Pharmacy Times

Introduction

Transmission and Prevention

SECTION 2
Treatment

Antibiotics

Antihistamines

Mast cell stabilizers

Nasal decongestants

Water vapor or mists

Antitussives

Analgesics/Antipyretics

Zinc lozenges

Herbal products

Combination products

SECTION 3
Table 1
Table 2
Table 3
Table 4
Table 5

SECTION 4

References

The Common Cold: 
Prevention and Treatment

Elaine D. Mackowiak,  RPh, PhD

Dr. Mackowiak is Professor, Department of Pharmacy Practice
Temple University, School of Pharmacy in Philadelphia, PA.

Behavioral Objectives

After completing this continuing education article, the pharmacist should be able to:

The name common cold describes an upper respiratory disease that is most often characterized by inflammation and irritation of the nose and throat. Everyone has had at least one cold in his or her lifetime, and colds strike every age group. Preschool age children have between six and ten colds per year, but that number increases as they are exposed to more people, especially other children in childcare facilities.¹ Adults have fewer colds, only about one to two per year. Although the common cold is caused by multiple etiologic agents, they produce a set of easily recognized symptoms that vary in severity and duration. However, except for the very young, everyone who has experienced a cold can easily recognize its symptoms and diagnose their illness. Colds are self-limiting but have the potential to cause complications that could be life-threatening in certain individuals. 

Colds are caused primarily by six families of viruses with more than 200 serotypes.² Rhinovirus, which is responsible for more than 30% of all colds, has more than 100 serotypes. The large number of serotypes is one reason why it has not been possible to develop an effective vaccine against the common cold. Coronavirus, which also has numerous serotypes, is the second leading cause of colds, while adenovirus, influenza, parainfluenza, and respiratory syncytial virus (RSV) are responsible for the remainder. RSV is most commonly seen in children less than 4 years of age and is associated with croup and bronchiolitis.² Enterovirus (coxsackie A and B and echovirus) is an occasional cause of the common cold.

Viruses tend to have a seasonal variation. Rhinoviruses predominate in the early fall and late spring; coronaviruses, RSV, and adenoviruses in the winter and spring; types 1 and 2 parainfluenza in the autumn; and type ³ parainfluenza in the late spring.3 Rhinorrhea, rhinitis, nasal congestion, sneezing, sore throat, and cough occur in most patients, but other symptoms seen include fever, headache, muscle aches, and malaise.⁴ Table 1 lists the frequency of occurrence of these symptoms for the primary etiologic agents. Probably the only positive news about getting a cold is that it is generally self-limiting and the symptoms usually last from about 3 to 7 days. However, some colds may persist for as long as 2 weeks or more.

The morbidity associated with the common cold is responsible for a major expense in the health care budget. Direct costs are estimated to be in the range of $15 billion per year, while indirect costs are about $9 billion.⁵ Expenditures for drugs or treatments to relieve the symptoms of colds account for the majority of the direct costs because there is no cure for the disease. Most colds are self-limiting, but a group of family practice physicians reported that 15% of patients’ visits during a single week in January were because of colds.⁶ Half the patients sought help because they were concerned about possible complications from their colds, and about 32% were simply frustrated with self-treatment of their symptoms.

 Indirect costs result from time lost from work and from a decrease in productivity by workers infected with colds. Smith et al have demonstrated an overall decrease in mental alertness and slowed reaction times resulting in impaired psychomotor functioning from both rhinovirus- and coronavirus- caused colds.⁷

Transmission and Prevention

Once a person is infected with a cold virus, a series of events occur that favor further transmission of the virus. The incubation period lasts for about 48 to 72 hours, and during this time the individual usually has no symptoms. Experimentally induced colds in human volunteers revealed that most rhinoviruses shed their coat and enter cells in the nasal passages by binding to an intercellular adhesion molecule (ICAM-1).⁸ Vascular engorgement and increased vascular permeability increased mucus production containing virus, serum proteins, and other cellular debris.⁹ These changes were temporary and did not cause cell necrosis or mucosal damage that persisted after the illness. Computed tomography of the nasal passages of patients with community-acquired colds confirmed these findings.¹⁰ 

Inflammatory mediators, including histamine, kinins, and interleukins, are released in the nasal passages during these viral upper respiratory tract infections.⁹ Host responses to these mediators cause rhinitis, rhinorrhea (copious, thin, watery nasal secretions), followed in a day or two by thick, sticky mucous secretions, nasal congestion, sneezing, sore throat, and cough. Nasal secretions continue to contain virus for a week or more after the overt symptoms of the cold are gone. Contact with infected nasal secretion from direct hand-to-hand contact, or from contaminated objects or surfaces (tissues, doorknobs, telephones, etc) and then touching or rubbing the nose or eyes provides the virus with the access it needs for transmission.¹¹ Transmission also may occur by airborne nasal droplets but is less important for rhinoviruses than some of the other viruses. 

Aspirin and acetaminophen, but not ibuprofen, were associated with a longer duration of virus shedding.¹² The use of aspirin and acetaminophen to treat sore throat, fever, headache, or myalgia was shown to suppress serum neutralizing antibody and increased nasal symptoms.¹² Naproxen did not have any effect on either serum neutralizing antibody nor did it prolong virus shedding.¹³ The importance of these findings in affecting the duration of colds or their transmission has not been examined.

Because most colds are caused by either rhinovirus or coronavirus, which have many serotypes, it is unlikely that an effective vaccine will be developed. Recent studies with intranasal tremacamra (formerly BIRR 4) administered either 7 hours before or 12 hours after inoculation with rhinovirus type 39 effectively blocked a receptor site on the ICAM-1 molecule preventing colds.¹⁴ Although this study showed that tremacamra has a potential use as a prophylactic agent, there are two serious limitations to its use. First, the drug was administered long before any symptoms appeared. Most individuals do not know they have been infected by the virus until symptoms appear, which normally takes 48 to 72 hours. Second, only one serotype of rhinovirus was used. Although a large number of serotypes of rhinovirus bind to the ICAM-1 molecule, the exact  nature of this binding is not known. Studies using coronavirus or any of the other viruses that cause colds have not been done.

The human body’s normal response to viral infections is to produce interferons, but research into their use for prevention of colds has been disappointing. Studies using intranasal interferons demonstrated a protective action against rhinoviruses only if they were administered just before or immediately after exposure to the virus.¹⁵ Unfortunately, interferon’s adverse effects cause nasal symptoms mimicking those of the common cold accompanied by an increased tendency to cause nose bleeds. These actions limit their use as prophylactic agents against the common cold.

Other antiviral drugs were examined for prophylactic use. Pirodavir binds to the capsid of most rhinoviruses in vitro, inhibiting either the uncoating of the virus or its attachment to nasal membranes. It was reported to significantly reduce colds if it was administered to study participants before they were inoculated with rhinovirus.¹⁶ Unfortunately, if patients were inoculated 24 hours before pirodavir was begun, there was no significant protection against colds, although there was a significant reduction in viral shedding. Adverse effects of pirodavir included excess nasal dryness and an unpleasant taste.ViroPharma recently reported that oral prophylaxis with the antiviral, pleconaril, significantly reduced both nasal viral shedding and the symptoms of upper respiratory infection caused by Coxsackiesvirus during a phase 2 trial.¹⁷ This drug requires much more study before any conclusions can be made about its efficacy. 

In 1970, Pauling proposed in his book, Vitamin C and the Common Cold,¹⁸ that large, daily doses of vitamin C could prevent colds or at least minimize the symptoms and/or duration of colds. In 1975, Chalmers reviewed the studies published on vitamin C and the common cold and concluded that it had no significant benefit.¹⁹ In 1995, Hemila and Herman analyzed Chalmers’ work and excluded studies that used very low doses of vitamin C, less than 50 mg daily. They concluded that vitamin C reduced the duration of colds by about 20%.²⁰ When 1 gram of vitamin C was administered daily for a period of 9 months in adults, it had only a weak beneficial effect on the duration and severity of colds.²¹

The best advice pharmacists can give patients for the prevention of the common cold is to avoid people who have colds, wash your hands frequently, and avoid touching or rubbing your nose and eyes with your hands. Wiping off items such as telephone receivers, door- knobs, etc, with antiseptic wipes or sprays will remove contaminants and reduce the spread of cold viruses. Stress, either physical or psychological, should be avoided because it increases susceptibility to many types of infections, including the common cold.²²

Vitamin C taken daily in doses of 1 gram or more may provide some protective effect, but the optimum dose has not been established. Prophylaxis with antiviral drugs or interferons is not feasible at this time.

Treatment

Antibiotics

Antibiotics continue to be inappropriately prescribed for the common cold in both children and adults, although numerous studies have shown that they have no significant impact on the clinical outcome of colds.^23-26 The old adage that the appearance of a green color in mucous secretions of patients with colds is indicative of secondary bacterial infection has been shown not to be true.^27,28 Viruses that cause the common cold are usually the etiologic agents for most cases of acute bronchitis. Antibiotic therapy is not useful unless patients have a history of chronic bronchopulmonary disease, cyanosis, or pneumonia.²⁹ 

Some physicians may succumb to pressure from patients requesting a prescription for an antibiotic drug. However, patients who expected to receive antibiotic therapy for a cold did not have any greater satisfaction with their physicians’ care.²³ Inappropriate use of antibiotics was found to contribute to the cost of health care and to increase the risk of developing resistant strains of bacteria.³⁰ 

How then do we symptomatically treat colds? A patient’s list of symptoms should be used to tailor our recommendations for drug therapy. It is a patient’s response to the virus that is responsible for symptoms, and the most annoying symptoms should be treated.²⁸ Table 2 lists the pharmacologic classes of drugs used to treat patients with upper respiratory complaints in a family practice clinic.³¹ The majority of drugs recommended were prescription antihistamines or multisymptom cold products containing an antihistamine, a decongestant, and an antitussive or expectorant. Many similar products are available as over- the-counter (OTC) drugs, providing pharmacists with the opportunity to make suitable recommendations to their patients. Each individual pharmacologic class of drugs is discussed below.

Antihistamines

Rhinorrhea, nasal congestion, and sneezing are the symptoms most often described by patients at the onset of a cold. These symptoms are also the hallmark of allergic rhinitis due to histamine release from mast cells; therefore, it is necessary to assess the situation so that the appropriate cause of the symptom is known. Patients should be questioned about exposure to any known allergens that are present in patients’ health histories. Seasonal allergies occur most often in the spring and summer from pollens, mites, and molds that are present in abundant quantities in the air during those seasons. Symptoms lasting for 2 weeks or more, usually without any sore throat or cough, are characteristic of allergies.

Because histamine-1 blockers, antihistamines, have demonstrated efficacy against the nasal symptoms of allergies, it seemed rational to use them to treat cold symptoms. Unfortunately, not all viruses responsible for colds produce the same degree of membrane permeability and nasal edema via the histamine pathway, thus limiting the effectiveness of antihistamines. 

Experimental colds induced by rhinovirus have little effect on histamine release in the nasal passages, and may mediate their effect by releasing inflammatory kinins and interleukins.^27,32 However, only a few serotypes of rhinovirus have been used to inoculate volunteers to produce colds, and it is not known whether all serotypes of rhinovirus act in an identical manner. Other cold viruses have a more pronounced effect on histamine release, making antihistamines more effective for nasal symptoms. 

These differences contribute to the contradictory results from many of the clinical studies that evaluated antihistamines in treating colds. A critical examination of these studies using meta-analysis techniques demonstrated that chlorpheniramine (Chlor-Trimeton) and doxylamine, both first-generation antihistamines, are effective in reducing the severity of rhinorrhea and sneezing in adolescents and adults, but not in children of preschool age.³³ 

Brompheniramine (Dimetapp Allergy) and clemastine fumarate (Tavist-1) were effective in relieving cold symptoms in adults.^34,35 Diphenhydramine (Benadryl) and triprolidine are also first-generation antihistamines included in the FDA monograph, but evidence of their effectiveness in treating colds is less clear in the literature.  Some investigators hypothesized that the anticholinergic action of these older antihistamines was responsible for their effectiveness in relieving cold symptoms. Studies using intranasal formulations of ipratropium bromide, a prescription anticholinergic, produced a reduction of cold symptoms but also produced excessive drying of nasal passages, mouth, and eyes.^36,37 The FDA does not permit the manufacture and sale of any OTC products containing anticholinergic drugs as cold remedies at this time. 

Herbal and homeopathic products are not classified as OTC drugs and are regulated in a different manner by the FDA. Some of these preparations contain belladonna alkaloids (atropine or hyoscyamine), which are anticholinergic agents, but their efficacy as cold remedies has not been demonstrated by clinical studies.

Studies using the second-generation, nonsedating antihistamine terfenadine (Seldane), which has little anticholinergic activity, did not produce any significant relief of rhinorrhea or sneezing.^38,39 (Terfenadine and astemizole [Hismanal] were withdrawn from the market because of drug interactions that produce potentially life-threatening cardiac arrhythmias.) There are no clinical studies in the literature evaluating the use of nonsedating antihistamines, such as loratadine (Claritin), fexofenadine (Allegra), or cetirizine (Zyrtec), as cold relief medications at this time. Nonsedating antihistamines are all prescription drugs, but they are potential Rx-to-OTC switch candidates in the near future.

Adverse effects of first-generation antihistamines, especially drowsiness, limit their usefulness in many patients. This effect is so pronounced for diphenhydramine and doxylamine that they are used as OTC sedatives. Patients should be warned not to take antihistamines and other central nervous system depressants at the same time. Antihistamines are contraindicated for patients who have narrow-angle glaucoma or benign prostatic hyperplasia (BPH).

Several manufacturers of popular combination cold products introduced formulations without antihistamines and promoted them for daytime use. For example, Procter & Gamble removed the antihistamine from some NyQuil products and created the DayQuil products. 

Schering-Plough introduced Chlor-Trimeton Non-Drowsy Decongestant Tablets, which removed the antihistamine, chlorpheniramine maleate. This was the first Chlor-Trimeton product lacking chlorpheniramine, causing much confusion among the lay public and many health professionals about the actual ingredients in the product. This product contains pseudoephedrine, a decongestant, as its active ingredient. Unfortunately, this practice of using the name of a popular, well-established product to introduce new products with different ingredients (product line extensions) is now a common practice among drug manufacturers. Pharmacists and patients should read labels carefully before choosing any product.

Mast Cell Stabilizers

Cromolyns are drugs that stabilize mast cells, preventing the release of histamine and other chemical mediators that produce inflammation if used before challenge with an allergen. They are approved for preventing symptoms associated with allergic rhinitis and asthma as prescription drugs. Cromolyn sodium was switched from Rx to OTC status for prevention of nasal allergy symptoms. A recent study suggests that it may have a future as a prophylactic for cold symptoms. Aberg et al reported a reduction in the severity and duration of nasal symptoms from colds in adult patients who used intranasal sodium cromoglycate within 24 hours after the appearance of cold symptoms.⁴⁰ Its adverse effects are minimal, and one advantage is that it does not cause drowsiness. It is not contraindicated for patients who have glaucoma or BPH.

Nasal Decongestants

Although there may be some doubt about the efficacy of antihistamines to relieve cold symptoms, there is no doubt about the effectiveness of nasal decongestants. Use of nasal decongestants, either orally or topically, results in vasoconstriction of edematous blood vessels in the nasal passages, thereby relieving nasal stuffiness. 

All OTC nasal decongestants are classified pharmacologically as alpha-adrenergic amines. Labels warn patients who have hypertension, heart disease, hyperthyroidism, diabetes mellitus, and difficulty in urinating because of enlargement of the prostate gland not to use the product unless their physician recommends it. Patients are warned not to use decongestants if they are taking a prescription drug containing a monoamine oxidase inhibitor (MAOI), because a sudden, serious rise in blood pressure may occur. Use of decongestants may cause nervousness, dizziness, or sleeplessness in some patients, and the use of other stimulants, such as caffeine, should be avoided.

Phenylpropanolamine is undergoing additional review by the FDA at this time because of concerns about its safety. Lake et al reviewed 142 case reports of adverse effects, which included eight deaths from stroke.⁴¹ Most of these reports occurred in women less than 30 years of age who were using OTC appetite suppressants containing phenylpropanolamine, another approved use for this drug. The majority of these patients used the products for extended periods of time and often in doses higher than those recommended. Some individuals used cold and diet products at the same time, resulting in doses exceeding the recommended daily dose of phenylpropanolamine.

If one considers the number of patients with hypertension who have used decongestant drugs, many of them unknowingly in multisymptom cold or sinus products, the risk of reported serious events is very low. Several studies have reported no significant changes in the blood pressure of patients whose hypertension was well controlled and who used either pseudoephedrine or phenylpropanolamine.^42-44 These drugs are approved for oral use only. 

Phenylephrine was approved for oral and topical use, but because of its erratic bioavailability when used orally, it is used primarily as a topical decongestant.⁴⁵ Table 3 lists the popular OTC decongestants. 

Topical nasal decongestants included phenylephrine, naphazoline, oxymetazoline, and xylometazoline. Nasal formulations of decongestants include drops, sprays, jellies, or inhalants, with drop formulations being preferred for pediatric use. One undesirable effect reported by patients using drops or sprays is dripping of the decongestant into the back of the throat, causing an undesirable taste. Schering-Plough recently introduced Afrin (oxymetazoline) No Drip Nasal Spray with a formulation that prevents the medication from dripping into the throat.

Decongestants vary in their duration of action, and the shorter acting drugs, such as phenylephrine (Neo-Synephrine) and naphazoline (Privine), are preferred for pediatric use. Oxymetazoline has the longest duration of action, about 12 hours. Products using the terms “twice a day” or “long acting” contain oxymetazoline, and they are not recommended for children. 

Levmetamfetamine (formerly l-desoxyephedrine), Vicks Inhaler, and propylhexadrine, Benzedrex Inhaler, are subject to fairly rapid degradation when exposed to air because of their volatile nature. They should not be used for longer than 3 months after they have been opened, even if the inhaler retains its aroma. Improper closing of an inhaler after it is used accelerates the deterioration of inhalant drugs. Inhalers are not recommended for use in children under 6 years of age.

Topical nasal decongestants are associated with rebound congestion and are likely to be overused by patients. Labels for topical decongestants limit their use to 3 days to prevent this problem. Oral decongestants are less likely to cause rebound congestion and their use is limited to 7 days. Patients are advised to see a doctor if their symptoms do not improve or if they have a concomitant fever. 

Because decongestants relieve uncomfortable nasal stuffiness without causing drowsiness, manufacturers promote their products by emphasizing the nondrowsy feature in their advertising.

Nasal drops or sprays containing sodium chloride solutions with concentrations less than 0.9% provide symptomatic relief for dry, irritated nasal membranes. Products such as Afrin Saline Mist, Ayr Saline, Dristan Saline Spray, HuMist, NaSal, Ocean, Sea Mist, and SalineX do not cause vasoconstriction. These products are safe for use by patients who have medical conditions where decongestants are contraindicated. Hypertonic solutions of sodium chloride were reported to have no beneficial effect on the nasal symptoms of the common cold and had a high incidence of nasal irritation and burning.⁴⁶

Another alternative to decreasing the resistance of air passing through nasal passages in patients with colds is the use of an adhesive strip device applied externally to the nostrils. It physically lifts the nostrils, keeping the nasal passages open. Breathe Right was the first device to be approved by the FDA and Breatheasy and Clear Passage are similar products that are available.

Water Vapor or Mists

A famous Norman Rockwell painting shows a man with a severe cold sitting by a stove, inhaling steam from a boiling pot. Is warm or hot, humidified air effective in relieving cold symptoms? The evidence is confusing on this issue. The lack of humidity in homes during the winter because of heating contributes to irritation of the nasopharyngeal membranes. Vaporizers, humidifiers, and ultrasonic humidifiers have been used successfully to reduce nasopharyngeal irritation. Liquid menthol and camphor preparations may be added to vaporizers to enhance their effect.

The appearance of TheraFlu, Flu and Cold Medicine Powder, in the marketplace introduced the concept of ingesting a hot, steaming medication to relieve cold symptoms. This type of product contains a combination of drugs supplied as a mixed powder or effervescent tablet in a packet. Contents of the packet are added to hot water and ingested. Tylenol Cold & Flu Medication Powder and Contac Severe Cold & Flu Hot Medicine Powder are popular products similar to TheraFlu. There is no evidence that the heated nature of these products adds to their effectiveness at this time. Many home remedies for colds include ingestion of hot chicken soup or hot beverages such as tea and have been used for centuries.

In 1989, Tyrrell et al reported that humidified air, heated to 43ÞC and delivered directly to the nasal passages, effectively relieved cold symptoms.⁴⁷ Other researchers who repeated this study arrived at opposite conclusions about its effectiveness.⁴⁸ The efficacy of the procedure remains in doubt.

Antitussives

Patients who have colds do not always have a cough (Table 1). The FDA recognized several OTC antitussives for topical or oral use in a monograph.⁴⁹ Topical antitussives exert a local action by blocking sensory nerves. Menthol and camphor are approved for topical use as chest rubs or as liquids for vaporizers. Only menthol is approved as a cough drop or lozenge formulation.⁴⁹ Zinc lozenges are classified as homeopathic drugs and were not included in the FDA’s OTC monograph. They will be discussed later. Oral antitussives act in the central nervous system and include dextromethorphan, diphenhydramine, and codeine.⁴⁹ Codeine and its salts are listed as Schedule 5 drugs by the Drug Enforcement Agency and are not available as OTC drugs in some states. The efficacy of codeine and dextromethorphan as antitussives continues to be questioned in the literature.⁵⁰ 

A recent study by Freestone and Eccles used a sound meter to determine cough sound-pressure levels, a microphone and chart recorder to measure cough frequency, and a subjective rating of cough by patients.⁵¹ This placebo-controlled, double-blind study resulted in a significant reduction of coughs in both groups as verified by all three measures, but there was no significant difference between the two groups. They proposed that two central pathways are involved in cough, a reflex path via the brain stem to the cough center which is affected by codeine, and a voluntary path via the cortex which is not.

Suppression of chronic coughs, or coughs associated with asthma, emphysema, or smoking are not suitable for OTC treatment; physician referral is needed. The literature frequently describes coughs as productive or nonproductive, but the FDA monograph for antitussives does not. Labeling for OTC antitussives uses the terms of excessive phlegm or mucus for productive coughs. Patients are advised not to use antitussives for this type of cough.⁵²

All oral antitussives have the potential to cause drowsiness, and codeine may cause constipation. In 1992, the FDA revised the labeling of dextromethorphan to include a drug interaction warning if patients are taking MAOIs.⁵³ Adverse effects from this interaction include hyperpyrexia (elevated body temperature), hypotension, muscle twitching, and coma. 

Patients’ coughs may be due to postnasal drip resulting from the rhinorrhea caused by the common cold. It was reported that patients who used antihistamines to decrease rhinorrhea had significant improvement in their cough symptoms.^33-35 This response is probably because of the anticholinergic properties of the antihistamines.^36,37 In view of the controversy over the effectiveness of codeine and dextromethorphan, diphenhydramine might be the preferred antitussive drug because it has both a central antitussive action and an anticholinergic action. Antibiotic therapy did not produce any significant reduction in coughs.²⁵

Guaifenesin (Robitussin), which is not an antitussive but an expectorant, appears in numerous multisymptom cold products. Its usefulness in treating cold symptoms is rather minimal, and it should not be used if patients have chronic coughs caused by smoking, asthma, or emphysema.⁵ 

Analgesics/Antipyretics

Table 2 shows that analgesic/ antipyretic drugs were the most frequently recommended OTC products by physicians treating patients with colds. High fevers are not usually seen in patients with uncomplicated colds, and if a fever persists, patients should be referred to their doctor. Some patients may experience slightly elevated temperatures and/or mild myalgia. All OTC analgesics/antipyretics are effective for these symptoms, and the choice of drug depends on the age of the patient, the presence of any concomitant disease, or the use of any other drug by the patient.

An irritated or sore throat frequently occurs during a common cold. Because this response may result from inflammatory mediators released in local tissues, ibuprofen (Advil, Nuprin, Motrin IB), naproxen sodium (Aleve), or ketoprofen (Acton or Orudis KT) may be preferred over acetaminophen or regular dose aspirin, unless there is some contraindication for their use in a particular patient. Acetaminophen and aspirin were shown to have a negative effect on serum neutralizing antibody and increases duration of viral shedding in nasal secretions in patients with colds.12 However, no study has demonstrated any negative clinical outcome in patients with colds who used these drugs.

These drugs may be used for 7 days if they are for pain relief, but only for 3 days for reducing fever. All patients with colds should consume fluids to prevent dehydration, especially if fever is present. 

Local anesthetics as lozenge formulations are alternatives to an oral analgesic to relieve sore throat discomfort. Benzocaine (Spect T Sore Throat, Cepacol Anesthetic Throat Lozenge), dyclonine (Sucrets Sore Throat, Cepacol Spray), and 1.4% phenol (Cepastat Sore Throat, Vicks Chloraseptic Sore Throat Spray) are all available as OTC drugs. Because lozenge formulations are not suitable for use by young children, oral analgesics are more appropriate recommendations for this age group.

Zinc Lozenges

Zinc gluconate, zinc gluconate with glycine (Cold-Eeze), and zinc acetate (Halls Zinc Defense) products are homeopathic medications used in lozenge formulations to treat cold symptoms. Zicam, an intranasal gel spray, was introduced in spring 1999 with “zincum gluconium 2x” as its active component. 

Three separate meta-analysis studies have failed to clarify the role of zinc lozenges in treating cold symptoms.^55-57 Each study concluded that half of the reports produced significant reductions in cold symptoms, while the other half demonstrated no effect. Reasons given for these discrepancies included lack of adequate placebo controls, use of complexing agents that prevented the release of free zinc ion, and inadequate doses of the elemental zinc administered to patients. The most recent study of zinc gluconate, a randomized, placebo-controlled study in children, did not produce any significant reduction in cold symptoms.⁵⁸ 

Novick et al proposed that zinc gluconate relieved cold symptoms within 2 to 3 minutes because it achieved high concentrations of free zinc ions in the saliva.⁵⁹ They suggested that zinc was reversibly bound to protein-rich nerve endings of the trigeminal and facial nerves.⁵⁹ They also proposed that zinc blocked the attachment of rhinovirus to ICAM-1, thus preventing the initiation of the inflammatory response in the nasal passages.⁶⁰

Zinc gluconate’s adverse effects include a bitter taste and irritation of the mouth and throat, causing a rather large number of patients to withdraw from these studies. The use of glycine and other flavoring aids attempt to reduce this effect. Chronic ingestion may affect the immune system. Oral doses of 150 mg of elemental zinc ingested twice a day for 6 weeks by healthy men decreased lymphocytes and neutrophils.⁶¹ The recommended dose of zinc in most lozenge preparations is 23 mg taken every 2 hours while awake. If 8 lozenges per day are consumed, the total daily dose of zinc is about 175 mg. Since colds are of relatively short duration, changes in lymphocytes and neutrophils would not be expected to be the same as the previous study, but this issue has not been examined. Studies that have a better design are needed before the role of zinc in treating colds is resolved.

Herbal Products

Numerous home remedies containing herbs and/or spices used by patients of different ethnic origins vary greatly but probably are safe.⁶² Studies of efficacy using placebo-controlled, double-blind techniques are rare. Some of the more widely used products will be studied in the near future because of the initiatives sponsored by the National Institutes of Health’s program to review complementary and alternative therapies.

Echinacea products are being examined under this process. Current results, such as those for zinc products, are contradictory. Brinkeborn et al reported that in a 7-day, randomized, double-blind study using three formulations of echinacea and placebo, only Echinaforce (a mixture of 95% Echinacea purpurea herba and 5% E purpurea radix) and a sevenfold concentrate of this mixture significantly reduced cold symptoms in adults. A special formulation of E purpurea radix and a placebo had no effect.⁶³

Two placebo-controlled, double-blind studies used extracts of E purpurea prophylactically, one for 8 weeks and one for 12 weeks.^64,65 Neither demonstrated any significant protection in preventing natural colds.

Consumers and pharmacists have a disadvantage in making any choice among the echinacea products already available because most do not identify the species or quantity of echinacea present in them.

Combination Products

Patients with a common cold exhibit a variety of symptoms. Rather than using multiple products with a single ingredient, many patients prefer taking one product that contains multiple ingredients. The FDA permits multiple-ingredient products if there are not two ingredients from the same pharmacologic category present. This provides manufacturers the opportunity to produce numerous products, and they do. The number of combination products is becoming overwhelming!

No studies are available that compare combination products with each other or compare different combinations of drugs for superiority in relieving cold symptoms. This author believes that the greater the number of drugs in a product, the greater the risk of adverse effects and drug interactions. Since rhinorrhea and nasal congestion occur most frequently, combinations of drugs addressing these symptoms are the most helpful for patients with colds. Patients experiencing headaches, especially those caused by inflammation of the nasal and frontal sinuses, will benefit from the use of anti-inflammatory analgesics, if there are no contraindications for their use. Table 4 lists some of the OTC combination products.

Unfortunately, most studies using a single antihistamine, a single decongestant, or a combination of both failed to demonstrate any significant effect on cold symptoms in young children.^33,39,66,67 These drugs also failed to reduce inner ear pressures and were not useful in preventing otitis media.⁶⁸ However, this evidence has not prevented parents from using these products in children. Kogan et al reported that 35% of more than 8,000 children in their study had received a cough/cold product in the preceding 30 days.⁶⁹ Table 5 lists some frequently used pediatric cold products. Pharmacists must educate parents about the proper dosing of products for their children to reduce the risk of adverse effects.

Confusion over the use of combination drug products will continue to worsen. Manufacturers are introducing new products containing many ingredients in home remedies to tap into the very profitable “natural” product market. Whitehall-Robins introduced a line of Robitussin Honey Flu products containing 50% honey and approved OTC drugs in August 1999. They introduced Robitussin Herbal with Natural Honey Center Cough Drops and Honey Lemon Tea Cough Drops in fall 1998. McNeil Consumer Healthcare will introduce Tylenol Sore Throat products containing acetaminophen and honey this fall. 

So many manufacturers plan extensions to their existing cough/ cold lines of products, that retailers will have a difficult time providing shelf space for all the new products. Tom’s of Maine, known for its oral dental products, entered the lucrative area of cough/cold products in August 1999. Pharmacists will have to pay close attention to all the advertising to keep up with products themselves. Reading labels before making recommendations is more important than ever if pharmacists are to make informed choices for their patients.

Drug manufacturers have attempted to improve the taste of medications over the years, but the W. K. Buckley company is taking an opposite position in an advertising campaign planned for the upcoming cold season. Buckley’s Mixture is an old cough remedy that boasts it works because of its terrible taste.

Common colds resolve themselves with or without drug treatment. Studies have shown that OTC drugs provide relief from cold symptoms by reducing their severity or duration. Pharmacists should recommend that patients who have colds get proper rest and increase their fluid intake. The ingestion of hot soups and beverages may provide some comfort. The use of vaporizers or humidifiers will relieve irritation of the nose and throat caused by dry air and will reduce coughs resulting from local irritation. These measures will not cause adverse effects in any patients regardless of their age or health status.

Additional recommendations depend on the specific complaints of each patient. Any medical condition that the patient has or any medication that the patient is taking must be considered before selecting a product. 

Decongestants reduce nasal stuffiness, and topical drugs are less likely to produce adverse systemic effects, but are more likely to cause rebound congestion (rhinitis medica mentosa) than oral products. Antihistamines are more beneficial for rhinorrhea when colds are caused by viruses other than rhinovirus, but identity of the virus causing the cold will not be available to pharmacists when they are making their decision. 

Patients complaining of headache, sore throat pain, or mild fever should use an OTC analgesic/ antipyretic drug. Throat lozenges containing a local anesthetic may be useful in adolescents or adults but not in young children. 

Although zinc lozenges may reduce cold symptoms in some patients, their effectiveness is still in doubt. If patients can tolerate the taste, flavored zinc gluconate preparations seem to be the most effective zinc formulations.

Patients who have nonproductive coughs may find antitussives helpful. Local acting antitussives such as menthol cough drops do not cause drowsiness associated with the use of codeine, dextromethorphan, or diphenhydramine. 

Guaifenesin, an expectorant, vitamin C, other vitamins and minerals, and echinacea have not established their efficacy in treating symptoms of the common cold at this time. The same can be said for the myriad of home remedies that are used for treating colds. 

There are many sugar-free products for patients with diabetes mellitus, including many popular brands, such as Benylin Multi-Symptom, Benylin Adult Cough, Halls Sugar Free Cough Drops, N’Ice Sore Throat, Ricola Sugar Free Throat Drops, Sudafed Children’s Cold & Cough, TheraFlu Maximum Strength Flu, Cold & Cough NightTime, Diabetic Tussin products, and Scot-Tussin products.

There is no cure for the common cold. Johnston recommended that a combination of an antiviral drug with an anti-inflammatory taken in the very early stages of a cold may be the most effective treatment.⁷⁰ Unfortunately, there is no effective antiviral at this time, and most patients usually wait until their symptoms are well developed before they seek treatment. Effective prevention and treatment for the common cold remains in the future.

Return to Introduction

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