What is the role of nicotine pouches in smoking cessation and nicotine replacement therapy (NRT)?

Role of Nicotine Pouches in Smoking Cessation and NRT

Nicotine pouches can be effective as part of nicotine replacement therapy for smoking cessation, but they should be used as a second-line option after established NRT products like patches combined with short-acting forms of nicotine replacement. 1

Evidence on Nicotine Pouches

Nicotine pouches are a relatively new tobacco-free oral nicotine delivery system that:

• Contain nicotine powder in flavored, microfiber pouches placed between the cheek and gums 2
• Deliver nicotine without tobacco leaf components 3
• Have lower levels of harmful and potentially harmful constituents compared to traditional smokeless tobacco products 4

Pharmacokinetics and Delivery

• Higher concentration pouches (6mg) deliver more nicotine than lower concentration pouches (3mg) and comparable or higher levels than cigarettes at 30 minutes post-administration 5
• Pouches containing >99% S-nicotine (tobacco-derived) deliver significantly higher plasma nicotine concentrations than those with racemic (synthetic) nicotine 6
• Despite adequate nicotine delivery, nicotine pouches do not relieve cravings as quickly as cigarettes at 5 minutes post-administration 5

Established NRT Options and Their Efficacy

Current guidelines strongly recommend the following NRT approaches for smoking cessation:

First-Line Options:

1. Combination NRT: Using a nicotine patch plus a short-acting form (gum, spray, lozenge)

   • Most effective NRT approach with odds ratio of 2.73 (95% CI, 2.07-3.65) compared to placebo 1
   • Provides both steady background nicotine levels and on-demand relief for breakthrough cravings

2. Varenicline: Most effective single pharmacotherapy

   • Increases odds of cessation by 2.88 (95% CI, 2.40-3.47) compared to placebo 1
   • Comparable efficacy to combination NRT (OR, 1.06; 95% CI, 0.75-1.48) 1

3. Nicotine Patch: Standard approach

   • 6-14 week use provides 23.4% abstinence rate at 6 months 1, 7
   • Longer-term use (>14 weeks) may provide additional benefits 1

Safety Considerations

Nicotine Pouches:

• Risk of nicotine toxicity with excessive use (case report of toxicity with 15 extra-strength pouches in 12 hours) 2
• May appeal to youth due to flavors and marketing claims of being "tobacco-free" 3

Established NRT:

• Generally safe even in patients with cardiovascular disease 1
• Low risk of dependence compared to cigarettes 7
• Pregnancy remains a relative contraindication, though NRT is likely safer than continued smoking 1

Algorithm for Smoking Cessation Therapy Selection

1. First-line options:

   • Combination NRT (patch + short-acting form) OR
   • Varenicline (if no contraindications)

2. Second-line options (if first-line unsuccessful or contraindicated):

   • Bupropion
   • Single NRT product
   • Nicotine pouches

3. For highly dependent smokers:

   • Consider higher-dose nicotine patch (>25 mg/day) 1
   • Nicotine nasal spray for faster nicotine delivery 1

Practical Implementation

• Start with higher-dose products for heavier smokers (>10 cigarettes/day) 1, 7
• Provide behavioral support alongside pharmacotherapy to significantly improve outcomes 1
• Prescribe for short durations initially and renew only if quit attempt continues 1
• Consider longer duration of therapy (>14 weeks) for those at high risk of relapse 1

Cautions and Limitations

• Nicotine pouches lack sufficient clinical trial evidence for smoking cessation compared to established NRT products 1
• Risk of appeal to non-smokers, especially youth, due to flavors and marketing 3
• Nicotine has neurotoxic effects on developing brains, raising concerns for use in adolescents 1
• Most research on nicotine pouches to date is tobacco industry-funded, highlighting the need for independent studies 3