Zicam
Encyclopedia
Zicam is a branded series of products marketed for cold
and allergy relief whose original formulations included the element zinc
. The Zicam name is derived from a combination of the words "zinc" and "ICAM-1
" (the receptor to which a rhinovirus
binds in order to infect cells). It is marketed as an "unapproved homeopathic" product.
Zicam was invented by Charles B. Hensley
in the mid 1990s and is produced, marketed and sold by Zicam, LLC, a wholly owned subsidiary of Matrixx Initiatives, Inc., an American over-the-counter drug
company. In 2009, the U.S. Food and Drug Administration (FDA) advised consumers to avoid intranasal versions of Zicam Cold Remedy because of a risk of damage to the sense of smell
, leading the manufacturer to withdraw these versions from the U.S. market. The Zicam brand has been expanded to include non-zinc formulations.
s present in Zicam Cold Remedy are slightly diluted zinc acetate
(2X = 1/100 dilution) and zinc gluconate
(1X = 1/10 dilution); the product's other originally active ingredients have been serially diluted to the point that Zicam should no longer contain any molecules of those ingredients, and are listed as "inactive ingredients" on the label.. Zicam is marketed as an "unapproved homeopathic" product; Some of the homeopathic ingredients used in the preparation of Zicam are galphimia glauca, histamine dihydrochloride (homeopathic name, histaminum hydrochloricum), luffa operculata
, and sulfur
.
Ion
ic zinc is proposed to interfere with the binding of rhinovirus
to its cellular receptor, ICAM-1
. Some research suggests that zinc-based remedies may reduce the duration of the common cold
and reduce the severity of cold symptoms. Another study indicates that zinc-based remedies can relieve symptoms of hay fever
and other upper respiratory allergies
.
A 2003 review in the Journal of the American Pharmacists Association reported that the majority of studies supported the value of zinc in reducing the duration and severity of symptoms of the common cold when administered within 24 hours of the onset of common cold symptoms.
A systematic review
published in 2006 in Clinical Infectious Diseases
found that many of the studies of zinc in the common cold suffered from methodologic flaws; restricting the analysis to well designed studies, the authors concluded that the therapeutic effectiveness of zinc lozenges has yet to be established.
A 2011 systematic meta analysis of studies conducted by the Cochrane Collaboration
indicates that zinc lozenges definitively shorten the duration and severity of cold symptoms but offers no recommendations as to dosage. Many over the counter zinc medications may be less effective or ineffective because they do not contain the optimum mix of ingredients. The zinc gluconate and zinc acetate salts may be better absorbed by the human body than other zinc salts. This variety of formulations has also been implicated in the prior lack of success in determining the effectiveness of zinc medicines. Methodological weaknesses are also thought to have contributed to the mixed results of previous studies (see below). The 2011 Cochrane review is widely regarded as the most authoritative assessment to date of the effectiveness of zinc as a treatment for the common cold. It is suspected that zinc gluconate lozenges shorten the duration of cold
symptoms by reducing inflammatory cytokine
s.
), although the company did not admit fault. As of 2009, "hundreds more such suits have since been filed."
with them. The advisory did not implicate other Zicam products. The FDA indicated that it had received reports of a loss of smell from approximately 130 Zicam Cold Remedy users since 1999. The FDA voiced concern that the loss of smell may be long-lasting or permanent, while the condition for which these Zicam products are marketed—the common cold—typically resolves on its own without lasting problems. The manufacturer stated that it had received an additional 800 reports of a loss of smell, but did not turn those over to the FDA as they did not feel they were required to do so. The FDA disagreed, and requested copies of any reports that had associated anosmia with intranasal Zicam Cold Remedy.
The FDA also issued a Warning Letter
to Matrixx, stating that the products cannot be marketed without FDA approval. The company initially refused to recall the products but later said that they would withdraw the products from sale and that, "based on the FDA’s recommendation, consumers should discard any unused product or contact Zicam ... to request a refund." On June 24, 2009, Matrixx recalled all affected products. The company maintained that most cases of anosmia are due to the common cold itself, and that complaints of anosmia among Zicam Cold Remedy users are unlikely to be more numerous than those expected among the general population. In contrast, the FDA had reported that cases of anosmia associated with intranasal Zicam Cold Remedy products were in excess of those seen with other nasal remedies for the common cold, and that cases associated with intranasal zinc presented more rapidly, and with different symptoms, than did unrelated cases.
In addition, the FDA's warning letter prompted the Securities and Exchange Commission to investigate the company. Through Freedom of Information Act (FOIA) filings, Matrixx has requested the FDA to provide the research and evidence that led them to request the withdrawal of Zicam swabs. The company said that "fundamental fairness" required a clear explanation of the FDA's methodology and analysis.
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
and allergy relief whose original formulations included the element zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
. The Zicam name is derived from a combination of the words "zinc" and "ICAM-1
ICAM-1
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system...
" (the receptor to which a rhinovirus
Rhinovirus
Human rhinoviruses are the most common viral infective agents in humans and are the predominant cause of the common cold. Rhinovirus infection proliferates in temperatures between 33–35 °C , and this may be why it occurs primarily in the nose...
binds in order to infect cells). It is marketed as an "unapproved homeopathic" product.
Zicam was invented by Charles B. Hensley
Charles B. Hensley
Charles B. Hensley is an American entrepreneur and Chairman of Hensley Group, Inc., an umbrella organization that controls a diverse set of corporate entities involved in pharmaceuticals, cosmetics, music, television and film....
in the mid 1990s and is produced, marketed and sold by Zicam, LLC, a wholly owned subsidiary of Matrixx Initiatives, Inc., an American over-the-counter drug
Over-the-counter drug
Over-the-counter drugs are medicines that may be sold directly to a consumer without a prescription from a healthcare professional, as compared to prescription drugs, which may be sold only to consumers possessing a valid prescription...
company. In 2009, the U.S. Food and Drug Administration (FDA) advised consumers to avoid intranasal versions of Zicam Cold Remedy because of a risk of damage to the sense of smell
Anosmia
Anosmia is a lack of functioning olfaction, or in other words, an inability to perceive odors. Anosmia may be either temporary or permanent. A related term, hyposmia, refers to a decreased ability to smell, while hyperosmia refers to an increased ability to smell. Some people may be anosmic for one...
, leading the manufacturer to withdraw these versions from the U.S. market. The Zicam brand has been expanded to include non-zinc formulations.
Ingredients and use
The only possibly biologically active ingredientActive ingredient
An active ingredient is the substance of a pharmaceutical drug or a pharmaceutical ingredient and bulk active in medicine; in pesticide formulations active substance may be used. Some medications and pesticide products may contain more than one active ingredient...
s present in Zicam Cold Remedy are slightly diluted zinc acetate
Zinc acetate
Zinc acetate is the chemical compound with the formula Zn2, which commonly occurs as a dihydrate Zn22. Both the hydrate and the anhydrous forms are colorless solids that are commonly used in chemical synthesis and as dietary supplements. Zinc acetates are prepared by the action of acetic acid on...
(2X = 1/100 dilution) and zinc gluconate
Zinc gluconate
Zinc gluconate is the zinc salt of gluconic acid. It is an ionic compound consisting of two moles of gluconate for each mole of zinc...
(1X = 1/10 dilution); the product's other originally active ingredients have been serially diluted to the point that Zicam should no longer contain any molecules of those ingredients, and are listed as "inactive ingredients" on the label.. Zicam is marketed as an "unapproved homeopathic" product; Some of the homeopathic ingredients used in the preparation of Zicam are galphimia glauca, histamine dihydrochloride (homeopathic name, histaminum hydrochloricum), luffa operculata
Luffa operculata
Luffa operculata is a species of Luffa. It is cultivated for its fruit, which is used to make a bath sponge. Its fruit is a capsule with spikes and toxicity. The fruit is dark-brown when mature. It is also grown in gardens and yards as an ornamental plant...
, and sulfur
Sulfur
Sulfur or sulphur is the chemical element with atomic number 16. In the periodic table it is represented by the symbol S. It is an abundant, multivalent non-metal. Under normal conditions, sulfur atoms form cyclic octatomic molecules with chemical formula S8. Elemental sulfur is a bright yellow...
.
Ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
ic zinc is proposed to interfere with the binding of rhinovirus
Rhinovirus
Human rhinoviruses are the most common viral infective agents in humans and are the predominant cause of the common cold. Rhinovirus infection proliferates in temperatures between 33–35 °C , and this may be why it occurs primarily in the nose...
to its cellular receptor, ICAM-1
ICAM-1
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system...
. Some research suggests that zinc-based remedies may reduce the duration of the common cold
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
and reduce the severity of cold symptoms. Another study indicates that zinc-based remedies can relieve symptoms of hay fever
Hay Fever
Hay Fever is a comic play written by Noël Coward in 1924 and first produced in 1925 with Marie Tempest as the first Judith Bliss. Laura Hope Crews played the role in New York...
and other upper respiratory allergies
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
.
A 2003 review in the Journal of the American Pharmacists Association reported that the majority of studies supported the value of zinc in reducing the duration and severity of symptoms of the common cold when administered within 24 hours of the onset of common cold symptoms.
A systematic review
Systematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
published in 2006 in Clinical Infectious Diseases
Clinical Infectious Diseases
Clinical Infectious Diseases in a peer-reviewed medical journal published by Oxford University Press covering research on the pathogenesis, clinical investigation, medical microbiology, diagnosis, immune mechanisms, and treatment of diseases caused by infectious agents...
found that many of the studies of zinc in the common cold suffered from methodologic flaws; restricting the analysis to well designed studies, the authors concluded that the therapeutic effectiveness of zinc lozenges has yet to be established.
A 2011 systematic meta analysis of studies conducted by the Cochrane Collaboration
Cochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
indicates that zinc lozenges definitively shorten the duration and severity of cold symptoms but offers no recommendations as to dosage. Many over the counter zinc medications may be less effective or ineffective because they do not contain the optimum mix of ingredients. The zinc gluconate and zinc acetate salts may be better absorbed by the human body than other zinc salts. This variety of formulations has also been implicated in the prior lack of success in determining the effectiveness of zinc medicines. Methodological weaknesses are also thought to have contributed to the mixed results of previous studies (see below). The 2011 Cochrane review is widely regarded as the most authoritative assessment to date of the effectiveness of zinc as a treatment for the common cold. It is suspected that zinc gluconate lozenges shorten the duration of cold
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
symptoms by reducing inflammatory cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s.
Litigation
In 2006, Matrixx Initiatives paid $12 million to settle 340 lawsuits from Zicam users who said that the product destroyed their sense of smell (medically termed anosmiaAnosmia
Anosmia is a lack of functioning olfaction, or in other words, an inability to perceive odors. Anosmia may be either temporary or permanent. A related term, hyposmia, refers to a decreased ability to smell, while hyperosmia refers to an increased ability to smell. Some people may be anosmic for one...
), although the company did not admit fault. As of 2009, "hundreds more such suits have since been filed."
FDA warning and product recall
On June 16, 2009, the FDA advised consumers to discontinue use of three nasally administered versions of Zicam Cold Remedy—Zicam Cold Remedy Nasal Gel, Zicam Cold Remedy Nasal Swabs, and Zicam Cold Remedy Swabs, Kids Size (a discontinued product)—because the FDA had associated a serious risk of anosmiaAnosmia
Anosmia is a lack of functioning olfaction, or in other words, an inability to perceive odors. Anosmia may be either temporary or permanent. A related term, hyposmia, refers to a decreased ability to smell, while hyperosmia refers to an increased ability to smell. Some people may be anosmic for one...
with them. The advisory did not implicate other Zicam products. The FDA indicated that it had received reports of a loss of smell from approximately 130 Zicam Cold Remedy users since 1999. The FDA voiced concern that the loss of smell may be long-lasting or permanent, while the condition for which these Zicam products are marketed—the common cold—typically resolves on its own without lasting problems. The manufacturer stated that it had received an additional 800 reports of a loss of smell, but did not turn those over to the FDA as they did not feel they were required to do so. The FDA disagreed, and requested copies of any reports that had associated anosmia with intranasal Zicam Cold Remedy.
The FDA also issued a Warning Letter
FDA Warning Letter
The United States Food and Drug Adminstration defines a Warning Letter as "...a correspondence that notifies regulated industry about violations that FDA has documented during its inspections or investigations...
to Matrixx, stating that the products cannot be marketed without FDA approval. The company initially refused to recall the products but later said that they would withdraw the products from sale and that, "based on the FDA’s recommendation, consumers should discard any unused product or contact Zicam ... to request a refund." On June 24, 2009, Matrixx recalled all affected products. The company maintained that most cases of anosmia are due to the common cold itself, and that complaints of anosmia among Zicam Cold Remedy users are unlikely to be more numerous than those expected among the general population. In contrast, the FDA had reported that cases of anosmia associated with intranasal Zicam Cold Remedy products were in excess of those seen with other nasal remedies for the common cold, and that cases associated with intranasal zinc presented more rapidly, and with different symptoms, than did unrelated cases.
In addition, the FDA's warning letter prompted the Securities and Exchange Commission to investigate the company. Through Freedom of Information Act (FOIA) filings, Matrixx has requested the FDA to provide the research and evidence that led them to request the withdrawal of Zicam swabs. The company said that "fundamental fairness" required a clear explanation of the FDA's methodology and analysis.