- nicotine resinate
GSL: General Sales Licence
This information is intended for use by health professionals
Adults and Children over 12 years of ageThis product 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 the lozenge and as soon as they are able, reduce the number of lozenges used until they have stopped completely. Smokers aiming to reduce cigarettes should take the lozenge, 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.Most smokers require 8 to 12 lozenges per day, not to exceed 15 lozenges.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 with the lozenge are recommended to contact their pharmacist or doctor for advice.
Method of administrationOne lozenge should be placed in the mouth and allowed to dissolve. Periodically, the lozenge should be moved from one side of the mouth to the other, and repeated, until the lozenge is completely dissolved. You should not chew or swallow the lozenge.
FertilityIn females tobacco smoking delays time to conception, decreases in-vitro fertilization success rates, and significantly increases the risk of infertility. In males tobacco smoking reduces sperm production, increases oxidative stress, and DNA damage. Spermatozoa from smokers have reduced fertilizing capacity.The specific contribution of nicotine to these effects in humans is unknown.
PregnancyStopping 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 this product 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.
LactationThe 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.
Effects of Smoking CessationSome symptoms may be related to nicotine withdrawal associated with stopping smoking. These can include: irritability/aggression, frustration/anger, 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 ulcer may occur after stopping smoking. The causality is unclear.
Adverse Drug ReactionsThis product 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 this product has not been found to cause any serious adverse effects. Excessive consumption of this product 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 3-4 weeks after start of treatment. During the first few days of treatment irritation in the mouth and throat may be experienced. Most patients will get used to this sensation after the first few days. The adverse reactions observed in patients treated with oral nicotine formulations during clinical trials and post-marketing experience are listed below by system organ class (SOC). Fequencies are defined in accordance with current guidance as: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); not known (cannot be estimated from the available data).
|Body System||Incidence||Reported adverse event (Preferred Term)|
|Immune system disorders||Common||Hypersensitivity a|
|Not known||Anaphylactic reaction a|
|Psychiatric disorders||Uncommon||Abnormal dreams*|
|Nervous system disorders||Very common||Headache a#|
|Common||Burning sensation c|
|Eye disorders||Not known||Blurred vision|
|Not known||Lacrimation increased|
|Cardiac disorders||Uncommon||Palpitations a|
|Very rare||Reversible atrial fibrillation|
|Vascular disorders||Uncommon||Flushing a|
|Respiratory, thoracic and mediastinal disorders||Very common||Cough**|
|Very common||Sore mouth or throat|
|Very common||Throat irritation|
|Gastrointestinal disorders||Very Common||Hiccups|
|Very common||Nausea a|
|Uncommon||Oral mucosal blistering and exfoliation|
|Not known||Dry throat|
|Not known||Gastrointestinal discomforta|
|Not known||Lip pain|
|Musculoskeletal and connective tissue disorders||Uncommon||Pain in Jaw b|
|Not known||Muscle tightness b|
|Skin and Subcutaneous Tissue Disorders||Uncommon||Hyperhidrosis a|
|General disorders and administration site conditions||Common||Fatigue a|
|Uncommon||Chest discomfort and pain a|
|Rare||Allergic reactions including angioedema|
***Reported the same or less frequently than placebo# Although the frequency in the active group is less than that of the placebo group, the frequency in the specific formulation in which the PT was identified as a systemic ADR was greater in the active group than the placebo group.
Reporting of Suspected Adverse ReactionsReporting 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 at: www.mhra.gov.uk/yellowcard.
|How strong was your urge to smoke?||Before start of administration of study treatment||After 2 minutes||After 5 minutes||After 10 minutes|
|Category 1 (No or very light urge to smoke)||0 (0%)||20 (23.5%)||43 (50.5%)||57 (68%)|
|Category 2 Category 4||80 (100%)||65 (76.5%)||42 (49.5%)||28 (32%)|
|Any relief in urges to smoke?||Before start of administration of study treatment||After 2 minutes||After 5 minutes||After 10 minutesa|
|Yes||0 (0%)||40 (47%)||70 (85%)||78 (93%)|
|No||90 (100%)||45 (53%)||15 (15%)||6 (7%)|
AbsorptionA Nicorette Cools 4mg Lozengedissolves completely, typically in 10-20 minutes. Assuming complete dissolution in the mouth, most of its nicotine is absorbed through the oral mucosa. This fraction is almost entirely delivered to the systemic circulation. The remaining nicotine released in the mouth is swallowed and undergoes considerable first-pass metabolism in the intestine and liver. As a consequence, only a small part of the total nicotine given with a lozenge reaches the circulation via the intestine.A maximum nicotine plasma concentration of about 5 ng/mL is achieved after a single-dose of the Nicorette Cools 2mg Lozenge, and about 8 ng/mL after a single-dose of the Nicorette Cools 4mg Lozenge. Area under the time vs. plasma concentration curve extrapolated to infinity (AUC∞) after a single-dose of a Nicorette Cools 2mg Lozengeis about 16 h*ng/mL, and about 31 h*ng/mL after a single-dose of a Nicorette Cools 4mg Lozenge.
DistributionThe volume of distribution following intravenous administration of nicotine is about 2 to 3 l/kg.Plasma protein binding of nicotine is less than 5%. Therefore, changes in nicotine binding from use of concomitant drugs or alterations of plasma proteins by disease states would not be expected to have any significant effects on the nicotine pharmacokinetics.
BiotransformationThe major eliminating organ is the liver, although the kidney and lung also metabolise nicotine. More than 20 metabolites of nicotine have been identified, all of which are believed to be less active than the parent compound.The primary metabolite of nicotine in plasma, cotinine, has a terminal half-life of 15 to 20 hours and concentrations that exceed nicotine by 10-fold.
EliminationThe average plasma clearance is about 70 l/h and the elimination half-life is approximately 2-3 hours.The primary urinary metabolites are cotinine (12% of the dose) and trans-3-hydroxy-cotinine (37% of the dose). About 10% of nicotine is excreted unchanged in the urine, but as much as 30% of nicotine may be excreted unchanged with high flow rates and acidification of the urine below pH 5.
Characteristics in specific groups of subjects
Renal ImpairmentProgressive severity of renal impairment is associated with decreased total clearance of nicotine. Nicotine clearance was decreased by on average 50% in subjects with severe renal impairment. Raised nicotine levels have been seen in smoking subjects undergoing hemodialysis.
Hepatic ImpairmentThe pharmacokinetics of nicotine is unaffected in individuals with liver cirrhosis and mild liver impairment (Child-Pugh score 5), and decreased by 40-50% in subjects with moderate liver impairment (Child-Pugh score 7). There is no information available in subjects with a Child-Pugh score > 7.A minor reduction in total clearance of nicotine has been demonstrated in healthy elderly subjects, however not justifying adjustment of dosage.
CoreMannitol (E421) Xanthan gum (E415) Winterfresh Flavour Sodium carbonate anhydrousSucralose (E955) Acesulfame potassium (E950) Magnesium stearate (E470b)
CoatingHypromellose (Methocel E3)Winterfresh Flavour Titanium dioxide (E171)Sucralose (E955)Sepifilm glossAcesulfame potassium (E950)Polysorbate 80Purified water
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