The patient should be urged to stop smoking completely when initiating NICOTROL (nicotine inhalation system)
Inhaler therapy (See DOSAGE AND ADMINISTRATION).
Patients should be informed that if they continue to smoke while using the product,
they may experience adverse effects due to peak nicotine levels higher than
those experienced from smoking alone. If there is a clinically significant increase
in cardiovascular or other effects attributable to nicotine, the treatment should
be discontinued (See WARNINGS). Physicians
should anticipate that concomitant medications may need dosage adjustment (See
DRUG INTERACTIONS). Sustained use (beyond
6 months) of NICOTROL (nicotine inhalation system) Inhaler by patients who stop smoking has not been studied
and is not recommended. (See Drug Abuse And Dependence).
NICOTROL (nicotine inhalation system) Inhaler has not been specifically studied in asthma or chronic pulmonary
disease. Nicotine is an airway irritant and might cause bronchospasm. NICOTROL (nicotine inhalation system)
Inhaler should be used with caution in patients with bronchospastic disease.
Other forms of nicotine replacement might be preferable in patients with severe
bronchospastic airway disease.
Cardiovascular or Peripheral Vascular Diseases
The risks of nicotine replacement in patients with cardiovascular and peripheral
vascular diseases should be weighed against the benefits of including nicotine
replacement in a smoking cessation program for them. Specifically, 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 and Raynaud's phenomena) should be evaluated carefully
before nicotine replacement is prescribed. Tachycardia and palpitations have
been reported occasionally with the use of NICOTROL Inhaler as well as with
other nicotine replacement therapies. No serious cardiovascular events were
reported in clinical studies with NICOTROL (nicotine inhalation system) Inhaler, but if such symptoms occur,
its use should be discontinued.
NICOTROL (nicotine inhalation system) Inhaler generally should not be used in patients during the immediate
post-myocardial infarction period, nor in patients with serious arrhythmias,
or with severe or worsening angina.
Renal or Hepatic Insufficiency
The pharmacokinetics of nicotine have not been studied in the elderly or in
patients with renal or hepatic impairment. However, given that nicotine is extensively
metabolized and that its total system clearance is dependent on liver blood
flow, some influence of hepatic impairment on drug kinetics (reduced clearance)
should be anticipated. Only severe renal impairment would be expected to affect
the clearance of nicotine or its metabolites from the circulation (See Pharmacokinetics).
NICOTROL (nicotine inhalation system) Inhaler therapy should be used with caution in patients with hyperthyroidism,
pheochromocytoma or insulin-dependent diabetes, since nicotine causes the release
of catecholamines by the adrenal medulla.
Peptic Ulcer Disease
Nicotine delays healing in peptic ulcer disease; therefore, NICOTROL (nicotine inhalation system) Inhaler
therapy should be used with caution in patients with active peptic ulcers and
only when the benefits of including nicotine replacement in a smoking cessation
program outweigh the risks.
Nicotine therapy constitutes a risk factor for development of malignant hypertension
in patients with accelerated hypertension; therefore, NICOTROL (nicotine inhalation system) Inhaler therapy
should be used with caution in these patients and only when the benefits of
including nicotine replacement in a smoking cessation program outweigh the risks.
Information for Patient
A PATIENT INFORMATION sheet is included
in the package of NICOTROL (nicotine inhalation system) Inhaler cartridges dispensed to the patient. Patients
should be encouraged to read the information sheet carefully and to ask their
physician and pharmacist about the proper use of the product (See DOSAGE
AND ADMINISTRATION). Patients must be advised to keep both used and
unused cartridges out of the reach of children and pets.
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 was mutagenic
in the Ames salmonella test. Nicotine induced reparable 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
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 (nicotine inhalation system) Inhaler therapy 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 (nicotine inhalation system) Inhaler therapy 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
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).
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 (nicotine inhalation system) Inhaler
therapy has not been studied in pregnant women.
Labor and Delivery
NICOTROL (nicotine inhalation system) Inhaler is not recommended for use during labor and delivery. The
effect of nicotine on a mother or the fetus during labor is unknown.
Use in Nursing Mothers
Caution should be exercised when the NICOTROL (nicotine inhalation system) Inhaler is administered to nursing
mothers. The safety of NICOTROL Inhaler 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 (nicotine inhalation system) Inhaler 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 (nicotine inhalation system)
Inhaler 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 the NICOTROL (nicotine inhalation system) Inhaler alone, or in combination with continued smoking.
Safety and effectiveness in pediatric and adolescent patients below the age
of 18 years have not been established for any nicotine replacement product.
However, no specific medical risk is known or expected in nicotine dependent
adolescents. NICOTROL (nicotine inhalation system) Inhaler should be used for the treatment of tobacco dependence
in the older adolescent only if the potential benefit justifies the potential
Clinical studies of NICOTROL (nicotine inhalation system) Inhaler did not include sufficient numbers of
subjects age 65 and over to determine whether they respond differently from
younger subjects. Other reports on clinical experience have not identified differences
between older and younger patients. In general, dosage selection for an elderly
patient should be cautious, usually starting at the low end of the dosage range
reflecting the greater frequency of decreased hepatic, renal, or cardiac function,
and of concomitant disease.