The role of NVPs in smoking cessation

While many people successfully quit smoking before causing serious damage to their health, for others smoking is a chronic disorder that may require multiple quit attempts over a long period before they achieve enduring abstinence.

Research has demonstrated a representative pattern of smoking cessation that will be familiar to pharmacists and other health professionals:

• Around 50% of smokers quit successfully on their first serious attempt;
• For the rest, it takes on average, 30 attempts (Chaiton, M. et al. BMJ Open 6, e011045 (2016) DOI: 10.1136/bmjopen-2016-011045) over 20 years (Borland, R. et al. Addiction 107, 673–682 (2012) DOI: 10.1111/j.1360-0443.2011.03685.x) before achieving abstinence; and
• After a failed quit attempt, it will take most smokers a year before they try again.

For long-term smokers, the typical outcome of a quit attempt is a relapse to smoking and, consequently, continued exposure to toxic smoke.

Morbidity and mortality typically start to compound after the age of 30. Dependent smokers who fail in their first serious quit attempt have a high risk of smoking in their 50s and beyond, having inflicted severe damage to their health and incurred a significant risk of early death.

On the other hand, successfully quitting smoking is beneficial to health at any age.

Clinical end-points in smoking cessation

Smoking cessation comprises two separable but interrelated clinical end-points:

• Stopping cigarette smoking; and
• Nicotine abstinence.

Historically, the treatment of smoking has considered nicotine abstinence as the single end-point. With this approach, abstinence follows nicotine-replaced smoking cessation within a few weeks. However, even in patients who adhere to treatment, a relapse to smoking is the norm.

NVPs: An alternative to smoking led by people who smoke

NVPs emerged as a user-innovated technology, and further innovations over the last half-decade mean that ‘new generation’ NVPs are capable of closely reproducing cigarettes’ pharmacological and behavioural properties.

NVPs do this without producing the toxic constituents of smoke. The widespread adoption of NVPs by smokers in markets worldwide demonstrates their appeal.

The unique potential of NVPs in managing smoking as a chronic disorder

NVPs have two principal advantages compared with other smoking cessation pharmacotherapies, to the extent that they:

• Replicate the nicotine pharmacokinetics of a cigarette; and
• Deliver a behavioural and sensory experience that is analogous, but not identical to smoking.

Accordingly, NVPs promote treatment adherence and create behavioural distance from patients’ smoking behaviours. NVPs become the new ‘default’ for patients’ nicotine consumption.

Clinicians may use NVPs to replace cigarettes in the cessation/ relapse cycle for appropriately selected patients.

The availability of an effective substitute means that if patients relapse while attempting abstinence they can restart the treatment rather than continue smoking. In this way, patients avoid the harms of continued smoking until their next attempt at abstinence.

Understanding nicotine concentration and dose Delivery from NVPs

Nicotine concentration is frequently used incorrectly as shorthand for “dose”. It is important that pharmacists understand how nicotine concentration interacts with other factors to determine the delivered dose.

Multiple factors determine the amount of nicotine an NVP delivers systemically:

• Device power: The mass of liquid that the device turns into aerosol per given puff
• Nicotine concentration: The amount of nicotine in the mass of aerosol per given puff
• User characteristics: How often the patient puffs, how long they puff for, how deep they inhale

Product design and characterisation

NVP manufacturers should complete a comprehensive evaluation of their NVP’s aerosol for harmful and potentially harmful compounds (HPHCs).

The Nicovape® Q device, cartridges and liquid composition are designed to minimise exposure to HPHCs.

Nicovape® Q is a closed-system NVP designed to deliver nicotine with a similar nicotine pharmacokinetic profile to cigarettes. In particular, Nicovape® Q contains design features to:

• Ensure satisfying nicotine delivery while minimising exposure to other excipients in the aerosol; and
• Minimise aerosol yields of HPHCs that are present in cigarette smoke.

In contrast, open-system NVPs with low levels of nicotine can lead to increased toxicants in the aerosol due to:

• Higher power settings, increased volumes of liquid, and many potential liquid/device combinations; and
• Compensatory (additional) puffing due to lower nicotine levels.

Initiating NVP treatment in new users

NVPs have emerged as a user-innovated technology, and further innovations over the last half-decade mean that ‘new generation’ NVPs are capable of closely reproducing cigarettes’ pharmacological and behavioural properties.

NVPs do this without producing the toxic constituents of smoke. The widespread adoption of NVPs by smokers in markets worldwide demonstrates their appeal.

The priority for new patients is to ensure the NVPs they use deliver sufficient nicotine to prevent them from craving cigarettes. Daily use is associated with the effectiveness of NVPs. Patients should be encouraged to replace all instances of smoking with NVP use as rapidly as possible.

Clinicians will typically prescribe the NVP’s highest nicotine concentration to ensure an optimal nicotine profile, adjusting the number of cartridges prescribed during follow-up consultations.

After a short duration of initial NVP use, patients will self-regulate their nicotine intake from NVPs in the same way that smokers self-regulate their nicotine from cigarettes.

Liber has found that patients typically reduce their consumption once they have gained some experience using Nicovape® Q.

Prescribers may use a lower nicotine concentration if a patient cannot tolerate the higher concentration or, later in treatment, to assist patients in down-titrating towards abstinence.

Prescribing patients with a nicotine concentration that is too low may result in the following outcomes:

• Treatment may fail because the patient cannot achieve the required nicotine blood levels in sufficient time; or
• Patients may use compensatory puffing, inhaling more non-active ingredients than required. In some NVPs, compensatory puffing can increase the exposure to toxic emissions from overheating.

The path to nicotine abstinence

The RACGP considers 12 months to be a reasonable duration of NVP use. However, doctors may prescribe beyond this point if they judge the patient to be highly dependent and at risk of relapse.

NVPs for smoking cessation under medical supervision is a developing field, with several areas still to be investigated. In particular:

• How best to down-titrate towards nicotine abstinence; and
• The effect on outcomes of using progressively lower nicotine concentrations.

Nicotine abstinence will always require patient motivation. It is currently unknown if NVPs increase patient motivation for abstinence or make it easier to achieve when attempted.
In attempting nicotine abstinence, clinicians may employ various approaches, such as:

• Down-titrating by limiting the number of cartridges the patient uses;
• Using a lower-concentration cartridge;
• Combination therapy with NRT or other available treatment; or
• Abrupt withdrawal (for highly motivated patients).

Relapse prevention

In practice, it may not be possible to determine whether a patient is likely to achieve enduring abstinence for any given quit attempt.

A relapse to smoking would represent a failure of treatment. In contrast, a relapse to therapeutic NVPs would (i) continue to achieve the primary aim of smoking cessation, meeting the most critical clinical outcome, and (ii) allow treatment to continue with the patient remaining under medical oversight.

Types of NVPs available under the framework

NVPs comprise a wide array of different products. The regulations permit only two categories to be prescribed and dispensed.

Closed system (New Generation)

Device and single-use cartridges containing e-liquid.

• Mitigates avoidable risks
• Allows uniform dosage
• Appropriate for pharmacy
• Recommended by RAGCP

Open System

Refillable devices where users add refill liquids.

• Old technology, unlikely to qualify for ARTG registration
• High risk of contamination or potentially toxic or illegal substances consumed
• Thousands of devices and E-liquids of differing qualities
• Not recommended by RAGCP, except for experienced vapers

Disposable

Non-rechargeable, single-use devices, discarded after use.

• Typically low quality and often counterfeit
• Responsible for widespread youth access
• Environmentally unsustainable battery and plastic waste
• Prohibited

New Generation closed-system NVPs have largely replaced the older open-system technology. Nevertheless, open-system NVPs are still used by some patients. The RACGP suggests that doctors prescribe open-system NVPs only to these patients if they need them, but that they encourage these patients to adopt a closed-system NVP, where possible.

Pharmacists should note that in the longer term, closed-system NVPs may be the only type available for dispensing. This is because only closed-system NVPs can be sufficiently characterised for listing on the ARTG.

Potential blockers to treatment success

While it is not possible to address all potential scenarios that pharmacists may encounter when dispensing NVPs, the practical considerations highlighted in this module are intended to provide guidance addressing most scenarios anticipated, including the following:

1. Insufficient NVP usage in early treatment

Underdosing or inadequate use of prescribed NVPs leaves patients with unmet nicotine cravings, increasing the risk of relapse.

Smokers who have previously failed to quit smoking typically relapse with current therapeutic methods.

2. Misinformation about vaping vs smoking risks:

• Many smokers, especially in disadvantaged groups, have inaccurate perceptions of NVP risks compared to smoking;
• Despite findings of toxic compounds in NVP aerosols, the scientific consensus is that NVP exposure is minimal compared to cigarettes; and
• Smoking for just days or weeks would exceed the toxic exposure from a lifetime of NVP use.