Cold sores ... not a trivial matter

Sept. 1, 2005
Each year, 150 million people in the United States (one-third of the population) suffer from the pain and embarrassment of cold sores.

By Dr. Michael L. Milligan

Each year, 150 million people in the United States (one-third of the population) suffer from the pain and embarrassment of cold sores. With a total of 380 million outbreaks annually nationwide, the average cold sore sufferer will have two to six outbreaks, lasting approximately seven to 10 days each. In the United States alone, more than $1 billion is spent every year on both over-the-counter (OTC) and prescription (Rx) treatments to help bring relief to this growing epidemic.

As an oral healthcare professional, you have probably seen your share of oral herpes (cold sores/fever blisters). Your patients are upset by the physical discomfort and, at times, are distraught by the social embarrassment. Many turn to you for answers and relief. As their doctor, you want to help. It is uniquely gratifying and rewarding when advances in medicine and pharmacology coincide with a business opportunity to make that possible.

Viroxyn® kills the virus that causes cold sores on contact. Quadex Pharmaceuticals, LLC has chosen an innovative approach to making Viroxyn® available to patients. Your practice can participate practically and financially in assuring that Viroxyn® gets to the cold sore sufferers who need it. Some Dental Equipment & Materials readers will remember Viroxyn® from when it was marketed in 1999-2000. Sales were temporarily suspended in order to respond to an FDA request for additional effectiveness data. Having responded appropriately to the FDA request, Quadex Pharmaceuticals, LLC reintroduced Viroxyn® to the market in late November 2003. In order to provide optimal chances for its successful application to cold sores, it is being reintroduced via dental and other healthcare professionals. This product offers dentists simultaneous opportunities to educate their patients about the importance of cold sores as one of the cutaneous herpes simplex (type 1 or HSV-1) infections, to teach them optimal administration techniques for the best therapeutic result, and to share in the revenues from the sales of this product by offering it to patients.

Background (Human Herpes Virus 101)

The human herpes viruses affect more than 90 percent of the world’s six billion inhabitants. While there are likely numerous variants, eight are known to infect man. Of these, the three that infect the skin and/or mucous membranes and become latent in the nervous system are perhaps the best known. These three are herpes simplex virus - type 1 (HSV-1 - the cold sore virus), herpes simplex virus, type 2 (HSV-2 - the genital herpes virus), and Varicella zoster virus (VZV - the chicken pox and shingles virus).

HSV-1 is the target of the Viroxyn® reintroduction, as the virus most commonly associated with cold sores/fever blisters. Cold sores are the recurrent form of HSV-1 infection, occurring after latent infection has been established during the primary HSV-1 infection. Primary HSV-1 infection is often subclinical or goes unnoticed, or it may cause gingivostomatitis that ranges from mild to severe, the latter of which may be accompanied by lymphadenitis, fever, and malaise.

HSV-2 is traditionally associated with genital herpes (herpes genitalis), although today more than half of first episodes of genital herpes are caused by HSV-1. Varicella zoster virus (VZV) is the cause of chicken pox in young children and shingles or zoster in older children and adults.

In addition to the traditional modes of infection with HSV-1, accidental self-inoculation of the eyes after touching one’s own oral lesion or coming into contact with another’s cold sore/fever blister can lead to herpes keratitis (ocular herpes), a leading cause of blindness. Dental and other healthcare professionals who treat oral pathologies correctly fear herpetic whitlow (HSV-1 infection of the terminal phalanx of the finger sometimes contracted after working without gloves in an infected mouth). Wrestlers and other sports enthusiasts who engage in close physical contact sports may experience herpes gladiatorum (widespread, cutaneous HSV-1 infection passed to an HSV-naive opponent by a person with an active recurrent HSV skin lesion).

HSV-1, HSV-2, and HZV have similar infection modalities. The cold sore virus (HSV-1) infects people initially as a result of contact with an infected person (human herpes viruses are very species-specific). The virus then reappears in subsequent months or later in life as recurrent infection following a period of latency. During reactivation, the latent virus “wakes up” following a stimulus and a viral load migrates from the nerve cell nucleus, retrograde down the axon sheath to the original site of skin infection. Here the virus exits the terminal neuron, reassembles its lipid coat, and infects the adjacent cells. Viral reproduction takes place in these infected cells and subsequent lysis of the infected cells leads to infection of still more adjacent cells. A lesion is the result of this process. A variety of stimuli have been shown to trigger cold sore recurrences including changes in immune status, physical trauma (such as dental procedures), emotional stress, concurrent illnesses (especially febrile illnesses), and exposure to UV-B radiation from the sun.

Cold sore infections (HSV-1) are typically transmitted by an infected person to an uninfected person during two distinct periods of life - ages 3 to 7 (childhood) and ages 12 to 21 (adolescence).

Cold sores: The wolf in sheep’s clothing

Oral herpes is of particular concern to the healthcare profession because of a general lack of appreciation that “cold sores” are actually orofacial herpes virus infections. This phenomenon may be fueling the current spread of HSV-1 infections to other people and to body parts besides the mouth. Since most cold sores heal spontaneously within one to two weeks with no treatment, they are often thought of as unimportant, medically speaking. Because cold sores are too often thought of as trivial, they may be characterized as the “wolf in sheep’s clothing.” Quite to the contrary, HSV-1 is capable of causing life-threatening and lethal herpes encephalitis in otherwise normal people, lethal and blinding infections in newborns, blindness in adults, and serious to life-threatening infections in immunocompromised patients. Herpes gladiatorum, alluded to earlier, can be as severe as smallpox in some people, and cold sores can be progressive and necrotizing in patients with atopic eczema or compromised immune systems. The challenge to managing such a “wolf in sheep’s clothing” requires that the patient who is destined to have a mild form of the infection not be put at undue risk of side effects from choosing too strong a treatment. However, at the same time, the treatment must offer strong enough effectiveness to stop the virus from progressing or spreading to vulnerable people.

Denial may be one dynamic that increases the risk of transmission of HSV-1 to susceptible individuals. It is socially embarrassing to acknowledge that the cold sore sufferer has a “herpes infection.” There is the potential stigma of having one’s associates believe that the cold sore may have been acquired through orogenital contact. The unwanted lip lesion is openly visible to friends, family, and all those who come in contact with the sufferer. This has led people to try almost any treatment, FDA-approved or not, to relieve the suffering and diminish the social embarrassment of having an active cold sore by trying to mask or eliminate it as soon as possible.

The size of the problem

The problem is a worldwide one with the more severe forms of disease occurring more often in immune-compromised people and people living in developing countries. In the United States, 150 million people (one-third of the population) annually experience approximately 338 million treatable episodes of cold sores. A recently reported phenomenon is that HSV-1 genital infection is now being seen in increasing frequency at multiple sites around the world. Half of all first-time genital herpes infections in all age groups and more than 70 percent of patients under the age of 25 have first episodes of genital herpes that are caused by HSV-1, rather than the usual HSV-2.

These findings offer a strong new argument for rapidly controlling the oral infection episodes, as doing so may help prevent the spread of HSV-1 to the genital area. Application of a treatment that immediately kills the virus on contact, such as Viroxyn®, may be especially vital to achieving this goal.

Current standard of care

Currently, there is no cure for any of the human herpes virus infections, as its latent form resides in the cells of the central nervous system, unreachable by any known therapy. However, there are treatments, both FDA-approved and “alternative” modalities, available by Rx, OTC, or through health food and alternative health stores.

Acyclovir (Zovirax®) was the first Rx drug to be proven both safe and effective for treating many of the herpes skin infections, even in low-risk patients. Acyclovir and acyclovir derivatives (Valtrex®, Denavir®, and Famvir®) act to interfere with viral reproduction by offering the virus a defective DNA building block (herpes viruses are lipid-coated DNA viruses) that is preferentially incorporated into the replicating viral DNA chain, thus stopping its continued replication. These drugs are all FDA-approved Rx therapies. They can be prescribed by physicians and dentists in topical (Denavir®), oral (Zovirax®, Valtrex®, and Famvir®), and injectable forms for the treatment of cold sores and the complications of cold sores. Some people have found them effective in reducing recurrence rates or lessening the severity of recurrences. Others do not enjoy similar benefits. Some people opt not to treat their infections due to cost concerns or concerns over the theoretical, long-term effects of nucleosides. The injectable prescription drugs remain particularly important for treating serious and life-threatening forms of HSV-1 infection, particularly in the immune-compromised.

Abreva is an FDA-approved OTC available to treat oral herpes. It acts in a manner that is similar to a skin protectant in that it provides a skin lesion coating or barrier that may prevent movement of the virus from infected to uninfected cells (Abreva Drug Approval). There are also numerous legally marketed skin protectants (Blistex, Carmex, etc.) and topical analgesic products which act to provide temporary relief of cold sore symptoms.

Finally, there is a host of non-approved, alternative remedies (lysine, colloidal silver, stannous fluoride, electric shock devices, plant extracts, etc.) that are tried by many in their attempts to shorten the course of a cold sore and to relieve the pain, suffering, and embarrassment that attend them.

An innovative approach to managing cold sores

Viroxyn® is an innovative presentation of the active ingredient benzalkonium chloride (BZK), the fat solvent isopropyl alcohol (IPA), the vehicle sterile water, and a unique single-use dosage form with its own built-in topical applicator. As a well-known microbicide with broad killing activity against many bacteria, fungi, and viruses, BZK is strongly microbicidal against lipid-coated viruses, such as the HSV-1. IPA is a strong solvent of cellular membrane fats, and both BZK and IPA are soluble in water. This unique, patented, composition of ingredients, presented in a single-dose, single-use unit with a built-in applicator lends itself especially well to the topical treatment of cold sores. The fat-solvent characteristics of IPA dissolve the high fat-content cellular debris that is the typical, treatment-blocking barrier to topical treatment of cold sores, and the applicator sweeps the debris aside so that BZK can make effective contact with the HSV-1. BZK strips the herpes virus of its lipid coat, killing it on contact and sparing the remaining, susceptible, uninfected skin cells from becoming infected. The unique applicator minimizes the potential for self-inoculation of other body parts. The single-use function avoids the potential for product contamination or use by others.

The cold sore may hurt badly and the patient may not want to comply with labeled directions. In order to achieve maximum therapeutic results, you will want to be sure that the patient understands the need to firmly rub the medication into the cold sore.

Human clinical experience

Viroxyn® was initially formulated by the founder of Quadex as a remedy for cold sores, based on his own personal experiences with a rather severe form of the disease. Interest in sharing his good experience with a broader range of cold sore sufferers led Quadex to seek the advice of various experts in the treatment of cold sores.

Quadex was advised to conduct a pilot study in a human model of the target disorder. An open-label, UV light-induced cold sore study was conducted at one clinical study center under IRB approval and supervision. The participants all had a history of sun-induced cold sore reactivation and ranged in age from 18-67 years of age. All were Caucasian, with 73 percent were women and 27 percent were men. Of those, 74 percent experienced cold sore reactivation after exposure to UV light.

Separate analyses were conducted on the intent-to-treat (ITT) population and per-protocol populations. The ITT population included all those who were issued study drug and experienced a lesion - whether or not they visited the site, followed directions, or actually used the study drug. Patients who did not visit the study site or who were lost to follow-up were treated as “last observation carried forward” to the maximum value of 10 days. Patients who had lesions, but did not actually use the drug or did not use it on all lesions, were followed and their actual healing time data included in the ITT analysis. The “per-protocol” population included all those who experienced one or more lesions, made all their scheduled visits, followed all study directions, and actually used the study drug at least once on all cold sore lesions. The endpoint for healing was loss of scab and return to intact skin. The endpoint was patient-reported and investigator-verified.

The study drug intent-to-treat population (n=41) experienced complete lesion healing within a mean of 5.4 (±2.6) days (median 4.4 days). The “per-protocol” (PP) population experienced complete lesion healing within a mean of 3.6 (±1.1) days (median 3.4 days).

These healing times were very exciting when compared to previously published data for Denavir-treated, UV light-induced lesions (mean 7.6 ±3.22, median 7.0 days) and to the placebo recipients in the Denavir study (mean 8.8 ±3.77 and median 8.0 days). No direct statistical analyses of these apparent differences were conducted, as these data were not collected in the same study.

Support for the usefulness of Viroxyn is further provided in the results of a second study in 120 participants. This controlled comparison has yielded information to reinforce the effectiveness of Viroxyn for treatment of cold sores. Early treatment effects are expressed as a threefold faster healing rate for Viroxyn recipients in the first 72 hours of treatment, and the accelerated healing time reported in the open-label study was duplicated with a mean healing time of four days.


Viroxyn® has been shown to be excitingly effective in clinical trials as a topical, germicidal (virucidal) approach to the treatment of cold sores in people who do not require systemic treatment for their herpesvirus infection. Viroxyn® is currently being marketed through professional healthcare providers, primarily dentists. It is presented in a unique, patented format with a built-in, single-use applicator. Your dental practice has the opportunity to become involved in the introduction of this new product to your cold sore suffering patients. Viroxyn® can be the vehicle for teaching your patients about the importance of cold sores as a source of herpes virus infection and how to treat it to relieve pain, shorten the disease course, and possibly reduce the risks of transmission to other body parts and to more vulnerable people. In doing so, an entrepreneurial opportunity to participate in the sales revenues presents itself to your office’s business management practices.

To participate

To order Viroxyn® or to learn more about becoming involved in its’ distribution, please call (888) 437-7374, email [email protected], or visit where you can access the “healthcare professional wholesale” section and read much more additional information on the website by entering in your healthcare provider number.


The author wishes to thank Ronald E. Keeney, MD, and James P. McCarthy, Ph.D. for providing the background research, clinical data, medical, technical, and regulatory information and support that made this article possible.

Dr. Michael L. Milligan is owner and CEO of Scientific Health Products, with best-in-class products to treat cold sores and canker sores. He began Dental Mastermind Group, “to advance oral and overall health through science.” He is advisory committee chairperson of, and has authored and lectured on a variety of dental topics. Dr. Milligan can be reached at [email protected] or (309) 452-0217 or (309) 663-4711.