Alprazolam dosage

A placebo-controlled study in 12 healthy subjects found that nefazodone 200 mg twice daily caused an almost twofold increase in the plasma levels of alprazolam 1 mg twice daily taken for 7 days. Another study found that impairment of psychomotor performance and increased sedation occurred when nefazodone was given with alprazolam. A case report describes benzodiazepine withdrawal symptoms in a woman taking alprazolam after nefazodone was withdrawn following several years of concurrent use. She needed an alprazolam dosage increase from 500 micrograms to 4 mg daily to control her symptoms. ... 

VALIDATED HPTLC DETERMINATION AND CONTENT UNIFORMITY TEST FOR ALPRAZOLAM AND MELATONINE IN TABLET DOSAGE FORM... 

The benzodiazepines currently available for clinical use vary substantially in pharmacokinetics, acute euphoriant effects, and frequency of reported dependence. It is likely, therefore, than not all benzodiazepines have the same potential for abuse. Diazepam, lorazepam, and alprazolam may have greater abuse potential than chlordiazepoxide and clorazepate (Wolf et al. 1990). Similarly, oxazepam has been reported to produce low levels of abuse (Eliding 1978). Jaffe et al. (1983) found that in recently detoxified alcoholic patients, halazepam produces minimal euphoria even at a supratherapeutic dosage. The development of partial agonist and mixed agonist/antagonist compounds at the benzodiazepine receptor complex may offer an advantage over approved benzodiazepines for use in alcoholic patients. 

Tr/azo/obenzocf/azep/nes-Triazolam and alprazolam, metabolized by cytochrome P-450 3A4, have increased plasma concentrations when administered concomitantly with nefazodone. If triazolam is coadministered with nefazodone, a 75% reduction in the initial triazolam dosage is recommended. It is recommended that triazolam not be used in combination with nefazodone. No dosage adjustment is required for nefazodone. 

For most child psychiatrists, the drug interactions most frequently encountered are interactions with other psychotropics. Fluoxetine inhibits the CYP3A isozymes and thus increase the plasma concentration of the tria-zolobenzodiazepines (alprazolam, midazolam, and triazolam), causing increased psychomotor effects (Shader and Greenblatt, 1995). To avoid unwanted psychomotor effects, the dosage of alprazolam should be decreased when it is coadministered with fluoxetine (Chouinard et ah, 1999). Nefazadone has also been shown to increase the pharmacodynamic effects of triazolam and, to a lesser extent, alprazolam (Chouinard et ah, 1999). 

Finally, it should be stressed again that certainly not all benzodiazepine prescribing to opioid maintenance patients need be long term. McDuff et al. (1993) reported on detoxification from alprazolam, the benzodiazepine most commonly used by their methadone subjects. With methadone dosage usually remaining the same, patients were offered a set reducing course of alprazolam over 11 weeks. Of 22 patients, four refused the treatment and 12 out of 18 subsequently completed detoxification, although timescales in practice proved variable. In a comparative study by Weizman et al. (2003) just over a quarter of benzodiazepine-dependent methadone maintenance patients remained free of benzodiazepines... 

Some evidence indicates that patients maintained on alprazolam therapy may require lower doses than those used initially. As noted earlier, Nagy et al. ( 35) found that many patients sustained their improvement with lower dosages, and others have reported similar findings ( 32, 38). By contrast, Rashid et al. (39) found an increase in alprazolam dose over time. 

Like alprazolam, clonazepam may cause treatment-emergent depression in some patients. Pollack et al. (42) also reported that only 10% of their patients who remained on clonazepam had a history of depression, although 47% lost to follow-up and 30% who eventually required alternate treatment had histories of dysthymia or depression. Of 31 patients without a prior history of affective illness, depression developed in three on low daily dosages (0.75, 1.5, and 2 mg), one was switched to alprazolam, and the others responded to the addition of desipramine or imipramine. These investigators recommend that, until further data are available, PD patients with chronic or concurrent depression should not be given clonazepam alone and that those in whom depression develops during clonazepam therapy should have their dose lowered or an adjunctive antidepressant added. 

Most of the minor tranquilizers in the BZD exhibit similar clinical effects they differ primarily in their duration of action and in the dosage required to achieve the same effect. The BZDs are classified as short- (triazolam [Halcion]), intermediate- (alprazolam [Xanax] and lorazepam [Ativan]), and long-acting (chlordiazepoxide [Librium] and diazepam [Valium]). Of the various BZDs available in the United States in 2002, those primarily prescribed as anxiolytics and hypnotics include the intermediate- and long-acting variety. 

Figure 2 Mean ( SE) plasma concentrations of triazolam (left) or alprazolam (right) in a series of healthy individuals who participated in a clinical pharmacokinetic study. In one phase of the study, they ingested a single 0.25-mg oral dose of triazolam with ketoco-nazole, 200 mg twice daily, or with placebo to match ketoconazole (control). In the second phase of the study, they took 1.0 mg of alprazolam orally, either with the same dosage of ketoconazole or with placebo to match ketoconazole (control). Note that ketoconazole increases AUC and reduces clearance of both triazolam and alprazolam. For triazolam (a high-extraction compound), the effect is evident as reduced presystemic extraction, increased Cmax, and prolonged half-life. However, for alprazolam (a low-extraction compound), the effect of ketoconazole is evident only as a prolongation of half-life. Abbreviation AUC, the plasma concentration-time curve. Source Adapted, in part, from Ref. 74.

In a study conducted on 13 patients with chronic psychiatric conditions who had received therapeutic dosage of benzodiazepines for several months, Sramek et al.3 were able to detect diazepam (0.2-1.6 ng/mg), but alprazolam and lorazepam were not detected. Inspection of diazepam results were not suggestive of a correlation between dosage and hair concentration. 

Alprazolam and alprazolam XR generally dosed abouf one fenfh fhe dosage of diazepam... 

Clonazepam is generally dosed half the dosage of alprazolam... 

Via CYP450 3A4 inhibition, fluvoxamine may reduce clearance of carbamazepine and benzodiazepines such as alprazolam and triazolam, and thus require dosage reduction... 

M. Hossain, E. Wright, R. Baweja, T. M. Ludden, and R. Miller, Nonlimear mixed effects modeling of single dose and multiple dose data for an immediate release (IR) and controlled release (CR) dosage form of alprazolam. Pharm Res 14 309-315 (1997). 

Benzodiazepine dosage reqnirements vary widely among patients and mnst be individnahzed. Therapy shonld be initiated using low doses (e.g., diazepam 2 mg three times daily, alprazolam 0.25 mg three times a day or eqnivalent doses of other benzodiazepines) and titrated npward to reheve anxiety symptoms and avoid adverse events. After an initial treatment response is achieved, agents with long elimination half-hves can be dosed at bedtime. Dosage adjustments shonld be made weekly. Three to four weeks of a daily dose at the maximum dose constitutes an adeqnate clinical trial. ... 

Patients taking alprazolam, clonazepam, or imipramine for up to 8 months maintained antipanic efficacy without dosage increases, suggesting that tolerance does not develop to the antipanic effects of these agents. The most important determinant of compliance with... 

Fluvoxamine inhibits liver drug-metabolizing enzymes. Dosages of alprazolam, theophylline, and warfarin must be reduced if any of these drugs are given concomitantly with fluvoxamine. Nefazodone may also decrease the metabolism of benzodiazepines, and venlafaxine may inhibit haloperidol metabolism. The answer is (B). 

It is very difficult to assess and compare the results of the very many studies of this interaction because of the differences between the tests, their duration, the dosages of the benzodiazepines and alcohol, whether given chronically or acutely, and a number of other variables. However, the overall picture seems to be that benzodiazepines and related drugs including diazepam, " alprazolam,bromazepam, brotizolam, chlo-rdiazepoxide, " clobazam, dipotassium clorazepate, flunitrazepam, flurazepam, loprazolam, " lorazepam, lormetazepam, medazepam, midazolam, nitrazepam, " " oxazepam, temazepam, " triazolam, and zopiclone enhance the effects of alcohol i.e. cause increased drowsiness, impaired performance and driving skills. 

The effects of alprazolam and brotizolam are increased and prolonged by ketoconazole and itraconazole, but the extent of this is less than that seen with midazolam or triazolam. However, some dosage reductions may still be necessary. 

There seems to be only one report (with temazepam) of a olinieally signif-ieant interaction between disiifiram and the benzodiazepines, and this report is unconfirmed, as the patient did not take temazepam alone. The other reports only describe potential interactions that have been identified by single-dose studies. These do not necessarily reliably predict what will happen in practice. However, it seems possible that some patients will experience increased drowsiness, possibly because of this interaction, and because drowsiness is a very common adverse effect of disulfiram. Reduce the dosage of the benzodiazepine if necessary. Benzodiazepines that are metabolised by similar pathways to diazepam and chlordiazepoxide, may possibly interact in the same way (e.g. bromazepam, clonazepam, clorazepate, prazepam, ketazolam, clobazam, flurazepam, nitrazepam, medazepam) but this needs confirmation. Alprazolam, oxazepam and lo-razepam appear to be non-interacting alternatives. 

The interactions of nefazodone with alprazolam, midazolam, triazolam and zopiclone are established and clinically important. The practical consequences are that the effects of alprazolam, midazolam and triazolam are expected to be increased but the extent is uncertain. Be alert for any evidence of any psychomotor impairment, drowsiness etc. and reduce the benzodiazepine dosage if necessary. More study is needed. Lorazepam does not interact with nefazodone. There seems to be no direct information about other benzodiazepines and related drugs. 

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