JANUARY                                                                                                             2001

 

University of Kansas Hospital

Adult Antiemetic Guidelines

Chemotherapy Induced Nausea and Vomiting

 

·        Ondansetron is the only 5HT3 antagonist on the formulary.

·        Ondansetron and other 5HT3 antagonists (Granisetron, Dolasetron) are not effective as a breakthrough agent and should not be given as such.  There should be no PRN orders.

·        Ondansetron should be given 30 to 60 minutes prior to chemotherapy and/or total body radiation.

 

Situations for which 5-HT3 Antagonists are considered inappropriate:

 (Adopted from the NIH Clinical Center Guidelines)

 

Nausea and Vomiting due to chemotherapy of low emetogenic potential

5-HT3 antagonists should not be used with chemotherapeutic agents that are considered to be of low emetic potential.  Several alternative agents are available on formulary.  Consult with your pharmacist or call the Pharmacy for assistance.

Delayed nausea and vomiting

5-HT3 antagonists have only modest activity in preventing and treating delayed emetic symptoms.   An example of such an effective regimen is Decadron, Reglan and Benadryl for 5 days after Cisplatin.  Prophylaxis, except in the non bone marrow transplant population, with these agents will be limited to 24 hours after the last antineoplastic dose. 

Anticipatory nausea and vomiting

5-HT3 antagonists are not useful as prophylaxis or for treatment of anticipatory nausea and vomiting.  Unless otherwise contraindicated, benzodiazepines (e.g., lorazepam ) should be used for this purpose.

 “PRN” orders

The goal of antiemetic therapy is to PREVENT nausea and vomiting.  Antiemetics are, therefore, best started BEFORE a patient receives emetogenic therapy.  Ondansetron should be ordered as a scheduled medication and not PRN.

Combination Chemotherapy

1.      Identify the most emetogenic agent in the combination.

2.      Assess the relative contribution of the other agents in the emetogenicity of the combination.

            When considering other agents, the following rules apply:

a.      Level 1 agents do not contribute to the emetogenicity of a given regimen

b.      Adding one or more level 2 agents increases the emetogenicity of the combination by one level greater than the most emetogenic agent in the combination.

c.      Adding level 3 or 4 agents increases the emetogenicity of the combination by one level per agent. 

                  Examples   4+4=5               3+3=4                     2+2=3

                                          4+3+4=5           3+3+3=5           2+2+2=3

                                          4+3+3+4=5       3+2+3=4           3+2+2+4=5

 

Other 5-HT3 Antagonists will be made available for documented Ondansetron failures.

Probability of Emesis

First Line Therapy

Breakthrough Therapy

Responsible Agents

Common Combinations

Level 5 (Very High)

 

Including BMT’s

 

 

Ondansetron 24mg po ($52.52)  or          IV ($80.16) qd Dexamethasone 20mg po/IV qd

 

Scheduled or PRN Compazine 10mg po/IV, q 4-6h

Ativan 1mg IV q 6h, or Benadryl po

25-50mg q 4-6h

Carmustine (³250mg/m2)

Cisplatin (³ 60mg/m2)

Cyclophosphamide (>1000mg/m2)

Dacarbazine

Mechlorethamine

Streptozocin

Amifostine

Melphalan (High Dose)

Thiotepa (High Dose)

ABVD            MITT

CMV              MOPP

CTC               TIME

ICE                TNT

MAID

M-VAC

Level 4 (High)

 

 

Same as Level 5

Same as Level 5

Busulfan (³ 4mg/kg/day)

Carmustine (£ 250mg/m2)

Carboplatin (>1000mg)

Cisplatin (< 60mg/m2)

Cyclophosphamide (600-1000mg/m2)

Cytarabine (>1000mg/m2)

Dactinomycin

Doxorubicin (> 60mg/m2)

Etoposide (> 200mg/m2)

Ifosfamide

Methotrexate (³ 1000mg/m2)

ACE               PVP

BEP               VIP

BUCY             MAI

CA

CAF

CAV

CHOP

EVDAC

FAC

Mini-ICE

HDARAC

ProMACE-CytaBOM

Level 3 (Moderate)

Ondansetron 16mg po ($37.66) /  or        IV  ($53.44)  qd

Dexamethasone 20mg po/IV qd or Compazine 10mg po/IV q4-6h

Metoclopramide 20mg or (2mg/kg) q 6h po/IV, Haloperidol  2-5mg q 6h, Benadryl 25-50mg q 4-6h

Azacitidine

Carboplatin (< 1000mg)

Cyclophosphamide (< 600mg/m2)

Cytarabine (250-1000mg/m2)

Daunorubicin

Doxorubicin (< 60mg/m2)

Fluorouracil (>1gm/m2)

Gemcitabine

Idarubicin

Irinotecan

Hexamethylmelamine

Lomustine

Methotrexate (250-1000mg/m2)

Mitomycin

Mitoxantrone

Pentostatin

Procarbazine

Plicamycin

Teniposide

Topotecan

ARAC CIVI + DAUN

CMF

COP

CVP

FAM

Level 2 (Low)

Ondansetron 16mg po ($37.66) /          IV ($53.44)  qd

Dexamethasone 20mg po/IV qd, or

Scheduled or PRN Compazine 10mg po/IV q 4-6h

Same as Level 3

Asparaginase

Cytarabine (< 250mg/m2)

Daunorubicin Lipo.

Docetaxel

Doxorubicin Lipo.

Etoposide (< 200mg/m2)

Floxuridine

Fluorouracil (< 1gm/m2)

Melphalan (Low Dose)

Mercaptopurine

Methotrexate (50-250mg/m2)

Paclitaxel

Thiotepa (Low Dose)

 

Level 1 (Very Low)

Scheduled or PRN Compazine 10mg po q 4-6 h

 

Busulfan (Low Dose)

Bleomycin

Chlorambucil

Cladribine

Fludarabine

Hydroxyurea

Methotrexate (< 50mg/m2)

Tamoxifen

6-Thioguanine

Vinblastine

Vincristine

Vinorelbine (IV)

VP

VAD

 

FORMULARY ADDITIONS

 

Tenecteplase (TNKase™)

50 mg Injection

Genetech, Inc.

 

Tenecteplase is indicated for use in reduction of mortality associated with acute myocardial infarction. Tenecteplase is a recombinant DNA form of human tissue plasminogen activator that binds to fibrin with minimal plasminogen activity in the absence of fibrin. Table 1 indications for alteplase, reteplase and tenecteplase.    Advantages of tenecteplase over reteplase include longer t ½ and faster plasma clearance. The use of a one-time bolus injection for tenecteplase versus two bolus injections separated by 30 minutes for reteplase does offer some advantages as reduced time in preparation and dispensing.   However, as with any of these agents’ errors in dosing can and will occur with medications that require dosing based upon weight. It is recommended at KUMC that all plasminogen activators be ordered by generic name to prevent any nomenclature errors with using the trade name.  Tenecteplase was voted to add to the formulary with order approval by Cardiology Attending, along with patient selection criteria guidelines. Inclusion criteria is defined as a presentation consistent with an acute myocardial infarction, ECG evidence of an acute MI (ST elevation > 1 mm in two continuous leads), onset of symptoms less than 12 hrs, and evidence of ongoing ischemia. These agents are contraindicated in the following types of patients due to an increased risk of bleeding; active internal bleeding, history of cerebrovascular accident, intracranial or intraspinal surgery or trauma within 2 months, intracranial neoplasm, arteriovenous malformation, or aneurysm, known bleeding diathesis or severe uncontrolled hypertension.

 

Table 1: Comparison of FDA-Approved Indications
Indication
Alteplase

Reteplase
Tenecteplase

Acute Myocardial Infarction

X

X

X

Acute Ischemic Stroke

X

 

 

Pulmonary Embolism

X

 

 

Thromboembolic Stroke

X

 

 

 

            Readministration of plasminogen activators has not been studied and should be undertaken with caution due to the possibility of possible development of antibodies and subsequent anaphylaxis reactions.  The most common complication encountered during plasminogen activator therapy is internal or superficial bleeding.  Intramuscular injections and non-essential handling of the patient should be avoided for the first few hours after plasminogen activator therapy.  Patients should also be monitored for cholesterol, embolism, arrhythmia and anaphylaxis. 

The most common adverse reaction associated with tenecteplase is bleeding, 4.7% major bleeds, 21.8% minor bleeds (major bleeding was defined as the need for blood transfusions or hemodynamic compromise).  Allergic-type reactions and anaphylaxis were reported in <1% of patients during clinical trials.  There has been no formal drug interaction studies performed with alteplase, reteplase and tenecteplase.  These agents carry the standard warning that increased risk of bleeding may occur if anticoagulants or antiplatelet drugs are administered prior, during, or after therapy.  During clinical trials patients were concomitantly administered heparin and aspirin with the use of plasminogen activator therapy and discontinued in the event of a serious bleed.

Tenecteplase dosing is weight-based (0.5 mg/kg) and should not exceed 50 mg.  A single bolus dose should be administered intravenously over 5 seconds. IV lines containing D5W must be flushed prior to drug administration. Weight adjusted dose information is described in Table 2.

 

 

 

 

 

 

 

Table 2: Weight-Adjusted Dose Information Table for Tenecteplase

Patient Weight (Kg)

Tenecteplase Dose (mg)

Volume to be administered (mL)

<60

30

6

³60 to <70

35

7

³70 to <80

40

8

³80 to <90

45

9

³90

50

10

*From one vial of tenecteplase reconstituted with 10 mL of sterile water for injection