THE PHARMACY ADVISOR
A Publication of the Beth Israel Deaconess Medical Center
Department of Pharmacy and Pharmacy & Therapeutics Committee
Volume II, Issue 1
BIDMC Medication Dosing Guidelines for
the Critically Ill Patient
Dosing guidelines for medications frequently prescribed for the
critically ill patient can now be found on the BIDMC intranet
within the Critical CareWeb site. The guidelines are the work
product of the collaborative efforts of the Department of Pharmacy
and the Critical Care Workgroup and have been approved by the
Critical Care Executive Committee as well as the Pharmacy &
Therapeutics Committee.
The guidelines provide general dosing regimens for several
medication classes frequently used in the critical care setting,
including: anticonvulsants, cardiac medications (antiarrhythmics,
antihypertensives, inotropes, vasodilators and vasopressors),
electrolytes, neuromuscular blocking agents and sedatives. Within
each medication class, information is provided with regard to
indication, loading dose, maintenance dose, dosing for organ
dysfunction and monitoring parameters. Special instructions are
provided for IV admixture preparation to facilitate the initiation of
medication emergently needed in the intensive care areas. Special
precautions and extravasation information are provided when
applicable.
In addition to references, information regarding BIDMC specific
laboratory values, serum drug levels and commonly used equations
and calculations pertinent to medication dosing are provided in the
appendices. For additional information or questions regarding the
dosing guidelines, contact the clinical pharmacy pager at 31195.
INSIDE THIS ISSUE
1
2
3
4
BIDMC Medication Dosing Guidelines for the Critically Ill
Patient
Formulary Update: Pegfilgrastim (Neulasta);
Darbepoetin (Aranesp); Mesna (Mesnex);
Non-Formulary Medication Use at BIDMC
BIDMC Department of Pharmacy
Top Pharmaceutical Purchases for FY02
Influenza Update
BIDMC Update on Drug Shortages
The Pharmacy Advisor is a publication of the Department Of
Pharmacy and the Pharmacy & Therapeutics Committee at
the Beth Israel Deaconess Medical Center, Boston, MA 02215
Writing/Editorial Board:
Katherine Giampietro, PharmD
Christopher McCoy, PharmD
Lisa Saubermann, PharmD
Diane Soulliard, PharmD
Bruce Bistrian, MD, Co-Chair P&T
James Heffernan, MD, Co-Chair P&T
Francis P. Mitrano, M.S., RPh
5
January 2003
P&T Formulary Update
The following medications have recently been approved for
addition to the BIDMC formulary
Pegfilgrastim (Neulasta) Pegfilgrastim is a covalent
conjugate of recombinant methionyl human G-CSF (filgrastim)
and monomethoxypolyethylene glycol, designed to provide a
sustained duration of action. Pegfilgrastim’s longer half-life is, in
part, attributable to both its pegylation with the filgrastim
molecule and its unique clearance mechanism. Pharmacokinetic
studies of pegfilgrastim show that serum concentrations remain
elevated during neutropenia, but rapidly decline during ANC
recovery post chemotherapy nadir, suggesting a saturable
neutrophil-mediated elimination
FDA Approved Indications: Neulasta is indicated to decrease
the incidence of infection, as manifested by febrile neutropenia,
in patients with non-myeloid malignancies receiving
myelosuppressive anti-cancer drugs associated with a clinically
significant incidence of febrile neutropenia.
Dosing: Adults and adolescents >45kg: Neulasta is
administered as a single subcutaneous injection of 6 mg
administered once per chemotherapy cycle. Neulasta should not
be administered in the period between 14 days before and 24
hours after the administration of cytotoxic chemotherapy.
BIDMC Restrictions: Outpatient oncology
Darbepoeitin (Aranesp): Darbepoetin is a long-acting
epoetin analog.
FDA Approved Indications: Aranesp is indicated for the
treatment of anemia associated with chronic renal failure,
including patients on dialysis and patients not on dialysis, and for
the treatment of anemia in patients with non-myeloid
malignancies where anemia is due to the effect of concomitantly
administered chemotherapy.
Dosing: Please note that dosing regimens are different for each
of the approved indications of Aranesp. Additionally, due to
the longer serum half-life, Aranesp should be dosed less
frequently than Epoetin alfa.
Based on literature evaluation and review of available data, the
P&T Committee has approved the recommended dosing regimen
for darbepoetin for oncology related anemia to be 100mcg weekly
or 200mcg every other week. The dose should be adjusted for
each patient to achieve and maintain a target hemoglobin level
not to exceed 12 g/dL.
Please refer to the package insert for dosing information for
patients with chronic renal failure.
BIDMC Restrictions: Outpatient treatment of anemia
associated with chronic renal failure and anemia in patients with
non-myeloid malignancies where anemia is due to the effect of
concomitantly administered chemotherapy. Darbepoetin
guidelines will be published in an upcoming issue of the
Pharmacy Advisor.
Formulary Update Continued on Page 3
The Pharmacy Advisor 1
BIDMC Pharmaceutical Purchases for FY02
Pharmaceuticals constitute a significant component of the cost associated with the provision of patient care at BIDMC. Each year the
Department of Pharmacy publishes a list of top pharmaceutical expenditures so as to provide caregivers insight to the fiscal impact of
prescribing at BIDMC. The chart below provides, in the left hand column, a listing of the top 25 pharmaceutical expenditures for FY02.
These 25 medications comprise more than half of the $22.5 million dollar pharmaceutical expenses for that year. Because of the significant
cost of chemotherapeutic medications used in the treatment of oncology related diseases and disorders, a second column is provided to list
the top 25 expenditures for non-oncology related pharmaceuticals.
Top 25 pharmaceutical expenditures for FY02
GENERIC
BRAND NAME
Top 25 non-oncology pharmaceutical expenditures for FY02
FY02
Purchases
GENERIC
BRAND NAME
FY02
Purchases
$1,563,586
Epoetin Alfa
Epogen Procrit
$1,563,586
Epoetin Alfa
Epogen Procrit
Trastuzumab
Herceptin
$1,022,368
Eptifibatide
Integrilin
$985,310
Eptifibatide
Integrilin
$985,310
Infliximab
Remicade
$691,009
Rituximab
Rituxan
$872,365
Propofol
Propofol
$545,251
Aldesleukin
Proleukin
$691,498
Amiodarone
Cordarone
$466,828
Infliximab
Remicade
$691,009
Zofran
$367,440
Gemcitabine
Gemzar
$656,881
Ondansetron
Lymphocyte Immune
Globulin
Thymoglobulin
$299,470
Carboplatin
Paraplatin
$619,432
Levofloxacin
Levaquin
$208,136
Paclitaxel
Taxol
$587,787
Fluconazole
Diflucan
$196,112
Propofol
Propofol
$545,251
Liposomal Amphotericin B
Ambisome
$195,110
Docetaxel
Taxotere
$503,842
Alteplase
Activase
$184,004
Amiodarone
Cordarone
$466,828
Enoxaparin
Lovenox
$183,059
Irinotecan
Camptosar
$459,894
Ceftriaxone
$164,299
Pamidronate Disodium
Aredia
$458,006
Lorazepam
Rocephin
Ativan and
Others
Interferon Alfa 2b
Intron A
$433,876
Desflurane
Suprane
$141,569
Ondansetron
Lymphocyte Immune
Globulin
Zofran
$367,440
Vancomycin
Vancomycin
$128,220
Thymoglobulin
$299,470
Beractant
Survanta
$116,496
Filgrastim
Neupogen
$227,592
Piperacillin/Tazobactam
Zosyn
$102,536
Levofloxacin
Levaquin
$208,136
Aprotinin
Trasylol
$94,492
Fluconazole
Diflucan
$196,112
Nesiritide
Natrecor
$91,970
Liposomal Amphotericin B
Ambisome
$195,110
Ceftazidime
Fortaz
$83,376
Leuprolide
$192,779
Metoprolol
Metoprolol
$82,952
Octreotide
Lupron
Sandostatin
and Others
$186,092
Lidocaine
Lidocaine
$81,189
Alteplase
Activase
$184,004
Atorvastatin
Lipitor
$75,588
Enoxaparin
Lovenox
$183,059
Ranitidine
Ranitidine
$73,562
$148,358
The Pharmacy Advisor 2
Influenza Update
Formulary Update continued:

Mesna Oral Tablets (Mesnex ): The oral formulation
of paraenteral mesna.
Alert Activated In POE for Automated Ordering
of Influenza Vaccine
FDA Approved Indications: Mesnex is indicated as a
prophylactic agent in reducing the incidence of ifosfamideinduced hemorrhagic cystitis.
Dosing: For the prophylaxis of ifosfamide-induced
hemorrhagic cystitis, mesna is administered as a single IV bolus
at the time of ifosfamide administration in a dose equal to 20%
of the ifosfamide dose (w/w). The IV mesna dose is followed
by two oral doses of mesna tablets, each in a dose equal to 40%
of the ifosfamide dose (w/w) given at 2 and 6 hours after each
dose of ifosfamide. The total daily dose of mesna is equal to
100% of the ifosfamide dose. Patients who vomit within two
hours of taking oral mesna should repeat the dose or receive
intravenous mesna. The dosing schedule of mesna should be
repeated on each day that ifosfamide is administered. When the
dosage of ifosfamide is adjusted, the dose of mesna should be
adjusted accordingly.
BIDMC Restrictions: Outpatient oncology
Recent publications and news stories have addressed the poor
rates of influenza and pneumococcal vaccination of patients
aged 65 years and older in the United States. This has been
particularly alarming with the abundant evidence demonstrating
that yearly vaccination against influenza virus can prevent the
illness that is associated with such high morbidity and mortality
in this population.
A recent Centers for Disease Control study published in the
Morbidity and Mortality Weekly Report on November 15th
summarizes the results of a large telephone interview based
survey of United States citizens. conducted in 2001 regarding
their vaccination status. The authors reported estimated point
prevalence of influenza and pneumococcal vaccination of <80%
among persons aged >65 years in all reporting areas. The
reported levels had decreased from a previous study from 1999
in more than half of the states summarized. The authors did
note that this decline in vaccination may have been caused by a
delay in the national supply of vaccine during that year. The
November 11th issue of Archives of Internal Medicine reported
the results of a retrospective chart review of over 100,000
Medicare covered inpatients for documentation of vaccination.
The patients were all aged 65 or older and were discharged from
hospitals in the United States between October and December
of 1998. Approximately 31.6 percent were vaccinated prior to
admission and of the approximately 68% of patients
unvaccinated prior to admission, a disappointing 2.7% of
patients were vaccinated during their hospitalization.
In an effort to stay ahead of this trend at BIDMC, an automated
reminder system for providers has been activated. As previously
reported in the Pharmacy Advisor, a supply of influenza vaccine
is stocked and available for inpatient use at BIDMC. In
November, the Provider Order Entry computer system was
programmed with a new screening and reminder tool to
encourage the vaccination of all eligible inpatients with the
influenza vaccine. Prescribers signing on to enter orders for a
new patient admission are prompted with a message reminder to
order influenza vaccine unless a contraindication is present.
High risk patients, in brief, include all patients over age 50,
patients older than 6 months old with select chronic diseases,
e.g., diabetes, obstructive and reactive airway disease,
cardiovascular disease, end stage renal disease. High-risk patients
and hospital inpatients should receive influenza immunization
unless previously administered or contraindicated.
Contraindications include a history of serious allergy or adverse
effect to the vaccine, including neuromuscular disease or serious
allergy to egg protein, latex or thimerosal. A relative
contraindication is the presence of an active fever in the setting
of acute illness (temperature greater than 100.50 F.) The vaccine
does not contain live or attenuated influenza virus and as such is
not contraindicated in immunocompromised patients.
Non-formulary Medication Use at BIDMC
Formulary development and maintenance is a dynamic process
requiring ongoing appraisal of new and existing medications. To
assure optimization of the formulary at BIDMC while ensuring
medication safety and fiscal management of clinical resources,
the P& T Committee will heighten its review process of nonformulary medication requests. Non-formulary requests will be
featured as a regular committee meeting agenda item, with the
goal being to expedite review of medications by the committee
for formulary evaluation and limiting the prescribing of nonformulary medication.
The BIDMC currently utilizes a formulary system by which
medications are approved for use within the medical center by
the P& T Committee. The committee reviews medications for
formulary status in all therapeutic categories and classes on the
basis of safety, effectiveness, and cost. Upon completion of the
review process, committee members vote to select appropriate
and cost-effective agent(s) in each medication class for formulary
status. Minimization of therapeutic duplication within the
formulary is also a consideration during the review process.
It is recognized that there are legitimate reasons why the
prescribing of a non-formulary medication may be medically
necessary for optimal patient care. In those instances when a
non-formulary medication is ordered, the unit-based pharmacist
will contact the prescriber to discuss formulary alternatives. If
there is a clinical rationale for no-substitution with a formulary
agent, the prescriber will be asked to complete a non-formulary
request. Should it be determined that a non-formulary
medication is medically necessary, the clinician will be informed
of the expected time to procure the medication and determine if
interim alternatives need to be ordered.
Practitioners are encouraged to prescribe formulary medications
whenever appropriate. Feedback from the non-formulary
review process will be provided to Department Chiefs as well as
to individual prescribers to assist in formulary management and
fiscal control of pharmaceutical expenditures. Requests for
formulary considerations of medications to the BIDMC
formulary should be forwarded to Kathy Giampietro, PharmD,
Director of Clinical Pharmacy programs and Secretary to the
P&T Committee.
This reminder program will continue through the influenza
season into March of 2003. While it is best to provide
immunization in November or December of the given year,
vaccination in January or February is not without merit.
Information provided by the state department of public health
indicates that the incidence of reported laboratory confirmed
influenza cases peaked in mid February of 2002 during the 20012002 influenza season. Please provide influenza immunization
to all inpatients, as appropriate.
The Pharmacy Advisor 3
BIDMC Update on Drug Shortages
The following update is a regular feature in the Pharmacy Advisor, providing information to clinicians at BIDMC regarding nation-wide
drug shortages. The Pharmacy Department actively monitors current drug shortages to ensure that product acquisition and inventory
management of pharmaceuticals are kept at levels necessary to provide optimal care to the patients at BIDMC. When it is determined that
a particular drug shortage will be ongoing and will exceed our inventory supplies, the pharmacy evaluates and reviews available alternatives
and formulates contingency plans. For immediate patient care needs relating to products that are unavailable, the unit-based pharmacist
will contact the prescriber directly to discuss therapy and make recommendations for alternate treatment.
The following list provides information regarding current drug shortages. The impact on prescribing at BIDMC is highlighted. Additional
information regarding these and other national drug shortages can be found via the link on the Pharmacy page of the BIDMC intranet.
This link connects to the ASHP website and provides detailed information regarding national medication shortages listed below and others.
Antibiotics/antivirals:

Ampicillin/sulbactam (Unasyn): Nationwide shortage. Currently BIDMC had been receiving intermittent supplies sufficient to provide
uninterrupted therapy when prescribed. Should BIDMC deplete its inventory, the pharmacy will work with the ID approval fellow on call
to formulate alternate antibiotic regimens.

Ganciclovir injection (Cytovene): Ganciclovir injection has been on a long-term nationwide back order due to production issues. Roche has
communicated that the shortage is resolved; however they are limiting orders. BIDMC is procuring inventory as allocated by the manufacturer.
The pharmacy will notify practitioners if sufficient supplies are not available to initiate therapy.

Meropenem (Merrem): Meropenem has been on nationwide back order for several months. At the end of 2002, AstraZeneca instituted a Medical
Necessity Program to ensure the availability of Merrem™ I.V. for critically ill patients. Limited supplies are now being released from the
manufacturer and the BIDMC has a small supply on hand which will be reserved for patients for whom treatment with
imipenem/cilistatin (Primaxin) or other therapy is not appropriate. Clinicians should contact the ID approval fellow on call to discuss
patient-specific circumstances and determine the most appropriate therapy.

Valganciclovir (Valcyte): Valganciclovir tablets are on nationwide back order due to increased demand and decreased supply. Roche is limiting
orders of valganciclovir tablets. BIDMC is procuring inventory as allocated by the manufacturer. The pharmacy will notify practitioners if
sufficient supplies are not available to initiate therapy.
Vancomycin hydrochloride for oral use: Lilly is having manufacturing difficulties with the oral capsules and has permanently discontinued
vancomycin oral solution. There are no other manufacturers of vancomycin hydrochloride for oral use. BIDMC prepares oral vancomycin for
inpatients by using the parenteral formulation and compounding an oral solution; and thus has not been affected by this shortage.
Patients discharged on oral vancomycin or prescribed oral vancomycin in the outpatient setting may experience difficulty filling
prescriptions. Prescribers should contact patient’s pharmacies to verify availability.

Antiemetics:

Prochlorperazine injection, CompazineSpansules, and Compazinesyrup: Continued nationwide back order due to increased demand for
product and a delay in obtaining raw material. Prochlorperazine rectal suppositories and oral tablets are not affected by this shortage and
should be prescribed as appropriate. Although metoclopramide and promethazine have intermittently been in short supply, BIDMC
currently has sufficient quantities in stock to recommend either agent as alternatives for patients requiring parenteral antiemetic therapy.
Diuretics:

Chlorothiazide (Diuril) injection: Long term back order with Merck. Currently, intermittent product is available from the manufacturer
and BIDMC is procuring inventory as allocated by the manufacturer. Verify availability with the pharmacy prior to initiating therapy.
Parenteral Steroids:

Betamethasone (Celestone Soluspan): Long-term nationwide back due to increased demand for the product. Schering-Plough has limited
supplies of betamethasone acetate and betamethasone sodium phosphate injection (Celestone Soluspan) which is available for use only in labor and
delivery settings. BIDMC will comply with regulations to provide allocated betamethasone injection (Celestone Soluspan) for use only in
the labor and delivery settings.

Hydrocortisone injection (Solu-Cortefand others): Nationwide backorder from all manufacturers due to increased demand and manufacturing
difficulties. BIDMC has been able to procure a supply of 1g vials and is currently manufacturing smaller doses on a patient-specific basis.
The pharmacy will continue to update practitioners with the hydrocortisone inventory status.

Methylprednisolone acetate suspension injection (Depo-Medrol): Nationwide back order due to manufacturing problems. Manufacturers are
allocating limited shipments on a monthly basis. BIDMC is allocating this limited supply within the medical center upon receipt.

Methylprednisolone sodium succinate (Solu-Medrol): Nationwide back order due to manufacturing problems. BIDMC has been receiving
intermittent shipments and currently has a limited supply of methylprednisolone sodium succinate (Solu-Medrol) injection in stock.

Triamcinolone diacetate injection (Aristocort) and triamcinolone hexacetonide injection (Aristospan): Fujisawa has temporarily
discontinued production of both products while correcting the manufacturing problems. Production is expected to resume in late 2003.
BIDMC does not have either Atristocort™ or Aristospan™ injection in stock.

Triamcinolone acetonide injection (Kenalog-10, Kenalog-40): Nationwide back order due to increased demand. BIDMC has been
receiving intermittent shipments and currently has a supply of Kenalog injection in stock.
Proton Pump Inhibitors:

Pantoprazole injection (Protonix ): Parenteral pantoprazole is currently on nationwide backorder from the manufacturer. Prior to this shortage,
pantoprazole injection had been available on an allocation basis and BIDMC was able to maintain an inventory sufficient to meet patient care needs.
The manufacturer indicates that product will be released on a reduced allocation basis beginning February 2003. Currently, BIDMC’s supply of
parenteral pantoprazole in exhausted. A committee is being convened to formulate guidelines for the limited pantoprazole allocation
when available. There is no shortage of oral pantoprazole. All patients requiring therapy with a PPI, and are able to tolerate oral or
nasogastric therapy, can be prescribed pantoprazole tablets or lansoprazole suspension respectively. Famotidine is available for patients
requiring parenteral acid suppression.
The Pharmacy Advisor 4