1. TRANSDERMAL NICOTINE PATCH
Approved for Rx use in 1991; OTC in 1996
Current products include
Nicoderm CQ PatchOTC (GlaxoSmithKline)
Nicotrol PatchOTC (Pharmacia)
Generic ProductsRx, OTC
FDA approved: 1991
Available OTC: 1996
Description of Product
Transdermal nicotine delivery systems consist of an impermeable surface layer, a nicotine reservoir, an adhesive layer and a removable protective liner. The technology for delivery of nicotine across the skin varies by manufacturer. Nicoderm, manufactured by Alza, utilizes a rate-controlling membrane. Generic patches (previously marketed as ProStep), manufactured by Elan, employ nicotine-containing hydrogel-matrix concentration gradient technology. The Nicotrol and generic patches (previously marketed as Habitrol) utilize drug-dispersion-type systems whereby release of nicotine is controlled by diffusion of the drug across an adhesive layer (Gore & Chien, 1998).
Clinical Efficacy (Silagy et al., 2002)
The transdermal nicotine patch significantly improves long-term abstinence rates compared to placebo. A meta-analysis of 34 studies revealed the following estimated abstinence rates (6-12 months follow-up):
Placebo %
Nicotine patch 14.4 %
The pooled odds ratio of abstinence for the transdermal nicotine patch relative to placebo was 1.74 (95% CI, ).
Gore AV, Chien YW. The nicotine transdermal system. Clin Dermatol 1998;16:599–615.
Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2002;4:CD

2. TRANSDERMAL NICOTINE PATCH
Nicotine is well absorbed across the skin
Delivery to systemic circulation avoids hepatic first-pass metabolism
Plasma nicotine levels are lower, fluctuate less than with smoking
Relieve nicotine withdrawal
Low potential for dependence (compared to rapid delivery systems)
The nicotine in the patch is well absorbed across the skin. The delivery of nicotine to the systemic circulation avoids hepatic first-pass metabolism. Plasma nicotine concentrations from the patch are lower and fluctuate less than those achieved with tobacco products. Plasma nicotine levels obtained via transdermal delivery are approximately 50% lower than those achieved with cigarette smoking. Lower levels of nicotine still alleviate the symptoms of withdrawal but are far less likely to lead to dependence when compared to tobacco or other forms of NRT (Gore & Chien, 1998).
Gore AV, Chien YW. The nicotine transdermal system. Clin Dermatol 1998;16:599–615.

3. TRANSDERMAL NICOTINE PATCH: PREPARATION COMPARISON
Product
Nicotrol
Nicoderm CQ
Generics
Nicotine delivery
16 hours
24 hours
Availability
5 mg patch
10 mg patch
15 mg patch
7 mg patch
14 mg patch
21 mg patch
11 mg patch
22 mg patch
Products Available
Nicotrol PatchOTC (Pharmacia; formerly distributed by McNeil)
Switched to OTC status: July 1996
Availability: 15 mg, 10mg, 5mg (16-hour nicotine delivery system)
Note: Prior to 2002, this product was available only as a 15 mg patch for use over six weeks, without taper. Current product labeling recommends a gradual dosage reduction over 10 weeks.
Nicoderm CQ PatchOTC (GlaxoSmithKline; manufactured by Alza)
Switched to OTC status: August 1996
Availability: 7 mg, 14 mg, 21 mg (24-hour nicotine delivery system); also available in a clear formulation
Generic nicotine patchRx,OTC (formerly Habitrol Transdermal System)
Manufacturers:
OTC product (Novartis Consumer Health)
Rx product (Schein Pharmaceuticals)
Available OTC: November 1999
Availability: 7 mg, 14 mg, 21 mg (24-hour nicotine delivery system)
Note: Novartis manufactures the OTC product but has sold the rights to a private label company that is responsible for marketing and distributing the product for various retail pharmacies (e.g. CVS, Duane Reade, Kroger, Longs, Rite-Aid, Sav-on Osco, Target, Walgreens, Walmart “Equate” label). The product is labeled as Nicotine Transdermal System Step 1, Step 2, and Step 3.
Generic nicotine patchOTC (previously ProStep [Lederle])
Switched to OTC status: December 1998
Availability: 11 mg, 22 mg (24-hour nicotine delivery system)
Note: This product is manufactured by Elan Pharmaceuticals and distributed by Perrigo Company to drug stores, grocery stores, and discount stores under private label.

4. TRANSDERMAL NICOTINE PATCH: DOSING
Product
Light Smoker
Heavy Smoker
Nicotrol
10 cigarettes/day
Not indicated
>10 cigarettes/day
Step 1 (15 mg x 6 weeks)
Step 2 (10 mg x 2 weeks)
Step 3 (5 mg x 2 weeks)
Nicoderm CQ
Step 2 (14 mg x 6 weeks)
Step 3 (7 mg x 2 weeks)
Step 1 (21 mg x 6 weeks)
Step 2 (14 mg x 2 weeks)
Generic
(formerly Habitrol)
Step 1 (21 mg x 4 weeks)
(formerly ProStep)
15 cigarettes/day
11 mg x 6 weeks
>15 cigarettes/day
22 mg x 6 weeks
The dosing schedules for the nicotine patches vary. When recommending a product and a dosing schedule for a patient, it is important to ask a few questions. Determine how many cigarettes the patient smokes per day and if he or she has strong morning cigarette cravings. In general, heavy smokers will require higher doses for a longer duration of therapy. Patients with sleep disturbances (insomnia) may tolerate the 16-hour patch better. Some data suggest that patients with strong morning cigarette cravings may have more success with a 24-hour patch (Shiffman et al., 2000).
Patients may need to switch patch strengths during the first 2 weeks of therapy to determine correct strength. For patients experiencing withdrawal symptoms or cigarette cravings, increase to a higher dose. Patients experiencing side effects (e.g., dizziness, perspiration, nausea, vomiting, diarrhea, headache, abdominal pain) should use the next lower dose.
♪ Note to instructor(s): Some students may ask about use of higher than recommended doses of transdermal nicotine for heavy smokers. High-dose transdermal nicotine (44 mg/day) appears to be safe (Dale et al., 1995; Fredrickson et al., 1995). However, trials evaluating higher doses of NRT have yielded conflicting results. Some studies suggest higher doses of NRT may be more effective in heavy smokers (Dale et al., 1995; Tonnesen et al., 1999), whereas others have demonstrated slight but not statistically significant improvements in cessation rates (Jorenby et al., 1995; Hughes et al., 1999). Thus, despite the small number of trials that have examined high-dose NRT therapy, the results appear promising and this approach may be appropriate for patients who have been unable to quit using conventional doses of transdermal NRT.
Dale LC, Hurt RD, Offord KP, Lawson GM. High-dose nicotine patch therapy; percentage of replacement and smoking cessation. JAMA 1995;274:1353–1358.
Fredrickson PA, Hurt RD, Lee GM, et al. Safety and tolerability of high dose transdermal nicotine therapy for heavy smokers. Psychopharmacology 1995;122:215–222.
Hughes JR, Lesmes GR, Hatsukami DK, et al. Are higher doses of nicotine replacement more effective for smoking cessation? Nicotine & Tobacco Research 1999;1:169–174.
Jorenby D, Smith SS, Fiore MC, et al. Varying nicotine patch dose and type of smoking cessation counseling. JAMA 1995;274:1347–1352.
Shiffman S, Elash CA, Paton SM, et al. Comparative efficacy of 24-hour and 16-hour transdermal nicotine patches for relief of morning craving. Addiction 2000;95(8):
Tonnesen P, Paoletti P, Gustavsson G, et al. Higher dosage nicotine patches increase one-year smoking cessation rates: Results from the European CEASE trial. Collaborative European Anti-Smoking Evaluation. European Respiratory Society. Eur Respir J 1999;13:238–246.

5. TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE
Choose an area of skin on the upper body or the upper outer part of the arm
Make sure the skin is clean, dry, and hairless
Hair will interfere with application of the patch
Do not shave; this may irritate the skin
♪ Note to instructor(s): Instruct students to remove the sample nicotine patch from the foil pouch and follow along with the directions for use. This is an optional exercise. Current tobacco users, former tobacco users, and women who are pregnant or breastfeeding should not participate in exercises with active drug formulations. Alternatively, distribute samples of the nicotine patch for students to handle but not apply.
♪ Note to instructor(s): Before distributing the patches during class, it is helpful to make a horizontal cut across the upper corner of the patch with scissors or clippers. This will allow the students to quickly open the foil pouch during class. If this step is not performed before class, participants may be unable to or have a extremely difficult time opening the child-resistant foil pouch.
Transdermal nicotine patch: Directions for use
Choose an area of skin on the upper body or the upper outer part of the arm.
To ensure that the patch will adhere well, make sure the skin is nonhairy, clean (not oily), dry, and free of creams, lotions, oils or powder.
Hair will interfere with the application of the patch.
Do not shave the area because this may cause skin irritation.

6. TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE (cont’d)
Do not apply patch to skin that is inflamed, burned, or irritated in any way (these conditions may alter nicotine absorption)
Apply patch to a different area each day
The same area should not be used again for at least 1 week
Transdermal nicotine patch: Directions for use (cont’d)
Do not apply the patch to skin that is inflamed, burned, broken out, or irritated in any way, because these conditions may alter the amount of drug absorbed.
The patch should be applied to a different area each day.
To minimize the potential for local skin reactions, the same area should not be used again for at least 1 week.

7. TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE (cont’d)
Remove patch from protective pouch
Transdermal nicotine patch: Directions for use (cont’d)
Remove patch from protective pouch (save pouch for later disposal of used patch).
♪ Note to instructor(s): The appearance of the transdermal patch will be slightly different for each manufacturer.
♪ Note to instructor(s): Scissors or clippers will be necessary for this step. It is recommended that the instructor perform this step before class to save time. If this is not done before class, instruct the student to use care while cutting the foil pouch so as not to damage the transdermal patch.

8. TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE (cont’d)
Peel off half of the backing from the patch
Transdermal nicotine patch: Directions for use (cont’d)
Remove half of the protective liner from the patch. Try not to touch the exposed adhesive (i.e., the sticky side) because nicotine on hands can get into the eyes or nose and cause stinging or redness.

9. TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE (cont’d)
Apply adhesive side of patch to the skin
Peel off remaining protective covering
Press firmly with palm of hand for 10 seconds
Make sure the patch sticks well to skin, especially around the edges
Transdermal nicotine patch: Directions for use (cont’d)
Immediately apply the sticky side of the patch to the skin.
Peel off remaining half of protective covering.
Press the patch firmly on the skin with the palm of the hand for 10 seconds.
Make sure the patch sticks well to the skin, especially around the edges. This is necessary to ensure a good seal.

10. TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE (cont’d)
Wash hands (nicotine on hands can get into eyes or nose and cause stinging or redness)
Do not leave the patch on skin for more than 16 hours (Nicotrol) or 24 hours (Nicoderm, generic patches—doing so may lead to skin irritation
Adhesive remaining on skin may be removed with rubbing alcohol or acetone
Dispose of a used patch by folding onto itself, completely covering the adhesive area
Transdermal nicotine patch: Directions for use (cont’d)
Wash hands after patch application as nicotine on hands could get into the eyes or nose and cause stinging or redness.
After 16 or 24 hours (depending on formulation and dosing regimen), remove old patch.
The patch should not be left on the skin for more than 16 hours (Nicotrol) or 24 hours (Nicoderm, generic patches) because this may lead to skin irritation.
Any adhesive remaining on the skin may be removed with rubbing alcohol or acetone
Dispose of a used patch by folding onto itself, completely covering the adhesive area.

11. TRANSDERMAL NICOTINE PATCH: ADDITIONAL PATIENT EDUCATION
Water will not harm the nicotine patch if it is applied correctly; patients may bathe, swim, shower, or exercise while wearing the patch
Do not cut patches to adjust dose
Nicotine will evaporate rapidly
Patch will be rendered useless
Keep new and used patches out of the reach of children and pets
Water will not harm the nicotine patch if it is applied correctly. Patients may bathe, swim, shower, or exercise while wearing the patch.
Due to the high cost of nicotine patches, patients will often try to economize by cutting patches in half to save money. It is important to tell patients that they should not cut patches to adjust the dose. The nicotine will evaporate rapidly from the edges of a cut patch, rendering the product useless.
Keep new and used patches out of the reach of children and pets.

12. TRANSDERMAL NICOTINE PATCH: ADD’L PATIENT EDUCATION (cont’d)
Side effects to expect in first hour:
Mild itching
Burning
Tingling
After patch removal, the skin may appear red for the next 24 hours
If skin stays red more than 4 days or swells, or if a rash appears, contact health care provider; do not put on a new patch
Shortly after applying the nicotine patch, patients may experience the following:
Mild itching
Burning
Tingling
This is normal and should resolve within an hour.
After removal, the skin under the patch may appear red for the next 24 hours.
If a skin rash develops after using a nicotine patch, or if the skin under the patch becomes swollen or very red, the patient should contact a health care provider. The patient should not apply a new patch.

13. TRANSDERMAL NICOTINE PATCH: ADD’L PATIENT EDUCATION (cont’d)
Additional possible side effects:
Vivid dreams or sleep disturbances
Headache
Local skin reactions (erythema, burning, pruritus)
Usually caused by adhesive
Up to 50% of patients experience this reaction
Incidence may be higher with 24-hour products
Less than 5% of patients discontinue therapy
Avoid use in patients with dermatologic conditions (e.g., psoriasis, eczema, atopic dermatitis)
Additional possible side effects:
Vivid dreams or sleep disturbances
More common with 24 hour formulations. Remove patch at bedtime if side effect becomes troublesome.
Headache
Local skin reactions (erythema, burning, pruritus)
Usually caused by irritation resulting from skin occlusion or a reaction to the adhesives.
Up to 50% of patients experience this reaction.
Incidence may be higher with 24 hour products.
Less than 5% discontinue therapy:
Make certain patient is rotating patch application sites.
Consider different brand of patch. Each manufacturer uses different adhesives.
Consider treating skin reactions with OTC hydrocortisone cream (1%) or oral antihistamines.
Patients with dermatologic conditions (e.g., psoriasis, eczema, atopic dermatitis) are more likely to experience skin irritation and should not use the nicotine patch.

14. TRANSDERMAL NICOTINE PATCH: SUMMARY
ADVANTAGES
The patch provides consistent nicotine levels.
The patch is easy to use and conceal.
Fewer compliance issues are associated with the patch.
DISADVANTAGES
Patients cannot titrate the dose.
Allergic reactions to adhesive may occur.
16-hr patch may lead to morning nicotine cravings.
Patients with dermatologic conditions should not use the patch.
Advantages of the nicotine patch include the following:
Steady-state nicotine levels are achieved throughout the day.
The patch is easy to use and conceal.
Fewer compliance issues are associated with the patch.
Disadvantages of the patch include the following:
Patients cannot titrate the dose.
Allergic reactions to the adhesive may occur.
The 16-hour patch may result in morning cravings for nicotine.
Patients with underlying dermatologic conditions (e.g., psoriasis, eczema, atopic dermatitis) should not use the patch because they are more likely to experience skin irritation.