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Basic and Clinical Pharmacology > Chapter 63. Therapeutic & Toxic Potential of Over-the-Counter Agents >

 

 

Case Study

A 66-year-old man presents to his primary care provider for worsening shortness of breath, chest congestion, and symptoms of a severe cold (cough, rhinorrhea, nasal congestion, drowsiness) over the past week. His past medical history is significant for heart failure, hypertension, and hyperlipidemia. His current medications include lisinopril 20 mg daily, simvastatin 40 mg daily, furosemide 40 mg daily, and potassium chloride 20 mEq daily. The patient reports sporadic compliance with his prescribed medications but admits to taking several over-the-counter (OTC) medications over the past 5 days for his recent cold symptoms, including Alka-Seltzer Plus Cold & Sinus Tablets (2 tablets every 4 hours during the day), Sudafed (60 mg every 6 hours), Advil PM (2 tablets at bedtime), and Afrin Nasal Spray (2 sprays twice daily). His social history is significant for alcohol use (3–4 beers/night). His vital signs include the following: afebrile, blood pressure 172/94 mm Hg, pulse 84 bpm, respiratory rate 16/min. On physical examination an S3 gallop is heard; 3+ pitting edema is noted in his lower extremities, and a chest examination reveals inspiratory rales bilaterally. Which of the OTC medications might have contributed to the patient's current hypertension? What drugs do OTC "cold" preparations typically contain? Are any of these preparations implicated in the signs of heart failure?

 

Therapeutic & Toxic Potential of Over-the-Counter Agents: Introduction

In the USA, drugs are divided by law into two classes: those restricted to sale by prescription only and those for which directions for safe use by the public can be written. The latter category constitutes the nonprescription or over-the-counter (OTC) drugs. In 2007, the American public spent more than $16 billion on over 100,000 OTC products to medicate themselves for ailments ranging from acne to warts. These products contain approximately 1000 active ingredients in various forms and combinations.

It is apparent that many OTC drugs are no more than "me too" products advertised to the public in ways that suggest significant differences between them. For example, there are over 100 different systemic analgesic products, almost all of which contain aspirin, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, or a combination of these agents as primary ingredients. They are made different from one another by the addition of questionable ingredients such as caffeine or antihistamines; by brand names chosen to suggest a specific use or strength ("women's," "migraine," "arthritis," "maximum"); or by special dosage formulations (enteric-coated tablets, geltabs, liquids, orally disintegrating strips and tablets, sustained-release products, powders, seltzers). There is a price attached to all of these features, and in most cases a less expensive generic product can be equally effective. It is probably safe to assume that the public is generally overwhelmed and confused by the wide array of products presented and will probably use those that are most heavily advertised.

Over the past 35 years, the FDA has been engaged in a methodical review of OTC ingredients for both safety and efficacy. There have been two major outcomes of this review: (1) Ingredients designated as ineffective or unsafe for their claimed therapeutic use are being eliminated from OTC product formulations (eg, antimuscarinic agents have been eliminated from OTC sleep aids, attapulgite and polycarbophil can no longer be marketed as OTC antidiarrheal products); and (2) agents previously available by prescription only have been made available for OTC use because they were judged by the review panel to be generally safe and effective for consumer use without medical supervision (Table 63–1). Since the appointment of the Nonprescription Drugs Advisory Committee in 1993, the rate of switches from prescription to OTC status has accelerated. Indeed, more than 700 OTC products contain ingredients and dosages that were available only by prescription less than 30 years ago. Some agents such as docosanol and the nicotine polacrilex lozenge have bypassed the prescription route altogether and have been released directly to the OTC market. Other OTC ingredients previously available in low doses only are now available in higher-strength or original prescription strength formulations. Examples of other prescription drugs with the potential for future OTC reclassification include nicotine replacement therapy (oral inhaler, nasal spray) for smoking cessation, proton-pump inhibitors (lansoprazole, pantoprazole) for heartburn, and second-generation nonsedating antihistamines (desloratadine, fexofenadine, levocetirizine) for relief of allergy and cold symptoms. The prescription to OTC reclassification process is very rigorous, and many agents have not been approved for OTC use. For example, the cholesterol-lowering agents cholestyramine, lovastatin, and pravastatin were denied OTC status on the basis that these agents could not be used safely and effectively in an OTC setting. The advisory committee believed that diagnosis and ongoing management by a health care professional was necessary for the management of hyperlipidemia, a chronic, asymptomatic condition with potentially life-threatening consequences. In a similar recommendation, oral acyclovir for OTC use in the treatment of recurrent genital herpes was not approved because of concerns about misdiagnosis and inappropriate use leading to increased viral resistance.

Table 63–1 Selected Agents Switched from Prescription to OTC Status by the Food and Drug Administration.

 

Ingredient

Indication

Year Ingredient First Switched

Single-Ingredient Product Examples

Systemic agents 

Cetirizine

Antihistamine

2007

Zyrtec

Cimetidine

Acid reducer (H2 blocker)
 

1995

Tagamet HB

Clemastine

Antihistamine

1992

Tavist Allergy

Famotidine

Acid reducer (H2 blocker)
 

1995

Pepcid AC

Ibuprofen

Analgesic, antipyretic (NSAID)

1984

Advil, Motrin IB

Levonorgestrel

Emergency contraceptive

2006

Plan B

Loratadine

Antihistamine

2002

Claritin, Alavert

Naproxen sodium

Analgesic, antipyretic (NSAID)

1994

Aleve

Nicotine transdermal system

Smoking cessation

1996

Nicoderm CQ

Nicotine polacrilex gum

Smoking cessation

1996

Nicorette

Nizatidine

Acid reducer (H2 blocker)
 

1996

Axid AR

Omeprazole

Acid reducer (proton pump inhibitor)

2003

Prilosec OTC

Orlistat

Weight loss aid

2007

Alli

Polyethylene glycol

Laxative

2006

MiraLax

Ranitidine

Acid reducer (H2 blocker)
 

1995

Zantac 75, Zantac 150

Topical agents 

Butenafine

Antifungal (topical)

2001

Lotrimin Ultra

Butoconazole

Antifungal (vaginal)

1995

Femstat-3

Clotrimazole

Antifungal (vaginal)

1990

Gyne-Lotrimin-7, Gyne-Lotrimin-3

Cromolyn

Nasal antiallergy

1997

Nasalcrom

Ketoconazole

Dandruff shampoo

1997

Nizoral A-D

Ketotifen fumarate

Ophthalmic antihistamine

2006

Alaway, Zaditor

Miconazole

Antifungal (vaginal)

1991

Monistat-7, Monistat-3

Minoxidil

Hair growth stimulant

1996

Rogaine Regular and Extra Strength For Men, Rogaine For Women

Naphazoline/Pheniramine

Ophthalmic decongestant antihistamine

1994

Naphcon A, Opcon A, Visine-A

Permethrin

Pediculicide (head lice)

1990

Nix

Terbinafine

Antifungal (topical)

1999

Lamisil AT

Tioconazole

Antifungal (vaginal)

1997

Monistat-1, Vagistat-1

 

There are three reasons why it is essential for clinicians to be familiar with the OTC class of products. First, many OTC medications are effective in treating common ailments, and it is important to be able to help the patient select a safe, effective product. Because managed-care practices encourage clinicians to limit the cost of drugs they prescribe, many will recommend effective OTC treatments to their patients, since these drugs are rarely paid for by the insurance plan (Table 63–2). Second, many of the active ingredients contained in OTC drugs may worsen existing medical conditions or interact with prescription medications. (See Chapter 66.) Finally, the misuse or abuse of OTC products may actually produce significant medical complications. Phenylpropanolamine, for example, a sympathomimetic previously found in many cold, allergy, and weight control products, was withdrawn from the United States market by the FDA based on reports that the drug increased the risk of hemorrhagic stroke. Dextromethorphan, an antitussive found in many cough and cold preparations, has been increasingly abused in high doses (eg, > 5–10 times the recommended antitussive dose) by adolescents as a hallucinogen. Although severe complications associated with dextromethorphan as a single agent in overdose are uncommon, many dextromethorphan-containing products are formulated with other ingredients (acetaminophen, antihistamines, and sympathomimetics) that can be fatal in overdose. Additionally, pseudoephedrine, a decongestant contained in numerous OTC cold preparations, has been used in the illicit manufacture of methamphetamine. A general awareness of these products and their formulations will enable clinicians to more fully appreciate the potential for OTC drug-related problems in their patients.

Table 63–2 Ingredients of Known Efficacy for Selected OTC Classes.

 

OTC Category

Ingredient and Usual Adult Dosage

Product Examples

Comments

Acid reducers (H2 antagonists)
 

Cimetidine, 200 mg once or twice daily

Tagamet HB, various generic

These products have been approved for the relief of "heartburn, acid indigestion, and sour stomach." They should not be taken for longer than 2 weeks and are not recommended for children < 12 years of age.

Famotidine, 10–20 mg once or twice daily

Pepcid AC, Maximum Strength Pepcid AC, various generic

Nizatidine, 75 mg once or twice daily

Axid AR

Ranitidine, 75–150 mg once or twice daily

Zantac 75, Zantac 150, various generic

Acid reducers (Proton pump inhibitors)

Omeprazole magnesium, 20.6 mg once daily for 14 days

Prilosec OTC, various generic

Omeprazole is the first proton pump inhibitor approved for the treatment of frequent heartburn in adults (≥ 18 years of age) with symptoms of heartburn 2 or more days per week. The product should not be taken for more than 14 days or more often than every 4 months unless directed by a physician. Omeprazole magnesium 20.6 mg is equivalent to 20 mg of omeprazole (prescription strength).

Acne preparations

Benzoyl peroxide, 5%, 10%

Clearasil, Oxy-10, various generic

One of the most effective acne preparations. Apply sparingly once or twice daily. Decrease concentration or frequency if excessive skin irritation occurs.

Allergy and "cold" preparations

Chlorpheniramine, 4 mg every 4–6 hours; 8–12 mg (extended-release) every 8–12 hours

Chlor-Trimeton Allergy, various generic

Antihistamines alone relieve most symptoms associated with allergic rhinitis or hay fever. Chlorpheniramine, brompheniramine, and clemastine may cause less drowsiness than diphenhydramine. Cetirizine and loratadine, both second-generation antihistamines, are therapeutically comparable to first-generation agents; these agents have minimal anticholinergic effects and are therefore associated with a lower incidence of sedation. Occasionally, symptoms unrelieved by the antihistamine respond to the addition of a sympathomimetic decongestant. OTC sale of products containing pseudoephedrine is restricted (see comments under Decongestants, systemic).

 

Clemastine, 1.34 mg every 12 hours

Tavist Allergy

 

Cetirizine, 10 mg every 24 hours

Zyrtec, various generic

 

Diphenhydramine, 25–50 mg every 4–6 hours

Benadryl Allergy, various generic

 

Loratadine, 10 mg every 24 hours

Alavert, Claritin, various generic

 

Brompheniramine (4 mg) with phenylephrine (10 mg) every 4 hours

Dimetapp Cold & Allergy, various generic

 

Cetirizine (10 mg) with pseudoephedrine (120 mg) every 12 hours

Zyrtec-D

 

Chlorpheniramine (2 mg) with phenylephrine (10 mg) every 4 hours

Allerest PE, Sudafed PE Sinus & Allergy, various generic

 

Loratadine (10 mg) with pseudoephedrine (240 mg) every 24 hours

Claritin-D 24 Hour

 

Triprolidine (2.5 mg) with phenylephrine (10 mg) every 4 hours

Actifed Cold & Allergy, various generic

Analgesics and antipyretics

Acetaminophen, 325–650 mg every 4–6 hours; 650–1300 mg (extended release) every 8 hours

Panadol, Tylenol, Tylenol 8-Hour, various generic

There are numerous product modifications, including the addition of antacids and caffeine; enteric-coated tablets and seltzers; long-acting or extra-strength formulations; and various mixtures of analgesics. None have any substantial advantage over a single-ingredient product. Acetaminophen lacks anti-inflammatory activity but is available as a liquid; this dosage form is used primarily for infants and children who cannot chew or swallow tablets. Do not exceed a total daily acetaminophen dose of 4 g (2 g/d in regular alcohol users). Aspirin should be used cautiously in certain individuals (see text). Use of OTC products containing aspirin, other salicylates, acetaminophen, ibuprofen, or naproxen may increase the risk of hepatotoxicity and gastrointestinal hemorrhage in individuals who consume 3 or more alcoholic drinks daily. Long-term continuous use of NSAIDs may increase the risk of heart attack or stroke.

Aspirin, 325–650 mg every 4–6 hours

Bayer Aspirin, Ecotrin, Bufferin, various generic

Ibuprofen, 200–400 mg every 4–6 hours (not to exceed 1200 mg daily)

Advil, Motrin IB, various generic

Naproxen sodium, 220 mg every 8–12 hours

Aleve, various generic

Antacids

Magnesium hydroxide and aluminum hydroxide alone or in combination; calcium carbonate, dosage varies; consult product labeling

Alternagel, Maalox, Milk of Magnesia, Mylanta, Tums, various generic

Combinations of magnesium and aluminum hydroxide are less likely to cause constipation or diarrhea and offer high neutralizing capacity. Some preparations include simethicone, an antiflatulent to relieve symptoms of bloating and pressure.

Antihelminthics (pinworm infection)

Pyrantel pamoate, 11 mg/kg (maximum: 1 g)

Pin-X, Reese's Pinworm

Treat all members of the household. Consult physician for children < 2 years of age or < 25 lb. Undergarments, pajamas, and linens should be washed daily until the infection is resolved. If symptoms persist beyond 2 weeks, contact a physician to determine if a repeat dose is indicated.

Antidiarrheal agents

Bismuth subsalicylate, 524 mg every 30–60 minutes as needed up to 8 doses daily

Kaopectate, Pepto-Bismol, various generics

Antidiarrheals should not be used if diarrhea is accompanied by fever > 101°F or if blood or mucus is present in stool. Bismuth salts can cause dark discoloration of the tongue and stools. Salicylates are absorbed and can cause tinnitus if coadministered with aspirin.

Loperamide, 4 mg initially, then 2 mg after each loose stool, not to exceed 8 mg daily

Imodium A-D, various generic

Loperamide, a synthetic opioid, acts on intestinal smooth muscle to decrease motility allowing for absorption of water and electrolytes. Poorly penetrates the CNS and has a lower risk of side effects compared with diphenoxylate or opiates. Not considered a controlled substance.

Antifungal topical preparations

Butenafine, 1% (cream) apply to affected areas once daily

Lotrimin Ultra

Effective for the treatment of tinea pedis (athlete's foot), tinea cruris (jock itch), and tinea corporis (ringworm). Clotrimazole and miconazole also effective against Candida albicans. Clinicians should be aware that products carrying the same brand name do not necessarily contain the same active ingredient. 

Clotrimazole, 1% (cream, solution), apply to affected areas twice daily (morning and evening)

Lotrimin AF cream, various generic

Miconazole, 2% (cream, powder, solution), apply to affected areas twice daily (morning and night)

Cruex, Desenex, Lotrimin AF (powder, spray), Zeasorb-AF

Terbinafine, 1% (cream, solution, spray), apply to affected areas once daily (ringworm) or twice daily (athlete's foot/jock itch)

Lamisil AT

Tolnaftate, 1% (cream, powder, spray, solution), apply to affected areas twice daily (morning and night)

Tinactin, Ting cream, various generic

Undecylenic acid, 12–25% (powder, solution) apply to affected areas twice daily

Blis-To-Sol, Elon Dual Defense Anti-Fungal

Antifungal vaginal preparations

Butoconazole, 2% cream, one applicatorful intravaginally at bedtime for 3 consecutive days

Femstat-3

Topical vaginal antifungals should only be used for treatment of recurrent vulvovaginal candidiasis in otherwise healthy, nonpregnant women previously diagnosed by a clinician.

Clotrimazole (1%, 2% vaginal cream, 100 mg, 200 mg tablet); see comments for dosage

Gyne-Lotrimin-7, Gyne-Lotrimin-3, various generic

Insert one applicatorful (1%) or one tablet (100 mg) intravaginally at bedtime for 7 consecutive days. Alternatively: Insert one applicatorful (2%) or one tablet (200 mg), intravaginally at bedtime for 3 consecutive days.

Miconazole (2%, 4% vaginal cream; 100 mg, 200 mg vaginal suppositories); see comments for dosage

Monistat-7, Monistat-3, Vagistat-3, various generic

Insert one applicatorful intravaginally at bedtime for 7 consecutive days (2%) or 3 consecutive days (4%). Alternatively: Insert one suppository intravaginally at bedtime for 7 consecutive days (100 mg) or 3 consecutive days (200 mg).

Tioconazole, 6.5% vaginal ointment, one applicatorful intravaginally at bedtime (single dose)

Monistat-1, Vagistat-1, various generic

 

Anti-inflammatory topical preparations

Hydrocortisone, 0.5% (cream, ointment, lotion), 1% (cream, ointment, lotion, spray)

Cortaid, Cortizone-10, Preparation H, various generic

Used to temporarily relieve itching and inflammation associated with minor rashes due to contact or allergic dermatitides, insect bites, and hemorrhoids. Apply sparingly to affected areas two to four times daily.

Antiseborrheal agents

Coal tar, 0.5-5% shampoo, dosage varies; consult product labeling

Denorex Therapeutic, Ionil T Plus, Pentrax 5%, various generic

Tar derivatives inhibit epidermal proliferation and may possess antipruritic and antimicrobial activity.

Ketoconazole, 1% shampoo, apply every 3–4 days

Nizoral A-D

Synthetic azole antifungal agent with activity versus Pityrosporum ovale, a fungus that may cause seborrhea and dandruff. Massage over entire scalp for 3 minutes. Rinse thoroughly and repeat application. 

Pyrithione zinc, 1–2% shampoo, apply once or twice weekly

Denorex Daily, Head & Shoulders, Sebulon, various generic

Both selenium sulfide and zinc pyrithione are cytostatic agents that decrease epidermal turnover rates. Massage into wet scalp for 2–3 minutes. Rinse thoroughly and repeat application. Selenium sulfide can be irritating to the eyes and skin.

Selenium sulfide, 1% shampoo, apply once or twice weekly

Head & Shoulders Intensive Treatment, Selsun Blue, various generic

Antitussives

Codeine, 10–20 mg every 4–6 hours, not to exceed 120 mg in 24 hours (with guaifenesin)

Guiatuss AC, Mytussin AC, various generic

Acts centrally to increase the cough threshold. In doses required for cough suppression, the addiction liability associated with codeine is low. Many codeine-containing antitussive combinations are schedule V narcotics, and OTC sale is restricted in some states.

Dextromethorphan, 10–20 mg every 4 hours or 30 mg every 6–8 hours; 60 mg (extended-release suspension) every 12 hours

Delsym 12-Hour Cough, Hold DM, Vicks 44 Dry Cough, various generic

Dextromethorphan is a nonopioid congener of levorphanol without analgesic or addictive properties. Often is used with antihistamines, decongestants, and expectorants in combination products. In high dosages (> 2 mg/kg) dextromethorphan can induce phencyclidine-like hallucinogenic effects.

Decongestants, topical

Oxymetazoline, 0.05% nasal solution, 2–3 sprays per nostril twice daily

Afrin, Neo-Synephrine 12 Hour, Sudafed OM, Vicks Sinex, various generic

Topical sympathomimetics are effective for the temporary acute management of rhinorrhea associated with common colds and allergies. Long-acting agents (oxymetazoline and xylometazoline) are generally preferred, although phenylephrine is equally effective. Topical decongestants should not be used for longer than 3 days to prevent rebound nasal congestion.

Phenylephrine (0.25%, 0.5%, 1%), nasal solution, 2–3 sprays/drops per nostril no more often than every 4 hours

Neo-Synephrine, various generic

Xylometazoline (0.05%, 0.1%), nasal solution, 2–3 drops or 1–3 sprays per nostril every 8–10 hours

Otrivin

Decongestants, systemic

Phenylephrine, 10 mg every 4 hours

Sudafed PE, various generic combination products

Oral decongestants have a prolonged duration of action but may cause more systemic effects, including nervousness, excitability, restlessness, and insomnia. Also available in antihistamine, antitussive, expectorant, and analgesic combination products. Federal regulations established to discourage the illicit manufacture of methamphetamine specify that all drug products containing pseudoephedrine must be stored in locked cabinets or behind the pharmacy counter and can only be sold in limited quantities to consumers after they provide photo identification and sign a logbook.

Pseudoephedrine, 60 mg every 4–6 hours or 120 mg (extended release) every 12 hours, or 240 mg (extended release) every 24 hours

Sudafed, various generic

Emergency contraceptive

Levonorgestrel, 0.75 mg tablet taken as soon as possible but no later than 72 hours after unprotected intercourse; repeat dosage 12 hours later

Plan B

Levonorgestrel prevents ovulation and may inhibit fertilization or implantation. Reduces the chance of pregnancy by up to 89% when taken as directed within 72 hours after unprotected intercourse. Plan B is available behind the counter at pharmacies and sold under the supervision of a licensed pharmacist. A prescription is needed for women ≤ 17 years of age.

Expectorants

Guaifenesin, 100–400 mg every 4 hours; 600–1200 mg (extended release) every 12 hours

Glytuss, Robitussin, various generic

The only OTC expectorant recognized as safe and effective by the FDA. Often used with antihistamines, decongestants, and antitussives in combination products.

Hair growth stimulants

Minoxidil, 2%, 5% solution, apply 1 mL to affected areas of scalp twice daily.

Rogaine for Men, Rogaine for Women, Rogaine Extra Strength for Men

Minoxidil appears to directly stimulate hair follicles resulting in increased hair thickness and reduced hair loss. Treatment for 4 months or longer may be necessary to achieve visible results. If new hair growth is observed, continued treatment is necessary as hair density returns to pretreatment levels within months following drug discontinuation.

Laxatives

Bulk formers: Polycarbophil, psyllium, and methylcellulose preparations. Dosage varies; consult product labeling

Citrucel, Fibercon, Konsyl, Metamucil, Perdiem, various generic

The safest laxatives for chronic use include the bulk formers and stool softeners. Saline laxatives and stimulants may be used acutely but not chronically (see text). Bulk formers hold water and expand in stool, promoting peristalsis.

Hyperosmotics: Glycerin, 2–3 g suppository per rectum daily. Polyethylene glycol 3350 (powder), 17 g dissolved in 4–8 oz of beverage daily

Fleet Glycerin Suppository, various generic; MiraLax

Glycerin induces a local irritant effect in combination with an osmotic effect. Polyethylene glycol formulations are large, poorly absorbed molecules that induce an osmotic effect causing distention and catharsis.

Stool softeners: Docusate sodium, 50–500 mg daily. Docusate calcium, 240 mg daily

Colace, Kaopectate Stool Softener, various generic

Softens fecal material via detergent action that allows water to penetrate stool.

Stimulant laxatives: Bisacodyl, 5–15 mg daily. Senna, dosage varies, consult product labeling

Correctol, Dulcolax, Ex-Lax, Senokot, various generic

Stimulant laxative actions include direct irritation of intestinal mucosa or stimulation of the myenteric plexus, resulting in peristalsis. These agents may also cause alteration of fluid and electrolyte absorption, resulting in luminal fluid accumulation and bowel evacuation.

Pediculicides (head lice)

Permethrin 1%

Nix

Instructions for use vary; consult product labeling. Avoid contact with eyes. Comb out nits. Linens, pajamas, combs, and brushes should be washed daily until the infestation is eliminated. For pyrethrin products, retreat in 7–10 days to kill any newly hatched nits. Permethrin products have residual effects for up to 10 days; therefore, reapplication is not required unless live nits are visible 7 days or more after the initial treatment.

Pyrethrins (0.3%) combined with piperonyl butoxide (3–4%)

A-200, RID

Sleep aids

Diphenhydramine, 25–50 mg at bedtime

Nytol, Simply Sleep, Sominex, various generic

Diphenhydramine and doxylamine are antihistamines with well-documented CNS depressant effects. Because insomnia may be indicative of a serious underlying condition requiring medical attention, patients should consult a physician if insomnia persists continuously for longer than 2 weeks.

Doxylamine, 25 mg 30 minutes before bedtime

Unisom, various generic

Smoking cessation aids

Nicotine polacrilex gum; dosage varies; consult product labeling

Nicorette, various generic

Nicotine replacement products in combination with behavioral support approximately double long-term cessation rates compared with placebo. Review directions for use carefully, since product strengths vary and self-titration and tapering may be necessary.

Nicotine polacrilex lozenge, dosage varies; consult product labeling

Commit, various generic

Nicotine (transdermal system), dosage varies; consult product labeling

Nicoderm CQ, various generic

Weight loss aids

Orlistat, 60 mg with each meal containing fat (not to exceed 180 mg/d)

Alli

Approved for weight loss in overweight adults ≥ 18 years of age when used in combination with a reduced-calorie, low-fat diet and exercise program. Orlistat is a nonsystemically absorbed inhibitor of gastrointestinal lipase that blocks the absorption of dietary fat. OTC formulation is a half-strength version of the prescription product (Xenical).

 

Table 63–2 lists examples of OTC products that may be used effectively to treat common medical problems. The selection of one ingredient over another may be important in patients with certain medical conditions or in patients taking other medications. These are discussed in detail in other chapters. The recommendations listed in Table 63–2 are based on the efficacy of the ingredients and on the principles set forth in the following paragraphs.

1.      Select the product that is simplest in formulation with regard to ingredients and dosage form. In general, single-ingredient products are preferred. Although some combination products contain effective doses of all ingredients, others contain therapeutic doses of some ingredients and subtherapeutic doses of others. Furthermore, there may be differing durations of action among the ingredients, and there is always a possibility that the clinician or patient is unaware of the presence of certain active ingredients in the product. Acetaminophen, for example, is in many cough and cold preparations; a patient unaware of this may take separate doses of analgesic in addition to that contained in the cold preparation, potentially leading to hepatotoxicity.

2.      Select a product that contains a therapeutically effective dose.

3.      Carefully read the product labeling to determine which ingredients are appropriate based on the patient's symptoms and underlying health conditions and whatever is known about the medications the patient is already taking.

4.      Recommend a generic product if one is available.

5.      Be wary of "gimmicks" or advertising claims of specific superiority over similar products.

6.      For children, the dose, dosage form, and palatability of the product are prime considerations.

Certain ingredients in OTC products should be avoided or used with caution in selected patients because they may exacerbate existing medical problems or interact with other medications the patient is taking. Many of the more potent OTC ingredients are hidden in products where their presence would not ordinarily be expected (Table 63–3). Although OTC medications have standardized label formatting and content requirements that specify the indications for use, dosage, warnings, and active and inactive ingredients contained in the product, many consumers do not carefully read or comprehend this information. Lack of awareness of the ingredients in OTC products and the belief by many physicians that OTC products are ineffective and harmless may cause diagnostic confusion and perhaps interfere with therapy. For example, innumerable OTC products, including analgesics and allergy, cough, and cold preparations, contain sympathomimetics. These agents should be avoided or used cautiously by type 1 diabetics and patients with hypertension, angina, or hyperthyroidism. Aspirin should not be used in children and adolescents for viral infections (with or without fever) because of an increased risk of Reye's syndrome. Aspirin and other NSAIDs should be avoided by individuals with active peptic ulcer disease, certain platelet disorders, and patients taking oral anticoagulants. Cimetidine, an H2-receptor antagonist, is a well-known inhibitor of hepatic drug metabolism and can increase the blood levels and toxicity of drugs such as phenytoin, theophylline, and warfarin.

Table 63–3 Hidden Ingredients in OTC Products.

 

Hidden Drug or Drug Class

OTC Class Containing Drug

Product Examples

Alcohol (percent ethanol)

Cough syrups, cold preparations

Theraflu Nighttime (10%); Vicks NyQuil Cold & Flu Liquid (10%); Vicks NyQuil Cough (10%)

Mouthwashes

Listerine (27%); Scope (15%); Cepacol (14%)

Antihistamines

Analgesics

Advil PM; Alka-Seltzer PM; Excedrin PM; Bayer PM; Extra Strength Doan's PM; Goody's PM Pain Relief Powder; Tylenol PM

Menstrual products

Midol Menstrual Complete; Pamprin Multi-Symptom

Sleep aids

Nytol; Simply Sleep; Sominex; Unisom

Aspirin and other salicylates

Antidiarrheals

Pepto-Bismol (bismuth subsalicylate); Kaopectate (bismuth subsalicylate)

Cold/allergy preparations

Alka-Seltzer Plus Flu

Caffeine (mg/tablets or as stated)

Analgesics

Alka-Seltzer Wake-Up Call (65); Anacin (32); Anacin Advanced Headache Formula (65); Arthritis Strength BC (38/pre-measured packet); BC Powder (33/pre-measured packet); Excedrin Extra Strength (65); Excedrin Migraine (65); Excedrin Tension Headache (65) Goody's Extra Strength Headache Powder (33/pre-measured packet); Goody's Cool Orange (65/pre-measured packet)

Menstrual products

Midol Menstrual Complete (60); Pamprin Max (65)

Stimulants

NoDoz (200); Vivarin (200)

Local anesthetics (usually benzocaine)

Antitussives/Lozenges

Cepacol Instant Relief Sore Throat Lozenges; Chloraseptic Sore Throat; Sucrets; Sucrets Complete

Dermatologic preparations

Americaine; Bactine; Dermoplast; Lanacane; Solarcaine

Hemorrhoidal products

Americaine Ointment; Nupercainal; Tronolane; Tucks Ointment

Toothache, cold sore, and teething products

Anbesol; Kank-A; Orajel; Zilactin-B

Sodium (mg/tablet or as stated)

Analgesics

Alka-Seltzer Original Effervescent Tablet (568); Alka-Seltzer Extra Strength Effervescent Tablet (588); Bromo-Seltzer Granules (959/pre-measured packet)

Antacids

Alka-Seltzer Original Effervescent Tablet (568); Alka-Seltzer Extra Strength Effervescent Tablet (588); Alka-Seltzer Gold (309); Alka-Seltzer Heartburn Relief (575); Brioschi (500/6 g dose); Bromo-Seltzer Granules (959/pre-measured packet); Citrocarbonate Effervescent Granules (701/tsp)

 

Cold/cough preparations

Alka-Seltzer Plus Formulations: Cold (503); Day Cold (416); Cold & Cough (416); Flu (387); Mucous & Congestion (296); Night Cold (477).

 

Laxatives

Fleets Enema (4,439 mg, of which 275–400 mg/enema is absorbed)

Sympathomimetics

Analgesics

Excedrin Sinus Headache; Sine-Off; Sinutab; Tylenol Congestion & Pain; Tylenol Sinus Severe Congestion

Asthma products

Bronkaid Dual Action; Primatene Mist; Primatene Tablets

Cold/cough/allergy preparations

Actifed Cold & Allergy; Advil Cold & Sinus; Alka-Seltzer Plus (many); Comtrex Severe Cold & Sinus; Congestac; Contac Day & Night Cold & Flu; Dimetapp Cold & Chest Congestion; Dristan Cold; PediaCare (many); Motrin Cold & Sinus; Ornex; Robitussin Cough, Cold & Flu; Robitussin Cough & Cold CF; Sudafed PE Cold & Cough; TheraFlu Warming Relief Multisymptom Cold; Triaminic (many); Tylenol Cold Multisymptom; Tylenol Cold Severe Congestion; Tylenol Allergy Multisymptom; Vicks 44 Congestion; Vicks DayQuil

Hemorrhoidal products

Hemorid; Preparation H (cream, ointment, suppository)

 

Overuse or misuse of OTC products may induce significant medical problems. A prime example is rebound congestion from the regular use of decongestant nasal sprays for more than 3 days. The improper and long-term use of some antacids (eg, aluminum hydroxide) may cause constipation and even impaction in elderly people, as well as hypophosphatemia. Laxative abuse can result in abdominal cramping and fluid and electrolyte disturbances. Insomnia, nervousness, and restlessness can result from the use of sympathomimetics or caffeine hidden in many OTC products (Table 63–3). The long-term use of some analgesics containing large amounts of caffeine may produce rebound headaches, and long-term use of analgesics has been associated with interstitial nephritis. OTC products containing aspirin, other salicylates, acetaminophen, ibuprofen, or naproxen may increase the risk of hepatotoxicity and gastrointestinal hemorrhage in individuals who consume three or more alcoholic drinks daily. Recent evidence suggests the long-term use of NSAIDs may increase the risk of heart attack or stroke. Furthermore, acute ingestion of large amounts of acetaminophen by adults or children can cause serious, and often fatal, hepatotoxicity. Antihistamines may cause sedation or drowsiness, especially when taken concurrently with sedative-hypnotics, tranquilizers, alcohol, or other central nervous system depressants. Antihistamines and other substances contained in OTC topical and vaginal products may induce allergic reactions.

Finally, use of OTC cough and cold preparations in the pediatric population has been under scrutiny by the FDA based on a lack of efficacy data in children less than 12 years of age and reports of serious toxicity in children. In October 2007, many pharmaceutical manufacturers recalled OTC cough and cold preparations marketed for children less than 2 years of age. In 2008, the FDA issued an advisory alert recommending that OTC cough and cold agents not be used in infants and children less than 2 years of age due to the potential for serious and possibly life-threatening adverse events. More recently, in October 2008, leading pharmaceutical manufacturers voluntarily modified product labels on OTC cough and cold preparations to state, "do not use" in children under 4 years of age. Further safety reviews by the FDA regarding the use of these agents in children between the ages of 2 and 11 are ongoing.

There are three major drug information sources for OTC products. Handbook of Nonprescription Drugs is the most comprehensive resource for OTC medications; it evaluates ingredients contained in major OTC drug classes and lists the ingredients included in many OTC products. Nonprescription Drug Therapy is an online reference that is updated monthly; it provides detailed OTC product information and patient counseling instructions. Physicians' Desk Reference for Nonprescription Drugs, Dietary Supplements and Herbs, a compendium of manufacturers' information regarding OTC products, is published annually but is somewhat incomplete with regard to the number of products included. Any health care provider who seeks more specific information regarding OTC products may find useful the references listed below.

 

References

Brass EP: Changing the status of drugs from prescription to over-the-counter availability. N Engl J Med 2001;345:810. [PMID: 11556302]

Consumer Healthcare Products Association website: http://www.chpa-info.org/

Handbook of Nonprescription Drugs, 16th ed. American Pharmacists Association, 2009.

Nonprescription Drug Therapy. Facts and Comparisons 4.0 (online). Wolters Kluwer Health, 2009.

Nonprescription Product Therapeutics, 2nd ed. Lippincott Williams & Wilkins, 2005.

Physicians' Desk Reference for Nonprescription Drugs, Dietary Supplements and Herbs, 30th ed. Thomson Healthcare, 2009.

Sharfstein JM, North M, Serwint JR. Over the counter but no longer under the radar—pediatric cough and cold medications. N Engl J Med 2007;357:232.

US Food and Drug Administration: Center for Drug Evaluation and Research. Office of Nonprescription Products website: http://www.fda.gov/cder/offices/otc/default.htm

US Food and Drug Administration: Center for Drug Evaluation and Research. Public Health Advisory. Nonprescription Cough and Cold Medicine Use in Children. http://www.fda.gov/cder/drug/advisory/cough_cold_2008.htm

Williams JF, Kokotailo PK. Abuse of proprietary (over-the-counter) drugs. Adolesc Med 2006;17:733. [PMID: 17030289]

 


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