Ophthalmic Medication Review and Update - 20/20 Memphis

Ophthalmic Medication Review and Update

Scott Ensor, OD, MS

Associate Professor

Southern College of Optometry

Financial Disclosures…

• None!

About Me…

• Native Memphian

• 2001 SCO Graduate

• Primary Care Residency 2004

• Joined SCO faculty in 2008

• Started teaching Systemic Pharmacology I and II in 2011

• Master’s Degree in Pharmacology and Toxicology in 2013• Michigan State University

Basic Pharmacology Review

Routes of Administration

• Determined by• Properties of the drug

• Solubility, ionization, etc

• Therapeutic objectives• Rapid onset

• Chronic adminstration

• Restriction to a local site

• Setting in which it will be used

• 2 major routes• Enteral (by mouth)

• Parenteral (any other route)

Ocular Medications

• 3 primary methods of administration• Topical

• Injection• Sub-conjunctival

• Intravitreal

• Retrobulbar

• Etc…

• Systemic (oral)

• Tissues of the anterior segment respond well to topical administration but posterior segment tissues usually require a different route

Topical Administration

• Delivery of medication directly to ocular tissues• Eye drops

• Solution

• Suspension

• Ointment

Topical Administration

• Advantages• Ease of administration

• Don’t forget to educate your patients

• Low cost (?)

• Good patient compliance (?)

Topical Administration

• Disadvantages• Waste

• Requires frequent dosing• Less than 5% of administered drug enters the eye

• Some medications are formulated for longer contact with ocular tissue and/or increased drug concentrations

Topical Administration

• Where does all of the medication go?• Nasolacrimal drainage

• Tear dilution

• Natural barriers• Cornea

• Conjunctiva

• Systemic absorption• All topically delivered medications can/will enter systemic absorption

• Conjunctival tissue is highly vascularized

• Bypasses first pass metabolism

• Watch for side effects

Enteral Administration

• Administration by Mouth• Pill, Capsule, Liquid

• Under tongue (sub-lingual)• Directly absorbed into the blood stream

Enteral Administration

• Advantages• Easily self-administered

• Low risk of systemic infections

• Easily overcome toxicities and overdose

Enteral Administration

• Disadvantages• Complicated pathway to absorption

• Harsh environment of stomach• Acidic environment breaks down many compounds

• Metabolism by liver• First-pass metabolism

Antibiotics

• ALL topical antibiotics that have widely used oral counterparts will eventually develop resistance• However, ophthalmic preparations of antibiotics achieve a very high MIC

(minimal inhibitory concentration) and almost always overpower resistant bacteria• Frequency of dose appears to be more important than choice of antibiotic

• Use of broad-spectrum drugs is important

A Word About Resistance

• Indication:• Evidence of a bacterial infection or a condition in which there is judged to be

a significant risk of opportunistic infection• IF no discharge – NO infection

• IF sector injection to conj – NO infection

• Usual dosage (depending on the choice of antibiotic)• Use frequently (every two hours) for first few days then switch to q.i.d. for 4

to 6 more days• Never use for less than 5 days

• Never taper antibiotics

Topical Antibiotics

• Mechanism of Action• Inhibit bacterial DNA Gyrase and topoisomerase IV

• Broad spectrum, potent• Gram positive

• Gram negative (including Pseudomonas)

• MRSA

• Widely prescribed systemically• Resistance is developing

• Higher concentrations are more potent

Fluoroquinolones

Ciprofloxacin

• Ciloxan (Ciprofloxacin .3%)

• Good against Pseudomonas

• Occasionally precipitates into the cornea• Not visually significant

Moxifloxacin

• Moxeza (Moxifloxacin .5%) formally Vigamox

• Preservative free

• Xanthan gum base allowing easier dosing schedule

Gatifloxacin

• Zymaxid (Gatifloxacin .5%) formally Zymar

• Effective choice

• Higher concentration allows for easier dosing schedule

Besifloxacin

• Besivance (Besifloxacin .6%)

• Suspension• Shake before using

• Unique chemistry among the fluoroquinolines

• NO systemic equivalent

• A 2013 article in Ophthalmology reported that repeated exposure to azithromycin and fluoroquinolones caused an increase in the number of Staph. epidermidis on the conjunctival surface.

• You may want to limit your use of these medications to severe corneal infections…

Think about it…

• Mechanism of Action• Inhibits protein synthesis

• Effective against gram positive and gram negative• NO systemic equivalent!

• Known to cause ototoxicity

• Occasional allergic reaction• Not serious• Patient often knows ahead of time

• Available in solution and ointment• Gentamicin • Tobramycin (Tobrex)• Neomycin

• No pseudomonas coverage – usually combined with Polymyxin B

Aminoglycosides

• Mechanism of Action• Prevents synthesis of Folic Acid

• Broad spectrum• Better against strep than staph

• Allergy is common• Patient will report sulfa (or sulfur) allergy

• Burns upon instillation

• Available in solution and ointment

Sodium Sulfacetamide

• Mechanism of Action• Inhibits Protein Synthesis

• Broad Spectrum

• Non-toxic to cornea/conj

• Very safe in pregnancy

• Only available as ointment

• Limited therapeutic role due to high resistance• Used mainly in prophylactic role

Erythromycin

• Mechanism of Action• Destroys bacterial cell wall

• Great gram-positive coverage

• Toxicity and allergic reactions are rare

• Safe in pregnancy

• Only available in ointment

• Used mainly for infectious blepharitis and for overnight coverage in treatment of bacterial corneal ulcers

Bacitracin

• Bacitracin + Polymyxin B• Polymyxin B

• Mechanism of Action – destroys cell membranes

• Highly effective against gram negative

• Toxicity and allergic reactions are rare

• Good to use due to increased gram negative coverage over Bacitracin alone

• Available only in ointment

Polysporin

• Polymyxin B + Trimethoprim• Trimethoprim

• Bacteriostatic

• Mechanism of Action – inhibits bacterial dihydrofolate reductase (similar MOA to sulfonamide)

• Not effective against pseudomonas

• VERY effective against Haemophilus and Strep. Pneumoniae

• Available in solution only• Solution of choice for peds!!

Polytrim

• Be comfortable prescribing!

• Can be VERY effective in treating ocular conditions• Esp internal soft-tissue infections where eye drops are unlikely to penetrate

• Indications• Meibomian gland disease

• Rosacea blepharitis

• Internal hordeola

Systemic Antibiotics

• Amoxicillin + Clavulanic Acid

• Useful in treating soft tissue infections• Great for pre-ceptal cellulitis or severe hordeolum

• CAN NOT use if patient is allergic to PCN

• Usual dosage is 500 mg or 875 mg bid x 1 week

• Can be taken with meals

• Digestive problems are a common side-effect• Make sure patient is aware

Augmentin

• 1st Generation Cephalosporin• Same MOA as PCN

• 5-10% cross-sensitivity with PCN• Avoid in pts allergic to PCN

• Useful in soft tissue staph infections• Hordeola or pre-ceptal cellulitis

• Usual dosage is 500mg bid x 1 week

Cephalexin (Keflex)

• Member of tetracycline family• Disrupts bacterial protein synthesis

• Contraindicated in pregnancy, nursing mothers, under age 8

• Photosensitivity warning

• Indicated in • Meibomianitis

• Adult Inclusion Conjunctivitis (Chlamydia)• Dose is 100 mg bid

• Recurrent Corneal Erosion

Doxycycline

• Doxycycline is primarily an antibiotic• Has a secondary property

• Modify and enhance the lipid metabolism in oil producing glands• Restores more physiological lipid production

• This is why doxy is so useful in treating tear film dysfunctions• Dose is 50 mg bid x 2 weeks then qd x 3-6 months

Unique Property

• Maintains effective concentration in soft tissue long after usual dose

• Usually given as Zpak (250 mg) or TriPak (500mg)• 2 tabs on day one followed by one tab for 4 days

• 1 tab a day for 3 days

• Drug of choice for chlamydial infections• 1000mg once for one day

• Very effective for hordeolum

• Potential cardiovascular problems…• May cause arrhythmias in some patients

Azithromycin (Zithromax)

Sulfamethoxazole + Trimethoprim

• Bactrim or Septra• Use “DS”

• Two tablets BID for one week

• Caution if allergic to sulfa medications

Corticosteroids

• General Principles• Correct diagnosis is essential before prescribing

• Dose is given on an individual basis

• Avoid prolonged use if possible• Aggressive short-term use is better than under treatment

• Incidence of side-effects increases with time

• Should be tapered• Maybe not if one week use or less…

Corticosteroids

• The hypothalamus produces corticotropic releasing factor (CRF)

• CRF travels to the pituitary and triggers the release of adrenocortotropic hormone (ACTH)

• ACTH causes the adrenal cortex to up-regulate the production of hydrocortisone and corticosterone

• When the level of steroid in plasma increases, production of ACTH declines

Biochemistry Review

• 2 reasons• 1. Taking synthetic steroids slows production of physiologic steroids and the

taper allows the body time to re-start production• More pronounced with systemic steroids but studies have shown that .1%

dexamethasone four times a day for 6 weeks resulted in a decreased level of natural hormones

• 2. Rebound inflammation• Steroids suppress inflammation but do not resolve – abruptly discontinuing topical

steroids may allow the suppressed inflammation to come back

Why Taper?

• The human body possesses abundant esterases but no ketones• Most topical steroids are ketone-based

• Ketone-bases steroids can not be broken down by the human body and thus linger in tissues• Good for therapeutic effect but bad for side effects

• Ester-based steroids generally have fewer side effects because they are broken down in the body

Another Biochemistry Review

• Topical ketone-based steroids• Prednisolone

• Fluorometholone

• Dexamethasone

• Medrysone

• Rimexolone

• Topical ester-bases steroids• Loteprednol

Ester vs. Ketone

• Ester-based• Greater safety profile

• Generally less chance of steroid-response increase in IOP

• Lotemax• Loteprednol 0.5% gel

• Becomes a liquid when out of bottle and even more when on the eye• Do NOT need to shake

• Loteprednol 0.5% ointment

• Alrex• Loteprednol 0.2%• Approved for treating allergic conjunctivitis

Loteprednol

• Greatest anti-inflammatory efficacy of all topical ophthalmic steroids

• Prednisolone acetate 1% suspension• Pred Forte

• Omnipred

• Econopred

• Generic equivalent

• Pred Forte is proven to be the most effective of the topical ohpthalmicsteroids for the treatment of uveitic and corneal inflammations

Prednisolone

• Prednisolone acetate .12%• Pred Mild

• Generic Equivalent

• Clinical Pearl:• Do not substitute generic for Pred Forte in the treatment of anterior uveitis

• Generic pred settles out of suspension too quickly (in my opinion…)

Prednisolone

• Ketone-based

• Less clinically effective than pred

• Greatest ocular hypertensive effect

• Rarely used alone

• Available as .1% susp• Maxidex

• Generic

• Common steroid used in combo drops

Dexamethasone

• Good to excellent anti-inflammatory properties

• Diminished effect on IOP

• Available as .1% susp and ointment• FML 0.1%

• Flarex

• FML Forte (0.25%)

• FML 0.1% ointment

Fluorometholones

• Durezol - Difluprednate 0.05% oph emulsion• Difluorinated derivative of prednisolone

• Emulsion• Do not need to shake

• Enhanced ocular surface contact time• Reduced dosage

• Studies are showing as effective as Pred Forte with half the dose

Difluprednate

• Methylprednisolone• Medrol dose pack

• Easily prescribed – dose is pre-divided

• Prednisolone

• Prednisone

• Triamcinolone• Also effective topically (cream)

Commonly Prescribed Systemic Steroids

Figure 26.6 (part 1)

Chapter 26 MENU >

Adverse Effects

Figure 26.6 (part 2)

Chapter 26 MENU >

Adverse Effects

Don’t forget cataracts!!

NSAIDS

• NSAIDS

• Inhibit the action of cyclo-oxygenase• Inhibits prostaglandin synthesis

• Prostaglandins are mediators of inflammation

• Uses• Prevention of intraoperative miosis

• Prevention/treatment of cystoid macular edema

• Topical analgesia and corneal photophobia

• NOT very effective for ocular inflammation

Non-Steroidal Anti-Inflammatory

• Bromfenac .07%

• Lower preservative concentration• Does not burn

• Now approved for once a day dosing

• Formally bromday

Prolensa

BromSite

• Bromfenac 0.075%

• First NSAID specifically approved for prevention of pain after cataract surgery

• Delivery vehicle developed to increase contact time with the ocular surface

• BID dosing

• Nepafenac .3%

• NSAID pro-drug

• Effective in controlling pain and post-operative inflammation associated with cataract surgery

• Dosage is qd

• Formally Nevanac

Ilevro

• 0.4% and 0.5% ophthalmic solution

• Available as a generic (formally Acular)

• Burns upon instillation

• QID dosing• Can be confusing to patients when substituted following cataract surgery

Ketorolac

Treatment of Dry Eye Disease

• Identify the cause• Meibomian glands

• Aqueous deficiency

• Treat any eyelid/meibomain issue first• Include lipid-based AT

• 2000 mg Omega-3 supplement

• 50mg Doxy

Treatment of Dry Eye Disease

• Consider early use of topical corticosteroid• Control inflammatory symptoms of dry eye

• Restasis• Cyclosporine 0.05 oph emulsion

• Now available in multi-dose bottle

• Can take 4-6 weeks for patient to notice improvement• Consider “jump-start” with corticosteroid

Treatment of Dry Eye Disease

• Xiidra• Lifitegrast 5% oph solution

• Specifically blocks the interaction of two different inflammatory molecules• Decreases T-cell activation

• BID dosing

• Most patients report relief of symptoms earlier than with Restasis

• Side effects (seem to ease up after 3-4 weeks)• Irritation

• Metallic aftertaste

• Blurred vision

Treatment of Glaucoma

• Controlled clinical trials have demonstrated that reduction of IOP slows the occurrence and progression of glaucoma• Many pharmacological options exist for the control of IOP

• The “weak-link” in glaucoma therapy seems to be in public health• Patient education

• Art is in balancing efficacy, cost, and effect on patient lifestyle

Topical Glaucoma Medications

• Timolol first introduced in 1978

• Decreases aqueous production

• Shown to decrease IOP an average of 25%

• Exist in .25% and .5% concentrations

Beta Blockers

• Traditionally prescribed .5% bid• Timolol has a very long half-life

• .25% has been shown to be as effective as .5%

• Aqueous production is naturally reduced during sleep

• Best dose may be .25% qam!

Beta Blockers

• Melanin pigment can bind drugs• Dose .5% qam for patients with darkly pigmented tissues

• Contraindications:• Asthma

• Decompensated CHF

• Symptomatic bradycardia or heart block

• History of syncope without diagnosis

• Heart rate <55 beats/min without known etiology

• Symptoms/complaints of dizziness without known etiology

• Diabetes?

Beta Blocker Reminders

• Timolol• Maleate

• Istalol

• Timoptic

• Timoptic XE• Timoptic PF (Ocudose)

• Hemihydrate• Betimol

• Levobunolol• Betagan

• Betaxolol• Betoptic-S

*Only Timolol and Levobunolol have half-lives appropriate for once-a-day dosing

Beta Blockers

• Have become “gold standard”

• Enhance aqueous outflow

• Achieve an average of 30% IOP reduction

• Use is once daily• Time of dose does NOT effect how the drug works

• Evening is preferred but NOT required

• Some evidence that every other day dosing may be effective

Prostaglandins

• Latanoprost (Xalatan)• Now available as a generic

• Travaprost (Travatan Z)• Travatan no longer produced

• Brimatoprost (Lumigan)• All three medications perform similarly

• Travatan Z does not contain BAK• Lumigan has been shown to cause increased conjunctival hyperemia

• Unoprostone (Rescula)• “prostaglandin like” – dosed bid

• Tafluprost (Zioptan)• Preservative free

Prostaglandins

• Side effects:• Conjunctival hyperemia

• Usually improves after a few months of use

• Increased pigmentation• Lashes, skin under eye, iris

• CME• Has been shown to increase risk after cataract surgery but most surgeons do not

discontinue use

Prostaglandins

• Usually a second line medication

• Decreases aqueous production (as well as CSF)

• Averages a 15% reduction in IOP

Carbonic Anhydrase Inhibitors

• Dorzolamide ophthalmic solution (Trusopt)• Currently difficult to get…

• Brinzolamide ophthalmic suspension (Azopt)• Dose for above is two to three times a day

• Acetazolamide• Systemic CAI• Usually used in angle closure situations• Available in 250mg tabs and 500mg ER tabs

• Avoid in patients with sulfa allergy?• Shares similar chemical structure• Questionable clinical evidence

CAIs

• Decrease aqueous production

• Average a 20% to 25% IOP reduction

• Brimonidine (Alphagan) is important example• .2%

• .15%

• .1% (Alphagan-P)

• Approved for tid dosing but often used bid when used as a second drop• 8 hr effective zone followed by 4 hr low level

• Sometimes described as “neuroprotector” but no evidence exists for this added benefit

Alpha-adrenergic Agonists

• Cosopt• Timolol .5% + dorzolamide 2%

• Bid

• Also available PF

• Combigan• Timolol .5% + brimonidine .2%

• q12h

• Simbrinza• Brinzolamide 1% + brimonidine .2%

• tid

Glaucoma Combinations