Source of Missed dose

{{Infobox concept | name = Missed dose | subtitle = Dosing 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 }} 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.{{r|drucker2018}} 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.{{r|knudsen2019}} 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.{{r|ada2024}} 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]].{{r|drucker2018}} == The governing arithmetic == 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.{{r|knudsen2019}} | 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.{{r|drucker2018,lau2015}} 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 == 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.{{r|drucker2018}} 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]]. Doubling a dose to compensate for an omission is not what any labelling in this class directs, and the pharmacokinetics do not support it: a double dose produces a peak exposure outside the studied range, which is where the dose-related adverse effects concentrate.{{r|knudsen2019}} == Practical corollaries == The main practical corollary of a long half-life is that the effect of any change — starting, stopping, escalating, or missing — is expressed slowly. A dose increase is not fully expressed for four to five weeks with a weekly agent, and neither is a decrease.{{r|knudsen2019}} That has a symmetrical consequence for interpreting adverse effects. An effect appearing three days after a dose change may be attributable to it; one appearing three weeks later, at a time when concentrations are still rising towards a new steady state, may equally be. For discontinuation the same reasoning applies at longer range: exposure persists for weeks after the last dose, and what follows is treated at [[Weight regain after discontinuation]]. Nothing in this article is medical advice.{{r|drucker2018}} == References == {{reflist}} <ref name="drucker2018">Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." ''Cell Metabolism'' 27(4):740–756 (2018). PMID 29617641.</ref> <ref name="knudsen2019">Knudsen LB, Lau J. "The discovery and development of liraglutide and semaglutide." ''Frontiers in Endocrinology'' 10:155 (2019). PMID 31031702.</ref> <ref name="ada2024">American Diabetes Association. "Pharmacologic approaches to glycemic treatment: Standards of Care in Diabetes." ''Diabetes Care'' 47(Suppl 1) (2024).</ref> <ref name="lau2015">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.</ref> == See also == * [[Dose escalation schedule]] * [[Dose titration]] * [[Prescribing information]] * [[Semaglutide]] * [[Weight regain after discontinuation]] {{DEFAULTSORT:Missed dose}} [[Category:Dosing and titration]] [[Category:Clinical practice]] [[Category:Pharmacokinetics]]