Nonprescription Products for the Baby

W. Steven Pray, PhD, DPh
Bernhardt Professor of Nonprescription Drugs and Devices
College of Pharmacy
Southwestern Oklahoma State University
Weatherford, Oklahoma


11/18/2008

US Pharm. 2008;33(11):12-15.

The pharmacist is on the front lines of pharmaceutical care when patients need assistance with minor health conditions. Quite often, parents and caregivers request assistance with infants. The pharmacist must have an acute understanding of which products are proven safe and effective for babies and which are not.

Age Limitations
When the FDA began its massive review of nonprescription products in 1972, one of the major tasks it had to accomplish was to determine the safe ages of use for each ingredient.¹ The agency sought data and eventually established the minimal safe ages for which specific ingredients could be given and the appropriate dosages for each age. When medications switched from prescription to nonprescription status, the sponsor and the FDA cooperated to establish the minimum age that would be safe for self-use.

What Is Safe for Babies?
The end result of the FDA's deliberations is that many nonprescription products are prohibited in children under the age of 2 years, while others are labeled against use in patients under the ages of 3, 4, 5, 6, 12, 17, or 18 years.¹ For example, the FDA recommends that OTC cough and cold medications not be used to treat infants and children under 2 years of age, and manufacturers have recently announced voluntary labeling changes for those under age 4.² Products safe for use in babies include the following: teething products, colic products, ibuprofen concentrated infants' drops (except when used for sore throat), ipecac syrup, sunscreens (with age restrictions), and some nonmedicated topical products, such as those used for diaper rash. It must be noted that many nonprescription products have never undergone scientific scrutiny to prove their safety and efficacy, regardless of age-group.¹ This includes most herbals, homeopathics, and dietary supplements. Because of lack of knowledge regarding safety and/or efficacy in babies, these products should be avoided.

Teething Products
The pharmacist can recommend topical products for teething if the child is 4 months or older.¹ As the central incisors usually do not begin to erupt until 6 to 10 months of age, this is an appropriate age limitation. Ingredients proven safe and effective for teething include benzocaine and phenol. Of the two, benzocaine 5% to 20% is more readily available and may be a better choice. It is found in Baby Anbesol (7.5% benzocaine), Baby Orajel (7.5%), and Zilactin Baby Teething Swabs (10%). Parents or caregivers should be cautioned against use of unproven and potentially dangerous teething remedies such as homeopathic teething tablets containing belladonna, coffee, magnets, tea tree oil, anise seed, clove oil, and cantharides.

Some parents may ask for assistance when the baby is experiencing fever, nasal congestion, or diarrhea.^3-5 When the pharmacist recommends a physician visit, the parent may assert that the potentially dangerous symptom is only due to teething. The pharmacist should stress that none of those symptoms are manifestations of teething, and the child's physician should be consulted for proper treatment.

Colic Products
Parents may ask for help with a baby whose violent and prolonged crying is assumed to be due to colic. The etiology of colic is not always clear, but some believe the underlying cause is trapped intestinal gas.^1,6 This has led to widespread acceptance of such simethicone-containing products as Infants' Mylicon Drops and Little Tummys Gas Relief Drops. Simethicone is nontoxic and can be given to infants according to the doses on the label. Pharmacists should be cautious about stocking or recommending various "gripe water" products, such as Little Tummys Gripe Water, Baby's Bliss Gripe Water, Wellements Gripe Water, and Gentle Care Gripe Water.⁷ These unproven products contain sodium bicarbonate, ginger, fennel, and/or chamomile, none of which is known to be safe in babies or effective for colic. Pharmacists should neither stock nor recommend these products.

Ibuprofen Infants' Drops
Ibuprofen concentrated infants' drops (e.g., Motrin) are approved for babies down to 6 months of age who experience minor aches and pains due to the common cold, influenza, headaches, toothaches, teething, and immunizations.¹ (The product is also indicated for sore throat but should not be used if the patient is under the age of 3 years.) Parents should ask a physician before using it if the child has not been drinking fluids, has lost a substantial amount of fluid due to continued vomiting or diarrhea, has stomach pain, or has experienced problems in the past when administered pain relievers or fever reducers. Parents should cease using the product and immediately consult the child's pediatrician or general practitioner if an allergic reaction occurs, as manifested by hives, facial swelling, asthma (wheezing), or shock. They should also seek medical help if pain or fever gets worse or lasts more than three days, if the child does not appear to obtain any relief within the first day (24 hours) of treatment, if stomach pain or upset worsens or persists, if redness or swelling is present in the painful area, or if any new symptoms appear. Before using the drops, the parent should check with the child's physician if the child is under a physician's care for any serious condition or is taking any other medications, including those containing ibuprofen, other pain relievers, or fever reducers.

Ipecac Syrup
For many years, ipecac syrup was considered to be a vital part of the medicine chest for every home with an infant. Given as quickly as possible after ingestion of a potentially toxic substance, it was allegedly useful in forcing the child to vomit. In recent years, however, its use has become the subject of substantial controversy. In 2003, a leading pediatric journal published research demonstrating that use of ipecac did not affect referral to emergency departments or the rate of adverse outcomes.^8-10 Furthermore, ipecac does not completely remove toxins from the stomach, causes adverse effects, is mistakenly given when it should not have been, may cause persistent vomiting, and is subject to abuse by anorexics and bulimics. As a result of ipecac's many problems, the American Academy of Pediatrics Committee on Injury, Violence, and Poison Control recommended against keeping it in the home and also took the unusual step of recommending that any ipecac already present in a household be disposed of safely. An FDA panel voted six to four to make ipecac prescription only, but the FDA has not yet acted as of this writing, and the drug remains available. Stocking and recommending it in light of the current climate is not prudent. Rather, parents should be urged to call the National Poison Hotline (800-222-1222) immediately for proper advice when a poisoning incident occurs.

Sunscreens
It is now general knowledge that sunscreens are highly effective in preventing the consequences of sun exposure when used as directed. Many parents try to place sunscreen on infants when they are about to enter the sun. However, the FDA does not wish to allow labeling on any sunscreen product for babies younger than 6 months.^1,11 There are several reasons for this. The first is that the FDA advises parents to keep babies less than 6 months of age out of the sun entirely. Therefore, having a sunscreen labeled for use under that age would give parents a false sense of security, perhaps conferring the mistaken idea that babies will be protected if the sunscreen is used. Babies cannot voluntarily move to shade when they are uncomfortable. They have underdeveloped sweat glands, which increases the risk of heat prostration. In addition, their ability to metabolize, detoxify, and eliminate the ingredients found in sunscreens is not fully developed. However, for babies above the age of 6 months, parents should choose a sunscreen with the highest sun protection factor (SPF) available (i.e., SPF 50+) to minimize the dangers of sun exposure.

Diaper Rash Products
Diaper rash products are a necessity for parents whose children are not yet toilet trained.¹² If skin is allowed to remain in prolonged contact with urine and feces, the pH becomes favorable for reactivation of skin-destructive enzymes.¹ The obvious method to avoid diaper rash is to change diapers as soon as they are wet or soiled. However, for a variety of reasons, this is not always practical. Therefore, parents often ask for advice concerning an ongoing case of diaper rash. If the skin is already broken, the baby should be referred to the pediatrician to assess the skin for the presence of a bacterial or candidal infection. If the skin is merely inflamed, however, the pharmacist can recommend a variety of diaper rash products.

Some diaper rash products are potentially dangerous and should be avoided.^1,13 They include A+D Original Ointment (contains lanolin, a potential allergen), Balmex (inactive ingredients include aloe vera and balsam of Peru, not known to be safe when applied to babies), Boudreaux's Butt Paste (contains Peruvian balsam, potentially dangerous boric acid, and castor oil [unknown safety/efficacy]), and Hyland's Diaper Ointment (contains calendula [unknown safety/efficacy] and lanolin).

The list of products with which to exercise caution also includes Johnson's Baby Oil.^1,13 This product contains mineral oil, which the FDA discussed as a possible cause of chronic irritation and folliculitis. Johnson's Original Baby Powder and Medicated Baby Powder contain talc and cornstarch, respectively. Using powders around the baby is a practice that can cause inhalation pneumonia. Thus, powdered products should be used very cautiously, if at all. The parent or caregiver who insists on their use should be instructed to place a small amount into the hand while away from the baby's head, then pat it gently on the diaper area without raising a cloud of injurious dust. The safest and most effective diaper rash ingredient may well be simple petrolatum, typified by Vaseline Nursery Jelly. Using this product avoids the potential allergenicity of lanolin, the possible toxicity of boric acid/borates, and the dangers of inhalation posed by powders.

Pediatric Dosing Charts
A final issue is that of pediatric dosing charts. Pharmacists noticed the widespread voluntary recall of various cough and cold medications advertised and promoted for infants while lacking any proof of safety and efficacy in that group. The recall was issued just prior to an FDA meeting that confirmed the need to remove these products from the market. The manufacturers have also engaged in a practice that may cause pediatric dangers. Since the 1980s, many have published pediatric dosing charts purporting to provide pediatric doses of antidiarrheal medications, analgesics, and cough/cold products.¹ These doses were not known to be safe and effective through legitimate research submitted to the FDA. If these charts are still to be found in pharmacies, they should be discarded and never consulted.

Understanding and Managing Lactose Intolerance

W. Steven Pray, PhD, DPh
Bernhardt Professor of Nonprescription Drugs and Devices
College of Pharmacy
Southwestern Oklahoma State University
Weatherford, Oklahoma


12/15/2008

US Pharm. 2008;33(12):12-15.

The inability to ingest milk as an adult, known as lactose intolerance (LI), is characteristic of many ethnic groups. The pharmacist must have a full understanding of LI and the various products that can be used to help prevent this condition from producing uncomfortable symptoms.

Lactose Digestion
Lactose in milk is a rich nutrient for infants, who develop the ability to break it down into glucose and galactose by producing lactase in the brush border membrane of the small intestine.¹ Lactase levels remain high during infancy, until weaning from the breast occurs. Then there is a gradual loss in the ability to digest milk, due to a loss of ability to produce lactase. This is called primary LI, also known as hypolactasia or lactase deficiency.^2,3 Some people retain the ability to digest milk as adults; these individuals are referred to as lactase persistent or lactose tolerant.

Prevalence
Approximately 70% of the world's peoples are lactose intolerant.⁴ The incidence of primary LI is about 90% to 100% in Native Americans, Africans, and Asians. It is estimated to be 80% in African Americans, and 55% to 80% in Hispanics. The lowest incidence (10%-15%) occurs in those descended from northern Europeans, residents of the northwestern Indian subcontinent, and desert nomads.⁵

The theory for this sharp difference in prevalence relies on archeological and anthropological evidence suggesting that the ancestors of those with lactase persistence herded cows or camels and learned to ingest their milk as a survival measure. Those who were lactase persistent survived to pass that mutation on, eventually becoming the predominant state in that subculture.

Secondary Lactose Intolerance
Some patients with lactase persistence lose the ability to digest lactose as a result of environmental triggers, a condition known as secondary LI. Lactase production is confined to the upper third of the intestinal villi.⁴ Due to its superficial location, conditions that affect villi often disrupt lactase production. One example is intestinal infection. Rotavirus is a common cause of diarrhea in infants, often contracted in daycare. After the child recovers from the effects of the rotavirus, parents may notice the infant cannot ingest formula or milk like before. Infection with Giardia lamblia or enteropathogenic Escherichia coli may also be causal. Patients who experience secondary LI from an infection may be advised to slowly reintroduce lactose-containing products to ascertain whether lactase is again present. If it is not tolerated, lactose should be withdrawn and reintroduced later.

Secondary LI may also be caused by celiac disease, malnutrition, irritable bowel syndrome (IBS), or intestinal surgery.⁴ Tetracyclines, neomycin, cimetidine, and antithyroid medications have all been implicated as causes.

Manifestations
The manifestations of primary and secondary LI are virtually identical. When a patient with LI ingests milk, lactose that cannot be digested reaches the small and large intestines in intact form. Symptoms usually begin about 30 to 120 minutes postingestion. Lactose is osmotically active and causes the intestines to draw in and retain additional water with a meal. This osmotic activity produces the same type of manifestations as ingestion of saline laxatives, such as magnesium citrate or Fleet Phospho-Soda.

Initial symptoms of the excessive intestinal fluid include nausea, rumbling in the stomach, cramping, and abdominal discomfort or pain.⁶ The excessive fluids are moved through the bowel more rapidly. When they reach the large intestine, resident bacteria ferment the lactose, causing excessive production of hydrogen, short-chain fatty acids, methane, and carbon dioxide.⁷ Thus, the patient also experiences flatulence, bloating, and added abdominal discomfort. The end result is the collection of large amounts of gas and fluids in the distal bowel. The patient usually feels an urgent need to defecate. If the individual is unable to do so, intense pressure may overcome the anal sphincter's ability to retain materials, causing involuntary leakage of stool, staining of undergarments, and incontinence. If the patient is able to defecate, stools will often be diarrheal and watery.

Diagnosis
There are several tests that can be used to diagnose LI. In the lactose tolerance test, blood glucose is examined at several points after lactose ingestion to determine whether it was digested.^8,9 A hydrogen breath test measures intestinal absorption of hydrogen after lactose inges­ tion.¹⁰ The hydrogen level in the breath is normally nil. Elevated levels imply colonic maldigestion of lactose with resultant hydrogen production.

Tolerance Level
Adults who retain the ability to ingest dairy products can take full advantage of their nutrients (i.e., calcium, vitamins A and D). Those whose diets completely restrict milk intake are especially prone to osteoporosis and osteopenia, increasing the risk of bone fractures in later life.⁴ Many Americans lie in the middle of these two extremes in that they can ingest a specific amount of lactose without experiencing symptoms. Unfortunately, they may assume that they are completely lactose intolerant and voluntarily cease ingestion of all dairy products.

The pharmacist can provide advice on determining the individual lactose tolerance level, allowing patients to still obtain the nutrients found in dairy products. Patients should be advised to identify all milk-containing foods and avoid them scrupulously for about three weeks. If symptoms persist, there are two possibilities.⁴ Either they are still ingesting lactose, or they have another condition such as IBS. If further lactose restriction does not cause symptoms to abate, they must seek a physician diagnosis. If the symptoms do remit, they should remain on the lactose-free diet for three more weeks. Then, adhering to the same diet, the patient should ingest one-quarter cup of milk with breakfast. If symptoms recur, the patient is highly lactose intolerant and should adhere to the diet without introducing milk. However, if they tolerate the milk without symptoms, they should repeat the diet and milk for several days. They should then increase the amount of milk to one-half cup and repeat the cycle. Eventually, they will come to a level that is comfortable for them.

OTC Lactase Products
Pharmacists can also aid patients by suggesting that they purchase lactase-containing tablets. The most well-known product is Lactaid.⁴ It is available in two strengths. Lactaid Original Strength Caplets contain 3,000 FCC units of lactase. The suggested dose is three caplets swallowed or chewed with the first bite of a dairy product. Lactaid Fast Act is available as caplets or chewable vanilla tablets. Each dosage form contains 9,000 FCC units, with a suggested dose of one caplet/tablet with the first bite of dairy. Generic products are also available.

Milk Substitutes
Patients may also be advised by the pharmacist on nonpharmacologic methods to prevent LI. The major thrust is to substitute normal dairy products with lactose-free versions. There are a wide variety of milk substitutes on the market. They include the Lactaid brand, real milk products to which lactase has been added, producing altered milk that is useful for those with LI.⁴ All require refrigeration. The Dairy Ease line of products includes whole milk, reduced-fat, and fat-free options. Consumers can also try a line of soy substitutes, such as Silk Soymilk products, or rice-based milk substitutes, such as Rice Dream.

Milk Allergy
Some patients with LI mistakenly believe that they have developed a milk allergy. It is critical to differentiate LI from a milk allergy.¹¹ Patients with a true allergy to cow's milk must scrupulously avoid it to prevent a constellation of allergic reactions, including fatal anaphylaxis. However, LI is not due to an allergic reaction--it is a food intolerance.¹² With proper advice from pharmacists, patients with LI can still ingest milk and gain the benefits of its nutrients.

Pediatric Otitis Media: Managing Ear Infections in Children

W. Steven Pray, PhD, DPh
Bernhardt Professor of Nonprescription Drugs and Devices
College of Pharmacy
Southwestern Oklahoma State University
Weatherford, Oklahoma

3/18/2009
US Pharm. 2009;34(3):12-15.

Most pharmacists have been confronted by a parent whose child has an apparent ear infection, usually otitis media. The parent understandably wants to relieve the child’s pain, but nonprescription products are of no use in ear pain or otitis media, which greatly limits the scope of advice the pharmacist can offer the parent. However, the pharmacist should understand various facts about the condition in order to answer the parent’s questions.

Prevalence of Pediatric Otitis Media

The annual number of cases of otitis media in all segments of the population is unknown, but is estimated to be approximately 2.2 million (otitis media with effusion) to 5 million (acute otitis media).^1,2 Focusing exclusively on pediatric cases, experts estimate that 75% of children will suffer one or more episodes by the age of 3.^3-5 Furthermore, approximately one-half of those who do contract an ear infection will experience three or more ear infections by the age of 3 years.⁴ These startling statistics are further buttressed by the fact that ear infections are the most common illnesses experienced by babies and young children and are the number one cause of consultations with physicians, and that otitis media is the most common cause of hearing loss in children.^3,6,7

Otitis media is responsible for at least $5 billion each year in medical costs and lost wages.⁴ Acute otitis media requires more than 20 million antibiotic prescriptions yearly, and it has been identified as the most common justification for prescribing antibiotics in children.^8-10 Approximately 20% of children develop a form of acute otitis media that is recalcitrant to treatment, being characterized by increased persistency and recurrences.¹¹

Subtypes of Otitis Media

Otitis media is subdivided into several separate conditions. One is acute otitis media(AOM). The National Institute on Deafness and Other Communication Disorders (NIDCD) explained that AOM denotes a painful infection in which certain ear structures are infected and inflamed, with fluid and mucus being trapped in the ear.³

By contrast, the NIDCD defines otitis media with effusion (OME) as a noninfectious condition in which fluid and mucus are trapped in the ear, possibly following a bout of AOM, a condition also referred to as “glue ear” or serous otitis media.² This condition makes it more difficult to resist future infections and can also affect hearing.

The National Institutes of Health defines chronic otitis media as a subcategory of otitis media in which fluid persists, and there may or may not be infection with bacteria or viruses.¹² The agency also defines suppurative chronic otitis as a situation in which the eardrum undergoes repeated bouts of rupture or draining or in which middle ear or mastoid inflammation persists.

The medical literature utilizes a third term for a subtype of otitis media, recalcitrant or difficult-to-treat otitis media.^1,11 The patient begins with a case of acute otitis media, but antibiotic therapy fails to effect an improvement in signs and symptoms after 48 to 72 hours or more. In addition, the patient with this condition has had three or more episodes in the past six months, or has experienced four or more episodes in the year prior to the present incident.

Epidemiology of Pediatric Otitis Media

Children are the most common targets for otitis media, as the peak incidence is four to 24 months.¹ This is due to a combination of genetic, infectious, immunologic, and environmental characteristic and factors peculiar to pediatric patients.¹ For instance, the shape and caliber of the eustachian tube in children favor infection, as does the fact that children’s immunologic systems are immature and still developing.⁴

Breast-fed children have a decreased incidence of otitis media as opposed to those who feed from a bottle while lying down.^1,4 This may be due to a specific position assumed during breast-feeding, to the movements required in suckling, or to breast milk’s well-known ability to protect from infection.¹ Use of pacifiers increases the incidence of otitis media.

Attending day care is associated with an increased incidence of the condition. Being around air pollution or smokers is also a risk factor, much more so if the smokers are the parents themselves.^1,3 The risk is greater in babies of Native American, Alaskan, or Canadian Inuit background. Otitis media is more common in children of lower socioeconomic status, perhaps secondary to such contributing factors as crowded conditions, inappropriate hygiene, improper nutrition, and limited access to medical care.⁸

Etiology of Pediatric Otitis Media

Otitis media occurs as the culmination of a sequence of events. The inciting factor in most cases is another condition that also causes congestion and inflammation of the nasal mucosa, nasopharynx, and eustachian tube.¹ Thus, otitis media may follow such causative conditions as allergic rhinitis or an upper respiratory tract infection.

When the patient has an infection, bacteria are able to move through the lining or passageway of the eustachian tube to reach the middle ear.⁴ Infection causes inflammation of the middle ear lining, obstructing the eustachian tube at its narrowest segment (also known as the isthmus).^1,4 White blood cells and bacterial residue collect to form thick, yellowish pus in the middle ear. Middle ear secretions and air cannot exit as they normally do, and they collect (effusion).

Eustachian tubes in children are smaller and straighter than those in adults.³ This anatomic distinction lessens the ability of water to drain from the ear, predisposing children to otitis media.

Adenoids, located in the throat in close proximity to the eustachian tubes, are also prone to infection and inflammation, which can block eustachian tube openings and cause the same problems as when the common cold is the cause.³ Adenoids in children are larger than those in adults, predisposing them to adenoid-induced eustachian blockage.

Microbiology of Pediatric Otitis Media

When effusion fluids from pediatric patients with acute otitis media are examined, the usual organisms isolated are Streptococcus pneumoniae (40%-50% of cases), Haemophilus influenzae (30%-40% of cases), and Moraxella catarrhalis (10%-15% of cases).¹ When a child has experienced persistent or recurrent acute otitis media, the most common offender is penicillin-resistant strains of S. pneumoniae.

Manifestations of Pediatric Otitis Media

Physicians establish a diagnosis of acute otitis media using three diagnostic criteria: 1) acute, rapid onset of symptoms; 2) middle ear effusion as noted by bulging of the tympanic membrane; and 3) signs and symptoms consistent with inflammation of the middle ear.¹³ Infants and young children may display such nonspecific manifestations as diarrhea, vomiting, anorexia, fever, headache, irritability, cough, rhinitis, listlessness, and pulling or tugging at the ears.¹ Overt ear pain is less common in children under the age of 2 years, but more common in adolescents and adults.

Complications of Pediatric Otitis Media

If the problem persists for a sufficient period, the child’s hearing is seriously compromised due to an inability of the tympanic membrane and middle ear bones to vibrate normally.⁴ Eventually, the child’s speech and language are affected.³ This occurs because the child must hear normally to allow him or her to interpret normal speech and imitate it as language and speaking skills evolve. Severe ear pain is common, and rupture of the tympanic membrane is a possibility.⁴ Infection can extend to areas such as the mastoid or brain.^4,12

Treatment of Pediatric Otitis Media

The goals of treating pediatric otitis media are to resolve symptoms and reduce the risk of its recurrence.¹ Antibiotics are the most often recommended medication in active otitis media, with analgesics for ear pain.⁴ Unfortunately, about 34% of streptococcal infections are now resistant to penicillin, and 22% are resistant to multiple medications.⁹

A set of guidelines from the National Guideline Clearinghouse states that amoxicillin should be the first choice for all cases of acute otitis media.¹⁴ The recommended dose is 80 mg/kg/day in two equally spaced, divided doses for five to 10 days in those aged less than 4 years, increased to 40 to 60 mg/kg/day for those aged 4 years and above. If the patient is allergic to amoxicillin, the guideline suggests a single dose of azithromycin dosed at 30 mg/kg. If the infection fails to respond to amoxicillin after 72 hours, the guideline recommends administration of
amoxicillin/clavulanate dosed at 80 mg/kg/day of amoxicillin component, divided into two equally spaced daily doses for 10 days, or azithromycin 20 mg/kg daily for three days.

If the child has OME, antibiotics are not indicated, as there is no infectious component. However, the child must have periodic examinations to ensure that the effusion has cleared, and possible appointments with otolaryngologists to assess the impact of hearing loss on language delay.¹⁴ If fluid persists for more than three months and the child has hearing loss, physicians may place tubes in the eardrum in the procedure known as a myringotomy.

Precautions in Pharmacist Recommendations

The patient with any type of ear pain or suspected otitis media must be referred to a physician or pediatrician for assessment. It is improper for the pharmacist to recommend any nonprescription product, such as decongestants (e.g., pseudo ephedrine), antihistamines, or analgesics and suggest that the patient will thereby be able to avoid an appointment with a physician.

Pharmacists may field questions about the use of olive oil (sweet oil) in the ear when the child has ear pain or an apparent ear infection.¹³ The patient may volunteer that the person who recommended this old home remedy also said the olive oil should be warmed prior to instillation. Placing warm oil in the ear may temporarily soothe the ear that is pained with otitis media. However, the pharmacist should explain that the source of the ear pain and infection is beyond the tympanic membrane. Olive oil cannot (and should not) pass through an intact tympanic membrane. Its use delays securing appropriate care for the child, and applying it only gives a false sense of security to parents and caregivers.

Recommendations for the Use of OTC Cough and Cold Medications in Children

Antihistamines

Antihistamines are reversible H₁-receptor antagonists that block histamine activity in the respiratory tract, gastrointestinal (GI) tract, and blood vessels. They may help prevent and treat nasal and ocular itching, rhinorrhea, and sneezing associated with the common cold, but they have not been proven to prevent colds, cure them, or shorten the course. Side effects of antihistamines include drowsiness, nervousness, insomnia, dry mouth, and dizziness. OTC cold and allergy formulas for children contain first- or second-generation antihistamines. There is no FDA-approved dosing of antihistamines for colds; however, dosing for allergic rhinitis is given. The two classes differ mainly in their sedative effects, with first-generation antihistamines causing more sedation.^3-6

First-generation antihistamines include chlorpheniramine, diphenhydramine, and brompheniramine. Appropriate dosing of chlorpheniramine in children aged 2 to 6 years is 0.35 mg/kg/day divided every four to six hours, with a maximum daily dose (MDD) of 6 mg. Recommended diphenhydramine dosing in children aged 2 to 6 years is 5 mg/kg/day divided six hours as needed, with an MDD of 300 mg. Diphenhydramine should not be used in neonates owing to possible central nervous system effects. Dosing of brompheniramine in patients aged 2 to 6 years is 1 mg every four to six hours.² Brompheniramine is not available OTC as a single-active-ingredient product, but it is found in combination with other active ingredients in pediatric cough and cold medications.

Second-generation antihistamines available OTC include cetirizine and loratadine. Appropriate cetirizine dosing in children is as follows: age 6 to 12 months, 2.5 mg/day; age 12 to 23 months, initial dosing 2.5 mg/day (may be increased to 2.5 mg twice/day); age 2 to 5 years, initial dosing 2.5 mg/day (may be increased to 5 mg/day in single or divided doses). The usual dose of loratadine for children aged 2 to 5 years is 5 mg once/day.²

Antihistamines should not be used to sedate children, and manufacturers of certain antihistamine products are making voluntary labeling changes that warn parents not to use the product with the intention of making a child sleepy.¹ Parents should avoid using antihistamines in children with glaucoma, breathing disorders, liver disease, or seizure disorders unless directed otherwise by their primary health care provider.^3-6

Decongestants

Nasal decongestants are sympathomimetic amines that exert their vasoconstrictive action by affecting sympathetic tone in the nasal mucosa. Decongestants decrease enlarged blood vessels and alleviate mucosal edema by acting on adrenergic receptors.^5,7,8 Phenylephrine stimulates alpha-1 receptors, whereas oxymetazoline, xylometazoline, and naphazoline stimulate alpha-2 receptors.⁸

Pseudoephedrine exerts its action by having both a direct and an indirect effect on adrenergic activity. Like phenylephrine and the imidazoline derivatives, pseudoephedrine stimulates alpha receptors but also indirectly causes the release of norepinephrine from its storage sites.^7,8

Systemic and nasal decongestants are available OTC. Systemic nasal decongestants are indicated for temporary relief of nasal congestion, to promote nasal or sinus drainage, and for cough caused by postnasal drip. Topical nasal decongestants are indicated for the symptomatic relief of both nasal and nasopharyngeal mucosal congestion.^5,7

Side effects from decongestants are more likely to occur in children than in adults. Effects include elevated blood pressure, tachycardia, palpitations, arrhythmia, restlessness, insomnia, anxiety, tremors, psychological disturbances, and hypersensitivity reactions. Because they are minimally absorbed, topical decongestants have systemic side effects that are milder and occur less frequently compared with systemic dosage forms. Topical use may cause burning, stinging, sneezing, or local irritation. The use of topical decongestants should be limited to three days, since prolonged use has been associated with tachyphylaxis, rebound nasal mucosa edema, and rebound nasal congestion.^5,7,8

The recommended dosing for phenylephrine nasal drops is 1 to 2 drops of 0.16% solution in each nostril every three hours as needed in infants older than 6 months; in children aged under 6 years, the dosing is 2 to 3 drops of 0.125% solution in each nostril every four hours as needed.² Appropriate dosing of oral phenylephrine in children aged 2 to 6 years is 2.5 mg every four hours or 3.75 mg every six hours, with an MDD of 15 mg.^2,9 Pseudoephedrine in children aged under 12 years is dosed at 4 mg/kg/day divided every six hours as needed with an MDD of 60 mg.^2,9

Expectorants

Guaifenesin is the only nonprescription expectorant available for use in children. It is an oral mucolytic that helps loosen phlegm and bronchial secretions by increasing respiratory-tract secretions, which leads to a more productive cough and better airway clearance.⁶ If the cough lasts for more than one week, recurs, or is accompanied by a fever, rash, or persistent headache, consultation with a primary health care provider is recommended. Adverse effects associated with guaifenesin include nausea, vomiting, dizziness, drowsiness, headache, and rash.

Guaifenesin should be taken with a full glass of water, and adequate hydration during use should be maintained. The extended-release tablets should not be chewed or crushed; therefore, if the patient cannot swallow the tablet, a different dosage form--such as syrup, solution, liquid, or minimelt (oral granule)--should be used. The most effective way to administer the oral granules is to place them on the tongue and swallow them without chewing; they may have an unpleasant taste if chewed. Appropriate dosing for children aged up to 6 years is as follows: age under 2 years, individualized dose (common dosing = 25-50 mg every four hours, with an MDD of 300 mg); age 2 to 6 years, 50 to 100 mg every four hours, with an MDD of 600 mg.^4-6

Antitussives

Codeine, although not available OTC in all states, is the gold-standard antitussive. Nonprescription antitussives that are available OTC to treat cough are dextromethorphan and diphenhydramine.¹⁰ Codeine produces cough suppression by acting centrally on the cough center located in the medulla portion of the brainstem. When used at antitussive doses, codeine should not exhibit addictive properties.¹⁰ Dextromethorphan, the d-isomer of codeine, exerts its pharmacologic action in the same way as codeine; however, it lacks analgesic and addictive properties when used at recommended doses.^4,5 In children, the recommended dose of both dextromethorphan and codeine is 1 mg/kg/day divided into four doses, with an MDD of 30 mg for children aged 2 to 5 years.^2,11 Recommended dosing for diphenhydramine, a first-generation antihistamine, in children aged less than 6 years is 5 mg/kg/day divided every six hours, with an MDD of 300 mg.²

Side effects of codeine include lightheadedness, dizziness, sedation, GI effects, and sweating. The most common effects resulting from an overdose are respiratory depression and a decreased level of alertness or consciousness. It has been reported that codeine is unlikely to produce significant side effects in children given less than 2 mg/kg; however, somnolence, ataxia, miosis, vomiting, rash, facial swelling, and itching have been reported in children receiving codeine doses of 3 to 5 mg/kg/day. Side effects of dextromethorphan include drowsiness, dizziness, nausea, GI upset, and abdominal discomfort.⁴ Dextromethorphan may cause behavioral disturbances and respiratory depression when overdosage occurs.

Insufficient evidence exists to support the use of codeine or dextromethorphan for antitussive purposes in the pediatric population.¹¹ Pharmacists should counsel parents about the lack of data supporting the use of these drugs for antitussive purposes as well as the potential risks associated with their use. Additionally, evidence suggests that second-generation nonsedating antihistamines such as loratadine are ineffective for lessening cough associated with the common cold, and therefore should not be used.¹²

Combination Products

Many nonprescription cough and cold formulations contain more than one active ingredient to treat two or more simultaneous symptoms. It is important to remember that combination cough and cold medications should be used only if the corresponding symptom is present and that combination products should not be given in addition to a different nonprescription product with the same active ingredient.

Nonprescription cough and cold formulations are available in the following combinations: antihistamine/decongestant, antihistamine/antitussive, antitussive/expectorant, decongestant/expectorant, antihistamine/antitussive/decongestant, and antitussive/decongestant/expectorant.⁵ In addition, some multisymptom products contain antipyretics and analgesics such as acetaminophen and ibuprofen. Weight-based dosing of oral acetaminophen in children is recommended at 10 to 15 mg/kg/dose every four to six hours as needed; daily dosing should not exceed 90 mg. Nonprescription ibuprofen dosing for children is 5 to 10 mg/kg/dose every six to eight hours, with an MDD of 40 mg/kg.²

Voluntary and Regulatory Changes

The safety of OTC cough and cold preparations in the pediatric population is of great concern owing to reports of severe adverse reactions and deaths in infants and children. In October 2007, the FDA's advisory committees on Nonprescription Drugs and Pediatrics met to discuss the safety and efficacy of nonprescription cough and cold medications in children. Ten days prior to the meeting, a voluntary withdrawal of 14 nonprescription infant cough and cold medications was announced by the Consumer Healthcare Products Association (CHPA) on behalf of the products' manufacturers. Manufacturers recalled these products even though they believed that they were safe. Cases of misuse leading to overdose of infants less than 2 years of age had been reported. The advisory committees concluded that evidence from pediatric studies was insufficient to prove the efficacy of cold and cough medications in children; they voted 13 to 9 to recommend that cough and cold products no longer be used in children under 6 years of age.^13,14

The FDA issued a public health advisory in January 2008 recommending that OTC cough and cold medications not be used in children under 2 years of age because of the risk of serious, life-threatening adverse events. Additionally, the FDA agreed to the manufacturers' request to change the product labeling to warn parents not to use antihistamine products to sedate children.^13,14

In 2008, the FDA held two public meetings to gather more information about the regulatory process for pediatric cough and cold medicines and about scientific testing in children. On October 8, 2008, the FDA issued a statement supporting the CHPA's announcement that manufacturers of nonprescription OTC cough and cold medicines for children were voluntarily modifying package labeling to state, "Do not use in children under 4 years of age."¹⁵

In addition to product-labeling changes, new child-resistant packaging and measuring devices for the products are being introduced. The manufacturers have been transitioning this new labeling and packaging throughout the 2008-2009 cough and cold season.¹

Complementary and Alternative Therapies

Alternative cough and cold therapies such as increased fluid intake, room humidifiers, nasal dilator strips, nasal aspiration or irrigation, and vitamin C can be used alone or in combination with an OTC cough and cold medication. Increased fluid intake helps prevent dehydration in a child suffering from a cough or cold. Room humidifiers provide relief from congestion by moistening the air.¹⁶ Warm-mist humidifiers work by boiling water in a reservoir, thereby posing a potential burn risk; for that reason, cool-mist humidifiers are generally recommended. Because bacteria thrive in moist settings, parents should be encouraged to empty water from the humidifier and wipe all surfaces dry on a daily basis.¹⁷

Nasal dilator strips are adhesive bands placed on the nose that dilate the nasal air passages or stiffen the nasal wall, leading to increased airflow and thus relieving nasal congestion.^18,19 Nasal dilator strips with or without added menthol are FDA-approved for use in children aged 5 years or older. Latex allergy is a potential concern with this product.¹⁸

Cleansing of the nasal passages with a bulb syringe and nasal irrigation with saline drops are two options for treating small children with congestion. Aspiration with a bulb syringe clears mucus from the nasal passages; 0.65% sodium chloride drops and sprays soothe irritated mucus membranes and rehydrate dried secretions for easier removal from the nasal passages.^7,18

Supplementation with vitamin C may decrease the duration of the common cold in children. A 2004 Cochrane systematic review suggests that, in children, doses of 0.2 g to 2 g vitamin C are beneficial for reducing a cold's duration. Studies have shown that children have a greater decrease in cold duration than adults, and that higher doses confer a greater benefit than lower doses. Studies evaluating 0.2 to 0.75 g/day vitamin C reported a 7% reduction in cold duration compared with an 18% reduction in studies evaluating 1 g/day.²⁰ Children given 2 g/day demonstrated a median decrease in cold duration of 26%, versus a 6% median decrease in adults receiving 1 g/day.²¹ At doses greater than 1 g, side effects including nausea, vomiting, increased iron absorption, and diarrhea may occur.⁵

Conclusion

Pharmacists are accessible members of the health care team and are often consulted by parents or guardians regarding selection of appropriate nonprescription cough and cold products for their children. The parent or guardian should be counseled to carefully follow certain guidelines for usage (see sidebar) when an OTC cough and cold medication is being considered for use in children.^22,23

3/18/2009

US Pharm. 2009;34(3):33-35.