Drug Profile

Do Not Use: Zaleplon (SONATA) is less effective than related drugs and can cause addiction.

Zaleplon is a sleeping pill that works the same way as the benzodiazepine sleeping pills for short-term relief of insomnia.[1] Like benzodiazepines, this drug is regulated as a controlled substance because of its potential to cause dependence.

Experts and researchers agree that zaleplon is not better than other available alternative prescribed medications on the market.

Patients should keep in mind that nondrug treatment is a viable option for managing insomnia.

Adverse effects

There have been reports of sleepwalking (inappropriate or strange automatic behavior while asleep, including binge eating and house painting) and serious allergic reactions in patients using sleeping pills such as zaleplon.[2]

In 2019, the FDA required that a black-box warning be added to the product labeling for zaleplon about complex sleep behaviors, including sleepwalking, sleep driving and engaging in other activities while not fully awake, that are associated with use of the drug. The warning notes that these events may result in serious injury or death and that the drug should be discontinued immediately if a patient experiences such sleep behaviors.[3]

The drug also increases the risk of hip fractures in elderly patients.[4]

After taking the first or subsequent doses of sedative hypnotics, including zaleplon, patients have reported rare cases of angioedema (swelling) involving the tongue, glottis and larynx.[5]

Studies say...

The editors of The Medical Letter on Drugs and Therapeutics found that zaleplon is “less potent and has a shorter duration of action than zolpidem (AMBIEN).”[6]

The Food and Drug Administration (FDA) medical officer who reviewed zaleplon had a similar opinion. He found the effects of this drug to be “mild to modest at best, yet they are comparable to active comparitors [sic, other sleeping pills].”

In the five clinical trials submitted to the FDA by then-manufacturer Wyeth-Ayerst in support of zaleplon’s approval, the median decrease in time to sleep onset ranged from only 8 to 20 minutes in patients taking zaleplon compared with those using an inactive placebo. Zaleplon was not consistently more effective than a placebo in the total time slept or the number of awakenings experienced by patients during the night.[7]

One meta-analysis compared the effectiveness of drug treatment with that of behavioral therapy in the management of persistent insomnia. The authors of the study concluded: “Overall, behavior therapy and pharmacotherapy produce similar short-term treatment outcomes in primary insomnia.”[8] Nondrug treatment is a viable option for managing insomnia.

A March 2014 study in the U.K. found an increase in the risk of death in people using tranquilizers or sleeping pills compared with people not using them. The results were similar to those from a 2012 study. Concerns about the effect of these drugs on premature mortality have been fueled by studies documenting increased risk of dementia, daytime fatigue, lack of coordination, falls, road traffic incidents, pneumonia and other infections.[9]

This is one of a limited number of drugs for which the FDA requires an FDA-approved Medication Guide to be dispensed when the prescription is filled. (By clicking here you can see the Medication Guide for this drug.) An FDA advisory committee has unanimously recommended that all prescription drugs be accompanied by such Medication Guides, but at present, less than 5% of drugs are. The other 95% of drugs are accompanied by unregulated, often dangerously incomplete information leaflets not approved by the FDA.[10]

Interactions with other drugs

The following products can cause “highly clinically significant” or “clinically significant” interactions when used together with zaleplon. The table below includes potentially serious interactions listed in the drug’s FDA-approved professional package insert or in published medical journal articles. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. Patients should be sure to tell their doctors and pharmacists the drugs they are taking and whether they are taking any of these interacting drugs:

Drugs That Can Interact With Zaleplon

Regulatory actions surrounding zaleplon

2007: In March, the FDA asked manufacturers of sedative hypnotic drugs, such as zaleplon, to update the drug product labels concerning potential risks associated with use of these medications, including “severe allergic reactions and complex sleep-related behaviors.” Allergic reactions included anaphylaxis (severe allergic reaction) and angioedema. Complex sleep-related behaviors included sleep-driving, making phone calls and preparing and eating food while asleep.

The following medications were specifically mentioned in the FDA advisory:

• zolpidem (AMBIEN/AMBIEN CR — Sanofi Aventis)
• butabarbital (BUTISOL SODIUM — Medpointe Pharmaceuticals HLC)
• pentobarbital and carbromal (CARBRITAL — Parke-Davis)
• flurazepam (DALMANE — Valeant Pharmaceuticals)
• quazepam (DORAL — Questcor Pharmaceuticals)
• triazolam (HALCION — Pharmacia & Upjohn)
• eszopiclone (LUNESTA — Sepracor)
• ethchlorvynol (PLACIDYL — Abbott)
• estazolam (PROSOM — Abbott)
• temazepam (RESTORIL — Tyco Healthcare)
• ramelteon (ROZEREM — Takeda Pharmaceutical)
• secobarbital (SECONAL — Eli Lilly)
• zaleplon (SONATA — King Pharmaceuticals)[11]