Currently Enrolling Trials
Nicotrol NS (nicotine nasal spray) is an aqueous solution of nicotine intended for administration as a metered spray to the nasal mucosa.
Nicotrol NS is specifically indicated as an aid to smoking cessation for the relief of nicotine withdrawal symptoms. Nicotrol NS therapy should be used as a part of a comprehensive behavioral smoking cessation program.
Nicotrol NS is supplied as a nasal spray. The dose of Nicotrol NS , should be individualized on the basis of each patient's nicotine dependence and the occurrence of symptoms of nicotine excess. Each actuation of Nicotrol NS delivers a metered 50 microliter spray containing 0.5 mg of nicotine. One dose is 1 mg of nicotine (2 sprays, one in each nostril). Patients should be started with 1 or 2 doses per hour, which may be increased up to a maximum recommended dose of 40 mg (80 sprays, somewhat less than 1/2 bottle) per day. For best results, patients should be encouraged to use at least the recommended minimum of 8 doses per day, as less is unlikely to be effective.
Mechanism of Action
Nicotine, the chief alkaloid in tobacco products, binds stereo-selectively to nicotiniccholinergic 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 is exerted mainly in the cortex via the locus ceruleus and a reward effect 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, norepinephrine, dopamine, serotonin, vasopressin, beta-endorphin, growth hormone, and ACTH.
Assessment of adverse effects is complicated by the occurrence of signs and symptoms of nicotine withdrawal in some patients and nicotine excess in others.
Common complaints experienced by the smokers in the study (users of both active and placebo spray) include: chest tightness, dyspepsia, paraesthesia (tingling) in limbs, constipation, and stomatitis.
Tobacco Withdrawal Symptoms: Symptoms of tobacco withdrawal were frequent in users of both active and placebo sprays. Common withdrawal symptoms seen in over 5% of patients included: anxiety, irritability, restlessness, cravings, dizziness, impaired concentration, weight increase, emotional lability, somnolence and fatigue, increased sweating, and insomnia.
Clinical Trial Results
The efficacy of Nicotrol NS therapy as an aid to smoking cessation was demonstrated in three single-center, placebo-controlled, double-blind trials with a total of 730 patients. One of the trials used Nicotrol NS with individual counseling while the other two used group support. Patients with severe or symptomatic cardiovascular disease, hypertension, asthma, diabetes or severe allergy were not included in the studies. The amount of Nicotrol NS used was left to the discretion of each patient, with a minimum dose of 8 mg/day and a maximum dose of 40 mg/day. In all three studies, the recommended duration of treatment was 3 months; however in two of these trials, 241 patients were permitted to continue to use the product for up to 1 year, if they wished. Among the 64 patients abstinent from cigarettes at the end of a year, 23 (36%) were still using the spray, and probable dependence on the spray was seen in several patients. Quitting was defined as total abstinence from smoking for at least 4 weeks. The “quit rates” are the percentage of all persons initially enrolled who continuously abstained after week 2 or 4. In all three studies, Nicotrol NS was more effective than placebo at 6 weeks, 3 months, 6 months, and 1 year. The two studies where Nicotrol NS could be used for more than 6 months did not have a better outcome at 1 year than the study in which Nicotrol NS was discontinued at 6 months.