Pharmacy And Therapeutics Committee

Clinical Practice Guidelines

Therapeutic Interchange Programs

Selection of Antimicrobials

O c t o b e r 2 0 0 0

WASHINGTON HOSPITAL CENTER

PHARMACY AND THERAPEUTICS COMMIT TEE

Washington Hospital CenterPharmacy and Therapeutics Committee


Therapeutic Interchange Programs

Selection of Antimicrobials

O C TO B E R 2 0 0 0

MedStar Health26000.092500

Pharmacy and Therapeutics Committee110 Irving Street, nw

Washington, dc 20010-2975phone: 202 877 6745

fax: 202 877 8925

Approved by Washington Hospital Center

Pharmacy and Therapeutics Committee

Arthur C. St. Andre, MD, ChairmanJay G. Barbaccia, PharmD

Tina M.Tezky, PharmD

October, 2000

MedStar Health

Section One:Clinical Practice Guidelines ..................................................................................................... 5

Vancomycin Utilization Guidelines .............................................................................................................. 6

Erythropoietin For Anemia .............................................................................................................................. 8

Use of Intravenous Immune Globulin ........................................................................................................ 10

Management of Neutropenic Fever ............................................................................................................ 12

Guidelines for the Use of Filgrastim ............................................................................................................ 14

Prevention & Treatment of Chemotherapy Associated Emesis ...................................................... 16

Intravenous Administration of Phytonadione (Vitamin K1, Aqua-Mephyton®) ...................... 20

Intravenous Administration of Potassium ................................................................................................ 21

Use of Hypertonic Sodium Chloride Injection ........................................................................................ 22

Amphotericin Utilization Guidelines ........................................................................................................... 24

Section Two:Therapeutic Interchange ........................................................................................................ 27

Ciprofloxacin – Transition from Intravenous to Oral Therapy............................................................ 29

H2 Blocker Therapeutic Interchange............................................................................................................. 30

Levofloxacin – Transition from Intravenous to Oral Therapy ............................................................. 31

Section Three:Recommendations for the Selection of Antimicrobial Drugs............................................ 33

Empiric Antibiotic Selection................................................................................................................ 34

Empiric Treatment of Intra-Abdominal Infections .................................................................................. 34

Empiric Treatment of Intrapelvic Infections............................................................................................... 35

Presumptive Treatment of Community Acquired Pneumonia ......................................................... 35

Empiric Treatment of Nosocomial Pneumonia ........................................................................................ 36

Presumptive Treatment of Nosocomial Sinusitis..................................................................................... 37

Empiric Treatment of Head and Neck Infections..................................................................................... 37

Empiric Treatment of Complicated Urinary Tract Infections ............................................................. 38

Empiric Treatment of Skin/Soft Tissue Infections.................................................................................... 39

Treatment of Documented Infections................................................................................................. 40

Treatment of Documented Staphylococcus aureus Infections .......................................................... 40

Treatment of Documented Pseudomonas Infections ......................................................................... 40

1999 Antibiograms ............................................................................................................................... 41

Gram Negative Rods — % Susceptible........................................................................................................ 42

Gram Positive Cocci — % Susceptible ......................................................................................................... 43

C O N T E N T S

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S E C T I O N O N E :

C L I N I C A L P R AC T I C E G U I D E L I N E S

WA S H I N G TO N H O S P I TA L C E N T E RP H A R M AC Y & T H E R A P E U T I C S CO M M I T T E E

O C TO B E R 2 0 0 0

MedStar Health

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I. Background

II. Clinical Practice Guideline

VA N C O M Y C I N U T I L I Z AT I O N G U I D E L I N E S

Effective Date: March 1995 Index # CPG-PT: 0001

Vancomycin is one of the most commonly used antibiotics at the Washington HospitalCenter. The literature has documented significant clinical issues regarding the relativeefficacy of vancomycin and its potential to promote the emergence of resistant organ-isms. Levine, et al (Annals of Internal Medicine, 1991; 115:674-680) and Karchmer, (Annalsof Internal Medicine, 1991; 115:739-740) document a definite clinical and microbiologicsuperiority of the beta lactam antibiotics (e.g., nafcillin) over vancomycin in treatinginfections caused by methicillin susceptible Staphylococcus aureus. Spera and Farber(JAMA, 1992; 268:2563-2564) document that nosocomial infections secondary to grampositive organisms have increased in incidence. Enterococci are now second only toEscherichia coli as a cause of nosocomial infections. Strains of Enterococci resistant tovancomycin, penicillins, and the aminoglycosides have been described in the literature,and a number of cases have occurred at the Washington Hospital Center. An essentialstep in limiting the spread of multiply resistant Enterococci is to limit the use of thoseantimicrobial agents that select for their isolation. Drugs which have been specificallyassociated with the emergence and spread of multiply resistant Enterococci are van-comycin and ceftazidime. Spera and Farber emphasize the importance of controllingthe use of vancomycin and the antipseudomonal beta lactams.

The current guidelines for the therapeutic use of vancomycin are intended to limit itsuse to the treatment of infections, documented by culture and susceptibility, caused bymethicillin resistant Staphylococcus aureus (MSRA), methicillin resistant Staphylococcusepidermidis (MSRE), or beta lactam resistant Enterococcus.

The adoption of these strategies aim to ensure the maximal benefit from vancomycinand optimal outcomes in patients with gram positive infections, while minimizing theadverse effects of vancomycin on hospital flora.

Vancomycin will only be dispensed by the pharmacy for patients meeting one of thefollowing criteria. The prescriber will be contacted and requested to modify therapy forother patients. Vancomycin will be provided outside of the treatment guidelines onlyupon the approval of the Medical Director or designee.

A. Treatment of Documented Infections

1. For treatment of serious infections due to beta-lactam resistant gram positivemicroorganisms.

(Note: vancomycin may be less rapidly bactericidal than beta lactams for beta-lactam susceptible Staphylococci, and vancomycin is bacteriostatic against Enterococci.)

2. For treatment of infections due to gram positive microorganisms in patients with a serious allergy to beta-lactam antimicrobials.

(Note: for serious Staphylococcal infections, e.g., endocarditis, beta-lactam skin testingand hyposensitization should be considered for reasons noted in A.1.)

3. For treatment of antibiotic associated colitis which is severe and potentially life threaten-ing or fails to respond to metronidazole therapy.The dose of oral vancomycin should be500 to 2000 mg/day divided in four doses. Even at the lower dose (125 mg four times per day) stool concentrations of vancomycin are much greater than needed. (Fekety and Shah, JAMA, 1993;269:71-75).

4. For treatment of susceptible infections where vancomycin poses a substantial pharma-cokinetic advantage than other available antibiotics (i.e., treatment of bacteremia in dialysis patients or provision of home antibiotic therapy).

B. Empiric Treatment

1. For empiric treatment of suspected gram positive infections in high risk patientswhere methicillin resistant Staphylococcus is strongly suspected. High risk patientsare defined as:

(a) intravenous drug users;

(b) patients with long term indwelling vascular access devices;

(c) those who have been hospitalized for more than seven days; and

(d) in other situations where the incidence of methicillin resistant Staphylococcus is known to be higher in this institution.

* Empiric use of vancomycin is limited to 72 hours of therapy.

C. Prophylaxis

1. Surgical procedures involving implantation of prosthetic materials or devices.

2. Endocarditis as recommended by the American Heart Association.

3. Cardiovascular surgical procedures.

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II. Clinical Practice Guideline (continued)

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E R Y T H R O P O I E T I N F O R A N E M I A

Effective Date: September 1999 Index # CPG-PT: 0002

I. Background

Patients with anemia secondary to AIDS or cancer, as is observed with anemia of chronicdisease due to other causes, may have erythropoietin levels which are abnormally low forthe degree of anemia. Antiretroviral and antineoplastic drug therapy may alter the relation-ship between the serum erythropoietin level and the hemoglobin concentration causing ashift of the regression line to the right.


Erythropoietin will only be dispensed by the pharmacy for patients meeting one of the following criteria.The prescriber will be contacted and requested to modify therapy forother patients. Erythropoietin will be provided outside of the treatment guideline only upon the approval of the Medical Director or designee.

Other correctable causes of anemia shall be ruled out prior to the initiation of erythropoietintherapy. Iron stores (serum iron, total iron binding capacity, and ferritin level) should bedetermined, and iron replacement given prior to the initiation of erythropoietin therapyif necessary. Also, vitamin B12 and folic acid serum levels should be evaluated and defi-ciencies corrected before initiating erythropoietin therapy.

B. Anemia in Patients with Renal Failure

1. Indication:

Erythropoietin will be given on the second and subsequent dialysis treatments in the hospital with the following considerations:

a. Erythropoietin will be held if the hematocrit is greater than 36.5%.

b. Erythropoietin will be held if a concomitant blood transfusion is given.

c. Erythropoietin will be held on the day of a surgical procedure.

d. Erythropoietin will not be administered on 2 consecutive days.

e. Erythropoietin will not be administered more than 3 times each week.

f. Erythropoietin will not be given to patients initiating dialysis during the first 3 treatments.

g. Erythropoietin will not be given on the day of discharge.

h. Erythropoietin dosage will not exceed 150 U/kg/dose.

i. Iron studies will be drawn on the 4th dialysis in the hospital in order to optimize the response.

2. Dosage:

50 – 100 units/kg three times weekly adjusted as follows:

a. Unless clinically indicated, dosage adjustments should not be made more frequently than monthly.

b. The hematocrit should be determined twice weekly for 2 – 6 weeks after any dosage adjustment.

c. The dosage should be reduced in patients with hematocrits approaching 36%.

d. The dosage should be reduced if the hematocrit rises by more than 4 points in a 2 week period.

e. The dosage should be increased if the hematocrit does not rise by 5 – 6 points after 8 weeks.

B. Anemia in Patients with AIDS

1. Indication:

a. The patient is HIV positive.

b. The patient is receiving antiretroviral therapy.

c. The hematocrit is less than 30.

d. The erythropoietin level has been measured and is less than 500 mU/L.

2. Dosage:

a. The hematocrit should be measured weekly.

b. The starting dose is 100 units/kg three times weekly for 8 weeks.

c. If the response at 8 weeks is not satisfactory, the dosage can be increased by 50 – 100 units/kg three times weekly at 4 – 8 week intervals.

C. Anemia in Patients with Cancer

1. Indication:

a. The hemoglobin is less than 11 g/dl and the patient is symptomatic.

b. The erythropoietin level has been measured and is less than 300 mU/ml.

c. The patient has been hospitalized for 7 days or longer.

2. Dosage:a. The starting dosage is 150 units/kg, subcutaneously, three times weekly, or

450 units/kg , subcutaneously, given weekly.

b. The hemogloblin should be measured weekly until stable.

c. If the response at 8 weeks is not satisfactory, the dosage may be increased to 300 units/kg, SC, three times weekly, or 900 units/kg, SC, weekly.

d. Further increases in dosage have not been shown to further correct the anemia.

e. Iron supplementation is needed if the serum iron saturation is less than 30% or the serum ferritin is ≤ 20 mcg/L.

D. Preoperative

1. Indication:a. Treatment of severe anemia in a patient who refuses preoperative transfusion.

b. Reduction of allogeneic blood transfusion in patients undergoing non-cardiac/non-vascular surgery with hemoglobin levels between 10 and 13.

c. Preoperative autodonation.

d. Preoperative hematocrit augmentation.

2. Dosage:

a. The dosage is 300 units/kg/day for 10 days prior to, the day of, and 4 days after surgery

b. An alternative dosage is 600 units/kg on preoperative days 21, 14, 7, and the day of surgery.

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U S E O F I N T R AV E N O U S I M M U N E G L O B U L I N


I. Background


IgG is the major immune globulin in serum. It accounts for approximately 20 percent of the total plasma protein. Until the 1980's, IgG preparations were suitable for intramuscularadministration only.These preparations were associated with a high incidence of adversereactions when given intravenously.These adverse reactions were attributed to extraneoussubstances which were not eliminated by the purification process. Methods were subsequentlydeveloped to improve the extraction of IgG, and make its intravenous administration possible.A shortage of intravenous immune globulin (IVIG) exists as a result of increased usage, export,and withdrawals of selected lots as a result of the theoretical contamination with Creutzfeldt–Jakob disease agent (CJD).The Centers for Disease Control (CDC) summarized indications forthe use of IVIG in the Morbidity and Mortality Weekly Reports (MMWR; 48:8; 159-162).Theseindications were compiled from FDA approved indications and recommendations from theNational Institutes of Health and the University Hospital Consortium.This document is thesource of the guidelines outlined below.

Intravenous immune globulin will only be dispensed by the pharmacy for patients meetingthe following criteria. Intravenous immune globulin will be provided outside of the treatmentguideline only upon the approval of the Medical Director or designee.

A. Idiopathic Thrombocytopenic Pupura

1. Indications:IVIG is indicated in patients expected to have a favorable outcome (i.e., is not terminally ill)who have an initial platelet count of less than 20,000 (patients with platelet counts greaterthan 20,000 may benefit from a corticosteroid such as prednisone 1 mg/kg/day) who have:

a. Active bleeding requiring red cell transfusion.

<or>

b. Fresh petechiae on mucosal surfaces above the neck.

<or>

c. Scheduled for an invasive procedure with a high potential to bleed (e.g., surgery, biopsy).

2. A therapeutic trial of Rho immune globulin shall be attempted in all Rh(–) patients who have not had a splenectomy.The drug is administered as a single dose at a range of 20 – 75 mcg/kg.

3. Dosage:

a. Divided dose regimen: 400 mg/kg/day for five consecutive days.

b. Single dose regimen: 2 grams/kg as a single dose.

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B. Primary Immunodeficiencies

1. Patients with IgA deficiency should receive a product low in IgA due to their potential to form IgA antibody on exposure.This could potentially lead to an accelerated allergicreaction.

2.2. DDosage:osage:The dosage should be individually titrated.The FDA approved dosage is 0.1 – 0.4 mg/kg asa single dose given monthly to maintain the patient free of infection or maintain an IgGlevel of > 500 mg/dL.

C. Recent Bone Marrow Transplant in Adults

1. Patients with allogeneic bone marrow transplants are at increased risk for cytomegalovirusinfection, bacterial infection,and graft vs.host disease (GVHD).Prevention of GVHD is considered to be the most established role for IVIG.

2. Dosage:a. 500 mg/kg weekly for the first 90 days followed by 500 mg/kg monthly for the

first post-transplantation year.

<or>

b. 1 gm/kg weekly for the first 120 days.

<or>

c. 500 mg/kg every other week for 120 days followed by 500 mg/kg monthly for the first post-transplantation year.

D. Chronic B Cell Lymphocytic Leukemia

1. Indicated in patients with stable disease who are hypogammaglobulinemic or have a history of recurrent bacterial infections.

2. Dosage:0.4 mg/kg every 3 – 4 weeks.

E. Post Transfusion Purpura

1. Indication:Indicated in patients where the treatment of choice, plasma exchange, is not tolerated orineffective.

2. Dosage:0.4 mg/kg for 2 – 10 days with the endpoint being an increase in platelet count and a cessation of bleeding.

F. Chronic Inflammatory Demyelinating Polyneuropathy

1. Indication:Indicated in patients who do not respond to or do not tolerate corticosteroid therapy.

2. Dosage:0.4 mg/kg for 5 consecutive days.

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M A N A G E M E N T O F N E U T R O P E N I C F E V E R

Effective Date: May 1999 Index # CPG-PT: 0004

A. Indication

Broad-spectrum antibiotics should be initiated following appropriate cultures when apatient with severe neutropenia (defined as a neutrophil count of < 500/�L, or < 1,000/�Lwith predicted decline to < 500/�L) becomes febrile [defined as a single elevation of oraltemperature to > 38.3oC (101oF), or > 38.0oC (100.4o F) over at least 1 hour].

B. Cultures

1. No indwelling IV catheter: obtain 2 sets of blood cultures

2. Indwelling IV catheter: obtain cultures from the catheter as well as from a peripheral vein(cultures should also be labeled with site); it is preferable to draw cultures from each lumenof a multi-lumen catheter.

C. Treatment Guidelines

(Note: if an indwelling intravascular device is present, the administration of antibiotics should berotated through each lumen of a multiple lumen catheter.)1. Empiric antibiotic treatment:

(antibiotic dosages are for average size adults with adequate renal function and mayrequire modification for extremes of body mass or impaired renal function).a. Initial Treatment – one of three regimens:

(1) If empiric vancomycin is indicated (severe mucositis,previous quinolone prophylaxis,colonization with MRSA or beta lactam resistant S. pneumoniae, obvious catheter related infection, or hypotension),combination therapy with:(a) Vancomycin: (1 gram IV Q12H)

<and> (b) Broad spectrum coverage (including Pseudomonas)

i) If not beta lactam allergic: ceftazidime (2 grams IV Q8H).ii) If allergic to beta lactams: aztreonam (2 grams IV Q6H)

<or> ciprofloxacin 400 mg Q12H with amikacin (5 mg/kg IV Q8H).

(2) If empiric vancomycin is not indicated:(a) Monotherapy:

i) If not beta lactam allergic: ceftazidime. (2 grams IV Q8H).ii) If allergic to beta lactams: monotherapy not recommended.

(b) Duotherapy: (note: if an aminoglycoside is contraindicated due to the use of concurrent nephrotoxic drugs, ciprofloxacin 400 mg IV Q12H should be used).i) If not beta lactam allergic: ceftazidime (2 grams IV Q8H) with gentamicin

(3 mg/kg loading dose followed by 1 mg/kg IV Q8H).ii) If allergic to beta lactams:

aztreonam (2 grams IV Q6H) <or>ciprofloxacin 400 mg IV Q12H with amikacin (5 mg/kg IV Q8H).

I. Background

I. Clinical Practice Guideline

An oncology drug utilization task force was convened at the Washington Hospital Center toidentify opportunities to optimize drug use.The following clinical practice guideline is one ofseveral which were developed by this task force and approved by the Pharmacy andTherapeutics Committee.The document was revised based on the “1997 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Unexplained Fever”(Clin Infec Diseases, 1997;25:551-73).

C. Treatment Guidelines (continued)

2. Reassessment

a. Afebrile within first 3 days of treatment:

(1) If etiology identified: adjust to most appropriate treatment based on culture and susceptibility data.

(2) If no etiology identified:

(a) Low risk (no discernible infectious disease): change to oral antibiotic:levofloxacin 500 mg PO Q24H or cefixime 200 mg PO Q12H.

(b) High risk (absolute neutrophil count <100/�L, mucositis, unstable signs):continue same antibiotics.

b. Persistent fever during first 3 days of treatment: continue therapy and reassess on day 4 or 5.

(Note: if vancomycin started on admission, consider discontinuation if cultures are negative.)

(1) No change: continue antibiotics.

(2) Progressive disease: add vancomycin (1 gram IV Q12H) if not started on admissionand consider using duotherapy as outlined above.

(3) If febrile on days 5-7: add amphotericin B 0.6 mg/kg IV Q24H (evaluate appropriate-ness of concomitant nephrotoxic drugs) with or without antibiotic changes.

3. Duration of TreatmentThe following are guidelines for duration of antibiotic therapy in patients with prolongedneutropenia:

a. Afebrile by day 3:

(1) Absolute neutrophil count > 500/�L by day 7: stop after 7 days of treatment.

(2) Absolute neutrophil count < 500/�L by day 7:

(a) Low risk (appear clinically well, no discernible infectious lesions, no laboratory or radiographic evidence of infection): stop when afebrile for 5-7 days.

(b) High risk (absolute neutrophil count <100/�L, mucous membrane lesions of mouth or GI tract, unstable vital signs): continue antibiotics throughout neutropenic period.

b. Persistent fever:

(1) Absolute neutrophil count > 500/�L: stop 4 – 5 days after absolute neutrophil count > 500/�L if no infectious lesions are discernible.

(2) Absolute neutrophil count < 500/�L: continue antibiotics for 2 weeks, reassess,and discontinue if clinically stable and no infectious lesions are identified.

(3) Amphotericin B: stop after 2 weeks of daily therapy if no discernible lesions are found by clinical examination, chest X-ray, or abdominal or chest CT.

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G U I D E L I N E S F O R T H E U S E O F F I L G R A S T I M (Neupogen, Granulocyte-Colony Stimulating Factor)


1. Chemotherapy-induced neutropenia

a. Prophylaxis against chemotherapy induced neutropenia:

(1) Primary prophylaxis for regimens with > 40% incidence of febrile neutropenia:

(a) Sarcoma protocols using doxorubicin 75 mg/m2

<and>either ifosfamide 10 gm/m2 or cisplatin 120 mg/m2.

(b) Ifosfamide > 10 gm/m2 as a single agent.

(c) Induction regimens for high-grade non-Hodgkin’s lymphoma using high dose chemotherapy with CNS prophylaxis.

(2) Secondary prophylaxis after chemotherapy induced febrile neutropenia as described in 1.b. below.

b. Treatment of chemotherapy induced neutropenia in the setting of fever associated with pneumonia, hypotension, sepsis syndrome, or fungal infection.

2. Progenitor cell transplantation.

3. Acute myeloid leukemia post induction chemotherapy.

4. Myelodysplasia with severe neutropenia and recurrent infections.

5. Neutropenia associated with HIV infection and the use of anti-retroviral agents for an absolute neutrophil count (ANC) of < 500/�L.

6. Other drug-induced neutropenia.

7. Recurrent infections due to hereditary forms of neutropenia.

I. Background

A. Indications

An oncology drug utilization task force was convened at the Washington Hospital Center toidentify opportunities to optimize drug use.The following clinical practice guideline is one ofseveral which were developed by this task force and approved by the Pharmacy andTherapeutics Committee.


Filgrastim will only be dispensed by the pharmacy for patients meeting the following criteria.Filgrastim will be provided outside of the treatment guidelines only upon the approval of theMedical Director or designee.

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1. Starting dose5 �g/kg/day, administered as a single daily injection by subcutaneous bolus,by short intravenous infusion (15 – 30 minutes), or by continuous subcutaneous or continuous intravenous infusion.The dosage should be rounded off to the nearest 300 mg vial.

2. Initiation of therapyFilgrastim should be administered no earlier than 24 hours after the administration of myelosuppressive chemotherapy and should not be administered in the period 24 hours before the administration of chemotherapy.

a. Filgrastim should not be administered to patients with chemotherapy induced neutropenia who have passed their nadir (generally around 10 – 14 days), and whose neutropenia is expected to be short-lived unless they have an active infection or exhibit fever.

b. For prophylaxis against chemotherapy induced neutropenia, filgrastim should be started 24 hours after chemotherapy and continued for at least 7 – 10 days, or until the absolute neutrophil count exceeds 10,000/mL.

3. MonitoringCBC and differential should be monitored at least two times a week during therapy.Filgrastim must be reordered every 72 hours after the need for continued therapy has been assessed.

4. Duration of Treatmenta. The maximum response to filgrastim generally occurs within 4 – 5 days of initiation

of therapy.

b. In cases of chemotherapy induced neutropenia, filgrastim can be administered daily until the absolute neutrophil count (ANC) is between 1000 – 3000/�L for three consecutive days.

c. The duration of filgrastim in patients with HIV infection should be dictated by the clinical response. If no response to filgrastim has occurred despite 1 – 2 weeks of treatment, filgrastim should be discontinued. If the patient has a response to treatment, the need for daily filgrastim should be reassessed. In many patients,subsequent filgrastim can be given one to two times a week to maintain the ANC in the recommended range of 500/�L. Each patient should be evaluated for this possibility.

d. The duration of prophylactic filgrastim in patients receiving chemotherapy should be dictated by the clinical situation. However, if the ANC exceeds 10,000/�L, the need for filgrastim should be reevaluated.

B. Treatment Guidelines


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P R E V E N T I O N & T R E AT M E N T O F C H E M OT H E R A P Y A S S O C I AT E D E M E S I S


I. Background

“Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines”have been prepared by the American Society of Clinical Oncology (ASCO).These guide-lines were published in the Journal of Clinical Oncology, 1999, 17:2971-2994.The followingClinical Practice Guideline is based on this review.

Nausea and vomiting are frequent adverse effects of cancer chemotherapy and may havea substantial impact on the patient's quality of life. In addition to the discomfort associatedwith the nausea and vomiting, the patient's ability to perform daily activities may be compromised and metabolic or physiologic complications may result.

The neuropharmacology of drug-induced emesis has been described. Drug-inducedemesis is initiated through the stimulation of specific receptors in the brain. The act ofvomiting is coordinated by the emetic center located in the lateral reticular formationof the brain. When activated, it sends efferent impulses to the salivary, vasomotor, andrespiratory centers of the brain as well as cranial nerves VIII and X. These, in turn, initiatesomatic and visceral impulses resulting in coordinated movement of the abdominalmuscles, diaphragm, stomach and esophagus to expel the stomach contents. Thechemoreceptor trigger zone (CTZ) is located in the area postrema in the floor of thefourth ventricle. It is not protected by the blood brain barrier and therefore is accessi-ble to stimuli in either the blood or the cerebrospinal fluid. The CTZ initiates emesisthrough stimulation of the emetic center. Chemotherapeutic substances, or theirmetabolites, may directly stimulate the CTZ, or may result in the release of serotonin (5-hydroxytryptamine) from the gastrointestinal tract. In addition to the CTZ, theemetic center can be stimulated by the vestibular center (motion sickness), higherbrain stem and cortical structures (anticipatory emesis), and the pharynx and gastro-intestinal tract. A number of neurotransmitters have been implicated in the emeticresponse. These substances include dopamine, serotonin, histamine, acetylcholine,and opiates.

There are three major types of chemotherapy associated nausea and vomiting. Mostcommon is the acute syndrome which begins within 1 – 2 hours of drug administration,peaks within 4-10 hours, and subsides within 12 – 24 hours. Delayed nausea and vomitingoccurs within 1 – 5 days of chemotherapy administration with a peak frequency between48 and 72 hours. It is usually less severe than acute nausea and vomiting, but lasts for alonger period of time.The two should be treated as separate entities. Anticipatory nauseaand vomiting is not associated with a specific time frame with chemotherapy adminis-tration. It is a conditioned reflex resulting from inadequate control of emesis with priortreatments, and may be triggered by environmental stimuli (sights, sounds, smells asso-ciated with chemotherapy).

A variety of medications are used as antiemetics.These agents have different mechanismsof action and adverse reactions and are summarized in the following table.

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Cancer chemotherapeutic agents vary in their potential for inducing acute emesisepisodes.They can be classified as having a high emetogenic potential (producing emesisin > 30% of recipients), intermediate emetogenic potential (10 – 30%) or low emetogenicpotential (< 10%).This classification and the Guidelines for the Prevention and Treatment ofChemotherapy Associated Emesis follow.

A. Chemotherapeutic Agents with Low Emetogenic Potential (< 10%)

1. Agents:

a. Vinblastine

b. Vinorelbine

c. Fluorouracil

d. Methotrexate

e. Thioguanine

f. Mercaptopurine

g. Bleomycin

h. L-asparaginase

i. Vincristine

Drug Class

Phenothiazines:e.g. prochlorperazine

Substituted benzamides:e.g. metoclopramide

Corticosteroids:e.g. dexamethasone

Benzodiazepines:e.g. lorazepam

Cannabinoids:e.g. dronabinol

Serotonin Antagonists:e.g. granisetronondansetron

Mechanism of Action

Dopamine receptor antagonist

Dopamine and serotoninreceptor antagonist

Unknown; may involvechanges in cellular perme-ability and/or prostaglandinblocking actions

Useful as an adjunct due to anxiolytic, sedative, andamnestic properties; especiallyuseful for anticipatory nauseaand vomiting

Unknown

Serotonin receptor antagonist

Adverse Reactions

extrapyramidal reactions,sedation, orthostatichypotension

extrapyramidal reactions,anxiety, depression, diarrhea,dizziness

hyperglycemia, insomnia,epigastric discomfort

somnolence, amnesia

dysphoria, hallucinations,sedation, vertigo, dry mouth,disorientation

headache, dizziness,light-headedness, rarelyextrapyramidal reactions


j. Melphalan

k. Vindesine

l. Busulphan

m.Chlorambucil

n. Hydroxyurea

o. Fludarabine

p. 2-chlorodeoxyadenosine

q. Tamoxifen


f. Topotecan

g. Gemcitabine

h. Etoposide

i. Teniposide

– 18 –

A. Chemotherapeutic Agents with Low Emetogenic Potential (< 10%) (continued)

2. Treatment:

a. Acute: no routine pretreatment antiemetics

(1) If treatment is necessary, prochlorperazine 5 – 10 mg IV or PO, or 25 mg PR will suffice; consider adding lorazepam 1 – 2 mg IV or PO PRN.

(2) For refractory nausea and vomiting, ondansetron 4 mg PO 60 minutes prior to chemotherapy and repeated at 3 and 7 hours after chemotherapy PRN nausea;continue prochlorperazine/ lorazepam PRN.

b. Delayed: no regular preventive use of antiemetics

B. Chemotherapeutic Agents with Intermediate Emetogenic Potential (10 – 30%)

1. Agents:

a. Irinotecan

b. Mitoxantrone

c. Paclitaxel

d. Docetaxel

e. Mitomycin

2. Treatment:

a. Acute: A corticosteroid (such as dexamethasone 4 – 8 mg by mouth, given once before chemotherapy)

(1) If treatment is necessary, prochlorperazine 5 – 10 mg IV or PO, or 25 mg PR will suffice; consider adding lorazepam 1 – 2 mg IV or PO PRN.

(2) For refractory nausea and vomiting, ondansetron 4 mg PO 60 minutes prior to chemotherapy and repeated at 3 and 7 hours after chemotherapy PRN nausea,continue prochlorperazine/lorazepam PRN.

b. Delayed: no regular preventive use of antiemetics.

C. Chemotherapeutic Agents with High Emetogenic Potential – Cisplatin (> 99%)

1. Acute: Pretreatment: ondansetron 8 mg or 0.15 mg/kg IV (rounded to the next highest4 mg dosage) given with dexamethasone 20 mg IV and lorazepam 1 – 2 mg IV, one time,30 minutes before chemotherapy.

2. Delayed: Dexamethasone 8 mg by mouth twice daily for 3 – 4 days plus either metoclopramide 30 – 40 mg, two or four times daily for 3 – 4 days, or ondansetron 8 mg PO, two to three times daily for 2 – 3 days.


– 19 –

D. Chemotherapeutic Agents with High Emetogenic Potential – Non-cisplatin (>30%)

1. Agents:

a. Dacarbazine

b. Actinomycin D

c. Mechlorethamine

d. Streptozocin

e. Hexamethylmelamine

f. Carboplatin

g. Cyclophosphamide

h. Lomustine

2. Acute: Pretreatment: ondansetron 8 mg or 0.15 mg/kg IV (rounded in the next highest4 mg dosage) given with dexamethasone 20 mg IV and lorazepam 1 – 2 mg IV, one time,30 minutes before chemotherapy.

3. Delayed: Dexamethasone 8 mg by mouth twice daily for 2 – 3 days plus either metoclopramide 30 – 40 mg, two or four times daily for 2 – 3 days, or ondansetron 8 mg PO, two to three times daily for 2 – 3 days.

i. Carmustine

j. Daunorubicin

k. Doxorubicin

l. Epirubicin

m. Idarubicin

n. Cytarabine

o. Hexamethylmelamine

– 20 –

I N T R AV E N O U S A D M I N I S T R AT I O N O F P H Y TO N A D I O N E ( V I TA M I N K 1, AQ UA - M E P H Y TO N ® )

Effective Date: April 1999 Index # CPG-PT: 0007

I. Background

A. Indications

Phytonadione (vitamin K1, Aqua-Mephyton®) is indicated for the management of coagula-tion disorders due to inadequate formation of clotting factors II, VII, IX and X when causedby vitamin K deficiency or interference with vitamin K activity. It should be recognized thatthe therapeutic response to phytonadione does not develop for 4 – 24 hours.Therefore, ifsevere bleeding is present, the direct administration of clotting factors as component ther-apy or fresh frozen plasma is indicated.

B. Adverse Reactions

Severe reactions, including fatalities have occurred during and immediately after the intra-venous administration of phytonadione.These reactions typically resemble hypersensitivity oranaphylaxis,and include shock and cardiac and/or respiratory arrest. Such reactions haveoccurred even when slow infusions of diluted drugs were administered.As a result of thepotential consequences of these adverse reactions,phytonadione should be administered bythe intravenous route of administration only when oral or intramuscular administration is notfeasible,and the potential risk is considered justified .


A. Phytonadione shall be administered by the intravenous route (using a buretrol toadminister the drug) only for patients who meet the criteria outlined below under indications, and only when oral or intramuscular administration is not feasible, and the potential risk is considered justified.

B. Documentation of the need for intravenous administration must be placed on the medical progress note by the physician prior to administration.

C. Nursing staff administering intravenous phytonadione by IV drip using buretrol musthave specific order outlining method of administration.

D. Licensed nursing staff (RN/SLPN) on any unit may administer intravenous phytonadioneby buretrol (IV drip only) when above criteria has been met.

E. Dosage and Administration:

1. Dosage: 2.5 – 25mg

2. Dilution:The prescribed dose should be diluted in a minimum of 50ml of preservative free5% dextrose,0.9% sodium chloride, or 5% dextrose of 0.9% sodium chloride injection.

3. Rate of administration:When nursing staff administer phytonadione, the appropriate dosage and fluid volumeshould be placed in a buretrol and dripped in over a period of not less than 30 minutes.Rarely a physician may wish to personally administer phytonadione. In any case the rate of infusion should not be greater than 1 mg/min.

4. Anaphylaxis precautions should be observed.

– 21 –

I N T R AV E N O U S A D M I N I S T R AT I O N O F P O TA S S I U M

Effective Date: October 1998 (Revised) Index # CPG-PT: 0008

I. Background

The purpose of this clinical practice guideline is to provide recommendations for the safeadministration of intravenous potassium chloride.

II. Clinical Practice Guidelines

A. Severe Potassium Depletion

1. Defined:

a. The serum potassium is less than 2.5 mEq/L.<or>

b. The patient has electrocardiographic manifestations of hypokalemia.<or>

c. The patient demonstrates non-cardiac manifestations of hypokalemia.

2. Recommendations for treatment:

a. The concentration of potassium should not exceed 80 mEq/L of solution given as an IV drip nor 10 mEq/100 ml of solution given via peripheral IV.When given by central IV line the concentration should not exceed 20 mEq/100 ml of solution.

b. A volumetric infusion pump should be used to administer all bolus doses i.e. those in 100 ml of solution or less.This technique should also be used to administer all infusions with a concentration of potassium > 40 mEq/L.

c. The rate of administration should not exceed 40 mEq/hour.

d. If clinical manifestations of hypokalemia exist, the electrocardiogram should be monitored continuously during potassium replacement.The potassium level should be checked after the administration of a total of 40 mEq of KCl given as 20 mEq/100 ml minibags or 1 Liter of the 80 mEq/liter solution before continuing therapy. In rare clinical settings it may be necessary to continue the administration of potassium while awaiting the laboratory results.

B. Mild Potassium Depletion

1. Defined:

a. The serum potassium is greater than or equal to 2.5 mEq/L.<and>b. the patient is asymptomatic.<and>c. the patient has no electrocardiographic manifestations of hypokalemia.

2. Recommendations for treatment:

a. In most cases potassium should be administered by continuous infusion or oral route only.

b. The concentration of potassium should not exceed 40 mEq/L.

c. The rate of administration should not exceed 20 mEq/hour.

d. If rapid repletion is justified by impending surgery, runs of 10 mEq KCl in 100 ml of solution may be given via peripheral IV.When given by central IV line the concentration should not exceed 20 mEq/100 ml of solution.

A volumetric infusion pump should be used to administer all bolus doses – i.e. those in 100 ml of solution or less.

A serum potassium should be rechecked after the administration of 40 mEq.

– 22 –

U S E O F H Y P E R T O N I C S O D I U M C H L O R I D E I N J E C T I O N


I. Management of Chronic, Severe, Symptomatic Hyponatremia

A. Patient selection:Serum sodium of < 125 with CNS symtoms.

B. Dosage/rate of administration:

1. If no active seizures:3% NaC1 at a rate to raise the serum sodium by 1 mmol/L per hour.

2. If active seizures:3% NaCl at a rate not to exceed raising the serum sodium by 4 – 5 mmol/L in the first hour or until seizures stop.

C. Monitoring:

1. Monitor serum sodium every 2 hours until neurologically stable.

2. Discontinue therapy when:

a. Patient becomes asymptomatic.

b. Plasma sodium has increased by 20 mmol/L.

c. The plasma sodium reaches a level of 120 – 125.

3. Avoid increasing the plasma sodium to normonatremic or hypernatremic levels and the level should not be elevated by more than 25 mmol/L over the first 48 hours of therapy.

II. Volume Resuscitation

A. Patient selection:Hypovolemic patients, serum sodium >125 and <150.

B. Dosage/rate of administration:250 ml of 3% NaCl over 15 minutes up to1,000 ml/hr; total quantity not to exceed1,000 ml within 6 hours depending on serum Sodium.

C. Monitoring:Serum sodium Q6H; generally discontinue therapy if the serum sodium exceeds 155 mmol/L.


Background

The purpose of this clinical practice guideline is to provide recommendations for thesafe administration of intravenous hypertonic sodium chloride.

III. Prevention of Hyponatremia in Patients with Salt Wasting Nephropathy Often Following Subarachnoid Hemorrhage or Head Trauma

A. Patient selection:Serum sodium of 125 – 135.

B. Dosage/rate of administration:500 ml of 3% NaCl at a rate not to exceed 500 ml/hr. Dosage not to be repeated untilserum sodium is measured.

C. Monitoring:Repeat serum sodium Q6H; not to be administered if serum sodium is > 155.

IV. Management of Severe Hyponatremia due to Systemic Absorption of Hypotonic Bladder Irrigation Fluid

A. Patient selection:Serum sodium of < 125 with associated hypo-osmolality with CNS symptoms.

B. Dosage/rate of administration:

1. If no active seizures:3% NaCl at a rate to raise the serum sodium by 1 – 1.5 mmol/L per hour.

2. If active seizures:3% NaCl in a quantity estimated to replace the sodium deficit [(126-measured sodium) x (0.6 x body weight in Kg)] infused at a rate estimated to increase the serum sodium by 1 –2 mmol/L per hour.

C. Monitoring:

1. Monitor serum sodium every 2 hours until neurologically stable.

2. Discontinue therapy when:

a. Patient becomes asymptomatic.

b. Plasma sodium has increased by 20 mmol/L.

c. The plasma sodium reaches a level of 120 – 125.

3. Avoid increasing the plasma sodium to normonatremic or hypernatremic levels and the level should not be elevated by more than 25 mmol/L over the first 48 hours of therapy.

Clinical Practice Guidelines (continued)

– 23 –

Amphotericin has long been the number one choice for treating severe systemic fungal infections. Most patients started on conventional amphotericin will experience chills, rigors,fever, electrolyte wasting, and/or rises in serum creatinine (SCr). Nephrotoxicity and infusion-related reactions are the major dose limiting factors when treating patients withamphotericin B. An attempt to lessen these adverse effects is by pre-medication withagents such as NSAIDs, acetaminophen, antihistamines, meperidine, and/or hydrocortisone.A slow rate of infusion may also help decrease the incidence of infusion related events.Manufacturers have incorporated amphotericin into lipid vehicles to allow higher doseswhile minimizing some of the adverse events. Incorporating amphotericin into a lipid medium adds another lipid for the amphotericin B to attach to, decreasing its affinity formammalian sterols.The lipid medium also increases the amount of amphotericin taken upby the reticuloendothelial system, and therefore decreases the amount of amphotericinbeing taken up by the kidneys. Formulations of amphotericin that are currently availableinclude conventional amphotericin B (Fungizone ®), amphotericin B cholesteryl sulfatecomplex (Amphotec ®), amphotericin B lipid complex (Ablecet ™), and liposomalamphotericin B (AmBisome ®).

In clinical studies, none of the lipid-based products demonstrated superior efficacywhen prospectively compared with conventional amphotericin in the treatment of documented infections. Acute infusion-related adverse events vary between the different products and nephrotoxicity appears to be reduced with the lipid-based formulations. Use of the lipid-based products should be restricted to those who areintolerant of or refractory to conventional amphotericin. Currently, there are no pub-lished, large-scale comparisons of the lipid-based products. Due to the lack of clinicaldata supporting a difference between the lipid-based |products and a significant difference in cost, the first line lipophilic amphotericin product at Washington HospitalCenter is amphotericin B lipid complex (Ablecet ™). Liposomal amphotericin B(AmBisome ®) is restricted as indicated by the treatment guidelines.

A M P H O T E R I C I N U T I L I Z AT I O N G U I D E L I N E S


I. Background

– 25 –

A. Conventional Amphotericin B

1. Indication

a. Severe fungal infections.

b. Febrile neutropenia after 5 – 7 days of continued fever while on antibiotics.

c. Empiric treatment in patients with a high index of suspicion for fungal infection.

2. Dosage and Administration

a. Test Dose of 1 mg over 10 – 30 minutes may be given.

b. Daily: 0.25 – 1.5 mg/kg.

Alternate Daily: 1 – 1.5 mg/kg.

c. Infuse over 4-6 hours

d. Patients should receive at least one liter of 0.9% NaCl per day of amphotericin B therapy via continuous infusion or 500 mL pre- and post-amphotericin B dose, if tolerable.

e. Observe patient closely during administration of first dose. Pre-medicate patient if the following infusion related reactions occur:

(1) Fever or Chills:acetaminophen 10-15 mg/kg PO and hydrocortisone 25 – 100 mg IV, 30 minutes prior to infusion.

(2) Severe Rigors:meperidine 25 – 50 mg IV, 30 minutes prior to infusion.

3. Monitoring Parameters

a. Renal function (SCr, BUN, creatinine clearance), Electrolytes ( K+, Mg+), LFTs, andCBC with differential – performed daily for first two weeks, then twice weekly until completion of amphotericin B therapy.

b. Fungal cultures – performed weekly.

c. More frequent testing is appropriate only if worsening clinical status or patient is on concomitant nephrotoxic medications.

II. Clinical Practice Guidelines

Conventional amphotericin should be first line treatment in all patients, with exceptions asindicated by the guidelines. Lipid-based formulations of amphotericin will only be dispensedby the pharmacy for patients meeting one of the following criteria.The prescriber will be contacted and requested to modify therapy for other patients. Lipid-based amphotericin willbe provided outside of the treatment guidelines only upon the approval of the MedicalDirector or designee.

– 26 –

B. Lipid-based Amphotericin B (Abelcet ™)

1. Indication

a. Unresponsiveness to conventional amphotericin B as defined by:

(1) no improvement in temperature

<or>

(2) no decrease in white blood cell count

<or>

(3) no sterilization of cultures after receiving a total dose of at least 500 mg conventional amphotericin.

b. Intolerance to conventional amphotericin B as indicated by:

(1) an increase in SCr to >2.5 mg/dL as determined by two measurements at least 24 hours apart in a patient not receiving peritoneal or hemodialysis

<and>

(2) no improvement in SCr after at least 24 hours of hydration, dopamine infusion,diuresis, or other measures to improve renal function

<and>

(3) need for continued administration of other nephrotoxic medications (eg: cyclosporine, aminoglycosides) has been re-evaluated, and discontinued or dose reduction of any such medication has not resulted in decreasing SCr to less than 2.5 mg/dL after at least 24 hours.

c. Decreased Renal Function – IIf initial SCr is greater than 3 mg/dL and the patient is not receiving dialysis.

d. Previous kidney transplant.


a. 2.5 – 5 mg/kg/day

b. Observe patient closely during administration of first dose. Premedicate patient as indicated under conventional amphotericin B.


a. As indicated under conventional amphotericin B.

C. Liposomal Amphotericin B (AmBisome ®)

1. Indication

a. Fungal infection located in the CNS.


a. CNS Fungal Infections: 5 mg/kg/day.

. b. Infuse over 1 – 2 hours (2.5 mg/kg/hour).

c. Shake bag prior to infusion, if infusion is > 2 hours bag should mixed every two hours by shaking.

d. Observe patient closely during administration of first dose. Pre-medicate patient as indicated under conventional amphotericin B.


a. As indicated under conventional amphotericin B.

II. Clinical Practice Guidelines (continued)

– 27 –

S E C T I O N T W O :

T H E R A P E U T I C I N T E R C H A N G E


O C TO B E R 2 0 0 0

MedStar Health

– 28 –

CIPROFLOXACIN – TRANSITION FROM INTRAVENOUS TO ORAL THERAPY

Effective Date: November 1995 Index #: TI-PT: 0001

I. BACKGROUND

The absolute bioavailability of oral ciprofloxacin is 70-80% with no substantial loss of drugdue to first pass metabolism. An intravenous infusion of 400 mg ciprofloxacin given over 60 minutes every 12 hours has been shown to produce an area under the serum concentra-tion time curve (AUC) equivalent to that produced by a 500 mg oral dose given every12 hours. A 400 mg IV dose administered over 60 minutes every 12 hours results in a Cmaxsimilar to that observed with a 750 mg oral dose.

The direct and indirect costs of providing intravenous ciprofloxacin differ considerably fromthose associated with providing the oral medication.The direct cost for a day of therapy withvarious dosages and dosage forms is summarized below:

Ciprofloxacin 400 mg IV Q12H $ 40.58

Ciprofloxacin 500 mg po Q12H $ 7.50

Ciprofloxacin 750 mg po Q12H $ 6.72

Significant savings can be realized through the preferential use of the oral medication without compromising patient care.

II.Therapeutic interchange:The use of intravenous ciprofloxacin will be limited to patientswho require the use of a fluoroquinolone and are unable to take oral medications.Ciprofloxacin tablets will be used for all patients able to take oral medications. All orders for intravenous ciprofloxacin will be changed to oral ciprofloxacin within 24 hours of the patient receiving other oral medications. Dosages will be appropriately modified.Intravenous ciprofloxacin will be provided outside of this therapeutic interchange programonly upon the approval of the Medical Director or designee.

– 29 –

II. THERAPEUTIC INTERCHANGE

H2 BLOCKER THERAPEUTIC INTERCHANGE

Effective Date: February 1994 Index #: TI-PT: 0002

I. BACKGROUND

The H2 blockers decrease the secretion of gastric acid and the resultant conversion ofpepsinogen to pepsin by inhibiting the binding of histamine to H2 receptors on the parietalcells.There are currently four H2 blockers on the market in the United States.These agentsare cimetidine (Tagamet®), ranitidine (Zantac®), famotidine (Pepcid®), and nizatidine (Axid®).While these drugs have been demonstrated to be equally effective in the treatment of acidpeptic disorders they do differ in their cost, dosage and dosage frequency, availability ofdosage forms, and drug interaction profile.

Cimetidine is known to inhibit the oxidative metabolism of other drugs due to its binding tothe cytochrome P-450 mixed function oxidase system. Ranitidine also disrupts this enzymesystem, but to a lesser extent than cimetidine. In equipotent doses, it is generally believedthat ranitidine has less potential to cause significant drug interactions than cimetidine.Famotidine and nizatidine do not effect the cytochrome P-450 mixed function oxidasesystem and their potential to cause drug interactions is limited.

The H2 blockers are well tolerated medications. For the most part, the incidence of adversereactions is similar among the various H2 receptor blockers and is extremely low.The mostcommonly observed adverse reactions are diarrhea, headache, drowsiness, fatigue, muscularpain, and constipation, all occurring in 1-3% of all patients receiving the drugs. Less com-monly observed adverse reactions (frequency <1%) include mental confusion, dizziness,somnolence, gynecomastia, galactorrhea, impotence, loss of libido, blood dyscrasias, elevatedliver enzymes, elevated serum creatinine levels, skin rashes, cardiac arrhythmias, andhypotension. Patients at highest risk for adverse drug reactions are those with hepatic orrenal dysfunction, advanced age, and multiple illnesses. Several of the rarely reported sideeffects have been associated with cimetidine only. It is uncertain as to whether or not thisrepresents a true difference in the side effect profiles of the drugs, or is a function of under-reporting of adverse drug reactions in the FDA’s voluntary ADR reporting program.

– 30 –


When cimetidine, ranitidine or nizatadine are prescribed, the prescriber will be contacteddirectly, advised of the therapeutic interchange, and requested to change the order to eitheroral or parenteral famotidine. (The dosing guidelines for these agents are summarizedbelow.) If the order has not been changed within 2 hours, the unit based clinical pharmacistwill stamp the order sheet with an order to discontinue the non-formulary medication, andinitiate treatment with the formulary agent. Requests to utilize non-formulary H2 blockersrequire authorization by the Medical Director or designee.

A. Famotidine:

1. Marketed by MSD under the brand name Pepcid®.

2. Dosage/Administration:

a. Normal renal function:

(1) Oral:20 mg PO Q12H or 40 mg PO QHS.

(2) IV:20 mg Q12H diluted in 50 ml of 5% dextrose and administered over 15 – 30 minutes.The literature also supports the administration of the drug as a continuous infusion with the daily dose administered over 24 hours.

The product is also stable in saline solutions and parenteral nutrition solutions..

b. The dosage of famotidine is reduced by 50% in patients with a creatinine clearance of less than 10 ml/min (i.e. 20 mg daily).

– 31 –

– 32 –

LEVOFLOXACIN – TRANSITION FROM INTRAVENOUS TO ORAL THERAPY

Effective Date: February 2000 Index #: TI-PT: 0004

I. BACKGROUND

The absolute bioavailability of oral levofloxacin is 99% with no substantial loss of drug due tofirst pass metabolism.The peak and trough serum levels and area under the concentrationtime curve are comparable for oral and intravenous administration of similar doses of thedrug.The oral and intravenous routes of administration are considered interchangable.

The direct and indirect costs of providing intravenous levofloxacin differ considerably fromthose associated with providing the oral medication.The direct cost for a day of therapy with various dosages and dosage forms is summarized below:

Levofloxacin 500 mg IV Q24H $20.79

Levofloxacin 500 mg PO Q24H $ 5.80

Significant savings can be realized through the preferential use of the oral medicationwithout compromising patient care.

The use of intravenous levofloxacin will be limited to patients who require the use of afluoroquinolone and are unable to take oral medications. Levofloxacin tablets will be usedfor all patients who are able to take oral medications. All orders for intravenous levofloxacinwill be changed to oral levofloxacin within 24 hours of the patient receiving other oralmedications. Intravenous levofloxacin will be provided outside of this therapeutic inter-change program only upon the approval of the Chairman of the Pharmacy and TherapeuticsCommittee or designee.

– 32 –


– 33 –

S E C T I O N T H R E E :

R E CO M M E N D AT I O N S F O R T H E S E L E C T I O N O F A N T I M I C R O B I A L D R U G S


O C TO B E R 2 0 0 0

Notes:

1. The doses listed are usual maintenance doses for serious infections in

patients with normal renal function. Please consult with the pharmacy

for loading dose recommendations, and for dosage modification in

patients with impaired physiologic (renal/hepatic) function.

2. The costs listed are pharmacy acquisition costs for the drug and

intravenous fluid.

MedStar Health

– 34 –

E M P I R I C A N T I B I O T I C S E L E C T I O N

B. Combined with agent with anti-anaerobic activity:

1. Clindamycin – 900 mg IV Q8H ($7.05/day)

<or>

2. Metronidazole – 500 mg IV Q6H($5.92/day)

A. Agent with activity against entericgram negative organisms:

1. Ceftriaxone – 1 gram IV Q24H($21.02/day)

<or>

2. Levofloxacin – 500 mg PO* Q24H($5.50/day)/500 mg IV Q24H($21.00/day)

*Oral levofloxacin achieves serum levels comparable to the intravenous drug and is much less expensive.The oral route should be used whenever possible.

<or>

3. Ceftazidime – 2 grams IV Q8H($49.53/day)

Use only where Pseudomonas is a highly suspected pathogen.Combine with an aminoglycoside as described in the Section on “Documented PseudomonasInfections”which follows in addition to an agent from Group B.

I. Empiric Treatment of Intra-Abdominal Infections

Monotherapy

1. Piperacillin/tazobactam – 3.375 grams IV Q6H ($41.68/day)

Combination Therapy

Combine an agent from Group A with an agent from Group B.

It has been demonstrated clinically that converting broad spectrum, empiric antimicrobial coverage to targeted, narrow spectrum coverage immediately upon the availability of cultureand susceptibility data is an important strategy in minimizing the emergence of strains of resistant bacteria and is generally cost effective (e.g. switching from levofloxacin to amoxicillinin the treatment of pneumonia caused by susceptible Streptococcus pneumoniae, switching from vancomycin to nafcillin for susceptible Staphylococcus aureus).

– 35 –

B. Agent with activity against Chlamydia:

Note – not necessary if regimen A.2. orA.4. is used.

1. Doxycycline – 100 mg IV Q12H ($7.48/day)/100 mg PO Q12H ($0.22/day)

<or>

2. Azithromycin – 500 mg IV Q24H($18.57/day) x 2 days, then 250 mg POQ24H ($4.93/day)

A. Agent with enteric gram negative and anti-anaerobic activity:

1. Piperacillin/tazobactam – 3.375 grams IV Q6H($41.68/day)

<or>2. Ceftriaxone – 1 gram IV Q24H ($21.02/day)

with Clindamycin – 900 mg IV Q8H ($7.05/day)<or>3. Cefoxitin – 2 grams IV Q6H ($54.16/day)<or>4. Levofloxacin – 500 mg PO* Q24H ($5.40/day)/

500 mg IV Q24H ($21.00/day)with Clindamycin – 900 mg IV Q8H ($7.05/day)

*Oral levofloxacin achieves serum levelscomparable to the intravenous drug and is much less expensive. The oral route should be used whenever possible.

B. Azithromycin – 500 mg IV ($18.57/day) x 2 daysfollowed by 500 mg PO Q24H ($4.93/day)

A. Ceftriaxone – 1 gram IV Q24H x 2 days($21.02/day)

B. Agent with activity against PCI1. Trimethoprim/sulfamethoxazole –

15 mg/kg/day of trimethoprim component (not to exceed 960 mg of trimethoprim component/day) in divided doses IV Q6H ($6.50/day)

<or if sulfa allergy>2. Pentamidine – 4 mg/kg/day

($58.00/day)

A.1. Levofloxacin – 500 mg PO* Q24H

($5.40/day)/500 mg IV Q24H($21.00/day)


II. Empiric Treatment of Intrapelvic Infections

III. Presumptive Treatment of Community Acquired Pneumonia

The use of levofloxacin should be reserved for situations where penicillin resistant Streptococcus pneumoniae is a highly suspected (i.e. previous use of antibiotics, nursing home resident, or contactwith small children) or confirmed pathogen.Treatment should be simplified to a beta lactam (e.g. ceftriaxone 1 gm IV Q24H or appropriately “stepped down”to amoxicillin 500 mg PO Q8H) onall occasions when culture and susceptibility information identify a beta lactam susceptible organismand the patient does not have a history of beta lactam allergy. In cases where a beta lactam allergyexists, consideration should be given to the use of a macrolide (e.g. azithromycin or clarithromycin).

Monotherapy

1. Levofloxacin – 500 mg PO* Q24H ($5.40/day)/500 mg IV Q24H ($21.00/day) *Oral levofloxacin achieves serum levels comparable to the intravenous route and is much less expensive. The oral route should be used whenever possible.

Combination Therapy


Combination Therapy when Pneumocystis Carinii (PCI) Is Suspected


These are infections arising from, or due to penetration of, the female genital tract.

Combination Therapy


– 36 –

B. Combined with aminoglycoside

Note: Aztreonam may be used in combination with any of the regimens listed in Group A as an alternative inpatients with rapidly deteriorating renalfunction.

1. Gentamicin – 1mg/kg IV Q8H($6.12/day)

<or>

2. Amikacin – 5 mg/kg IV Q8H($17.73/day)

It is recommended that amikacinbe used for empiric therapy with aztreonam or ciprofloxacin due to the high incidence of resistance to these agents.

C. Combined with agent with anti-anaerobic activity

1. Clindamycin – 900 mg IV Q8H($7.05/day)

<or>

2. Metronidazole – 500 mg IV Q6H($5.92/day)

A. Agent with gram negative activity (not including Pseudomonas)

1. Ceftriaxone – 1 gram IV Q24H($21.02/day)

<or>2. Piperacillin/tazobactam – 3.375 grams

IV Q6H ($41.68/day)

A1. Agent with gram negative activity(including Pseudomonas)

1. Ceftazidime – 2 grams IV Q8H($49.53/day)

<or>

2. Piperacillin/tazobactam – 3.375 gramsIV Q4H ($62.52/day)

A2. Patients allergic to beta lactams

1. Aztreonam – 2 grams IV Q6H($105.15/day)

<or>2. Levofloxacin – 500 mg PO* Q24H

($5.50/day)/500 mg IV Q24H($21.00/day)


<or>3. If Pseudomonas infection suspected:

Ciprofloxacin – 750 mg PO* Q12H($5.50/day)400 mg IV Q12H($45.00/day)

*Oral ciprofloxacin achieves serum levels comparable to the intravenous drug and is much less expensive.The oral route should be used whenever possible.

IV. Empiric Treatment of Nosocomial Pneumonia

The following guidelines are based on clinical scenarios commonly encountered at WashingtonHospital Center.To provide Staphylococcus aureus coverage (e.g. ICU or ventilator patient) whensuspected, the regimen must include either piperacillin/tazobactam from Group A or clin-damycin from Group C below. If methicillin resistant Staphylococcus aureus (MRSA) is suspected,vancomycin should be considered as discussed in the Section on “Staphylococcal Infections.”

Combination Therapy Only

Combine an agent from Group A with an agent from Group B.If aspiration is suspected, an antianerobic agent from Group C should also be added.

High Suspicion of Legionella

Add a macrolide or levofloxacin to one of the above regimens.

– 37 –

V. Presumptive Treatment of Nosocomial Sinusitis

VI. Empiric Treatment of Head and Neck Infections

Treat as outlined in previous Section IV,“Presumptive Treatment of Nosocomial Pneumonia.”If failing therapy, drainage, for both therapeutic and diagnostic purposes, is strongly recommended.

IMMUNOCOMPETENT PATIENTS

Monotherapy

1. Ampicillin/sulbactam (Unasyn) – 3 grams IV Q6H ($48.00/day)

Combination Therapy

Combine an agent from Group A with an agent from Group B

A. 1. Penicillin G – 4 million units IV Q4H($13.80/day)

<or>

2. Levofloxacin – 500 mg PO* Q24H($5.50/day)/500 mg IV Q24H($21.00/day)


B. 1. Clindamycin – 900 mg IV Q8H($7.05/day)

IMMUNOCOMPROMISED PATIENTS

Patients who have primary immunodeficiency disorders or are immunocompromised secondary to corticosteroids, chemotherapy, or other immunosuppressive medications.

Monotherapy

1. Ampicillin/sulbactam – 3 grams IV Q6H ($48.00/day)

Combination Therapy


A. 1. Ceftriaxone – 1 gram IV Q24H B. 1. Clindamycin – 900 mg IV Q8H ($21.02/day) ($7.05/day)

<or>

2. Levofloxacin – 500 mg PO* Q24H ($5.50/day)/500 mg IV Q24H ($21.00/day)


– 38 –

VII. Empiric Treatment of Complicated Urinary Tract Infections

These are infections associated with kidney stones, urinary obstruction, or pyelonephritis and/or those with coexisting bacteremia.

Monotherapy

1. Levofloxacin – 500 mg PO* Q24H ($5.50/day)/500 mg IV Q24H ($21.00/day)

*Oral levofloxacin achieves serum levels comparable to the intravenous drug and is much less expensive. The oral route should be used whenever possible.

<or>

2. Ceftriaxone – 1 gram IV Q24H ($21.02/day)

<or>


<or>

4. Gentamicin* – 1mg/kg IV Q8H ($6.12/day)

*Note: Dosage must be based on ideal body weight and adjusted for renal functions

<or>

5. If infection is of nosocomial origin:

Amikacin – 5 mg/kg IV Q8H ($17.73/day).

– 39 –

VIII. Empiric Treatment of Skin/Soft Tissue Infections

A. Community Origin

Although cultures are typically polymicrobial, infections are usually of gram positive origin,treatment with the regimens suggested below should be continued unless there is evidence of treatment failure or a culture from a definitive site.

1. Cefazolin – 1gram IV Q8H ($5.82/day)

<or>

2. Clindamycin – 900 mg IV Q8H ($7.05/day)

<or>

3. Vancomycin* – 1 gram IV Q12H ($13.88/day)

*Note: may be approriate if the patient is at high risk for MRSA as described in the Section on “Documented Staphylococcus Aureus Infections.”

B. Decubitus Ulcer/Diabetic Foot with Objective Signs of Infection

Objective signs of infection include cellulitis, gross pus production, or microabcesses.


<or>

2. Ceftriaxone – 1 gram IV Q24H ($21.02/day) with Metronidazole 500 mg IV Q6H ($5.92/day)

<or>

3. Levofloxacin – 500 mg PO* Q24H ($5.50/day)/500 mg IV Q24H ($21.00/day)with Clindamycin – 900 mg IV Q8H ($7.05/day)


Nosocomial Origin

These infections include post bypass surgery, secondary to a foreign body, etc.

Treat as outlined in (B) above with the addition of vancomycin – 1 gram IV Q12H ($13.88/day).

Fasciitis

Surgical intervention is imperative. Adunctive antimicrobial coverage is recommended with:

1. Levofloxacin – 500 mg PO* Q24H ($5.50/day)/500 mg IV Q24H ($32.42/day)with clindamycin – 900 mg IV Q8H ($7.05/day)


– 40 –

T R E A T M E N T O F D O C U M E N T E D I N F E C T I O N S

B. Combined with aminoglycosideNote: In patients who are not allergic tobeta lactams, aztreonam may be used incombination with either of the regimenslisted in Group A as an alternative to anaminoglycoside in patients with rapidlydeteriorating renal function.

B1. Patients not allergic to beta lactams:Gentamicin – 3 mg/kg IV ($6.12) loadingdose followed by 1mg/kg IV Q8H($6.12/day)

Dosage must be based on ideal body weight and adjusted for renal function.

B2. Patients allergic to beta lactams:Amikacin – 5 mg/kg IV Q8H ($17.73/day)

It is recommended that amikacin be usedfor empiric therapy with aztreonam orciprofloxacin due to the high incidence of resistance to these agents.

A. Agent with antipseudomonal activity

A1. Patients not allergic to beta lactams:1. Ceftazidime – 2 grams IV Q8H

($49.53/day)

<or>

2. Piperacillin/tazobactam – 3.375 gramsIV Q4H ($62.52/day)

A2. Patients allergic to beta lactams:1. Aztreonam – 2 grams IV Q6H

($105.15/day)

<or>

2. Ciprofloxacin – 400 mg IV Q12H($45.00/day)/750 mg PO Q12H($5.50/day)

I. Treatment of Documented Staphylococcus Aureus Infections

II. Treatment of Documented Pseudomonas Infections

1. Cefazolin* – 1gram IV Q8H ($5.82/day)

<or>

2. Nafcillin* – 2 grams IV Q4H ($10.36/day)

*Nafcillin and Cefazolin are the treatments of choice for methicillin susceptible strains ofStaphylococcus aureus (MSSA) and Staphylococcus epidermidis (MSSE).

<or>

3. Vancomycin – 1 gram IV Q12H ($13.88/day)The indiscriminate use of vancomycin is associated with the emergence of vancomycinresistant Enterococcus. As a result, the use of vancomycin should be limited to patients with documented MRSA, or started empirically in patients at high risk for infection withMRSA:

a. history or IV drug abuse,

b. presence of a chronic indwelling intravascular device including dialysis catheters (e.g. Hickman catheter, Broviac catheter, Mediport, etc.),

c. history of prolonged hospitalization or chronic institutionalization (e.g. nursing home).

Note: Nafcillin has been demonstrated to be clinically superior to vancomycin in the treatment of infections caused by susceptible strains of Staphylococcus aureus.Penicillin allergic patients with serious Staphylococcus aureus infections should be skin tested and hyposensitized if necessary, so that nafcillin can be utilized.

Combination Therapy Only


– 41 –

1 9 9 9 A N T I B I O G R A M S

D E P A R T M E N T O F P A T H O L O G Y

I. GRAM NEGATIVE RODS — % SUSCEPTIBLE

II. GRAM POSITIVE COCCI — % SUSCEPTIBLE

MedStar Health

– 42 –

D E P A R T M E N T O F P A T H O L O G Y — 1 9 9 9 A N T I B I O G R A M

GRAM NEGATIVE RODS — % SUSCEPTIBLE

Acinetobacter species 3 4 0 55 3 42 48 56 48

Citrobacter freundii 3 75 9 69 73 75 90 78 71

Citrobacter species 0 99 94 97 99 97 100 98 98

Enterobacter aerogenes 3 81 6 76 81 98 98 83 95

Enterobacter agglomerans 20 100 60 100 100 100 100 100 100

Enterobacter cloacae 3 69 2 64 66 86 85 77 83

Enterobacter species 0 52 10 50 52 66 73 52 63

Escherichia coli 50 96 87 91 96 91 94 96 77

Klebsiella pneumoniae 0 92 85 90 92 91 93 90 83

Klebsiella oxytoca 0 86 54 93 86 91 96 83 95

Morganella morganii 1 83 3 84 81 68 75 88 62

Proteus mirabilis 90 99 92 99 100 87 94 99 90

Proteus vulgaris 11 100 16 100 100 100 94 100 88

Providencia species 10 100 36 91 96 34 90 100 50

Pseudomonas aeruginosa — 60 — 85 — 59 72 86 —

Serratia marcescens 0 100 0 100 96 93 100 97 89

Stenotropho-monas 7 10 1 76 9 74 37 48 87maltophilia

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D E P A R T M E N T O F P A T H O L O G Y — 1 9 9 9 A N T I B I O G R A M

GRAM POSITIVE COCCI — % SUSCEPTIBLE

Staphylococcusaureus 4 58 60 58 87 100 39

Coagulase-negativeStaphylococci 7 26 53 26 43 100 22

Enterococcus* 87 89

** Note:Streptococcus pneumoniae –Penicillin is the drug of choice for allpenicillin-susceptible isolates.For isolates with documented resistanceto penicillin, ceftriaxone, levofloxacin orvancomycin may be indicated.

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Streptococcus 67 95pneumoniae**

Pharmacy And Therapeutics Committee

Education

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