4.1. Therapeutic indications

Relief of nicotine withdrawal symptoms, in nicotine dependency as an aid to smoking cessation.

The 2 mg strength is used when severe withdrawal symptoms are experienced.

Patient counselling and support normally improve the success rate.

4.2. Posology and method of administration

Posology

Adults over 18 years and the elderly

Users should stop smoking completely during treatment with Boots NicAssist lozenge.

Boots NicAssist 2 mg lozenge is intended to be used by smokers with a strong or very strong nicotine dependency and those who have previously failed to stop smoking with the aid of nicotine replacement therapy.

The optimal dosage form is selected according to the following table:

If an adverse event occurs with the use of the high dose form (2 mg lozenge), use of the low dose form (1 mg lozenge) should be considered.The initial dosage should be individualised on the basis of the patients nicotine dependence. One piece of lozenge to suck when the user feels the urge to smoke.

Initially, 1 lozenge should be taken every 1-2 hours. Do not use more than 1 lozenge per hour. The usual dosage is 8-12 lozenges per day. The maximum daily dose is 15 lozenges.

The treatment duration is individual. Normally, treatment should continue for at least 3 months. After 3 months, the user should gradually reduce the number of lozenges or alternatively the user should switch to nicotine 1 mg lozenges and then gradually reduce the number of lozenges per day.

Treatment should be discontinued when the dose has been reduced to 1-2 lozenges per day. Use of nicotine medicinal products like Boots NicAssist 2 mg lozenge beyond 6 months is generally not recommended. Some ex-smokers may need treatment with the lozenge longer to avoid returning to smoking.

Patients who have been using oral nicotine replacement therapy beyond 9 months are advised to seek additional help and information from health care professionals.

Counselling may help smokers to quit.

Children and Adolescents (aged 12-17 years)

Boots NicAssist lozenge should not be used by people under 18 years of age without recommendation from a physician. There is no experience in treating adolescents under the age of 18 with Boots NicAssist lozenge. The use of NRT in adolescents should only be used when the benefits of abstinence outweigh the risks of continued smoking. Adolescents (12-17 years) should follow the schedule of treatment for abrupt cessation of smoking as given above. Boots NicAssist lozenge should preferably be used in conjunction with a behavioural support programme as this normally improves the success rate.

Children below 12 years of age

Boots NicAssist lozenges are not recommended for use in children under 12 years.

Method of administration:

1. One lozenge to be sucked until the taste becomes strong.

2. The lozenge should then be lodged between the gum and cheek.

3. When the taste fades, sucking of the lozenge should commence again.

4. The sucking routine will be adapted individually and should be repeated until the lozenge dissolves completely (about 30 minutes).

Concomitant use of acidic beverages such as coffee or soda may decrease the buccal absorption of nicotine. Acidic beverages should be avoided for 15 minutes prior to sucking the lozenge.

4.3. Contraindications

Hypersensitivity to nicotine or to any of the excipients (listed section 6.1).

Boots NicAssist lozenge should not be used by non-smokers.

4.4. Special warnings and precautions for use

Cardiovascular disease

Dependent smokers with a recent myocardial infarction, unstable or worsening angina including Prinzmetal's angina, severe cardiac arrhythmias, uncontrolled hypertensions or recent cerebrovascular accident should be encouraged to stop smoking with non-pharmacological interventions (such as counselling). If this fails, Boots NicAssist lozenges may be considered but as data on safety in this patient group are limited, initiation should only be under close medical supervision. If there is a clinically significant increase in cardiovascular or other effects attributable to nicotine, the nicotine lozenge dose should be reduced or discontinued.

Diabetes mellitus:

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

Seizures:

Use with caution in subjects taking anti-convulsant therapy or with a history of epilepsy as cases of convulsions have been reported in association with nicotine.

Boots NicAssist lozenges should be used with caution in patients with hypertension, stable angina pectoris, cerebrovascular disease, occlusive peripheral arterial disease, heart failure, diabetes mellitus, hyperthyroidism or pheochromocytoma and severe hepatic and/or renal impairment.

Patients should initially be encouraged to stop smoking with non-pharmacological interventions (such as counselling).

Swallowed nicotine may exacerbate symptoms in subjects suffering from active oesophagitis, oral and pharyngeal inflammation, gastritis, gastric ulcer or peptic ulcer.

Doses of nicotine that are tolerated by adult smokers during treatment may produce severe symptoms of poisoning in small children and may prove fatal (please see Section 4.9). Keep out of the sight and reach of children.

Special warnings about excipients

Boots NicAssist lozenges contain sweeteners, including aspartame and maltitol.

Each Boots NicAssist 2 mg lozenge contains aspartame (E951), a source of phenylalanine equivalent to 5 mg/dose and may be harmful for people with phenylketonuria.

Because Boots NicAssist 2 mg lozenge contains maltitol (E965), a source of fructose:

- patients with rare hereditary conditions of fructose intolerance should not take this medicine,

- patients may experience a mild laxative effect.

Calorific value 2.3 kcal/g maltitol.

Boots NicAssist 2 mg lozenge contains less than 1 mmol sodium (23 mg) per lozenge, that is to say essentially `sodium-free'.

4.5. Interaction with other medicinal products and other forms of interaction

Drug Interactions: No information is available on interactions between Boots NicAssist lozenge and other medicinal products.

Smoking Cessation: Smoking but not nicotine is associated with increased CYP1A2 activity. After stopping smoking there may be reduced clearance of substrates for this enzyme and increased plasma levels of some medicinal products of potential clinical importance because of their narrow therapeutic window e.g. theophylline, tacrine, olanzapine and clozapine. Smoking cessation itself may require adjustment of some drug therapy.

The plasma concentrations of other active substances metabolised by CYP1A2 e.g. caffeine, paracetamol, phenazone, phenylbutazone, pentazocine, lidocaine, benzodiazepines, warfarin, oestrogen and vitamin B12 may also increase. However the clinical significance of this effect for these active substances is unknown.

Smoking may lead to reduced analgesic effects of propoxyphene, reduced diuretic response to furosemide (frusemide), reduced effect of propranolol on blood pressure and heart rate and reduced responder rates in ulcer healing with H2-antagonists.

Smoking and nicotine may raise the blood levels of cortisol and catecholamines, i.e. may lead to a reduced effect of nifedipine or adrenergic antagonists and to an increased effect of adrenergic agonists.

Increased subcutaneous absorption of insulin which occurs upon smoking cessation may necessitate a reduction in insulin dose.

4.6. Fertility, pregnancy and lactation

Pregnancy

Adverse reproductive and developmental effects have been reported following exposure to tobacco and nicotine during pregnancy. In pregnant women, complete cessation of tobacco smoking should always be recommended without nicotine replacement therapy.

Nevertheless, in the case of failure in highly dependent pregnant smokers, tobacco withdrawal via nicotine replacement therapy may be recommended. Indeed, foetal risk is probably lower than that expected with tobacco smoking, due to:

- lower maximal plasma nicotine concentration than with inhaled nicotine

- no additional exposure to polycyclic hydrocarbons and carbon monoxide

- improved chances of quitting smoking by the third trimester.

Smoking during pregnancy may lead to intra-uterine growth retardation or even premature birth or stillbirth, depending on the daily amount of tobacco.

Tobacco withdrawal with or without nicotine replacement therapy should not be undertaken alone but as part of a medically supervised smoking cessation program.

However, oral forms of nicotine replacement therapy should only be used if the expected benefits to the mother outweigh the potential risks to the foetus.

Breast-feeding

Nicotine is excreted in breast milk in quantities that may affect the child even in therapeutic doses. The lozenge, like smoking itself, should therefore be avoided during breast-feeding. Should smoking withdrawal not be achieved, use of the lozenge by breast feeding smokers should only be initiated after advice from a physician. Oral forms of nicotine replacement therapy should only be used if the expected benefits to the nursing mother outweigh the potential risks to the infant. Where nicotine replacement therapy is used whilst breast-feeding, the lozenge should be taken just after breast-feeding and not during the two hours before breast-feeding.

Fertility

Smoking increases the risk for infertility in women and men. Both in humans and in animals, it has been shown that nicotine can adversely affect sperm quality. In animals, reduced fertility has been shown.

4.7. Effects on ability to drive and use machines

There is no evidence of any risks associated with driving or operating machinery when the lozenge is used following the recommended dose. Nevertheless one should take into consideration that smoking cessation can cause behavioural changes.

4.8. Undesirable effects

Boots NicAssist lozenge can cause adverse reactions similar to those associated with nicotine administered by smoking. These can be attributed to the pharmacological effects of nicotine, which are dose-dependent. Non dose-dependent adverse reactions are as follows: hypersensitivity, angioneurotic oedema and anaphylactic reactions.

Most of the adverse reactions which are reported by patients occur generally during the first 3-4 weeks after initiation of therapy.

Nicotine from lozenges may sometimes cause a slight irritation of the throat and increased salivation at the start of the treatment. Excessive swallowing of nicotine which is released in the saliva may, at first, cause hiccups. Those who are prone to indigestion may suffer initially from minor degrees of dyspepsia or heartburn; slower sucking will usually overcome this problem.

Excessive consumption of lozenges by subjects who have not been in the habit of inhaling tobacco smoke, could possibly lead to nausea, faintness and headache.

Increased frequency of aphthous ulcer may occur after abstinence from smoking.

The following undesirable effects detailed in Table 1 are nicotine related adverse events for all oral dosage forms. Table 1 shows events which were identified from a double-blind, randomised, placebo-controlled lozenge clinical study involving 1818 patients. Adverse events reported in this study have been considered for inclusion, where the incidence in the 2 mg or 4 mg nicotine arm was higher than the corresponding placebo arm. Frequencies are calculated from safety data of the study.

Table 1: Adverse Reaction from clinical trial data

Adverse reactions are listed below, by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000, <1/1,000) or very rare (<1/10,000).

System Organ Class

Adverse Reaction

Frequency

Psychiatric Disorders

insomnia*

Common

Nervous system disorders

Dizziness*, headache*

Common

Seizures

Not Known

Respiratory, Thoracic and Mediastinal Disorders

pharyngitis, cough*, pharyngolaryngeal pain

Common

Gastrointestinal disorders

nausea, vomiting, dyspepsia, abdominal pain upper, diarrhoea, constipation, oral discomfort, flatulence, hiccups, gastritis, dry mouth, stomatitis and oesophagitis

Common

Cardiac disorders

palpitations

Uncommon

atrial arrhythmia

Rare

Immune system disorders

hypersensitivity, angioneurotic oedema and anaphylactic reactions

Rare

* These events may also be due to withdrawal symptoms following smoking cessation.

Post Marketing Data

Table 2 shows events which were identified from post-marketing experience of nicotine oral forms. As these reactions are reported voluntarily from a population of uncertain size, the frequency of these reactions is unknown.

Table 2: Adverse Reactions from post-marketing data

System Organ Class

Adverse Reaction

Immune system disorders

Hypersensitivity, angioedema, urticaria, ulcerative stomatitis, angioneurotic oedema and very rare anaphylactic reactions.

Nervous system disorders

Tremor

Cardiac disorders

Palpitations, tachycardia, arrhythmias, atrial fibrillation.

Respiratory, Thoracic and Mediastinal Disorders

Dyspnoea

Gastrointestinal Disorders

Dysphagia, eructation, salivary hypersecretion.

General Disorders and Administration Site Conditions

Asthenia**, fatigue**, malaise**, influenza type illness**

** These events may also be due to withdrawal symptoms following smoking cessation.

Cold sores may develop in connection with smoking cessation, but any relation with the nicotine treatment is unclear.

The patient may still experience nicotine dependence after smoking cessation.

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Overdosage

In overdose, symptoms corresponding to heavy smoking may be seen.

Even small quantities of nicotine are dangerous in children, and may result in severe symptoms of poisoning which may prove fatal. If poisoning is suspected in a child, a doctor must be consulted immediately.

Symptoms and Signs

Overdose with Boots NicAssist 2 mg lozenge may only occur if many pieces are sucked simultaneously. Nicotine toxicity after ingestion will most likely be minimised as a result of early nausea and vomiting that occur following excessive nicotine exposure.

General symptoms of nicotine poisoning include: pallor, hyperhidrosis, dizziness, tremor, confusion, asthenia, weakness, perspiration, salivation, throat burn, nausea, vomiting, diarrhoea, abdominal pain, hearing and visual disturbances, headache, tachycardia and cardiac arrhythmia, dyspnoea, coma and terminal convulsions.

Prostration, hypotension, circulatory collapse, respiratory failure and convulsions may ensue with large overdoses.

Treatment of overdose

Treatment of overdose should be immediate as symptoms may develop rapidly. Emesis is usually spontaneous. All nicotine intake should cease immediately and the patient be treated symptomatically, monitor vital signs and treat symptomatically.

Further management should be as clinically indicated or as recommended by the national poisons centre, where available.