Side Effects of Intermezzo (zolpidem)

Intermezzo (zolpidem) is a sedative/hypnotic used to treat insomnia in the middle of the night (awakening and experiencing difficulty returning to sleep).

Intermezzo contains the same active ingredient as Ambien. Intermezzo shares characteristics with benzodiazepines, a family of sedatives that includes diazepam.

Benzodiazepines cause sedation, muscle relaxation, act as anticonvulsants (antiseizure medications), and reduce anxiety. Intermezzo primarily functions as a sleep medication, with little muscle relaxant and antiseizure effects.

Common side effects of Intermezzo include

Serious side effects of Intermezzo include

• confusion,
• insomnia,
• euphoria,
• balance problems, and
• visual changes.

Abrupt discontinuation of Intermezzo can lead to abnormal behavior, confusion, and sleep-related behaviors such as sleep-driving (driving with no memory of having done so).

Drug interactions of Intermezzo include alcohol, which has an additive effect with Intermezzo and should not be combined.

Intermezzo should not be combined with other sedative drugs due to additive effects.

Itraconazole and ketoconazole may increase the blood concentration of Intermezzo by reducing the activity of the enzymes that break down Intermezzo in the liver. Rifampin may reduce the concentration of Intermezzo by increasing the activity of the enzymes that break it down.

No adequate studies have been conducted on Intermezzo use in pregnant women.

Intermezzo is excreted in human breast milk and may adversely affect the infant. Consult your doctor before breastfeeding.

What are the important side effects of Intermezzo (zolpidem)?

The most common side effects of zolpidem are:

Other important side effects include:

• confusion,
• insomnia,
• euphoria,
• ataxia (balance problems), and
• visual changes.

If these side effects occur, zolpidem use should be discontinued. Zolpidem is a controlled substance due to its potential for abuse and dependence.

Intermezzo (zolpidem) side effects for healthcare professionals

The following serious adverse reactions in zolpidem-treated patients are discussed in greater detail in other sections of the labeling:

• CNS-depressant effects and next-day impairment
• Serious anaphylactic and anaphylactoid reactions
• Abnormal thinking and behavioral changes, and complex behaviors
• Withdrawal effects

Clinical Trials Experience

The safety data described below are based on two double-blind placebo-controlled trials of Intermezzo in adult patients with insomnia characterized by difficulty returning to sleep after a middle-of-the-night awakening.

• These two trials included 230 and 82 patients treated with 3.5 mg and 1.75 mg of Intermezzo, respectively.
• In Study 2, patients took Intermezzo during the night on 62% of study nights.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in actual practice.

Table 1 shows the incidence of adverse reactions reported in Study 2 that occurred in 2% or more of Intermezzo-treated (3.5 mg) patients in which the incidence was greater than the incidence in placebo-treated patients.

For women and other patients taking the 1.75 mg dose in Study 1, the incidence of adverse reactions was similar to the incidence seen with 3.5 mg of Intermezzo in Table 1.

The most commonly reported adverse reactions in all treatment groups were

Table 1: Summary of Adverse Reactions ( ≥ 2%) in Outpatient, Double-Blind, Parallel-Group, Placebo-Controlled Study (Study 2)

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Intermezzo. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to establish a causal relationship to drug exposure.

• Application site reactions, primarily in the sublingual area, have been reported. These application site reactions included

• oral ulcers,
• blisters, and
• mucosal inflammation.

What drugs interact with Intermezzo (zolpidem)?

CNS-active Drugs

• Co-administration of zolpidem with other CNS depressants increases the risk of CNS depression.
• Zolpidem tartrate was evaluated in healthy volunteers in single-dose interaction studies.

Imipramine

• Imipramine in combination with zolpidem produced no pharmacokinetic interaction other than a 20% decrease in peak levels of imipramine, but there was an additive effect of decreased alertness.
• Similarly, chlorpromazine in combination with zolpidem produced no pharmacokinetic interaction, but there was an additive effect of decreased alertness and psychomotor performance.

Haloperidol

• A study involving haloperidol and zolpidem revealed no effect of haloperidol on the pharmacokinetics or pharmacodynamics of zolpidem.
• The lack of a drug interaction following single-dose administration does not predict the absence of an effect following chronic administration.

Alcohol

• An additive adverse effect on psychomotor performance between alcohol and oral zolpidem was demonstrated.

Sertraline

• Concomitant administration of zolpidem and sertraline increases exposure to zolpidem and may increase the pharmacodynamic effect of zolpidem.

Fluoxetine

• After multiple doses of zolpidem tartrate and fluoxetine, an increase in the zolpidem half-life (17%) was observed.
• There was no evidence of an additive effect in psychomotor performance.

Drugs That Affect Drug Metabolism Via Cytochrome P450

• Some compounds known to inhibit CYP3A may increase exposure to zolpidem.
• The effect of other P450 enzymes on the exposure to zolpidem is not known.

Rifampin

• Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem.
• Use of rifampin in combination with zolpidem may decrease the efficacy of zolpidem.

Ketoconazole

• Ketoconazole, a potent CYP3A4 inhibitor, increased the pharmacodynamic effects of zolpidem.
• Consideration should be given to using a lower dose of zolpidem when ketoconazole and zolpidem are given together.

Does Intermezzo (zolpidem) cause addictional or withdrawal symptoms?

Drug Abuse And Dependence

Controlled Substance

• Zolpidem tartrate is classified as a Schedule IV controlled substance.

Abuse

• Abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances.
• Tolerance is a state of adaptation in which exposure to a drug induces changes that result in diminution of one or more of the drug effects over time.
• Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations.

Dependence

• Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome.
• Sedative-hypnotics have produced withdrawal signs and symptoms following abrupt discontinuation.
• These reported symptoms range from mild dysphoria and insomnia to a withdrawal syndrome that may include

• abdominal and muscle cramps,
• vomiting,
• sweating,
• tremors, and
• convulsions.
• fatigue,
• nausea,
• flushing,
• lightheadedness,
• uncontrolled crying,
• emesis,
• stomach cramps,
• panic attack,
• nervousness, and
• abdominal discomfort.

Summary

Intermezzo (zolpidem) is a sedative/hypnotic used to treat insomnia in the middle of the night. Common side effects of Intermezzo include headache, nausea, drowsiness, dizziness, and diarrhea. Intermezzo should not be combined with other sedative drugs. No adequate studies have been conducted on Intermezzo use in pregnant women. Intermezzo is excreted in human breast milk and may adversely affect the infant.