Friday, 5 September 2014

Medications used to stop smoking

Medications Used for Smoking Cessation

by Mandy Leonard, Pharm.D., BCPS
In This Issue:



Smoking Cessation

Formulary Update

Introduction: It is estimated that over



40 million adults in the United States

smoke cigarettes and more than 8 million

of those have at least one severe

illness caused by smoking.1 Patients



should be encouraged to quit smoking

with the assistance of counseling and

pharmacotherapies. Because it is a

chronic condition, nicotine or tobacco

dependence may require multiple and

repeated interventions.2

Nicotine3-5: Nicotine is a ganglionic



cholinergic receptor agonist, and its

effects are highly dependent on dose.

It causes central and peripheral nerve

stimulation as well as depression.

The other effects of nicotine include:

respiratory stimulation, skeletal muscle

relaxation, catecholamine release

by adrenal medulla, peripheral vasoconstriction,

and increases in blood

pressure and heart rate. At lower

doses, nicotine stimulates the cerebral

cortex which increases alertness and

cognitive function. However, at

higher doses, nicotine stimulates the

“reward” center in the limbic system

of the brain.

As tobacco smoke, nicotine is absorbed

rapidly through the lungs and

one cigarette contains 10 to 25 mg of

nicotine. The half-life is 1 to 2 hours,

therefore, frequent and repeated administration

is necessary. There is

accumulation of nicotine over 6 to

9 hours with regular smoking. Nicotine

is rapidly and extensively

metabolized by the liver to approximately

20 less active metabolites.

The main metabolite is cotinine, and

its half-life is 15 to 20 hours.

Chronic nicotine ingestion is associated

with both physical and psychological

dependence. Therefore, abrupt

cessation of nicotine can cause withdrawal

symptoms in physically dependent

smokers (e.g., anxiety, depression,

difficulty concentrating,

drowsiness, irritability, impatience,

gastrointestinal disturbances, headache,

hostility, increased appetite/

weight gain, and insomnia). These

symptoms may occur within 24 hours

of cessation and last for days, weeks,

or longer.

In 1997, the Food and Drug Administration

(FDA) attempted to classify

nicotine in cigarettes and smokeless

tobacco as a drug and cigarettes as

devices. The U.S. Supreme Court

ruled in favor of the tobacco industry

and decided that nicotine in cigarettes

and smokeless tobacco would not be

classified as a drug and cigarettes

would not be classified as a device.4

Pharmacotherapy: The goal of nicotine



replacement therapy (NRT) is to

assist in smoking cessation while the

patient focuses on modifying his or

her behavior and coping with the psychological

aspects of quitting.4,5 The



from the Department of Pharmacy
N E W S

LETTER

Update
Department of Pharmacy / Hb03, Drug Information Center, 9500 Euclid Avenue, Cleveland, Ohio 44195 (216)444-6456

TH E CLEVELAND CLINIC FOUNDATION


Pharmacotherapy


from the Department of Pharmacy
N E W S

LETTER

Update
Department of Pharmacy / Hb03, Drug Information Center, 9500 Euclid Avenue, Cleveland, Ohio 44195 (216)444-6456

TH E CLEVELAND CLINIC FOUNDATION


Pharmacotherapy
onset of action for NRT is not as rapid as that of nicotine

obtained from smoking, therefore patients become less accustomed

to the nearly immediate, reinforcing effects of

inhaled tobacco.



The available FDA-approved smoking cessation aids include

nicotine replacement products (e.g., nicotine gum,

lozenge, patch, nasal spray, and inhaler), bupropion

(Zyban®), and varenicline (Chantix®). Except in the presence



of contraindications, nicotine replacement products

and/or bupropion should be used as first-line therapy in all

patients who are attempting to quit smoking to increase

smoking abstinence rates.4-7 Second-line therapy, such as



clonidine or nortriptyline, can be used if first-line therapies

are not effective.4-7 It has yet to be determined if varenicline



will be recommended as first- or second-line therapy.

Nicotine Replacement Products:
Nicotine gum and lozenge3,6-8: Nicotine gum and lozenge



contain nicotine bound to an ion exchange resin (nicotine

polacrilex and nicotine polacrilin, respectively). Approximately

1.1 to 2.9 mg of nicotine are extracted from the

2- and 4-mg dosage forms, respectively. Long-term abstinence

rates for nicotine gum and lozenge range from 30 to

80%. Both nicotine gum and lozenges are available without

a prescription. For cost information regarding these

products, please see Table 2.

For the gum, the dose is dependent on how much a patient

smokes per day. For patients smoking >25 cigarettes per

day, the starting dose is 4 mg. For patients smoking

<25 cigarettes per day, the starting dose is 2 mg. Once the

dose is determined, one piece of the gum may be used

every 1 to 2 hours and no more than 24 to 30 pieces per day

(See Table 1 for detailed dosing schedule). Acidic beverages

should be avoided while chewing the gum because of

interference with buccal absorption. Additionally, eating

and drinking (except for water) should be avoided 15 minutes

before and after chewing. If the gum is accidentally

swallowed, there is little to no absorption of nicotine. Over

an extended time, nicotine gum may cause severe occlusal

stress (dental) such as loosening in inlays or fillings, sticking

to dentures, damage to the oral mucosa, jaw muscle

fatigue, and hypersalivation. It is recommended to use the

gum for no longer than 12 weeks.

For the lozenge, the dose is dependent on when the first

cigarette of the day is smoked. Patients who smoke their

first cigarette within 30 minutes of waking should use the

4 mg lozenge; otherwise, the 2 mg lozenge should be used.

Once the dose is determined, the patient should use at least

9 lozenges per day for the first 6 weeks, but no more than

5 lozenges in 6 hours or >20 lozenges per day. The patient

should be educated to place the lozenge in the mouth

and then allow it to slowly dissolve (otherwise known as

the “park method”) for 20 to 30 minutes and try to minimize

swallowing. The lozenge should not be chewed or

swallowed. The patient should not use more than one lozenge

at a time, or continuously use one lozenge after another

due to increased side effects (e.g., hiccups, heartburn,

and nausea). If the lozenge is allowed to dissolve

completely, it delivers 25% more nicotine compared to

gum. Similar to the gum, eating and drinking (except for

water) should be avoided 15 minutes before and after using

the lozenge. It is recommended to use the lozenge for

no longer than 12 weeks.

Nicotine transdermal patch3,6-8: Nicotine transdermal



patches contain a multi-layered unit containing nicotine

that delivers up to 24 hours of nicotine via the skin. Sixtyeight

percent of nicotine released from the patch reaches

the systemic circulation (i.e., the dose documented on the

product [e.g., 14 mg/24 hours] is the actual amount of absorbed

nicotine). Since the patch contains metal

(aluminum), it needs to be removed prior to MRI. The

long-term abstinence rates double with the use of nicotine

patches. Nicotine patches have been available since 1991

with a prescription and since 1996 without a prescription.

Patients must completely stop smoking, chewing tobacco,

or using other nicotine-containing products before using

the patch. For Nicoderm® CQ, it is worn for 16 to



24 hours (24 hours specifically for patients who crave a

cigarette upon waking). For light smokers (<10 cigarettes

per day), the patient should start with 14 mg per day for

6 weeks. For Nicotrol®, it is worn for 16 hours (taken off



at bedtime). This product should be used in patients who

experience sleep disruption (See Table 3 for detailed dosing

schedule). Patients should not wear more than one

patch at a time and the patches should not be cut. Adverse

reactions include erythema, pruritis, and burning at application

site. Local skin irritation may be decreased by rotating

the location of the patch.

Nicotine nasal spray3,6-8: Nicotine nasal spray (Nicotrol®



NS) delivers 0.5 mg nicotine/actuation (10 mg/mL), and

there are 200 sprays or 100 doses per bottle. One mg in

two sprays is delivered to the nasal mucosa and 53%

reaches systemic circulation. The long-term abstinence

rates double with the use of nicotine nasal spray. However,

there is an intermediate abuse potential because of a



more rapid penetration of nicotine into the central nervous

Table 1. Dosing Schedule for Nicotine Gum and Lozenge6-8



Weeks 1 to 6 Weeks 7 to 9 Weeks 10 to 12


One piece of gum or lozenge

every 1 to 2 hours

One piece of gum or lozenge

every 2 to 4 hours

One piece of gum or lozenge

every 4 to 8 hours

Table 2. Retail Cost Comparison of Smoking Cessation Medications6
Nicorette® Gum



F

2 mg (original): $47 (108 pieces;

$0.44/piece)

Maximum dose of 24 pieces per day,

168 pieces = ~7 day supply

Approximately $295 for one month supply

4 mg (original): $52 (108 pieces;

$0.48/piece)

Maximum dose of 24 pieces per day,

168 pieces = ~7 day supply

Approximately $322 for one month supply

Commit® Lozenge NF



$45 (72 pieces; nominal pricing) 72 lozenge/9 lozenge per day = 8 day supply

Approximately 4 boxes for one month

supply = $180

Nicoderm® CQ Patch



F

Step 1/Step 2/Step 3:

$47 (14 patches; nominal pricing)

2 boxes for one month supply = $94

Available as clear patches $52

Nicotrol® Patch



NF

Step 1/Step 2/Step 3:

$47 (14 patches; nominal pricing)

2 boxes for one month supply = $94

Generic nicotine

transdermal patch

F $30 (14 patches)



$60/month

Nicotrol® Nasal Spray NF



$38 per bottle 4 bottles for one month supply = $152

8 - 40 doses/day

Nicotrol® Inhaler NF



$121 per inhaler Approximately one month supply

(6 - 16 cartridges/day)

Zyban® SR NF



$120 (60 tablets)

One month supply

Generic bupropion SR F $70 (60 tablets) One month supply

Chantix® NF

$167.99* (11 tablets of 0.5 mg



and 42 tablets of 1 mg)

One month starter pack

$167.99* (56 tablets of 1 mg) One month maintenance pack



NOTE: *Average wholesale price

NF = Non-formulary; F = Formulary

system (CNS). The nasal spray has been available with a

prescription since 1996.

Patients must completely stop smoking before using the nasal

spray. The recommended dose is 1 to 2 doses per hour

(and one dose equals two sprays, one in each nostril). Patients

should use at least eight doses per day. The maximum

recommended doses per hour is five with 40 doses being the

maximum number of doses per day. Nicotine nasal spray

should not be used for >3 months, and there is no optimal

tapering strategy. Caution should be used in patients with

chronic nasal disorders (e.g., rhinitis and sinusitis) and the

nasal spray is not recommended in patients with reactive

airway disease (e.g., asthma and COPD). Adverse reactions

include headache, back pain, dyspnea, and nausea.

Nicotine inhaler3,6-8: For the usual pack-per-day smoker,



the hand-to-mouth motion is at least 200 times per day (or

73,000 times per year). Nicotine inhaler (Nicotrol® Inhaler)



delivers 4 mg (10 mg/cartridge) of nicotine, but only

2 mg is systemically absorbed. The majority of nicotine

from the inhaler is deposited in the mouth with only a fraction

reaching lower respiratory tract. If the inhaler is used

correctly, 100 puffs on the inhaler over 20 minutes is equal

to 10 puffs of one cigarette over 5 minutes. The nicotine

inhaler has a lower abuse potential compared to the nicotine

nasal spray. The inhaler has been available with a prescription

since 1997.

Patients self-titrate the initial dose, but should use at least

six cartridges per day for the initial 3 to 6 weeks of therapy.

4 days, therefore, it does not reach steady-state concentrations

for 5 to 8 days. It is hepatically metabolized. Bupropion

(brand name Zyban®) is FDA-approved for smoking



cessation with a prescription, but bupropion (brand

name Wellbutrin®) is FDA-approved for the management



of depression.

Patients must select a quit date because it takes bupropion

5 to 8 days to reach steady-state concentrations. The initial

recommended dose is 150 mg by mouth every morning for

3 days followed by a dose increase to 150 mg by mouth

twice daily. The set quit date should be within 2 weeks of

beginning bupropion therapy. The duration of therapy is

7 to 12 weeks. Bupropion can be used in combination with

other nicotine replacement products. Because Zyban® is an



extended-release product, it should not be crushed. Common

adverse reactions include insomnia, neuropsychiatric

symptoms (e.g., delusions and hallucinations), hypertension

(especially when used in combination with NRT), and dry

mouth. The use of bupropion is contraindicated in patients

with a history of bulimia and anorexia nervosa (due to an

increased risk of seizures), seizure disorders (dosedependent),

head trauma, tumor, hepatic cirrhosis, and in

patients that are on medications that decrease the seizure

threshold or patients that are on a monoamine oxidase inhibitor.

There are no reports of seizures in the smoking

cessation trials which evaluated bupropion. Bupropion is

classified as a pregnancy-risk category B which means either

animal-reproduction studies have not demonstrated a

fetal risk but there are no controlled studies in pregnant

women or animal-reproduction studies have shown an adverse

effect that was not confirmed in controlled studies in

women in the first trimester. Bupropion may be best used

in patients that also have depression or who are unable to

consistently use short-acting NRT. For cost information,

please see Table 2.

Varenicline9,10: Varenicline (ChantixTM) is an α4β2 nicotinic



acetylcholine partial agonist. FDA-approved in May

2006, it is the newest addition to the armamentarium of

smoking cessation agents. Varenicline’s mechanism of

action is two-fold. It binds to the α4β2 neuronal nicotinic


Table 3. Recommended Dosing Schedule of Transdermal Nicotine for Healthy Patients6-8



Dose Duration Per Strength of Patch Entire Course of Therapy


Nicoderm CQ®



21 mg/day

14 mg/day

7 mg/day

First 6 weeks

Next 2 weeks

Last 2 weeks

8 to 10 weeks

Nicotrol®



15 mg/16 hr

10 mg/16 hr

5 mg/16 hr

First 6 weeks

Next 2 weeks

Last 2 weeks

10 weeks

The maximum recommended dose is 16 cartridges per

day. The patient should taper the doses down during the

6 to 12 weeks of therapy, and the inhaler should not be

used for more than 12 weeks. Adverse reactions include

local irritation, coughing, rhinitis, and dyspnea. Additionally,

it may cause accelerated hypertension in patients

with cardiovascular disease.

Summary of Adverse Drug Reactions and Drug Interaction



with Nicotine Replacement Products3,4,6-8: Patients



may experience nausea and light-headedness if too much

nicotine is administered. Additionally, up to 23% of patients

on nicotine replacement complain of sleep disturbances.

For patients that decide to use the nicotine patch,

skin irritation is often a problem, and it is recommended

to rotate the application site. Some patients may decide

to continue to smoke while taking nicotine replacement

products which increases the risk of adverse effects and

causes higher peak nicotine levels compared to smoking

alone. All nicotine replacement products are classified as

a pregnancy-risk category D, except for nicotine gum

which is classified as a pregnancy-risk category C. Pregnany-

risk category D means there is positive evidence of

human fetal risk, but the benefits from use in pregnant

women may be acceptable despite the risk. Pregnancyrisk

category C means either studies in animals have revealed

adverse effects on the fetus and there are no controlled

studies in women or studies in women and animals

are not available (risk versus benefit).

Cigarette smoking induces the cytochrome P450 (CYP)

1A2 isoenzyme. This is due to the polycyclic aromatic

hydrocarbons (PAHs) in tobacco smoke. Therefore,

doses of drugs that are substrates of the CYP 1A2

isoenzyme may need to be decreased upon smoking

cessation (e.g., estradiol, diazepam, theophylline, and

select opioids).

Bupropion3,6-8: Bupropion is a non-nicotine medication.



It inhibits neuronal uptake of dopamine and norepinephrine

in the CNS, but the exact mechanism for smoking

cessation is unknown. Bupropion has a half-life of 3 to

acetylcholine receptors, stimulating the release of dopamine

to curb nicotine cravings and withdrawal. At the

same time it prevents the binding of nicotine to these

receptors, interrupting the activation of the mesolimbic

dopamine system. Therefore, smokers receiving varenicline

therapy will not experience the usual reward associated

with smoking.

Similarly to bupropion, patients must select a quit date

because varenicline does not reach steady state for

4 days. Varenicline tablets should be initiated at least

1 week prior to the established quit date. Patients

should receive therapy as described in Table 4. Varenicline

should be administered with food and a full glass

of water to decrease gastric upset. No dosing adjustments

are necessary for hepatic or renal impairment. It

is recommended that patients receive therapy for

12 weeks. Patients who have stopped smoking after

12 weeks of therapy should receive another 12 weeks of

therapy to increase the likelihood of long-term abstinence.

For those patients still smoking after 12 weeks

of therapy or those who relapse, another course of

varenicline therapy may be tried. Nausea is the most

common side effect associated with initial varenicline

use, occurring in 30% of patients. The severity of nausea

may decrease with continued use. Other frequently

occurring adversities include insomnia and headache.

No clinically significant drug-drug interactions with

varenicline have been identified, and it is not contraindicated

in any patients. Varenicline is classified as a pregnancy-

risk category C. Its place in smoking cessation

therapy has yet to be determined. For cost information,

please see Table 2.

Conclusion: Nicotine dependence is a chronic, relapsing



disease that needs continual monitoring and likely repeated

intervention. There are effective pharmacotherapies

for nicotine dependence and should be offered to all

patients with nicotine addiction. First-line therapy is

NRT such as nicotine gum and transdermal patches, as

well as bupropion. Second-line therapy should be offered

for patients unable to use first-line medications

because of contraindications or if first-line therapy is not

effective. Varenicline is a new oral smoking cessation

product, and its place in therapy has not yet been determined.

Healthcare professionals should discuss smoking

cessation options with their patients and continually play

an integral role in encouraging patients to quit.

Note: For Cleveland Clinic employees to receive assistance



to quit smoking, there is access to a toll-free number (1-800-

QUIT-NOW) that will connect employees to a counselor

and provide access to free nicotine replacement therapy.

Also, employees may go to the following website

www.cchs.net/wellness/WellnessFAQ.pdf for additional

smoking cessation information. Furthermore, the Cleveland

Clinic Employee Health Plan covers prescription smoking



cessation products, including varenicline.

References:


1. Anon. FDA approves novel medication for smoking cessation. FDA news.

May 11, 2006. http://www.fda.gov/bbs/topics/NEWS/2006/NEW01370.html



(Accessed August 15, 2006).

2. Flore MC, Bailey WC, Cohen SJ. Treating tobacco use and dependence,

clinical practice guideline. U.S. Department of Health and Human Services.

Public Health Service. June 2000. http://www.surgeongeneral.gov/tobacco/

treating_tobacco_use.pdf. (Accessed August 15, 2006).



3. McEvoy GK, Snow EK, Kester L, Litvak K, Miller J, Welsh OH, et al, eds. In:

AHFS Drug Information. Bethesda: American Society of Health-System

Pharmacists; 2006:1394-1411.

4. Doering PL. Substance-related disorders:alcohol, nicotine, and caffeine. In:

DiPiro J, Tolbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy:

a pathophysiologic approach. 6th ed. New York: McGraw-Hill;



2005:1198-1205.

5. Taylor P. Agents acting at the neuromuscular junction and autonomic ganglia.

In: Brunton LL, Lezo JS, Parker KL, eds. Goodman & Gilman’s: the pharmacological

basis of therapeutics. 11th ed. New York: McGraw-Hill; 2006:231-3



6. www.crlonline.com/crlonline Accessed September 6, 2006 Nicotine

7. Nicotine. In: DRUGDEX® System [Internet database]. Greenwood Village,



CO: Thomson Micromedex. Updated periodically Accessed September 6,

2006

8. Nicotine. Drug Facts and Comparisons. Drug Facts and Comparisons 4.

[online]. Available from Health, Inc. Accessed September 6, 2006.

9. Varenicline package insert. Pfizer Inc, NY: Pfizer Labs; 2006 May.

10. Oncken C, Gonzales D, Nides M, Rennard S, Watsky E, Billing C, et al.

Efficacy and safety of the novel selective nicotinic acetylcholine receptor

partial agonist, varenicline, for smoking cessation. Arch Intern Med

2006;166:1571-77.

Table 4: Vareniciline Dosing9
Days 1-3 0.5 mg once daily

Days 4-7 0.5 mg twice daily

Day 8 - End of treatment 1 mg twice daily

Upcoming Topics:


Bisphosphonate-Associated Osteonecrosis

of the Jaw
Gardasil® (Human Papillomavirus (Types


6,11,16,18) Recombinant Quadrivalent

Vaccine)
New Drugs: Opana® and Daytrana®




Automatic Therapeutic Interchange Program for Pancreatic Enzymes


Pancreatic enzyme (i.e., lipase, protease, and amylase) replacement therapy is indicated for patients with: 1) deficient exocrine pancreatic secretions

such as in cystic fibrosis, 2) chronic pancreatitis, 3) post-pancreatectomy, 4) ductal obstructions caused by cancer of the pancreas or

common bile duct, pancreatic insufficiency, and 5) for steatorrhea of malabsorption syndrome and postgastrectomy or post-gastrointestinal

surgery. It can also be used as a presumptive test for pancreatic function, especially in pancreatic insufficiency due to chronic pancreatitis.1



Some pancreatic enzyme formulations are enteric-coated, whereas others are uncoated. Enteric-coated preparations are typically used to treat

pancreatic insufficiency and steatorrhea. The enteric-coating protects the enzymes from gastric acidity thereby allowing them to reach the

proximal jejunum where they aid in fat digestion.2 Uncoated preparations are beneficial in treating chronic pancreatic pain syndromes. The

pain is caused by high levels of cholecystokinin (CCK) over-stimulating the pancreas.2 Trypsin, an activated protease enzyme, inhibits CCKreleasing

factor, a peptide responsible for stimulating the release of CCK.2,3 Nonenteric-coated enzymes allow the release of trypsin and other

proteases in the duodenum, the site where the CCK feedback mechanism is most sensitive.2



For both the enteric-coated and uncoated pancreatic enzymes, dosing is based on lipase units. In July 2006, the Cleveland Clinic Pharmacy

and Therapeutics Committee approved an automatic therapeutic interchange program for all pancreatic enzymes.

1.) The preferred Formulary enteric-coated pancreatic enzyme will be Creon® Capsules (delayed-release, enteric-coated microspheres). All

orders written for enteric-coated pancreatic enzymes will be automatically therapeutically interchanged to Creon® Capsules based on the lipase



content.

2.) The preferred Formulary nonenteric-coated pancreatic enzyme will be Viokase® Tablets (immediate-release tablets). All orders written

for nonenteric-coated pancreatic enzymes will be automatically therapeutically interchanged to Viokase® Tablets based on the lipase content.

Please contact the Drug Information Center for detailed dosing conversions of Creon® and Viokase®.




References:


1. Digestive enzymes. Drug Facts and Comparisons. Drug Facts and Comparisons 4.0 [online]. 2006. Available from Health, Inc. Accessed April 18, 2006.

2. Forsmark CF. Chronic pancreatitis. In Feldman M, Friedman L, Sleisenger M, editors. Gastrointestinal and liver disease: pathophysiology/diagnosis/management. 7th ed.



Philadelphia: Saunders; 2002. p. 943-69.

3. Pandol SJ. Pancreatic physiology and secretory testing. In Feldman M, Friedman L, Sleisenger M, editors. Gastrointestinal and liver disease: pathophysiology/diagnosis/

management. 7th ed. Philadelphia: Saunders; 2002. p. 871-80.


Revised Warnings for Long-Acting Beta2-Agonists
Long-acting beta2-agonists (LABAs), including salmeterol (Serevent® Diskus®), the combination inhaler salmeterol/fluticasone (Advair

Diskus®) and formoterol (Foradil® AerolizerTM), may increase the risk of asthma-related death.



LABAs are used for long-term control and prevention of asthma symptoms, for prevention of exercise-induced wheezing in adults and children,

and for long-term control of wheezing in adults with chronic obstructive pulmonary disease (COPD). The new warnings for LABAs,

however, are specific for patients with asthma as there is currently no data to extrapolate these concerns to other indications.

Data from a large placebo-controlled US study (Salmeterol Multicenter Asthma Research Trial [SMART]) compared the safety of salmeterol

or placebo when added to usual asthma therapy. This study showed an increase in asthma-related deaths in patients receiving salmeterol

(13 deaths out of 13,176 patients treated for 28 weeks on salmeterol versus 3 deaths out of 13,179 patients on placebo). This risk was found to

be higher in African-American patients, with no increase in events among Caucasians. Serevent®, however, is not contraindicated in the African-

American population since the patients who died in the SMART study had severe asthma and a direct correlation to the use of Serevent®



was not implicated. In August 2003, black-box warnings were added to the product labeling of all products containing salmeterol and in June

2006, a black box warning was added to the Foradil® AerolizerTM due to the potential that this increased risk of death is a class effect. The



Food and Drug Administration (FDA) emphasized that the benefits of salmeterol outweigh the small risk of asthma-related deaths found in the

SMART study.

In May 2006, the FDA issued a public health advisory to highlight the following recommendations:

1) LABAs should not be the first medication used to treat asthma, but should be added to the asthma treatment plan if other medications

do not control asthma (including the use of low-or-medium dose inhaled corticosteroids).

2) LABAs should not be discontinued without first discussing with a healthcare professional.

3) LABAs do not relieve sudden wheezing; therefore, the patient should always have a short-acting bronchodilator for this indication.

At this time, per the Cleveland Clinic P&T committee, salmeterol containing products and Foradil® AerolizerTM remain on the inpatient formulary.



The majority of LABA use in the hospital is due to continuation of therapy from home. Additional information including copies of the

Patient and Healthcare Professional information sheets can be found at http://www.fda.gov/cder/drug/infopage/LABA/default.htm.




Formulary Update


The Cleveland Clinic Pharmacy and Therapeutics Committee met on Tuesday, July 11, 2006, and the following decisions were made:

Formulary Additions:


1.) Oral Cephalosporins: cefdinir (Omnicef®), cefixime (Suprax®), and cefpodoxime (Vantin®)

2.) Efavirenz 600 mg/Emtricitabine 200 mg/Tenofovir 300 mg (Atripla™): Atripla™ is a single tablet, once-a-day therapy for the



treatment of HIV.

3.) Iloprost (Ventavis™): Iloprost is an inhaled synthetic analogue of prostacyclin PGI2 indicated for the treatment of pulmonary hypertension.

Its use is restricted to the Pulmonary Hypertension Committee for use in patients unable to tolerate or use continuous



IV prostacyclin therapy.

4.) Human Papillomavirus (Types 6,11,16,18) Recombinant Quadrivalent Vaccine (Gardasil®): Gardasil® is a vaccine indicated



for girls and women aged 9-26 years for the prevention of disease caused by Human Papillomavirus types 6,11,16, and 18. Its use

is restricted to outpatients.

5.) Insulin glulisine (Apidra®): Insulin glulisine is a rapid-acting human insulin analog. Its use is restricted to the Department of



Endocrinology. To help distinguish it from other insulin products, please write orders as “insulin glulisine (Apidra)”.

6.) Lidocaine/epinephrine/tetracaine (LET): LET is used as a topical anesthetic. It has an improved safety profile compared to tetracaine/



epinephrine/cocaine (TAC).

7.) Micafungin (Mycamine™): Micafungin is an echinocandin antifungal agent. In vitro activity is comparable to caspofungin with

activity against Candida sp including C. albicans, C. glabrata, C. tropicalis, and C. kruesi. Micafungin, like caspofungin, is also

active against Aspergilus sp and other molds. The echinocandins have no activity against Cryptococcus neoformans. Micafungin



appears to be well-tolerated and unlike caspofungin does not appear to interact with cyclosporine, tacrolimus, rifampin, or phenytoin.

Micafungin is currently only FDA-approved for treatment of esophageal candidiasis and prophylaxis following bone marrow

transplantation. However, clinical trials and reports have demonstrated efficacy in candidemia and invasive fungal infections. In

addition, micafungin has been well-studied in the pediatric population. Micafungin, at the recommended dose of 150 mg daily, has

substantial cost savings compared to the daily dose of caspofungin. Micafungin also appears to be comparable to caspofungin in

terms of safety and efficacy. For the above reasons, micafungin has been added to the Formulary, replacing caspofungin. Its use is

restricted to the Department of Infectious Diseases.

8.) Natalizumab (Tysabri®): Natalizumab is FDA-approved for the treatment of patients with relapsing forms of multiple sclerosis

(MS) to reduce the frequency of clinical exacerbations. It is a humanized anti-α4 integrin monoclonal antibody that acts as a selective

adhesion-molecule inhibitor on activated lymphocytes and monocytes. Its use is restricted to the Department of Neurology at



the Mellen Center for the outpatient treatment of MS.

9.) Omega-3-acid ethyl esters (Omacor®): Omacor® is the only FDA-approved omega-3-fatty acid product. It is indicated as an



adjunct to diet to reduce triglyceride levels >500 mg/dL in adults.

10.) Ramelteon (Rozerem®): Ramelteon is a melatonin MT1 and MT2 receptor agonist FDA-approved for treating insomnia characterized

by difficulty in falling asleep. Its use is restricted to the Departments of Psychiatry, Neurology, and Pulmonary Medicine.

11.) Ranibizumab (Lucentis™): Ranibizumab, an angiogenesis inhibitor, is administered as an intravitreal injection for the treatment



of neovascular age-related macular degeneration. Its use is restricted to the Cole Eye Institute.

12.) Rotavirus Vaccine (RotaTeq®): Rotavirus vaccine is a live, oral pentavalent vaccine indicated for the prevention of rotavirus gastroenteritis



in infants and children.

13.) Zoster Vaccine (Zostavax®): Zoster vaccine is a live vaccine indicated for the prevention of herpes zoster (shingles) in patients

>60 years. Its use is restricted to outpatients.




Formulary Deletions:


1.) Benzocaine and benzocaine-containing Non-Metered Dose Topical Sprays (Hurricaine®, Cetacaine®): Due to the potential for development

of methemoglobinemia when topical benzocaine is administered incorrectly, Topex®, a topical benzocaine metered-dose spray,



will be the only topical benzocaine product on Formulary.

2.) Caspofungin (Cancidas®)

3.) Lepirudin (Refludan®)

4.) Quinupristin/dalfopristin (Synercid®)



5.) Tetracaine, epinephrine, and cocaine (TAC)

Cleveland Clinic

Department of Pharmacy/Hb-03

Drug Information Center



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