Ambien and Nicotine Interaction Profile: What Smokers Need to Know Before Taking Zolpidem

Does the Ambien label mention nicotine or smoking?

The Ambien drug interactions section includes alcohol and other CNS depressants, opioids, imipramine, chlorpromazine, sertraline, fluoxetine, haloperidol, rifampin, St. John's wort and ketoconazole; neither nicotine nor tobacco smoke appears in it [1]. The same section states that 'the effect of drugs that induce or inhibit other P450 enzymes on the exposure to zolpidem is not known' [1]. CYP1A2 is one of those other enzymes, and absence from an interactions list does not mean the combination has been shown safe.

Why cigarette smoke, not nicotine, is the enzyme story

Polycyclic aromatic hydrocarbons in tobacco smoke are believed to be responsible for induction of CYP1A1 and CYP1A2, and possibly CYP2E1 [2][3]. Nicotine is not the inducer: a review of drugs affected by quitting states the enzyme effect is not related to the nicotine component of tobacco, so nicotine replacement will not alter it [4]. A single rat dose of nicotine raised lung CYP1A1 activity 4.4-fold at 6 hours and 14.7-fold at 12 hours without significantly changing liver CYP1A2 protein or mRNA; human relevance is unknown [7].

In 12 people smoking 20 or more cigarettes a day who stopped abruptly, caffeine clearance, a marker of CYP1A2 activity, fell 36.1%, from 2.47 to 1.53 mL/min/kg, with an apparent half-life of the decline of 38.6 hours [8]. This shows that smoking-related CYP1A2 activity can change quickly after quitting.

What nicotine does to sleep on its own

A 2009 review of 52 studies reported that during nicotine consumption the main findings were insomnia symptoms: increased sleep latency, fragmentation, decreased slow-wave sleep, reduced sleep efficiency and daytime sleepiness, with most studies indicating REM suppression [6]. In a double-blind crossover trial, 20 non-smoking habitual snorers wore an 11 mg/24 h nicotine patch or placebo overnight; nicotine cut total sleep by 33 minutes, dropped sleep efficiency from 89.7% to 83.5%, reduced REM from 18.8% to 15.1% of sleep and lengthened sleep onset from 6.7 to 18.2 minutes [5]. Nicotine is also a stimulant, causing vasoconstriction, tachycardia and higher blood pressure [2].

What the Ambien label flags

Ambien carries a boxed warning for complex sleep behaviors such as sleep-walking and sleep-driving, which the label says can occur after the first or any later dose at recommended doses, with or without alcohol or other CNS depressants [1]. The label says next-day impairment risk rises with dose, with less than 7 to 8 hours of sleep remaining, and with alcohol, other CNS depressants or drugs that raise zolpidem levels. It gives the recommended initial dose as 5 mg for women and 5 or 10 mg for men, taken once nightly immediately before bed with at least 7 to 8 hours remaining before waking [1].