Safety Profile of a Nicotine Lozenge Compared with That_x000D_of Nicotine Gum in Adult Smokers with Underlying Medical_x000D_Conditions: A 12-Week, Randomized, Open-Label Study

Introduction
Nicotine lozenges deliver 25–27% more nicotine than equivalent doses of nicotine gum, raising questions about comparative safety.
Safety concerns are particularly relevant for smokers with underlying medical conditions (e.g., cardiovascular disease, hypertension, diabetes).
This study aimed to compare the safety and tolerability of 4-mg nicotine lozenges versus 4-mg nicotine gum in a real-world clinical population.
Key Points
Study design: 12-week, multicenter, randomized, open-label trial including 901 adult smokers with label-restricted medical conditions.
Population: Mean age ~54 years; most participants had hypertension, heart disease, and/or diabetes.
Nicotine exposure: Despite higher nicotine delivery from lozenges, overall tolerability was similar between treatments.
Adverse events (AEs):
Incidence of AEs was comparable between lozenge and gum during the first 2 weeks and over the entire study.
Most common AEs: nausea, hiccups, headache, dyspepsia.
Vomiting was slightly more frequent with lozenges early in treatment but remained uncommon.
Serious adverse events: Rare and similar between groups; most were judged unrelated to study products.
Cardiovascular safety: Cardiac-related AEs were infrequent and showed no clinically meaningful differences between groups.
Disease status: >90% of participants experienced no worsening of underlying medical conditions during the study.
Concurrent smoking: Most participants continued to smoke occasionally, yet AE rates remained comparable between products.
Conclusion
The 4-mg nicotine lozenge and 4-mg nicotine gum demonstrated comparable safety profiles in smokers with underlying medical conditions.
Increased nicotine exposure from lozenges did not result in clinically significant safety concerns.
Both products were well tolerated, supporting their use as safe nicotine replacement options in medically complex populations

Marsh, Howard S., et al. “Safety Profile of a Nicotine Lozenge Compared with That of Nicotine Gum in Adult Smokers with Underlying Medical Conditions: A 12-Week, Randomized, Open-Label Study.” Clinical Therapeutics, vol. 27, no. 10, 2005, pp. 1571–1587.