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Medicines > fda max : 10 mg/d or 100 mg/d or 400 mg/d

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mechanism:
None (2) · 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) · Cardioselective β1-adrenergic antagonist. Selectivity is dose-dependent and partially lost at higher doses. (1) · Competitive antagonist at OX1R and OX2R. Faster receptor association/dissociation kinetics than suvorexant (~16 sec dissociation vs ~57 sec) hypothesized to support sleep onset, with sufficient duration for maintenance. (1) · GABA-A positive allosteric modulator'"`UNIQ--ref-00000067-QINU`"' '"`UNIQ--vote-00000068-QINU`"' (1) · '"`UNIQ--vote-00000073-QINU`"' The long half-life gives smooth, once-daily BP control with low rebound. CYP3A4 substrate; pedal edema is the characteristic, dose-related, non-fluid-overload side effect'"`UNIQ--ref-00000074-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) · '"`UNIQ--vote-00000D7A-QINU`"' Substantial QT-interval prolongation — the most QT-prolonging fluoroquinolone — limits use in patients on other QT-prolonging agents or with electrolyte abnormalities'"`UNIQ--ref-00000D7B-QINU`"'. (1) · '"`UNIQ--vote-0000113A-QINU`"' Concomitant β-blocker or CCB is required when used for AF to prevent 1:1 atrial flutter conduction (flecainide can slow atrial rate to a level where AV conduction allows dangerous ventricular rates). CYP2D6 substrate'"`UNIQ--ref-0000113B-QINU`"'. (1)
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pregnancy:
'''Avoid in pregnancy where alternatives exist''' (animal cartilage toxicity).<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · '''Contraindicated in pregnancy''' (all trimesters); fetal renal injury, oligohydramnios, hypocalvaria, hypotension. Stop on detection'"`UNIQ--ref-000000BE-QINU`"' (1) · Avoid in second and third trimesters; fetal SGLT2 inhibition disrupts kidney development.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Category C (1) · Category D'"`UNIQ--ref-0000006C-QINU`"' (1) · Limited data; avoid (1) · Limited data; case series and registries suggest no major teratogenicity but other antihypertensives (labetalol, nifedipine) are typically preferred.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Limited data; generally avoided particularly in combination with statin.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Limited data; switch to insulin where feasible.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Not indicated; pregnancy effects unknown (1) · Use in fetal SVT (transplacental antiarrhythmic therapy) is established; otherwise weigh against alternatives.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1)

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