, are less potent than PGAs and beta-blockers but can be used as adjunctive therapy or first line in those unresponsive to other agents. The most common side-effects of topical CAI include a foreign-body sensation, conjunctival hyperaemia and a bitter taste in the mouth. Selective alpha-2 agonists Selective alpha-2 agonists lower IOP by reducing aqueous formation as well as a possible increase in uveoscleral outflow. Apraclonidine (Iodipine) is indicated for short-term use in patients on maximum drug therapy or perioperatively who require further IOP lowering. Brimonidine (Alphagan) can be used long-term as monotherapy where beta-blockers are contraindicated or as adjunctive therapy in primary open angle glaucoma (POAG) and ocular hypertension (Table 9). Combination products The effect of different drugs used together is not necessarily additive. Some drugs work synergistically and the overall effect is greater than the sum of their individual responses. This is particularly true where the drugs reduce IOP by different mechanisms. Several combination products are available commercially, such as timolol with prostaglandin/prostamide analogues, and timolol combined with the carbonic anhydrase inhibitor dorzolamide. Combined preparations can potentially improve compliance and reduce exposure to preservatives (compared to two separate preparations). Other medications Miotics, such as pilocarpine, have been used for many years for the treatment of chronic glaucoma. They reduce IOP by improving outflow through the conventional drainage pathway. Miotics are no longer prescribed as first line therapy in POAG, although they still have a role in the treatment of angle closure. Artificial tears and ocular lubricants A distinction is often made between products that are marketed as artificial tears or tear substitutes and lubricant ointments and gels. Artificial tears are characterised by hypotonic or isotonic buffered solutions that are formulated at a neutral or slightly alkaline ph. They are the mainstay of treatment for dry eye or an unstable tear film. However, since most products also contain viscosityenhancing agents that help to facilitate the movement of the eyelid across the Optician 40