Nicorette (Nicotine Polacrilex)

NICORETTE®

Hoechst Marion Roussel

Nicotine Polacrilex

Smoking Cessation Aid

Action And Clinical Pharmacology: The active component of Nicorette is nicotine in the form of a natural extract from the tobacco plant.

In small doses, nicotine stimulates autonomic ganglia. Larger doses of the drug result in a blockage of the ganglia. The effects on autonomic ganglia vary according to the degree of tolerance to nicotine. The major cardiovascular effects of nicotine are vasoconstriction, tachycardia and elevated blood pressure resulting from stimulation of sympathetic ganglia and the adrenal medulla as well as from the activation of chemoreceptors of aortic and carotid bodies.

The pharmacokinetics of nicotine favor buccal (rather than gastrointestinal) absorption. Absorption from the mouth is more rapid than from the stomach and the absorbed nicotine avoids immediate and rapid inactivation by the liver (first pass effect).

Nicorette is formulated to provide blood nicotine levels via buccal absorption that will approximate those produced by the inhalation of tobacco smoke. The nicotine in Nicorette is bound to an ion exchange resin and is released only during chewing. The rate of release of nicotine and, as a consequence, nicotine blood levels, are related to the rate and vigor with which Nicorette is chewed. The chewing of a Nicorette piece over a 30-minute period on a one-time-only basis produces peak blood nicotine levels of 5 ng/mL. This peak is reached by about the 25th minute and compares with a peak of 16 to 35 ng/mL reached within 5 minutes from smoking a cigarette of mild to moderate nicotine content. Blood nicotine levels increase and stabilize at 25 ng/mL, following repeated administration at half-hourly intervals. Thus, with Nicorette, it is possible to produce nicotine blood levels of the same order as those produced by smoking cigarettes.

The elimination half-life of nicotine in plasma is 120 minutes. Both nicotine and its metabolites are rapidly eliminated by the kidney. The rate of urinary excretion is dependent on the pH of the urine; excretion diminishes when the urine is alkaline.

Indications And Clinical Uses: Nicorette is designed to provide partial substitution for the nicotine in cigarette smoke and is intended as a temporary aid in cushioning the patient against the psychopharmacological effects of the withdrawal symptoms of smoking cessation.

Assign the appropriate score indicated in each column according to the patient’s answer to the questions (note that not all questions have an answer in Column C). The highest possible score is 11.

If the score is 6 or less, Nicorette 2 mg is recommended for use. If the score is 7 or greater, Nicorette Plus (4 mg) should be used.

Contra-Indications: In patients during the immediate postmyocardial infarction period, patients with life-threatening arrhythmias, and in patients with severe or worsening angina pectoris; in patients with active temporomandibular joint disease; in pregnant women; in breast-feeding mothers, as nicotine is excreted in breast milk, and in nonsmokers and children under 18 years of age (see Warnings).

Manufacturers’ Warnings In Clinical States: The amounts of nicotine that are tolerated by adult smokers can produce symptoms of poisoning and could prove fatal if ingested by children or pets. Patients should be warned to keep Nicorette out of the reach of children and pets.

Simultaneous smoking and chewing of Nicorette should be avoided.

In patients with certain cardiovascular and endocrine diseases, the risks of using nicotine should be carefully weighed against the benefits of including Nicorette in a smoking cessation program. Patients with coronary heart disease (history of myocardial infarction and/or angina pectoris), serious cardiac arrhythmias, or vasospastic diseases (Buerger’s disease, Prinzmetal’s variant angina) should be carefully screened and evaluated before Nicorette is used. Occasional reports of tachyarrhythmias occurring in association with the use of Nicorette have been reported; therefore, if an increase in cardiovascular symptoms occurs with the use of Nicorette it should be discontinued.

As the action of nicotine on the adrenal medulla (release of catecholamines) does not appear to be affected by tolerance, Nicorette should be used with caution in patients with hyperthyroidism, pheochromocytoma or insulin-dependent diabetes.

Cigarette smoking is felt to play a perpetuating role in hypertension and peptic ulcer disease. Therefore, Nicorette should be used in patients with systemic hypertension or peptic ulcer (active or inactive) only when the benefits of including Nicorette in a smoking cessation program outweigh the risks.

Pregnancy: Women of childbearing age should be advised to take adequate precautions to avoid becoming pregnant while using Nicorette. Nicorette therapy should be discontinued if pregnancy is suspected (see Contraindications).

Lactation: Nicotine passes freely into the breast milk. Because of the potential for adverse reactions in nursing infants from nicotine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see Contraindications).

Children: Safety and effectiveness in children and adolescents who smoke has not been evaluated. The use of Nicorette is not recommended in smokers under 18 years of age (see Contraindications).

Precautions: General: Nicorette should be used with caution in patients with oral or pharyngeal inflammation and in patients with a history of esophagitis or peptic ulcer.

The Nicorette dosage form dictates that it be used with caution in patients whose dental problems might be exacerbated by chewing gum. In such patients, prior dental evaluation may be advisable.

Nicorette is sugar-free and has been formulated to minimize stickiness. As with other gums, however, the degree to which Nicorette may stick to dentures, dental caps or partial dentures may depend on the materials from which they are made and other factors such as amount of saliva produced, possible interaction with denture adhesives, denture cleaning compounds, dryness of mouth due to other causes and salivary constituents. Should an excessive degree of adherence to dental work occur, there is the possibility that, as with other gums, Nicorette may damage dental work. If this should occur, the patient should discontinue its use and consult a physician or dentist.

The sustained use of Nicorette by former smokers is not to be encouraged because the chronic consumption of nicotine is addicting. The relative risks of a possible return to smoking should be weighed against the long-term use of Nicorette.

Nicotine was not mutagenic in the Ames Salmonella test. Literature reports indicate that nicotine is neither an initiator nor a tumor-promoter in mice. There is inconclusive evidence to suggest that cotinine, an oxidized metabolite of nicotine, may be carcinogenic in rats. Cotinine was not mutagenic in the Ames Salmonella test.

Studies have shown a decrease of litter size in rats treated with nicotine during the time of fertilization.

Drug Interactions: Physicians should anticipate that the pharmacokinetics of certain concomitant medications may be altered by smoking cessation, with or without nicotine replacement. Therefore, the dosage of certain concomitant medications may require adjustment.

Other reported effects of smoking, which do not involve enzyme induction, include reduced diuretic effects of furosemide and decreased cardiac output, and reduced efect on blood pressure with propranolol, which may also relate to the hormonal effects of nicotine. Smoking cessation may reverse these actions.

Weight Gain: Weight gain is commonly associated with abstention from smoking. The mechanism for this is believed to be a combination of the abstention from the oral habit of cigarette smoking and its replacement by increased intake of food and reduced GI motility due to the absence of the stimulant nicotine. Patients who quit smoking should always be monitored for weight gain.

Liquid Consumption: Patients should be advised not to consume liquids while chewing Nicorette, as the pH of the oral cavity may be reduced and interfere with absorption of nicotine.

Adverse Reactions: Adverse reactions reported in association with the use of Nicorette include both local effects and systemic effects representing the pharmacological action of nicotine.

Local Side Effects: Mechanical effects of gum chewing include traumatic injury to oral mucosa or teeth, jaw ache, and eructation secondary to air swallowing. These side effects may be minimized by modifying chewing technique. Oral mucosa changes such as stomatitis, glossitis, gingivitis, pharyngitis, and aphthous ulcers, in addition to changes in taste perception, can occur during smoking cessation efforts with or without the use of Nicorette.

Systemic Side Effects: Although the type of systemic adverse drug effects seen in clinical trials are similar from one trial to the other, the incidence of individual effects vary considerably from trial to trial. In 2 well-controlled clinical trials (1 performed in the United States and 1 in England) designed to evaluate the safety and efficacy of Nicorette this variation was evident.

Due to its inherent variability, the list of adverse event incidences can be used only as an indication of the relative frequency of adverse events reported in representative clinical trials. It cannot predict expected incidences of these effects during the course of usual medical practice.

In addition to the reported effects in clinical trials, the following events have been reported: Cardiovascular: edema, flushing, hypertension, palpitations, tachyarrhythmias, tachycardia, chest pain; CNS: confusion, convulsions, depression, euphoria, numbness, paresthesia, syncope, tinnitus, weakness; Dermatologic: erythema, itching, rash, urticaria; Gastrointestinal: alteration of liver function tests, constipation, diarrhea; Respiratory: breathing difficulty, cough, hoarseness, sneezing, wheezing; Other: dry mouth, systemic nicotine intoxication.

Reports of myocardial infarction, congestive heart failure, cerebrovascular accident and cardiac arrest, including death have been received. A cause and effect relationship between these reports and the use of Nicorette has not been established.

Rare reports of miscarriage have been received and a relationship to drug therapy as a contributing factor cannot be excluded.

In addition, rare reports of an apparent severe allergic reaction have been received.

Symptoms And Treatment Of Overdose: Overdosage could occur if many pieces were chewed simultaneously or in rapid succession. The risk of poisoning by swallowing the gum is small because absorption in the absence of chewing is slow and incomplete. The consequences of overdosage will most likely be minimized by the early nausea and vomiting known to occur with excessive nicotine intake. Should an overdosage occur the symptoms would be those of acute nicotine poisoning.Symptoms: Mild to moderate poisoning causes nausea, salivation, abdominal pain, vomiting, diarrhea, cold sweat, headache, dizziness, disturbed hearing and vision, mental confusion, and marked weakness. Faintness and prostration will likely ensue and hypotension may occur; breathing is difficult; the pulse may be rapid, weak, and irregular; circulatory collapse may be followed by terminal convulsions. Death may result within a few minutes from respiratory failure caused by paralysis of the respiratory muscles.

The oral minimum acute lethal dose for nicotine in human adults is 40 to 60 mg. In human volunteer studies, ten 4 mg nicotine polacrilex pieces were deliberately swallowed and blood nicotine levels followed over a 24-hour period. At no time did the blood nicotine level exceed 5 ng/mL in that period, a level that is considerably less than that produced by smoking a mild cigarette. An analysis of the Nicorette pieces recovered from the feces of the volunteers showed that only 32% of the original nicotine content had been released.

Treatment: In a conscious, alert patient, prompt evacuation of the stomach should be performed. When evacuation is complete, activated charcoal may be administered by mouth, if necessary.

In comatose patients, a clear airway must be established immediately and ventilatory support may be required. Other therapeutic measures are purely symptomatic and should be conducted according to the attending physician’s assessment of the patient. When the patient’s clinical status stabilizes, consideration may be given to gastric lavage and administration of activated charcoal. Hypotension and/or cardiovascular collapse may occur and should be treated vigorously.

Dosage And Administration: Nicorette should be regarded as an adjunct to, and a pharmaceutical and psychological reinforcer of a program to quit smoking, and not as a long-term nicotine substitute. Nicorette consumption should be terminated once the patient has successfully broken the smoking habit. This can take up to 6 months in some smokers. It is strongly recommended that Nicorette pieces be carried by the patient for up to 3 months following cigarette abstention in case a sudden overpowering urge to smoke occurs.

For optimum results, the initial treatment should be based on the patient’s level of nicotine dependence.

If the score is 6 or less, Nicorette 2 mg is recommended for use. If the score is 7 or greater, Nicorette Plus (4 mg) should be used.

Most patients require approximately 10 pieces of Nicorette 2 mg/day during the first month of treatment. Patients should be instructed not to exceed 20 pieces of Nicorette 2 mg/day . One piece should be chewed for up to half an hour when the desire to smoke arises.

Availability And Storage: Each off-white, mint- or fruit-flavored square, buffered to maintain a pH of 8.5 in the mouth, contains: nicotine 2 mg. Nonmedicinal ingredients: gum, menthol, magnesium oxide, peppermint oil, sodium bicarbonate, sodium carbonate and xylitol. Blister packs of 30 pieces and 105 pieces. Store at room temperature, between 15 and 30°C. Protect from light.

NICORETTE® Hoechst Marion Roussel Nicotine Polacrilex Smoking Cessation Aid

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