Zolpidem Side Effects: Common Reactions, FDA Boxed Warning and Safety Tips

Short answer: The most common zolpidem side effects are drowsiness, dizziness, headache, a “drugged” feeling and stomach upset such as diarrhea or nausea. The most serious risks are complex sleep behaviors (sleepwalking, sleep driving and other activities done while not fully awake), which carry an FDA boxed warning, plus next-morning impairment, dangerous sedation when combined with alcohol or opioids, and dependence with longer use. If you take zolpidem (Ambien, Ambien CR, Edluar, Intermezzo, Zolpimist), use the lowest dose your prescriber recommends, allow a full 7 to 8 hours in bed, and call your doctor about any unusual nighttime behavior.

Key Takeaways

• Common side effects include daytime drowsiness, dizziness, headache, diarrhea and a “drugged” feeling. In the Ambien label’s longer trials, dizziness and a drugged feeling were the most frequent complaints.^[4]
• Since 2019, zolpidem carries an FDA boxed warning for complex sleep behaviors. The FDA reviewed 66 cases with serious injury or death, 20 of them fatal.^[2]
• In 2013 the FDA lowered the recommended starting dose for women to 5 mg (immediate release) and 6.25 mg (extended release) because enough drug can remain in the blood the next morning to impair driving.^[3]
• Never mix zolpidem with alcohol, and use extra caution with opioids, benzodiazepines or other sedatives because the combined effect on alertness and breathing can be dangerous.^[1][4]
• Zolpidem is a Schedule IV controlled substance meant for short-term use. Do not stop suddenly after weeks of use without a plan from your prescriber.^[1][4]

What Zolpidem Is and How It Works

Zolpidem is a prescription sedative-hypnotic used to treat insomnia. It is sold as immediate-release tablets (Ambien), extended-release tablets (Ambien CR), sublingual tablets that dissolve under the tongue (Edluar and Intermezzo) and an oral spray (Zolpimist).^[1] It belongs to a group sometimes called “Z-drugs,” along with eszopiclone (Lunesta) and zaleplon (Sonata). All three share the same FDA boxed warning, described below.

Zolpidem acts quickly and, in healthy adults, has a short average elimination half-life of about 2.5 hours according to the prescribing information.^[4] That short half-life is one reason it is popular, but it does not mean the drug is gone by morning for everyone. Women clear zolpidem more slowly than men, and the label reports peak levels and total exposure about 45% higher in women at the same dose. In people with cirrhosis, the average half-life stretches to roughly 9.9 hours.^[4] Those differences explain much of the side effect pattern described below.

Common Zolpidem Side Effects

Most people who take zolpidem as directed have mild side effects or none at all. According to MedlinePlus and the Cleveland Clinic, the side effects reported most often include:^[1][5]

• Drowsiness, tiredness or a “drugged” feeling, including the next day
• Dizziness, lightheadedness and unsteady walking or balance problems
• Headache
• Diarrhea, nausea, constipation, gas, heartburn or stomach pain
• Unusual dreams
• Dry mouth or throat; tongue irritation with the under-the-tongue forms
• Muscle or joint aches, numbness or tingling in the hands or feet

In the Ambien label’s short-term trials (up to 10 nights), the adverse reactions that occurred more often than with placebo included drowsiness (2%), dizziness (1%) and diarrhea (1%). In longer trials of 28 to 35 nights, dizziness (5%) and a drugged feeling (3%) stood out.^[4] These figures describe how much more often the effect appeared compared with placebo, not the total share of users who noticed it.

Serious Side Effects and the FDA Boxed Warning

Complex sleep behaviors

On April 30, 2019, the FDA added its strongest warning, a boxed warning, to zolpidem, eszopiclone and zaleplon. The warning covers complex sleep behaviors: sleepwalking, sleep driving, preparing and eating food, making phone calls, having sex or doing other activities while not fully awake, usually with no memory of the event afterward.^[1][2]

The FDA identified 66 cases of complex sleep behaviors that led to serious injuries or death: 62 from its adverse event reporting system and 4 from the medical literature. Twenty were fatal. Reported outcomes included falls with brain bleeding or fractures, fatal car crashes, hypothermia, carbon monoxide poisoning, burns, near drowning, gunshot wounds and suicide attempts.^[2] The agency stressed three points that surprise many patients:

• The behaviors occurred even at the lowest recommended doses.
• They can happen after just one dose, not only after long-term use.
• They can happen with or without alcohol or other sedating drugs.^[2]

Anyone who has had a complex sleep behavior on zolpidem, eszopiclone or zaleplon should not take these drugs again; the label lists this as a contraindication.^[2][4] If you or someone in your household notices signs that you did things you cannot remember (food missing, a moved car, messages you do not recall sending), stop the medicine and call your prescriber right away.

Other serious reactions

Call your doctor promptly, or seek emergency care if symptoms are severe, if you notice:^[1][4][5]

• Allergic reactions: hives, swelling of the face, lips, tongue or throat, a feeling that the throat is closing, or trouble breathing or swallowing. Anaphylaxis and angioedema are listed in the label.
• Behavior and mood changes: aggression, agitation, confusion, hallucinations, feeling outside your body, memory problems, new or worsening depression, or suicidal thoughts.
• Breathing problems: slowed or shallow breathing, especially in people with sleep apnea or lung disease.
• Other warning signs: yellow skin or eyes, light-colored stools, persistent vomiting, racing heartbeat, chest pain or vision changes.

Next-Morning Impairment and Dosing Differences

Feeling awake does not guarantee you are safe to drive. Zolpidem can leave enough drug in the blood the next morning to slow reaction time, reduce alertness and impair coordination, even when you feel fine.^[1][3] MedlinePlus advises against driving or operating machinery the day after taking an extended-release product and asks users of other forms to discuss next-day risk with their doctor.^[1]

In 2013 the FDA required lower recommended doses because next-morning levels were high enough in some people to impair driving. Women appeared more susceptible because they clear the drug more slowly, and extended-release forms carried the highest risk.^[3] The current label also recommends a 5 mg dose for older or debilitated adults and for people with mild to moderate liver impairment, and says to avoid zolpidem in severe liver impairment.^[4]

Sources: FDA and Ambien label.^[3][4] Always follow your own prescription.

A few practical rules lower the risk of next-day impairment:^[1][3][4]

• Do not take a bedtime dose unless you can stay in bed for a full 7 to 8 hours.
• Do not take a second dose, or a second sleep product, in the same night.
• Take it without food or not right after a meal; MedlinePlus notes it works faster that way.
• Do not drive until you know how the medicine affects you the next morning.

Who Should Not Take Zolpidem (or Needs Extra Caution)

Zolpidem is not right for everyone. Tell your prescriber about every condition below before starting.^[1][4]

• Prior complex sleep behavior on zolpidem, eszopiclone or zaleplon: do not take it.
• Known allergy to zolpidem: do not take it.
• Adults 65 and older: MedlinePlus says older adults should not usually take zolpidem because safer or more effective options exist; falls and confusion are a particular concern.
• Sleep apnea, heavy snoring, COPD or other lung disease, or myasthenia gravis: the label advises caution in these conditions and notes that oxygen levels worsened compared with placebo in people with mild to moderate sleep apnea. If you snore loudly or a partner notices pauses in your breathing at night, ask to be evaluated before starting a sleep medicine.
• Depression, other mental illness or suicidal thoughts: zolpidem can worsen depression, and intentional overdose is more common in this group.
• Liver or kidney disease: dose changes or avoidance may be needed.
• History of alcohol or drug misuse: dependence risk is higher.
• Pregnancy or breastfeeding: use near the end of pregnancy can cause breathing problems and sedation in newborns, so discuss it with your doctor.

Interactions: Alcohol, Opioids and Other Medicines

Alcohol

Do not drink alcohol while taking zolpidem. Alcohol adds to its sedating effect, worsens psychomotor impairment and increases the chance of side effects.^[1][4] The FDA also tells patients not to drink before taking any of the boxed-warning insomnia drugs.^[2] If you are unsure how much you drink, our guide on how much alcohol is too much is a useful starting point for a talk with your doctor.

Opioids and other central nervous system depressants

Combining zolpidem with opioid pain medicines, benzodiazepines, other sleep medicines, tricyclic antidepressants or sedating antihistamines increases central nervous system depression, which can slow breathing to dangerous levels. The label warns that opioids may increase respiratory depression and advises limiting the dose and duration when the two must be used together.^[4] Never add an over-the-counter sleep aid to zolpidem; the FDA specifically warns against combining it with other sleep medicines, including nonprescription ones.^[2]

Drugs that change zolpidem levels

Zolpidem is broken down mainly by the liver enzyme CYP3A4, so some drugs and herbs raise or lower its blood levels. Give your pharmacist a full list of everything you take, including supplements:^[4]

• Raise levels (more side effects): ketoconazole raised zolpidem exposure by about 70%, itraconazole by about 34%, and sertraline raised peak levels by about 43%. The label also lists fluvoxamine and ciprofloxacin as likely to increase exposure.
• Lower levels (less effect): rifampin reduced exposure by about 73%, and St. John’s wort may also lower levels. Combining zolpidem with either is not recommended.

Because herbal products can matter too, give your pharmacist a full list of everything you take, including supplements.

Dependence, Tolerance and Stopping Safely

Zolpidem is a Schedule IV controlled substance. MedlinePlus describes it as habit forming, and the label states that the risk of dependence rises with higher doses and longer use, and is greater in people with a history of alcohol or drug misuse.^[1][4] After about 2 weeks of nightly use it may also start to work less well.^[1]

Stopping abruptly after regular use can trigger withdrawal. Reported symptoms include shakiness, lightheadedness, cramps, nausea, vomiting, sweating, flushing, nervousness, panic attacks, crying spells, uncontrolled muscle twitching and, rarely, seizures.^[1] The Cleveland Clinic advises not stopping on your own after several weeks of use; your care team may lower the dose gradually.^[5]

Guidelines favor treating chronic insomnia without long-term pills. The American College of Physicians recommends cognitive behavioral therapy for insomnia (CBT-I) as the first-line treatment for adults with chronic insomnia, and notes that FDA-approved sleep medicines are intended for short-term use of about four to five weeks.^[6] CBT-I combines sleep-focused cognitive therapy, sleep restriction, stimulus control and sleep hygiene education. If you want to work on habits alongside your doctor’s plan, our guides to better sleep routines for men and insomnia in men cover the basics, and our overview of sleeping pills side effects compares zolpidem with other common sleep aids.

When to Call a Doctor or Get Emergency Help

Call your prescriber soon if:^[1][2][5]

• You or someone else notices you did things while not fully awake that you do not remember. Stop the medicine and call right away, even if no one was hurt.
• You feel groggy, unsteady or slow the next morning, or you have had a near miss while driving.
• You notice new confusion, agitation, hallucinations, worsening mood or thoughts of self-harm.
• Your sleep has not improved after 7 to 10 days, or it is getting worse.
• You want to stop after taking zolpidem for more than 2 weeks.

Call 911 if someone taking zolpidem has collapsed, had a seizure, has trouble breathing or cannot be woken. Signs of overdose include deep drowsiness, coma and slowed breathing or heart rate. In the US, Poison Control is available at 1-800-222-1222.^[1]

Frequently Asked Questions

How long do zolpidem side effects last?

Most mild side effects, such as drowsiness or dizziness, fade as the drug clears, often by morning. Next-day impairment can last longer in women, older adults, people with liver disease and anyone who took an extended-release form or slept less than 7 to 8 hours.^[3][4] Rebound insomnia after stopping usually settles in one or two nights.^[1]

Can zolpidem cause memory loss?

Yes. Memory problems are listed among the side effects to report, and people who have complex sleep behaviors usually do not remember them afterward.^[1][2] Any episode of activity you cannot recall is a reason to stop and call your doctor.

Is it safe to take zolpidem every night?

Zolpidem is intended for short-term use. It may become less effective after about 2 weeks, and the dependence risk grows with dose and duration.^[1][4] If you have needed it for weeks, ask your doctor about a tapering plan and about CBT-I.^[6]

Does zolpidem affect men and women differently?

Yes. Women clear zolpidem more slowly, which is why the FDA lowered the recommended starting dose for women to 5 mg (immediate release) and 6.25 mg (extended release), and asked prescribers to consider those lower doses for men as well.^[3]

References

1. MedlinePlus (U.S. National Library of Medicine). Zolpidem. medlineplus.gov
2. U.S. Food and Drug Administration. FDA adds Boxed Warning for risk of serious injuries caused by sleepwalking with certain prescription insomnia medicines. Drug Safety Communication, April 30, 2019. fda.gov
3. U.S. Food and Drug Administration. Questions and Answers: Risk of next-morning impairment after use of insomnia drugs; FDA requires lower recommended doses for certain drugs containing zolpidem. fda.gov
4. Ambien (zolpidem tartrate) prescribing information. drugs.com
5. Cleveland Clinic. Zolpidem Extended-Release Tablets. my.clevelandclinic.org
6. American College of Physicians. ACP recommends cognitive behavioral therapy as initial treatment for chronic insomnia. May 3, 2016 (guideline published in Annals of Internal Medicine). acponline.org

This article is for general information only and is not medical advice. It does not replace the Medication Guide that comes with your prescription or the advice of your doctor or pharmacist. Safety information summarized here comes from the U.S. Food and Drug Administration and the other sources listed above. Never start, stop or change the dose of a prescription medicine without talking to your prescriber.