Nicotine

Drug Interactions The extent of absorption and peak plasma concentration is slightly reduced in patients with the common cold/rhinitis. In addition, the time to peak concentration is prolonged. The use of a nasal vasoconstrictor such as xylometazoline in patients with rhinitis will further prolong the time to peak (See PHARMACOKINETICS ). Smoking cessation, with or without nicotine replacement, may alter the pharmacokinetics of certain concomitant medications.

May Require a Decrease in Dose at Cessation of Smoking Possible Mechanism Acetaminophen, caffeine, imipramine, oxazepam, pentazocine, propranolol, or other beta-blockers, theophylline Deinduction of hepatic enzymes on smoking cessation. Insulin Increase of subcutaneous insulin absorption with smoking cessation. Adrenergic antagonists (e.g. prazosin, labetalol) Decrease in circulating catecholamines with smoking cessation. May Require an Increase in Dose at Cessation of Smoking Possible Mechanism Adrenergic agonists (e.g. isoproterenol, phenylephrine) Decrease in circulating catecholamines with smoking cessation.

Pregnancy The harmful effects of cigarette smoking on maternal and fetal health are clearly established. These include low birth weight, an increased risk of spontaneous abortion, and increased perinatal mortality. The specific effects of NICOTROL NS on fetal development are unknown. Therefore pregnant smokers should be encouraged to attempt cessation using educational and behavioral interventions before using pharmacological approaches. Spontaneous abortion during nicotine replacement therapy has been reported; as with smoking, nicotine as a contributing factor cannot be excluded.

NICOTROL NS should be used during pregnancy only if the likelihood of smoking cessation justifies the potential risk of using it by the pregnant patient, who might continue to smoke. Teratogenicity Animal Studies Nicotine was shown to produce skeletal abnormalities in the offspring of mice when toxic doses were given to the dams (25 mg/kg IP or SC). Human Studies Nicotine teratogenicity has not been studied in humans except as a component of cigarette smoke (each cigarette smoked delivers about 1 mg of nicotine). It has not been possible to conclude whether cigarette smoking is teratogenic to humans.

Other Effects Animal Studies A nicotine bolus (up to 2 mg/kg) to pregnant rhesus monkeys caused acidosis, hypercarbia, and hypotension (fetal and maternal concentrations were about 20 times those achieved after smoking one cigarette in 5 minutes). Fetal breathing movements were reduced in the fetal lamb after intravenous injection of 0.25 mg/kg nicotine to the ewe (equivalent to smoking 1 cigarette every 20 seconds for 5 minutes). Uterine blood flow was reduced about 30% after infusion of 0.1 µg/kg/min nicotine to pregnant rhesus monkeys (equivalent to smoking about six cigarettes every minute for 20 minutes).

Human Experience Cigarette smoking during pregnancy is associated with an increased risk of spontaneous abortion, low birth weight infants and perinatal mortality. Nicotine and carbon monoxide are considered the most likely mediators of these outcomes. The effects of cigarette smoking on fetal cardiovascular parameters have been studied near term. Cigarettes increased fetal aortic blood flow and heart rate and decreased uterine blood flow and fetal breathing movements. NICOTROL NS has not been studied in pregnant women.

Use in Nursing Mothers Caution should be exercised when NICOTROL NS is administered to nursing mothers. The safety of NICOTROL NS therapy in nursing infants has not been examined. Nicotine passes freely into breast milk; the milk to plasma ratio averages 2.9. Nicotine is absorbed orally. An infant has the ability to clear nicotine by hepatic first-pass clearance; however, the efficiency of removal is probably lowest at birth. Nicotine concentrations in milk can be expected to be lower with NICOTROL NS when used as recommended than with cigarette smoking, as maternal plasma nicotine concentrations are generally reduced with nicotine replacement.

The risk of exposure of the infant to nicotine from NICOTROL NS therapy should be weighed against the risks associated with the infant's exposure to nicotine from continued smoking by the mother (passive smoke exposure and contamination of breast milk with other components of tobacco smoke) and from NICOTROL NS alone, or in combination with continued smoking.