Missed dose (revision 9)
Old revision·08:20, 7 Feb 2025·Chromatokid
| Missed doseDosing practice | |
|---|---|
| Governing quantity | Half-life relative to dosing interval |
| Weekly agents | Long half-life; concentration falls slowly |
| Daily agents | Steady state re-established within days |
| Topic infobox · conventions | |
A missed dose is a scheduled administration that is not taken. How much it matters depends almost entirely on the ratio between the drug's half-life and its dosing interval: a long half-life relative to the interval means concentrations fall slowly and a single omission changes exposure little.[1]
For a weekly agent with a half-life of several days, the concentration at the end of a normal dosing interval has fallen to a substantial fraction of its peak, and a missed week extends that decline rather than producing a sudden loss of exposure. For a daily agent with a half-life of hours, a missed day is a larger proportional change but is corrected within a day or two of resuming.[2]
Prescribing information for individual products states how a missed dose is to be handled, and those statements differ between products; general treatment guidance does not attempt to supply a single rule.[3] This article describes the pharmacokinetic reasoning; it is not medical advice, and it is not a substitute for the labelling of any particular product. See Prescribing information.[1]
The governing arithmetic
[edit]After a dose, concentration falls by half each half-life. For a peptide with a half-life of seven days on a weekly schedule, trough concentration is about half the peak and steady-state accumulation is roughly two-fold. Omitting one dose allows a further halving before the next dose is taken.[2]
| Half-life | Interval | Fall over one missed interval |
|---|---|---|
| ≈7 days | Weekly | To about half |
| ≈5 days | Weekly | To about two fifths |
| ≈13 hours | Daily | To a few per cent |
| ≈2.4 hours | Twice daily | Essentially complete |
The final row explains why short-acting agents lose effect promptly on omission and long-acting agents do not. It also explains why a resumed long-acting agent does not need re-titration after a short gap while a resumed short-acting one may.[1][4]
Re-escalation after a longer interruption is a tolerability question rather than an efficacy one: gastrointestinal tolerance to these agents is partly adaptive, and adaptation is lost over a sufficiently long gap.
What product labelling addresses
[edit]Labelling for weekly incretin products typically permits a missed dose to be taken within a defined window and otherwise omitted, with the next dose taken on the regular schedule; and it typically addresses changing the day of the week, which is possible when the half-life is long.[1]
The windows differ between products because the half-lives differ, which is why a rule learned for one product does not transfer to another. This is a specific instance of the general point that class membership does not imply interchangeability. See GLP-1 receptor agonist.
See also
References
- ^ a b c d Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." Cell Metabolism 27(4):740–756 (2018). PMID 29617641.
- ^ a b Knudsen LB, Lau J. "The discovery and development of liraglutide and semaglutide." Frontiers in Endocrinology 10:155 (2019). PMID 31031702.
- ^ American Diabetes Association. "Pharmacologic approaches to glycemic treatment: Standards of Care in Diabetes." Diabetes Care 47(Suppl 1) (2024).
- ^ Lau J, Bloch P, Schäffer L, et al. "Discovery of the once-weekly glucagon-like peptide-1 analog semaglutide." Journal of Medicinal Chemistry 58(18):7370–7380 (2015). PMID 26308095.