NICOTROL SIDE EFFECTS

SIDE EFFECTS

Assessment of adverse events in the 1,439 patients (730 on active drug) who participated in controlled clinical trials (including three dose finding studies) is complicated by the occurrence of signs and symptoms of nicotine withdrawal in some patients and nicotine excess in others. The incidence of adverse events is confounded by: (1) the many minor complaints that smokers commonly have, (2) continued smoking by many patients and (3) the local irritation from both the active drug and the placebo.

Local Irritation

NICOTROL (nicotine inhalation system) Inhaler and the placebo were both associated with local irritant side effects. Local irritation in mouth and throat was reported by 40% of patients on active drug as compared to 18% of patients on placebo. Irritant effects were higher in the two pivotal trials with higher doses being 66% on active drug and 42% on placebo. Coughing (32% active versus 12% placebo) and rhinitis (23% active versus 16% placebo) were also higher on active drug. The majority of patients rated these symptoms as mild. The frequency of cough, and mouth and throat irritation declined with continued use of NICOTROL (nicotine inhalation system) Inhaler. Other adverse events that occurred in over 3% of patients on active drug in placebo controlled pivotal trials considered possibly related to the local irritant effects of the NICOTROL (nicotine inhalation system) Inhaler are taste comments, pain in jaw and neck, tooth disorders and sinusitis.

Withdrawal

Symptoms of withdrawal were common in both active and placebo groups. Common withdrawal symptoms seen in over 3% of patients on active drug included: dizziness, anxiety, sleep disorder, depression, withdrawal syndrome, drug dependence, fatigue and myalgia.

Nicotine-Related Adverse Events

The most common nicotine-related adverse event was dyspepsia. This was present in 18% of patients in the active group compared to 9% of patients in the placebo group. Other nicotine related events present in greater than 3% of patients on active drug include nausea, diarrhea, and hiccup.

Smoking Related Adverse Events

Smoking related adverse events present in greater than 3% of patients on active drug include chest discomfort, bronchitis, and hypertension.

Other Adverse Events

Adverse events of unknown relationship to nicotine occurring in greater than 3% of patients on active drug include headache (26% of patients on active and 15% of patients on placebo), influenza-like symptoms, pain, back-pain, allergy, paresthesias, flatulence and fever.

Drug Abuse And Dependence

NICOTROL (nicotine inhalation system) Inhaler is likely to have a low abuse potential based on differences between the product and cigarettes in three characteristics commonly considered important in contributing to abuse: slower absorption, smaller fluctuations in blood levels and lower blood levels of nicotine. NICOTROL Inhaler, like many other nicotine-based smoking cessation therapies, does not produce arterial concentrations similar to cigarettes. However, nicotine withdrawal symptoms were noted in clinical trials at the time of NICOTROL (nicotine inhalation system) Inhaler tapering and after NICOTROL (nicotine inhalation system) Inhaler discontinuation.

Dependence might occur from transference of tobacco-related nicotine dependence to the NICOTROL (nicotine inhalation system) Inhaler. The use of the inhaler beyond 6 months has not been evaluated in clinical trials and is not recommended. To minimize the risk of dependence, patients should be encouraged to withdraw gradually from NICOTROL (nicotine inhalation system) Inhaler therapy after 3 months of usage. If necessary, dose reduction can be achieved by gradual reduction of the dose over a 6 to 12 week period.