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IBANDRONATE (BONIVAT)
A NEW BISPHOSPHONATE FOR THE
PREVENTION AND TREATMENT OF
OSTEOPOROSIS


Daniel Brum, Pharm.D./M.B.A. Candidate



Introduction
Osteoporosis is a disease characterized by
deterioration of bone tissue and low bone density
that increases the risk of fractures. Observational
studies suggest that the risk of fractures increases
approximately two-fold for a one standard devia-
tion decrease in bone mineral density (BMD).1 In
the United States alone, 10 million people (8 mil-
lion women, 2 million men) have osteoporosis and
34 million more are believed to have low bone
mass with an increased risk for osteoporosis.2 Ap-
proximately one out of three postmenopausal
women =50 years old is affected by osteoporosis.3
In fact, 50% of women over the age of 50 will suf-
fer an osteoporosis-related fracture during their life-
time.3 Of the 1.5 million annual fractures, 700,000
are vertebral, 300,000 hip, 250,000 wrist, and
300,000 other.2 In 2001, the estimated direct cost
for osteoporosis-related fractures was $17 billion or
roughly $47 million each day.2
There are several risk factors that have been
associated with development of the disease. Risk
factors include but are not limited to advanced age,
family history of osteoporosis, or a fracture in a 1st
degree relative. Other risk factors include early
menopause, a diet low in calcium, having a small
frame, being Caucasian or Asian, and certain medi-
cations such as long-term systemic corticosteroids.


Currently, there are several treatment options for
osteoporosis including hormone replacement ther-
apy, raloxifene (Evista), and calcitonin
(Miacalcin) often in combination with supplemen-
tal calcium and vitamin D. Additionally, the
bisphosphonates are frequently used for the preven-
tion and treatment of osteoporosis.
Ibandronate (BonivaTM) is a new bisphos-
phonate that was approved by the FDA in May
2003 but is not yet commercially available.4 Iban-
dronate 2.5 mg tablets given once-daily is indicated
for the treatment and prevention of osteoporosis in
postmenopausal women (see Table 1).6 It will be
co-promoted by Roche and GlaxoSmithKline, how-
ever, the launch date, commercial dosage form, and
cost of the product are still pending. Currently, re-
searchers are trying to find more convenient alter-
natives to the approved once-daily dosage form.5
Investigators are studying weekly and monthly oral
and parenteral dosage forms, respectively.11'12 Simi-
lar to alendronate (Fosamax) and risedronate
(Actonel), ibandronate has been shown to decrease
the risk of new fractures and increase BMD of the
lumbar spine in postmenopausal women.6'7'8 Of
these agents, only alendronate and risedronate have


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INSIDE THIS ISSUE:

IBANDRONATE (BONIVATM)
A NEW BISPHOSPHONATE FOR THE PREVENTION
AND TREATMENT OF OSTEOPOROSIS

TERIPARATIDE (FOR 11I II )
PROMISING TREATMENT FOR PATIENTS AT
INCREASED RISK FOR OSTEOPOROSIS-RELATED
FRACTURES
-s


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Pha rma Note Volume 18, Issue 11 August 2003


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Table 1. FDA-approved bisphosphonates13

Agent Dosage Form Indications
alendronate (Fosamax)* Oral Glucocorticoid-induced osteoporosis
Paget's disease
osteoporosis in men
prevention and treatment of postmenopausal osteoporosis
etidronate disodium (Didronel) IV, Oral Paget's disease
heterotopic ossification
hypercalcemia of malignancy
ibandronate sodium (BonivaTM) OralP Prevention and treatment of postmenopausal osteoporosis

pamidronate (Aredia) IV Hypercalcemia of malignancy
Paget's disease
osteolytic bone lesions associated with multiple myeloma or
metastatic breast cancer
risedronate (Actonel)* Oral Glucocorticoid-induced osteoporosis, Paget's disease, and
prevention and treatment of postmenopausal osteoporosis

zoledronate (Zometa) IV Hypercalcemia of malignancy, multiple myeloma, and oste-
olytic metastases

FDA Food and Drug Adminstration, IV intravenous
*Fosamax and Actonel are available in both daily and weekly dosage forms. Not commercially available in the U.S.


been proven in large randomized clinical trials to
decrease the risk of hip fracture.7'8'9 This article will
focus on the pharmacokinetics, safety, and efficacy
of ibandronate in women with postmenopausal os-
teoporosis.

Mechanism of Action
Similar to other bisphosphonates, ibandro-
nate inhibits osteoclast activity thereby reducing
bone resorption. Bisphosphonates possess a double
phosphate functional group that allows them to bind
to calcified bone matrix.10 When bisphosphonates
adsorb to hydroxyapatite in the bone matrix, the
matrix becomes less soluble and more stable.10
Binding of the bisphosphonates to the mineralized
hydroxyapatite may inhibit the attachment of osteo-
clast precursors thereby preventing their transfor-
mation into functional osteoclasts.10

Pharmacokinetics
The mean oral bioavailability of ibandronate
is only 0.6% compared to intravenous (IV) dosing.6
Also, concomitant administration with foods or
beverages other than plain water can impair absorp-
tion of the drug by approximately 90%.6 Ibandro-
nate should be taken at least one hour prior to in-
gesting any foods or beverages (other than plain


water).6
Based on two studies, in vitro protein bind-
ing ranged from approximately 85% to 99%.6 Ap-
proximately 40 to 50% of the absorbed dose is ex-
pected to be absorbed into the bone.6 Ibandronate is
not metabolized by the liver and does not inhibit
the hepatic cytochrome P450 system, therefore, no
dosage adjustment is necessary in patients with he-
patic impairment.6
Unabsorbed ibandronate is excreted in the
feces. Of the portion that is absorbed into the circu-
lation, 50 to 60% is eliminated in the urine as the
parent compound.6 While peak plasma levels are
only 10% eight hours after oral dosing, the terminal
half-life may be up to 60 hours.6 Renal clearance of
the drug is linearly related to creatinine clearance
(CrC1). Therefore, it is not recommended that pa-
tients with CrCl <30 mL/min use this drug.6 No
dosage adjustment is necessary in patients with
mild to moderate renal impairment (e.g. CrCl =30
mL/min) or in the elderly.6

Clinical Studies

Treatment ofPostmenopausal Osteoporosis
In a randomized, double-blind, placebo-
controlled, parallel group study, 2946 postmeno-


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Table 2. Incidence of new vertebral fractures in 3-year treatment study6

SPlacebo Ibandronate ARR RRR
Type of Fracture
(N=975) (N=977) (95% CI) (95% CI)

New Vertebral Fracture 9.6 4.7 4.9 (2.3, 7.4) 52 (29,68)
New and Worsening Vertebral Fracture 10.4 5.1 5.3 (2.6, 7.9) 52 (30, 67)
Clinical (Symptomatic) Vertebral Fracture 5.3 2.8 2.5 (0.6, 4.5) 49 (14, 69)
N= number of patients, QD= once daily, ARR absolute risk reduction, CI confidence interval, RRR relative risk reduction
* Data based on an intent-to-treat analysis with the last measured value carried forward.


pausal women with osteoporosis aged 55 to 80
years were given either ibandronate 2.5 mg daily,
20 mg intermittently, or placebo.6 Women who had
a lumbar spine BMD T-score two to five standard
deviations below the pre-menopausal mean in at
least one vertebra (L1-L4), and who had one to four
prevalent fractures were included in the study.6 The
primary endpoint of the study was new vertebral
fractures after 3 years of treatment. All of the
women in the study received concomitant calcium
500 mg and vitamin D 400 IU each day. After 3
years, the patients taking ibandronate 2.5 mg daily
(n=977) had a 4.9% absolute risk reduction for new
vertebral fractures compared to placebo (n=975)
(p<0.001) (see Table 2). There were no differences
among the groups with respect to the number of
fractures reported in the pelvis, femur, wrist, fore-
arm, rib, or hip. While not identified as primary
endpoints, patients in the ibandronate 2.5 mg daily
treatment arm demonstrated a 6.4%, 3.1%, 2.6%,
and 5.3% mean increase from baseline in BMD of
the lumbar spine, total hip, femoral neck, and tro-
chanter, respectively (see Table 3).


Table 3. Mean % change in BMD from baseline in 3-year
treatment study6

Site Placebo Ibandronate
1.4 6.4
Lumbar Spine 1. 6.
Lumbar Spine (N=693) (N=714)
-0.7 3.1
Total Hip (N=638) (N=654)
-0.7 2.6
Femoral Neck
(N=683) (N=699)
0.2 5.3
Trochanter
(N=683) (N=699)
BMD bone mineral density
Data based on an intent-to-treat analysis with the last measured value
carried forward.


Prevention ofPostmenopausal Osteoporosis
In a randomized, double-blind, placebo-
controlled study, 653 postmenopausal women with-
out osteoporosis (lumbar spine BMD T-scores >-
2.5) aged 41 to 82 years were given either ibandro-
nate 0.5 mg, 1.0 mg, 2.5 mg, or placebo in addition
to 500 mg of supplemental calcium daily.6 Patients
were stratified according to baseline lumbar spine
BMD and time since menopause. The primary end-
point of the study was the change in BMD of the
lumbar spine after 2 years of treatment. Patients
given ibandronate 2.5 mg daily had a mean increase
in lumbar spine BMD of 3.1% compared to placebo
(p<0.001). Although not the primary endpoint, pa-
tients randomized to ibandronate 2.5 mg demon-
strated a mean increase in BMD of 1.8%, 2.0%, and
2.1% of the total hip, femoral neck, and trochanter,
respectively.

Adverse Events
The percentage of patients who withdrew
from the studies described above due to adverse
events was 17% in both the active and placebo
arms with the most common reason being related to
the digestive tract.6 According to the prescribing
information, the incidence of adverse events ap-
peared to be similar between the ibandronate 2.5
mg daily and placebo groups. The most common
adverse effects experienced in the placebo and
ibandronate groups respectively included: upper
respiratory infection (33.2%, 33.7%), back pain
(12.2%, 13.5%), dyspepsia (9.8%, 11.9%), and
bronchitis (6.8%, 10.0%) (see Table 4).6

Dosage and Administration
Ibandronate should be administered on an
empty stomach at least 60 minutes prior to eating or
drinking anything other than plain water.6 The 2.5


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Volume 18, Issue 11 August 2003







Table 4. Adverse events occurring in >5% of patients6

A e E t Placebo Ibandronate
Adverse Event
(N=1134) (N=1140)
Upper respiratory infection 33.2 33.7
Back pain 12.2 13.5
Dyspepsia 9.8 11.9
Bronchitis 6.8 10.0
Pain in extremity 6.4 7.8
Diarrhea 5.0 6.8
Headache 5.8 6.5
Pneumonia 4.3 5.9

Myalgia 5.1 5.7
* Table adapted from CDER approved labeling for ibandronate.


mg tablets, if marketed, should be swallowed whole
with 8 ounces of plain water, and the patient should
avoid lying down for at least one hour after taking
the drug. Recommend that women with postmeno-
pausal osteoporosis obtain up to 1500 mg of cal-
cium and 400 IU of Vitamin D daily either from
their diet or from dietary supplements.2'14

Summary
Bisphosphonates play a central role in the
prevention and treatment of osteoporosis. Use of
ibandronate in postmenopausal women reduced the
risk of new vertebral fractures and demonstrated
increased mean lumbar BMD compared to placebo.
The adverse event profile of the drug appeared to
be similar to placebo in these controlled clinical
studies. The methodologies and statistical analyses
of the studies summarized above were not evalu-
ated because they have not been published in the
primary literature.

References
1. Royal College of Physicians Report on Osteoporosis.
http://www.doh.gov.uk/pub/docs/doh/osteo.pdf.
(Accessed July 14, 2003)
2. Fast facts on osteoporosis. NIH Osteoporosis and Related
Bone Diseases-National Resource Center; http://www.
nof.org/osteoporosis/stats.htm; Revised Feb., 2003.
(Accessed July 4, 2003)
3. Dipiro JT et al. Pharmacotherapy: A Pathophysiological
Approach, 5th ed.; Appleton and Lange; 2002.
4. Roche's Boniva Cleared by U.S. FDA. Marketletter Pub-
lications Ltd. Pharma Marketletter; May 23, 2003. http://


web.lexis-nexis.com. (Accessed July 4, 2003)
5. FDA approves new drug application for osteoporosis
drug Boniva (ibandronate sodium). Roche Investor Up-
date May 19, 2003 http://www.roche.com. (Accessed
July 4, 2003)
6. Boniva [Package Insert]. Nutley, NJ and Research Trian-
gle Park. Roche Pharmaceuticals and GlaxoSmithKline.
Draft-0503; Issued May 2003.
7. Fosamax [Package Insert]. Whitehouse Station, NJ;
Merck & Co., Inc.; Jan. 2001.
8. Actonel [Package Insert]. Cincinnati, OH and Kansas
City, MO; Procter & Gamble and Aventis Pharmaceuti-
cals; May 2002.
9. Solomon CG. Bisphosphonates and osteoporosis. NEJM
2002;346(9):642.
10. Clinical Pharmacology. Version 2.08. Gold Standard
Multimedia, 2003.
11. Schimmer RC et al. Effect of daily and intermittent use of
ibandronate on bone mass and bone turnover in post-
menopausal osteoporosis: A review of three phase II
studies. Clinical Therapeutics 2003;25(1).
12. Tanko LB et al. Oral weekly ibandronate prevents bone
loss in postmenopausal women. J Intern Med. 2003
Aug;254(2):159-167.
13. Lacy CF et al. Drug Information Handbook, 11th ed.;
LexiComp, 2003.
14. NIH panel issues recommendations for optimal calcium
intake. http://consensus.nih.gov/news/
releases/097_release.htm. (Accessed July 24, 2003)




New Formulations

Prempro In addition to the recently
approved 0.45mg/1.5mg dose of
conjugated estrogens/MPA,
Wyeth has received approval for
a 0.3mg/1.5mg dose. Both agents
are approved for the treatment of
moderate to severe vasomotor
symptoms associated with
menopause and for the prevention
of postmenopausal osteoporosis.
The 0.45mg dose should be
available this summer, while the
0.3mg product is expected to be
available by the end of the year.

Avonex Biogen will soon have available
new prefilled syringes that will
make their once-a-week treatment
for multiple sclerosis more
convenient to administer.


-
Pha rma Note Volume 18, Issue 11 August 2003


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Volume 18, Issue 11 August 2003







TERIPARATIDE (FORTEO)
PROMISING TREATMENT FOR
PATIENTS AT INCREASED RISK FOR
OSTEOPOROSIS-RELATED FRACTURES


Patria Rorie, Pharm.D. Candidate



Introduction
Osteoporosis is prevalent worldwide, and
its occurrence is projected to increase as life expec-
tancy increases and the population ages. It is esti-
mated that 18 million Americans have low hip
bone density, with an additional 10 million having
osteoporosis of the hip. Approximately 1.5 million
osteoporotic fractures occur annually in the United
States.
It may be difficult to differentiate between
osteoporosis and bone abnormalities associated
with aging, however evidence supports that low
bone density increases in both men and women as
they age. Osteoporosis is more common among
women than men due to the following factors: 1)
women live longer than men; 2) most healthy men,
before the age of 50, have approximately 33%
more bone mass than women: 3) men have the ten-
dency to be more active physically than women of
the same age; and 4) osteoporosis progresses more
rapidly in postmenopausal women, especially
within 5 years after menopause, due to the sudden
decline in hormonal production vs. men who ex-
perience a gradual reduction in testosterone levels
with age.
Immediately after menopause, there is
about 5 to 10 times more bone loss in women com-
pared to men of the same age. It appears that
whites have lower bone mass than blacks. The inci-
dence of hip fractures and complications associated
with osteoporosis among white women 65 years of
age and older is higher than strokes, breast cancer,
and diabetes. By the age of 70, approximately 40%
of women experience at least one fracture; by the
age of 90, more than 33% of women and 17% of
men will have suffered a bone fracture and, be-
tween 12% and 20% of this group die of complica-
tions of osteoporosis, particularly hip fractures.
The economic burden caused by osteoporosis is


high. The annual costs of fractures associated with
this disease in the USA range from $10 to $15 bil-
lion.
Teriparatide, manufactured by Eli Lily, was
approved by the Food and Drug Administration
(FDA) in November 2002 for the treatment of os-
teoporosis in postmenopausal women who are at
high risk for having a fracture. The drug is also ap-
proved to increase bone mass in men with primary
or hypogonadal osteoporosis who are at high risk
for fractures.2 This article will examine the phar-
macology, pharmacokinetics, clinical trial data,
safety, cost, and dosing considerations of teri-
paratide.

Pharmacology and Pharmacokinetics
Forteo [teriparatide (rDNA origin) injec-
tion] contains recombinant human parathyroid hor-
mone (1-34), [rhPTH(1-34)], which has an identi-
cal sequence to the 34 N-terminal amino acids (the
biologically active region) of the 84-amino acid hu-
man parathyroid hormone. Studies have shown that
PTH promotes new bone formation by preferen-
tially stimulating osteoblastic activity over osteo-
clastic activity, a fundamentally different mecha-
nism than seen in antiresorptive agents (i.e. estro-
gen and bisphosphonates) already in use, which
merely prevent further bone loss.3
Teriparatide is administered as a subcutane-
ous injection with an absolute bioavailability
reaching approximately 95%. The rates of absorp-
tion and elimination of the drug are rapid; a 20-
mcg dose results in peak serum concentrations ap-
proximately 30 minutes after administration and
concentrations decline to non-quantifiable levels
within 3 hours. Systemic clearance (approximately
62 L/hr in women and 94 L/hr in men) of teri-
paratide exceeds the rate of normal liver plasma
flow, consistent with both hepatic and extra-hepatic
clearance.
Volume of distribution following intrave-
nous injection is approximately 0.12 L/kg. Inter-
subject variability in systemic clearance and vol-
ume of distribution is 25-50%. The half-life of
teriparatide in serum is 5 minutes when adminis-
tered by intravenous injection and approximately 1
hour when administered by subcutaneous injection.
The longer half-life following subcutaneous ad-
ministration reflects delayed absorption from the


Pha rma Note Volume 18, Issue 11 August 2003


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Table 1. Effects of teriparatide on risk for new nonvertebral fractures in postmenopausal women with osteoporosis5
Fr e Se Teriparatidet Placebot
(N=541) (N=544)
Wrist 2 (0.4%) 7 (1.3%)
Ribs 3 (0.6%) 5 (0.9%)
Hip 1 (0.2%) 4 (0.7%)
Ankle/Foot 1 (0.2%) 4 (0.7%)
Humerus 2 (0.4%) 2 (0.4%)
Pelvis 0 (0.0%) 3 (0.6%)
Other 6(1.1%) 8(1.5%)
Total (%) 14 (2.6%)* 30 (5.5%)
*p< 0.05 compared with placebo, j data shown as number (%) of women with fractures


injection site. Peripheral metabolism of intact PTH,
the 34 N-terminal amino acids, and, presumably,
teriparatide, is believed to occur by non-specific
enzymatic mechanisms in the liver followed by ex-
cretion via the kidneys.
The pharmacokinetic parameters of teri-
paratide appear to be similar across an age range of
31-85 years. The systemic exposure of teri-
paratide is 20-30% lower in men compared to
women, although the recommended dose for both
genders is 20 mcg/day. Teriparatide, as a single
dose, has no pharmacokinetic differences in a lim-
ited number of patients with mild to moderate renal
insufficiency (i.e., CrCl 30-72 ml/min) compared
to healthy controls. In patients with severe renal
insufficiency (i.e., CrCl <30 ml/min), the area un-
der the curve (AUC) and half-life were increased
by 73% and 77% respectively; however, maximum
serum concentrations of teriparatide were not in-
creased.
No information is available for patients un-
dergoing dialysis. The pharmacokinetic parameters
of teriparatide appear to be similar in patients with
NYHA Class I-III heart failure, and no clinically
relevant changes in blood pressure or pulse rate
were noted. Teriparatide has not been studied in pa-
tients with hepatic impairment.4

Clinical Trials
The FDA's approval of teriparatide was
based on 24 clinical trials enrolling more than
2,800 postmenopausal women and men with osteo-
porosis. Phase III clinical trial data showed that
teriparatide stimulated new bone formation, low-


ered the risk of vertebral (spinal) fractures and in-
creased bone mineral density (BMD) compared
with placebo in postmenopausal women with os-
teoporosis during an average of 19 months of treat-
ment. The data also showed that teriparatide re-
duced the relative risk of spinal fractures by 65 per-
cent (9.3% absolute risk reduction) and lowered the
overall relative risk of non-spinal fractures (wrist,
ribs, hip, ankle/foot, etc.) by 53% (2.6% absolute
risk reduction) when compared to placebo (Table
1).
Teriparatide also significantly increased
spine BMD in postmenopausal women with osteo-
porosis beginning at three months of treatment. The
data showed that 96% of women had an increase in
BMD from baseline, with 72 percent achieving at
least a 5% increase in spine BMD and 44 percent
gaining 10% or more compared to placebo. The in-
creases in BMD seen in patients treated with teri-
paratide were statistically significant (p<0.001).4

Postmenopausal Women i/hl Osteoporosis
The largest clinical study with teriparatide
was the Fracture Prevention Trial. This trial was a
double-blind, randomized, placebo-controlled mul-
tinational trial in 1637 women with osteoporosis
and prior vertebral fractures. Subjects received teri-
paratide 20 mcg, 40 mcg, or placebo as a once
daily subcutaneous injection for a median duration
of 19 months. Teriparatide reduced the incidence of
1 or more vertebral fractures from 14.3% of
women in the placebo group to 5.0% in the teri-
paratide group. This difference was found to be sta-
tistically significant (p<0.001).5


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Table 2. Summary of adverse events occurring in > 1% of placebo and teriparatide-treated patients4
Adverse Event Placebo Teriparatide 20 mcg p-value
Back Pain 22.6% 16.8% 0.017
Nausea 7.5% 9.4% 0.264
Headache 8.3% 8.1% 0.934
Leg Cramps 1.1% 3.1% 0.020
Cyst 0.9% 1.7% 0.277
Syncope 1.7% 3.1% 0.109
Nail Disorder 0.4% 1.3% 0.093


Men
The efficacy and safety of teriparatide were
investigated in a double-blind, randomized, pla-
cebo-controlled multinational trial that involved
437 men with hypogonadal or primary osteoporosis
and a BMD of the spine or hip of > 2 SD below the
mean. Subjects received teriparatide 20 mcg, 40
mcg, or placebo as a once daily subcutaneous in-
jection for a median duration of 11 months. The
primary study endpoint was the number of subjects
experiencing a change in lumbar spine BMD. Teri-
paratide significantly increased lumbar spine BMD
(5.9%) compared to the placebo group (0.5%);
(p<0.001).4

Comparison to Alendronate
A randomized double-blind clinical trial en-
rolled 146 postmenopausal women with osteoporo-
sis to compare the efficacy of teriparatide 40 mcg
to alendronate 10 mg. Median duration of exposure
was 14 months. The primary endpoint of the study
was the change in lumbar spine BMD, which
showed an increase of 12.2% in the teriparatide
group compared to a 5.6% increase in the alendro-
nate group (p<0.001).4

Dosing and Administration
Teriparatide is administered by injection
once a day in the thigh or abdomen. The recom-
mended dose is 20 mcg per day. Teriparatide
should initially be administered under circum-
stances where the patient can sit or lie down in case
symptoms of orthostatic hypotension occur. Visu-
ally inspect teriparatide injection solution for par-
ticulate matter and discoloration prior to admini-
stration. Do not use injection solutions that are
cloudy or colored. Each ForteoTM Pen can be used


for up to 28 days after the first injection. After a
28-day use period, the pen should be discarded,
even if it still contains unused solution. The
ForteoTM Pen administration device should not be
shared. Persons with hyperkalemia, women who
are pregnant or nursing, or persons who have ever
been diagnosed with bone cancer or other cancers
that have spread to the bones, should not use teri-
paratide. Because the effects of long-term treatment
with teriparatide are not known at this time, ther-
apy for more than 2 years is not recommended.6

Toxicity and Safety
In animal studies with teriparatide, there
was an increase in the number of rats developing
osteosarcoma, a rare but serious cancer of the bone.
In the human studies, no osteosarcomas were re-
ported, but the possibility that humans treated with
teriparatide may face an increased risk of develop-
ing this cancer cannot be ruled out. This safety is-
sue is highlighted in a black box warning in the
drug's label for health professionals and explained
in a brochure, called a Medication Guide, for pa-
tients. To help ensure that patients are aware of im-
portant information about teriparatide, the Medica-
tion Guide will be distributed by the pharmacist
each time the drug is dispensed. Because people
with growing bones and people with Paget's dis-
ease of the bone have a higher risk for developing
osteosarcoma, it is important that they not be
treated with teriparatide.
Teriparatide has not been studied in pediat-
ric populations and should not be used in pediatric
patients or young adults with open epiphyses. Most
side effects reported in association with teriparatide
in clinical trials were mild and included nausea,
dizziness, and leg cramps (Table 2). During the


Ph ra ot Vlue 8,Isue11Auus 20


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Volume 18, Issue 11 August 2003







Table 3. Cost Comparison of Forteo' 20 mcg/day
Pharmacy Price
Retail (chain) $567.95
Independent $583.00
Internet $515.96
Mean Price $555.64


clinical trials, early discontinuation due to adverse
events occurred in 5.6% of patients assigned to pla-
cebo and 7.1% of patients taking teriparatide.

Cost
The retail cost for a 30-day supply is sum-
marized in Table 3.

Summary
Teriparatide is the first treatment for osteo-
porosis that has been proven to promote new bone
formation and has been proven effective in clinical
trials for both women and men who are at risk of
osteoporosis-related fractures. Although it is gener-
ally well-tolerated, some safety concerns remain
and the drug is labeled with a black box warning,
indicating the need for additional safety studies. It
appears to be an effective treatment option for pa-
tients at risk for fractures from advanced osteopo-
rosis.

References
1. O'Connell, MB. Osteoporosis and Osteomalacia. In:
Dipiro, JT, et al, editors. Pharmacotherapy: A
Pathophysiologic Approach. 4th ed. McGraw-Hill; 1999.
p. 1406-1426.
2. FDA Talk Paper: FDA APPROVES TERIPARATIDE
TO TREAT OSTEOPOROSIS. TO2-49, Nov. 26, 2002.
http://www.fda.gov/bbs/topics/ANSWERS/2002/
ANS01176.html
3. W.B. Saunders, Mosby, Churchill Livingstone, Butter-
worth-Heinemann, and Hanley & Belfus; Mosby's Drug
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4. U.S. FORTEOPrescribing Information, Eli Lily and
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5. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of
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7. Drug Prices and Information; drugstore.com hup \\ \ .
drugstore.com


FuzeonTM (enfuvirtide) is the first of a new
class of drugs called fusion inhibitors. It is
also the first class of drugs developed and
approved for the treatment of HIV since
1996. It should be used in combination with
other antiretroviral agents in treatment-
experienced patients with evidence of HIV-1
replication despite ongoing antiretroviral
therapy. The usual dose is 90 mg SQ twice a
day.






Velcade TM(bortezomib) is the first in a new
class of antineoplastic agents known as
proteosome inhibitors. Inhibition of this
enzyme complex has demonstrated to disrupt
cell homeostasis and in vitro, has lead to
death of a variety of cancer cell types. It has
been approved for the treatment of multiple
myeloma in patients who have demonstrated
disease progression despite receiving at least
two prior therapies. The initial dosage is 1.3
mg/m2/dose IV bolus twice weekly for 2
weeks followed by a 10-day rest period.





The PharmaNote is Published by:
The Department of Pharmacy Services,
UF Family Practice Medical Group,
Departments of Community Health
and Family Medicine and Pharmacy
Practice
University of Florida


John G. Gums Editor
Pharm.D.

R. Whit Curry, M.D. Associate Editor

John M. Tovar Assistant Editor
Pharm.D.


Pha rma Note Volume 18, Issue 11 August 2003


PharmaNote


Volume 18, Issue 11 August 2003




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