Drug interactions with anxiolytics and hypnotics (Table 8.14L)

Drug interactions with anxiolytics and hypnotics (Table 8.14L)

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Anxiolytics include benzodiazepines and buspirone. Hypnotics include benzodiazepines, zolpidem and zopiclone.
Drug	Rating [NB1]	Interaction	Recommended action
Analgesics, opioid (including tramadol)	2	Respiratory depression with benzodiazepines, especially if given parenterally.	Monitor for respiratory depression.
Antiretrovirals: ritonavir, saquinavir	3	Increase plasma concentration of alprazolam, buspirone and triazolam (CYP3A4 inhibition).	Monitor for adverse effects. Consider use of an alternative anxiolytic or hypnotic, eg lorazepam, oxazepam or temazepam.
Azole antifungals: fluconazole, itraconazole, ketoconazole	2	May increase plasma concentrations of alprazolam, triazolam, buspirone, zolpidem and zopiclone (CYP3A4 inhibition).	Monitor for adverse effects. Use an alternative benzodiazepine or alternative antifungal drug, eg terbinafine.
Calcium channel blockers	3	Diltiazem and verapamil may increase plasma concentrations of buspirone and triazolam (CYP3A4 inhibition).	Monitor for adverse effects. Use an alternative calcium channel blocker or alternative anxiolytic, eg lorazepam, oxazepam or temazepam.
Cimetidine	3	Increases plasma concentrations of alprazolam, diazepam, nitrazepam and triazolam (CYP3A4 inhibition).	Monitor for adverse effects. Use an alternative H2-receptor blocker or alternative benzodiazepine, eg lorazepam, oxazepam or temazepam.
Clarithromycin -
Disulfiram	3	Decreases diazepam metabolism.	Monitor for adverse effects. Use an alternative drug, eg alprazolam, oxazepam or lorazepam.
ECT	2	Benzodiazepines raise seizure threshold, which may impair the efficacy of the ECT.	Taper and cease benzodiazepines before ECT.
Erythromycin -
Esomeprazole -
Macrolide antibiotics: clarithromycin, erythromycin	2	Increase plasma concentrations of alprazolam, triazolam, buspirone, and zopiclone (CYP3A4 inhibition).	Monitor for adverse effects. Use an alternative antibiotic, eg roxithromycin, or alternative anxiolytic, eg lorazepam, oxazepam or temazepam.
MAOIs, irreversible nonselective	3	Hypertension reported rarely with buspirone.	Monitor for increased blood pressure or use an alternative drug.
Nefazodone -
Omeprazole -
Proton pump inhibitors: esomeprazole, omeprazole	3	Decreased clearance of diazepam reported (possibly inhibition of CYP3A, CYP2C9 or CYP2C19).	Monitor for adverse effects of diazepam or use alternative benzodiazepine or alternative proton pump inhibitor, eg rabeprazole
Rifabutin, rifampicin	3	Increased buspirone, diazepam, nitrazepam, triazolam, zolpidem and zopiclone metabolism. Temazepam not affected.	Monitor for decreased effect of anxiolytic or hypnotic.
Ritonavir -
Saquinavir -
SSRIs and nefazodone	2	Nefazodone inhibits metabolism (CYP3A4) of alprazolam, triazolam and zopiclone. Fluoxetine and fluvoxamine increase plasma alprazolam and diazepam concentrations. Unlikely with paroxetine or sertraline.	Monitor for benzodiazepine adverse effects or use alternative anxiolytic, eg lorazepam, oxazepam or temazepam.
	3	Several reports of adverse effects with fluoxetine and buspirone.	Monitor for increased adverse effects such as worsening of psychiatric symptoms, serotonergic effects or seizure with buspirone and fluoxetine.
Tramadol -
NB1: Rating 1 – Avoid combination; risk always outweighs benefit. Rating 2 – Usually avoid combination; use combination only under special circumstances. Rating 3 – Minimise risk; take action as necessary to reduce risk.