Consumer medicine information

Nicabate and Nicabate P Transdermal Patch

Nicotine

BRAND INFORMATION

Brand name

Nicabate Clear Patch, Nicabate Pre-Quit and Nicabate P

Active ingredient

Nicotine

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Nicabate and Nicabate P Transdermal Patch.

What is in this leaflet

This leaflet answers some common questions about NICABATE Patches. It does not contain all the available information.

It does not take the place of talking to your pharmacist or doctor.

All medicines have risks and benefits. Your pharmacist or doctor has weighed the risks of you using NICABATE Patches against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your pharmacist or doctor.

Keep this leaflet with the medicine. You may need to read it again.

What are NICABATE Patches used for?

NICABATE Patches *are tan or clear square patches for sticking on your skin. They are a stop smoking aid which helps you to give up smoking by replacing some of the nicotine you are used to getting from cigarettes. It is the nicotine in cigarettes that can make you physically addicted to them. This type of treatment is called Nicotine Replacement Therapy (NRT). NICABATE Patches provide a steady amount of nicotine to your body, generally at a level lower than from cigarettes. This nicotine relieves some of the unpleasant symptoms such as feeling ill or irritable that smokers often feel when they try to give up. The nicotine can also reduce your cravings for a cigarette and help you to resist the urge to smoke.

Because NICABATE Patches do not contain the tar, carbon monoxide or other toxins in cigarette smoke, they do not have the health dangers of tobacco.

If possible, when giving up smoking, NICABATE Patches should be used with a stop smoking behavioural support programme.

There are no health benefits to smoking. It is always better to give up smoking and using NRT can help. In general, any possible side effects associated with NRT are far outweighed by the well established dangers of continuing to smoke.

Your pharmacist or doctor may have given you this medicine for another reason.

If you need more information ask your pharmacist or doctor.

Before you use NICABATE Patches

When you must not use it

Do not use NICABATE patches if:

  • You are allergic to nicotine or any of the ingredients listed at the end of this leaflet.
  • You are a non-smoker.
  • You are under 12 years of age. Children are more likely to be affected by nicotine and it could cause severe toxicity which may be fatal.
  • You have a skin condition or disease such as allergic eczema or dermatitis.

In addition, do not use Nicabate Pre-Quit patches if:

  • You smoke less than 15 cigarettes a day.
  • You have heart problems.
  • You weigh less than 45 kg.

Do not use this medicine after the expiry date (EXP) printed on the pack. If you use it after the expiry date has passed, it may not work as well.

Do not use if the packaging is torn or shows signs of tampering.

Do not use this medicine to treat any other complaint unless your doctor or pharmacist says it is safe. Do not give this medicine to anyone else even if they have the same symptoms as you.

Nicabate Patches should be removed prior to undergoing MRI procedures.

If you are not sure whether you should start taking this medicine, talk to your doctor or pharmacist.

Before you start to use it

You must tell your pharmacist or doctor if:

  • You have an uncontrolled, overactive thyroid gland. Nicotine may make your symptoms worse.
  • You have heart or circulation problems including heart failure or stable angina or high blood pressure or have had a stroke. If you are in hospital because of a heart attack, severe heart rhythm disturbances or a stroke, you should try to quit smoking without using NRT unless your doctor tells you to use it. Once you are discharged from hospital, you may use NRT in consultation with your doctor.
  • You have any serious liver or kidney disease. You may be more prone to side effects.
  • You are a diabetic. If you have diabetes you should monitor your blood sugar levels more often than usual when starting NICABATE patches as you may find your insulin or other medication requirements alter.
  • You have been diagnosed as having a tumour of the adrenal glands (phaeochromocytoma). Nicotine may make your symptoms worse.
  • You have any allergies to any other medicines such as an itchy skin rash or swelling of the lips, face and throat.
  • You have had allergic reactions that involve swelling of the lips, face and throat (angioedema) or itchy skin rash (urticaria), using NRT can sometimes trigger this type of reaction.
  • You have a history of epilepsy or are taking medicine to control any fits or seizures
  • You have stomach or duodenal ulcers or an inflamed oesophagus or gullet (the passage between the mouth and the stomach) because NRT can make your symptoms worse.

If you have not told your pharmacist or doctor about any of the above, tell them before you use NICABATE Patches or NICABATE PRE-QUIT Patches.

Tell your doctor if you are pregnant (or intend to become pregnant) or you are breastfeeding (or planning to breastfeed).

If you are pregnant
Smoking during pregnancy has risks such as poor growth of your baby before birth, premature birth or still birth. Stopping smoking is the best way to improve both your health and that of your baby. The earlier you stop smoking, the better.

Ideally, if you are pregnant, you should stop smoking without using NRT. However, if you have tried and this hasn’t worked, your doctor may recommend you use NRT to help you stop smoking. This is because it is better for your developing baby than if you carry on smoking. The decision to use NRT should be made as early on in your pregnancy as possible and you should aim to use it for only 2-3 months. Remember, the most important thing is to stop smoking. You should only use NRT if your doctor has told you to.

NRT products that are taken intermittently, such as gum or lozenges, are preferable to nicotine patches. However, patches may be preferred if you have nausea or sickness. If you are going to use NICABATE Patches, make sure you remove the patches before going to bed.

If you are breastfeeding
Tobacco smoke causes breathing difficulties and other problems in babies and children. Ideally, if you are breastfeeding, you should try to stop smoking without using NRT. If you need to use NRT to help you quit, the amount of nicotine your baby may receive is much smaller and less harmful than breathing in second hand smoke. NICABATE Patches should not be used while breastfeeding. You should use NRT products that are taken intermittently (eg gum or lozenges) and breastfeed just before you take the product. This helps your baby to get the smallest amount of nicotine possible.

Using other medicines

Tell your pharmacist or doctor if you are using any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop.

Stopping smoking, with or without nicotine replacement products such as NICABATE Patches, may alter the absorption of some medicines. The doses of the other medicines that you are using may need to be changed.

Other medicines may be affected by NICABATE Patches or affect how well NICABATE Patches work.

Your pharmacist or doctor can advise you what to do if you are using any of these medicines.

If you have not told your pharmacist or doctor about any of these things, tell him/her before you use nicotine patches.

How to use NICABATE Patches

Follow all directions given to you by your doctor or pharmacist carefully. These may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

After your quit date it is important that you make every effort to stop smoking completely. However, if you do smoke a cigarette while you are using NICABATE Patches, you should continue your quit attempt. Talking to your pharmacist or doctor may help.

People who smoke 15 or more cigarettes a day who want to begin their quit attempt without giving up cigarettes immediately, can use NICABATE PRE-QUIT Patches in the first 2 weeks of a quit attempt. After the 2 week course is completed, NICABATE Patches may be used as described below

In some cases, the use of more than one NRT product may help them to make a quit attempt successful (see Using Combination Therapy). People who have used NICABATE PRE-QUIT Patches could use combination therapy after the initial 2 week Pre-Quit course.

How to use

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

NICABATE PRE-QUIT Patches

These 24 hour patches are for smokers who smoke 15 or more cigarettes a day and who choose to smoke while preparing to quit.

Adults
Patch to be applied once daily for the first 2 weeks of the quit attempt.

After 2 weeks, stop smoking and start on the treatment schedule with regular patches. (see NICABATE Patches below)

Adolescents
Adolescents should not quit with Nicabate Pre-Quit Therapy.

NICABATE Patches

Adults
NICABATE patches are designed to be worn for 24 hours and to be used as part of a 10-12 week nicotine replacement therapy step down programme.

For smokers who have 10 or more cigarettes a day, treatment should start with the NICABATE 21mg patch and consists of:

Firstly, 6 weeks on a patch delivering 21mg of nicotine over 24 hours.

Next, 2 weeks on a smaller patch delivering 14mg of nicotine over 24 hours.

Followed by, 2-4 weeks on a very small patch delivering 7mg of nicotine over 24 hours.

Commence use in the morning after a smoke-free night. (Shift workers may need to adjust the timing.)

Your pharmacist or doctor may vary this schedule, eg, for people who weigh less than 45 kgs or who smoke less than 10 cigarettes per day or who suffer from heart problems to:

Firstly, 6 weeks on a patch delivering 14mg of nicotine over 24 hours.

Followed by, 2-4 weeks on a patch delivering 7mg of nicotine over 24 hours.

NOTE: The nicotine strength of the cigarettes you smoked does not normally influence the patch dosage needed.

Adolescents
Young people aged 12 to 17 years should only use NICABATE Patches for 12 weeks. Use as described above for adults.

If you think you may need to use them for longer, talk to your pharmacist or doctor.

NRT should only be used by those aged 12 to 17 years if a counselling programme is used at the same time. NRT is not likely to work in this age group if there is no counselling with it.

Children
Children under 12 years of age should not use NICABATE Patches.

NICABATE Combination Therapy

Combination therapy can be used by smokers who have been unsuccessful giving up smoking when they have used just one type of Nicotine Replacement Therapy (NRT).

NICABATE Patches can be combined with NICABATE Gum 2 mg or NICABATE Mini Lozenges 1.5 mg. You should start with the 21 mg patch and you should use at least 4 pieces of gum or mini lozenges each day. Most people use 4 to 5 pieces a day. Do not use more than 12 pieces of NICABATE gum 2 mg or NICABATE Mini Lozenges 1.5 mg a day.

Do not use NICABATE Gum 4 mg or NICABATE Mini Lozenges 4 mg together with NICABATE patches.

The combination treatment of 21 mg patch and gum or mini lozenges should be used for 12 weeks. After this time you should begin weaning yourself off NRT. You can do this by:

  1. Using the 14 mg patch for 2 weeks and then the 7 mg patch for 2 weeks while continuing to take the same number of mini lozenges or pieces of gum you routinely use. Once you are not using any patches, you can gradually reduce the number of mini lozenges or pieces of gum until you are not using any.

OR

  1. Stop using the 21 mg patch and then gradually reduce the number of mini lozenges or pieces of gum you are using.

Adolescents.
Adolescents should not quit using combination therapy’.

Smoking while using oral forms of NRT

If you are not able to stop smoking abruptly, you can use NICABATE Gum, or NICABATE Mini Lozenges while you gradually reduce the number of cigarettes you smoke over several weeks.

How to apply the patch

Before you open the pouch choose an area of skin and make sure it is clean, dry and hairless. We recommend the upper body or arms. Areas where the skin creases should be avoided. Do not apply a patch to skin that is red, broken or irritated. Wear only one patch at a time.

Cut or tear open the pouch at the top.

Remove the stiff, transparent protective cover (one half at a time) and apply the sticky surface to the prepared skin area.

When applying the patch, avoid touching eyes and nose.

Press the patch firmly onto the skin with the palm of your hand and hold in place for 10-20 seconds, making sure the patch adheres properly at the edges, then wash your hands well to remove any traces of nicotine.

Dispose of the transparent protective covers carefully, away from children or pets.

When replacing the NICABATE Patch, choose a new skin site. Do not apply to previously used skin site for approximately one week.

You can swim, bathe and shower for short periods with the patch on. It is best not to use soap on the patch or skin immediately surrounding the patch as the soap may increase nicotine absorption.

If the patch peels off you may use a strip of adhesive tape to secure it. The patch is effective as long as it is against your skin.

How long to use it

If you are using NICABATE PRE-QUIT Patch, use for 2 weeks whilst smoking. By the end of the two weeks you should stop smoking completely and start using the NICABATE Patches for the recommended 10-12 week step down programme.

The patches should not be used for longer than 4 months. However, intermittent use products such as NICABATE Mini Lozenges or NICABATE 7Gum can be used for up to 9 months.

It is recommended you wear the patch for 24 hours for best effect. However, if you are experiencing vivid dreams, try taking the patch off at bedtime (after 16 hours) and putting a new one on when you get up the next day.

If you are pregnant remove the patch at bedtime and replace when you get up the next day. (see Before you start to use)

If you find it difficult to give up NICABATE Patches or you are worried that you may start smoking again then speak to your pharmacist or doctor.

If you do start smoking again, you may want to talk to your pharmacist or doctor about how to get the best results from further courses of NICABATE Patches.

While you are using NICABATE Patches

If you forget to change the patch at your usual time, simply change it when you remember and then change the patch at the usual time the following day.

Side Effects

Tell your pharmacist or doctor as soon as possible if you do not feel well while you are using NICABATE Patches or NICABATE PRE-QUIT Patches.

Nicotine patches help most people but they may have unwanted side effects in a few people.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Stopping smoking itself can cause some symptoms such as dizziness, headache, sleep disturbance, cough and cold-like symptoms. Symptoms such as depression, irritability, anxiety and insomnia may also be related to withdrawal symptoms associated with giving up smoking. You may also get more mouth ulcers than usual.

Do not be alarmed by the following list of side effects. You may not experience any of them.

Ask your pharmacist or doctor to answer any questions you may have.

Tell your pharmacist or doctor if you notice any of the following and they worry you:

  • Nausea
  • Stomach upsets
  • Vomiting
  • Diarrhoea
  • Dizziness
  • Headache
  • Dry mouth
  • Indigestion
  • Constipation
  • Sleep disturbances
  • Tremors
  • Nervousness
  • Tiredness or weakness
  • Increased sweating
  • Joint and muscle pain
  • Shortness of breath/difficulty breathing
  • Sore throat
  • Cough

The above list includes the more common side effects. Mostly these are mild and short-lived. You may also experience these side effects as you decrease the strength of the patches that you use.

These patches may cause other unwanted side effects in some people. You may get a slight redness and itching, burning and tingling of the skin where a patch has been. This usually disappears within a day.’

Tell your doctor as soon as possible if you notice any of the following:

  • Changes from your normal heartbeat.
  • Severe red or itchy skin at the sticking site.
  • Sensitivity of the skin to sunlight

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

If any of the following happen, stop using NICABATE Patches or NICABATE PRE-QUIT Patches and tell your doctor immediately or go to accident and emergency at your nearest hospital:

  • Fast or very irregular heartbeat.
  • Swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing. You may have a serious allergic reaction to the medicine.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Other side effects not listed above may also occur in some people. Tell your pharmacist or doctor if you notice anything else that is making you feel unwell.

Transferred dependence
Some people worry that they will quit smoking but become dependent on nicotine patches. This is very rare and, if it did happen, it is less harmful to you than continuing to smoke and an easier habit to break.

If you use too much (Overdose)

If you smoke or use any other nicotine containing product while you are using NICABATE Patches, you may suffer an overdose of nicotine. However, if used correctly, nicotine overdose is unlikely.

If you use more than one patch at once you may start to feel sick, dizzy and unwell. Remove all patches and wash and dry the skin with water only (no soap).

If you have started your quit attempt with NICABATE PRE-QUIT Patches and experience symptoms as listed below you should discontinue smoking and if symptoms persist remove the patch.

Symptoms of nicotine overdosage include:

  • Headache
  • Dizziness
  • Stomach upset
  • Drooling
  • Vomiting
  • Diarrhoea
  • Cold sweat
  • Blurred vision
  • Hearing distortion
  • Confusion
  • Weakness
  • Fainting
  • Pale skin
  • Tremor

If it is a large overdose, there may be exhaustion, convulsions, low blood pressure, circulatory collapse and breathing difficulty.

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26) or go to accident and emergency at your nearest hospital if you think you or anyone else may have used too many NICABATE Patches.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

The patches are not suitable for children under 12 or for non-smokers. They may develop signs of nicotine overdose including headache, sickness, stomach pains and diarrhoea. Even small amounts of nicotine can be dangerous to children.

In the event of a child applying or playing with a new or used patch contact a doctor or the Poisons Information Centre (telephone 13 11 26) immediately.

After using NICABATE Patches

Storage

STORE OUT OF THE REACH OF CHILDREN AND PETS (New and used NICABATE patches contain nicotine, which can be harmful). A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep the patch sealed in the pouch until needed.

Keep it in a cool dry place where the temperature stays below 30ºC

Do not store it or any other medicine in the bathroom or near a sink.

Do not leave it in the car on hot days. Heat and dampness can destroy some medicines.

Disposal

If your pharmacist or doctor tells you to stop using the patches or the patches have passed their expiry date, ask you pharmacist what to do with any patches that are left over.

Used patches should be folded in half and placed back in the pouch. Dispose of carefully. Do not flush down the toilet.

Product Description

NICABATE is available in 2 forms of patch: Clear Patch (NICABATE CLEAR PATCH and NICABATE PRE-QUIT)) and Opaque Patch (NICABATE P).

NICABATE CLEAR PATCH is available in 3 nicotine dosage strengths:
21mg per 24hr (Step 1), 14mg per 24hr (Step 2) and 7mg per 24hr (Step 3). All strengths are available as one week supply (7 patches per box). (Step 1) patches are also available as two week supply (14 patches per box).

NICABATE PRE-QUIT is available in packs of 14 patches in a strength of 21 mg/24 hr. NICABATE PRE-QUIT Patch is available in clear only.

NICABATE P is available as a 21 mg /24 hour opaque patch. It is available in a pack of 28 patches. NICABATE P is only available on the PBS.

The main components of the patch are:

  • A supply of nicotine in a co-polymer base. Base contains ethylene vinyl acetate with ethylene dioleamide.
  • A polyisobutylene adhesive layer to stick the patch to the skin.

A rate controlling membrane to control the delivery rate of nicotine to the skin which contains polyethylene

Only difference between the two patches is colour; one is tan and the other clear.

Marketed by:

GlaxoSmithKline
Consumer Healthcare,
82 Hughes Avenue,
Ermington NSW 2115, Australia
ACN 603 310 292

Trade marks are owned by or licensed to the GSK group of companies.

©2019 GSK group of companies or its licensor.

AUST R 81035 (NICABATE Clear Patch 21 mg/24 hr.)

AUST R 81034 (NICABATE Clear Patch 14 mg/24 hr.)

AUST R 81033 (NICABATE Clear Patch 7 mg/24 hr.)

AUST R 151699 (NICABATE PRE-QUIT)

AUST R 171308 (NICABATE P 21mg/24hr.)

Date of preparation: June 2019

www.nicabate.com.au

*Nicabate P is only available on the PBS

PC1007113

Published by MIMS November 2020

BRAND INFORMATION

Brand name

Nicabate Clear Patch, Nicabate Pre-Quit and Nicabate P

Active ingredient

Nicotine

Schedule

Unscheduled

 

1 Name of Medicine

Nicotine.

2 Qualitative and Quantitative Composition

Active ingredients.

Nicotine is S-3-(1-methyl-2-pyrrolidinyl)-pyridine and is the major pharmacologically active alkaloid of tobacco.
See Table 1.
Nicotine is the active ingredient; other components of the system are pharmacologically inactive.
The Nicabate Pre-Quit patch has the same formulation as the Nicabate Clear Patch 21 mg/24 hour patch.
*Nicabate P transdermal nicotine patch is only available in 21 mg patches.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

The free alkaloid is absorbed rapidly through the skin and respiratory tract.
The rate of delivery of nicotine to the patient from each system (40 microgram/cm2/h) is proportional to the surface area. About 73% of the total amount of nicotine remains in the system 24 hours after application. Nicabate is labelled by the dose actually absorbed by the patient (i.e. 7 mg/d, 14 mg/d or 21 mg/d). The dose of nicotine absorbed from Nicabate represents 68% of the amount released in 24 hours. The other 32% evaporates from the edge of the system.
Nicabate is a multilayered rectangular film containing nicotine as the active agent. For the three doses the composition per unit area is identical. Proceeding from the visible surface toward the surface attached to the skin are: (1) an occlusive backing consisting of polyethylene/ aluminium/ polyethylene terephthalate/ ethylene-vinyl acetate copolymer; for Nicabate and Nicabate P and polyethylene terephthalate/ ethylene-vinyl acetate copolymer for Nicabate Clear Patch; (2) a drug reservoir containing nicotine (in an ethylene-vinyl acetate copolymer matrix containing ethylene dioleamide as slip agent); (3) a rate-controlling membrane (polyethylene); (4) a polyisobutylene adhesive; and (5) a protective liner that covers the adhesive layer and must be removed before application to the skin.

4 Clinical Particulars

4.1 Therapeutic Indications

Nicabate Clear patches and Nicabate P patches.

For the treatment of nicotine dependence as an aid to smoking cessation.

Nicabate Pre-Quit patches and Nicabate P patches.

Treatment with Nicabate is indicated as an aid to smoking cessation. Nicabate Pre-Quit patches and Nicabate P patches may be used by people who smoke 15 or more cigarettes per day for two weeks prior to quitting smoking.

4.2 Dose and Method of Administration

Prior to initiation of therapy users should be committed to stopping smoking. During an abrupt quit attempt every effort should be made to stop smoking during treatment with Nicabate patches. The patient should read the patient instruction booklet on Nicabate therapy and be encouraged to ask any questions.
Generally, treatment should be initiated with Nicabate 21 mg/day* or 14 mg/day.
In patients who smoke less than 10 cigarettes/day, have cardiovascular disease or weigh less than 45 kg should start with the Nicabate 14 mg/day patches.
All other patients should start with the Nicabate 21 mg/day patches.
*Nicabate P transdermal nicotine patch (21 mg/day) is available on the PBS and can be used for a total of twelve weeks. The product may be used in an abrupt quit setting or it may be used for two weeks prior to quit date while continuing to smoke and then for 10 weeks from the quit date.

Nicabate Pre-Quit patch therapy.

Nicabate Pre-Quit patches can be used for the first 2 weeks of a quit attempt by smokers of 15 or more cigarettes a day who choose to smoke while preparing to quit. This should then be followed by the use of 21 mg, 14 mg and 7 mg patches in the established dosage regimen (see Nicabate Pre-Quit patch therapy).

Nicabate Abrupt Quit patch therapy.

Adults (18 years and over).

Once the appropriate dosage is selected, the patient should begin 6 weeks of therapy at that dosage.
Users should make every effort to stop smoking completely during an abrupt quit attempt with Nicabate patches.
Behavioural therapy, advice and support will normally improve the success rate.
See Table 2.
Nicabate should be applied promptly upon its removal from the protective pouch to prevent evaporative loss of nicotine from the system. Nicabate should be used only when the pouch is intact to assure that the product has not been tampered with. The user should wash hands with water after handling the patch and avoid contact with eyes and nose.
Nicabate should be applied only once a day to a nonhairy, clean, dry skin site on the upper body or upper outer arm. After 24 hours, the used Nicabate patch should be removed and a new patch applied to an alternate skin site.
Skin sites should not be reused for at least a week. Areas where the skin creases should be avoided. It should not be applied to skin that is red, broken or irritated. It should be pressed firmly on the skin with the palm of the hand for 10 seconds. Water will not harm the nicotine transdermal patch, if it has been applied properly. The user can bathe, swim or shower for short periods while wearing the patch. Patients should be cautioned not to continue to use the same patch for more than 24 hours. The patch is recommended to be worn for 24 hours to minimise the chance of morning cravings. However, if the user experiences any vivid dreams or other disruptions of sleep while wearing the patch for 24 hours, the patch may be removed at bedtime (after 16 hours) and a new one put on upon waking the next day.
Intermittent dosing products (e.g. Nicabate lozenges or gums) could be used beyond 12 weeks if they are needed to stay cigarette free, however, those who use NRT beyond 9 months are recommended to seek additional help and advice from a healthcare professional who may consider alternate quit strategies, such as combination therapy.
Further courses may be used a later time for Nicabate patch users who continue or resume smoking.

Children and adolescents.

Children.

Safety and efficacy in children who smoke have not been evaluated. Nicabate patches are not recommended for use in children under 12 years of age.

Adolescents (12 to 17 years).

Data are limited in relation to the value of NRT use in young people where the demand for cessation products and the motivation to quit is low. Nevertheless NRT is safe in this group. NRT should only be used by adolescents in conjunction with a counselling programme. Counselling is needed in this age group because NRT is likely to be ineffective in the absence of counselling.
Adolescents (12 to 17 years) should follow the schedule of treatment for an abrupt quit attempt in adults presented above but as data are limited, duration of NRT in this age group is restricted to 12 weeks. If longer treatment is required advice from a healthcare professional should be sought who can then reassess the patient for their commitment to quitting and the benefits of continued treatment. If treatment is continued, it should not be extended for more than another four weeks.
Adolescents should not quit with Pre-Quit or combination therapy.

Nicabate Pre-Quit patch therapy.

For smokers of 15 or more cigarettes a day who chose to smoke while preparing to quit, Nicabate Pre-Quit patches should be applied once daily for the first 2 weeks of the quit attempt.
After the 2 week Pre-Quit course is completed, the patient should stop smoking completely then continue their quit attempt with the regular Nicabate or Nicabate Clear 21 mg, 14 mg and 7 mg patches. Nicabate 21 mg patches should be used for 6 weeks, followed by use of the 14 mg patches for the next 2 weeks and use of the 7 mg patches for 2-4 weeks. Combination therapy may also be used once smoking has ceased (see Combination therapy).
The Nicabate Pre-Quit patches, and Nicabate and Nicabate Clear patches, should be applied as indicated under Nicabate patch therapy, Adults (18 years and over).

Combination therapy.

In some instances, it may be beneficial to utilize more than one form of NRT concurrently. For example, combination therapy could be used by smokers who have relapsed with NRT monotherapy in the past, who experience breakthrough cravings or have difficulty controlling cravings for cigarettes using single therapy. This would allow users to identify the combination most appropriate for their individual quit attempt. If required, Nicabate gum 2 mg or Nicabate lozenges 2 mg or Nicabate Minis 1.5 mg may be combined with Nicabate 21 mg patches. Nicabate 4 mg lozenges and/or Nicabate 4 mg gums and/or Nicabate 4 mg Minis should not be used with Nicabate patches.
When using Nicabate 21 mg patches in addition to Nicabate 2 mg gums, 2 mg lozenges or 1.5 mg Minis, it is recommended that a minimum of 4 pieces of gum/ 4 lozenges/ 4 Minis are used daily. Most people will use 4-5 pieces. The maximum number of gums or lozenges or Minis used in conjunction with the patch is 12 pieces per day.
Combination treatment should be used for 12 weeks after which weaning may be initiated. If required, weaning may be done by either:
1. Using Nicabate 14 mg patch for 2 weeks and then Nicabate 7 mg patch for 2 weeks while maintaining the number of pieces of 2 mg gum/ lozenges or 1.5 mg Minis that have been routinely used. Then, when a patch is no longer used, the number of pieces of gum/ lozenges/ Minis can be gradually reduced; or
2. Stopping use of Nicabate 21 mg patch and then gradually reducing the number of pieces of 2 mg gum/ lozenges or 1.5 mg Minis that are being used.

Reduce to quit.

For smokers who are unwilling or unable to quit abruptly, Nicabate gum or lozenge or Minis should be used as the number of cigarettes is gradually reduced over a number of weeks.

Drug abuse and dependence.

To minimise the risk of dependence, patients should be encouraged to withdraw gradually from Nicabate after 4 to 8 weeks of use. Recommended dose reduction is to progressively decrease the dose every 2 to 4 weeks (see Section 4.2 Dose and Method of Administration).

4.3 Contraindications

Nicabate Clear patches should not be used by: nonsmokers; children under 12 years of age; those with hypersensitivity to nicotine or any of the excipients; those with diseases of the skin that may complicate patch therapy.
Nicabate Pre-Quit patches should not be used by: those who smoke less than 15 cigarettes per day; those with cardiovascular disease; those who weigh less than 45 kg.
Nicabate P patches should not be used by: those who smoke less than 10 cigarettes per day; those who weigh less than 45 kg.

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.
Patients hospitalised for myocardial infarction, severe dysrhythmia or CVA (cerebrovascular accident) who are considered to be haemodynamically unstable should be encouraged to stop smoking with nonpharmacological interventions.
If this fails, Nicabate lozenges or soft gums may be considered, but as data on safety in this patient group are limited, initiation should only be under medical supervision. Once patients are discharged from hospital they can use NRT on medical advice. If there is a clinically significant increase in cardiovascular or other effects attributable to nicotine, the nicotine dose should be reduced or Nicabate patch use discontinued.
The precessation or combination NRT regimens should not be used in people with known cardiovascular disease without evaluation of the risk/ benefit by a healthcare professional.

Diabetes mellitus.

Patients with diabetes mellitus should be advised to monitor their sugar levels more closely than usual when NRT is initiated as catecholamines released by nicotine can affect carbohydrate metabolism and vasoconstriction may delay/ reduce insulin absorption. Blood glucose levels may be more variable when stopping smoking, with or without NRT, so it is important for diabetics to continue monitoring their blood sugar levels while using this product.

Seizures.

Potential risks and benefits of nicotine should be carefully evaluated before use in subjects taking anticonvulsant therapy or with a history of epilepsy as cases of convulsions have been reported in association with nicotine.

Allergic reactions.

The user should stop use and consult a healthcare professional if he/she gets skin redness, swelling or rash that does not go away after 4 days, or if a generalised skin reaction occurs. This may be more likely if there is a history of dermatitis.

Susceptibility to angioedema and urticaria.

NRT should be used with caution by patients who are susceptible to angioedema and/or urticaria.

Atopic or eczematous dermatitis (due to localised patch sensitivity).

In the case of severe or persistent local reactions at the site of application (e.g. severe erythema, pruritus or oedema) or a generalised skin reaction (e.g. urticaria, hives or generalised skin rashes), users should be instructed to discontinue use of Nicabate patches and contact their physicians.

Contact sensitisation.

Patients with contact sensitisation should be cautioned that a serious reaction could occur from exposure to other nicotine containing products or smoking.
A risk-benefit assessment should be made by an appropriate healthcare professional for patients with the following conditions:

Use in hepatic impairment.

Use with caution in patients with moderate to severe hepatic impairment as the clearance of nicotine or its metabolites may be decreased with the potential for increased adverse effects.

Use in renal impairment.

Use with caution in patients with severe renal impairment as the clearance of nicotine or its metabolites may be decreased with the potential for increased adverse effects.

Use in the elderly.

No data available.

Pheochromocytoma and uncontrolled hyperthyroidism.

Use with caution in patients with uncontrolled hyperthyroidism or pheochromocytoma as nicotine causes release of catecholamines.

GI disease.

Nicotine replacement therapy may exacerbate symptoms in persons suffering from active oesophagitis, oral and pharyngeal inflammation, gastritis, gastric ulcer or peptic ulcer.
Patients who initiate quitting with pre-cessation NRT and experience exaggerated effects as listed (see Section 4.9 Overdose) should discontinue smoking and remove the patch.

Paediatric use.

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. The patches should be folded in half with the adhesive side innermost and disposed of with care.

Transferred dependence.

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

Safety on handling.

Nicabate patches are potentially a dermal irritant and can cause contact sensitisation. Care should be taken during handling and, in particular, contact with the eyes and nose avoided. After handling, wash hands with water alone as soap may increase nicotine absorption. Nicabate patches should be removed prior to undergoing MRI procedures.

Effects on laboratory tests.

No data available.

Drug abuse and dependence.

Nicabate therapy is likely to have a low abuse potential based on differences between it and cigarettes in four characteristics commonly considered important in contributing to abuse: much slower absorption; much smaller fluctuations in blood levels, lower blood levels of nicotine, and less frequent use (i.e. once daily).
Dependence on nicotine polacrilex chewing gum replacement therapy has been reported. Such dependence might also occur from transference to Nicabate of tobacco-based nicotine dependence.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No clinically relevant interactions between nicotine replacement therapy and other drugs have been established, however nicotine may possibly enhance the haemodynamic effects of adenosine. Healthcare professionals are reminded that smoking itself may require the adjustment of some drug therapy.
Polycyclic aromatic hydrocarbons in tobacco smoke induce the metabolism of drugs metabolised by CYP1A2 (and possibly CYP1A1). When a smoker stops this may result in a slower metabolism and a consequent rise in blood levels of such drugs.
Smoking cessation, with or without nicotine replacement, may alter the individual's response to concomitant medication and may require adjustment of dose. In particular, anticonvulsants may require special monitoring and/or dosage adjustment. See Table 3.
Other reported effects of smoking include reduced analgesic efficacy of propoxyphene, reduced diuretic response to frusemide and altered pharmacological response to propranolol, as well as altered rates of ulcer healing with H2-antagonists. Both smoking and nicotine can increase levels of circulating cortisol and catecholamines. Dosages of nifedipine, adrenergic agonists or adrenergic blocking agents may need to be adjusted.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

In rats and rabbits, implantation can be delayed or inhibited by a reduction in DNA synthesis that appears to be caused by nicotine. Studies have shown a decrease in litter size in rats treated with nicotine during gestation.
(Category D)
Smoking during pregnancy is associated with risks, such as intrauterine growth retardation, premature birth or stillbirth. Stopping smoking is the single most effective intervention for improving the health of both pregnant smoker and her baby. The earlier abstinence is achieved the better.
Ideally smoking cessation during pregnancy should be achieved without NRT. However, for women unable to quit on their own, NRT should only be used on the advice of a healthcare professional. Nicotine is harmful to the foetus. However, the risk of using NRT to the foetus is lower than that expected with tobacco smoking, due to lower maximal plasma nicotine concentration and no additional exposure to polycyclic hydrocarbons and carbon monoxide.
However, as nicotine passes to the foetus affecting breathing movements and has a dose dependent effect on placental/ foetal circulation, the decision to use NRT should be made as early on in the pregnancy as possible. The aim should be to use NRT for only 2-3 months.
While no data exist to support one form of NRT over another, intermittent dosing products (i.e. Nicabate lozenges and soft gums) should preferably be used while pregnant as these usually provide a lower daily dose of nicotine than patches. However, patches may be preferred if the woman is suffering from nausea during pregnancy. If patches are used they should be removed before going to bed.
 Nicotine from smoking and NRT is found in breast milk. However, the amount of nicotine the infant is exposed to from NRT is relatively small and less hazardous than the second hand smoke they would otherwise be exposed to. Nicabate patches should not be used while breastfeeding. Intermittent dosing products, such as Nicabate soft gums or lozenges, should be used while breastfeeding and women should breastfeed just before they use the product to allow as long a time as possible between NRT use and feeding.

4.7 Effects on Ability to Drive and Use Machines

Used as recommended there are minimal risks associated with the use of Nicabate in driving vehicles or operating machinery.

4.8 Adverse Effects (Undesirable Effects)

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.
NRT may cause adverse reactions similar to those associated with nicotine administered by other means, including smoking. These may be attributable to the pharmacological effects of nicotine, some of which are dose dependent. At recommended doses, Nicabate patches have not been found to cause any serious adverse effects. Excessive use of Nicabate patches by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches.
Certain symptoms which have been reported such as depression, irritability, nervousness, restlessness, mood lability, anxiety, drowsiness, impaired concentration, insomnia and sleep disturbances may be related to withdrawal symptoms associated with smoking cessation. Subjects quitting smoking by any means could expect to suffer from asthenia, headache, dizziness, sleep disturbance, coughing or influenza-like illness.
The following undesirable effects have been reported in clinical trials or spontaneously postmarketing (very common ≥ 1/10; common ≥ 1/100, < 1/10; uncommon ≥ 1/1,000, < 1/100 and very rare < 1/10,000). See Table 4.
Hypersensitivity reactions, including contact dermatitis and allergic dermatitis, have also been reported. In the case of severe or persistent local reactions at the application site (e.g. severe erythema, pruritus or oedema) or a generalised skin reaction (e.g. urticaria, hives or generalised skin rashes) users should be instructed to discontinue use of Nicabate and contact their physician.
If there is a clinically significant increase in cardiovascular or other effects attributable to nicotine, the Nicabate dose should be reduced or discontinued.

4.9 Overdose

The effects of applying several Nicabate patches simultaneously, or swallowing Nicabate patches are unknown (see Section 4.4 Special Warnings and Precautions for Use).
The minimum lethal dose of nicotine in a nontolerant 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.

Symptoms and signs.

Signs and symptoms of an overdose from a nicotine patch would be expected to be the same as those of acute nicotine poisoning, including pallor, cold sweat, salivation, vomiting, abdominal pain, diarrhoea, headache, dizziness, disturbed hearing and vision, tremor, mental confusion and weakness. Prostration, hypotension, respiratory failure and convulsions may ensue with large overdoses.

Overdose from topical exposure.

Nicabate should be removed immediately in the event of an overdose or if the patient shows signs of overdosage, and the patient should seek immediate medical care. The skin surface may be flushed with water and dried. No soap should be used, since it may increase nicotine absorption. Nicotine will continue to be delivered into the bloodstream for several hours (see Section 5.2 Pharmacokinetic Properties) after removal of the system because of a depot of nicotine in the skin.

Overdose from ingestion.

All nicotine intake should stop immediately. The patient should seek medical attention immediately and be treated symptomatically. Due to the possibility of nicotine induced seizures, activated charcoal should be administered. In unconscious patients with a secure airway, instil activated charcoal via a nasogastric tube. A saline cathartic or sorbitol added to the first dose of activated charcoal may speed gastrointestinal passage of the system. Repeated doses of activated charcoal should be administered as long as the patch remains in the gastrointestinal tract since it will continue to release nicotine for many hours.

Management of nicotine poisoning.

All nicotine intake should stop immediately and the patient should be treated symptomatically. Artificial respiration with oxygen should be instituted if necessary. Activated charcoal may reduce the absorption of nicotine if given within one or two hours after ingestion. In patients who are not fully conscious or have an impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
Other supportive measures include diazepam for seizures, atropine for excessive bronchial secretions or diarrhoea, respiratory support for respiratory failure, and vigorous fluid support for hypotension and cardiovascular collapse.
For information on the management of overdose, contact the Poison Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacological action.

Nicotine, the chief alkaloid in tobacco products, binds stereoselectively to acetylcholine receptors at the autonomic ganglia, in the adrenal medulla, at neuromuscular junctions and in the brain. Two types of central nervous system effects are believed to be the basis of nicotine's positively reinforcing properties. A stimulating effect, exerted mainly in the cortex via the locus ceruleus, produces increased alertness and cognitive performance. A "reward" effect via the "pleasure system" in the brain is exerted in the limbic system. At low doses the stimulant effects predominate, while at high doses the reward effects predominate. Intermittent intravenous administration of nicotine activates neurohormonal pathways, releasing acetylcholine, noradrenaline, dopamine, serotonin, vasopressin, beta-endorphin, growth hormone and ACTH.

Pharmacodynamic effects.

The actions of nicotine in man are complex, depending on dose, rate of delivery, prevalent autonomic tone, individual variation and prior exposure (tolerance).
The cardiovascular effects of nicotine include peripheral vasoconstriction, tachycardia and elevated blood pressure. Acute and chronic tolerance to nicotine develops from smoking tobacco or ingesting nicotine preparations. Acute tolerance (a reduction in response for a given dose) develops rapidly (less than 1 hour), but at distinct rates for different physiological effects (skin temperature, heart rate, subjective effects). Withdrawal symptoms, such as cigarette craving, can be reduced in some individuals by plasma nicotine levels lower than those for smoking.
Withdrawal from nicotine in addicted individuals is characterised by craving, nervousness, restlessness, irritability, mood lability, anxiety, drowsiness, sleep disturbances, impaired concentration, increased appetite, minor somatic complaints (headache, myalgia, constipation, fatigue) and weight gain. Nicotine toxicity is characterised by nausea, abdominal pain, vomiting, diarrhoea, diaphoresis, flushing, dizziness, disturbed hearing and vision, confusion, weakness, palpitations, altered respiration and hypotension.
The cardiovascular effects of Nicabate 21 mg/day used continuously for 24 hours were compared with smoking every 30 minutes during waking hours for 5 days. Both regimens elevated heart rate (about 10 beats/min) and blood pressure (about 5 mmHg) compared with an abstinence period and these increases were similar between treatments throughout the 24 hour period, including during sleep.
The circadian pattern and release of plasma cortisol following 5 days of treatment with Nicabate 21 mg/day did not differ from that following 5 days of nicotine abstinence. Urinary excretion of noradrenaline, adrenaline and dopamine was also similar for Nicabate 21 mg/day and abstinence.

5.2 Pharmacokinetic Properties

Absorption.

Following application of Nicabate to the upper body or upper outer arm, approximately 68% of the nicotine released from the system enters the systemic circulation (e.g. 21 mg/day for the highest dose patch). The remainder of the nicotine released from the system is lost via evaporation from the edge. All Nicabate systems are labelled with the actual amount of nicotine absorbed by the patient.

Distribution.

The volume of distribution following IV administration of nicotine is approximately 2 to 3 L/kg and the half-life of nicotine ranges from 1 to 2 hours. 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 significant consequences.

Metabolism.

The metabolism of nicotine primarily occurs in the liver but also in the lung and kidney. There is no significant skin metabolism of 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.

Elimination.

The major eliminating organ is the liver and average plasma clearance is about 1.2 L/min.
The primary urinary metabolites are cotinine (15% of the dose) and trans-3-hydroxycotinine (45% of the dose). About 10% of nicotine is excreted unchanged in the urine. As much as 30% may be excreted in the urine with high urine flow rates and urine acidification below pH 5.
After Nicabate application, plasma concentrations rise rapidly, plateau within 2 to 4 hours, and then slowly decline until the patch is removed, after which they decline more rapidly.
The pharmacokinetic model that best fits the plasma nicotine concentrations from Nicabate systems is an open, two compartment disposition model with a skin depot through which nicotine enters the central circulation compartment. Nicotine in the adhesive layer is absorbed into and then through the skin, causing the initial rapid rise in plasma concentrations. The nicotine from the reservoir is released slowly through the membrane with a release rate constant approximately 20 times smaller than the skin absorption rate constant, as demonstrated in vitro in cadaver skin flux studies and verified by pharmacokinetic trials. Therefore, the slow decline of plasma nicotine concentrations from 4 to 24 hours is determined primarily by the release of nicotine from the system.
Following the second daily Nicabate application, steady-state plasma nicotine concentrations are achieved and are on average 30% higher compared with single dose applications. Plasma nicotine concentrations are proportional to dose (i.e. linear kinetics are observed) for the three strengths of Nicabate patches. Nicotine kinetics are similar for all sites of application on the upper body and upper outer arm. Plasma nicotine concentrations from Nicabate 21 mg/day are the same as those from simultaneous use of Nicabate 14 mg/day and 7 mg/day.
Following removal of the Nicabate system, plasma nicotine concentrations decline in an exponential fashion with an apparent mean half-life of 3 to 4 hours compared with 1 to 2 hours for IV administration, due to continued absorption from the skin depot. Most nonsmoking patients will have nondetectable nicotine concentrations in 10 to 12 hours.
See Table 5.
Half-hourly smoking of cigarettes produces average plasma nicotine concentrations of approximately 44 nanogram/mL. In comparison, average plasma nicotine concentrations from Nicabate 21 mg/day are about 17 nanogram/mL.
There are no differences in nicotine kinetics between men and women using Nicabate systems. Linear regression of both AUC and Cmax vs total bodyweight shows the expected inverse relationship. Obese men using Nicabate had significantly lower AUC and Cmax values than normal weight men. Men and women having low bodyweight are expected to have higher AUC and Cmax values.

5.3 Preclinical Safety Data

Genotoxicity.

Nicotine and cotinine were not mutagenic in the Ames Salmonella test. Nicotine induced repairable DNA damage in an E. coli test system. Nicotine was shown to be genotoxic in a test system using Chinese hamster ovary cells.

Carcinogenicity.

Nicotine itself does not appear to be a carcinogen in laboratory animals. However, nicotine and its metabolites increased the incidence of tumours in the cheek pouches of hamsters and forestomach of F344 rats, respectively, when given in combination with tumour initiators. One study, which could not be replicated, suggested that cotinine, the primary metabolite of nicotine, may cause lymphoreticular sarcoma in the large intestine in rats.

6 Pharmaceutical Particulars

6.1 List of Excipients

Excipients: Nicabate is a multilayered rectangular film containing nicotine as the active agent. For the three doses the composition per unit area is identical. Proceeding from the visible surface toward the surface attached to the skin are: (1) an occlusive backing consisting of polyethylene/ aluminium / polyethylene terephthalate/ ethylene-vinyl acetate copolymer; for Nicabate and Nicabate P and polyethylene terephthalate/ ethylene-vinyl acetate copolymer for Nicabate Clear; (2) a drug reservoir containing nicotine (in an ethylene-vinyl acetate copolymer matrix containing ethylene dioleamide as slip agent); (3) a rate-controlling membrane (polyethylene); (4) a polyisobutylene adhesive; and (5) a protective liner that covers the adhesive layer and must be removed before application to the skin.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

7 mg/day containing 36 mg nicotine with a 7 cm2 release area.

Nicabate Clear: packs of 3, 7.

14 mg/day containing 78 mg nicotine with a 15 cm2 release area.

Nicabate Clear: packs of 3, 7.

21 mg/day containing 114 mg nicotine with a 22 cm2 release area.

Nicabate Clear: packs of 3, 7 and 14.
Nicabate Pre-Quit: packs of 3, 14.
Nicabate P: packs of 14 and 28.
Not all packs may be marketed.

6.6 Special Precautions for Disposal

Nicabate can be a dermal irritant and can cause contact sensitisation. Although exposure of health care workers to nicotine from Nicabate systems should be minimal, care should be taken to avoid unnecessary contact with active systems. When the used patch is removed from the skin, it should be folded over and placed in the protective pouch that contained the new system. The used system should be immediately disposed of in such a way to prevent its access by children or pets. Because Nicabate contains residual nicotine after use, it must therefore be kept out of reach of children at all times. As with other nicotine containing transdermal patches, accidental application by small children could produce severe symptoms of poisoning, and may prove fatal.
In Australia any unused medicine or waste material should be disposed of by taking to your local pharmacy or in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Nicotine is S-3-(1-methyl-2-pyrrolidinyl)-pyridine.

CAS number.

54-11-5.

7 Medicine Schedule (Poisons Standard)

Unscheduled.

Summary Table of Changes