Expert Nurse
Kathleen Madden

HI Julia,

Thank you for your inquiries!

Question # 1 RE dilutions for Nivo

Your pt who is 90 kg receiving 270mg Nivo (3mg/kg) q2Wks over 60 min for Melanoma
PER the PI, Max recommended total volume of Nivo in dilution should not exceed 160ml per infusion
Your pts vial requirements are as follows:
Nivolumab 240mg/24ml vial = 24ml, + 40mg/4ml vial (minus 10mg or 1 ml) = 27ml or 270mg of actual Nivolumab undiluted
27ml + 50ml of NS= 77 ml infusion
27ml + 100ml of NS= 127 ml infusion
Either dilution is acceptable as they do not exceed the maximum recommended volume of 160ml
Infusion time recommendations are 30 or 60 mins, for your lower dilution volume and more concentrated dosing, considering adhering to a 60 min infusion time as pd-1 inhibitors do carry ~10% infusion reaction rate.

My center for example for a 480mg IV q 4 wk dosing is using the following:
40mg/4ml vial= 48 ml + 110 NS
total volume 158ml over 30 min
We typically provide a higher volume for the infusion and a lower volume flush for the line.

Question #2 re IV line flush:
Standard IV lines carry between a 20 ml & 25ml priming volume ( noted on packaging) , so a 25 to 50 ml flush- either is acceptable to clear drug from the line

My personal bias is a higher diluent fluid volume and a lower flush volume.

I would like to note that the 240mg IV q 2 week & 480mg Q 4 weeks are approved and part of the Prescriber indications for melanoma in the adjuvant setting & maintance post combination therapy induction (in the US, Canada & EU).
Flat dose was approved through pharmacokinetic analyses taken from phase III trials across tumor types and established flat dose exposure relationships and clinical safety. I have included a current article noted below discussing flat dosing. The consensus is for the same efficacy & safety, there is also cost efficiency as well as time flexibility for patients and staff. Your center may want to investigate the possible benefits of expanding it’s dosing regimen choices for nivolumab. Nurses are great change agents and advocates, I hope that you may consider bringing back to your center some updated evidence to support that discussion as well as the evidence that supports the expanded dosing regimens.

Assessment of nivolumab exposure and clinical safety of 480 mg every 4 weeks flat-dosing schedule in patients with cancer
G V Long S S Tykodi J G Schneider C Garbe G Gravis M Rashford S Agrawal E Grigoryeva A Bello A Roy S
Annals of Oncology, mdy408, https://doi.org/10.1093/annonc/mdy408
Published: 12 September 2018

Thank you again for your inquiry, I hope this was helpful and answered your questions.
Best Regards,