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Medicines > routes : Sublingual or intramuscular or vaginal

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classes:
[[:Category:Anxiolytics|Anxiolytic]] (2) · [[:Category:Hormone_replacement_therapy|Hormone replacement therapy]] (2) · [[:Category:Schedule IV controlled substances|Schedule IV controlled substance]] (2) · [[:Category:Sex_hormones|Sex hormone]] (2) · [[:Category:Sleep aids|Sleep aid]] (2)
uses:
No approved medical problem. Encountered as a designer/research benzodiazepine and, increasingly, as an adulterant in illicit opioid supplies. (1) · '"`UNIQ--vote-00000015-QINU`"', '"`UNIQ--vote-00000016-QINU`"' (1) · '"`UNIQ--vote-00000017-QINU`"', '"`UNIQ--vote-00000018-QINU`"', '"`UNIQ--vote-00000019-QINU`"' (1) · '"`UNIQ--vote-0000001B-QINU`"', '"`UNIQ--vote-0000001C-QINU`"', '"`UNIQ--vote-0000001D-QINU`"', '"`UNIQ--vote-0000001E-QINU`"', '"`UNIQ--vote-0000001F-QINU`"' (1) · '"`UNIQ--vote-0000001B-QINU`"', '"`UNIQ--vote-0000001C-QINU`"', '"`UNIQ--vote-0000001D-QINU`"', '"`UNIQ--vote-0000001E-QINU`"', '"`UNIQ--vote-0000001F-QINU`"', '"`UNIQ--vote-00000020-QINU`"' (1) · '"`UNIQ--vote-0000001F-QINU`"', '"`UNIQ--vote-00000020-QINU`"', '"`UNIQ--vote-00000021-QINU`"', '"`UNIQ--vote-00000022-QINU`"', '"`UNIQ--vote-00000023-QINU`"', '"`UNIQ--vote-00000024-QINU`"', '"`UNIQ--vote-00000025-QINU`"' (1) · '"`UNIQ--vote-00000023-QINU`"', '"`UNIQ--vote-00000024-QINU`"', '"`UNIQ--vote-00000025-QINU`"', '"`UNIQ--vote-00000026-QINU`"', '"`UNIQ--vote-00000027-QINU`"', '"`UNIQ--vote-00000028-QINU`"' (1) · '"`UNIQ--vote-000003B5-QINU`"', '"`UNIQ--vote-000003B6-QINU`"', '"`UNIQ--vote-000003B7-QINU`"', '"`UNIQ--vote-000003B8-QINU`"', '"`UNIQ--vote-000003B9-QINU`"' (1) · '"`UNIQ--vote-00000607-QINU`"', '"`UNIQ--vote-00000608-QINU`"', '"`UNIQ--vote-00000609-QINU`"', '"`UNIQ--vote-0000060A-QINU`"' (1) · '"`UNIQ--vote-00000661-QINU`"', '"`UNIQ--vote-00000662-QINU`"', '"`UNIQ--vote-00000663-QINU`"', '"`UNIQ--vote-00000664-QINU`"', '"`UNIQ--vote-00000665-QINU`"' (1) · '"`UNIQ--vote-00000722-QINU`"', '"`UNIQ--vote-00000723-QINU`"', '"`UNIQ--vote-00000724-QINU`"', '"`UNIQ--vote-00000725-QINU`"' (1) · '"`UNIQ--vote-000007C1-QINU`"', '"`UNIQ--vote-000007C2-QINU`"', '"`UNIQ--vote-000007C3-QINU`"', '"`UNIQ--vote-000007C4-QINU`"', '"`UNIQ--vote-000007C5-QINU`"', '"`UNIQ--vote-000007C6-QINU`"', '"`UNIQ--vote-000007C7-QINU`"' (1) · '"`UNIQ--vote-00000BE3-QINU`"', '"`UNIQ--vote-00000BE4-QINU`"', '"`UNIQ--vote-00000BE5-QINU`"', '"`UNIQ--vote-00000BE6-QINU`"', '"`UNIQ--vote-00000BE7-QINU`"', '"`UNIQ--vote-00000BE8-QINU`"', '"`UNIQ--vote-00000BE9-QINU`"', '"`UNIQ--vote-00000BEA-QINU`"' (1) · '"`UNIQ--vote-00000C0A-QINU`"', '"`UNIQ--vote-00000C0B-QINU`"', '"`UNIQ--vote-00000C0C-QINU`"', '"`UNIQ--vote-00000C0D-QINU`"', '"`UNIQ--vote-00000C0E-QINU`"' (1) · '"`UNIQ--vote-00000D13-QINU`"', '"`UNIQ--vote-00000D14-QINU`"', '"`UNIQ--vote-00000D15-QINU`"', '"`UNIQ--vote-00000D16-QINU`"' (1) · '"`UNIQ--vote-00000F40-QINU`"', '"`UNIQ--vote-00000F41-QINU`"', '"`UNIQ--vote-00000F42-QINU`"', '"`UNIQ--vote-00000F43-QINU`"', '"`UNIQ--vote-00000F44-QINU`"' (1) · '"`UNIQ--vote-0000143C-QINU`"', '"`UNIQ--vote-0000143D-QINU`"', '"`UNIQ--vote-0000143E-QINU`"', '"`UNIQ--vote-0000143F-QINU`"', '"`UNIQ--vote-00001440-QINU`"', '"`UNIQ--vote-00001441-QINU`"' (1)
starting dose:
'''5 mg PO at bedtime for women, 5-10 mg for men''' (per FDA's 2013 sex-specific dose reduction for women due to slower clearance). Ambien CR 6.25 mg women / 6.25-12.5 mg men. Intermezzo SL 1.75 mg women / 3.5 mg men (1) · 0.5-3 mg PO 30-60 minutes before bedtime. Some patients respond to micro-doses (0.3 mg) without additional benefit at higher doses. For circadian phase shifting, timing relative to dim-light melatonin onset matters more than absolute dose (1) · 500 mg PO TID × 7-10 days (most indications); 2 g single dose for trichomoniasis; 500 mg IV q8h for severe anaerobic infection; rectal 1 g BID (1) · Anxiety: 0.5-1 mg PO BID-TID. Insomnia: 1-2 mg PO at bedtime. Status epilepticus: 4 mg IV (adult), repeat after 5-10 minutes if needed. Acute agitation: 1-2 mg IM (1) · Anxiety: 25-50 mg PO QID. Pruritus: 25 mg PO TID-QID. Insomnia: 25-50 mg PO at bedtime. Pediatric: 50-100 mg/day divided (1) · HRT cyclic: 200 mg PO HS days 1-12 of each month; continuous: 100 mg PO daily; ART luteal support 100 mg vaginal TID or 90 mg gel daily (1) · IR oral: 15-30 mg every 4 hours as needed. ER opioid-naive: 15-30 mg every 12 hours. IV/IM/SC: 2-10 mg every 3-4 hours. Epidural / intrathecal: see surgical or palliative-care protocols (1) · No medical dose. Active recreational doses reported in the 0.5–1.5 mg range (similar potency to alprazolam). (1) · Oral 1-2 mg daily; transdermal patch 0.025-0.05 mg/d twice weekly; transdermal gel 0.5-1 g/d; vaginal 10 mcg tablet twice weekly for GSM. Always combine with a progestogen in patients with an intact uterus. (1) · Oral 300-450 mg PO QID; IV 600-900 mg q8h; topical 1% solution/gel BID; vaginal 100 mg ovule × 3 days or 2% cream × 7 days (1) · Oral: 1500 mg PO QID for 2-3 days (load), then 750-1500 mg QID maintenance. IV/IM: 1000 mg every 8 hours for acute spasm (1) · Oral: 4-6 mL (400,000-600,000 units) suspension QID swish-and-swallow; topical: BID-QID; vaginal tablet 1 daily for 2 weeks (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) · Rheumatologic: 7.5-15 mg PO or SC '''once weekly''' (not daily — daily dosing is a recognized fatal error); folic acid 1 mg PO daily on non-MTX days; oncology dosing is far higher and indication-specific (1) · SL 0.3-0.6 mg every 5 minutes up to 3 doses for acute angina (call EMS if not resolved after the third); IV infusion 5-10 mcg/min titrated; transdermal patch 0.2-0.4 mg/hr for 12-14 hours daily (nitrate-free interval prevents tolerance) (1) · Topical 0.025-0.5% cream/ointment BID; intra-articular 5-40 mg per joint q3-6 months; intranasal Nasacort 110 mcg/spray, 2 sprays/nostril daily; oral paste 0.1% to lesion 2-3×/d (1) · Topical: 1% cream BID × 2-4 weeks; vaginal: 1% or 2% cream nightly × 7 days, or 100/200/500 mg vaginal tablet single or 3-day regimens; troche: 10 mg PO five times daily × 2 weeks for thrush (1)
preparations:
1% topical cream, lotion, solution; 1%, 2% vaginal cream; 100, 200, 500 mg vaginal tablets; 10 mg oral troches; combination with betamethasone (Lotrisone, Rx) (1) · 100, 250, 500, 1000, 5000 mcg tablets (OTC and Rx); 1000 mcg/mL injection; intranasal spray; sublingual (1) · 100,000 units/mL oral suspension; 500,000 unit tablets; 100,000 units/g cream, ointment, powder; vaginal tablets (1) · 2.5 mg tablets; 10-50 mg/mL injection; pre-filled subcutaneous autoinjectors (Otrexup, Rasuvo); 2.5 mg/mL oral solution (Xatmep) (1) · 250, 500 mg tablets; 750 mg ER; 500 mg/100 mL IV; 0.75-1% topical gel/cream; 0.75% vaginal gel; suppository (1) · 75, 150, 300 mg capsules; 75 mg/5 mL solution; 150 mg/mL IV; 1% topical; 2% vaginal cream (1) · Illicit tablets ("bars"), powders, blotter, occasionally solutions. No pharmaceutical product exists. (1) · IR tablets 15, 30 mg; oral solution 10 mg/5 mL, 20 mg/mL, 100 mg/5 mL (concentrated); suppositories; ER tablets and capsules in multiple strengths; injectable 0.5-50 mg/mL (1) · IR tablets 5, 10 mg; CR tablets 6.25, 12.5 mg; SL tablets 1.75, 3.5, 5, 10 mg; oral spray (1) · Oral 0.5, 1, 2 mg tablets; transdermal patches (twice-weekly and once-weekly); 0.06% gel; 1.53 mg/spray topical; vaginal ring (Estring); vaginal tablet (Vagifem/Yuvafem); vaginal cream (1) · Oral 100, 200 mg capsules (peanut oil; check allergy); 100 mg vaginal insert (Endometrin); 4%, 8% vaginal gel (Crinone); IM 50 mg/mL (1) · OTC tablets, sublingual tablets, gummies, liquid, extended-release tablets and capsules; common strengths 0.5, 1, 3, 5, 10 mg (1) · SL 0.3, 0.4, 0.6 mg tablets; lingual spray 0.4 mg/spray; ER 2.5-9 mg capsules; transdermal patch 0.1-0.8 mg/hr; 2% ointment; 0.4% rectal ointment; 5 mg/mL IV (1) · Tablets 0.5, 1, 2 mg; oral concentrate 2 mg/mL; injection 2 mg/mL and 4 mg/mL; Loreev XR capsules 1, 2, 3 mg (1) · Tablets 10, 25, 50 mg (HCl); capsules 25, 50, 100 mg (pamoate); oral suspension 25 mg/5 mL; injection 25, 50 mg/mL (IM only, never IV) (1) · Tablets 500, 750 mg; injection 100 mg/mL (1) · Topical creams, ointments, lotions, dental paste (0.025-0.5%); Kenalog 10 mg/mL, 40 mg/mL injection; Nasacort 55 mcg/spray intranasal; oral inhaler discontinued in US (1)
routes: (Click arrow to add another value)
halflife:
1-2 hours'"`UNIQ--ref-00000017-QINU`"' (1) · 1-3 minutes (very short)'"`UNIQ--ref-00000C0F-QINU`"' (1) · 12-15 hours (intermediate); '''no active metabolites''' (key clinical feature)'"`UNIQ--ref-00000029-QINU`"' (1) · 14-25 hours (longer in elderly and hepatic impairment)'"`UNIQ--ref-00000026-QINU`"' (1) · 3-10 hours (low dose); 8-15 hours (high dose); much longer in third-space accumulation (pleural effusion, ascites)'"`UNIQ--ref-000007C8-QINU`"' (1) · 30-50 minutes (short)'"`UNIQ--ref-00000021-QINU`"' (1) · 6-8 hours'"`UNIQ--ref-00000BEB-QINU`"' (1) · Estimated ~12–17 h (some sources cite up to ~21 h); active metabolites prolong effect. (1) · Morphine 2-4 hours; morphine-6-glucuronide active metabolite 2-4 hours (longer with renal impairment)'"`UNIQ--ref-00000020-QINU`"' (1) · Not meaningfully described (minimal systemic absorption from topical use)'"`UNIQ--ref-00000F45-QINU`"' (1) · Not meaningfully described (not systemically absorbed)'"`UNIQ--ref-00000D17-QINU`"' (1) · Plasma ~3-5 hours; biologic effect substantially longer (~12-36 hours for intermediate-acting glucocorticoids)'"`UNIQ--ref-00000666-QINU`"' (1) · ~13-20 hours (oral); transdermal pharmacokinetics buffer the peaks/troughs of oral dosing'"`UNIQ--ref-000003BA-QINU`"' (1) · ~2.5 hours'"`UNIQ--ref-0000001A-QINU`"' (1) · ~2.5-3 hours'"`UNIQ--ref-00001442-QINU`"' (1) · ~5-20 hours (oral micronized; highly variable)'"`UNIQ--ref-00000726-QINU`"' (1) · ~6 days (plasma); hepatic stores last 3-5 years (1)
bioavailability:
60-70% PO at low doses; saturable at high doses (parenteral routes preferred above 15-25 mg/week)'"`UNIQ--ref-000007C9-QINU`"' (1) · Essentially zero systemic absorption from oral or topical routes — the topical-action-only profile is the basis of its safety'"`UNIQ--ref-00000D18-QINU`"' (1) · Highly route-dependent: SL bypasses first-pass; oral has extensive first-pass (used only for chronic ER preparations); transdermal predictable'"`UNIQ--ref-00000C10-QINU`"' (1) · Not formally characterized in humans. (1) · Oral ~1-3% via passive diffusion at high doses (independent of intrinsic factor); IM/SC ~100% (1) · Oral ~5% (extensive first-pass to estrone and conjugates); transdermal bypasses first-pass, giving more physiologic estradiol:estrone ratio'"`UNIQ--ref-000003BB-QINU`"' (1) · Oral: very low (extensive first-pass); micronization improves uptake somewhat. Vaginal: high local effect with lower systemic levels (first-uterine-pass concentration)'"`UNIQ--ref-00000727-QINU`"' (1) · Topical/intranasal: high local, low systemic; intra-articular: local depot then systemic absorption'"`UNIQ--ref-00000667-QINU`"' (1) · Topical: minimal systemic; troche: ~3% systemic'"`UNIQ--ref-00000F46-QINU`"' (1) · ~100% (oral; near-complete absorption)'"`UNIQ--ref-00000018-QINU`"' (1) · ~15% (oral; highly variable due to extensive and variable first-pass metabolism)'"`UNIQ--ref-00000022-QINU`"' (1) · ~25-40% (oral; extensive first-pass)'"`UNIQ--ref-00000021-QINU`"' (1) · ~70% (oral)'"`UNIQ--ref-0000001B-QINU`"' (1) · ~80% (oral)'"`UNIQ--ref-00000027-QINU`"' (1) · ~80% (oral)'"`UNIQ--ref-00000BEC-QINU`"' (1) · ~90% (oral)'"`UNIQ--ref-0000002A-QINU`"' (1) · ~90% (oral)'"`UNIQ--ref-00001443-QINU`"' (1)
pregnancy:
None (1) · '''Contraindicated in pregnancy''' (Category X); abortifacient and teratogenic. Discontinuation 3-6 months before conception is standard.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Avoid. Benzodiazepines are associated with neonatal sedation, floppy-infant syndrome, and withdrawal; teratogenic signal weak but non-zero. Designer benzo with no safety data, assume worst-case. (1) · Chronic third-trimester exposure produces neonatal opioid withdrawal syndrome and respiratory depression at delivery.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Contraindicated in pregnancy (use is not appropriate during gestation; class label X). Lactation considerations vary by indication.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Generally considered safe after the first trimester; first-trimester use weighed against indication.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Generally considered safe in pregnancy (no systemic absorption).<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Generally considered safe.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (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; case reports of neonatal sedation with late-pregnancy exposure.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Limited human data; endogenous hormone, but supplemental pharmacological doses are not well characterized in pregnancy.<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; some signal for first-trimester exposure but not conclusive.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Routinely supplemented in vegan pregnancies and pernicious anemia.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Some signal for cleft lip/palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Topical and vaginal generally considered safe; widely used.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Topical/intranasal generally low-risk; intra-articular and high-dose injection: weigh risk individually.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1) · Used in obstetric emergencies (uterine relaxation, severe hypertension) when needed; otherwise limited routine use.<sup class="pcp-cn" title="This claim needs a citation.">&#91;[[Pharmacopedia:Citation needed|citation&nbsp;needed]]&#93;</sup> (1)
legal:
None (1) · OTC (low/mid-dose oral) and [[USLegal:Prescription only|Rx-only]] (injection, intranasal) in US (1) · OTC (lower strengths) and [[USLegal:Prescription only|Rx-only]] (combination with betamethasone) in US (1) · OTC (lowest-strength topicals) and [[USLegal:Prescription only|Rx-only]] (higher strengths, injectable) in US (1) · [[USLegal:Over-the-counter|OTC]] dietary supplement in the US ('''not FDA-regulated as a medicine'''; multiple studies show OTC products contain 50-470% of labeled melatonin content); [[USLegal:Prescription only|Rx-only]] in the EU and UK (1) · [[USLegal:Prescription only|Rx-only]] in US (6) · [[USLegal:Prescription only|Rx-only]] in US. Carries a '''Boxed Warning''' for Clostridioides difficile colitis (one of the most C. difficile-inducing antibiotic classes)'"`UNIQ--ref-00001444-QINU`"' (1) · [[USLegal:Prescription only|Rx-only]] in US. Not a controlled substance, distinguishing it from carisoprodol which is Schedule IV'"`UNIQ--ref-00000019-QINU`"' (1) · [[USLegal:Prescription only|Rx-only]] in US. Not a controlled substance, which is a meaningful clinical advantage over the benzodiazepine alternatives for short-term anxiety'"`UNIQ--ref-00000028-QINU`"' (1) · [[USLegal:Schedule II|Schedule II controlled substance]] in US; WHO essential medicine'"`UNIQ--ref-00000022-QINU`"' (1) · [[USLegal:Schedule IV|Schedule IV controlled substance]] in US. Carries the benzodiazepine class '''Boxed Warning''' for risk of fatal respiratory depression, coma, and death when combined with opioids'"`UNIQ--ref-0000002B-QINU`"' (1) · [[USLegal:Schedule IV|Schedule IV controlled substance]] in US. Carries the FDA '''Boxed Warning''' for '''complex sleep behaviors''' (sleep-driving, sleep-walking, sleep-eating, other parasomnias) added in 2019'"`UNIQ--ref-0000001C-QINU`"' (1)

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