Nicorette, 10 mg/16 h 7 pcs.

Pharmacodynamics:

After abrupt smoking cessation in patients who have used tobacco-containing products daily for a long time, development of “withdrawal” syndrome is possible, which includes: dysphoria or depressed mood, insomnia, increased irritability, frustration or anger, anxiety, impaired concentration, anxiety or impatience, reduced heart rate, increased appetite or increased body weight. An important symptom of withdrawal syndrome is also a desire to smoke.

In the treatment of tobacco addiction nicotine replacement therapy reduces the number of cigarettes smoked, reduces the severity of withdrawal symptoms arising from complete smoking cessation in those who choose to quit smoking; facilitates temporary abstinence from smoking, and helps to reduce the number of cigarettes smoked by those who can not or do not want to give up smoking completely.

Pharmacokinetics:

Nicotine is slowly released from the Nicorette® patch and is continuously absorbed through the skin. The Nicorette® patch is designed to be used during waking hours, i.e. for approximately 16 hours, which coincides with the period of nicotine intake from smoking. This prevents sleep disturbances caused by nicotine intake during sleep. Absolute bioavailability exceeds 90%, regardless of where the patch is applied.

In the therapeutic range (10-25 mg/16 hours), the relationship between the plasma nicotine concentration and its dose is linear. The values of maximum nicotine concentrations (Cmax ) at different doses are shown below.

Nicotine dose (mg/16 hours) Cmax (ng/ml)
10 10
15 15 15.5
25 26.5

The maximum plasma nicotine concentrations calculated from the model correspond to those measured: 11 ng/mL for the 10 mg transdermal patch and 25 ng/mL for 25 mg. The maximum plasma concentration value obtained by interpolation when using the 15 mg transdermal patch was 16 ng/ml.

The time of reaching maximum plasma concentration (tmax) is approximately 9 hours and is created in the afternoon or evening, when the risk of relapse is maximum.

The volume of distribution after intravenous administration of nicotine is approximately 2-3 L/kg and its half-life is approximately 2-3 hours. Nicotine is primarily excreted by the liver, the average plasma clearance is about 70 liters/hour. Nicotine is also metabolized in the kidneys and lungs. More than 20 metabolites of nicotine have been identified, the activity of which is inferior to that of the original substance.

The binding of nicotine to plasma proteins is less than 5%.

The main metabolite of nicotine – cotinine – has a half-life of 15-20 hours and is found in plasma at a concentration 10 times higher than that of nicotine.

The main metabolites of nicotine excreted in the urine are cotinine (12% of the administered dose) and trans-3-hydroxy-cotinine (37% of the administered dose).

About 10% of nicotine is excreted unchanged in the urine. At high filtration rate and urine pH below 5, the amount of nicotine excreted unchanged in the urine may reach 30%.

Progression of renal failure may be accompanied by decreased total nicotine clearance. Smokers with concomitant chronic renal failure treated with hemodialysis have increased plasma nicotine concentration.

Pharmacokinetics of nicotine in mild hepatic failure (5 points on the Child-Pugh scale) does not change, in moderate hepatic failure (7 points on the Child-Pugh scale) nicotine clearance is reduced.

A slight decrease in total nicotine clearance has been noted in healthy elderly patients, which, however, does not require dose adjustment.

Plasma nicotine concentration increases with the three types of transdermal patches in proportion to the dose.

No differences in nicotine pharmacokinetics were observed in men and women.

Indications

Smoking cessation To treat tobacco dependence by reducing the need for nicotine, relieving the “withdrawal” symptoms that occur when patients who are motivated to quit smoking.

Active ingredient

Nicotine

Composition

Nicotine base:

Active ingredient:

nicotine – 15.75 mg;

Excipients: triglycerides (medium chain length) – 18.27 mg, basic butyl methacrylate copolymer – 14.58 mg, polyethylene terephthalate film 19 μm (one side may be varnished) – carrier layer containing the active ingredient.

Acrylate base: acrylic adhesive solution – 123.84 mg, potassium hydroxide – 0.70 mg, croscarmellose sodium – 5.00 mg, aluminum acetylacetonate – 0.06 mg, 100 μm polyethylene terephthalate film, aluminized on one side and siliconized on both sides – carrier, serves as a protection for the adhesive layer (removable substrate), discarded before use.

How to take, the dosage

The Nicorette® Transdermal Patch mimics the fluctuations in nicotine concentration during the day in a smoker; there is no nicotine intake during sleep. The use of nicotine transdermal patch during the day does not cause abnormalities observed in nicotine intake during sleep.

Nicorette® transdermal patch can be used as monotherapy or in combination with Nicorette® chewing gum 2 mg, Nicorette® sublingual tablets 2 mg or Nicorette® spray for local use 1 mg/dose.

If symptoms of overdose occur (see section “Overdose”) the drug should be stopped immediately.

Children and adolescents

Nicorette® patch has not been used by adolescents under 18 years of age; therefore the drug should be used by persons under 18 years of age strictly by medical prescription.

Adults

Nicorette® transdermal patch can be used for abrupt smoking cessation, as well as for increasing the time intervals between smoking in order to reduce smoking as much as possible until the complete cessation of smoking.

Patients should do everything possible to quit smoking permanently when treated with the Nicorette® patch.

Patients with high dependence (more than 20 cigarettes a day) are recommended to start with Stage 1 therapy, applying 1 patch 25 mg/16 hours, daily, for 8 weeks.

Then begin gradual dose reduction: 1 patch of 15 mg/16 hours, daily, for 2 weeks, and then 1 patch of 10 mg/16 hours, daily, for the next 2 weeks.

Patients with low dependence (10-20 cigarettes per day) are recommended to begin therapy with Stage 2, using 1 patch of 15 mg/16 hours, daily, for 8 weeks. Then begin a gradual reduction of the drug dosage to Stage 3: 1 patch 10 mg/16 hours, daily, for the next 4 weeks.

How to apply the transdermal patch

The patch is applied to an intact area of skin immediately after waking up in the morning and removed before bedtime. The patch should be applied to dry, clean, undamaged, hair-free skin such as the thighs, upper extremity or chest. It is necessary to change the place of application every day: the same area should not be used for the next two days. After applying the patch, wash your hands thoroughly to avoid eye irritation from possible nicotine ingestion.

1. Wash your hands thoroughly before applying the patch.
2. Slit the patch packaging with scissors along the edge as indicated on it. Choose a clean, dry area of skin free of hair (e.g. thighs, upper extremity or chest).
3. Remove one half of the silver aluminized protective film without touching the adhesive surface of the patch.
4. Reinforce the part of the patch freed from the protective film on the skin and remove the remaining half of the silver aluminized protective film.
5. Press the patch firmly against the skin with the palm of your hand or fingertips.
6. Run your finger along the edge of the patch to ensure that it is firmly adhered.
7. If the patch loosens, apply a new one. The use of skin care oil or talcum powder may prevent the patch from sticking properly.

In combination with chewing gum, sublingual tablets, topical spray

For smokers with strong nicotine addiction (more than 20 cigarettes a day), or those who have irresistible craving for smoking, or smokers who were not able to quit smoking with only one type of nicotine replacement therapy, for rapid relief of smoking cravings, the Nicorette® patch can be used in combination with Nicorette® gum in 2 mg dose/ 2 mg Nicorette® tablets/ Nicorette® syringe spray for topical application in 1 mg dose/dose.

The patch is applied to an intact area of skin immediately after waking up in the morning and removed before bedtime. The patch should be applied to dry, clean, undamaged, hair-free skin such as the thighs, upper extremity, or chest. It is necessary to change the place of application every day: the same area should not be used for the next two days. After applying the patch, wash your hands thoroughly to avoid eye irritation from possible nicotine ingestion.

Initial therapy:

Treatment should begin with the patch 25 mg/16 hours (Stage 1) in combination with chewable gum 2 mg / sublingual tablets 2 mg / topical spray 1 mg/dose. Usually 5-6 chewable gum/diarrheal tablets per day or 13 doses of topical spray per day are sufficient. The maximum daily dose for chewable gum is 15 units, for sublingual tablets 24 units, and for topical spray 32 doses.

Patients should completely stop smoking during therapy. Usually the total course of treatment lasts for 8 weeks. Thereafter, the nicotine dose should be gradually reduced.

Cancellation of combination therapy:

Cancellation of combination therapy can be done in two ways.

Method 1: For the next 2 weeks, switch from the 25 mg/16 hour patch (Stage 1) to the 15 mg/16 hour patch (Stage 2) and then, for the next 2 weeks, to the 10 mg/16 hour patch (Stage 3), while maintaining the amount of chewable gum/tongue tablets/doses of topical spray used, if necessary, as with Initial Therapy. Then gradually reduce the amount of gum chews/epipharyngeal tablets/ topical spray doses until complete elimination within the time that the patient needs depending on his/her needs, but no later than 12 months after the start of combined therapy.

Method 2: consists in complete elimination of the patch immediately after the end of Initial Therapy. Then gradually reduce the amount of chewable gum/tablets/ doses of topical spray until complete elimination within the time that the patient needs, depending on his/her needs, but no later than 12 months after the start of combined therapy.

Interaction

No clear clinically significant interaction between nicotine replacement therapy and other drugs has been established. Nevertheless, theoretically, nicotine can increase the hemodynamic effects of adenosine, i.e., it can lead to an increase in blood pressure and heart rate, as well as increase the response to pain (angina-like chest pain) provoked by adenosine administration.

Special Instructions

Nicorette® use is associated with less risk than smoking.

The Nicorette® transdermal patch should be removed before MRI (magnetic resonance imaging) to avoid burns.

Danger to young children

Doses of nicotine easily tolerated by adult smokers and teenage smokers can cause severe intoxication in children, which can lead to death. It is important not to leave preparations containing nicotine unattended, as this can lead to misuse and ingestion by children (see “Overdose”).

Forming an addiction

Addiction to the drug may develop, but it is less dangerous to health and more easily overcome than addiction to smoking.

Smoking cessation

The polycyclic aromatic hydrocarbons in tobacco smoke induce the metabolism of drugs metabolized by the CYP1A2 isoenzyme (and possibly CYP1A1). Smoking cessation may cause slower metabolism and, consequently, increased blood concentrations of these drugs. This has potential clinical implications for drugs with a narrow therapeutic index, such as theophylline, tacrine, clozapine, and ropinirole.

Plasma concentrations of other drugs that are partially metabolized by the CYP1A2 isoenzyme, such as imipramine, olanzapine, clomipramine, and fluvoxamine, may also increase after smoking cessation, although data supporting this hypothesis are lacking and the possible clinical significance of this effect is unknown.

Limited data suggest that smoking may induce the metabolism of flecainide and pentazocine.

After use, the patch should be folded adhesive side inward and disposed of out of the reach of children.
Warnings and precautions for combined therapy of Nicorette® transdermal patch with chewing gum/lingual lozenges/spray for topical use are similar to warnings and precautions for each of the drugs separately.

If the drug is out of date or expired – do not throw it into drains or the street! Place the medication in a bag and put it in a trash container. These measures will help protect the environment!

Synopsis

Rectangular patch with rounded corners, translucent, beige in color, on a rectangular aluminized and siliconized separable substrate.

• 10 mg/16 hr area 9 cm2 +2%, 27.7×33.2 mm
• 15 mg/16 hr area 13.5 cm2 +2%, 33.2×41.3 mm
• 25 mg/16 hr area 22.5 cm2 +2%, 43×53 mm.

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Contraindications

Hypersensitivity to nicotine or other ingredients of the drug.

Side effects

Regardless of the drug used as a treatment for tobacco dependence, some symptoms may be due to nicotine withdrawal due to smoking cessation.

These include: dysphoria or depressed mood; insomnia; irritability, frustration or anger; anxiety; difficulty concentrating; restlessness or impatience; decreased heart rate; increased appetite or weight gain; dizziness or pre-smoking states; coughing, constipation and bleeding gums.

The incidence of aphthous ulcers, coughing, and nasopharyngitis may also increase after stopping smoking. A causal relationship has not been established.
Nicotine cravings, considered a clinically significant symptom, are an important manifestation of nicotine withdrawal after smoking cessation.

The Nicorette® patch may cause nicotine-related adverse reactions similar to those observed with other nicotine-containing drugs. Most adverse reactions are reported by patients during the early phase of therapy and are mostly dose-dependent.

Approximately 20% of patients develop mild local skin reactions during the first weeks of therapy.

Allergic reactions (including anaphylactic reactions) may rarely occur in predisposed individuals.

Overdose

Excessive nicotine intake during substitution therapy and/or smoking can cause symptoms of overdose.

Symptoms of nicotine overdose may occur in patients with low nicotine intake before treatment or with the simultaneous use of different nicotine sources.

In overdose, the same symptoms as in acute nicotine poisoning are noted, namely nausea, vomiting, increased salivation, abdominal pain, diarrhea, sweating, headache, dizziness, hearing disturbances, and marked general weakness. In high doses, these symptoms may be followed by the following symptoms: decreased blood pressure, weak and irregular pulse, difficulty breathing, loss of strength, collapse and generalized convulsions.

Nicotine in doses tolerated by adult smokers can cause symptoms of severe poisoning in children and even lead to death. Suspicion of nicotine poisoning in children should be treated as an emergency requiring immediate hospitalization.

Treatment of overdose: nicotine use should be stopped immediately and symptomatic treatment administered. It is necessary to remove the patch and rinse the place of application with water. Activated charcoal reduces the absorption of nicotine in the gastrointestinal tract.

Minimum lethal dose in acute overdose for a non-smoking adult is 40-60 mg of nicotine.

Pregnancy use

Smoking during pregnancy is associated with risks such as intrauterine delay, premature birth or stillbirth. Smoking cessation is the single most effective intervention to improve the health of both the pregnant woman and her baby. Early smoking cessation is the best option.

Nicotine penetrates the placental barrier and affects fetal respiratory activity and circulation. The effect on circulation is dose-dependent. Smoking can have serious adverse effects on the fetus and the newborn, and should therefore be stopped. Therefore, ideally, smoking cessation during pregnancy should be done without nicotine replacement therapy.

The risks to the fetus when using Nicorette® have not been fully studied. However, the benefits of nicotine replacement therapy in pregnant women who are unable to quit smoking without such treatment far outweigh the risk of continued smoking. Nicorette® patch should only be used in pregnant women with high dependence after consulting a physician.

Nicotine passes into breast milk in amounts that may affect the baby, even when used in therapeutic doses. Therefore, you should refrain from using Nicorette® patch during breastfeeding. If it is not possible to stop smoking, the drug should be started only after consulting a physician.

Smoking increases the risk of infertility in men and women. In vitro studies have shown that nicotine negatively affects sperm quality in men.