What are the contraindications for Zolpidem (Ambien)?

From the Guidelines

Zolpidem is contraindicated in patients with a history of complex sleep behaviors, severe hepatic impairment, untreated sleep apnea, and those who are pregnant or breastfeeding, due to the risk of adverse effects and potential harm to the fetus or infant.

Key Contraindications

• Known hypersensitivity to zolpidem or other components of the formulation
• Severe hepatic impairment due to decreased metabolism and increased risk of adverse effects
• History of complex sleep behaviors, such as sleep-walking, sleep-driving, or engaging in other activities while not fully awake
• Untreated sleep apnea, as zolpidem can worsen respiratory depression
• Pregnancy, especially the third trimester, and breastfeeding due to potential risks to the fetus or infant
• Combination with other CNS depressants, including alcohol, benzodiazepines, opioids, or other sedative-hypnotics, which can lead to dangerous respiratory depression
• Myasthenia gravis, severe respiratory insufficiency, or acute narrow-angle glaucoma, as zolpidem can worsen conditions involving CNS depression or respiratory compromise, as reported in studies such as 1.

Additional Considerations

• The FDA recommends dosages lower than those used in many studies, especially for older adults, and suggests that patients with insomnia that does not remit within 7 to 10 days of treatment should be further evaluated, as stated in 1.
• Observational studies have shown that hypnotic drugs, including zolpidem, may be associated with infrequent but serious adverse effects, such as dementia, serious injury, and fractures, as noted in 1.
• The medication works by enhancing the effect of GABA, an inhibitory neurotransmitter in the brain, which explains why it can worsen conditions involving CNS depression or respiratory compromise.

From the FDA Drug Label

1. Contraindications Zolpidem tartrate tablets are contraindicated in patients who have experienced complex sleep behaviors after taking zolpidem tartrate tablets [see WARNINGS AND PRECAUTIONS (5.1). with known hypersensitivity to zolpidem. Observed reactions include anaphylaxis and angioedema [see WARNINGS AND PRECAUTIONS (5.4)].

The contraindications for Zolpidem are:

• Patients who have experienced complex sleep behaviors after taking zolpidem tartrate tablets
• Patients with known hypersensitivity to zolpidem, including reactions such as anaphylaxis and angioedema 2

From the Research

Zolpidem Contraindications

• Zolpidem has been associated with an increased risk of falls in hospitalized patients, with an odds ratio (OR) of 4.28 (P < 0.001) 3.
• The relative risk (RR) for hip fractures in patients taking zolpidem was 1.92 (95% CI 1.65-2.24; P < 0.001), with hip fractures being the most commonly seen 3.
• Zolpidem has been linked to central nervous system (CNS)-related adverse reactions, such as confusion, dizziness, and daytime sleepiness, particularly in elderly patients 3.
• There is a significant association between zolpidem use and suicide attempts or completion, with an OR of 2.08 (95% CI 1.83-2.63) 3.
• Zolpidem has been reported to cause complex sleep behaviors, including sleepwalking, sleep-related eating disorder, and driving while asleep, in some patients 4.
• The FDA has classified zolpidem as a category C drug due to adverse outcomes seen in animal fetal development, including low birth weight, preterm delivery, and small for gestational age babies 3.
• Patients with a history of substance abuse or dependence, as well as those with psychiatric conditions, may be at increased risk of abusing zolpidem 5.
• Zolpidem may not be suitable for patients with obstructive sleep apnea, as it can increase the threshold for arousal and pharyngeal dilator muscle responsiveness, potentially worsening sleep apnea severity 6.