℞
FYDI ℞
……………For Your Drug
Information ………….
May – June 2003
New FDA marketing approvals:
(work in progress)
1. (Factive®) Gemafloxacin mesylate – a new fluoroquinolone approved
for the treatment of pneumonia. Available from LG Life Sciences as a 320
mg tablet, the drug is dosed once daily for 5 days for acute exacerbations of
chronic bronchitis OR once daily for 7 days for community-acquired pneumonia.
2. (Suboxone®) Buprenorphine/Naloxone – sublingual tablet combination
approved for treatment of opioid dependence. The tablet comes in two sizes
containing 2 mg buprenorphine/0.5 mg naloxone OR 8 mg buprenorphine/2 mg
naloxone. Prescribing will be limited to
specific physicians and strict accountability of drug supply is required. Manufactured by Reckitt Benckiser
Pharmaceuticals.
3. (Zymar®) Gatifloxacin 0.3% Opthalmic Solution – fluoroquinolone antibiotic solution used for treatment of bacterial conjunctivitis. On Day 1 & 2 instill one drop every 2 hours into affected eye while awake (up to 8 times daily). For day 3 through 7, instill one drop four times daily while awake. The drug is manufactured by Allergan, Inc.
4. (Velcade®) Bortezomib – a new chemotherapeutic agent used in the
treatment of refractory multiple myeloma for patients who have failed at least
two other conventional treatments. Bortezomib
is in a new class of anti-neoplastics called proteasome inhibitors. Proteasomes are enzymes found in all
eukaryotic cells, both healthy and malignant, which help to regulate cell
function and growth. Velcade® reversibly inhibits the 26S
proteasome preventing proteolysis of enzymes involved in cellular
homeostasis. This inhibition alters the
intracellular concentration of certain proteins and affects multiple signaling
cascades. Ultimately, the inhibition
disrupts normal homeostatic mechanisms and may lead to cell death. Velcade®
is available as a 3.5mg vial and the usual dose is 1.3 mg/m2 per dose given as an IV bolus twice weekly for 2
weeks and cycled every 3 weeks. There
should be at least 72 hours between doses and 10 days between each cycle. The most commonly reported side effects
include nausea, vomiting, diarrhea, constipation, tiredness, thrombocytopenia
(40%), orthostatic hypotension (12%), decreased appetite, and fever. Velcade® was approved by the FDA in less than four months via a rapid approval
process. Safety and efficacy studies are
now underway. The approximate cost for a
course of therapy will be $20,000. Velcade® is manufactured by Millennium Pharmaceuticals Inc.
5. (Iressa®)
Gefitinib – a new chemotherapeutic agent used in the treatment of advanced
cases of non-small cell lung cancer.
Gefitinib is a new class of anti-neoplastics called epidermal growth
factor receptor inhibitors. Available as
a 250mg tablet and will be dosed at 250 mg orally once daily. If the patient is on a potent CYP3A4 inducer
such as rifampin or phenytoin the dose may be increased to 500 mg daily. The drug is manufactured by AstraZeneca.
6.
(Restasis®) Cyclosporine – a
new eye drop preparation from Allergan. Available as a 0.05% opthalmic emulsion
which is used to increase tear production in patients whose tear production is
suppressed due to inflammation seen in kerato-conjunctivitis sicca. One drop of the emulsion is instilled twice
daily.
7.
(Prilosec® OTC) Omeprazole –
On June 20th, the FDA approved Prilosec® OTC as the first over-the-counter
treatment for heartburn that occurs two or more days per week (frequent heartburn). Prilosec®
OTC will be available as a 20mg delayed release tablet and should be taken once
daily before a meal for fourteen days.
Per the package labeling, consumers are cautioned to contact their
healthcare provider if heartburn returns soon after finishing the fourteen day
course. In addition, consumers are
warned not to take a fourteen day course more frequently than every four months
unless under the care of a physician. Astra
Zeneca will has a three year exclusivity agreement which will block the sale of
generic equivalents until the agreement has expired. Prilosec®
will continue to be available per a prescription for ulcers, GERD, esophagitis,
or other conditions requiring the care of a doctor.
8. (Reyataz®) Atazanavir sulfate – a new protease
inhibitor from Bristol-Meyers Squibb.
This once daily protease inhibitor will help to decrease the pill burden
of HIV patients. The most common lab
abnormality with Reyataz® was
hyperbilirubinemia. 15-24% of subjects became
jaundiced or had scleral icterus (yellowing of the eyes). These conditions were reversed with
discontinuation of Reyataz® and did
not correlate with an increase risk of hepatic damage. The most common reported side effects during
clinical trials were nausea, infection, headache, vomiting, diarrhea, abdominal
pain, somnolence, insomnia, and fever.
Unlike other protease inhibitors which may cause hyperlipidemia, Reyataz® appears to have a minimal effect on
cholesterol and triglycerides.
Drug Safety Notes:
New Warning – [Risperdal®] - incidence of
cerebrovascular adverse events were increased in elderly patients taking
risperidone for dementia-related psychosis.
Events included stroke and transient ischemic attack. See Dear Healthcare Provider Letter dated
16April2003 from Janssen Pharmaceuticals.
New Warning – [Paxil®] - The FDA is currently
reviewing reports of a possible increase in the number of suicidal thoughts and
attempts in children under the age of eighteen who are being treated with
Paxil® for a major depressive disorder. The
safety data under review resulted from clinical trials with Paxil® in pediatric
patients. Even though the investigation
is still underway, the FDA recommends that Paxil® not be used in adolescents
and children for the treatment of depression.
Presently, there is no approved indication for the use of Paxil® in
children and adolescents. Patients,
caregivers, and healthcare providers should be cautioned against abrupt
discontinuation of Paxil®.
Drug in Review
Ximelagatran (ExantaÒ)
By Christine Slingsby , Pharm.D. candidate.
An oral direct thrombin inhibitor that provides competitive,
direct inhibition of both free and clot bound thrombin. Thrombin is responsible for thrombus
formation by activating platelets, subsequent platelet aggregation, and
inducing formation of fibrin.
Ximelagatran is a prodrug, that when taken orally, is
converted to the active drug melagatran.
Ximelagatran has been studied and has proven to be as effective as
warfarin for the prevention of DVT or PE after total knee arthroplasty1. Unlike warfarin, ximelagatran does not
require frequent drug monitoring or dosing adjustments. Ximelagatran produces anticoagulant effects
through a vitamin K independent mechanism, therefore does not require strict
diet or vitamin K intake.
Currently, Ximelagatran is being studied for stroke
prevention in patients with atrial fibrillation2. Dosing for Ximelagatran for DVT prophylaxis
is 24mg BID, beginning on post-op day 1.
Melagatran is excreted renally; therefore caution should be used in
patients with renal failure. Further studies are also needed to adequately
establish safety for long term use of this drug since it appears to elevate
liver enzymes more than warfarin in the
SPORTIF trial ( ALT > 3x ULN : 6.5% ximelagatran vs 0.7% warfarin)2. Until
FDA issues its final approval, this product is considered investigational.
Edited by:
Ruth Avelino, Pharm.D.
Reference:
1. Francis
CW, Davidson BL,
2. SPORTIF
III trial – presented for
Drug Information Notes:
1. New neonatal dosing
for Acetaminophen: (CHOI – NICU protocol)
Acetaminophen dosing for CHOI NICU
Scheduled dosing as follows for 24 hours post op, post vaccination, etc. then change to PRN dosing if desired.
|
|
Loading
dose (mg/kg) |
Maintenance
dose (mg/kg) |
Dosing
interval (hours) |
|
Oral dosing |
|
|
|
|
≤32 weeks PMA |
25 |
12 |
12 |
|
32-36 weeks PMA |
25 |
15 |
8 |
|
≥36 weeks PMA |
25 |
15 |
6 |
|
Rectal dosing |
|
|
|
|
≤32 weeks PMA |
35 |
15 |
12 |
|
32-36 weeks PMA |
35 |
20 |
8 |
|
≥ 36 weeks PMA |
35 |
20 |
6 |
PMA= postmenstrual age
References:
Arana. Acta Anaesthesiol Scand 2001; 45(1):20-29.
Hansen. Acta Anaesthesiol Scand 1999; 43(8):855-859.
VanLingen. Arch Dis Child Fetal Neonatal Ed 1999; 80(1):59F-63F.
2. Which weight would you use to dose an obese
patient for ABELCET?
A: Studies done by the drug company
suggested using Lean body weight for which the closest estimate would be the
IBW.
By Ruth Avelino
Reference:
3.
IV Administration of oral N-acetylcysteine in Acetaminophen Overdose
By:
Azra Hussain
N-acetylcysteine
(NAC) is the only treatment approved by the FDA for acetaminophen
poisoning. Currently, only the oral
preparation is available commercially.
An investigational intravenous formulation does exist; however, it is
only available through an investigational protocol at a limited number of
poison control centers in the
Consent: Inform
physician and/or patient that the IV preparation is not pyrogen free.
Prepare the
physician and /or administering nurse what to expect for side-effects and
potential treatments available.
Indications
for IV Administration:
Oral NAC cannot be tolerated
Necessary ongoing GI decontamination
(due to coingestant)
GI bleeding or obstruction
Medical or surgical conditions
preventing oral NAC administration
Acetaminophen toxicity presenting as
encephalopathy
Neonatal acetaminophen toxicity from
maternal overdose
Dose: The typical oral loading dose and maintenance
dose of NAC is 140mg/kg
x 1 dose,
then 70mg/kg Q4h x 17 doses (72 hours) respectively. However, when oral NAC is given
intravenously, the guidelines become less defined. The most common dosing regimen for oral NAC
administered intravenously is a loading dose of 140mg/kg x 1 dose followed by
12 doses of 70mg/kg Q4h (for a total of 48 hours).
IV
Preparation:
Dilute 20% NAC solution
to 3% solution with D5W
Administration:
LD & MD = Infuse over 1 hour through a peripheral line
using an in-line 0.2
micron Millipore
filter
Adverse
Events Associated with IV Administration of Oral NAC:
Initial
Infusion related events :( Did not interfere with further NAC treatment)
1.)
Blotchy red face and confluent redness
over neck upper chest (resolved spontaneously without tx)
2.)
Itching
(resolved with benadryl)
3.)
Anaphylactic
reaction (resolved with benadryl)
4.)
Red
streak along IV site (resolved with rotating injection sites)
References:
Bailey B,
McGuigan M: Management of Anaphylactoid
Reactions to Intravenous
N-acetylcysteine. Annals
of Emergency Medicine 1998; 31: 710-715.
We
shouldn’t have to, but we must. Critical Care Medicine 1998; 26: 7.
Smilkstein
MJ, Bronstein AC, Linden C, et al:
Acetaminophen overdose: a 48-
hour intravenous N-acetylcysteine
treatment protocol. Annals of
Emergency Medicine 1991; 20: 1058-1063.
Yip L, Dart
RC, Hurlbut KM: Intravenous
administration of oral N-acetylcysteine.
Crtical Care Medicine 1998; 26: 40-43.
4.
How is Erythropoietin (Epogen®/Procrit®) dosed in the treatment of
anemia due to critical care? (amc)
This
protocol has been purposed for use in SICU/MICU if Hematocrit is 30-36% /
hemoglobin (10-13 g/dl). The regimen is
to start erythropoietin at 300 IU/kg/day on day 3 of ICU stay and continue for
a total of 5 days. Continue the patient
on the same dose on a QOD regimen to achieve a hematocrit of >38%, for a
minimum of 2 weeks or until discharged from the ICU or goal hematocrit is
achieved. The study utilizing this
dosing regimen concluded the patients given erythropoietin required less
transfusion of RBCs and the drug raised the hematocrit concentrations.
Patients
must also be started on concurrent iron therapy with oral or parenteral
iron. Start oral therapy when bowel
sounds are present at a dose of >/= 150 mg of elemental iron (a 325 mg
tablet of ferrous sulfate is 65 mg of elemental iron) daily in divided
doses. Use parenteral iron therapy if unable
to take oral therapy or if there is an inadequate response to oral therapy as
measured by a transferrin saturation < 20% and a decrease in serum ferritin
to < 100 ng/ml.
There are
other dosing regimens that have been studied but this should be the one most
commonly seen in the ICUs at
The primary
reason to use Epogen® in this patient population was to reduce the need for and
risk of blood transfusion. These studies
were conducted in patients who were in an ICU setting and use on the general
surgical floors should be investigated thoroughly by the pharmacist who
receives an order for Epogen® for a non-ICU surgical patient. The intent of these studies was to focus on
“long-term” ICU patients who are likely to have the most transfusions.
It is also
suggested that patients receiving these agents should have had a baseline iron
studies done and should be on some iron supplement since the hormone would most
likely put demands on the body’s existing iron stores.
References:
Corwin, HL.
Gettinger, A. et al. Efficacy of
recombinant human erythropoietin in the critically ill patient: A randomized,
double blind, placebo-controlled trial. Critical Care Medicine 1999 Vol.27 (11); 234-2350.
Corwin, HL,
Gettinger, A. et al. Efficacy of
recombinant human erythropoietin in critically ill patients: A randomized
controlled trial. JAMA December 2002 Vol 288(22); 2827-2835.
5.
How is NovoSeven® (recombinant activated factor VII) used for control of
hemorrhaging in non-hemophiliac trauma patients? (amc)
Trauma
patients who develop extensive, life-threatening bleeds suffer from a
combination of trauma-induced coagulopathies and surgical bleeding. Hemorrhage is often unresponsive to
transfusion therapy or surgical intervention.
Case reports are starting to surface in the medical literature about the
off-label use of NovoSeven® for the adjunctive treatment of hemorrhage in this
trauma population. The mechanism of
action NovoSeven® at the site of injury suggests that it may stop bleeding
without causing a systemic, hypercoagulable state. The NovoSeven® reacts with tissue factor at
the site of injury and triggers platelet aggregation. In these case reports the NovoSeven® utilized
after other conventional therapeutic options had been exhausted. The doses that were utilized ranged from 40
mcg/kg to 144 mcg/kg as a one time dose in most cases. There were a few cases that received repeat
doses, with 3 total doses listed in several of the case studies. The NovoSeven® was reconstituted and
administered according to package insert instructions.1,2,3
NovoSeven® has also been used for
the rapid reversal of warfarin-induced anticoagulation in patients with life-threatening
hemorrhage. This is again an off-label use for the drug. A
treatment protocol and standing orders are currently under review by the
P&T Committee which would outline specific criteria for use and provide
dosing information utilizing a weight based nomogram to determine the amount of
NovoSeven® to be given. The NovoSeven® would be given in conjunction
with the usual “standard of care” for treating warfarin induced bleeding: fresh
frozen plasma and Vitamin K.4, 5
Reference:
1. O’Neill, PA.
Bluth, M. et al. Successful Use
of Recombinant Activated Factor VII for Trauma-Associated Hemorrhage in a
Patient without Preexisting Coagulopathy.
The Journal of TRAUMA Injury,
Infection, and Critical Care. Feb.
2002 Vol.52(2); pp.400-405.
2. Dutton, RP.
Hess, JR. Scalea, TM. Recombinant factor VIIa for control of
hemorrhage: early experience in critically ill trauma patients. Journal
of Clinical Anesthesia. May 2003
Vol.15(3).
3. Martinowitz, U. Kenet, G. et al. Recombinant Activated Factor VII for
Adjunctive Hemorrhage Control in Trauma.
The Journal of TRUAMA Injury,
Infection, and Critical Care. Sept.
2001 Vol.51 (3); pp.431-439.
4. Micromedex 2003. Volume 116. Drug
Evaluations: Factor VII, therapeutic uses: Anticoagulation reversal
5. Deveras RAE. Kessler, CM. Reversal of Warfarin-Induced Excessive
Anticoagulation with Recombinant Human Factor VIIa Concentrate. Annals
of Internal Medicine. Dec. 2002. Vol.137
(11); pp.884-888.
Investigational
Drug Services Updates:
Acetaminophen
Study Medication will
be taken from Suremeds
ANGIOMAX
Study Medication will be stored in Main
Pharmacy
AT-3 ECMO
Study Medication will be stored in Gerlach
Pharmacy
CAPS Study Medication will be stored in Gerlach
Pharmacy
Ketorolac
Study Medication
will be stored in Gerlach Pharmacy
RESOLVE
Study Medication
stored in Gerlach Rx refrigerator
RSV Thickened Formula Study Randomization list will be in Gerlach
Pharmacy ID Binder (no drug involved)
ADDRESS
Study Medication stored in Gerlach Rx
refrigerator
APOLLO
Study Medication
will be stored in Main Pharmacy
BAXTER
rAHF-PFM Study Medication will be stored in Main Pharmacy
CORLOPAM
Study Medication will be stored in Gerlach
Pharmacy
CancerVax
Study Medication
stored in Main Rx Nitrogen freezer
DEDAS Study Medication stored
in Gerlach Rx refrigerator
ESAI Study Medication
stored in Gerlach Rx refrigerator
EXCLAIM
Study Medication
will be stored in Main Pharmacy
ONO Stroke
Study Medication will be stored in Gerlach
Pharmacy
PREVENT
Study Medication will be stored in Main
Pharmacy
SYNERGY
Study Medication will be stored in Gerlach
Pharmacy