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Medicines > onset : 1-2 hours or 30-60 minutes or Weeks for psychosis/depression; AD agitation benefit emerges over weeks

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classes:
None (1) · 5HT1A activity than aripiprazole (1) · 5HT2A (1) · Atypical antipsychotic (1) · D2/5HT1A partial agonist with stronger α1A (1) · gut-restricted)]] (1) · selective COX-2)]] (1) · weak)]] (1) · [[:Category:Alpha-2 adrenergic agonists|Alpha-2 adrenergic agonist]] (1) · [[:Category:Analgesics|Analgesic]] (2) · [[:Category:Antidiarrheals|Antidiarrheal]] (1) · [[:Category:Antihistamines|Antihistamine]] (3) · [[:Category:Antihistamines|First-generation antihistamine]] (1) · [[:Category:Antihyperglycemic_agents|Antihyperglycemic agent]] (1) · [[:Category:Antipyretics|Antipyretic]] (1) · [[:Category:Antispastics|Antispastic]] (1) · [[:Category:Barbiturates|Barbiturate (butalbital)]] (2) · [[:Category:Basal_insulins|Basal insulin]] (2) · [[:Category:Decongestants|Decongestant]] (1) · [[:Category:Fixed-dose_combinations|Fixed-dose combination]] (3) · [[:Category:H1_receptor_antagonists|Histamine H1 receptor antagonist (second-generation)]] (3) · [[:Category:Insulins|Insulin]] (2) · [[:Category:Insulin_secretagogues|Insulin secretagogue]] (1) · [[:Category:Long-acting_insulins|Long-acting insulin analog]] (2) · [[:Category:Methylxanthines|Methylxanthine (caffeine)]] (2) · [[:Category:Non-opioid_analgesics|Non-opioid analgesic (acetaminophen)]] (2) · [[:Category:NSAIDs|Non-steroidal anti-inflammatory (NSAID (1) · [[:Category:NSAIDs|Non-steroidal anti-inflammatory (NSAID)]] (1) · [[:Category:NSAIDs|NSAID (aspirin)]] (1) · [[:Category:Opioid_analgesics|Opioid analgesic (codeine (1) · [[:Category:Opioid_receptor_agonists|Peripheral opioid receptor agonist (μ-selective (1) · [[:Category:Orexigenics|Appetite-promoting medicine (orexigenic)]] (1) · [[:Category:Schedule_III_controlled_substances|Schedule III controlled substance]] (2) · [[:Category:Serotonin antagonists|Serotonin 5-HT2 antagonist]] (1) · [[:Category:Skeletal muscle relaxants|Skeletal muscle relaxant (centrally-acting)]] (1) · [[:Category:Sulfonylureas|Sulfonylurea (third-generation)]] (1) · [[:Category:Sympathomimetics|Sympathomimetic (indirect-acting)]] (1)
mechanism:
None (10) · 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) · '"`UNIQ--vote-00000017-QINU`"' Anticholinergic and sedating, with the standard first-generation antihistamine Beers-list concerns in elderly patients'"`UNIQ--ref-00000018-QINU`"'. (1) · '"`UNIQ--vote-00000237-QINU`"' Binds the same insulin receptor as endogenous insulin with comparable mitogenic-to-metabolic ratio; provides basal hepatic glucose suppression and peripheral glucose uptake without prandial peaks'"`UNIQ--ref-00000238-QINU`"'. (1) · '"`UNIQ--vote-00000391-QINU`"' Minimal CYP metabolism; mostly renally cleared unchanged. Cetirizine is the active racemate; levocetirizine is the active R-enantiomer marketed separately'"`UNIQ--ref-00000392-QINU`"'. (1) · '"`UNIQ--vote-00000950-QINU`"' Mostly renally cleared unchanged; dose-reduce in renal impairment. Like cetirizine, retains slightly more sedation than fexofenadine in some users'"`UNIQ--ref-00000951-QINU`"'. (1) · '"`UNIQ--vote-00000CC9-QINU`"' Mostly excreted unchanged in feces and urine; P-glycoprotein substrate (the basis of the fruit-juice interaction). (1) · '"`UNIQ--vote-00001513-QINU`"' The combination with acetaminophen provides additive non-opioid analgesia and lowers required codeine dose. CYP2D6 PGx is one of the most clinically actionable in current pharmacology; CPIC supports genotype-guided opioid selection'"`UNIQ--ref-00001514-QINU`"'. (1)
uses:
Schizophrenia (FDA-approved 2015). Adjunctive treatment of major depressive disorder (2015). '''Agitation associated with dementia due to Alzheimer disease''' (FDA-approved May 2023, first agent specifically approved for this problem). Investigational for PTSD (combined with sertraline). (1) · '"`UNIQ--vote-00000017-QINU`"', '"`UNIQ--vote-00000018-QINU`"', '"`UNIQ--vote-00000019-QINU`"', '"`UNIQ--vote-0000001A-QINU`"' (1) · '"`UNIQ--vote-00000019-QINU`"', '"`UNIQ--vote-0000001A-QINU`"', '"`UNIQ--vote-0000001B-QINU`"', '"`UNIQ--vote-0000001C-QINU`"' (1) · '"`UNIQ--vote-00000019-QINU`"', '"`UNIQ--vote-0000001A-QINU`"', '"`UNIQ--vote-0000001B-QINU`"', '"`UNIQ--vote-0000001C-QINU`"', '"`UNIQ--vote-0000001D-QINU`"' (1) · '"`UNIQ--vote-00000021-QINU`"', '"`UNIQ--vote-00000022-QINU`"', '"`UNIQ--vote-00000023-QINU`"', '"`UNIQ--vote-00000024-QINU`"', '"`UNIQ--vote-00000025-QINU`"', '"`UNIQ--vote-00000026-QINU`"', '"`UNIQ--vote-00000027-QINU`"', '"`UNIQ--vote-00000028-QINU`"' (2) · '"`UNIQ--vote-00000239-QINU`"', '"`UNIQ--vote-0000023A-QINU`"' (1) · '"`UNIQ--vote-00000393-QINU`"', '"`UNIQ--vote-00000394-QINU`"', '"`UNIQ--vote-00000395-QINU`"' (1) · '"`UNIQ--vote-00000491-QINU`"' (1) · '"`UNIQ--vote-00000952-QINU`"', '"`UNIQ--vote-00000953-QINU`"' (1) · '"`UNIQ--vote-00000CCA-QINU`"', '"`UNIQ--vote-00000CCB-QINU`"' (1) · '"`UNIQ--vote-00000FCF-QINU`"', '"`UNIQ--vote-00000FD0-QINU`"', '"`UNIQ--vote-00000FD1-QINU`"' (1) · '"`UNIQ--vote-00001372-QINU`"', '"`UNIQ--vote-00001373-QINU`"' (1) · '"`UNIQ--vote-00001515-QINU`"', '"`UNIQ--vote-00001516-QINU`"' (1) · '"`UNIQ--vote-0000152F-QINU`"' (1) · '"`UNIQ--vote-0000159D-QINU`"', '"`UNIQ--vote-0000159E-QINU`"' (1) · '"`UNIQ--vote-000015B6-QINU`"' (1)
starting dose:
1-2 capsules (50 mg butalbital / 325 mg acetaminophen / 40 mg caffeine each) PO every 4 hours as needed; maximum 6 capsules/d (1) · 1-2 capsules (50 mg butalbital / 325 mg aspirin / 40 mg caffeine each) PO every 4 hours as needed; maximum 6 capsules/d (1) · 1-2 mg PO once daily with breakfast; titrate by glycemic response (1) · 1-2 tablets (15-60 mg codeine, 300-600 mg acetaminophen) PO every 4-6 hours as needed (1) · 10 mg PO once daily (5 mg in older adults or if sedation occurs) (1) · 2 mg PO every 6-8 hours; titrate by 2-4 mg per dose every 1-4 days; maximum single dose 16 mg, maximum daily dose 36 mg (1) · 2 tablets (75 mg tramadol / 650 mg acetaminophen) PO every 4-6 hours as needed; maximum 8 tablets/day for ≤5 days (1) · 4 mg PO initially, then 2 mg after each loose stool, '''not to exceed 16 mg/d''' (8 mg OTC); chronic-use lower (1) · 5 mg PO once daily in the evening (1) · 60 mg PO BID or 180 mg PO once daily (1) · Allergy: 4 mg PO TID. Serotonin syndrome: 12 mg loading dose PO or by nasogastric tube, then 2 mg every 2 hours until clinical improvement. Appetite stimulation: 2-4 mg PO TID-QID (1) · IR: 60 mg PO every 4-6 hours. 12-hour ER: 120 mg PO every 12 hours. 24-hour ER: 240 mg PO once daily. Pediatric: weight-based (1) · Osteoarthritis: 200 mg PO once daily or 100 mg BID. Rheumatoid arthritis: 100-200 mg PO BID. Acute pain: 400 mg loading, then 200 mg every 12 hours (1) · OTC: 220 mg PO every 8-12 hours, max 660 mg/24h. Rx: 250-500 mg PO BID. Acute gout: 750 mg loading then 250 mg every 8 hours (1) · Schizophrenia: 1 mg PO daily × 4 days, then 2 mg daily × 3 days, then 4 mg daily. MDD adjunct: 0.5-1 mg daily, increase to 2 mg max. AD agitation: 0.5 mg daily, titrate to 2-3 mg daily. (1) · ~10 units SC at the same time daily, or 0.1-0.2 units/kg/d; titrate by fasting glucose (1) · ~10 units SC at the same time daily, or 0.1-0.2 units/kg/d; titrate by fasting glucose. Frequently dosed BID at moderate-to-high doses (1)
onset: (Click arrow to add another value)
bioavailability:
Butalbital well-absorbed; aspirin 50-75%; caffeine ~100%'"`UNIQ--ref-000015B8-QINU`"' (1) · Butalbital well-absorbed; caffeine ~100%; acetaminophen 85-98%'"`UNIQ--ref-000015A0-QINU`"' (1) · Codeine ~60% (oral); acetaminophen 85-98%'"`UNIQ--ref-00001518-QINU`"' (1) · High (oral); not significantly affected by food'"`UNIQ--ref-00000397-QINU`"' (1) · Tramadol ~75% (oral); acetaminophen 85-98%'"`UNIQ--ref-00001531-QINU`"' (1) · ~0.3% (oral; extensive first-pass via CYP3A4 and P-glycoprotein-mediated efflux at the intestinal and blood-brain barriers limit systemic and CNS exposure at therapeutic doses)'"`UNIQ--ref-00000FD3-QINU`"' (1) · ~100% (oral; not significantly affected by food)'"`UNIQ--ref-00000493-QINU`"' (1) · ~100% from subcutaneous depot (by definition of the route) (1) · ~33% (oral; fruit juices including grapefruit, orange, and apple reduce absorption substantially via OATP1A2 inhibition — distinctive interaction not seen with most other H1s)'"`UNIQ--ref-00000CCD-QINU`"' (1) · ~40% (oral); food and formulation substantially alter the absorption profile'"`UNIQ--ref-0000001E-QINU`"' (1) · ~60% from subcutaneous depot (reduced by reversible albumin binding via the myristic acid side chain that also extends duration)'"`UNIQ--ref-00001375-QINU`"' (1) · ~85-90% (oral; not significantly affected by food)'"`UNIQ--ref-00000955-QINU`"' (1) · ~90% (oral, low first-pass)'"`UNIQ--ref-0000001C-QINU`"' (1) · ~95% (1) · ~95% (oral)'"`UNIQ--ref-0000001F-QINU`"' (1) · ~95% (oral)'"`UNIQ--ref-0000002A-QINU`"' (1) · ~99% (oral)'"`UNIQ--ref-0000002A-QINU`"' (1)
pregnancy:
None (1) · Avoid from 20 weeks gestation onward per FDA's 2020 expanded NSAID warning (fetal renal dysfunction, oligohydramnios); contraindicated from 30 weeks (risk of premature ductus arteriosus closure)'"`UNIQ--ref-0000002B-QINU`"' (2) · Avoid; neonatal opioid withdrawal documented.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Avoid; switch to insulin. Neonatal hypoglycemia reported.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Avoided; barbiturate + aspirin teratogenicity and bleeding concerns.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Generally avoided; barbiturate exposure in late pregnancy can produce neonatal withdrawal and respiratory depression.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Generally considered acceptable when needed.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Generally considered safe; loratadine and cetirizine have more pregnancy data and are typically preferred.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Generally considered safe; widely used. Cetirizine and loratadine remain the more-studied alternatives.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Generally considered safe; widely used. Levocetirizine (the R-enantiomer) is an alternative with similar safety.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Insulin is the preferred glucose-lowering therapy in pregnancy; glargine has reassuring observational data, though NPH and detemir remain the traditional choices.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Limited data; National Pregnancy Registry available (1) · Limited human data.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Limited human data; older agent with substantial use experience.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · One of the better-studied basal insulin analogs in pregnancy; reassuring data.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Some controversial signal for first-trimester gastroschisis association in observational studies; limited use is generally considered acceptable after the first trimester.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1)

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