Chemotherapy-Inducted Nausea and Vomiting Guidelines for Adult ...

Chemotherapy-Inducted Nausea and Vomiting Guidelines for
Adult and Pediatric Patients at UK Hospital
Drug Information Center
C-113 Chandler Medical Center, (859) 323-5320
The Pharmacy and Therapeutics Committee is implementing guidelines for the prevention of
chemotherapy-induced emesis (CIE) in adult and pediatric patients at the University of Kentucky. These
guidelines are based on scientific evidence and published national guidelines which address the efficacy,
safety and cost. Highlights of the guidelines follow, and the actual guidelines can be found on pages 2
and 3.
• Oral granisetron (Kytril ® ) is the first-line 5-HT3 receptor antagonist for the prevention of acute
emesis from chemotherapy with an emetogenicity greater than 30 percent (Level 3 or higher).
Many studies have demonstrated the equivalency in efficacy and safety of 5-HT3 receptor antagonists
at equipotent doses in patients treated with moderately or highly emetogenic chemotherapy (Navari et
al, 1995; Roila et al, 1995). Therefore, the choice of agent was primarily based on acquisition costs
for comparable dosage regimens.
• Granisetron should be administered orally unless a patient has a contraindication to oral
therapy. Studies comparing granisetron 2 mg PO and ondansetron (Zofran ® ) 32 mg IV have
determined the antiemetic regimens to be similar in efficacy and safety in patients receiving
moderately and highly emetogenic chemotherapeutic regimens (Perez et al, 1998; Gralla et al, 1998).
• An intravenous dose of 10 mcg/kg of granisetron should be used for patients requiring
intravenous therapy or those unresponsive to oral therapy. Orders written as granisetron 1 mg IV
will be automatically converted by Pharmacy to a weight-based dose. Pharmacy will record the
dosage change in the patient’s chart.
• If a patient fails oral granisetron therapy, switch to granisetron IV 10 mcg/kg, add an agent from
a different pharmacological class, or use a combination of the above approaches.
• If a patient fails granisetron IV, switch to ondansetron 16 mg IV.
• For the prevention of delayed emesis, use either metoclopramide (Reglan ® ) or prochlorperazine
(Compazine ® ), both in combination with dexamethasone (Decadron ® ). Metoclopramide in
combination with dexamethasone is effective in the prevention of delayed CIE (Kris et al, 1989).
Serotonin (5-HT3) is not believed to be a primary mediator of symptoms for delayed emesis, as
evidenced by the lower efficacy rate of 5-HT3 receptor antagonists in preventing delayed emesis, as
well as conflicting literature regarding the benefit of continuing 5-HT3 receptor antagonists beyond 24
hours (Pater et al, 1997; Latreille et al, 1998).

Emetogenicity of Chemotherapeutic Agents
Level 1 (60 mg/m 2 )
Epirubicin hydrochloride (≤90 mg/m 2 )
Mechlorethamine
Idarubicin
Pentostatin
Ifosfamide
Streptozocin
Methenamine (oral)
Methotrexate (250-1000 mg/m 2 )
Mitoxantrone (≤15 mg/m 2 )
*Intrathecal coadministration of methotrexate and cytarabine to pediatric patients increases the emetogenicity level to 3.
Calculating Emetogenic Potential of Multiple-Agent Regimens
Identify the agent with the highest emetogenic level, then determine the contribution of the remaining agents by using the
following rules:
Examples:
(1) Level 1 agents do not contribute to emetogenicity. Level 1+1=0 2+1=2 3+1=3 4+1=4
(2) Adding one or more level 2 agents increases the highest level by 1. Level 2+2=3 3+2=4 2+2+2=3 3+2+2=4
(3) Adding level 3 or 4 agents increases the highest level by 1 per agent. Level 3+3=4 3+3+3=5 4+3=5
PEDIATRIC GUIDELINES FOR CHEMOTHERAPY-INDUCED EMESIS
Prevention of Acute Emesis
Level 1
Level 2-5
Granisetron PO (patients able to take PO medications)
OR
Granisetron IV (patients who are not candidates for PO)
PLUS
Dexamethasone PO or IV
No preventative therapy necessary
2 mg 30 minutes prior to chemotherapy
10 mcg/kg IV 30 minutes prior to chemotherapy
10 mg/m 2 PO or IV in single or divided doses
Prevention of Acute Emesis – History of Refractory Emesis
Ondansetron IV 0.15 mg/kg 30 minutes prior to chemotherapy and q4h x 2
PLUS
Dexamethasone PO or IV
10 mcg/kg IV 30 minutes prior to chemotherapy
Treatment of Breakthrough Emesis
Dexamethasone
OR
Lorazepam (children >5 yrs only)
OR
Promethazine
5-10 mg/m 2 PO or IV q12h prn
0.05 mg/kg (max 2 mg) IV q12h prn
0.25-0.5 mg/kg (max 25 mg) IV q6-8h prn
Treatment of Refractory Emesis
• Increase dose of current agent (within recommended range), OR
• Add agent from different pharmacologic class, OR
• Use a combination of above approaches

ADULT GUIDELINES FOR CHEMOTHERAPY-INDUCED EMESIS
ACUTE EMESIS
PREVENTION
None
5-10 mg PO, IM, or IV q6h PRN, OR
Level 1 Prochlorperazine 25 mg PR q12h PRN, OR
15 mg SR PO q12h PRN
Promethazine
Dexamethasone
12.5-25 mg PO, IM, IV or PR q4-6h PRN
20 mg PO or IV 30 min. before chemotherapy
5-10 mg PO, IM, or IV q6h, OR
Level 2 Prochlorperazine 25 mg PR q12h, OR
15 mg SR PO q12h
Levels 3-5
Levels 3-5
Promethazine
Dexamethasone
Plus
Granisetron
Dexamethasone
Plus (if IV required)
Granisetron
12.5-25 mg PO, IM, IV or PR q4-6h
20 mg PO 30 min. before chemotherapy
2 mg PO 30 min. before chemotherapy
20 mg IV 30 min. before chemotherapy
10 mcg/kg IV 30 min. before chemotherapy
DELAYED EMESIS
Cisplatin
Cyclophosphamide
Ifosfamide
Doxorubicin
Carboplatin
Dexamethasone
Plus
Metoclopramide
Or
Prochlorperazine
PREVENTION
Days 2-5
8 mg PO q12h x 2 days, THEN