If the study subject develops severe chills and fever despite pre- 
medication, hospitalization may be indicated. Meperedine 25-50 mg IV 
q 4-6 hours or Morphine 4-6 mg IV q 2 hours may be used. Administer 
at the first indication of chills. 
IV fluids will be administered according to study subject need. If 
hypotension (systolic pressure <90 mm Hg) develops, then the fluid rate 
will be increased and the level titrated to maintain the blood pressure 
between 80 and 90 mm Hg. 
Dopamine 3-5 mg/kg/minute will be administered for symptomatic 
hypotension below 80 mm Hg not responsive to an initial fluid challenge. 
All study subjects should receive antibiotics, anti-emetics and other 
medications as clinically indicated. 
10.3 IFNaA Toxicity 
a) Human Studies: Subcutaneous or intramuscular administration of IFNaA as a 
single agent is reported in the package insert. Mild or moderate symptoms are 
seen at low doses, more severe toxicity is observed at higher doses and resolve 
with dose reduction. Symptoms include flu-like symptoms including fever, 
fatigue, myalgia, headache and chills. For additional information see product 
insert (Appendix IX). 
10.4 Treatment of Possible Toxicity and Side Effects of IFNaA. 
Study subjects experiencing toxicity or side effects of IFNa may be treated 
according to the treatment regimen in Section 10.2.2. During treatment, grades 
of toxicity, as defined in Appendix III, will be used to determine the 
administration of the next dose. 
a) Grades 1 and 2 Toxicity and Grade 3 granulocytopenia and 
thrombocytopenia: Treatment may continue on schedule. For patients 
intolerant of grades 1 and 2 toxicity who would choose to discontinue 
treatment, the dose of rIL-2 may be attenuated to 1 x 10 6 U/m 2 /day while 
the IFNaA dose will remain at 6 x 10 6 U/m 2 /day and treatment may 
continue uninterrupted. Breaks in the treatment schedule, taken because 
of toxicity should not be made up. All subsequent courses of treatment 
should continue at this attenuated level of rIL-2 unless the subject 
experiences > grade 3 toxicity. 
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Recombinant DNA Research, Volume 15 
