A drug reaches steady state after about four to five half-lives. For fluoxetine, whose active metabolite norfluoxetine has a half-life of days to weeks, that can mean several weeks — longer in older adults. Increasing the dose before steady state is reached stacks one rise on another.
- Estimate time to steady state as four to five half-lives before titrating
- Allow longer in older adults and those with hepatic impairment
- Expect adverse effects to appear late with long half-life drugs
- Remember a long half-life also means a long washout before switching to an interacting drug
Why it matters
Titrating before steady state is a common route to delayed toxicity in older patients.
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