Lorazepam drug interactions

FLUOXETINE, FLUVOXAMINE, PAROXETINE BZDs - ALPRAZOLAM, DIAZEPAM, MIDAZOLAM t in plasma concentrations of these BZDs. Likely t sedation and interference with psychomotor activity Alprazolam, diazepam and midazolam are subject to metabolism by CYP3A4. Fluvoxamine, fluoxetine and possibly paroxetine are inhibitors of CYP3A4 sertraline is a weak inhibitor. SSRIs are relatively weak compared with ketoconazole, which is possibly 100 times more potent as an inhibitor Warn patients about risks associated with activities that require alertness. Consider use of alternatives such as oxazepam, lorazepam and temazepam, which are metabolized by glucuronidation >- For signs and symptoms of CNS depression, see Clinical Features of Some Adverse Drug Interactions, Central nervous system depression... 

In addition to pharmacokinetic drug-drug interactions, pharmacodynamic effects have been reported as well. Halothane increases the susceptibility to ventricular arrhythmias under theophylline therapy as a result of increased sensitivity of the myocardium to endogenous catecholamine release by theophylUne. Ketamine lowers the theophyUine seizure threshold. Benzodiazepines Uke midazolam, diazepam, lorazepam, and Uurazepam increase the central nervous system concentration of adenosine, a potent central nervous system depressant. As theophyUine also blocks adenosine receptors, it counteracts benzodiazepine-induced sedation, resulting in increased dosage requirements for these compounds. ... 

Oxycodone/Lorazepam/Ethanol Multiple oral doses of pregabalin were coadministered with oxycodone, lorazepam, or ethanol. Although no pharmacokinetic interactions were seen, additive effects on cognitive and gross motor functioning were seen when pregabalin was coadministered with those drugs. 

The potentiation of sedative effects from benzodiazepines when combined with centrally acting drugs with antihistamine properties (for example first-generation antihistamines, tricyclic antidepressants, and neuroleptic drugs) can pose problems (143). Antihistamines that do not have central actions do not interact with benzodiazepines as in the case of mizolastine and lorazepam (144), ebastine and diazepam (145), and terfenadine and diazepam (143). 

The metabolism of lorazepam (e.g., Ativan), oxazepam (e.g., Serax), and temazepam (e.g., Restoril) are not likely to be affected, and one of these agents may be preferred when a benzodiazepine is indicated in a patient being treated with cimetidine. The experience with ranitidine (e.g., Zantac), famotidine (Pepcid), and nizatidine (Axid) suggests that these agents are not likely to inhibit hepatic enzyme systems, and these other histamine H2-receptor antagonists are less likely than cimetidine to interact with other drugs that are metabolized via these pathways. 

Oral contraceptives alter the metabolism of some benzodiazepines that undergo oxidation (alprazolam, chlordiazepoxide, diazepam) or nitroreduction (nitrazepam) (166). For these drugs, oral contraceptives inhibit enzyme activity and reduce clearance. There is nevertheless no evidence that this interaction is of clinical importance. It should be noted that for other benzodiazepines that undergo oxidative metabolism, such as bromazepam or clotiazepam, no change has ever been found in oral contraceptive users. Some other benzodiazepines, such as lorazepam, oxazepam, and temazepam, are metabolized by glucuronic acid conjugation. The clearance of temazepam was increased when oral contraceptives were coadministered, but the clearances of lorazepam and oxazepam were not (167). Again, it is unlikely that this is an interaction of clinical importance. 

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. 

Benzodiazepines such as lorazepam, oxazepam and temazepam, which are mainly conjugated without prior phase I metabolism, are unlikely to be involved in interactions with inhibitors or inducers of cytochrome P450. Benzodiazepines themselves do not significantly induce cytochrome P450 isoenzymes, so interactions involving enhanced metabolism of other drugs are not usual. 

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. 

A man with sehizophrenia taking tryptophan, lorazepam, vitamin C, ben-zatropine and nicotinic acid, developed a severe urticarial rash covering his faee, neek and trunk 3 days after starting clozapine 150 mg daily. All of the drugs except lorazepam were stopped, and the rash subsided. It did not recur when clozapine was restarted, even at a dose of 600 mg daily, nor when small doses of benzatropine and fluphenazine were briefly added. The authors draw the inference that tryptophan, vitamin C and nicotinic acid may have been responsible for this alleged interaction with clozapine. ... 

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