Management
of Missed or Delayed Doses
Patients
should be instructed to inject a missed dose as soon as possible and
then resume monthly dosing.1
Do
not take a double dose to make up for forgotten injection.2
If
you have forgotten to inject a dose of Emgality, inject the missed
dose as soon as possible and then inject the next dose after a month
from that date.2
Dose
Administration in Phase 3 Migraine Prevention Studies
Galcanezumab
has been studied in phase 3 randomized, double-blind,
placebo-controlled studies in adult patients for the prevention of
episodic
migraine (EVOLVE-1 and EVOLVE-2),3,4
and
chronic
migraine (REGAIN).5
In
the phase 3 clinical trials, injections were allowed to be
administered within ±2 days of the scheduled visit.6
The
recommended dose is 120 mg injected subcutaneously once monthly, with
a 240 mg loading dose as the initial dose.6
Considerations
for Repeating a Loading Dose After Missed Doses
Clinicians
should use their judgment to determine whether a repeat loading dose
is needed.
The
PK profile of galcanezumab enables some flexibility with regard to
when doses are administered. Prolonged dosing delays will decrease
galcanezumab concentrations and potentially reduce efficacy.6
It may require some time to re-establish steady-state galcanezumab
plasma concentrations when dosing is resumed. Please consider the
t1/2 and
PK characteristics of galcanezumab to determine whether a repeat
loading dose is warranted.
In
healthy subjects and patients with episodic or chronic migraine,
galcanezumab has a
Tmax
of 5 days, and
t1/2
of 27 days.1,7
Steady
state concentrations are achieved by month 1 for the 120-mg monthly
dose with a 240-mg loading dose.7
After
missing 3 consecutive monthly doses, approximately 12% of the
galcanezumab concentration relative to steady-state will be remaining
(Table 1).6
Therefore, after missing 3 consecutive monthly doses, repeating a
loading dose should be considered from a PK perspective. Clinicians
should use their judgment to determine whether a repeat loading dose
is needed.
Table
1. Effect of Missed Monthly Doses on Galcanezumab Steady State
Concentrations6
|
Number
of Consecutive
Missed Monthly Doses
|
Time
Since Last Dose
Administration (Months)
|
Concentration
Relative to
Steady State (%)a
|
|
1
|
2
|
50
|
|
2
|
3
|
25
|
|
3
|
4
|
12.5
|
|
4
|
5
|
6.3
|
a
Assuming 1 month for galcanezumab half-life.
Management
of Missed or Incomplete Loading Dose
The
galcanezumab steady-state Cmax
(Cmax, ss)
at monthly doses of 120 mg is achieved after the 240 mg loading
dose.1
In
the phase 2 dose-ranging study, a loading dose was not implemented.8
In that study, the galcanezumab 120 mg dose did not achieve
statistically significant separation from placebo in mean change from
baseline migraine headache days until month 3.
Pharmacokinetic
modeling of phase 3 data confirmed that the 240 mg loading dose
achieved steady-state galcanezumab concentrations by month 1 for the
120 mg/month dose regimen.6
In
the event of a missed or incomplete loading dose, complete the
loading dose as soon as possible. Then continue with the monthly
maintenance dose from the date of last dose.
Therapeutic
Indication
Galcanezumab
is indicated for the prophylaxis of migraine in adults who have at
least 4 migraine days per month.1
References
1.
Emgality [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
2.
Emgality [package leaflet]. Eli Lilly Nederland B.V., The
Netherlands.
3.
Stauffer VL, Dodick DW, Zhang Q, et al. Evaluation of galcanezumab
for the prevention of episodic migraine: the EVOLVE-1 randomized
clinical trial. JAMA Neurol. 2018;75(9):1080-1088.
http://dx.doi.org/10.1001/jamaneurol.2018.1212
4.
Skljarevski V, Matharu M, Millen BA, et al. Efficacy and safety of
galcanezumab for the prevention of episodic migraine: results of the
EVOLVE-2 phase 3 randomized controlled clinical trial. Cephalalgia.
2018;38(8):1442-1454. http://dx.doi.org/10.1177/0333102418779543
5.
Detke HC, Goadsby PJ, Wang S, et al. Galcanezumab in chronic
migraine: the randomized, double-blind, placebo-controlled REGAIN
study. Neurology. 2018;91(24):e2211-e2221.
http://dx.doi.org/10.1212/WNL.0000000000006640
6.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
7.
Kielbasa W, Helton DL. A new era for migraine: Pharmacokinetic and
pharmacodynamic insights into monoclonal antibodies with a focus on
galcanezumab, an anti-CGRP antibody. Cephalalgia.
2019;39(10):1284-1297. http://dx.doi.org/10.1177/0333102419840780
8.
Skljarevski V, Oakes TM, Zhang Q, et al. Effect of different doses
of galcanezumab vs placebo for episodic migraine prevention: a
randomized clinical trial. JAMA Neurol. 2018;75(2):187-193.
http://dx.doi.org/10.1001/jamaneurol.2017.3859
Glossary
PK =
pharmacokinetics
t1/2
= elimination half-life
Tmax
= time of maximum observed drug concentration
▼ This
medicinal product is subject to additional monitoring. This will
allow quick identification of new safety information. Healthcare
professionals are asked to report any suspected adverse reactions.