Sticking to the Facts On E-Cigarettes & Nicotine Medicines

A dentist colleague notes that the American Dental Association was one of 28 medical societies that signed a letter to the FDA in opposition to a change in the deeming date for e-cigarettes (here):  “Changing this date would significantly weaken FDA’s ability to take prompt action to protect children from thousands of fruit and candy flavored e-cigarettes and cigars, including products in flavors such as cotton candy, gummy bear and fruit punch that clearly appeal to kids.”

Ironically, nicotine medicines also come in appealing flavors, like cinnamon surge, fruit chill, fresh mint, spearmint burst and white ice mint (here).  Evidently, marketers of both product categories view flavoring as a necessary and effective device to attract adult smokers.

While e-cigarettes are often tagged with groundless or exaggerated claims of health threats, my colleague cites specific health issues associated with nicotine medicines, as reported by a reputable clinical drug information service:

Adverse Effects that Occur Greater than 10% of the Time:

Headache (18% to 26%), Mouth/throat irritation (66%), dyspepsia (18%), cough (32%), rhinitis (23%).

Adverse Effects that Occur 1% to 10% of the Time:

Acne (3%), Dysmenorrhea (3%), flatulence (4%), gum problems (4%), diarrhea, hiccup, nausea, taste disturbance, tooth abrasions, back pain (6%), arthralgia (5%), jaw/neck pain, nasal burning (nasal spray), sinusitis, withdrawal symptoms

Adverse Effects that Occur Less than 1% of the Time:

Allergy, amnesia, aphasia, bronchitis, bronchospasm, edema, migraine, numbness, pain, purpura, rash, sputum increased, vision abnormalities, xerostomia

Adverse Effects For Which the Frequency is Not Defined:

Concentration impaired, depression, dizziness, headache, insomnia, nervousness, pain, aphthous stomatitis, constipation, cough, diarrhea, gingival bleeding, glossitis, hiccups, jaw pain, nausea, salivation increased, stomatitis, taste perversion, tooth abrasions, ulcerative stomatitis, xerostomia, rash, application site reaction, local edema, local erythema, Arthralgia, myalgia, paresthesia, sinusitis, allergic reaction, diaphoresis.

Any of these adverse effects could be needlessly exaggerated to condemn nicotine medicines, but they aren’t.  Nicotine can be consumed safely in gum, patches or vapor products.

Scaremongering Tactics Against Smoke-Free Tobacco Could Also Undermine Nicotine Medicines

Tobacco prohibitionists routinely cherry-pick data to put tobacco products in the worst possible light.  For example, crusaders have used calls to poison control centers to paint smokeless tobacco (here) and, more recently, e-cigarettes (here) as toxic time-bombs.  To underscore how deceptively simple and grossly misleading such scaremongering can be, I offer this demonstration of selective data analysis applied to nicotine medicines.

Opponents of safer smoke-free tobacco promote nicotine medicines as quit-smoking aids that are “safe and effective.”  In previous posts I have shown that nicotine medicines are not effective; their success rates are pitifully low (here and here). The question remains: Are nicotine medicines safe?

Data from the FDA Adverse Event Reporting System provides the starting point for a scaremonger case against nicotine medicines’ safety.  The FAERS is a collection of volunteered reports from consumers and health professionals, plus mandatory reports from manufacturers.  The dataset is difficult to use and interpret, so I worked with Joe Fuisz and Tom O'Connell of Vapor Tobacco Manufacturing LLC and Paul Danese of FDAble.com to prepare this analysis.

We looked at adverse events linked to nicotine medicines from 2007 to 2014, a period consistent with the availability of e-cigarettes.  Adverse events for e-cigarettes were also recorded by the FDA during this timeframe, however, those numbers may be underestimated, as e-cigs are not considered medicines by most consumers and health professionals.

During this period, there were 690 adverse events related to nicotine gum/lozenges, 2,006 related to patches, 1,123 for the spray and 28 for e-cigarettes.   

Table 1 illustrates the top 5 adverse events for each product.  It is not possible to make direct comparisons or to calculate rates, as these are individual reports, but it is noteworthy that “ineffective” was a top 5 adverse event for both gum/lozenges and patches.  The spray is commonly known to produce throat symptoms and cough, and nausea is also a frequent complaint for smokers who switch to smoke-free tobacco products.

Table 1. Top Five Adverse Events (Number) for Nicotine Medicines and E-Cigarettes, 2007-2014
Gum/Lozenges (690)	Patches (2,006)	Nasal Spray (1,123)	E-Cigarettes (28)
Intentional drug misuse (243)	Itching (396)	Cough (96)	Headache (6)
Nicotine dependence (216)	Redness (395)	Product quality issue (71)	Nausea (5)
Administration error (86)	Drug ineffective (368)	Throat irritation (64)	Dizziness (4)
Drug ineffective (65)	Administration error (364)	Nausea (63)	Muscle spasms
Nausea (56)	Nausea (199)	Dizziness (47)	Chest pain (3)

While the most common adverse events were not serious, the list of outcomes in the following table is worrisome at first glance.  There is no representation in the reporting system that the products “caused” the negative outcomes, but those aiming to trash nicotine medicines would make that linkage and issue press releases with hyperbolic safety warnings to drive their point home.  It’s that simple.

Table 2. Number of Serious Outcomes* for Adverse Events Related to Nicotine Medicines and E-Cigarettes, 2007-2014
Outcome	Gum/Lozenges	Patches	Nasal Spray	E-Cigarettes
Congenital Anomaly	0	5	1	0
Disability	4	7	13	1
Hospitalization	17	101	78	7
Life Threatening	3	7	3	6
Death	6	18	8	0

*Numbers are not mutually exclusive

Scaremongering is a despicable, yet all too common practice that undercuts legitimate scientific discourse, distorts public health policymaking and ultimately costs smokers’ lives.  Recreational use of nicotine in smoke-free delivery systems, like recreational use of caffeine, is relatively safe for consumers.  

FDA: Adverse Events Related to E-Cigarettes Are Almost Nonexistent

The FDA Center for Tobacco Products’s Dr. Ii-Lun Chen describes in Nicotine and Tobacco Research (citation here) adverse events related to e-cigarettes reported to the agency from 2008 to the first quarter of 2012.  

Adverse Events Reported to the FDA for E-cigarettes and Other Tobacco Products
Year	E-cigarettes	Other Tobacco Products
Up to 2008	1	17
2009	10	6
2010	16	11
2011	11	19
1st Quarter 2012	9	2

Dr. Chen notes: “…approximately half of all tobacco-related [adverse event] reports [since the late 1980s] concern electronic cigarettes, the first of which was submitted in 2008.”  A look at details of the events reveals that few reflect legitimate e-cigarette health impact.

Some “serious” complaints variously involved hospitalization for pneumonia, congestive heart failure, disorientation, seizure, hypotension, possible aspiration pneumonia, second-degree burns (from a battery explosion), chest pain and rapid heartbeat, possible infant death from choking on a cartridge, and loss of vision.  The single burn case may have been related to an e-cigarette, as there have been media reports of rare battery-related incidents (here).  The infant choking death, while tragic, implicates irresponsible adults who put children in proximity of ingestible objects; it is not an e-cigarette health issue.  All of the other “serious” complaints were nonspecific and probably unrelated to the product.

Dr. Chen reports that “…other e-cigarette complaints include concerns about false advertising, headache/migraine, chest pain, cough/sputum, nausea/vomiting, dizziness, feeling sick, confusion/stupor, sore throat, shortness of breath, abdominal pain, pleurisy, blurry vision, and sleepy/tired.”  He correctly adds, “Of note, there is not necessarily a causal relationship between AEs reported and e-cigarette use, as some AEs could be related to pre-existing conditions or due to other causes not reported.”

E-cigarettes are relatively new products, so it is not surprising that adverse events have surfaced in the form of “…voluntary communications from consumers, health care professionals, and concerned members of the public.” 

The bottom line is: Among millions of e-cigarette users, credible adverse events are almost nonexistent.