Triazolam dosing

Seizures have been reported after withdrawal of high doses of triazolam or relatively low doses combined with alcohol ( 347, 348 and 349). The FDA has reported a signal of an association for withdrawal seizures associated with triazolam ( 350). In a chart review of 150 consecutive patients withdrawn from BZDs, three of 25 triazolam patients experienced seizures, compared with two of 125 given other BZDs ( 351). Psychosis with delirium also has been reported after discontinuation of high triazolam doses (352). 

Roehrs T, Zorick F, Wittig R, et al. Efficacy of a reduced triazolam dose in elderly insomniacs. Neurobioi Aging 1985 6 292-296. 

Limited results from clinical laboratory evaluations suggested that the GABAj l agonists zaleplon (Rush et al. 1999b) and Zolpidem (Rush et al. 1999a) produce effects that are consistent with abuse potential comparable to that of the benzodiazepine triazolam. The reported incidence of dependence on Zolpidem in the medical literature is low, compared with that for benzodiazepines, and is characterized by use of high doses, often in individuals with a history of substance abuse (Hajak et al. 2003 Vartzopoulos et al. 2000). 

A rebound sleep disturbance has been found after only 7—10 days of treatment with therapeutic doses of triazolam (Greenblatt et al. 1987). Others have described a withdrawal syndrome after substitution of a short-acting benzodiazepine for a long-acting benzodiazepine (Conell and Berhn 1983). Rebound insomnia may occur with zolpidem. 

Ator NA, Weerts EM, Kaminski BJ, et al Zaleplon and triazolam physical dependence assessed across increasing doses under a once-daily dosing regimen in baboons. Drug Alcohol Depend 61 69-84, 2000... 

Rebound insomnia occurs frequently with high doses of triazolam, even when used intermittently. 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

Efavirenz (Sustiva) [Antiretroviral/NNRTI] Uses Hiv infxns Action Antiretroviral nonnucleoside RTI Dose Adults. 600 mg/d PO qhs Feds. See package insert avoid high-fat meals Caution [D, ] CDC recommends HIV-infected mothers not breast-feed Contra Component sensitivity Disp Caps SE Somnolence, vivid dreams, dizziness, rash, N/V/D Interactions T Effects W/ ritonavir T effects OF CNS depressants, ergot derivatives, midazolam, ritonavir, simvastatin, triazolam, warfarin X effects W/ carbamazepine, phenobarbital, rifabutin, rifampin, saquinavir, St. John s wort i effects OF amprenavir, carbamazepine, clarithromycin, indinavir, phenobarbital, saquinavir, warfarin may alter effectiveness OF OCPs EMS Concurrent EtOH usage can t CNS d ression OD May cause muscle contractions and adverse CNS effects activated charcoal may be effective... 

WARNING Co administration w/ ritonavir assoc w/ Hep hepatic decomp w/ fatalities. D/C w/ S/Sxs of H Uses HIV 1 Infxn w/ highly Tx-experienced pts or HIV 1 strains resistant to multiple protease inhibitors. Must be used w/ ritonavir 200 mg Action Antiretroviral HIV-1 protease inhibitor Dose 500 mg PO bid w/ food, administer w/ ritonavir 200 mg PO bid Caution [C, -] Sulfa aU gy, Uvct Dz Contra Mod-severe hepatic insuff concomitant use w/ amiodarone, astemizole, bepridil, cisapride, ergots, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, rifampin, simvastatin, terfenadine, triazolam, St. John s wort Disp Caps SE HA, GI distress, rash, fati e, fat redistribution, hyperglycemia, Hep, liver Dz, lipid elevations Interactions T Effects OF anticoagulants, antipits, azole antifun-... 

Doses of short-acting benzodiazepines doses greater than lorazepam (Ativan) 3 mg oxazepam (Serax), 60 mg alprazolam (Xanax), 2 mg temazepam (Restorll), 15 mg and triazolam (Halcion), 0.25 mg Because of increased sensitivity to benzoadiazepines in elderly patients, smaller doses may be effective as well as safer. Total daily doses should rarely exceed the suggested maxim urns. High... 

Whether hypnotic efficacy is retained with lower recommended doses of many BZDs is unclear. The efficacy of lower doses of triazolam (0.25 and 0.125 mg) has not been well established (112, 115,116, 117,118 and 119). Flurazepam (15 mg) may be effective for 1 week but not for 2 weeks (119,120 and 121). Temazepam (15 mg) was reported effective for 2 weeks in one study but not in another (95,123). Estazolam (1.0 and 2.0 mg) has been reported effective for 1 week, but longer term efficacy with the lower dose has not been reported (124). 

In high doses, triazolam (e.g., 0.5 to 1.0 mg) may cause a syndrome of severe anxiety, paranoia, hyperacusis, altered smell and taste, and paraesthesia. Increased daytime anxiety typically occurs between doses of triazolam when it is used regularly as a hypnotic. These symptoms may be withdrawal effects because of triazolam s rapid elimination rate (see also Chapter 14). 

This non-BZD hypnotic, cyciopyrroione, is indicated for short-term management of insomnia. Zopiclone has a BZD-like profile, a short half-life of 3.5 to 6.5 hours, no active metabolites, minimal rebound effects, and less abuse potential than BZDs. The usual therapeutic dose is oral 7.5 mg administered 30 to 60 minutes before bedtime. Zopiclone has a well-documented capacity to reduce sleep latency, improve quality and duration of sleep, and reduce the frequency of nighttime awakenings. In clinical trials, 7.5 mg doses of zopiclone have been found to be as effective as triazolam 0.5 mg, temazepam 20 mg, flurazepam 15-30 mg, and nitrazepam 5 to 10 mg for the short-term treatment of insomnia (136). 

Zopiclone is relatively well tolerated (137). The most common adverse reaction is taste alteration. A postmarketing analysis of 10,000 cases revealed that zopiclone has a relatively low incidence of side effects (about 8%) (138). Like BZDs, zopiclone has a dose-related hangover effect (139). Rebound insomnia has occurred after short-term use (5 to 14 days) but does not appear to be as severe, even after abrupt withdrawal (140, 141). Abuse, tolerance, and physical and psychological dependence have been reported with zopiclone (142). Zopiclone has been shown to be as effective a hypnotic as triazolam in the elderly ( 143). More comparisons with short to medium half-life BZDs for the treatment of insomnia are needed to show that zopiclone has an advantage over the BZDs. 

Zaleplon s onset time, time to maximal drug effect, and duration of action are shorter than with triazolam. Hence, despite its non-BZD structure and unique BZD receptor binding profile, its behavioral pharmacological profile is similar to that of triazolam ( 157). Like zolpidem, zaleplon in recommended doses decreases sleep latency with minimal effect on sleep stages. Thus, it differs from BZDs, which prolong the first two stages of sleep and shorten stages 3 and 4 REM sleep ( 158). 

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