Not long ago, it was virtually unthinkable for optometrists to prescribe oral medications. However, today we recognize that several classes of medications, both topical and oral, are valuable in the treatment and management of ocular disease.

As noted in the AOA 2004 Scope of Practice Survey, optometrists are adopting a greater role in the medical eye care of patients, and there is value in being aware of the roles of different medications.¹

Here, we review the more common oral antivirals, antibiotics, antihistamines, analgesics, cortico-steroids and carbonic anhydrase inhibitors that are used to manage a variety of ocular conditions.

Antivirals
Oral antivirals (table 1) are primarily used to treat varicella zoster virus (VZV), which is responsible for herpes zoster ophthalmicus. Oral antiviral therapy for VZV is especially effective if taken within three days of the initial vesicular skin eruptions. Early use of antiviral agents reduces viral shedding, allowing the patient to have decreased signs and symptoms as well as earlier resolution and a decrease in secondary complications, such as postherpetic neuralgia.

In addition, oral antivirals can be used as adjunctive treatment for keratitis and uveitis associated with herpes simplex virus (HSV). Oral antiviral therapy may be particularly beneficial in active HSV infections if the patient is allergic to topical trifluridine or has developed trifluridine resistance, is a pediatric patient, or is using concurrent topical corticosteriods. Notably, the Herpetic Eye Disease Study (HEDS) demonstrated the benefit of prophylactic oral acyclovir against recurrent ocular HSV, with a 50% reduction in recurrences over a period of one year.²

The primary side effects of oral antivirals are related to the gastrointestinal system; nausea is the most common. In addition, give special consideration to patients who have renal and hepatic disease.

Table 1: Antivirals Mechanism of Action (MOA): Inhibit DNA replication

Generic	Trade	Formulations	Condition	Dosage
acyclovir	Zovirax (GlaxoSmithKline)	200mg capsule; 400mg and 800mg tablets; 200mg/5ml suspension	VZV	800mg 5x/d for 7 to 10 days
			HSV	400mg 5x/d for 7 days
			HSV (pediatric)	20mg/kg/d divided q.i.d. for 7 days
			HSV prophylaxis	400mg b.i.d.
valacyclovir	Valtrex (GlaxoSmithKline)	500mg, 1,000mg (1g) caplets	VZV	1g t.i.d. for 7 to 10 days
			HSV	500mg t.i.d. for 7 days
			HSV prophylaxis	500mg b.i.d.
famciclovir	Famvir (Novartis)	125mg, 250mg, 500mg tablets	VZV	500mg t.i.d. for 7 to 10 days
			HSV	250mg t.i.d. for 7 days
			HSV prophylaxis	250mg b.i.d.

The information in the tables is meant as a guide and is intended for healthy adults who have no contraindications to the medication.

Antibiotics
There are numerous indications for oral antibiotics (table 2) in the care of patients who have ocular disease. Perhaps the most common uses in optometric practice are treatment of lid disease and ocular surface disease. For patients with severe or multiple internal hordeola, oral antibiotics are often required to achieve a clinical resolution. Prudent use of oral antibiotics may also help prevent more serious complications, including pre-septal cellulitis and orbital cellulitis. Most commonly, cephalosporins, such as  Keflex (cephalexin, Eli Lilly), are employed for infectious lid disease. However, numerous antibiotics may be effective, including fluoroquinolones, macrolides or penicillins. Because of their outstanding efficacy and desirable dosing regimen, oral fluoroquinolones, such as levofloxacin, gatifloxacin and moxifloxacin, should be considered when compliance is an issue or resistance is a concern.

Ocular surface disease does not need to be infectious to warrant use of an oral antibiotic. For example, dry eye syndrome is often associated with meibomian gland dysfunction (MGD), which responds favorably to oral tetracycline and its derivatives (e.g., doxycycline). Tetracycline drugs have a distinct therapeutic mechanism; they not only diminish bacterial growth but also modify meibomian secretions.

Another important ocular condition that warrants oral antibiotic use is toxoplasmosis retinitis. The classic treatment regimen for an immunocompetent patient is a combination of pyrimethamine (a 50 to 100mg p.o. loading dose for one to two days, followed by 25mg p.o. b.i.d. for two to four weeks) and sulfadiazine (2g loading dose, then 1g p.o. q.i.d. for two to four weeks). Both medications inhibit the folic acid metabolism necessary for the Toxoplasma organism to survive.

Adult inclusion conjunctivitis secondary to chlamydial infection is an absolute indication for oral antibiosis. While certain new topical agents (e.g., moxifloxacin 0.5% solution) have demonstrated efficacy against Chlamydia trachomatis, the overwhelming likelihood of concurrent genital infection in these cases requires systemic therapy. The treatment of choice for chlamydial infection is oral azithromycin, 1,000mg in bolus form at the time of diagnosis.

The primary side effects of oral antibiotics include vaginal yeast infections and gastrointestinal distress and diarrhea because these drugs tend to disrupt the normal intestinal flora. Taking these medications with food typically helps to limit the severity of these symptoms. Tetracyclines are somewhat notorious for their potential adverse effects. They are contraindicated in pregnant females, nursing mothers and children younger than age 8 because discoloration of teeth and bones can occur in infants and children exposed to these medications. Other side effects of tetracyclines include photosensitivity, gastrointestinal upset and secondary yeast infections. Also, the therapeutic effect of tetracyclines may be rendered inert by concurrent ingestion of lactose, so advise patients to limit or avoid dairy products when taking these drugs.

If a patient reports an allergy to penicillin, avoid using cephalosporins because a cross-allergy response to this class of medications often occurs. Lastly, prior to prescribing antibiotic agents, be sure to consider pseudomembranous colitis in patients who present with diarrhea. Pseudomembranous colitis ranges in severity from mild to life-threatening and can be associated with almost all antibiotic agents.

Table 2: Antibiotics Tetracyclines MOA: Inhibit protein synthesis, anticollagenolytic activity

Generic	Trade	Formulations	Dosage
tetracycline	Sumycin (Apothecon)	250mg, 500mg tablets/ capsules; syrup 125mg/tsp	250mg, 500mg q.i.d.
doxycycline	Vibramycin (Pfizer)	50mg, 100mg capsules; 100mg tablet; suspension 25mg/tsp syrup; 50mg/tsp	50mg or 100mg b.i.d.
coated doxycycline hyclate pellets	Doryx (Faulding Pharmaceuticals)	75mg, 110mg coated pellets	50mg or 100mg b.i.d.

Macrolides MOA: Inhibit protein synthesis

erythromycin	E-Mycin (Pacific)	250mg, 500mg tablets	250mg to 500mg b.i.d-q.i.d.
azithromycin	Zithromax (Pfizer)	250mg capsules; 500mg, 600mg tablets; suspension 100mg/5ml; 200mg/ml; Z-PAK: six 250mg capsules; TRI-PAK: three 500mg tablets	1g one-dose administration for Chlamydia; 500mg q.d., followed by 250mg q.d. for 4 days for soft tissue infection.

Penicillins MOA: Inhibit bacterial cell wall formation

amoxicillin and clavulanate	Augmentin (GlaxoSmithKline)	250mg, 500mg, 875mg + 125mg tablets	500mg + 125mg b.i.d./t.i.d
amoxicillin and clavulanate extended release	Augmentin XR (GlaxoSmithKline)	1,000mg + 62.5mg extended-release tablets	two tablets b.i.d.

Cephalosporins MOA: Inhibit bacterial cell wall formation

cephalexin	Keflex (Eli Lilly)	250mg, 500mg capsules	500mg b.i.d.
cefaclor	Ceclor (Eli Lilly)	250mg, 500mg capsules	250 to 500mg t.i.d.

Fluoroquinolones MOA: Inhibit bacterial DNA synthesis

levofloxacin	Levaquin (Ortho-McNeil)	250mg, 500mg and 750mg tablets; 25mg/ml oral solution	250 to 750mg q.d.
ciprofloxacin	Cipro (Bayer)	100mg, 250mg, 500mg, 750mg and 1,000mg tablets	500 to 750mg b.i.d.
gatifloxacin	Tequin (Bristol-Myers Squibb)	200mg, 400mg tablets	400mg q.d.
moxifloxacin	Avelox (Bayer)	400mg tablet	400mg q.d.

Sulfonamides MOA: Inhibit folic acid aynthesis

trimethoprim and sulfamethoxazole

Bactrim DS (Roche)

160mg + 800mg (double-strength) tablets

160mg + 800mg b.i.d.

Antihistamines
Because todays topical allergy medications are effective and fast-acting for allergic conjunctivitis, oral antihistamines (table 3) are generally indicated only when multiple components and non-ocular expressions of allergic disease are present. Consider using oral antihistamines in a patient who has significant allergic rhinitis, urticaria or contact dermatitis, severe eczema or atopic asthma associated with ocular symptoms.

Use of first-generation antihistamines is limited due to their adverse sedative and anticholinergic effects. The second-generation agents are similar in efficacy to the first-generation antihistamines but do not cross the blood-brain barrier to the same degree. Therefore, they are relatively non-sedating.³ In addition, second-generation antihistamines are preferable, due to an easier dosing schedule.

Many of the oral antihistamines are also available in combination with pseudoephedrine or other decongestants to help relieve sinus pressure and nasal congestion. The name of such a medication usually has -D following the antihistamine.

Notable side effects of oral antihistamines include headache, dizziness, drowsiness, back pain and cough. They are also known to diminish exocrine secretions, often resulting in dry mouth or dry eye. When using oral antihistamine treatment, ocular lubricants are often necessary to mitigate against diminished tear volume and ocular surface drying. Of historical note: Seldane (terfenadine, Hoechst Marion Roussel) and Hismanal (astemizole, Janssen) were removed from the U.S. market because of serious heart side effects when combined with certain medications. The concentration of Seldane in the blood increases when used concurrently with erythromycin or ketoconozole, resulting in serious or fatal cases of cardiac arrhythmias. A new medicine to compete with the antihistamines, Singulair (montelukast, Merck), has recently been marketed as a once-a-day anti-allergy medication that functions as a leukotriene receptor antagonist. Montelukast was traditionally used for prophylaxis and chronic treatment of asthma. Drug interactions  may occur between montelukast and phenobarbital and rifampin.

Table 3: Antihistamines First Generation MOA: Block histamine

Generic	Trade	Formulations	Dosage
diphenhydramine	Benadryl (Warner Lambert)	25mg, 50mg tablets/capsules; 12.5mg/5ml elixir	25 to 50mg q6 to 8h
chlorpheniramine	Chlor-Trimetron (Schering-Plough)	4mg, 8mg, 12mg tablets	4mg q6 to 8h

Second Generation MOA: Block histamine

desloratidine	Clarinex (Schering-Plough)	5mg tablets, 0.5mg/1ml syrup	5mg q.d., 5mg/10ml q.d.
loratidine	Claritin (Schering-Plough)	10mg tablets, 1mg/ml syrup	10mg q.d.
fexofenadine	Allegra (Aventis)	30mg, 60mg, 180mg tablets; 60mg capsule; 60mg, 120mg extended-release tablets	60mg b.i.d., 120mg or 180mg q.d.
cetirizine	Zyrtec (Pfizer)	5mg, 10mg tablets, chewable tablets; 5mg/5ml syrup	5 to 10mg q.d.

Analgesics
The goal of prescribing oral analgesics (table 4) is to use the weakest agent to achieve the desired effect. Both the need for analgesics and the effect of analgesics vary among patients. Common ocular conditions that call for analgesics include corneal abrasions, corneal erosions, ultraviolet keratitis, uveitis, ocular trauma and post-surgical discomfort.

Therapeutic agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), inhibit peripheral pain receptors by blocking metabolic pathways. In contrast, narcotics function centrally on the opioid receptors to block the signal from the peripheral pain receptors.

Aspirin is the oldest and most widely used of the commercially available analgesic agents. Reyes syndrome is a rare but serious illness associated with aspirin. Children and teenagers should not use aspirin for chicken pox or flu symptoms secondary to the association with Reyes syndrome and salicylate-containing medications. Of the remaining OTC medications, acetaminophen is considered the safest, but it lacks the anti-inflammatory effects of other medications. Furthermore, chronic alcohol abusers are at risk for liver toxicity with acetaminophen use. A primary side effect of OTC analgesics and anti-inflammatory medications is gastrointestinal upset.

The COX-2 inhibitors were touted as safer analgesics than the older NSAIDS with a perceived benefit of being as effective as the OTC medications, but with fewer side effects.⁴ However, there has recently been much controversy involving this class of medication. Vioxx (rofecoxib, Merck) was removed from the market due to an increased relative risk of heart attack and stroke. Most recently, Bextra (valdecoxecib, Pfizer) was also withdrawn from the U.S. market due to similar concerns. Although Celebrex (celecoxib, Pfizer) remains on the market, give serious consideration before prescribing this class of medi-cation, even for short-term therapy.

Ultram (tramadol, Ortho-McNeil) is a unique medication because it is a non-narcotic non-NSAID. Tramadol is a good choice when a strong analgesic effect is desired without the use of a narcotic. The mechanism of action is as an opioid agonist and a weak noradrenaline and serotonin reuptake inhibitor. Tramadol is contraindicated in patients with a history of seizure disorder.

Narcotic analgesics are indicated only for short-term use due to their addictive nature. Prior to prescribing narcotic analgesics, question patients about prior substance abuse or dependency, as well as use of other central nervous system depressants, including antihistamines. Individuals who take narcotics should be warned to avoid alcohol. Once a single dose of codeine exceeds 60mg, the increase of these side effects begins to outweigh the benefits. At elevated doses, narcotics may result in respiratory failure or death. Signs of an overdose include seizures, confusion, restlessness, excessive drowsiness, excessive dizziness, pupillary miosis, excessive weakness and labored breathing.

The drug selection and dose will be dictated by the patients amount of pain and tolerance of that pain. Again, the goal is to effectively treat the patient short term with the weakest agent to achieve the desired effect.

Table 4: Analgesics/Anti-inflammatories Over-the-counter MOA: Inhibit the synthesis of prostaglandins

Generic	Trade	Formulations	Dosage
acetylsalicylic acid	Aspirin (Bayer)	multiple	2400 to 4000mg/d (divided doses)
acetaminophen	Tylenol (McNeil)	325mg tablets; 500mg, 650mg capsules/tablets; 160mg, 325mg/5ml syrups	325 to 650mg q4 to 6h; maximum 4,000mg/d
naproxen sodium	Aleve (Bayer)	220mg, 250mg, 275mg, 375mg, 500mg, 550mg tablets	550mg b.i.d.
ibuprofen	Advil (Wyeth)	100mg caplet; 200mg capsule; 200mg, 400mg 600mg, 800mg tablets	200 to 400mg q4 to 6h; maximum 3,200mg/d

Non-narcotic NSAIDs MOA: Inhibits the synthesis of prostaglandins. One set of enzymes involved is cyclooxgenase (COX-1 and COX-2). (Celecoxib is selective for COX-2)

ketorolac	Toradol (Roche)	10mg tablet	20mg starting, then 10mg q.i.d.; maximum 40mg/d for no more than 5 days
celecoxib	Celebrex (Pfizer)	100mg, 200mg, 400mg capsules	400mg starting, then 200mg b.i.d.

Non-narcotic non-NSAIDs MOA: Opioid agonist; weak noradrenaline and serotonin reuptake inhibitor

tramadol

Ultram (Ortho-McNeil)

50mg tablet

50 to 100mg q4 to 6h; maximum 400mg/d (300mg/d in elderly patients)

Narcotics MOA: Stimulate opioid receptors in the brain

acetaminophen and codeine	Tylenol No. 3 (OrthoMcNeil)	300mg + 60mg tablets	300 to 1,000mg + 15-60mg q.i.d. Maximum 24-hour dose is 4,000mg of acetaminophen and 360mg of codeine
acetaminophen and oxycodone	Percocet (Endo Pharmaceuticals)	325mg + 2.5, 5, 7.5 or 10mg; 500mg + 7.5mg; 10mg + 650mg tablets	one tablet q.i.d.

Corticosteroids MOA: Glucocorticoid receptor agonist

prednisone	Deltason (Pfizer)	2.5mg, 5mg, 10mg, 20mg and 50mg tablets; 5mg/5ml solution/syrup	Varies based on condition
methylprednisolone	Medrol Dosepak (Pfizer)	2mg, 4mg, 8mg, 16mg, 24mg and 32mg tablets Medrol Dose Pak 21 4mg tablets	Varies based on condition

Anti-inflammatories
NSAIDs are excellent analgesics that may help in the management of patients who have less severe ocular inflammatory conditions. However, consider oral corticosteroids (table 4) when ocular inflammation is deep, associated with systemic conditions, or when topical corticosteroids are ineffective. Common conditions that may require use of oral corticosteroids include scleritis, recalcitrant episcleritis, uveitis, periocular insect bites, acute allergic blepharodermatoconjunctivitis, inflammatory orbital pseudotumor, giant cell arteritis and pseudotumor cerebri. A retrospective study found that approximately 17% of patients with episcleritis required supplemental treatment with oral NSAIDs to achieve resolution, whereas 30% of patients with scleritis needed oral NSAIDs. A total of 32% needed oral prednisolone, and 26% required systemic immunosuppressive drugs as definitive treatment.⁵ Although clinical studies have not been conclusive, oral corticosteroids are commonly effective when used in conjunction with antivirals, as they help manage the pain associated with herpes zoster ophthalmicus in patients older than 50.

In acute, short-term situations, a taper regimen for oral corticosteroids may not be necessary. However, when ocular corticosteroids are used for longer periods and a taper is indicated, the taper depends on dosage and duration of treatment.

Side effects of oral corticosteroids include reduced immune response, adrenal insufficiency, induced secondary diabetes, Cushings syndrome, delayed wound healing, weight gain and mood swings. Be sure to consult with the patients primary-care physician prior to starting oral corticosteroids. Blood pressure monitoring, blood glucose or urinalysis for glycosuria, and assessment of osteoporosis risk are important in the management of any patient chronically using systemic steroids.

Carbonic Anhydrase Inhibitors
Carbonic anhydrase inhibitors (CAIs) (table 5) diminish production of extracellular fluids in the eye and cerebral ventricular system. Therefore, they may have a profound role in diminishing intraocular and intracranial pressure. Although oral CAIs may reduce IOP by as much as 50%, their role in treating glaucoma has diminished in recent years because of better topical and surgical treatment options. However, CAIs are still valuable in the management of acute angle-closure glaucoma and pseudotumor cerebri.

CAIs are contraindicated in patients with sulfa allergies because these drugs are sulfonamide-type compounds. Additionally, CAIs are not recommended for patients diagnosed with chronic obstructive pulmonary disease, liver disease, kidney disease, Addisons disease, poorly controlled diabetes and sickle-cell disease or trait.

The side effects of CAIs can be significant and include renal calculi (i.e., kidney stones), frequent urination, diarrhea, nausea, tinnitus, depression, blood dyscrasias, fatigue, a metallic taste and paresthesias. Methazolamide tends to be better tolerated than acetazolamide, although similar adverse reactions can occur. For individuals with chronic conditions (e.g., pseudotumor cerebri), Diamox Sequels (acetazolamide, Wyeth) is a time-released formulation that offers similar therapeutic efficacy, but with reduced side effects. However, this product is not recommended for acute ocular conditions, such as angle-closure glaucoma.

Table 5: Carbonic Anhydrase Inhibitors MOA: Reduce cerebrospinal fluid and aqueous production

Generic	Trade	Formulations	Dosage
acetazolamide	Diamox (Wyeth)	125mg, 250mg tablets; 500mg Sequels	Acute angle closure: 500mg, additional 250mg p.r.n.Chronic use: 500mg b.i.d.
methazolamide	Neptazane (Wyeth)	25mg, 50mg tablets	Chronic use: 25 to 50mg b.i.d.

Now that 45 states allow optometrists to prescribe some type of oral medications, the arsenal to treat our patients has expanded significantly. However, along with this newfound authority comes great responsibility. Prior to writing a prescription, optometrists must know the side effects, drug interactions, contraindications and correct dosing regimen to obtain the desired outcome in the safest manner possible.

Drs. Black and Tyler are assistant professors and chiefs of their respective primary care clinics at Nova Southeastern University College of Optometry. Dr. Kabat is an associate professor at Nova Southeastern and a contributing editor for Review of Optometry. The authors do not have a financial interest in any products mentioned.

1. AOA News 2005 Feb;43(14).
2. Sudesh S, Laibson PR. The impact of the Herpetic Eye Disease Studies on the management of herpes simplex virus ocular infections. Curr Opin Ophthalmol 1999 Aug;10(4):230-3.
3. Simons FE. Advances in H1-antihistamines. N Engl J Med 2004 Nov 18;351(21):2203-17.
4. Sunshine A. A comparison of the newer COX-2 drugs and older nonnarcotic oral analgesics. J Pain 2000 Sep;1(3 Suppl 1):10-3.
5. Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and treatment results. Am J Ophthalmol 2000 Oct;130(4):469-76.