THE PHARMACY ADVISOR
A Publication of the Beth Israel Deaconess Medical Center
Department of Pharmacy and Pharmacy & Therapeutics Committee
Volume 1, Issue 3
Influenza Vaccine Update
Influenza vaccination is the primary method for preventing influenza
and its severe complications. As we enter the 2002-2003 influenza
season, we are fortunate to announce that communications from all
influenza vaccine manufacturers indicate that there will be no
shortage of vaccine this year. It was reported in a recent Centers for
Disease Control and Prevention (CDC) bulletin that based on
aggregate manufacturers’ estimates, approximately 94 million doses of
flu vaccine will be produced for the 2002-2003 influenza season. This
exceeds the 87 million doses produced last season. Additional
information from the manufacturers indicates that approximately 80
percent of the total production is anticipated to be distributed by
November 1st. Consistent with this information, the BIDMC has
received scheduled deliveries of vaccine on time and allocation to
various clinics and patient care areas is underway and ongoing.
Recommendations for the Prioritization of Influenza Vaccine for the
2002-2003 influenza season are published by several public health
organizations, including the CDC ( www.cdc.gov/nip/flu/) and the
Massachusetts Department of Public Health Immunization Program
(MIP) [www.state.ma.us/dph]. Excerpts from the guidelines are
provided later in this article.
In accordance with the aforementioned recommendations, the
BIDMC has allocated initial supplies of vaccine to those patients at
highest risk for complications from influenza. Sufficient vaccine has
been received at the BIDMC so that expanded immunization
initiatives are now possible.
Planned employee immunization
programs will begin the first week in November. Specific dates, times
and locations will be forthcoming from Employee Health.
INSIDE THIS ISSUE
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2
3
Influenza Vaccine: BIDMC Update for the 2002-2003
Influenza Season
Pharmacy Care Note: BIDMC Department of
Pharmacy Care Note and Unit-Based Pharmacy Practice
Model
Formulary Update:
Voriconazole (Vfend); Argatroban
BIDMC Medication Dosing Guidelines for the
Critically Ill: Electrolyte Repletion Sliding Scale
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
4
October 2002
Additional efforts will be made this year at BIDMC to provide
expanded access to influenza vaccine to inpatients. The
Massachusetts Department of Public Health (MDPH), the
Massachusetts Peer Review Organization (MassPRO), the
Department for Health and Human Services and others, have
asked all health care providers to vaccinate patients against
influenza and pneumococcal disease, which are the most
common vaccine-preventable causes of death in the U.S. It is
further stated that to avoid missed opportunities, persons at
highest risk for complications from influenza should be
vaccinated when they are seen for routine health care or are
hospitalized. Beginning in early November, clinicians at BIDMC
will be alerted by the hospital’s Provider Order Entry computer
system (POE) to prescribe influenza vaccine to inpatients unless
contraindications are present. Additional details regarding this
initiative will be announced prior to the program roll out.
Based on guidelines from the Advisory Committee on
Immunization Practices (ACIP), the MIP provides the following
recommendations for groups recommended for vaccination:
People at highest risk for complications from influenza, and
who therefore should be the first priority for flu vaccine,
include:
 All adults > 65 years of age.
 Residents of any age in long-term care facilities housing
persons with chronic medical conditions.
 People 6 months through 64 years of age who have: chronic
pulmonary or cardiovascular disease, including asthma.
 People 6 months through 64 years of age who required
regular medical follow-up or hospitalization during the
preceding year for chronic metabolic diseases (including
diabetes); renal dysfunction; hemoglobinopathies; HIV
infection; or immunosupression caused by other diseases,
medications or treatments.
 Children and teenagers (aged 6 months to 18 years) on longterm aspirin therapy.
 Women who will be in the second or third trimester of
pregnancy during flu season.
Other groups:
Influenza vaccine is also recommended for persons who can
transmit influenza to persons at highest risk for complications:
 Household contacts of high-risk persons
 Health-care workers
 Persons who provide home care to persons in high-risk
groups
 Out-of-home caretakers of children 0-23 months of age
 It is also recommended for healthy persons 50-64 years
of age
Because influenza season in New England generally does not
begin until December and does not peak until February,
vaccination efforts should continue through December and
throughout the entire influenza season, as long as influenza
vaccine is available.
The Pharmacy Advisor 1
BIDMC Department of Pharmacy
Unit-Based Pharmacist Practice Model and Pharmacy Care Note
Inpatient pharmacy services at BIDMC are provided by decentralized clinical pharmacists in a unit-based practice model. Within this
model, pharmacists are assigned to cover several patient care areas and are responsible for the pharmaceutical care of the patients on
those units. The recent interface of the new pharmacy computer system with the hospital’s Provider Order Entry (POE) system
facilitates this practice model by allowing pharmacists to review and acknowledge patient’s medication orders while on any nursing unit
within the medical center. The ability of the pharmacists to practice directly in patient care areas allows greater interaction with the
medical team and other care-givers and ultimately is aimed at improving patient care. On the nursing unit, pharmacists are able to screen
medication orders for potential problems with dosing, drug allergies, drug interactions, and other medication-related issues and inform
prescribers of potential problems and possible drug therapy modification.
In addition to medication order processing, each unit-based pharmacist performs a number of other clinical activities relating to
medication therapy. Pharmacists are actively involved in providing drug information, performing pharmacokinetic evaluation and dosing
of select medications, reviewing medications for renal dose adjustment, evaluating medication profiles for potential intravenous to oral
medication interchange and monitoring target medications. Should you need to contact the pharmacy to assist with drug-related
questions or issues, the unit-based pharmacist is accessible by pager. Pager numbers for the unit-based pharmacist are posted in each
patient care area.
Interdisciplinary communication is integral in the provision of optimal patient care. To facilitate timely communications regarding
medication therapy, the BIDMC Department of Pharmacy has developed a Pharmacy Care Note, which will be placed in the progress
notes section of the patient’s medical record. This new communication document features several common areas of medication therapy
where pharmacist interventions are frequently made to optimize pharmaceutical care. Additionally, the unit-based pharmacist
responsible for providing coverage for the patient on a particular day, will utilize the Care Note to provide pertinent information
regarding their assessment and recommendations regarding specific medication therapy when appropriate.
It is recognized that direct interdisciplinary communication is essential when immediate intervention regarding medication therapy is
required. For such instances, the unit-based pharmacist will contact prescribers directly to discuss said therapy and make
recommendations.
The list below features the target interventions on the Pharmacy Care note. A brief description of each is provided.

Non-Formulary Medications Request: The BIDMC has a formulary system by which medications are approved for inpatient use
by the P&T Committee. 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, clinicians are
informed of the expected time to procure the medication and determine if interim alternatives need to be ordered. If it is determined
that a non-formulary medication cannot be ordered, the unit-based pharmacist will provide that information on the Care Note.

Therapeutic Interchange/Substitution: The P&T Committee has approved an automatic therapeutic interchange for select
medications determined to have therapeutic equivalents [e.g.: pantoprazole has been selected as the preferred proton pump inhibitor
(PPI) on formulary.] When orders are received for a medication within a class that has such a preferred formulary agent, the
pharmacy will automatically change the order to the preferred formulary selection, unless indicated as medically necessary. POE
facilitates this process by directing the prescriber to select the preferred formulary medication for select medication classes.

Patient’s Own Medication Supply: The pharmacy department supplies all formulary medications to inpatients. If a nonformulary medication is medically necessary for a patient and it is determined that the patient will “take their own supply” of the
prescribed medication, then the pharmacy will identify and approve these medications for the patient’s own use. This information
will be documented on the Care Note. If the medications are not identifiable or there are reasons why the medication/s are not
approved for a patient’s own use, this information will be documented. The unit-based pharmacist will collaborate with the
prescriber to determine if substitution with a formulary agent is possible or if procurement of the non-formulary medication is
required.

Medication History/Compliance Assessment/Medication Information: The unit-based pharmacist will communicate if
he/she has obtained medication history information from the patient, has provided medication counseling or is leaving pertinent
medication information in the chart.

Therapeutic Drug Monitoring/Optimization: Therapeutic drug monitoring and medication optimization are ongoing clinical
functions performed by the unit-based pharmacist. Pertinent information will be provided in the Care Note as applicable.

Renal Dosing/Schedule Adjustment: Reviewing medications for required adjustment in patients with renal insufficiency and
renal failure is an ongoing clinical function performed by the unit-based pharmacist. Recommendations for adjustment will be
provided in the Care Note as applicable.

Intravenous to Oral Therapy Interchange: For certain medications, parenteral and oral bioavailability is nearly equivalent and
published outcomes with utilization of either formulation are similar. For these medications, the unit-based pharmacist will review
patient’s medication profiles and determine if interchange is appropriate. Recommendations will be communicated in the Care Note.
The Pharmacy Advisor 2
P&T Formulary Update
The following medications have been approved by the P&T Committee as additions to the formulary
Voriconazole (Vfend)
Argatroban
Voriconazole (Vfend TM) is a triazole antifungal agent derived
from fluconazole with activity against resistant fungal infections.
Voriconazole exhibits similar MIC’s to itraconazole and
amphotericin B for aspergillus species.
Overview: Argatroban is a synthetic, reversible direct thrombin
inhibitor that is highly selective for both free and clot-associated
thrombin. By inhibiting the catalytic site of thrombin,
Argatroban subsequently affects the conversion of fibrinogen
to fibrin, the formation of the thrombin-antithrombin III
complex, platelet aggregation, the release of plasminogen
activator from vessel walls and activation of factors V, VIII and
XIII.
FDA Approved Indications: Voriconazole is indicated for use
in the treatment of invasive aspergillosis and infection with
Scedosporium apiospermum and Fusarium species in patients
intolerant of, or refractory to, other therapies, particularly
amphotericin B deoxycholate.
Pharmacokinetics: Like fluconazole, voriconazole’s 96% oral
bioavailability is very high; making the two dosage forms
relatively interchangeable in patients without malabsorptive or
obstructive gastrointestinal tracts. The kinetics of voriconazole
is nonlinear. Due to metabolic saturation, changes in plasma
concentration are not directly proportional to changes in dose.
Unlike fluconazole, voriconazole is primarily eliminated via
metabolism by the cytochrome P450 enzyme system to relatively
inactive metabolites. In patients with mild to moderate hepatic
disease, the concentration is increased by as much as 3.2 fold.
Drug Interactions: Voriconazole is both a substrate of and a
powerful inhibitor of the cytochrome P450 enzymes (2C9, 2C19
and 3A4). Pharmacokinetic studies of select substrates, inducers
and inhibitors of the cytochrome system with voriconazole
reveal that the concomitant administration of voriconazole and
the potent enzyme inducers, rifampin, rifabutin, carbamazepine,
and long-acting barbiturates are contraindicated as the levels of
voriconazole are significantly diminished below therapeutic
concentration. Concomitant administration of voriconazole with
sirolimus, pimozide, or quinidine is also contraindicated, as
voriconazole will inhibit their metabolism precipitating
supratherapeutic levels and potential toxicities. Other agents
affected by concomitant voriconazole administration include
phenytoin, diltiazem and the protease inhibitors.
Potential Adverse Drug Reactions: Visual disturbances (e.g.,
abnormal vision, photophobia, chromatopsia, eye hemorrhage)
can occur with voriconazole, particularly with initial doses. This
event usually occurs within 30 to 60 minutes following a dose
and is transient. Other potential adverse effects include
hepatotoxicity, hypersensitivity, and QT prolongation.
Dosing: The intravenous loading dose for empiric or
documented fungal infection treatment is 6 mg/kg Q12H for
two doses, then 4mg/kg IV Q12H rounded to the nearest 50
mg. For patients able to tolerate oral therapy, tablets should be
used. The oral dose for prophylaxis is 200 mg po bid.
Patients with mild-to-moderate hepatic impairment (Child-Pugh
Class A and B) should receive the standard loading dose, but the
maintenance dose should be reduced by 50%. Accumulation of
the intravenous vehicle (SBECD) occurs in patients with
moderate renal impairment (CrCl 30-50 mL/min) and use of the
IV formulation should be avoided in such patients. No dosing
adjustments are required for oral voriconazole.
BIDMC Restrictions: Voriconazole had been added to
formulary and requires Infectious Disease approval. This agent
should be reserved for suspected or confirmed resistant fungal
infections. Guidelines for appropriate use are forthcoming.
FDA Approved Indications: Argatroban is indicated as an
anticoagulant for the prophylaxis and treatment of thrombosis in
patients with heparin-induced thrombocytopenia (HIT).
Argatroban is also indicated for use as an anticoagulant in
patients with or at risk for HIT undergoing percutaneous
coronary interventions (PCI).
Dosing/Monitoring: The recommended initial dose for adult
patients with HIT and without hepatic impairment is 2
mcg/kg/min, administered as a continuous infusion. No loading
dose is required. The aPTT should be checked 2 hours after
initiation of therapy. Dose adjustments should be made as
clinically indicated to aPTT of 1.5 to 3 times the initial baseline,
however the rate should not exceed 10 mcg/kg/min. For
patients with moderate hepatic impairment (AST/ALT levels  3
times the upper normal limit) an initial dose of 0.5 mcg/kg/min
is recommended with close monitoring of the aPTT. No dose
adjustments are required in the presence of renal impairment.
When therapy is to be discontinued it is recommended that the
infusion be tapered since abrupt discontinuation of therapy may
result in a hypercoagulable state.
Side Effects/Precautions: Argatroban is contraindicated in
patients with overt major bleeding or risk of bleeding. The most
frequent non-hemorrhagic events reported are dyspnea,
hypotension and fever. Patients with hepatic impairment should
be initiated at a lower dose with careful titration. Argatroban  is
classified as Pregnancy Category B. It is not known whether this
drug is excreted in human milk. Because of the potential for
serious adverse reactions in nursing infants, a decision should be
made whether to discontinue nursing or to discontinue the drug,
taking into account the importance of the drug to the mother.
Excessive anticoagulation, with or without bleeding, may be
controlled by discontinuing Argatroban or by decreasing the
infusion dosage. In clinical studies at therapeutic levels,
anticoagulation parameters generally returned to baseline within
2 to 4 hours after discontinuation. Reversal of anticoagulant
effect may take longer in patients with hepatic impairment. No
specific antidote to Argatroban is available. If life-threatening
bleeding occurs and excessive plasma levels of Argatroban are
suspected, discontinue Argatroban and monitor aPTT.
Symptomatic and supportive therapy should be provided.
Conclusion: Argatroban is a direct thrombin inhibitor that may
be used in patients with HIT who require an anticoagulant for
prophylaxis or treatment of thrombosis. It is preferred when
lepirudin therapy is contraindicated or in patients with significant
renal impairment. Bivalirudin remains the formulary direct
thrombin inhibitor used in patients undergoing percutaneous
coronary intervention in the catheterization laboratory.
The Pharmacy Advisor 3
BIDMC Medication Dosing Guidelines for the Critically Ill
Electrolyte Repletion Sliding Scale
The management of electrolyte imbalances in the critically ill patient is an integral component of patient care. As a process improvement
initiative to standardize the practice of electrolyte repletion, the Critical Care workgroup has developed general guidelines for the repletion
of magnesium, calcium, phosphorous and potassium in the critical care setting. Included in the guidelines are suggested doses and
administration rates for each electrolyte. The guidelines are not intended to replace clinical judgment, where patient specific factors,
including the underlying disease, comorbid conditions, concomitant medications, fluid status and other factors may warrant modification of
the recommendations.
Endorsed by the Critical Care Executive Committee, the guidelines are posted on the Clinical portal of the BIDMC Intranet website, on
the Critical CareWeb page.
Magnesium Sliding Scale
Replace with Magnesium Sulfate (1 gram/2 ml vial).
Dilute 1 to 2 gram doses in at least 50 ml NS or D5W
Serum magnesium (1.6-2.6 mEq/L)
1.6 – 2.0
1.2 – 1.5
< 1.2
Dose (grams) §
1-2 grams over 1 hour
3-4 grams over 2 hours
4 grams over 2 hours and Call H.O.
Calcium Sliding Scale
Replace with Calcium Gluconate (1 gram/10 ml vial).
Dilute 1 to 2 gram doses in at least 100 ml NS or D5W
Total calcium (8.4-10.2 mg/dL)
Ionized calcium (1.12-1.32 mmol/L)
Total calcium 7.6 – 8.0 g/dL and
Ionized calcium  1.00
Total calcium 7.1 – 7.5 g/dL and
Ionized calcium < 1.00
Total calcium 6.5 – 7.0 or
Ionized calcium < 0.9
Total calcium  6.4 g/dL or
Ionized calcium < 0.8
Dose (grams) §
1-2 gram over 60 minutes
2-3 grams over 60 minutes
3-4 grams over 120 minutes
4 grams over 120 minutes and Call H.O.
Phosphate Sliding Scale
If Potassium < 4.0 mEq/L consider POTASSIUM phosphate as replacement salt
If Potassium  4.0 mEq/L consider SODIUM phosphate as replacement salt
** Consider serum creatinine levels when ordering potassium and phosphate salts**
Serum phosphate (2.7-4.5 mg/dL)
1.5 - 2.4
< 1.4
Dose (mM) §
15 mM in 250 to 500 ml over 6 hours
15 – 30 mM in 250 to 500 ml over 6 hours and Call H.O.
Potassium Sliding Scale
Replace with Potassium chloride. Give 20 mEq/50 ml by Central Line Only
May give 20 - 60 mEq per Liter of solution of choice centrally or peripherally
Central max rate is 20 mEq/hr and Peripheral max rate is 10 mEq/hr
** Consider serum creatinine levels when ordering potassium and phosphate salts **
Serum potassium (3.5-5.3 mEq/L)
3.4 – 4.3
2.8 – 3.3
< 2.8
Dose (mEq) §
20 - 40
40 - 60
60 mEq and Call H.O.
§ Electrolyte replacement is patient-specific and may depend upon clinical status and trends
Monitor serum electrolyte levels and administer doses based on individual patient needs and clinical status. Patients with significant
electrolyte depletion may require more intense monitoring and more frequent dosing. In general, levels should be checked 3 to 6 hours
after administration of a dose to allow time for distribution to body compartments.
The Pharmacy Advisor 4