SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

e-Voke 10 mg Electronic Inhaler

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each inhalation cartridge contains 10 mg nicotine.

Every 10 inhalations (each comprising 50 ml) contain approximately 0.38 mg of nicotine.

The actual delivered dose is not metered and is dependent on the inhalation topography of the patient.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Inhalation vapour, liquid.

A light brown plastic mouthpiece debossed with ‘N10’ containing a foil sealed colourless cartridge containing a clear colourless to faint yellow coloured solution held within a foam matrix.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

e-Voke relieves and/or prevents craving and nicotine withdrawal symptoms associated with tobacco dependence. It is indicated to aid smokers wishing to quit or reduce prior to quitting, to assist smokers who are unwilling or unable to smoke, and as a safer alternative to smoking for smokers and those around them.

e-Voke is indicated in pregnant and lactating women making a quit attempt.

4.2 Posology and method of administration

Posology

The medicinal product is intended for inhalation use only. The cartridge can only be inserted and used in the e-Voke Electronic Inhaler.

e-Voke should be used whenever the urge to smoke is felt or to prevent cravings in situations where these are likely to occur.

Smokers willing or able to stop smoking immediately should initially replace all their cigarettes with e-Voke and as soon as they are able, reduce the number of e-Voke inhalation cartridges used until they have stopped completely.

Smokers aiming to reduce cigarette dependence should use e-Voke, as needed, between smoking episodes to prolong smoke-free intervals and with the intention to reduce smoking as much as possible.

As soon as they are ready smokers should aim to quit smoking completely.

Maximum daily dose: 5 e-Voke inhalation cartridges.

When making a quit attempt behavioural therapy, advice and support will normally improve the success rate. Those who have quit smoking, but are having difficulty discontinuing e-Voke are recommended to contact their pharmacist or doctor for advice.

Each inhalation cartridge can be used for approximately of 13 uses, each use comprising 10 inhalations. The actual number will depend on the depth and duration of inhalations.

The more the subject is able to use e-Voke, the easier it will be to achieve maximum reduction of cigarettes and/or quit smoking completely.

Paediatric population

e-Voke is contraindicated in children under the age of 18 years.

Method of administration

e-Voke inhalation cartridges are exclusively for use with the e-Voke Electronic Inhaler. Details of how to assemble and use e-Voke are provided in the instructions for use in the patient information leaflet.

The cartridge is inserted onto the e-Voke Electronic Inhaler according to the instructions. The patient should inhale on the mouthpiece of the e-Voke inhalation cartridge which is attached to the e-Voke Electronic Inhaler for up to 3 seconds per inhalation.

When a patient draws air into the mouth through the mouthpiece, nicotine is vaporised and inhaled. The exhaled vapour forms a plume. The amount of nicotine from a puff is less than that from a cigarette. To compensate it might be necessary to inhale more frequently or deeper than when smoking a cigarette.

The actual time that the cartridge is active depends on the intensity of use. It is important that the patient does not continue to use the cartridge once the plume concentration starts to decrease, as the cartridge is becoming exhausted: There is a decrease in nicotine delivery and the potential for an increase in the formation of thermal degradants.

4.3 Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

e-Voke is contraindicated in children under the age of 18 years.

4.4 Special warnings and precautions for use

Any risks that may be associated with NRT are substantially outweighed by the well established dangers of continued smoking.

Underlying cardiovascular disease: In stable cardiovascular disease e-Voke presents a lesser hazard than continuing to smoke. However dependent smokers currently hospitalised as a result of myocardial infarction, severe dysrhythmia or CVA and who are considered to be haemodynamically unstable should be encouraged to stop smoking with non-pharmacological interventions. If this fails, e-Voke may be considered, but as data on safety in this patient group are limited, initiation should only be under medical supervision.

Diabetes mellitus: Patients with diabetes mellitus should be advised to monitor their blood sugar levels more closely than usual when NRT is initiated as catecholamines released by nicotine can affect carbohydrate metabolism.

GI disease: Swallowed nicotine may exacerbate symptoms in patients suffering from oesophagitis, gastritis or peptic ulcers and oral NRT preparations should be used with caution in these conditions. Ulcerative stomatitis has been reported.

Renal or hepatic impairment: e-Voke should be used with caution in patients with moderate to severe hepatic impairment and/or severe renal impairment as the clearance of nicotine or its metabolites may be decreased with the potential for increased adverse effects.

Phaeochromocytoma and uncontrolled hyperthyroidism: As nicotine causes release of catecholamines, e-Voke should be used with caution in patients with uncontrolled hyperthyroidism or phaeochromocytoma.

Transferred dependence: Transferred dependence is rare and is both less harmful and easier to break than smoking dependence.

Stopping smoking: Polycyclic aromatic hydrocarbons in tobacco smoke induce the metabolism of drugs metabolised by CYP 1A2 (and possibly by CYP 1A1). When a smoker stops smoking, this may result in slower metabolism and a consequent rise in blood levels of such drugs. This is of potential clinical importance for products with a narrow therapeutic window, e.g. theophylline, clozapine and ropinirole.

Lung Disease: Patients with obstructive lung disease may find use of e-Voke difficult. Nicotine Gum, Patch, Nasal Spray or Sublingual tablet may be preferred in such cases. e-Voke should be used with caution in patients with chronic throat disease and bronchospastic disease.

Allergic reactions: Susceptibility to angioedema and urticaria.

Paediatric population:

Danger in small children: Doses of nicotine tolerated by adult and adolescent smokers can produce severe toxicity in small children that may be fatal. Products containing nicotine should not be left where they may be misused, handled or ingested by children.

Potential choking hazard: The cartridges represent a significant choking hazard. Any unused cartridges should remain in the cartridge tray to minimise this risk.

4.5 Interaction with other medicinal products and other forms of interaction

No clinically relevant interactions between nicotine replacement therapy and other drugs have definitely been established. However nicotine may possibly enhance the haemodynamic effects of adenosine i.e. increase in blood pressure and heart rate and also increase pain response (angina-pectoris type chest pain) provoked by adenosine administration.

4.6 Fertility, Pregnancy and lactation

Pregnancy

Stopping smoking is the single most effective intervention for improving the health of both the pregnant smoker and her baby, and the earlier abstinence is achieved the better. Ideally smoking cessation during pregnancy should be achieved without NRT. However, if the mother cannot (or is considered unlikely to) quit without pharmacological support, NRT may be used as the risk to the foetus is lower than that expected with smoking tobacco. Stopping completely is by far the best option but if this is not achievable e-Voke may be used in pregnancy as a safer alternative to smoking. Because of the potential for nicotine-free periods, intermittent dose forms are preferable, but patches may be necessary if there is significant nausea and/or vomiting. If patches are used they should, if possible, be removed at night when the foetus would not normally be exposed to nicotine.

Lactation

The relatively small amounts of nicotine found in breast milk during NRT use are less hazardous to the infant than second-hand smoke. Intermittent dose forms would minimise the amount of nicotine in breast milk and permit feeding when levels were at their lowest.

4.7 Effects on ability to drive and use machines

This medicinal product has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Some symptoms may be related to nicotine withdrawal associated with stopping smoking. These can include; irritability/aggression, dysphoria/depressed mood, anxiety, restlessness, poor concentration, increased appetite/weight gain, urges to smoke (cravings), night-time awakenings/sleep disturbance and decreased heart rate.

Increased frequency of aphthous ulceration may occur after abstinence from smoking. The causality is unclear.

e-Voke may cause adverse reactions similar to those associated with nicotine given by other means, including smoking, and these are mainly dose-dependent. At recommended doses e-Voke has not been found to cause any serious adverse effects. Excessive use of e-Voke by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches.

Most of the undesirable effects reported by the patient occur during the first weeks after starting treatment. Reported adverse events associated with inhaled nicotine include:

Body System	Incidence*	Reported adverse event
Nervous system disorders:	Very common:	Headache
	Common:	Dizziness
Cardiac disorders:	Uncommon:	Palpitations
	Very rare:	Reversible atrial fibrillation
Respiratory, thoracic and mediastinal disorders:	Very common:	Coughing
Gastrointestinal disorders:	Common:	Gastrointestinal discomfort, hiccups, nausea, vomiting
General disorders and administration site disorders:	Very common:	Irritation in mouth and throat
	Common:	Nasal congestion

* Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1 000, <1/100); rare (>1/10 000, <1/1 000); very rare (<1/10 000), including isolated reports.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard).

4.9 Overdose

Symptoms: The minimum lethal dose of nicotine in a non-tolerant man has been estimated to be 40 to 60 mg. Symptoms of acute nicotine poisoning include nausea, salivation, abdominal pain, diarrhoea, sweating headache, dizziness, disturbed hearing and marked weakness. In extreme cases, these symptoms may be followed by hypotension, rapid or weak or irregular pulse, breathing difficulties, prostration, circulatory collapse and terminal convulsions.

Management of an overdose: All nicotine in-take should stop immediately and the patient should be treated symptomatically. Artificial respiration should be instituted if necessary. Activated charcoal reduces the gastro-intestinal absorption of nicotine.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic Group: Drugs used in nicotine dependence. ATC Code: N07B A01.

Use of e-Voke results in absorption of nicotine into the venous circulation. The amount taken up alleviates the craving symptoms caused by the absence of nicotine from smoking.

Increased appetite is a recognised symptom of nicotine withdrawal and postcessation weight gain is common. Clinical trials have demonstrated that Nicotine Replacement Therapy can help control weight following a quit attempt.

5.2 Pharmacokinetic properties

Nicotine given i.v. has a volume of the distribution of 2 or 3 l/kg with a half life of 1-2 hours. Average plasma clearance is about 1-2 l/min mainly in the liver. More than 20 metabolites are known, all less active than nicotine: cotinine, with a half life of 15-20 hours and concentrations ten times that of nicotine is the main one.

Plasma binding of nicotine below 5% means significant displacement of drugs or nicotine is unlikely. Nicotine is excreted in the urine principally as cotinine (15%), 3-hydroxycotinine (45%), nicotine (10%).

Absorption of nicotine from e-Voke is slower than from cigarette smoking, but the pharmacokinetic profile is qualitatively similar with an early sharp peak followed by rapid re-distribution/elimination. On repeated use, average peak plasma levels of around 6.2 ng/ml nicotine are obtained. Peak plasma levels occur within 8 minutes after the end of inhalation.

When e-Voke is used in accordance with the directions in section 4.2, this would result in delivery of approximately 38 micrograms of nicotine per inhalation from the 10 mg cartridge and 56 micrograms per inhalation for the 15 mg cartridge (averaged over 10 inhalations), compared with 60 to 100 micrograms per inhalation for cigarette smoking.

The delivery of nicotine from the device is unaffected by ambient temperature.

Because the pattern of use is decided by the patient up to a limit of 5 cartridges per day to relieve craving, therapeutic levels of nicotine are individual, dictated by the level of dependence.

5.3 Preclinical safety data

None stated.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Glycerol

Water for injections

6.2    Incompatibilities

Not applicable

6.3    Shelf life

e-Voke inhalation cartridges:

24 months.

In-use shelf life: Once inserted into the mouthpiece the cartridge should be disposed of within 24 hours.

It is recommended to remove the inhalation cartridge and dispose of it when eVoke is not used for more than 24 hours.

e-Voke Electronic Inhaler:

2 years

In-use shelf life: 6 weeks

Special precautions for storage

Store below 25°C.

Protect from light.

6.5 Nature and contents of container

e-Voke inhalation cartridge is a colourless polypropylene cartridge, containing a polyurethane foam matrix, which is sealed with an aluminium/polyethylene co-extrusion foil. This cartridge is contained within a light brown polypropylene mouthpiece, which is packed in polyethylene terephthalate/polyester/aluminium blisters.

e-Voke Electronic Inhaler comprises a stainless steel vaporiser and battery unit with a clear polypropylene protective cap which fits over the vaporiser and is removed before use. A USB charger is also provided to recharge the battery.

Each blister contains 5 cartridges.

Pack sizes:

One e-Voke Electronic Inhaler and 5 inhalation cartridges Replacement cartridge packs: 5, 10 or 20 inhalation cartridges.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Keep away from animals.

The e-Voke Electronic Inhaler should not be disposed of in household waste. It should be returned to the pharmacy or place of purchase for disposal.

7 MARKETING AUTHORISATION HOLDER

Nicovations Ltd Globe House 1 Water Street London WC2R 3LA United Kingdom

MARKETING AUTHORISATION NUMBER(S)

PL 42601/0003

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

16/11/2015

DATE OF REVISION OF THE TEXT

19/11/2015