Zolpidem Caffeine

Cysneiros R, Farkas D, Harmatz JS, et al. Pharmacokinetic and pharmacodynamic interactions between zolpidem and caffeine. Clin Pharmacol Ther 2007 82 54-62. 

A 36-year-old woman with a history of psychiatric illness, including paranoid disorder, depression with panic episodes, and stress disorder, was found dead in bed. Caffeine, risperidone, and zolpidem were found in her urine. 

Clinically important, potentially hazardous interactions with acenocoumarol, alfuzosin, aminophylline, anisindione, anticoagulants, buprenorphine, butorphanol, caffeine, carmustine, dobazam, cocoa, dicumarol, dofetilide, duloxetine, epirubicin, eszopiclone, fentanyl, floxuridine, fluorouracil, galantamine, gliclazide, hydromorphone, itraconazole, ketoconazole, lidocaine, meptazinol, midazolam, mizolastine, modobemide, morphine, narcotic analgesics, oxprenolol, oxycodone, pentazocine, phenytoin, posaconazole, prednisone, propranolol, sufentanil, tolazoline, warfarin, xanthines, zaleplon, zofenopril, zolmitriptan, zolpidem... 

Also analyzed aspirin, chlordiazepoxide, chlorprothixene, clonazepam, caffeine, diazepam, doxylamine, ethosuximide, furosemide, haloperidol, hydrochlorothiazide, methocarbamol, methotrimeprazine, nicotine, oxazepam, procaine, promazine, propafenone, propranolol, salicylamide, temazepam, tetracaine, thiopental, triamterene, veraptimil, zolpidem, zopiclone... 

Simultaneous alimemazine, amitriptyline, amphetamine, bupivacaine, buprenorphine, clomipramine, cocaine, codeine, ethylmorphine, glafenine, meperidine, methampheta-mine, methotrimeprazine, morphine, norcodeine, nortriptyline, pentazocine Noninterfering acetaminophen, aspirin, barbiturates, benzoylecgonine, caffeine, diazepam, flunitrazepam, lidocaine, lorazepam, nalorphine, naloxone, nitrazepam, nordiaze-pam, norflunitrazepam, normorphine, oxazepam, prazepam, triazolam, zolpidem Interfering cyamemazine, desipramine, imipramine... 

The probable reason for the reduction in sedative effects with these drugs is that some of the components of tobacco smoke are enzyme inducers, which increase the rate at which the liver metabolises these benzodiazepines, thereby reducing their effects. The inference to be drawn is that smokers may possibly need larger doses than non-smokers to achieve the same therapeutic effects. Smoking also possibly reduces the drowsiness that the benzodiazepines and non-benzodiazepine hypnotics, such as zolpidem, can cause. However, one study suggested that caffeine intake, and others suggest age, may affect the response to benzodiazepines, so the picture is not altogether clear. Whether any of these interactions has much clinical relevance awaits assessment. 

Zopiclone appears to counter the stimulant effects of caffeine more easily than caffeine counters the sedative effects ofzopiclone. No pharmacokinetic interaction occurred between zolpidem and caffeine (given as one cup of coffee containing caffeine 300 mg), and the hypnotic effects of zolpidem were unchanged. ... 

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