Omeprazole benzodiazepines

Amiodarone Benzodiazepines Chloramphenicol Cimetidine Disulfiram Ethanol (acute ingestion) Fluconazole Isoniazid Metronidazole Miconazole Omeprazole Phenacemide Phenylbutazone Succinimides Sulfonamides Trimethoprim Valproic acid Salicylates Tricyclic antidepressants Valproic acid... 

Diazepam (Valium, Diastat) [C-IVj [Anxiolytic, Skeletal Muscle Relaxant, Anticonvulsant, Sedative/Hypnotic/ Benzodiazepine] Uses Anxiety, EtOH withdrawal, muscle spasm, status epilepticus, panic disorders, amnesia, preprocedure sedation Action Benzodiazepine Dose Adults. Status epilepticus 5-10 mg IV/IM Anxiety 2-5 mg IM/IV Preprocedure 5-10 mg IV just prior to procedure Peds. Status epilepticus 0.5-2 mg IV/IM Sedation 0.2-0.5 mg/kg IV (onset w/in 5IV and 30 min IM duration about 1 h IV and IM) Caution [D, / -] Contra Coma, CNS depression, resp d es-sion, NAG, severe uncontrolled pain, PRG Disp Tabs 2, 5, 10 mg soln 1, 5 mg/mL inj 5 mg/mL rectal gel 2.5, 5, 10, 20 mg/mL SE Sedation, amnesia, bradycardia, i BP, rash, X resp rate Interactions T Effects W/ antihistamines, azole antifungals, BBs, CNS depressants, cimetidine, ciprofloxin, disulfiram, INH, OCP, omeprazole, phenytoin, valproic acid, verapamil, EtOH, kava kava, valman T effects OF digoxin, diuretics X effects w/ barbiturates, carbamazepine. 

Zhao and Lou [164] studied the metabolism of omeprazole to its two major metabolites, hydroxyomeprazole and omeprazole sulfone, in rat liver microsomes by a reversed-phase HPLC assay. The formation of metabolites of omeprazole depended on incubation time, substrate concentration, microsomal protein concentration, and was found to be optimal at pH 7.4. The Pmax and Km of omeprazole hydroxylation in the rat liver microsomal preparation were 2033 nmol /(min mg protein), and 46.8 ymol/l, respectively. The effects of seven drugs on omeprazole metabolism were tested. Mephenytoin, five benzodiazepines and pava-verine caused inhibition of omeprazole metabolism. 

Omeprazole can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

Benzodiazepines, profens, sulphonamidcs, P-blockers, barbiturates, hydantoins, omeprazole, mefloquine, chlorthalidone, sulphoxides, 1, r -binaphth-2,2 -diol 0.0 -bis(3,5-dimethylbenzoyl)-/V.fV -diallyl-(/ ./ )-tartaric acid diamide (Kromasil CHI-DMB) 11941... 

CYP2C19 Benzodiazepines diazepam Antidepressants imipramine, amitriptyline, clomipramine, citalopram Others propranolol, hexobarbital, mephobarbital, proguanil, omeprazole, S-mephenytoin 2 no activity 23%-39% in Asians 13% in Caucasians 25% in African Americans 3 no activity 6%-10% in Asians 0% in others... 

Ketoconazole and other azoles Benzodiazepines, cisapride, cyclosporine, fluoxetine, lovastatin, omeprazole, quinidine, toibutamide, warfarin Risk of toxicity due to inhibition of metabolism of these drags... 

The UK manufacturers report that in interaction clinical studies there was no evidence of clinically relevant interactions between letrozole and other commonly prescribed drugs, namely benzodiazepines such as diazepam, barbiturates, diclofenac, fiirosemide, ibuprofen, omeprazole, and paracetamol (acetaminophen). ... 

Gait disturbances (attributed to benzodiazepine toxicity) occurred in two patients given triazoiam and lorazepam or flu-razepam with omeprazoie, and another patient taking diazepam and omeprazole became wobbly and sedated. Lansoprazole, pan-toprazole, or rabeprazole appear not to interact to a clinically relevant extent with diazepam. Diazepam serum levels are increased by esomeprazole but the clinical relevance of this is unknown. 

Two elderly patients, both smokers, taking triazolam with lorazepam or flurazepam, developed gait disturbances when they were given omeprazole 20 mg daily. They rapidly recovered when eitherthe benzodiazepines or the omeprazole were stopped. A brief report deseribes a patient taking omeprazole who became wobbly and sedated by small, unspeeified doses of diazepam, and another report describes a patient who developed toxie levels of nordiazepam and remained unconscious for 13 days after reeeiv-ing a high dose of clorazepate (1500 mg over about 29 hours) and omeprazole 80 mg daily. ... 

Information is limited, but what is eurrentiy known suggests that patients given omeprazole, and possibly esomeprazole, with diazepam may expe-rienee inereased benzodiazepine effeets (sedation, unstable gait ete). If this oeeurs the benzodiazepine dosage should be reduced. Lansoprazole, pantoprazole and rabeprazole do not appear to interaet with diazepam. 

Further, an in vitro study suggests that omeprazole may possibly interaet similarly with midazolam," although this needs confirmation. There seems to be no information regarding other benzodiazepines. 

Kfeirti-Masso JF, Lopez de Munain A, Lopez de Dicastillo G. Ataxia following gastric bleed-ii due to omeprazole-benzodiazepine interaction Ann Pharmacother( 99 26,429-30. 

Usually, diazepam is dosed according to individual susceptibility, and the possibility of high plasma levels reached in poor metabolizers is not thought to constitute a need for drug monitoring. Hence not much relevance can be attributed to the action of 20 mg of omeprazole. For general reasons, the use of benzodiazepines that are not subject to phase I metabolism (e.g., oxazepam) is advisable in the elderly and those with severely impaired hepatic function [47]. The same may hold for the use of high-dose omeprazole. 

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