Nicorette, spray 1 mg/dose 150 doses mint

Pharmacodynamics: Nicotine is an agonist of nicotinic receptors in the peripheral and central nervous system (CNS), has a pronounced effect on the CNS and cardiovascular system.

Abrupt withdrawal from smoking causes development of characteristic withdrawal syndrome, including craving for smoking.

Clinical studies have shown that nicotine replacement therapy drugs allow smokers to abstain from smoking, relieving the symptoms of “withdrawal”. A single-dose study in 200 healthy smokers showed that using two 1mg doses of the spray reduced the desire to smoke from the first minute after application of the spray and to a much greater extent than when using nicotine-containing snuff tablets. Compared to nicotine gum chewing or lozenge tablets, absorption of nicotine from the oral spray is faster (see section “Pharmacokinetics”) and, based on the accumulated experience of nicotine replacement therapy, it leads to a more rapid reduction in cravings and other symptoms.

Increased appetite is a well-known symptom of nicotine “withdrawal”, often after stopping smoking there is an increase in body weight. The desire to smoke is also an important symptom of “withdrawal”.
Pharmacokinetics: The pharmacokinetics of nicotine has been extensively studied; it has been found that the method of delivery of the substance into the body has a significant impact on the rate and extent of absorption.

The pharmacokinetics of oral mucosal spray have been studied in four studies involving 141 subjects.

Absorption

The oral mucosal spray dosage form suggests that the dose of nicotine is delivered immediately and, as a consequence, its absorption from the oral cavity is rapid.

The maximum concentration, equal to 5.3 ng/ml, is reached within 13 min after 2 mg of nicotine is administered. Ten minutes after administration of the 1 and 2 mg doses of the spray, the area under the concentration-time curve (AUC) exceeded those obtained in studies of chewing gum and tablets containing 4 mg nicotine (0.48 and 0.64 h×ng/ml, compared with 0.33 and 0.33 h×ng/ml).

The AUC∞ values indicate that the bioavailability of nicotine when the spray is applied to the oral mucosa is similar to that of the tablets and slightly higher than that of nicotine chewing gum. The AUC∞ for the 2 mg spray was 14.0 h×ng/mL compared with 23.0 h×ng/mL for the 4 mg chewing gum and 26.7 h×ng/mL for the 4 mg tablets.

The average equilibrium plasma nicotine concentration reached after the maximum dose was administered (i.e. 2 injections of 1 mg spray every 30 min) was approximately 28.8 ng/mL compared with 23.3 ng/mL for 4 mg chewing gum (1 pill every hour) and 25.5 ng/mL for 4 mg nicotine tablets (1 tablet every hour).

Given the rapid absorption and similar high relative bioavailability, most of the nicotine released from the spray is apparently absorbed through the mucous membrane of the cheeks.

Distribution

The volume of distribution after intravenous administration of nicotine is from 2-3 L/kg.

The binding of nicotine to plasma proteins is less than 5%. For this reason, changes in nicotine binding when using concomitant drugs or changes in plasma protein content in a number of diseases, presumably, should not have a significant impact on the pharmacokinetics of nicotine.

Biotransformation

Metabolism and excretion of nicotine are independent of the dosage form, and therefore the results of studies of nicotine during intravenous administration are appropriate to describe them.

The primary organ that eliminates nicotine is the liver. However, nicotine is also metabolized in the kidneys and lungs. More than 20 metabolites of nicotine are known, with all of them apparently less active than the original compound.

Plasma elimination half-life of the main metabolite of nicotine – cotinine – is 15-20 hours, and its concentration is 10 times greater than that of nicotine.

Excretion

The average plasma clearance of nicotine is 70 liters/hour and the elimination half-life is 2-3 h.

The main nicotine metabolites found in the urine are cotinine (12% of the administered dose) and trans-3-hydroxycotinine (37% of the administered dose). Approximately 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 can reach 30%.

Linearity/non-linearity

Only a slight deviation from linearity of AUC∞ and Cmax was found at 1, 2, 3, and 4 pressings of the 1 mg/dose spray.

Special patient groups

Renal impairment

The progression of renal impairment is accompanied by a decrease in overall nicotine clearance. Nicotine clearance in patients with severe renal impairment is reduced by an average of 50%. In patients on hemodialysis an increase in nicotine concentration was noted.

Hepatic impairment

Pharmacokinetics of nicotine in patients with mild hepatic impairment (5 points on the Child-Pugh scale) was not changed, but with moderate hepatic impairment (7 points on the Child-Pugh scale) decreased by 40-50%. There are no data on nicotine pharmacokinetics in liver dysfunction greater than 7 Child-Pugh points.

Elderly patients

In healthy elderly patients, a slight decrease in total nicotine clearance has been observed, not requiring changes in the drug dose.

Indications

Smoking Cessation Nicorette® Spray alleviates and/or prevents smoking cravings and withdrawal symptoms that occur with tobacco dependence.

It is indicated as support for smokers who intend to quit smoking or reduce the number of cigarettes smoked before giving up completely; to help smokers who do not want to smoke or in the absence of such an option; and as a safer alternative to smoking.

Active ingredient

Nicotine

Composition

1 ml of product contains:

Active ingredient:

nicotine – 13.6 mg;

Excipients: Propylene glycol – 150.0 mg, ethanol – 97.0 mg, tromethamol – 40.5 mg, poloxamer – 40.0 mg, glycerol – 25.0 mg, sodium hydrocarbonate – 14.3 mg, levomenthol – 10.0 mg, mint flavoring QL24245 – 4.0 mg, Cooler 2 flavoring SN046680 – 3.0 mg, sucralose – 1.5 mg, acesulfame potassium – 1.5 mg, 10% hydrochloric acid – sufficient amount to pH 9, purified water – sufficient amount to 1 ml.

How to take, the dosage

For application on the mucous membrane of the oral cavity.

The patient should do everything possible to quit smoking permanently during the treatment with Nicorette® Spray.

Adults over 18 years

Nicorette® Spray should be used at the moment when there is an irresistible desire to smoke. After preparing the spray for use (see below Instructions for use when using the spray for the first time) put the tip of the spray as close as possible to the open mouth. Press the dispenser upward, thus releasing one dose of the product into your mouth; avoid getting the spray on your lips. To prevent the substance from entering the respiratory tract, do not inhale while pressing the pipette. For best results, do not swallow saliva for a few seconds after injection.

It is not recommended to eat or drink liquid during the use of the spray.

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

Complete smoking cessation

Nicorette® Spray should be used in all cases of craving for smoking or to avoid cravings in situations that may provoke it.

Smokers who are willing or able to stop smoking immediately should immediately replace cigarette smoking with Nicorette® Spray and, as soon as possible, reduce the number of injections until they cease completely.

For complete smoking cessation, make 1 or 2 injections at a time when you would normally have smoked a cigarette and when cravings arise. If cravings do not decrease within a few minutes after a single injection, a second injection should be given. If two doses are required, the subsequent application of the spray may consist of 2 consecutive injections.

No more than 4 dosed injections of the spray may be taken every hour. No more than 2 doses of spray should be injected at a time or more than 64 doses over a 24-hour period (or 4 doses per hour for 16 hours).Each vial contains at least 150 doses.

The average course of application of the spray at the indicated dose is 6 weeks. The number of injections should then begin to be reduced so that by the end of week 9, the number of doses is half of the average daily dose received during the first 6 weeks, and during week 12, no more than 4 doses per day. When the daily dose is reduced to 2-4 injections, the spray should be discontinued.

After therapy to prevent a return to smoking, patients may use Nicorette® Spray if they have an irresistible desire to smoke. In such situations, 1 injection can be made, and if after a single injection the craving for smoking is not reduced within a few minutes, a second injection should be made. This should not exceed 4 metered injections per day.

Regular use of the spray for more than 6 months is generally not recommended, but some patients may require longer therapy to avoid relapse to smoking.

Reducing the number of cigarettes smoked

Smokers who wish to reduce the number of cigarettes smoked should use the spray as needed between smoking episodes in order to increase the intervals between smoking and to reduce smoking as much as possible.

As soon as readiness is felt, smokers should aim for complete smoking cessation.

After smoking cessation, the recommendations of therapy and gradual dose reduction outlined above for complete smoking cessation should be followed.

Behavioral therapy and psychological support usually increase treatment success. Those who have been successful in quitting smoking but have difficulty quitting the spray are advised to seek medical advice from a physician.

Temporary smoking cessation

The spray can be used at times when you need to abstain from smoking, such as when you are in non-smoking areas or other situations where you need to abstain from smoking. The maximum daily dose for temporary smoking cessation is 64 doses.

In combination with transdermal patch

For smokers with strong nicotine addiction (more than 20 cigarettes per day) or those who have irresistible craving for cigarettes or smokers who could not give up smoking with only one nicotine replacement therapy, oral mucosa spray Nicorette ® can be used in combination with nicorette ® transdermal patch for quick relief of smoking craving.

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 extremities or chest. It is necessary to change the place of application every day: you should not use the same area 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 be started with the patch 25 mg/16 hours (Stage 1) in combination with a 1 mg/dose spray. Thirteen doses of spray per day are usually sufficient. The maximum daily dose of the spray is 32 doses.

Patients should completely stop smoking during therapy. Usually the total course of treatment lasts for 8 weeks. After that 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 number of Nicorette® spray doses used, if necessary, as with Initial Therapy. Then gradually reduce the number of doses of the spray until complete abolition 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 abolition of the patch immediately after the end of the Initial Therapy phase. Then gradually reduce the number of doses of Nicorette® Spray until complete withdrawal within the time required by the patient depending on their needs, but no later than 12 months after the start of combined therapy.

Children and adolescents under 18 years

The drug is not recommended for persons under 18 years of age. There is no experience in treating adolescents under 18 years of age with the spray.

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 accompanied by lower risks than smoking.

The risk-benefit ratio should be evaluated by a physician of the appropriate specialty in patients with the following conditions:

Comorbid cardiovascular disease

In the stable course of cardiovascular disease, Nicorette® Spray causes less harm than continued smoking. However, smokers with recent myocardial infarction, unstable angina or worsening angina, including Prinzmetal angina, severe arrhythmias, recent cerebrovascular disease and/or patients with uncontrolled hypertension should be advised to stop smoking without pharmacological intervention. If such attempts are unsuccessful, Nicorette® Spray may be considered, but since safety data in this patient population are limited, such treatment should only be initiated under close medical supervision.

Diabetes mellitus

Patients with diabetes mellitus after stopping smoking and starting nicotine replacement therapy are advised to monitor blood glucose concentrations more closely, since a decrease in catecholamines whose release is induced by nicotine may affect carbohydrate metabolism.

Allergic reactions

The drug should be used with caution in patients prone to angioedema and urticaria.

Gastrointestinal diseases

Ingested nicotine may exacerbate symptoms of esophagitis, gastritis or peptic ulcer, so the use of oral nicotine replacement therapy in the above pathology should be used with caution.

Hepatic and renal disorders

In patients with moderate to severe hepatic failure and (or) severe renal failure, the drug should be used with caution because the clearance of nicotine and its metabolites may be reduced, which may increase the risk of adverse events.

Dangers 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” section).

Pheochromocytoma and uncontrolled hyperthyroidism

In patients with uncontrolled hyperthyroidism and pheochromocytoma, the drug should be used with caution because nicotine causes catecholamine release.

Formation of dependence

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

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 – for example, theophylline, tacrine, clozapine, and ropinirole.

Excipients

Nicorette® Spray contains a small amount of ethanol (alcohol) – less than 10 mg per dose.

When using Nicorette® Spray, care should be taken to avoid getting the spray in the eyes.

Warnings and precautions for combined therapy with Nicorette® Transdermal Patch are similar to those for each drug separately.

If the drug has expired or is out of date, do not throw it in the sewage or outdoors! Place the medication in a bag and put it in a trash container. These measures will help protect the environment!

Synopsis

Oral mucosal spray is a dosed colorless to light yellow transparent or slightly opalescent solution with a peppermint odor.

Contraindications

– Hypersensitivity to nicotine or other ingredients of the drug.

– Children under 18 years of age.

Side effects

Regardless of the form of nicotine medication used, some symptoms may result from 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; cough; aphthous ulcers; nasopharyngitis. A causal relationship has not been established.

In addition, other symptoms associated with smoking cessation have also been reported in individuals using oral mucosa spray: dizziness, presyncopal conditions, coughing, constipation, and bleeding gums.

Nicotine craving, considered a clinically significant symptom, is an important manifestation of nicotine withdrawal after smoking cessation.

Nicorette® Spray may cause nicotine-related adverse reactions similar to those observed with other nicotine-containing medications, these reactions are primarily dose-dependent.

Allergic reactions (such as angioedema, urticaria and anaphylactic shock) may occur in predisposed persons.

Most adverse reactions to Nicorette® Spray were observed in the early phase of treatment and are similar to those for oral drugs. In the first few days of treatment there may be irritation of the mucous membranes of the oral cavity and pharynx, hiccups are common. Continuation of treatment leads to adaptation.

Daily data collection from the subjects of the study showed that very often the emerging adverse events are manifested in the first 2-3 weeks of application of the spray and subsequently disappear.

Overdose

When used as directed, nicotine overdose symptoms may occur in patients with low nicotine intake prior to treatment or when different nicotine sources are used simultaneously.

Symptoms

The minimum lethal dose in acute overdose for an unaccustomed adult is 40-60 mg of nicotine. In overdose, the same symptoms as in acute nicotine poisoning are observed, namely nausea, vomiting, increased salivation, abdominal pain, diarrhea, sweating, headache, dizziness, hearing impairment and marked general weakness. At higher doses, arterial hypotension, a weak and irregular pulse, respiratory disturbance, impaired consciousness, collapse and generalized seizures may join them.

Doses of nicotine that are well tolerated during treatment by adult smokers may cause symptoms of severe poisoning in young children and even lead to death. Suspicion of nicotine poisoning in children should be treated as an emergency requiring immediate hospitalization.

Treatment

Nicotine use should be stopped immediately and symptomatic treatment started. If necessary, artificial pulmonary ventilation should be started. Taking activated charcoal prevents absorption of nicotine in the gastrointestinal tract.

Pregnancy use

Pregnancy

Smoking during pregnancy is associated with risks such as delayed intrauterine development, 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 blood flow. The effect on circulation is dose-dependent.

Therefore, ideally smoking cessation during pregnancy should be done without nicotine replacement therapy. However, if a woman is unable (or it is assumed) to quit smoking without pharmacological support, nicotine replacement therapy is used because continued smoking carries a greater risk to the fetus than nicotine replacement therapy. Complete smoking cessation is the best option, but if that is not achievable, Nicorette® spray can be used as a safer alternative to smoking during pregnancy. Because of potential nicotine-free periods, intermittent dosage forms are preferred, but patches may be necessary if there is significant nausea and/or vomiting. The use of Nicorette® Spray by pregnant women should be initiated only after consultation with a physician.

Breastfeeding

Nicotine penetrates into breast milk in amounts that may affect the baby even when the drug is used in therapeutic doses. Therefore, you should refrain from using Nicorette® spray during breastfeeding. If you have not managed to stop smoking, the drug should be started only after consultation with your doctor.

Medicinal forms for occasional use minimize the nicotine content in breast milk and allow breast-feeding at the lowest concentration of nicotine in it. In order to reduce the negative effects of nicotine on the baby, the drug should be used immediately after breastfeeding. The periods between the use of the drug and the next feeding should be as long as possible (recommended at least 2 hours).

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