- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Directions for useIf you are using Nicorette QuickMist for the first time or if you have not used the spray for 2 days, you must first prime the spray pump. Priming 1. Point the spray safely away from you and any other adults, children or pets that are near you.2. Press the top of the QuickMist with your index finger 3 times until a fine spray appears. Note: priming reduces the number of sprays you may get from Nicorette QuickMist.After priming, point the spray nozzle as close to the open mouth as possible. Press the top of the dispenser and release one spray into your mouth, avoiding the lips. Do not inhale while spraying to avoid getting spray down your throat. For best results, do not swallow for a few seconds after spraying.The patient should not eat or drink when administering the oromucosal spray. Care should be taken not to spray the eyes whilst administering the mouth spray.
Adults and Children over 12 years of ageUse 1 or 2 sprays when cigarettes normally would have been smoked or if cravings emerge. If after the first spray cravings are not controlled within a few minutes, a second spray should be used. If 2 sprays are required, future doses may be delivered as 2 consecutive sprays.Most smokers will require 1-2 sprays every 30 minutes to 1 hour.You may use up to 4 sprays per hour. Do not exceed 2 sprays per dosing episode and 64 sprays (4 sprays per hour over 16 hours) in any 24-hour period. Each mouthspray contains at least 150 sprays.Nicorette QuickMist 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 Nicorette QuickMist and as soon as they are able, reduce the number of sprays used until they have stopped completely. Smokers aiming to reduce cigarettes should use the Mouthspray, 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.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 their Mouthspray are recommended to contact their pharmacist or doctor for advice.
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 fetus is lower than that expected with smoking tobacco. Stopping completely is by far the best option but if this is not achievable Nicorette QuickMist 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 fetus 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 the following: dysphoria or depressed mood; insomnia; irritability, frustration or anger; anxiety; difficulty concentrating, restlessness or impatience; decreased heart rate; and increased appetite or weight gain. These have been observed in those using the mouthspray.Increased frequency of aphthous ulcer, cough and nasophyringitis may occur after abstinence from smoking. The causality is unclear. In addition to this, other cessation-associated symptoms were seen in those using the mouth spray: dizziness, presyncopal symptoms, constipation, and gingival bleeding.Nicotine craving, which is recognised as a clinically relevant symptom, is an important element in nicotine withdrawal after smoking cessation.
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. Most adverse events reported with this product occur during the early phase of treatment and are similar to those seen with other orally delivered forms. During the first few days of treatment irritation to the mouth and throat may be experienced and hiccups are particularly common. Tolerance is normal with continued use. Daily collection of data from trial subjects demonstrated that very commonly occurring adverse events were reported with onset in the first 2-3 weeks of use of the spray, and declined thereafter.Allergic reactions (including symptoms of anaphylaxis) occur rarely during use of this product.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).Frequencies 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 Not known||HypersensitivityaAnaphylactic reactiona|
|Psychiatric disorders||Uncommon||Abnormal dreams*|
|Nervous System Disorders||Very common Common Common Common Common||Headachea# Burning sensationc Dizziness Dysgeusia Paraesthesiaa|
|Eye Disorders||Not known Not known||Blurred Vision Lacrimation increased|
|Cardiac Disorders||Uncommon Uncommon Not known||Palpitationsa TachycardiaaAtrial fibrillation|
|Vascular Disorders||Uncommon Uncommon||Flushinga Hypertensiona|
|Respiratory, Thoracic and Mediastinal Disorders||Very common Very common Very common Uncommon Uncommon Uncommon Uncommon Uncommon Uncommon Uncommon Uncommon||Cough** Hiccups Throat irritation Bronchospasm Dysphonia DyspnoeaaNasal congestion Oropharyngeal pain Rhinorrhoea Sneezing Throat tightness|
|Gastrointestinal Disorders||Very common Common Common Common Common Common Common Common Common Common Uncommon Uncommon Uncommon Uncommon Uncommon Rare Rare Rare Not known Not known Not known||NauseaaAbdominal pain Diarrhoea*** Dry mouth Dyspepsia Flatulence Salivary hypersecretion Stomatitis Toothache VomitingaEructation Gingivitis Glossitis Oral mucosal blistering and exfoliation Paraesthesia oral*** Dysphagia Hypoaesthesia oral*** Retching Dry throat Gastrointestinal discomfortaLip pain|
|Musculoskeletal and connective tissue disorders||Uncommon Uncommon Not known||Pain in jawbMusculoskeletal pain Muscle tightnessb|
|Skin and Subcutaneous Tissue Disorders||Uncommon Uncommon Uncommon Uncommon Uncommon Not known Not known||Dry skin HyperhidrosisaPruritusaRashaUrticaria** Angioedemaa Erythemaa|
|General disorders and administration site conditions:||Common Uncommon Uncommon Uncommon||FatigueaAstheniaaChest discomfort and painaMalaise|
AbsorptionThe oral spray form means that the nicotine dose is administered instantaneously, and as a result the absorption of nicotine from the mouth spray is rapid: In trials, nicotine uptake from the oral nicotine spray was detected at 2 minutes, the first timepoint tested.A maximum concentration of 5.3 ng/mL is reached within 13 minutes after administration of a 2 mg dose. The nicotine AUCs over the first 10 minutes after administration of the mouth spray at a dose of 1 and 2 mg exceeds those of nicotine gum as well as nicotine lozenge at doses of 4 mg (0.48 and 0.64 h*ng/mL vs. 0.33 and 0.33 h*ng/mL).AUC∞ estimates show the bioavailability of nicotine administered by mouth spray is somewhat higher than that of nicotine gum or lozenge. The AUC∞ of the mouth spray 2 mg measured 18.9 h*ng/mL as compared with 16.2 h*ng/mL for nicotine gum 2 mg. Allowing for differences in administered dose, bioavailability was also higher in a second study. The nicotine AUC∞ of the mouth spray 2 mg measured 14.0 h*ng/mL in comparison with 23.0 h*ng/mL and 26.7 h*ng/mL for and nicotine gum 4 mg and nicotine lozenge 4 mg, respectively.Steady-state average nicotine plasma concentrations achieved after adminstration of the maximum dose (i.e. 2 sprays of the mouth spray 1 mg every 30 minutes) are approximately 28.8 ng/mL as compared with 23.3 ng/mL for nicotine gum 4 mg (1 gum, hourly) and 25.5 ng/mL for nicotine lozenge 4 mg (1 lozenge, hourly). Given the rapid absorption and the similar, high relative bioavailability, the majority of the nicotine released from the mouth spray is apparently absorbed through the buccal mucosa.
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.
BiotransformationNicotine metabolism and elimination are independent of the choice of nicotine formulation, and thus results from studies with intravenous administration of nicotine are used to describe, biotransformation and elimination.The major nicotine-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 half-life of 15 to 20 hours and concentrations that exceed nicotine by 10-fold.
EliminationThe average plasma clearance of nicotine is 70 l/hour and the half-life is 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. As much as 30% of nicotine may be excreted unchanged in the urine with high flow rates and acidification of the urine below pH 5.
Linearity/non-linearityThere is only a small deviation from dose-linearity of AUC∞ and Cmax as shown when single doses of 1, 2, 3 and 4 sprays of the 1 mg mouth spray are given.Characteristics in specific groups of subjects:
Renal ImpairmentProgressive severity of renal impairment is associated with decreased total clearance of nicotine. Nicotine clearance was on average decreased by 50%, in subjects with severe renal impairment. Raised nicotine levels have been seen in smokers undergoing hemodialysis.
Hepatic ImpairmentIn smokers with liver cirrhosis but only mild liver impairment (Child-Pugh score 5) the pharmacokinetics of nicotine is unaffected. However, in smokers with moderately impaired liver (Child-Pugh score 7) total clearance has been reported to be reduced by 40-50%. There is no information available in subjects with a Child-Pugh score > 7.
ElderlyA minor reduction in total clearance of nicotine, not justifying adjustment of dosage, has been demonstrated in healthy elderly patients.
McNeil Products Ltd
Foundation Park, Roxborough Way, Maidenhead, Berks, SL6 3UG