Nicorette, spray 1 mg/dose 150 doses of fruit and mint 2 pcs

Pharmacotherapeutic group: treatment of nicotine addiction.

ATC code: N07BA01.

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 the 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 doses of 1 mg spray reduced the desire to smoke from the first minute after application of the spray and to a significantly greater extent than when using nicotine-containing snorting tablets.

Compared to nicotine gum chewing gum or lozenges, nicotine absorption from oral mucosal spray is faster (see “Pharmacokinetics of oral mucosa. section “Pharmacokinetics”) and, based on the accumulated experience of nicotine replacement therapy, this 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 mode of delivery of the substance into the body has a significant effect on the rate and extent of absorption.

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

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

The maximum concentration of 5.3 ng/mL is reached within 13 min after administration of 2 mg of nicotine. 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 achieved after administration of the maximum dose (i.e. 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 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 rates and urine pH below 5, the amount of nicotine excreted unchanged in the urine can be as high as 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

Active ingredient

Composition

How to take, the dosage

Interaction

Special Instructions

Contraindications

Side effects

Overdose

Pregnancy use