14 days past a due dose is 2 half-lives at the seven-day half-life this class runs on, which leaves about 25 per cent of that dose still circulating. One line of arithmetic: remaining fraction is one half raised to days over half-life, so 0.5^(14÷7) = 0.25. At 25 per cent you have not been off it in any meaningful sense. The interval stretched from 7 days to 21 and the trough went lower than usual; that is the whole of what happened. What the product label says and what the pharmacokinetics say are two different answers here, and the first is the one that governs. Restarting, holding or stepping down after a gap is decided under supervision, and nothing here is medical advice.
Never double up to catch up. The exposure spike is real and the tolerability cost is immediate.
Never take two doses close together to compensate. The peak exposure is roughly doubled, and gastrointestinal tolerability tracks peak exposure closely.
With a one-week half-life dosed weekly, missing one dose means exposure falls by about half over the following week — the same trough you would reach if you simply extended the interval. That is well within the range the agent operates in.
Loss of tolerance during a treatment gap is documented and is the basis for re-titration after an interruption.
Never double up. Peak exposure is what drives the symptoms.
edited 15 Mar 2026 by triple_agonist_q — updated for the 2026 guidance change
Worth flagging that the maximum dose is not the target for most people. – Dr_Aoife_Brennan 6 months ago Adding that re-titrating after a gap is not optional, as I discovered. – tobias_reint 4 months ago add a comment