Table 8.

Example of the standard RCUH RDD protocol for a total dose of 500 mg of infliximab meant to be administered in a volume of 250 ml over two hours

Total dose	500 mg	Solution concentration	Total dose in each solution (mg)	Drug
Solution A	250 ml	0.04 mg/ml	10	Infliximab
Solution B	250 ml	0.4 mg/ml	100	Infliximab
Solution C	250 ml	2 mg/ml	500	Infliximab

Step	Solution	Rate (ml/h)	Administered volume (ml)	Time (min)	Administered dose (mg)	Fold increase per step (mg/min)	Approximative cumulative dose infused (mg)
1	A	88	22	15	0.0	NA	0.0
2	A	100	25	15	1	NA	1.0
3	A	200	50	15	2	×2	3.0
4	A	400	100	15	4	×2	7.0
5	B	88	22	15	0.0	NA	7.0
6	B	100	25	15	10	×2.5	17.0
7	B	200	50	15	20	×2	37.0
8	B	400	100	15	40	×2	77.0
9	C	88	22	15	0.0	NA	77.0
10	C	125	212.5	101.5	425	×1.6	500.0
Total infusion time: 236.5 min (3 h, 57 min, 30 s)
Premedication: Ideally, they should comply with the manufacturer's instructions and institutional protocols for standard infliximab infusion. We do not recommend systematic additional premedication (e.g. with steroids or antihistamines) as a measure to prevent breakthrough reactions, however, tailored premedication may be added depending on a personalized case-to-case approach.
Total dose calculation and discarded volume: Not all the volume in solutions A, B, or C is infused. The protocol starts with one solution A, which contains a 1:50 dilution. Solution B contains a 1:5 dilution, and the final solution C contains the full concentration (1:1) of the culprit drug. The total dose to be infused during solution C is calculated by subtracting the cumulative dose administered in steps 1–9 from the total desired dose.
Adjustments to the volume of the bags: The standard volume in the solution bags for the RCUH RDD protocol is 250 ml. In some cases, bag volume might need adjustment depending on the manufacturer's instructions and/or product information.
Additional bags for high-risk patients: The standard RCUH flexible protocol uses 3 bags to be administered over 10 steps. This can be flexibly adapted for high-risk patients by adding a solution A’ (1:500 dilution) with additional 4 steps before solution A. This modification provides a lower starting dose. In patients with positive ST, the starting dose can potentially be determined based on an endpoint titration according to local protocols.
Flushing steps: Each solution uses an individual infusion line previously primed with 22 ml of the solvent serum (be aware that infliximab needs saline serum as solvent). Steps 1, 5, and 9 are considered “line flushing steps” (in which 22 ml of the solvent serum are administered). Line flushing steps must be adapted to local circumstances. For example, in this case, RCUH used 22 ml infusion systems for the infusion pumps (Alaris® SE I pump smartsite infusion set), hence the 22 ml flushing steps.
Adjustments to final infusion rate: Step 10 may be adapted to the desired final infusion rate according to the standard regimes indicated by the referring physician (additional steps may be added to reach higher infusion rates while maintaining a maximum dose increasing by 2-fold to 2.5-fold with each step).
Avoiding human errors: Infusion pumps with automatic multi-step infusion options (e.g., RCUH used Alaris® SE double channel for this protocol) should be used to avoid human errors associated with manually changing infusion rates every 15 min.

RCUH, Ramon y Cajal University Hospital; NA, not applicable; RDD, rapid drug desensitization; ST, skin testing.