Niquitin Strips Mint 2.5mg Oral Film
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
NiQuitin Strips Mint 2.5 mg Oral Film
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each orodispersible film contains 2.5 mg nicotine Contains ethanol, no more than 3.9 mg per film For full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Orodispersible Film
Transparent film approximately 20 mm by 30 mm
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
NiQuitin Strips relieve and/or prevent craving and nicotine withdrawal symptoms associated with tobacco dependence. They are 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.
NiQuitin Strips are indicated in pregnant and lactating women making a quit attempt.
NiQuitin Strips should preferably be used in conjunction with a behavioural support programme.
4.2 Posology and method of administration
Directions for use:
NiQuitin Strips are suitable for smokers who have their first cigarette of the day more than 30 minutes after waking up.
Place one film on the tongue. Close the mouth and press the tongue gently to the roof of the mouth until the nicotine film dissolves (approximately 3 minutes). The film should not be chewed or swallowed whole.
Users should not eat or drink while a nicotine film is in the mouth.
Behavioural therapy, advice and support will normally improve the success rate.
Adults (18 years and over):
Abrupt cessation of smoking:
Users should make every effort to stop smoking completely during treatment with NiQuitin Strips.
Recommended treatment schedule:
|
Step 1 Weeks 1 to 6 |
Step 2 Weeks 7 to 9 |
Step 3 Weeks 10 to 12 |
|
Initial treatment period |
Step down treatment period |
Step down treatment period |
|
1 nicotine film every 1 to 2 hours |
1 nicotine film every 2 to 4 hours |
1 nicotine film every 4 to 8 hours |
During weeks 1 to 6 it is recommended that users take a minimum of 9 films per day. Users should not exceed 15 films per day.
To help stay smoke free beyond 12 weeks, users may take 1-2 NiQuitin Strips per day only on occasions when they are strongly tempted to smoke.
Those who have quit smoking but are having difficulty discontinuing using NiQuitin Strips are recommended to seek additional help and advice from a healthcare professional.
Gradual cessation of smoking:
For smokers who are unwilling or unable to quit abruptly.
Use a NiQuitin Strips whenever there is a strong urge to smoke in order to reduce the number of cigarettes smoked as far as possible and to refrain from smoking as long as possible.
The number of films a day is variable and depends on the patient’s needs. Nonetheless it should not exceed 15 films per day.
If a reduction in cigarette consumption has not been achieved after 6 weeks of treatment, a healthcare professional should be consulted.
Reduced tobacco consumption should lead to complete cessation of smoking. This should be attempted as soon as possible. When the number of cigarettes has been reduced to a level from which the user feels able to quit completely, then start on the schedule for “abrupt cessation” as given above.
If an attempt to stop smoking completely has not been started within 6 months after the beginning of treatment, it is recommended to consult a healthcare professional.
Reduction in smoking:
For smokers who wish to cut down with no immediate plans to quit.
Use a NiQuitin Strips whenever there is a strong urge to smoke in order to reduce the number of cigarettes smoked as far as possible and to refrain from smoking as long as possible. Users should be encouraged to stop smoking completely as soon as possible.
The number of films a day is variable and depends on the patient’s needs. Nonetheless it should not exceed 15 films per day.
If users are still feeling the need to use NiQuitin Strips on a regular basis 6 months after the start of treatment and have still been unable to undertake a permanent quit attempt, then it is recommended to seek additional help and advice from a healthcare professional.
Temporary Abstinence:
Use a NiQuitin Strips every 1-2 hours to control troublesome withdrawal symptoms including craving. Users should not take more than 15 films per day. Users should be encouraged to stop smoking completely as soon as possible. If users are still feeling the need to use NiQuitin Strips on a regular basis 6 months after the start of treatment and have still been unable to undertake a permanent quit attempt, then it is recommended to seek additional help and advice from a healthcare professional.
Adolescents and children:
Adolescents (12-17 years) should follow the schedule of treatment for abrupt cessation of smoking as given above. Where adolescents are unwilling or unable to quit smoking abruptly, advice from a healthcare professional should be sought.
Safety and effectiveness in children who smoke has not been evaluated. NiQuitin Strips are not recommended for use in children under 12 years of age.
4.3 Contraindications
• people with hypersensitivity to nicotine or any of the excipients
• children under the age of 12 years
• non-smokers
4.4 Special warnings and precautions for use
The risks associated with the use of NRT are substantially outweighed in virtually all circumstances by the well established dangers of continued smoking.
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 nonpharmacological interventions (such as counselling). If this fails, NiQuitin Strips 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 film dose should be reduced or discontinued.
Diabetes: Blood glucose levels may be more variable when stopping smoking, with or without NRT as catecholamines released by nicotine can affect carbohydrate metabolism, so it important for diabetics to monitor their blood glucose levels more closely than usual while using this product.
Allergic reactions: Susceptibility to angioedema or urticaria.
A risk-benefit assessment should be made by an appropriate healthcare professional for patients with the following conditions:
• Renal and hepatic impairment: Use 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: Use with caution in patients with uncontrolled hyperthyroidism or phaeochromocytoma as nicotine causes release of catecholamines.
• Gastrointestinal Disease: Swallowing of nicotine may exacerbate symptoms in persons suffering from active oesophagitis, oral or pharyngeal inflammation, gastritis, gastric ulcer or peptic ulcer and oral NRT preparations should be used with caution in these conditions. Ulcerative stomatitis has been reported.
• Seizures: Potential risks and benefits of nicotine should be carefully evaluated before use in subjects taking anti-convulsant therapy or with a history of epilepsy as cases of convulsions have been reported in association with nicotine.
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.
Stopping smoking: Polycyclic aromatic hydrocarbons in tobacco smoke induce the metabolism of drugs catalysed by CYP 1A2 (and possibly by CYP 1A1). When a smoker stops this may result in a slower metabolism and a consequent rise in blood levels of such drugs.
Transferred dependence: Transferred dependence is rare and is both less harmful and easier to break than smoking dependence.
Ethanol (alcohol): This medicinal product contains small amounts of ethanol (alcohol), less than 100 mg per nicotine film.
4.5. Interactions with other medicinal products and other forms of interaction
Adults and paediatric (12-17 years inclusive) population
No clinically relevant interactions between nicotine replacement therapy and other medicinal products have definitely been established, however nicotine may possibly enhance the haemodynamic effects of adenosine.
Smoking cessation itself may require the adjustment of some drug therapy.
Pregnancy and lactation
4.6
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.
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 NRT 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 minimize 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
There are no known effects of NiQuitin Strips on the ability to drive and use machines. However, users of nicotine replacement products should be aware that smoking cessation can cause behavioural changes
4.8 Undesirable effects Adults
NiQuitin Strips can cause adverse reactions similar to those associated with nicotine from tobacco. Many of the observed adverse reactions are consistent with the pharmacological effects of nicotine, which are dose dependent.
The following undesirable effects detailed in Table 1 and Table 2 are nicotine lozenge and gum adverse reactions which are considered relevant for the NiQuitin Strips formulation based upon 2 small clinical studies involving nicotine films.
Table 1
|
Psychiatric Disorders | |
|
Common >1/100 to <1/10 |
insomnia* |
|
Nervous system disorders | |
|
Common >1/100 to <1/10 |
headache*, dizziness* |
|
Respiratory, Thoracic and Mediastinal Disorders | |
|
Common >1/100 to <1/10 |
pharyngitis, cough*, pharyngolaryngeal pain |
|
Gastrointestinal Disorders | |
|
Very common >1/10 |
nausea |
|
Common >1/100 to<1/10 |
vomiting, dyspepsia, abdominal pain upper, diarrhoea, dry mouth, constipation, hiccups, stomatitis, flatulence, oral discomfort |
• May also be due to withdrawal symptoms following smoking cessation
Post Marketing Data
Table 2 shows adverse reactions which were identified from post-marketing experience of oral gum and lozenge nicotine products. This is considered relevant for NiQuitin Strips (which is bioequivalent to these formulations) based on 2 small clinical studies with the film formulation.
Table 2
|
Immune System Disorders | |
|
Frequency: Unknown |
hypersensitivity, angioedema, urticaria, ulcerative stomatitis, and very rare anaphylactic reactions |
|
Psychiatric Disorders | |
|
Frequency: Unknown |
nervousness* |
|
Nervous System Disorders | |
|
Frequency: Unknown |
tremor |
|
Frequency: Not Known |
seizures |
|
Cardiac Disorders | |
|
Frequency: Unknown |
palpitations, tachycardia |
|
Respiratory, Thoracic and Mediastinal Disorders | |
|
Frequency: Unknown |
dyspnoea |
|
Gastrointestinal Disorders | |
|
Frequency: Unknown |
dysphagia, eructation, salivary hypersecretion |
|
General Disorders and Administration Site Conditions | |
|
Frequency: Unknown |
asthenia*, fatigue*, malaise*, influenza type illness* |
• May also be due to withdrawal symptoms following smoking cessation
Paediatric population (12 - 17years inclusive)
There are no specific adverse event data for this population. However, the frequency, type and severity of adverse reactions in adolescents are expected to be the same as adults, based upon a pharmacokinetic study demonstrating a similar pharmacokinetic profile in the adolescent age group compared to adults.
4.9 Overdose
The minimum lethal dose of nicotine in a non tolerant man has been estimated to be 40 to 60 mg. Even small quantities of nicotine may be dangerous in children and may prove fatal. Suspected nicotine poisoning in a child should be considered a medical emergency and treated immediately.
Symptoms
Signs and symptoms of an overdose from nicotine films would be expected to be the same as those of acute nicotine poisoning, including pallor, cold sweat, salivation, nausea, vomiting, abdominal pain, diarrhoea, headache, dizziness, disturbed hearing and vision, tremor, mental confusion and weakness. Prostration, hypotension, respiratory failure, rapid or weak or irregular pulse, circulatory collapse and convulsions (including terminal convulsions) may ensue with large overdoses.
Management
In the event of an overdose (e.g. too many films ingested) the user should seek medical attention immediately. All nicotine intake should cease immediately and the patient be treated symptomatically. Artificial respiration with oxygen should be instituted if necessary. Activated charcoal reduces the gastrointestinal absorption of nicotine.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drugs used in nicotine dependence
ATC Code: N07BA01
Nicotine is an agonist at nicotine receptors in the peripheral and central nervous system and has pronounced CNS and cardiovascular effects. When consumed in tobacco products, it has been shown to be addictive and abstinence is linked to craving and withdrawal symptoms. These craving and withdrawal symptoms include urge to smoke, depressed mood, insomnia, irritability, frustration or anger, anxiety, difficulty in concentrating, restlessness and increased appetite or weight gain. Cravings and other symptoms of nicotine withdrawal are at their most intense during the first few weeks of a quit attempt, diminishing thereafter. The nicotine films replace some of the nicotine provided by tobacco. Clinical studies for the bioequivalent 2 mg lozenge have shown a reduction in intensity of cravings.
5.2 Pharmacokinetic properties
Nicotine films completely dissolve in the oral cavity, and the entire amount of nicotine contained in the nicotine film becomes available for buccal absorption or ingestion (swallowing). The complete dissolution of a nicotine film is typically achieved in approximately 3 minutes. The peak plasma concentrations of nicotine achieved after a single dose are approximately 4.13 ng/ml.
As the plasma protein binding of nicotine is low (4.9% - 20%), the volume of distribution of nicotine is large (2.5 l/kg). The distribution of nicotine to tissue is pH dependent, with the highest concentrations of nicotine found in the brain, stomach, kidney and liver.
Nicotine is extensively metabolised to a number of metabolites, all of which are less active than the parent compound. The metabolism of nicotine primarily occurs in the liver, but also in the lung and kidney. Nicotine is metabolised primarily to cotinine but is also metabolised to nicotine N'-oxide. Cotinine has a half-life of 15-20 hours and its blood levels are 10 times higher than nicotine. Cotinine is further oxidised to trans^'-hydroxycotinine, which is the most abundant metabolite of nicotine in the urine. Both nicotine and cotinine undergo glucuronidation.
The elimination half-life of nicotine is approximately 2 hours (range 1 - 4 hours). Total clearance for nicotine ranges from approximately 62 to 89 l/hr. Non-renal clearance for nicotine is estimated to be about 75% of total clearance. Nicotine and its metabolites are excreted almost exclusively in the urine. The renal excretion of unchanged nicotine is highly dependent on urinary pH, with greater excretion occurring at acidic pH.
5.3 Preclinical safety data
The general toxicity of nicotine is well known and taken into account in the recommended posology. Nicotine was not mutagenic in appropriate assays. The results of carcinogenicity assays did not provide any clear evidence of a tumorigenic effect of nicotine. In studies in pregnant animals, nicotine showed maternal toxicity, and mild foetal toxicity. Additional effects included pre- and postnatal growth retardation and delays and changes in postnatal CNS development.
Effects were only noted following exposure to nicotine at levels in excess of those which will result from recommended use of nicotine films. Effects on fertility have not been established.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Methacrylic Acid - Ethyl Acrylate Copolymer (1:1), Type A
Triethyl Citrate (E1505)
Peppermint Flavour TAK - 032230 Sucralose (E955)
Sodium Hydrogen Carbonate (E500 ii) Ethanol
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Do not store above 30 oC. Store in the original package to protect from light and moisture.
6.5 Nature and contents of container
Each NiQuitin Strips Film is contained in a polyethyleneterephthalate (PET)/aluminium/polyacrylnitrile (PAN) laminate sachet.
Each pack contains 10, 15, 30 or 60 sachets. Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Beecham Group plc 980 Great West Road Brentford Middlesex TW8 9GS
United Kingdom
T/A GlaxoSmithKline Consumer Healthcare Brentford TW8 9GS, UK.
8 MARKETING AUTHORISATION NUMBER(S)
PL 00079/0662
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 14/09/2011
10 DATE OF REVISION OF THE TEXT
31/03/2014