Nicorette spray for external use 1mg/dose 150 doses fruit and mint, 13,2ml

Product description

Nicorette® spray helps reduce cravings for smoking. Activation of the spray occurs in 60 seconds 1.1 – When using 2 doses of 1 mg according to the instructions for use.

Composition

>1 ml of the drug contains:  Active substance: nicotine is 13.6 mg;Auxiliary substances: propylene glycol – 150,0 mg, ethanol – 97,0 mg trometamol is 40.5 mg poloxamer – 40,0 mg, glycerol – 25.0 mg, sodium bicarbonate – 14,3 mg, flavoring red fruit 911441 to 8.0 mg, levomenthol – 5.0 mg, flavoring Cooler 2 SN046680 – 3.0 mg, Sucralose – 1.5 mg, Acesulfame potassium 1.5 mg, hydrochloric acid 10% – a sufficient number to pH 9, purified water – a sufficient number to 1 ml.

Pharmacological properties

Pharmacotherapeutic group: a remedy for the treatment of nicotine addiction. ATX code: N07BA01. Pharmacodynamicanicotine is an agonist of nicotine receptors in the peripheral and central nervous system( CNS), has a pronounced effect on the central nervous system and the cardiovascular system. Abrupt quitting causes the development of a characteristic withdrawal syndrome, including cravings for smoking. Clinical studies have shown that nicotine replacement drugs allow smokers to refrain from smoking, alleviating the symptoms of”withdrawal”. A single-dose study in 200 healthy smokers showed that when using two doses of 1 mg spray, the desire to smoke decreases, starting from the first minute after applying the spray and to a significantly greater extent than when using nicotine-containing resorption tablets. Compared to nicotine gum or resorption tablets, the absorption of nicotine from oral mucosal spray is faster (see section “Pharmacokinetics”) and, based on the accumulated experience with nicotine replacement therapy, this leads to a faster reduction in cravings and other symptoms. Increased appetite is a well-known symptom of nicotine “withdrawal”, often after smoking cessation, an increase in body weight occurs. An important symptom of “withdrawal” syndrome is also the desire to smoke. Pharmacokineticspharmacokinetics of nicotine has been extensively studied; it has been found that the method of delivery of the substance to the body has a significant effect on the rate and degree of absorption. The pharmacokinetics of oral mucosal spray were studied in four studies involving 141 subjects. Suctionthe medicinal form of oral mucosal spray assumes that the dose of nicotine is received immediately and, as a result, its absorption from the oral cavity is rapid. The maximum concentration of 5.3 ng / ml is reached within 13 minutes after use of 2 mg of nicotine. 10 minutes after applying the spray at doses of 1 and 2 mg, the area under the concentration-time curve (AUC) exceeded similar values obtained in studies of chewing gum and tablets containing 4 mg of nicotine (0.48 and 0.64 h×ng/ml, compared with 0.33 and 0.33 h×ng/ml). AUC∞ values indicate that the bioavailability of nicotine when applied to the oral mucosa is similar to the bioavailability when using tablets and slightly higher than when using nicotine chewing gum. AUC∞ for the 2 mg spray was 14.0 h × ng / ml, compared to 23.0 h×ng/ml for the 4 mg chewing gum and 26.7 h×ng/ml for the 4 mg tablet. The average steady-state plasma nicotine concentration achieved after the maximum dose (i. e.,2 injections of 1 mg spray every 30 minutes) was approximately 28.8 ng/ml, compared with 23.3 ng/ml for 4 mg chewing gum (1 tablet 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 cheek mucosa. Distributionthe volume of distribution after intravenous nicotine use 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 medications or changes in the content of plasma proteins in a number of diseases, presumably, should not have a significant effect on the pharmacokinetics of nicotine. Biotransformationmetabolism and nicotine elimination do not depend on the dosage form, and therefore the results of the study of nicotine with intravenous use are suitable for their description. The main organ that eliminates nicotine is the liver. However, nicotine is also metabolized in the kidneys and lungs. More than 20 nicotine metabolites are known, all of which appear to be less active than the parent compound. The plasma half-life of the main metabolite of nicotine – cotinine-is 15-20 hours, and its concentration exceeds that of nicotine by 10 times. Elimination The average plasma clearance of nicotine is 70 l / h, with a half-life of 2-3 hours. The main nicotine metabolites detected 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. With a high filtration rate and a urine pH below 5, the amount of nicotine excreted unchanged in the urine can reach 30%. Linearity / Non-linearity With 1,2,3 and 4 taps of the 1 mg/dose spray, only a slight deviation from the linearity of AUC∞ and Cmax was detected. Special patient groups Renal dysfunction Progression of renal failure is accompanied by a decrease in total 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. Impaired liver function The pharmacokinetics of nicotine in patients with mild hepatic impairment (5 points on the Child-Pugh scale) did not change, but in the presence of moderate hepatic impairment (7 points on the Child-Pugh scale) decreased by 40-50%. There are no data on the pharmacokinetics of nicotine in patients with impaired liver function of more than 7 points on the Child-Pugh scale. Elderly patients In healthy elderly patients, there was a slight decrease in total nicotine clearance, which does not require a change in the dose of the drug.

Clinical pharmacology

Pharmacodynamics : Nicotine is an agonist of nicotine receptors in the peripheral and central nervous system( CNS), has a pronounced effect on the central nervous system and the cardiovascular system. Abrupt quitting causes the development of a characteristic withdrawal syndrome, including cravings for smoking. Clinical studies have shown that nicotine replacement drugs allow smokers to refrain from smoking, alleviating the symptoms of”withdrawal”. A single-dose study in 200 healthy smokers showed that when using two doses of 1 mg spray, the desire to smoke decreases, starting from the first minute after applying the spray and to a significantly greater extent than when using nicotine-containing resorption tablets. Compared to nicotine gum or resorption tablets, the absorption of nicotine from oral mucosal spray is faster (see section “Pharmacokinetics”) and, based on the accumulated experience with nicotine replacement therapy, this leads to a faster reduction in cravings and other symptoms. Increased appetite is a well-known symptom of nicotine “withdrawal”, often after smoking cessation, an increase in body weight occurs. An important symptom of “withdrawal” syndrome is also the desire to smoke. Pharmacokinetics: The pharmacokinetics of nicotine have been extensively studied; it has been found that the method of delivery of the substance to the body has a significant effect on the rate and degree of absorption. The pharmacokinetics of oral mucosal spray were studied in four studies involving 141 subjects. Suctionthe medicinal form of oral mucosal spray assumes that the dose of nicotine is received immediately and, as a result, its absorption from the oral cavity is rapid. The maximum concentration of 5.3 ng / ml is reached within 13 minutes after use of 2 mg of nicotine. 10 minutes after applying the spray at doses of 1 and 2 mg, the area under the concentration-time curve (AUC) exceeded similar values obtained in studies of chewing gum and tablets containing 4 mg of nicotine (0.48 and 0.64 h×ng/ml, compared with 0.33 and 0.33 h×ng/ml). AUC∞ values indicate that the bioavailability of nicotine when applied to the oral mucosa is similar to the bioavailability when using tablets and slightly higher than when using nicotine chewing gum. AUC∞ for the 2 mg spray was 14.0 h × ng / ml, compared to 23.0 h×ng/ml for the 4 mg chewing gum and 26.7 h×ng/ml for the 4 mg tablet. The average steady-state plasma nicotine concentration achieved after the maximum dose (i. e.,2 injections of 1 mg spray every 30 minutes) was approximately 28.8 ng/ml, compared with 23.3 ng/ml for 4 mg chewing gum (1 tablet 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 cheek mucosa. Distributionthe volume of distribution after intravenous nicotine use 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 medications or changes in the content of plasma proteins in a number of diseases, presumably, should not have a significant effect on the pharmacokinetics of nicotine.Biotransformationmetabolism and nicotine elimination do not depend on the dosage form, and therefore the results of the study of nicotine with intravenous use are suitable for their description. The main organ that eliminates nicotine is the liver. However, nicotine is also metabolized in the kidneys and lungs. More than 20 nicotine metabolites are known, all of which appear to be less active than the parent compound. The plasma half-life of the main metabolite of nicotine – cotinine-is 15-20 hours, and its concentration exceeds that of nicotine by 10 times. Elimination The average plasma clearance of nicotine is 70 l / h, with a half-life of 2-3 hours. The main nicotine metabolites detected 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. With a high filtration rate and a urine pH below 5, the amount of nicotine excreted unchanged in the urine can reach 30%. Linearity / Non-linearity With 1,2,3 and 4 taps of the 1 mg/dose spray, only a slight deviation from the linearity of AUC∞ and Cmax was detected. Special patient groups Renal dysfunction Progression of renal failure is accompanied by a decrease in total 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. Impaired liver function The pharmacokinetics of nicotine in patients with mild hepatic impairment (5 points on the Child-Pugh scale) did not change, but in the presence of moderate hepatic impairment (7 points on the Child-Pugh scale) decreased by 40-50%. There are no data on the pharmacokinetics of nicotine in patients with impaired liver function of more than 7 points on the Child-Pugh scale. Elderly patients In healthy elderly patients, there was a slight decrease in total nicotine clearance, which does not require a change in the dose of the drug.

Indications

Nicorette ® spray alleviates and / or prevents cravings and withdrawal symptoms associated with tobacco addiction. It is indicated as a support for smokers who intend to quit smoking or reduce the number of cigarettes they smoke before quitting completely; to help smokers who do not want to smoke or are unable to do so; and as a safer alternative to smoking.

Use during pregnancy and lactation

Pregnancy Smoking during pregnancy is associated with risks such as intrauterine growth retardation, premature birth, or stillbirth. Quitting smoking 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 the fetal respiratory activity and blood circulation. The effect on blood circulation is dose-dependent. Therefore, ideally, quitting smoking during pregnancy should be done without nicotine replacement therapy. However, if a woman is unable (or is expected to) quit smoking without pharmacological support, then nicotine replacement therapy is used, since continuing to smoke carries a greater risk to the fetus compared to nicotine replacement therapy. The best option is to completely stop smoking, but if this is not possible, Nicorette®spray can be used as a safer alternative to smoking during pregnancy. Due to the potential for non-nicotine periods, dosage forms for periodic use are preferred, but patches may be required for significant nausea and / or vomiting. The use of Nicorette® spray by a pregnant woman should only be started after consulting a doctor. Breast-feeding Nicotine penetrates into breast milk in amounts that can have an effect on the child even when the drug is used in therapeutic doses. Therefore, you should refrain from using Nicorette® spray during breastfeeding. If you can’t stop smoking, you should start using the drug only after consulting your doctor. Dosage forms for periodic use minimize the nicotine content in breast milk and allow you to breastfeed at the lowest concentration of nicotine in it. In order to reduce the negative effect of nicotine on the child, the drug should be used immediately after feeding. The periods between the use of the drug and the next feeding should be as long as possible (at least 2 hours are recommended). Smoking increases the risk of infertility in both men and women. In vitro studies have shown that nicotine negatively affects sperm quality in men.

Contraindications

* Hypersensitivity to nicotine or other components of the drug. * Children under 18 years of age.

Side effects

Regardless of the dosage form of the drug containing nicotine used, some symptoms may be due to nicotine withdrawal due to smoking cessation. These include the following symptoms: dysphoria or depressed mood; insomnia; irritability, dissatisfaction or anger; anxiety; difficulty concentrating, restlessness or impatience; decreased heart rate; increased appetite or weight gain; cough; aphthous ulcers; nasopharyngitis. No causal relationship has been established. In addition, those using the oral spray also experienced other symptoms associated with smoking cessation: 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 can cause nicotine-related adverse reactions similar to those observed with other nicotine-containing drugs, these reactions are mainly dose-dependent. Allergic reactions (such as angioedema, urticaria, and anaphylactic shock) may occur in predisposed individuals. Most of the adverse reactions to Nicorette spray were observed in the early phase of treatment and are similar to those for oral medications. In the first few days of treatment, irritation of the oral and pharyngeal mucosa may occur, and hiccups are common. Continuation of treatment leads to adaptation. Daily data collection from study subjects showed that very often occurring adverse events appear in the first 2-3 weeks of spray application and then disappear.

Interaction

There is no clear clinically significant interaction between nicotine replacement therapy and other drugs. However, theoretically, nicotine can enhance the hemodynamic effects of adenosine, i. e., lead to an increase in blood pressure and heart rate, as well as increase the response to pain (chest pain like angina pectoris) provoked by the introduction of adenosine.

How to take, course of use and dosage

For application on the oral mucosa. The patient should do everything possible to permanently stop smoking during treatment with Nicorette®spray. Adults over 18 years of age Nicorette ® spray should be used at a time when there is an overwhelming desire to smoke. After preparing the spray for use (see below for instructions on how to use it for the first time), bring the spray tip as close to your open mouth as possible. Press the dispenser from the top, releasing one dose of the drug into the oral cavity; avoid contact with the spray on the lips. To prevent the substance from entering the respiratory tract, do not inhale when pressing the dispenser. For best results, do not swallow saliva for several seconds after the injection. During the use of the spray, food and liquids are not recommended. If symptoms of overdose occur (see section “Overdose”), the drug should be discontinued immediately. Complete cessation of smokespray Nicorette® should be used in all cases of craving for smoking or to avoid cravings in situations that may provoke it. Smokers who wish or are 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 are completely stopped. If you completely quit smoking, make 1 or 2 injections during the time period when you usually smoked a cigarette, as well as in case of cravings for smoking. If the craving for smoking does not decrease for several minutes after a single injection, a second injection should be performed. If two doses are required, then the subsequent application of the spray may consist of 2 consecutive injections. It is allowed to take no more than 4 metered-dose injections of the spray every hour. Do not inject more than 2 doses of the spray at a time or apply more than 64 doses per day (or 4 doses per hour for 16 hours). Each vial contains at least 150 doses. The average course of application of the spray in the specified dose is 6 weeks. Then you should start reducing the number of injections so that by the end of the 9th week, the number of doses is half of the average number of doses per day received in the first 6 weeks, and during the 12th week-no more than 4 doses per day. When the daily dose is reduced to 2-4 injections, the spray should be discontinued. After the end of therapy, to prevent a return to smoking, patients can use Nicorette® spray if they have an overwhelming desire to smoke. In such situations, you can make 1 injection, and if after a single injection, the craving for smoking does not decrease for several minutes, you should make a second injection.In this case, do not exceed 4 metered-dose injections per day. Regular use of the spray for more than 6 months is usually not recommended, but some patients may need longer therapy to avoid resuming smoking. Reducing the number of cigarettes smoked Smokers who want to reduce the number of cigarettes smoked should apply the spray as needed between smoking episodes in order to increase the time interval between smoking and to reduce smoking as much as possible. As soon as you feel ready, smokers should aim for complete quitting. After quitting smoking, you should follow the recommendations of therapy and gradual dose reduction indicated above for complete quitting. Behavioral therapy and psychological support usually increase the success rate of treatment. Those who have managed to quit smoking, but it is difficult to give up the spray, it is recommended to consult a doctor for medical help. Temporary smoking cessation Spray can be used during periods when it is necessary to refrain from smoking, for example, when you are in places where smoking is prohibited, or in other situations when you need to refrain from smoking. The maximum daily dose for temporary smoking cessation is 64 doses. In combination with a transdermal patch, Nicorette® oral mucosal spray may be used in combination with Nicorette® transdermal patch to quickly relieve cravings for smokers who are severely addicted to nicotine (more than 20 cigarettes a day) or who have an overwhelming craving for smoking, or smokers who have not been able to quit smoking with only one type of nicotine replacement therapy. The patch is applied to an undamaged area of skin immediately after waking up in the morning and removed before going to bed. The patch should be applied to dry, clean, undamaged skin that does not contain hair, such as the thighs, upper limbs or chest. You must change the overlay location every day: do not use the same area for two consecutive days. After applying the patch, wash your hands thoroughly to avoid eye irritation from possible nicotine ingestion. Initial therapy:Treatment should begin with a 25 mg/16 hour patch (stage 1) in combination with a 1 mg/dose spray. Usually,13 doses of spray per day are sufficient. The maximum daily dose of the spray is 32 doses. Patients should completely stop smoking during therapy. Usually, the general course of treatment lasts for 8 weeks. After that, the nicotine dose should be gradually reduced. Discontinuation of combination therapy:There are two ways to cancel combination therapy. Method 1: during the next 2 weeks, it is necessary to switch from the 25 mg/16 hours patch (stage 1) to the 15 mg/16 hours patch (stage 2), and then, during the next 2 weeks, to the 10 mg/16 hours patch (Stage 3), while maintaining, if necessary, the number of doses of Nicorette® spray used, as with Initial therapy. Then gradually reduce the number of spray doses until complete withdrawal during the time that the patient needs, depending on his needs, but not later than 12 months after the start of combination therapy. Method 2: consists in complete cancellation of the patch immediately after the end of the Initial therapy stage. Then gradually reduce the number of doses of Nicorette® spray until complete withdrawal during the time that the patient needs, depending on his needs, but not later than 12 months after the start of combination therapy. Children and adolescents under 18 years of age It is not recommended to use the drug for persons under 18 years of age. There is no experience in treating adolescents under the age of 18 with a spray.

Overdose

When used in accordance with the instructions for use, symptoms of nicotine overdose may occur in patients with low nicotine intake before treatment or when using different sources of nicotine at the same time. Symptomthe minimum lethal dose in acute overdose for an unaccustomed adult is 40-60 mg of nicotine. Overdose causes the same symptoms as acute nicotine poisoning, such as nausea, vomiting, increased salivation, abdominal pain, diarrhea, sweating, headache, dizziness, hearing loss, and severe general weakness. At higher doses, hypotension, weak and irregular pulse, respiratory disorders, impaired consciousness, collapse, and generalized convulsions may occur. Nicotine doses that are well tolerated during treatment by adult smokers can cause symptoms of severe poisoning in young children and even lead to death. Suspected nicotine poisoning in children should be considered as an emergency requiring immediate hospitalization. Treatment You should immediately stop using nicotine and start symptomatic treatment. If necessary, artificial ventilation should be initiated. Taking activated charcoal interferes with the absorption of nicotine in the gastrointestinal tract.

Description

Spray for the oral mucosa dosed from colorless to light yellow transparent or slightly opalescent solution with the smell of mint.

Special instructions

The use of Nicorette ® is associated with a lower risk than smoking. The risk-benefit ratio should be evaluated by a physician of the appropriate specialty in patients with the following conditions::Concomitant cardiovascular diseasesin a stable course of cardiovascular diseases, Nicorette® spray causes less harm than continuing smoking. However, smokers with a recent history of myocardial infarction, unstable or worsening angina, including Prinzmetal angina, severe arrhythmia, recent history of cerebrovascular disease, and / or patients with uncontrolled hypertension should be advised to stop smoking without pharmacological intervention. If such attempts are unsuccessful, the use of Nicorette spray may be considered, but since safety data are limited in this category of patients, such treatment should only be initiated under strict medical supervision. Diabetespatients with diabetes mellitus are advised to monitor their blood glucose levels more carefully after smoking cessation and after starting nicotine replacement therapy, as a decrease in the content of catecholamines, the release of which is induced by nicotine, can affect carbohydrate metabolism. Allergic reactionsthe drug should be used with caution in patients predisposed to angioedema and urticaria. Diseases of the gastrointestinal tract Ingested nicotine can exacerbate the symptoms of esophagitis, gastritis or peptic ulcer, so use drugs for oral nicotine replacement therapy for this pathology should be used with caution. Impaired liver and kidney function in patients with moderate to severe hepatic insufficiency and / or severe renal insufficiency, the drug should be used with caution, since the clearance of nicotine and its metabolites may be reduced, which may increase the risk of adverse events. Nicotine overdoses, which are easily tolerated by adult smokers and adolescent smokers, can cause severe intoxication in children, which can lead to death. It is important not to leave nicotine-containing products unattended, as this may result in their misuse and ingestion by children (see the section “Overdose”). Pheochromocytoma and uncontrolled hyperthyroidism patients with uncontrolled hyperthyroidism and pheochromocytoma should use the drug with caution, since nicotine causes the release of catecholamines. Addiction Developmentmay develop drug addiction, but it is less dangerous to health and more easily overcome than smoking addiction. Smoking cessation: Polycyclic aromatic hydrocarbons found in tobacco smoke induce the metabolism of drugs that are metabolized by the CYP1A2 isoenzyme (and possibly CYP1A1). Stopping smoking can cause your metabolism to slow down and, as a result, increase the concentration of these drugs in your blood. This has potential clinical implications for drugs with a narrow therapeutic index – such as theophylline, tacrine, clozapine, and ropinirole. Excipients Spray Nicorette® contains a small amount of ethanol (alcohol) – less than 10 mg per dose. When using Nicorette® spray, you should be careful not to let the spray get into your eyes. Warnings and precautions for the combination therapy of Nicorette ® spray with transdermal patch are similar to the warnings and precautions for the use of each of the drugs separately. If the medicine has fallen into disrepair or the expiration date has expired, do not throw it into the sewer or on the street! Place the medicine in a plastic bag and put it in the trash can. These measures will help protect the environment!

Form of production

Spray for the oral mucosa dosed

Storage conditions

Store at a temperature not exceeding 25 °C. Keep out of reach of children.

Active ingredient

Nicotine

Dosage Form

Oral spray