Quazepam dosing

Quazepam (Doral) [C IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia Action Benzodiazepine Dose 7.5-15 mg PO hs PRN i in elderly hqjatic failure Caution [X, /-] NA glaucoma Contra PRG, sleep apnea Disp Tabs SE Sedation, hangovCT, somnolence, resp depression Interactions T Effects W/ azole antifungals, cimetidine, digoxin, disulfiram, INH, levodopa, macrolides, neuroleptics, phenytoin, quinolones, SSRIs, verapamil, grapefruit juice, EtOH effects W/carbamazepine, rifampin, rifabutin, tobacco EMS Use caution w/ other benzodiazepines, antihistamines, opioids and verapamil, can T CNS depression concurrent EtOH and grapefruit juice use T CNS depression OD May cause profound CNS depression, confusion, bradycardia, hypotension, and altered reflexes flumazenil can be used as antidote activated charcoal may be effective... 

For healthy adults, quazepam therapy is best initiated with a 15 mg dose. In some patients, because of individual variations in response, the dose may be reduced to 7.5 mg. Elderly and debilitated patients should be started on 7.5 mg. 

Nevertheless, other studies have found no or inconsistent residual impairment with lower doses of flurazepam and quazepam ( 101, 284, 285, 286, 287,... 

Even after relatively short periods of administration, discontinuation of short and intermediate half-life BZDs, such as triazolam and temazepam, may result in marked worsening of sleep, even worse than baseline levels (i.e., rebound insomnia), although this does not seem to occur with zolpidem (95, 102, 103, 109, 110, 113, 285, 297, 316, 325, 326, 327, 328, 329, 330, 331,332, 333, 334, 335, 336 and 337). Gradual dose reduction may attenuate the incidence of rebound, and with flurazepam and quazepam, little sleep disturbance occurs, even after abrupt drug withdrawal ( 99, 100, 101, 102, 103,104, 105 and 106, 280, 338, 339, 340 and 341). 

Consistent with their depressant and sedative effects, benzodiazepines administered acutely typically decrease CFF threshold.119 120 Specifically, significant decreases have been reported for 1 mg alprazolam, 10 mg diazepam, and 15 mg quazepam 121 4 to 11 mg midazolam 122 7.5 to 50 mg oxazepam 123 1 and 2 mg lorazepam 124 and 0.5 mg triazolam and 1 mg flunitrazepam.120 As is evident, this effect on CFF threshold was observed at therapeutic doses of each drug, and when multiple doses were tested, the effect was dose-related. However, there are reports of acute, therapeutic doses of diazepam (5 mg)125 and lorazepam (1 and 2 mg)125,126 having no effect on CFF threshold. One study investigating numerous benzodiazepines120 reported next-day impairment after acute doses of triazolam (0.5 mg) and lormetazepam (1 to 2 mg). No studies were found that examined the effect of chronic benzodiazepine administration on CFF threshold. 

Kales A, Scharf MB, Bixler EO, Schweitzer PK, Jacoby JA, Soldatos CR (1981) Dose-response studies of quazepam. Clin Pharmacol Ther 30 194—200... 

The effects of itraconazole 100 mg/day for 14 days on the pharmacokinetics of a single oral dose of quazepam 20 mg and its two active metabolites have been studied in 10 healthy men in a double-blind, randomized, placebo-controlled crossover study (3). Itraconazole did not change the pharmacokinetics of quazepam but significantly reduced the peak plasma concentration and AUC of 2-oxoquazepam and N-desalkyl-2-oxoquazepam. Itraconazole did not affect psychomotor function. The results suggested that CYP3A4 is partly involved in the metabolism of quazepam. 

Kato K, Yasui-Furukori N, Fukasawa T, Aoshima T, Suzuki A, Kanno M, Otani K. Effects of itraconazole on the plasma kinetics of quazepam and its two active metabolites after a single oral dose of the drug. Ther Drug Monit 2003 25 473-7. 

Rebound insomnia occurs more often with short-acting and intermediate-acting benzodiazepines, when given in high doses and withdrawn abruptly. Conversely, very long-acting benzodiazepines (such as flurazepam and quazepam) show milder rebound effects. 

Lorazepam (la) in 2 or 4 mg doses showed hypnotic activity in insomniacs and good sedation in surgical premedication.41 Flurazepam (2h) is useful in the long term treatment of insomnia42 and shows no rebound effect after withdrawal.43 Flunitrazepam (2 ) has hypnotic activity in man at 2.5 mg, but does not induce physiological sleep.44 Fosazepam (2j) at 60-80 mg decreased sleep onset and awakening in healthy subjects.45 Quazepam (Sch 16134 2k) has been entered in the USAN listing as a sedative, hypnotic.46 Clobazam (9a) at 10—20 mg, but not triflubazam (9b) was useful for limited sleep difficulties in healthy males.47... 

The choice of a particular benzodiazepine is based on its pharmacokinetic profile. When used as a single dose, the extent of distribution and elimination half-life is important in predicting the duration of action. However, after multiple dosing, the elimination half-life and formation of active metabolites determine the extent of drug accumulation and resultant clinical effects." The benzodiazepine pharmacokinetic profiles are summarized in Table 71-4. The onset of action depends on the rate of absorption. Flurazepam and triazolam are absorbed rapidly. Temazepam is less lipophilic and has a slower onset of effect. Sedation after flurazepam, estazolam, and quazepam occurs within 1 to 2 hours after ingestion." Triazolam is redistributed quickly because of its high lipophilicity and thus has a short duration of effect." Estazolam and temazepam are intermediate in their duration of action. The therapeutic effects of flurazepam and quazepam are long in comparison because of the active metabolites. 

A-DAF accounts for most flurazepam pharmacologic effects. Quazepam and one of its metabolites, 2-oxo-quazepam, have elimination half-lives of 39 hours." Quazepam s oxo-quazepam metabolite is metabolized to A-DAF. If oxidation of A-DAE is impaired its half-life becomes prolonged, and complications of drug accumulation may result with repeated dosing however, tolerance may develop to these effects. A-DAE may be useful when daytime anxiety or early morning awakening are complaints, but daytime sedation and impaired psychomotor performance may complicate therapy. ... 

Midazolam markedly potentiates the anaesthetic action of haloth-ane. Similarly, the effects of propofol or thiopental are greater than would be expected by simple addition when midazolam is given concurrently, although the extent varies between the endpoints measured (analgesic, motor, hypnotic). Quazepam reduces induction time for propofol anaesthesia and premedication with diazepam reduces the dose of ketamine required. 

A study in 33 patients found that quazepam 15 or 30 mg given the night before induction of anaesthesia with propofol and fentanyl reduced the induction time when compared with a third group of patients not given a hypnotic. Quazepam did not affect blood pressure or heart rate, but the 30 mg dose of quazepam did increase anterograde amnesia. ... 

In a placebo-controlled study in 12 healthy subjects it was found that fluvoxamine 25 mg twice daily for 14 days had no effect on the pharmacokinetics of a single 20-mg dose of quazepam. However, formation of the metabolite 2-oxoquazepam was decreased, and there was a minor deerease in the sedative effects of quazepam at 4 hours, although these ehanges were considered to be of little clinical significance. ... 

St John s wort decreases the plasma levels of quazepam, although this did not reduce its effects in one study. Alprazolam appears not to interact, although this needs confirmation. The bioavailability of midazolam was reduced by long-term but not single doses of St John s wort... 

In a placebo-controlled study, 13 healthy subjects were given St John s wort (TruNature., hypericin content standardised at 0.3%) 300 mg three times daily for 14 days with a single 15-mg dose of quazepam on day 14. Although St John s wort did not affect the pharmacodynamic effects of quazepam it did decrease the quazepam AUC by 26% and the maximum plasma levels by 29%.This was attributed to the effects of St John s wort on the cytochrome P450 isoenzyme CYP3A4, by which quazepam is metabolised. ... 

In healthy volunteers orally administered a single dose of quazepam before or after oral administration of 900 mg St. John s wort daily for 14 days, a significant reduction in plasma levels of quazepam was observed after St. John s wort dosing. In subjective testing of volunteers, no significant effects of St. John s wort on quazepam activity were observed. Quazepam is metabolized by CYP3A4 (Kawaguchi et al. 2004). 

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