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None (7) · Ascorbic acid (vitamin C) (1) · Bisacodyl (1) · Cyanocobalamin (vitamin B12) (1) · Docusate (sodium or calcium) (1) · Ferrous sulfate (1) · Folic acid (folate, pteroylglutamic acid) (1) · Lactulose (1) · Omega-3-acid ethyl esters (1) · Polyethylene glycol 3350 (PEG 3350) (1)

Caplyta (1) · Colace (sodium), Surfak (calcium); many generics OTC (1) · Dulcolax, Correctol, Bisac-Evac (1) · Feosol, Fer-In-Sol, Slow Fe; mostly generic and OTC (1) · Folvite; mostly generic (1) · Generic; huge OTC presence (1) · Kristalose, Constulose, Generlac, Enulose (1) · Lovaza, Omtryg (1) · Many OTC and Rx; Nascobal (intranasal); generic injection (1) · MiraLAX (OTC), GlycoLax, GoLYTELY (with electrolytes for bowel prep), CoLyte, MoviPrep, NuLYTELY (1) · Nuplazid (1) · Qelbree (1) · REL-1017 / esmethadone (investigational; not yet FDA-approved as of mid-2024) (1) · Rexulti (1) · Trintellix (US), Brintellix (formerly) (1) · Viibryd (1)

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) · Selective inverse agonist at 5HT2A receptors with weaker activity at 5HT2C. Has no significant dopamine D2 affinity, unique among approved antipsychotics. Inverse agonism (rather than antagonism) reduces constitutive 5HT2A receptor activity below baseline. (1) · Selective NET inhibitor (no significant DAT activity, distinguishes from amphetamine/methylphenidate). Also: 5HT1A receptor partial agonism, 5HT2B and 5HT7 receptor antagonism. The serotonergic actions may underlie better tolerability and possibly different efficacy spectrum than atomoxetine. (1) · '"`UNIQ--vote-0000004E-QINU`"' The EPA+DHA mix is biochemically and clinically distinct from icosapent ethyl'"`UNIQ--ref-0000004F-QINU`"'. (1) · '"`UNIQ--vote-00001067-QINU`"' Chronic use is associated with cathartic colon (colonic dilation, loss of haustration), hypokalemia, and laxative dependence; reserved for short-term use or bowel prep with breaks between courses'"`UNIQ--ref-00001068-QINU`"'. (1) · '"`UNIQ--vote-0000132D-QINU`"' Electrolyte-balanced bowel-prep formulations are designed to be iso-osmotic with plasma so the volume passes through without net fluid or electrolyte shifts, the basis of their safety for whole-bowel evacuation. (1)

0.4 mg PO daily (general prevention); 0.8-1 mg/d in pregnancy; 4 mg/d for women with prior NTD-affected pregnancy; 1 mg/d during methotrexate therapy (1) · 10 mg PO once daily × 7 days, then 20 mg × 7 days, then 40 mg as target dose (take with food) (1) · 10 mg PO once daily; may increase to 20 mg as tolerated, or decrease to 5 mg if needed (1) · 100-200 mg PO once or twice daily; pediatric weight-based (1) · 325 mg PO daily to TID (=65 mg elemental iron/tablet); alternate-day dosing is now favored by hepcidin physiology for better absorption with less GI burden (1) · 34 mg PO once daily (1) · 4 g PO daily (as 4 x 1 g capsules once daily, or 2 capsules BID) (1) · 42 mg PO once daily with food (no titration) (1) · 5-15 mg PO once at bedtime; 10 mg PR for faster effect; bowel prep regimens use higher single doses (1) · Constipation: 15-30 mL PO daily (titrate to 1-2 soft stools/day); hepatic encephalopathy: 20-30 g (30-45 mL) PO/PR every 1-2 hours acutely until soft stools, then BID-QID to target 2-3 soft stools/day (1) · Constipation: 17 g (one capful) PO daily dissolved in 4-8 oz fluid; bowel prep: 4 L of PEG-electrolyte solution split-dose evening before and morning of procedure (1) · General supplementation 75-90 mg/d (RDA); scurvy treatment 100-1000 mg/d for several weeks; megadose claims unsupported (1) · Pediatric 6-11: 100 mg PO daily, titrate weekly to max 400 mg. Adolescent 12-17: 200 mg, max 400 mg. Adult: 200 mg, max 600 mg. (1) · Replacement: 1000 mcg IM daily for 1 week, then weekly for 4 weeks, then monthly; or 1000-2000 mcg PO daily (effective even in pernicious anemia via passive diffusion); intranasal 500 mcg weekly (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) · Trials use 25 mg or 50 mg PO daily (1)

0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg tablets (1) · 0.4, 0.8, 1 mg OTC; 1 mg Rx; 5 mg/mL injection (1) · 1 g soft gelatin capsules containing ~465 mg EPA + ~375 mg DHA as ethyl esters (1) · 10 g/15 mL solution (Constulose); 10 g, 20 g powder packets (Kristalose) (1) · 10 mg, 20 mg, 40 mg tablets (1) · 10 mg, 34 mg capsules/tablets (1) · 100 mg, 150 mg, 200 mg extended-release capsules (can be sprinkled on food) (1) · 100, 250, 500, 1000 mg tablets, chewables, gummies, effervescent; IV (specialty) (1) · 100, 250, 500, 1000, 5000 mcg tablets (OTC and Rx); 1000 mcg/mL injection; intranasal spray; sublingual (1) · 17 g (OTC) and 14 g (Rx) powder packets; 238, 510, 527 g bottles; PEG-electrolyte preparations 4 L (GoLYTELY, NuLYTELY) (1) · 325 mg tablets (65 mg elemental Fe); 220 mg/5 mL liquid (44 mg elemental Fe/5 mL); 142 mg/mL drops; OTC and Rx (1) · 42 mg capsules (1) · 5 mg enteric-coated tablets; 10 mg rectal suppositories; OTC and Rx (1) · 5 mg, 10 mg, 20 mg tablets (1) · 50, 100, 250 mg capsules; 50 mg/5 mL syrup; OTC (1) · Investigational oral capsule (1)

1 mg/d typical Rx; higher in specific indications (1) · 20 mg/d (1) · 30 mg/d for short-term use (1) · 34 mg/d (1) · 4 g/d (1) · 4 mg/d (schizophrenia); 3 mg/d (AD agitation); 3 mg/d (MDD adjunct) (1) · 40 mg/d (1) · 400 mg/d (pediatric); 600 mg/d (adult) (1) · 42 mg/d (1) · Indication-specific; bowel prep regimens reach 4 L cumulative (1) · Indication-specific; HE may require high-volume dosing (1) · No strict ceiling; water-soluble vitamin, low toxicity (1) · Not yet approved (1) · UL 2000 mg/d in adults (1) · ~200 mg elemental iron/d typical practical limit (1) · ~500 mg/d typical (1)

especially in acute HE) (1) · IM (2) · intranasal (1) · IV (3) · Oral (16) · rectal (2) · rectal (enema (1) · SC (2) · sublingual (1)

1-3 days (1) · 4-6 weeks for full antidepressant effect (claimed earlier onset for some patients due to 5HT1A partial agonism) (1) · ADHD symptom improvement reported within 1-2 weeks (faster than atomoxetine which takes 4-6 weeks) (1) · Antipsychotic effect over weeks (1) · Benefit over weeks of dosing (1) · Constipation: 1-3 days; bowel prep: 1-3 hours after starting (1) · Constipation: 24-48 hours; HE: ammonia reduction within hours of stool production (1) · Days for symptom improvement in scurvy (1) · Hematologic response within days (1) · PO 6-12 hours; PR 15-60 minutes (1) · Rapid (within 1 week in trials) (1) · Reticulocyte response at 3-5 days; neurologic recovery weeks to months (and may be incomplete if longstanding) (1) · Reticulocyte response at 7-10 days; hemoglobin rise of ~1 g/dL per 3 weeks (1) · Triglyceride lowering at 2-4 weeks; max at 8 weeks (1) · Typical antidepressant 4-6 week onset (1) · Weeks for psychosis/depression; AD agitation benefit emerges over weeks (1)

N/A (incorporated into hemoglobin and tissue stores) (1) · Not formally established (1) · Not meaningfully described (1) · Not meaningfully described (negligible systemic absorption) (1) · Not meaningfully described — lactulose is not significantly absorbed (1) · Not well characterized; tissue incorporation over weeks'"`UNIQ--ref-00000051-QINU`"' (1) · Variable; effect dependent on local intestinal action rather than systemic kinetics'"`UNIQ--ref-0000106B-QINU`"' (1) · ~0.5 hours plasma; tissue retention longer (1) · ~10-20 days (steady-state body pool); single dose plasma ~2 hours (1) · ~18 hours (terminal) (1) · ~25 hours (1) · ~57 hours (parent), ~200 h (active metabolite) (1) · ~6 days (plasma); hepatic stores last 3-5 years (1) · ~66 hours (1) · ~7 hours (1) · ~91 hours (1)

10-20% (oral; reduced by food, calcium, antacids, PPIs, tea/coffee; enhanced by ascorbate) (1) · <0.1% systemic absorption (PEG 3350 is too large to absorb intact) (1) · <3% systemic absorption (the basis of the safety and mechanism)'"`UNIQ--ref-00000F5E-QINU`"' (1) · Adequate oral bioavailability with extended-release formulation (1) · High (oral) (1) · Improved with food'"`UNIQ--ref-00000052-QINU`"' (1) · Limited but adequate; take with food (1) · Local action; minimal systemic effect (1) · Low systemic absorption (enteric coating delivers drug to colon)'"`UNIQ--ref-0000106C-QINU`"' (1) · Not characterized; oral dosing once daily (1) · Oral bioavailability suitable for daily dosing (1) · Oral ~1-3% via passive diffusion at high doses (independent of intrinsic factor); IM/SC ~100% (1) · ~70-90% at typical doses; saturable at high doses (>500 mg) (1) · ~72% (with food); much lower fasting (~36%) (1) · ~75% (1) · ~95% (1)

Investigational (1) · OTC (low-dose) and [[USLegal:Prescription only|Rx-only]] (1 mg, injectable) in US (1) · OTC (low/mid-dose oral) and [[USLegal:Prescription only|Rx-only]] (injection, intranasal) in US (1) · OTC (MiraLAX) and [[USLegal:Prescription only|Rx-only]] (electrolyte solutions for bowel prep) in US (1) · OTC in US (4) · Rx (4) · Rx, '''not a controlled substance''' (no DEA scheduling) (1) · Rx. FDA black-box warning for increased mortality in elderly patients with dementia-related psychosis (class warning shared with all antipsychotics) (1) · [[USLegal:Prescription only|Rx-only]] in US (2)