NICOTINE REPLACEMENT THERAPY IN

SMOKING CESSATION

SCOTT SLEDGE, MD

FEBRUARY 2, 1999

CIGARETTE SMOKING RELATED MORTALITY

• Cigarette Smoking is the single most preventable cause of premature death in the United States.

• >400,000 deaths in the U.S. / year

• > 10 million deaths attributed directly to smoking since 1964; about 2 million from lung CA

MMWR. Nov ‘98

SMOKING ATTRIBUTABLE HEALTH CARE COSTS:

• In 1993, estimated at $50 billion– $27 billion for hospitals

– $15.5 billion for physician expenditures

– $4.9 billion for nursing homes

– $1.8 billion for prescription drugs

– $900 million for home health care MMWR ‘94

IN 1995...

• 25% of adults in U.S. - current smokers

(47 million adults)

• Of these, 32 million wanted to quit (68%)

• And 17 million (45%) had stopped for > one day

MMWR. Dec ‘97

INCIDENCE of SMOKING: NORTH CAROLINA

• 26% of those > 18 years smoke; compared with 23% for all states

• Gender– 30% of males smoke

– 22% of females smoke

CAN PHYSICIANS HELP SOLVE THIS PROBLEM?

• >70% smokers see MD yearly

• ~70% report wanting to quit

• Physician’s advice -- an important motivator

UNFORTUNATELY...

• 50% smokers-- report being asked about smoking or urged to quit

• Fewer report specific advice on quitting

OBSTACLES TO HELPING PATIENTS QUIT SMOKING

• Time constraints

• A perceived lack of skills to be effective

• Frustration due to low success rates

• Belief that smoking cessation is not an important part of professional responsibility

METHODS TO HELP PATIENTS STOP SMOKING:

• HEALTH CARE PROVIDER ADVICE AND FOLLOWUP

• BEHAVIOR MODIFICATION PROGRAMS

• PHARMACOTHERAPY

• ALTERNATIVE THERAPIES (e.g.. ACCUPUNCTURE, HYPNOSIS)

NICOTINE REPLACEMENT THERAPY

• NICOTINE POLACRILEX “NICOTINE GUM”

• NICOTINE PATCH

• NICOTINE NASAL SPRAY

• NICOTINE INHALER

NICOTINE GUM

NICOTINE GUM

• Available in two strengths

• 2 mg form was approved by the FDA in 1984 and 4 mg form approved in 1992

• Both strengths became over the counter in April 1996

EFFICACY of NICOTINE GUM

• Hjalmarson, et al published RCT on effectiveness of 2 mg nicotine gum

• 205 subjects in smoking cessation clinic randomized to nicotine gum or placebo gum

• At one year, 29% of nicotine gum subjects were abstinent vs. 16% of the placebo group --JAMA ‘84

HIGHER DOSING OF NICOTINE GUM

• In 1995, Herrera N, et al showed “highly dependent” smokers need 4 mg gum

• Highly dependent smokers given 4 mg gum or 2 mg gum. *

• Lowly dependent smokers given 2 mg gum or placebo.*

*(Randomized at “quit phase”)

-Chest ‘95

AT 2 YEAR FOLLOW-UP...

• Highly dependent group--

Abstinence rates :

– 34% for 4 mg and 16% for 2 mg

• Lowly dependent group--

Abstinence rates:

– 39% for 2 mg and 17 % for placebo

--Chest ‘95

WHAT ABOUT PATIENTS IN A PRIMARY CARE SETTING?• Hughes, et al published RCT performed at

2 family practice clinics in suburbs

• 315 smokers assigned 2 mg gum or placebo

• Patients shown 13 minute video on gum and instructed to use prn for craving

• Brief follow-up visit at 1 to 2 weeks

-JAMA ‘89

RESULTS AT ONE YEAR:

• 10% of active gum users passed observer and biochemical verification

• 7% of placebo users passed observer and biochemical verification

• NOT STATISTICALLY SIGNIFICANT

• *31 dropouts and 24 noncontacts counted as smokers

PROPER USE OF NICOTINE GUM

• NICOTINE GUM IS NOT CHEWED LIKE OTHER CHEWING GUM– COMPRESS with teeth until peppery– “PARK” between the cheek and gum.– REPEAT every minute or so for ~ 30 minutes

per dose

EATING AND DRINKING:

• Avoid 15 minutes prior to and during use of the gum

• Acidic beverages (e.g. coffee, fruit juices) reduce nicotine absorption

DOSING:

• Specify a fixed dosing schedule.

• > one pack per day begin on 4 mg dose.

• At least one piece per hour for 1 to 3 mos.

• MAX = 30 pieces of 2 mg gum/day

= 20 pieces of 4 mg gum/day

WATCH OUT...• It is possible to become addicted to

nicotine gum.

• Not recommended for more than 6 months.

• Gradual tapering IS recommended

ADVERSE EFFECTS

• THROAT BURNING

• DIZZINESS

• NAUSEA

• HICCUPS

• ABDOMINAL PAIN

• JAW ACHE

NICOTINE PATCH

FIVE FDA-APPROVED TRANSDERMAL PATCHES:

Habitrol Nicoderm Nicotrol

Nicoderm-CQ Prostep

• Available in US in December 1991

• Nicoderm CQ and Nicotrol-- available over the counter

• Nicotrol-- delivers nicotine for 16 hours

EFFICACY

• Fiore et al performed meta-analysis of RCTS of four weeks or longer that:– Had biochemical confirmation

– Subjects not selected on basis of specific diseases (e.g.. coronary artery disease).

- JAMA ‘94

META-ANALYSIS:

• Seventeen studies with total 5098 pts

• At 6 months...abstinence rates for active patch 22% vs 9% for placebo

• Included primary care settings and behavior modification programs.

• Combined ODDS RATIOS = 3.0 (6 mo.)

ANALYSIS ALSO FOUND...

• 16 hour and 24 hour patch--equally efficacious.

• Intensive counseling enhanced clinical success, but patch was effective with minimal adjuvant therapy.

• Extending patch treatment > 8 weeks did not increase efficacy.

• Weaning patients did not have an added beneficial effect in cessation rate.

REGARDING DOSING...

• Available patches = 5 to 22 mg/day of nicotine

• Pack per day smoker receives 25 to 40 mg of nicotine/day from cigarettes

Will higher patch doses be more effective in heavier smokers?

In 1995, Dale et al looked at percentage of nicotine replacement and

smoking cessation

• Subjects randomized to 11-, 22-, or 44- mg doses of patch

• At one year...higher abstinence rates with the 44 mg patch were not found.

• BUT 44 mg patch was safe & superior in relieving withdrawal symptoms.

-JAMA 1995

Current Dosage Recommendations:

• > 10 cigarettes per day--use highest available dose

• 10 cigarettes per day or fewer -- start with the mid-range dose

• Fewer than 5 cigarettes per day probably do not need nicotine replacement.

PROPER USE OF THE NICOTINE PATCH

• On the quit date-- apply to a hairless portion of skin after cleansing with soap and water.

• Apply new patch daily-- preferably at new site

• Use > 8 weeks is not proven beneficial, and weaning may be unnecessary.

ADVERSE EFFECTS:

• SKIN IRRITATION

• ITCHING

• NAUSEA

• INSOMNIA

• ABNORMAL DREAMS

NICOTINE NASAL SPRAY

NICOTINE NASAL SPRAY

• Available in the United States in 1996 as a prescription product

• Designed for rapid delivery of nicotine--mimicking the effects of cigarette smoking

EFFICACY

• Sutherland, et al. published RCT examining nicotine nasal spray in a smoking cessation clinic

• 227 smokers received 4 weeks of supportive group therapy + active nicotine nasal spray or placebo

--Lancet Aug. 92

Main end point was biochemically validated complete abstinence from

smoking

• At one year...26% of active group abstinent vs. 10% assigned placebo

• Greatest advantage in the heaviest smokers

• Withdrawal symptoms, craving for cigarettes, and weight gain were all reduced by active spray

WARNING!

• Blood nicotine levels achieved are higher and faster than with the patch or gum

• Approximately 43% of smokers started on the nicotine nasal spray will continue using for 12 months after smoking cessation

PROPER USE

• Instruct the patient on how to “prime the pump” to ready it for use

• After priming, patient tilts head back and sprays once in each nostril

• Do not intentionally inhale or sniff while spraying! (absorption is in the nasal mucosa not the sinuses)

DOSING...

• Each spray delivers 0.5 mg of nicotine (each dose = 1 mg)

• Recommend 1 to 2 doses per hour with a maximum of 5 doses per hour (40 mg per day max.)

• Treat for 4 to 6 weeks and then wean over an additional 4 to 6 weeks

SIDE EFFECTS

• Almost all patients report nasal and throat irritation, sneezing, and watery eyes during week 1

• Symptoms should diminish over the first week of use

• If not improving after week 1, consider diseontinuing nasal spray

NICOTINE INHALER

NICOTINE ORAL INHALER

• Introduced in mid-1998

• Prescription product

• Intended to mimic the smoker’s hand-to-mouth ritual

EFFICACY

• A one year RCT conducted by Tonnesen et al.

• 286 volunteers recruited through a newspaper ad (each smoked 10+ cigarettes/day)

• Subjects randomly assigned to nicotine inhaler or placebo inhaler

--JAMA, March 1993

RESULTS...

• At one year, smoking abstinence rate in the active inhaler group was 15% vs. 5% in the placebo inhaler group

• Minimal levels of advice and support were used in this study

• Treatment was well tolerated and no serious adverse effects were reported

NICOTINE DELIVERY

• Each cartridge delivers 4 mg of nicotine

• About 80 puffs on the inhaler equal nicotine from 8 to 12 puffs on a cigarette

• Nicotine absorbed in buccal and pharyngeal mucosa -- not the bronchi

• Nicotine plasma concentrations rise more quickly than with gum (slower nasal spray)

DOSING AND USE

• Use 6 to 16 cartridges per day

• Frequent, continuous puffing over 20 minutes yields the best effects

• Recommended duration of treatment is 3 months (max. 6 months)

SIDE EFFECTS

• Most common are irritation in the mouth and throat and coughing

• Generally improve with use

• In the Tonneson study, no subjects discontinued the inhaler secondary to side effects

SMOKING CESSATION CLINICAL PRACTICE

GUIDELINES

• Published by the Agency for Health Care Policy and Research (AHCPR) in 1996

• Approximately 3000 research articles and abstracts were reviewed for appropriateness

Inclusion criteria for each article:

• Concerned a randomized controlled trial

• Follow-up end point at least 5 months after the quit date

• Published in English in a peer-reviewed journal between 1975 and 1994

Panel Recommendations Address Three Audiences:

• Primary Care Clinicians

• Smoking Cessation Specialists

• Health Care administrators, insurers, and purchasers

STRATEGIES FOR IMPLEMENTATION

• Step1. ASK - Systematically Identify All Tobacco Users at Every Visit

• Step2. ADVISE - Strongly Urge All Smokers to Quit

• Step 3. Identify Smokers Willing to Make a Quit Attempt

• Step 4. ASSIST - Aid the Patient in Quitting

• Step 5. ARRANGE - Schedule Follow-up Contact

In Regard to Nicotine Replacement...• Identified as the only pharmacologic

therapy proven effective

• Panel recommended that all patients planning a quit attempt be offered NRT (unless contraindicated)

Panel opinion was that the patch was preferable to gum in routine

clinical use.

• Fewer compliance problems

• Less clinician time and effort to train patients in proper use

QUESTIONS YET TO BE ANSWERED

• Which form of nicotine replacement is the most effective?

• How effective are nicotine replacement combinations? (e.g. patch and inhaler)

CONCLUSIONS

• Nicotine Replacement Therapy is effective in helping patients to quit smoking

• At this time, patient preference may be the best guide in choosing a form of nicotine replacement

• Success rates for smoking cessation remain low even with the best interventions

AN UNSUCCESSFUL QUIT ATTEMPT SHOULD BE SEEN AS A LEARNING

OPPORTUNITY FOR THE NEXT TIME !

SPECIAL THANKSTO

RAMON VELEZ, MDAMANDA EBRIGHT, MD

HAPPYGROUND

HOG’SDAY!