TABLE 1.

Comparison of current US Food & Drug Administration (FDA) and European Medicines Agency (EMA) Summary of Product Characteristics (SmPC), Polyanalgesic Consensus Conference (PACC) treatment algorithms, and other recommendations for ziconotide administration; closer alignment of the EMA SmPC with the FDA SmPC is anticipated in early 2021

Parameter	FDA SmPC	EMA SmPC	Other recommendations
Maximum daily dose	19.2 µg/day (0.8 µg/h)	21.6 µg/day	19.2 µg/day (0.8 µg/h) a
Starting dose	≤2.4 µg/day (0.1 µg/h)	2.4 µg/day	0.5–1.2 µg/day (0.02–0.05 µg/h) a ; initiation with ≤ 0.5 µg/day (0.02 µg/h) may be preferred b
Dose increments	≤2.4 µg/day (0.1 µg/h)	≤2.4 µg/day	≤0.5 µg/day (≤0.02 µg/h) on a no more than weekly basis b , according to individual patient's pain reduction and tolerability (Fisher; Prager b )
Minimum interval between dose increases	≤2–3/week (56–84 h)	24 hr	Titration slow and not more than once weekly b
Recommended interval (safety)	≤2.4 µg/day and ≤2–3/week	≥48 hr	Not more than once weekly b
Minimum concentration, external pump reservoir	5 µg/ml; change dose rate by adjusting flow rate or solution concentration	5 µg/ml	–
Minimum concentration, internal pump reservoir	25 µg/ml	25 µg/ml	–

Sources: (FDA SmPC, 2019); (EMA SmPC, 2019).

^a(Deer, Hayek, Pope, et al., 2017; Deer, Pope, Hayek, Bux, et al., 2017; Deer, Pope, Hayek, Lamer, Veizi, et al., 2017).

^b(Fisher et al., 2005; McDowell & Pope, 2016; Prager et al., 2014).