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Topical Therapeutics for the Pediatric Patient
Topical allergy medications are indicated for the treatment of seasonal allergic conjunctivitis, and vernal conjunctivitis. Children experience symptoms and decreased quality of life from allergic conjunctivitis at a rate similar to adults.(33) Anti-allergy medications are available as antihistamines, mast-cell stabilizers, vasoconstrictors, anti-inflammatory agents, and steroids. These medications are available as prescription only and over-the-counter. Children tend to rubs their eyes when they experience itch. Thus, hand washing as an adjunct therapy to topical medications is particularly important in children with allergies. Also keep in mind the drying effect of oral antihistamines, adding to children�s propensity to rub their eyes. Most of the topical allergy medications are approved for children 3 years of age and older. The only one exception is lodoxamide tromethamine (Alomide), which is approved for age 2 years. Agents approved for age 4 years and older include azelastine (Optivar), and the cromolyns (Crolom and Opticrom). Loteprednol etabonate (Alrex) is approved for age 12 years and older.
Vasoconstrictors are available over the counter and are approved for use in children older than age 6 years. Accidental oral ingestion can lead to central nervous system depression, coma, and marked hypothermia. The ocular side effects of vasoconstrictors include burning, stinging, and mydriasis, especially in those of lighter irides. Two such products are naphzoline 0.025%-pheniramine 0.3% (Naphcon-A) and naphazoline 0.05%-antazoline 0.5% (Vasocon-A).
Dual agents, with mast-cell stabilizers and antihistamines are well-tolerated in children and have a twice daily dosing only.(34) Olopatadine hydrochloride (Patanol), epinastine (Elestat), azelastine (Optivar), and ketotifen fumarate (Zaditor) are four such drugs. All are approved for age 3 years and older, except for Optivar, approved for age 4 years and older. The next generation olopatadine is given once daily and is awaiting FDA approval.
Second generation antihistamines such as emedastine difumarate (Emadine) are also frequently used, though a notable side effect is somnolence. While the adverse effect of somnolence is much less likely with the second compared to first generation antihistamines, none of them are completely free of central nervous system effects, such as impaired concentration, dizziness, headache, and insomnia.(35) These side effects should be included in the differential diagnoses of like symptoms elicited in the course of examining a pediatric patient.
A review of the most common topical anti-allergy ophthalmic medications shows 100% (10 out of 10) drugs have pediatric labeling information.(Table 2)
Corticosteroids are used to treat ocular inflammation and severe allergic reactions. Side effects from corticosteroid use include elevation of intraocular pressure and posterior subcapsular cataracts. There is some evidence suggesting children have a greater ocular hypertensive response to steroids than adults.(36,37) Such dose-dependent differences are of significance in situations, such as treatment of uveitis, when the course may be prolonged.
There are several mild steroids approved for pediatric use in patients age 2 years and older. They are the fluorometholones, FML, eFlone, Flarex, and Fluor-Op. Safety in pediatric patients has not been established for any of the maximum strength steroids, such as the presdnisolones (Inflamase Forte, Pred Forte, Pred Mild), loteprednol (Lotemax), and rimexolone (Vexol).
Nonsteroidal anti-inflammatory drugs (NSAIDs) may play a role in the management of corneal abrasions, post foreign body removal, strabismus surgery, and allergic conjunctivitis. Ketorolac (Acular LS) is a preservative-free non-steroidal anti-inflammatory topical ophthalmic agent safe and effective in the treatment of seasonal allergic conjunctivitis in children age 3 years and older.(38) Nepafenac (Nevanac) is approved for age 10 years and older. Diclofenac (Voltaren) and bromfenac (Xibrom) are nonsteroidal anti-inflammatory agents whose safety and efficacy profiles for use in children have not been established.
Table 4: Nonsteroidal Anti-Inflammatory Medications (NSAIDs)
A review of the most commonly prescribed anti-inflammatory medications show that 40% (6 out of 15) have pediatric safety information, specifically 27% (3 out of 11) of corticosteroids and 75% (3 out of 4) of NSAIDs.(Tables 3 and 4)
Combination corticosteroid-antibiotic medications are used in the treatment of corneal abrasions or burns, postsurgical management, and inflammatory conditions of the ocular surface or eyelids. A combination steroid-antibiotic provides prophylactic protection while decreasing inflammation. Frequently prescribed combination medications tobramycin/dexamethasone (Tobradex) as well as fluorometholone, sodium sulfacetamide (FML-S) are approved for use in patients age 2 years and older. And dexamthasone/neomycin/polymyxin B. Others combinations with pediatric use labeling are sulfacetamide/prednisolone combinations, Blephamide and Vasocidin, both approved for use in age 6 years and older.
A review of the most commonly prescribed corticosteroid-antibiotic combinations shows that 31% (4 out of 13) have pediatric use safety profiles.(Table 5)
When Herpes Simplex Virus (HSV) and Herpes Zoster Virus (HZV) infections occur in children, the disease frequently result in severe ocular inflammation. This is in contrast to adenoviral infections, which usually result in less ocular effects in children than in adults.
The drug of choice for the treatment of HSV is trifluoridine (Viroptic), approved for use in patients age 6 years and older. Vidarabine (Vira-A), approved for age 2 years and older, is reserved for cases of hypersensitivity to trifluridine, but is no longer commercially available.
Medical treatment of pediatric glaucomas is usually adjunctive to surgical interventions. Topical medications are generally used temporarily until surgery can be performed, in later childhood onset glaucomas, and glaucoma secondary to ocular or systemic diseases. The glaucoma medications include cholinergic agonists (miotics), sympathomimetics, beta-adrenergic antagonists, carbonic anhydrase inhibitors, alpha-2-slective agonists, and prostaglandin analogs. All of the commonly prescribed topical glaucoma medications have a pediatric safety profile of either not established or not recommended in pediatric patients. However, some practitioners are more comfortable prescribing beta-adrenergic antagonists and the carbonic anhydrase inhibitor acetazolamide to infants based on its safe in lactation status established by the American Academy of Pediatrics.(39)
Side effects from glaucoma medications are of concern particularly in cases of prolonged treatment. It has been found that one drop of 0.5% timolol can reach cardiac beta-blockade levels in infants under 2 years of age.(40) Timolol can also exacerbate asthma, and thus is contraindicated in children with cardiac arrhythmias and bronchospasm.(41) Alpha-adrenergic agonists are contraindicated in children due to side effects of somnolence and fatigue. Sleep disturbances and sweating have been reported in children prescribed prostaglandin drugs.
Only one glaucoma medication, alphagan, has established safety in pediatric patients. Many of the other medications are not recommended for use in children.
There is only one commercially available topical antifungal, it is natamycin and its safety in pediatric patients has not been established.
Dilating agents are frequently used for refraction and retinal examination. Dilating agents are composed of sympathomimetics and parasympatholytics, with potentially significant side effects of hypertension, tachycardia, arrhythmias, headache, restlessness, seizures, psychosis, gastrointestinal disturbances, and respiratory depression. Premature infants are especially sensitive to side effects. Phenylephrine can cause hypertension and tachycardia and should be used with caution in children with hyperthyroidism or tachyarrhythmias.(42)
Cycloplegic agents are indicated for refraction in infants and young children, penalization therapy for amblyopia, postoperative cycloplegia, and uveitis management. Some patients are especially susceptible to toxic systemic side effects from use of atropine and cyclopentolate, including those with spastic paralysis or brain damage, lightly pigmented individuals, and Down syndrome. Cyclopentolate and atropine in concentrations greater than 0.5% are not recommended in small infants because of possible central nervous system disturbances. The combination of cyclopentolate 0.2% and phenylephrine 1% (Cyclomydril) provides adequate mydriasis while minimizing unwanted systemic effects, particularly for the examination of premature infants.(42) Atropine 1% solution has been shown to be a safe and effective treatment of moderate amblyopia in three to seven year olds.(43) The recommended dosage is once daily or weekends only in the sound eye.(44)
Clinicians should be aware of the increasing number of topical ophthalmic drugs that are approved for pediatric use. Changes in FDA requirements along with economic factors suggest that the trend is for more and more pharmaceutical companies to provide pediatric use labeling. This paper provides clinicians with a summary of the most commonly prescribed topical ophthalmic medications and indicates which drugs are currently FDA approved for young children. Clinicians should use the variety of resources available for up-to-date pediatric use information when treating their younger patients, and choose those with established pediatric safety profiles.
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