Carcinogenesis, Mutagenesis, Impairment Of Fertility
Nicotine itself does not appear to be a carcinogen in laboratory animals. However, nicotine and its metabolites increased the incidences of tumors in the cheek pouches of hamsters and forestomach of F344 rats, respectively, when given in combination with tumor-initiators. One study, which could not be replicated, suggested that cotinine, the primary metabolite of nicotine, may cause lymphoreticular sarcoma in the large intestine of rats.
Neither nicotine nor cotinine were mutagenic in the Ames salmonella test. Nicotine induced repairable DNA damage in an E. coli test system. Nicotine was shown to be genotoxic in a test system using Chinese hamster ovary cells. In rats and rabbits, implantation can be delayed or inhibited by a reduction in DNA synthesis that appears to be caused by nicotine. Studies have shown a decrease in litter size in rats treated with nicotine during gestation.
Pregnancy Category D (See WARNINGS sections).
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.
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).
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.
The oral LD50 for nicotine is >5 mg/kg in dogs and >24 mg/kg in rodents. Death is due to respiratory paralysis. The oral minimum acute lethal dose for nicotine in adult humans is reported to be 40 to 60 mg (<1 mg/kg). A full bottle of NICOTROL NS contains 100 mg of nicotine.
NICOTROL NS would be expected to be irritating if sprayed in the eyes, mouth or ears. Eye exposure should be treated with copious irrigation with water for 20 minutes. Large oral nicotine ingestions cause vomiting, and the consequences of an overdose will vary; should this occur, patients should contact their physician immediately. For additional emergency information, call your regional poison center.
Signs and Symptoms of Nicotine Toxicity
Signs and symptoms of an overdose of NICOTROL NS would be expected to be the same as those of acute nicotine poisoning including: pallor, cold sweat, nausea, salivation, vomiting, abdominal pain, diarrhea, headache, dizziness, disturbed hearing and vision, tremor, mental confusion, and weakness. Prostration, hypotension, and respiratory failure may ensue with large overdoses. Lethal doses produce convulsions quickly and death follows as a result of peripheral or central respiratory paralysis or, less frequently, cardiac failure.
Overdose from Ingestion
If emesis has not occurred, it should be induced in conscious patients with a suitable emetic followed by an appropriate dose of activated charcoal. In unconscious patients with a secure airway, instill activated charcoal via a nasogastric tube. A saline cathartic or sorbitol may be added to the first dose of activated charcoal.
Management of Nicotine Poisoning
Other supportive measures include diazepam or barbiturates for seizures, atropine for excessive bronchial secretions or diarrhea, respiratory support for respiratory failure, and vigorous fluid support for hypotension and cardiovascular collapse.
DRUG ABUSE AND DEPENDENCE
NICOTROL NS has a dependence potential intermediate between other nicotine-based therapies and cigarettes. This is the result of differences between cigarettes, NICOTROL NS, nicotine gum and nicotine patches in pharmacokinetic and dosing characteristics commonly associated with abuse and dependence. NICOTROL NS is distinct from other nicotine-based smoking cessation therapies in its greater speed of onset, greater capacity for self-titration of dose, and frequent and rapid fluctuations in plasma nicotine concentration.
Dependence on nicotine nasal spray occurred in the clinical trials. Feelings of dependency on the spray were reported by 32% of active spray users and 13% of placebo spray users. Such dependence may represent transference of tobacco-related nicotine dependence to NICOTROL NS.
Fifteen to 20% of patients used the active spray for longer periods than recommended (6 months to 1 year) and 5% used the spray at a higher dose than recommended. Some of these patients experienced anxiety about stopping the spray and some reported craving for the spray rather than for cigarettes.