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Medicines > fda max : 100 mg/d or 4 mg/d (schizophrenia); 3 mg/d (AD agitation); 3 mg/d (MDD adjunct) or No fixed maximum; titrated to TSH target

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mechanism:
5-HT1A agonist, 5-HT2A antagonist, with weaker activity at D4 and other receptors. Net effect involves enhanced prefrontal dopaminergic/noradrenergic tone with decreased serotonergic inhibition of sexual desire. (1) · Partial agonist at D2 and 5HT1A. Antagonist at 5HT2A, α1A, α1B, α2C. More potent 5HT2A antagonism, 5HT1A partial agonism, and α1 antagonism (relative to D2 partial agonism) than aripiprazole, proposed to reduce akathisia and enhance affective/cognitive effects. (1) · Synthetic T4 (thyroxine); peripherally deiodinated to T3 (triiodothyronine), the active hormone. '"`UNIQ--vote-00000031-QINU`"' Narrow therapeutic index; brand-to-generic switches can shift TSH and require re-titration'"`UNIQ--ref-00000032-QINU`"'. (1) · '"`UNIQ--vote-00000016-QINU`"' Brand-to-brand and lot-to-lot variability in T3:T4 ratio is greater than with synthetic levothyroxine, which is why endocrine guidelines prefer the synthetic'"`UNIQ--ref-00000017-QINU`"'. (1) · '"`UNIQ--vote-000000B6-QINU`"' Active metabolite EXP3174 is ~10-40-fold more potent than the parent and accounts for most of the antihypertensive effect; CYP2C9 polymorphism affects conversion'"`UNIQ--ref-000000B7-QINU`"'. (1) · '"`UNIQ--vote-00000762-QINU`"' Largely renally cleared, hence the eGFR-tiered dosing. Rare but well-documented signals: acute pancreatitis (uncertain causal contribution), severe joint pain, and bullous pemphigoid (class effect, especially in older Asian patients)'"`UNIQ--ref-00000763-QINU`"'. (1)
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