Review of Cornea






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Oral Meds in Eye Care

As doctors, we tend to settle into habitual prescribing patterns—but, we must make sure that we always fully consider the patient’s needs.
Jill Autry, O.D., R.Ph.

11/18/2009

As a pharmacist practicing in a hospital setting, I could tell you the physician’s name based solely on his or her admitting medication orders. Most doctors become comfortable using certain medications and dosing regimens, and we all have a preferred drug of choice for most conditions. We become well educated in the proper use, contraindications and side effects of our chosen agent, and we usually have a standard second choice when confronted with an allergic history or other patient-specific concern. As an optometrist and pharmacist, I am fortunate to have a view from both sides of the counter.  

Oral Antibiotics
Optometrists’ most commonly used oral medications are antibiotics. We treat skin and soft tissue infections, such as preseptal cellulitis, dacryocystitis and dacryoadenitis. Most of these infections are caused by gram-positive organisms—namely, strains of Staphylococcus or Streptococcus—and my drug of choice is amoxicillin. This aminopenicillin has extended coverage for gram-positive and some gram-negative organisms and demonstrates increased resistance to beta-lactamases when compared to standard penicillin. It is inexpensive and causes few side effects. In the past, Augmentin (amoxicillin/clavulanic acid, GlaxoSmithKline) was my drug of choice due to concerns about periorbital infections and the gram-negative organism Haemophilus influenzae, especially in young children.

With the advent of the Haemophilus influenzae B (Hib) vaccine, which has been given routinely to all children in the U.S. since 1985, the incidence of H. influenzae cellulitis has decreased dramatically.1 Augmentin, however, remains an excellent choice and is preferred by some clinicians. Keep in mind that the generic formulation is still somewhat costly, and that more gastrointestinal side effects are likely than with standard amoxicillin.2 The adult dose for both amoxicillin and amoxicillin/clavulanic acid is 875mg b.i.d. Both can be used in pregnancy. The pediatric dose is 20 mg/kg/day to 40mg/kg/day, divided q8h.

A Case Study in Pediatric Dosage Adjustment13
A 6-year-old Hispanic female presents with preseptal cellulitis. She is not allergic to any medications, she has no other pertinent systemic health conditions, and her mother tells us she weighed 49 lbs. at her pediatric appointment last month. We would like to start her on oral antibiotic therapy in addition to hot compresses locally. We decide to use amoxicillin for her treatment because of its gram-positive coverage. The pediatric dosage range for amoxicillin is 20mg/kg/day to 40mg/kg/day in three divided doses, or q8h. A lower dosage is recommended for milder infections, while the higher dose is reserved for more severe conditions. For preseptal cellulitis in a child, consider a dosage on the high side: 35mg/kg/day.

So, 49 lbs. divided by 2.2 = 22.3kg. And 22.3kg x 35mg/kg is 780.5mg. Divide 780.5mg by three for q8h dosing, and we arrive at approximately 260mg per eight-hour dose for this patient. But, if you write a prescription for 260mg every eight hours, the pharmacist is going to call you for clarification. Complete the prescription by writing for a dosage strength and formulation available from the manufacturer. Amoxicillin is supplied in multiple suspension dosage forms and bottle sizes. The closest to our desired dosage is 250mg/5ml. So, we can write our prescription for amoxicilllin 250mg/5ml. We need 5ml every eight hours for 10 days. So, 15ml/day x 10 days = 150ml bottle. The directions would be to take one teaspoon (approximately equivalent to 5ml) every eight hours for 10 days.  
Dosage Conversion Formula
Step 1: Convert pounds to kilograms. 49 lbs. / 2.2 = 22.3kg
Step 2: Multiply kilograms by dosage recommendation. 22.3kg x 35mg/kg = 780.5mg
Step 3: Divide daily milligram total by number of doses per day.   780.5mg / 3 = 260mg
Step 4: Choose from available manufactured doses.  Closest available dose: 250mg
Step 5: Write prescription. 
See below
Final Prescription 
Dr. John Smith
2020 North Main Street
Anytown, TX 12345
(555) 123-4567  

Name: Laura Hernandez                   Age: 6
Address: 4000 Avenue A                  Date: 10-15-2009    

Rx:     Amoxicillin 250/5 #150ml          
         1 tsp q8h x 10 days  

Refills—ZERO                                John Smith, O.D.
 
Because amoxicillin and amoxicillin/clavulanic acid both originate from the penicillin family of medications, they are contraindicated in patients who report a penicillin or cephalosporin allergy. When faced with this type of patient, I generally prescribe sulfamethoxazole/trimethoprim (i.e., Septra by Monarch Pharmaceuticals, or Bactrim, by Roche Laboratories), one double-strength tablet b.i.d., as it is an excellent broad-spectrum antibiotic with little resistance and generic availability. This is also my choice in patients who report a history of methicillin-resistant Staphylococcus aureus (MRSA) infections or who have an inordinate amount of pain at the infection site, which can signal a MRSA infection.3 Septra is a sulfonamide antibiotic and is contraindicated in sulfa-allergic patients. Any discussion of dry eye disease must include the use of oral doxycycline. In the management of dry eye, this tetracycline derivative is used not for its antibiotic action (although it is an excellent broad-spectrum anti-infective agent), but for its anti-inflammatory action in the meibomian glands of the eyelid.

The recommended dosage of doxycycline in chronic posterior blepharitis has changed from the earlier antibiotic amount of 100mg b.i.d. to its collagenase-inhibiting, anti-inflammatory dosage of 20mg b.i.d.4 When cost is a concern (the monthly cost for the 20mg tablet is six times that of the generic 50mg tablet), I prescribe generic doxycycline 50mg tablets b.i.d. instead of the 20mg brand-only version. And, the dose of the generic can be decreased to 50mg q.d. or even three times weekly as maintenance therapy.

Doxycycline is a Pregnancy Category D medication and contraindicated in pregnancy and lactation due to permanent discoloration of teeth and detrimental effects on bone development. It should be used cautiously even in non-pregnant women of childbearing years. Doxycycline can be taken with food and/or milk but should be avoided before bedtime or lying down due to the possibility of erosive esophagitis. Also, warn patients of increased photosensitivity.  

Pain Control
Due to the increased sensitivity of the cornea and other ocular structures, pain control is paramount for patients with abrasions and other traumatic or surgically induced ocular pain. The most common class of pain medications is the opioid family.

Codeine is the naturally occurring prototype, and there are semisynthetic derivatives of codeine, such as hydrocodone. All codeine and hydrocodone products, when combined with acetaminophen or ibuprofen, are Class III controlled substances and must be prescribed only by a licensed prescriber with a valid DEA license. Some states also have stricter prescription requirements for these substances. Codeine allergies are frequently described, but most patients actually experience codeine-related side effects—not true allergic reactions. Gastrointestinal side effects, such as nausea, vomiting and constipation, are common with codeine.5 Codeine is known to initiate a histamine release, causing itching, flushing and hives—all of which are often mistaken for an allergic reaction.5 True codeine allergies, on the other hand, cause trouble breathing, hypotension and swelling of the lips or tongue.6

One very commonly prescribed oral pain medication is a mixture of hydrocodone 5mg and acetaminophen 500mg, known by the brand name Vicodin (Abbott Laboratories). When prescribing this drug, it is recommended to prescribe one to two tablets every four to six hours as needed. The semisynthetic opioids are far less likely to invoke the side effects commonly seen with naturally occurring opioids, such as codeine.7 With larger patients or those already tolerant to pain medications due to a history of chronic use, consider a stronger combination: hydrocodone 7.5mg/acetaminophen 750mg, branded as Vicodin ES. The directions mimic those of regular Vicodin except for the number of tablets at each dose: one tablet every four to six hours p.r.n. For patients who can’t take acetaminophen due to hepatic disease, use Vicoprofen (Abbott Laboratories), a class III mixture of hydrocodone 7.5mg and ibuprofen 200mg, which is also available generically.

As discussed, most reports of a codeine allergy are reactions induced by histamine release. But, patients can be treated with Darvocet-N (propoxyphene/acetaminophen, Xanodyne Pharmaceuticals) 100mg q6h if a true allergy is suspected.6 In conditions requiring less aggressive pain control, consider Ultram (tramadol, Ortho-McNeil Pharmaceutical), a non-narcotic opioid receptor agonist or Toradol (oral ketorolac, Roche Laboratories) a nonsteroidal anti-inflammatory agent. Ultram is available in 50mg tablets and is dosed every four to six hours, whereas Toradol is dosed at 10mg every four to six hours.8 These agents are not controlled substances, so O.D.s without DEA privileges can use them to provide much needed pain control to their patients. (Note: Ultram is controlled in Kentucky.) For corneal abrasions or other causes of pain in children, acetaminophen with codeine is available in a elixir of 120mg acetaminophen/12mg codeine per teaspoon, which can be dosed as follows: one teaspoonful three or four times daily for ages three to six; two teaspoonfuls three or four times daily for ages seven to 12; and three teaspoonfuls every four hours for children older than 12.8 All pain meds can cause sedation and other central nervous system disturbances. Although uncommon in eye care, pain medications can be addictive upon extended use.

Oral Hypotensive Meds
Topical hypotensive medications may be inadequate when severe acute or chronic increases in intraocular pressure are encountered. Although acute angle closure requires oral anti-glaucoma agents, these medications are also utilized in other types of increased IOP, such as postoperative pressure spikes, steroid induced glaucoma, or inflammatory cases where prostaglandin analogues are contraindicated. My oral agent of choice is the carbonic anhydrase inhibitor (CAI) Diamox (acetazolamide, Lederle Laboratories), at a dosage of 500mg stat (two 250mg immediate release tablets) and 250mg b.i.d. thereafter. If necessary to control IOP, the dose can be increased to 500mg b.i.d. (use the 500mg sequels), but a dose-response increase in side effects may be seen.8

Side effects to oral CAIs include paresthesias (“pins and needles” or numbness in the extremities), sedation and changes in taste (especially with carbonated sodas).8 Also, Neptazane (methazolamide, Storz/Lederle Laboratories) can be used at a dosage of 25mg to 50mg t.i.d. This oral CAI causes fewer side effects with similar efficacy, which makes it beneficial in cases that require longer-term dosing. Although both oral CAI agents contain a sulfa moiety in their chemical compounds, true sulfa allergies are associated with sulfa-containing antibiotics, such as Septra, and generally do not cause a reaction with non-antibiotic sulfa-containing medications, such as topical or oral CAIs.6,9

In patients who have a life-threatening history of sulfa allergy, however, use these with caution. Oral CAIs are contraindicated in hepatic disease and severe renal insufficiency. Also, individual disease states may result in complications, such as sickle cell disease. Contact the patient’s internist or nephrologist for recommendations on use and/or dosage changes for these medications if using more than in an acute, one-dose-only situation.

Oral Antivirals
Oral antiviral agents inhibit both the herpes simplex and herpes zoster viruses. The current herpetic oral antiviral armamentarium includes Zovirax (acyclovir, GlaxoSmithKline), Famvir (famciclovir, Novartis Pharmaceuticals) and Valtrex (valacyclovir, GlaxoSmithKline). These medications are very well tolerated and demonstrate few side effects and little resistance—even when used long-term. Allergic reactions are very rare, and dosages only need to be reduced in severe renal disease.8 For the treatment of herpes zoster, a high-dose antiviral is the drug of choice; best outcomes are achieved when treatment is started within 72 hours of the appearance of lesions.10

Recommended dosages are acyclovir 800mg five times daily, famciclovir 500mg t.i.d. or valacyclovir 1g t.i.d. Acyclovir is, by far, the least expensive of the three agents—but, at five-times-daily dosing, this may come at the possible cost of decreased compliance. Because antiviral levels are achieved in the tears with oral antiviral agents, many eye care practitioners are now using oral antivirals rather than the corneotoxic Viroptic (trifluridine, GlaxoSmithKline) for the treatment of epithelial herpes simplex keratitis, for cover when treating stromal disease with a topical steroid, and for prevention of long-term recurrences.11

Dosage preference will vary by practitioner—e.g., for epithelial disease, we prefer acyclovir 400mg five times daily, famciclovir 250mg t.i.d., or valacyclovir 500mg t.i.d. for seven to 10 days or until the epithelial lesions have resolved. For prevention of recurrences or to cover for a steroid, I recommend acyclovir 400mg b.i.d., famiclovir 250mg q.d., or valacyclvir 500mg q.d. In choosing among the three agents, I tend to prescribe acyclovir for patients without pharmaceutical coverage. Some reports suggest famciclovir has better bioavailability, but my experience has shown them all to be therapeutically similar except for dosing regimens and cost.12  

Oral Steroids
Proceed with caution when it comes to oral steroids. They are unmatched in the treatment of inflammation and prevention of scarring, but steroids have the potential for serious side effects—steroid-induced glaucoma, diabetes, cataracts, osteoporosis, stomach ulceration and adrenal suppression. Most ophthalmic conditions do not require long-term or increased dosages; often, they only require just enough to aid topical agents, as in the case of a severe allergic reaction or difficult anterior uveitis. For these instances, I recommend a Medrol dose pack (methylprednisolone 4mg, Pfizer), which is dispensed in its own packaging with a six-day tapering schedule. Using higher doses of oral steroids for longer periods of time should be prescribed by—or at least comanaged with—an internist or ophthalmologist.  

Prescribing is not an exact science. Doctors must evaluate the condition and allergy information, systemic conditions, insurance coverage and drug profile of each patient before deciding upon a medication and dosing regimen. With this routine and a little experience, you will develop your own list of preferred medications.

Dr. Autry practices in a referral center in Houston. She lectures extensively on pharmaceuctical and ocular disease topics.  

1. Ambati BK, Ambati J, Azar N, et al. Periorbital and orbital cellulitis before and after the advent of Haemophilus influenzae type B vaccination. Ophthalmology. 2000 Aug;107(8):1450-3. 
2. Salvo F, De Sarro A, Caputi AP, Polimeni G. Amoxicillin and amoxicillin plus clavulanate: a safety review. Expert Opin Drug Saf. 2009 Jan;8(1):111-8.
3. Pangilinan R, Tice A, Tillotson G. Topical antibiotic treatment for uncomplicated skin and skin structure infections: review of the literature. Expert Rev Anti Infect Ther. 2009 Oct;7(8):957-65.
4. Yoo SE, Lee DC, Chang MH. The effect of low-dose doxycycline therapy in chronic meibomian gland dysfunction. Korean J Ophthalmol. 2005 Dec;19(4):258-63.
5. Mathelier-Fusade P. Drug-induced urticarias. Clin Rev Allergy Immunol. 2006 Feb;30(1):19-23. 6. Golembiewski JA. Allergic reactions to drugs: implications for perioperative care. J Perianesth Nurs. 2002 Dec;17(6):393-8.
7. Cherny NI. Opioid analgesics: comparative features and prescribing guidelines. Drugs. 1996 May;51(5):713-37.
8. Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug Information Handbook. 12th ed. Hudson, Ohio: Lexi-Comp; 2004:87-89.
9. Ponka D. Approach to managing patients with sulfa allergy: use of antibiotic and nonantibiotic sulfonamides. Can Fam Physician. 2006 Nov;52(11):1434-8.
10. Lang PO, Hasso Y, Michel JP. Stop shingles in its tracks. J Fam Pract. 2009 Oct;58(10):531-4.
11. Wilhelmus KR. Therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD002898.
12. Perry CM, Wagstaff AJ. Famciclovir: a review of its pharmacological properties and therapeutic efficacy in herpes virus infections. Drugs. 1995 Aug;50(2):396-415.
13. Autry J. Prescribe properly for challenging patients. Rev Optom. 2007 Dec 15;144(12):58-65.


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