1. NICOTINE NASAL SPRAY Nicotrol NS (Pharmacia)
Approved for Rx use in 1996
Aqueous solution of nicotine, 10 ml spray bottle
Each metered dose actuation delivers
50 µL spray
0.5 mg nicotine
Rapidly absorbed across nasal mucosa
 FDA approved: March 1996 (prescription only)
Description of Product
Nicotrol NS (nicotine nasal spray) is an aqueous solution of nicotine available in a metered-spray pump for administration to the nasal mucosa. Each actuation delivers a metered 50 µL spray containing 0.5 mg of nicotine.
Nicotine is rapidly absorbed, and plasma nicotine concentrations attained via the nasal spray are comparable (but lower) to those achieved by smoking. The nasal spray has a faster onset of action (tmax 11–13 minutes) compared to the gum, patch, or inhaler (Schneider et al., 1996).
Clinical Efficacy (Silagy et al., 2002)
The nicotine nasal spray significantly improves long-term abstinence rates compared to placebo. A meta-analysis of 4 studies revealed the following estimated abstinence rates (6-12 months follow-up):
Placebo %
Nicotine nasal spray 23.9 %
The pooled odds ratio of abstinence for the nicotine nasal spray relative to placebo was 2.27 (95% CI, ).
Schneider NG, Lunell E, Olmstead RE, Fagerström KO. Clinical pharmacokinetics of nasal nicotine delivery. A review and comparison to other nicotine systems. Clin Pharmacokinet 1996;31:65–80.
Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2002;4:CD

2. NICOTINE NASAL SPRAY: DOSING & ADMINISTRATION
One dose = 1 mg nicotine
(2 sprays, one 0.5 mg spray in each nostril)
Start with 1–2 doses per hour
Increase prn to maximum dosage of 5 doses per hour or 40 mg (80 sprays; ~½ bottle) daily
For best results, patients should use at least 8 doses daily for the first 6–8 weeks
Termination: gradual tapering over an additional 4–6 weeks
Patients should be instructed to stop smoking completely while using the nicotine nasal spray.
One dose is 1 mg of nicotine—two sprays, one (0.5 mg spray) in each nostril. The recommended starting regimen is one or two doses per hour for 6–8 weeks. This may be increased up to a maximum recommended dose of 40 mg (80 sprays, about half a bottle) per day.
For best results, patients should be encouraged to use at least the recommended minimum of 8 doses per day during the first 6–8 weeks of therapy. Less frequent administration may be less effective.
After 6–8 weeks, the dose should be gradually decreased over an additional 4–6 weeks.

3. NICOTINE NASAL SPRAY: DIRECTIONS for USE
Press in circles on sides of bottle and pull to remove cap
♪ Note to instructor(s): Demonstrate for students, using nicotine nasal spray sample or placebo. Pass around sample for class to see and handle. Students should NOT use this prescription product.
Nicotine nasal spray: Directions for use
Remove cap. Using your thumb and index finger, press in on the circles on sides of bottle. Pull off cap. Note: This child-resistant cap can be very difficult to remove. It is important to press firmly on the circles on the side of the bottle to unlock the cap.

4. NICOTINE NASAL SPRAY: DIRECTIONS for USE (cont’d)
Prime pump (before first use)
Obtain tissue
Hold bottle and press on bottom with thumb
Pump into tissue until fine spray is observed (6–8 times)
Nicotine nasal spray: Directions for use (cont’d)
Before using the nasal spray for the first time, the pump must be primed. This is done by actuating the device into a tissue:
Obtain a tissue or paper towel.
Hold bottle and press firmly on glass bottom of unit with thumb.
Pump into tissue until a fine spray is visible (about 6–8 times). The tissue should be discarded after use.

5. NICOTINE NASAL SPRAY: DIRECTIONS for USE (cont’d)
Blow nose (if not clear)
Tilt head back slightly and insert tip of bottle into nostril as far as comfortable
Breathe through mouth and spray once in each nostril
Do not sniff or inhale while spraying
Nicotine nasal spray: Directions for use (cont’d)
Before using the spray, blow nose if it is not clear.
Tilt head back slightly and insert tip of bottle into nostril as far as is comfortable.
Breathe through mouth and spray once in each nostril.
Do not sniff, swallow, or inhale through the nose while administering the medication because this increases the irritating effects of the spray.

6. NICOTINE NASAL SPRAY: DIRECTIONS for USE (cont’d)
If nose runs, gently sniff to keep nasal spray in nose
Wait 2–3 minutes before blowing nose
Avoid contact with skin, eyes, and mouth
If contact occurs, rinse with water immediately
Nicotine is absorbed through skin and mucous membranes
Nicotine nasal spray: Directions for use (cont’d)
If nose runs, gently sniff to keep nasal spray in nose.
Wait 2–3 minutes before blowing nose to allow the nicotine to be absorbed across the nasal mucosa.
Place cap back on bottle after use.
Avoid contact with skin, eyes, and mouth. If contact occurs, immediately rinse with water because nicotine is readily absorbed across the skin and mucous membranes.

7. NICOTINE NASAL SPRAY: GRADUAL REDUCTION of DOSE
Recommended strategies for discontinuing use of nicotine nasal spray:
Use only ½ dose (1 spray) at a time
Use product less frequently
Skip doses by not medicating every hour
Keep a tally of daily usage and try to meet a steadily reducing target
No tapering strategy has been shown to be optimal in clinical studies. Many patients simply stopped using the spray at their last clinic visit.
Recommended strategies for discontinuing use include the following:
Use only half a dose (one spray) at a time.
Use the spray less frequently:
Skip a dose by not medicating every hour.
Keep a tally of daily usage and try to meet a steadily reducing usage target.

8. NICOTINE NASAL SPRAY: ADDITIONAL PATIENT EDUCATION
What to expect (first week):
Hot peppery feeling in back of throat or nose
Sneezing
Coughing
Watery eyes
Runny nose
Side effects should lessen over a few days— regular use during the first week will help patient adapt to the irritant effects of the spray
What to expect during first week:
Hot peppery feeling in back of throat or nose
Sneezing
Coughing
Watery eyes
Runny nose
These adverse effects should lessen over a few days. Regular use during the first week will help the patient adapt to the irritant effects of the spray. Some investigators have found that with regular use during the first week, tolerance to the irritant effects of the spray develops (Benowitz et al., 1997). However, the irritant effects of the spray should not be minimized because nasal or airway reactions are common (Fiore et al., 2000):
94% of patients report moderate-to-severe irritation in the first 2 days of therapy.
81% still report nasal irritation (mild to moderate) after 3 weeks.
Benowitz NL, Zevin S, Jacob P. Sources of variability in nicotine and cotinine levels with use of nicotine nasal spray, transdermal nicotine and cigarette smoking. Br J Clin Pharmacol 1997;43;259–267.
Fiore MC, Bailey WC, Cohen SJ, et al. Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, 2000.

9. NICOTINE NASAL SPRAY: ADD’L PATIENT EDUCATION (cont’d)
If side effects do not decrease after a week, contact health care provider
Do not use product more than 5 times/hour or 40 times/day (i.e., 80 sprays/day)
If pump is not used for 24 hours, prime pump in tissue 1–2 times
Each bottle contains about 100 doses or about a 1- week supply
If side effects do not lessen after a week, the patient should contact his or her health care provider.
Patients should not use the product more than 5 times an hour or 40 times (i.e., 80 sprays) in 24 hours.
If the pump is not used for 24 hours, it should be primed into a tissue 1–2 times. Avoid excessive priming of the pump to minimize drug wastage.
Each bottle contains approximately 100 doses (200 sprays) or about 1-week supply (about 15 doses per day).

10. NICOTINE NASAL SPRAY: SUMMARY
ADVANTAGES
Patients can easily titrate therapy to rapidly manage withdrawal symptoms.
DISADVANTAGES
Nasal/throat irritation may be bothersome.
Dependence can result.
Patients must wait 5 minutes before driving or operating heavy machinery.
Patients with chronic nasal disorders or severe reactive airway disease should not use the spray.
Advantages of the nicotine nasal spray include the following:
The dose can be easily titrated to rapidly manage withdrawal symptoms.
Disadvantages of the nasal spray include the following:
The initial nasal or throat irritation can be bothersome; it may take up to 3 weeks for the patient to tolerate therapy.
Dependence can result. The nicotine nasal spray has a dependence potential intermediate between tobacco products and other NRT products. About 15–20% of patients continue to use the nicotine nasal spray for longer periods than recommended (6–12 months), and 5% use the spray at higher doses than recommended (Fiore et al., 2000).
Patients should wait 5 minutes before driving or operating heavy machinery (due to the potential for tearing, coughing, and sneezing).
Patients with chronic nasal disorders (e.g., rhinitis, polyps, sinusitis) or patients with severe reactive airway disease should not use the nicotine nasal spray because of the irritant effects of the spray. Asthma exacerbation has been noted in some patients after administration of nicotine nasal spray.
Fiore MC, Bailey WC, Cohen SJ, et al. Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, 2000.