FDA

Zolpidem Tartrate

Approved 11 Sept 2017Under the tongueTablet

The FDA lists this product in 60 strengths and forms.

Indications

Zolpidem tartrate sublingual tablets are indicated for use as needed for the treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep. Limitations of Us e: Zolpidem tartrate sublingual tablets are not indicated for the treatment of middle-of-the-night insomnia when the patient has fewer than 4 hours of bedtime remaining before the planned time of waking. Zolpidem tartrate sublingual tablets are a GABA A agonist indicated for use as needed for the treatment of insomnia when a middle-of-the-night awakening is followed by difficulty returning to sleep Limitation of Use : Not indicated for the treatment of middle-of-the night awakening when the patient has fewer than 4 hours of bedtime remaining before the planned time of waking

Contraindications

Zolpidem tartrate is contraindicated in patients who have experienced complex sleep behaviors after taking zolpidem tartrate [see Warnings and Precautions (5.1)]. Zolpidem tartrate is contraindicated in patients with known hypersensitivity to zolpidem. Observed reactions with zolpidem include anaphylaxis and angioedema [see Warnings and Precautions (5.4)]. Patients who have experienced complex sleep behaviors after taking zolpidem tartrate (4, 5.1) Known hypersensitivity to zolpidem (4)

Warnings and precautions

CNS depressant effects: Impairs alertness and motor coordination, including risk of morning impairment. Risk increases with dose and use with other CNS depressants and alcohol. Instruct patients on correct use (5.2) Evaluate for co-morbid diagnoses: Re-evaluate if insomnia persists after 7 to 10 days of use (5.2) Severe anaphylactic/anaphylactoid reactions: Angioedema and anaphylaxis have been reported. Do not re-challenge if such reactions occur (5.3) Abnormal Thinking and Behavioral Changes: Changes including decreased inhibition, bizarre behavior, agitation and depersonalization have been reported.

Immediately evaluate any new onset behavioral changes (5.5) Depression: Worsening of depression or suicidal thinking may occur. Prescribe the least number of tablets feasible to avoid intentional overdose (5.6) Respiratory Depression: Consider this risk before prescribing in patients with compromised respiratory function (5.7)

5.1COMPLEX SLEEP BEHAVIORS

Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur following the first or any subsequent use of zolpidem. Patients can be seriously injured or injure others during complex sleep behaviors. Such injuries may result in a fatal outcome. Other complex sleep behaviors (e.g., preparing and eating food, making phone calls, or having sex) have also been reported.

At a glance

Brand name: Zolpidem Tartrate
Route: Under the tongue
Dosage form: Tablet
Applicant: PH Health
Status: Prescription
FDA approval: 11 Sept 2017
Application: ANDA204229-001

Indications

Contraindications

Warnings and precautions

5.1COMPLEX SLEEP BEHAVIORS

Interactions

CNS depressants, including alcohol: Possible adverse additive CNS depressant effects (5.1, 7.1) Imipramine: Decreased alertness observed (7.1) Chlorpromazine: Impaired alertness and psychomotor performance observed (7.1) Rifampin: Combination use may decrease effects (7.2) Ketoconazole: Combination use may increase effects (7.2)

7.1CNS-active Drugs Co-administration

of zolpidem with other CNS depressants increases the risk of CNS depression [see Warnings and Precautions (5.1, 5.2)]. Zolpidem tartrate was evaluated in healthy volunteers in single-dose interaction studies for several CNS drugs. 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 [see Warnings and Precautions (5.1, 5.2)]. 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 [see Clinical Pharmacology (12.3)].

7.2 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.

Adverse reactions

The following serious adverse reactions in zolpidem-treated patients are discussed in greater detail in other sections of the labeling: Complex Sleep Behaviors [See Warnings and Precautions (5.1)] CNS-Depressant Effects and Next-Day Impairment [See Warnings and Precautions (5.2)] Serious Anaphylactic and Anaphylactoid Reactions [See Warnings and Precautions (5.2)] Abnormal Thinking and Behavioral Changes [See Warnings and Precautions (5.5)] Withdrawal Effects [See Warnings and Precautions (5.8)] Most commonly observed adverse reactions (> 1% in adult patients) are headache, nausea, and fatigue.

(6.1) To report SUSPECTED ADVERSE REACTIONS, contact Par Health at 1-800-828-9393 or FDA at 1-800-FDA-1088 or http://w ww.fda.gov/medwatch .

6.1Clinical Trials Experience

The safety data described below are based on two double-blind placebo-controlled trials of zolpidem tartrate in adult patients with insomnia characterized by difficulty returning to sleep after a middle-of-the-night awakening [see Clinical Studies (14.1)]. These two trials included 230 and 82 patients treated with 3.5 mg and 1.75 mg of zolpidem tartrate, respectively. The first study was a 3-way crossover sleep-laboratory study in 82 patients (58 female and 24 male; median age 47 years; 51% Caucasian, 44% African-American) of 1.75 mg and 3.5 mg of zolpidem tartrate compared to placebo (Study 1).

The second study was a 4-week, parallel-group at-home study in 295 patients (201 female and 94 male; median age 43 years) of 3.5 mg of zolpidem tartrate compared to placebo, used on an as-needed basis after spontaneous middle-of-the-night awakenings (Study 2). In Study 2, patients took zolpidem tartrate 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 zolpidem tartrate-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 zolpidem tartrate in Table 1. The most commonly reported adverse reactions in all treatment groups were headache, nausea, and fatigue.

Table 1: Summary of Adverse Reactions (≥ 2%) in Outpatient, Double-Blind, Parallel-Group, Placebo-Controlled Study (Study 2) MedDRA System Organ Class Preferred Term 3.5 mg Z olpidem Tartrate (n=150) Placebo (n=145) Gastrointestinal Disorders 4% 2% Nausea 1% 1% General Disorders and Administration Site Conditions 3% 0% Fatigue 1% 0% Nervous System Disorders 5% 3% Headache 3% 1%

Consideration should be given to using a lower dose of zolpidem when ketoconazole and zolpidem are given together.

Zolpidem Tartrate

Indications

Contraindications

Warnings and precautions

5.1COMPLEX SLEEP BEHAVIORS

At a glance

Two medicines in one question?

Zolpidem Tartrate

Indications

Contraindications

Warnings and precautions

5.1COMPLEX SLEEP BEHAVIORS

At a glance

Two medicines in one question?

5.2CNS Depressant Effects and Next-Day Impairment

5.3Need to Evaluate for Co-morbid Diagnoses

5.4Severe Anaphylactic and Anaphylactoid Reactions Cases

5.5Abnormal Thinking and Behavioral Changes

5.6Use in Patients with Depression

5.7Respiratory Depression

5.8Withdrawal Effects

Interactions

7.1CNS-active Drugs Co-administration

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Category C

Adverse reactions

6.1Clinical Trials Experience

Composition

Strengths and forms

Official product information