Zolpidem Tartrate

ZOLPIDEM TARTRATE- zolpidem tartrate tablet, film coated
RedPharm Drug, Inc.

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use ZOLPIDEM TARTRATE TABLETS safely and effectively. See full prescribing information for ZOLPIDEM TARTRATE TABLETS.
ZOLPIDEM TARTRATE tablets, for oral use CIV
Initial U.S. Approval: 1992

RECENT MAJOR CHANGES

Dosage and Administration, Dosage in Adults (2.1)

8/2016

Dosage and Administration, Special Populations (2.2)

12/2016

Warnings and Precautions, CNS Depressant Effects and Next-Day Impairment (5.1)

8/2016

Warnings and Precautions, Precipitation of Hepatic Encephalopathy (5.7)

12/2016

INDICATIONS AND USAGE

Zolpidem tartrate tablets, a gamma-aminobutyric acid (GABA) A agonist, are indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. (1)

DOSAGE AND ADMINISTRATION

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Use the lowest dose effective for the patient and must not exceed a total of 10 mg daily ( 2.1)
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Recommended initial dose is a single dose of 5 mg for women and a single dose of 5 or 10 mg for men, immediately before bedtime with at least 7 to 8 hours remaining before the planned time of awakening ( 2.1)
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Geriatric patients and patients with mild to moderate hepatic impairment: Recommended dose is 5 mg for men and women ( 2.2)
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Lower doses of CNS depressants may be necessary when taken concomitantly with zolpidem tartrate tablets ( 2.3)
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The effect of zolpidem tartrate tablets may be slowed if taken with or immediately after a meal ( 2.4)

DOSAGE FORMS AND STRENGTHS

5 mg and 10 mg tablets. Tablets not scored. (3)

CONTRAINDICATIONS

Known hypersensitivity to zolpidem (4)

WARNINGS AND PRECAUTIONS

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CNS depressant effects: Impairs alertness and motor coordination. Instruct patients on correct use. (5.1)
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Need to evaluate for co-morbid diagnoses: Reevaluate if insomnia persists after 7 to 10 days of use. (5.2)
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Severe anaphylactic/anaphylactoid reactions: Angioedema and anaphylaxis have been reported. Do not rechallenge if such reactions occur. ( 5.3)
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“Sleep-driving” and other complex behaviors while not fully awake. Risk increases with dose and use with other CNS depressants and alcohol. Immediately evaluate any new onset behavioral changes. (5.4)
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Depression: Worsening of depression or suicidal thinking may occur. Prescribe the least amount of tablets feasible to avoid intentional overdose. ( 5.5)
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Respiratory Depression: Consider this risk before prescribing in patients with compromised respiratory function. ( 5.6)
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Hepatic Impairment: Avoid zolpidem use in patients with severe hepatic impairment. ( 5.7)
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Withdrawal effects: Symptoms may occur with rapid dose reduction or discontinuation. ( 5.8, 9.3)
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Severe Injuries: Drowsiness may lead to fall including severe injuries. ( 5.9)

ADVERSE REACTIONS

Most commonly observed adverse reactions were:

Short-term (< 10 nights): Drowsiness, dizziness, and diarrhea

Long-term (28 to 35 nights): Dizziness and drugged feelings (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at 1-866-832-8537 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

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CNS depressants, including alcohol: Possible adverse additive CNS-depressant effects ( 5.1, 7.1)
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Imipramine: Decreased alertness observed ( 7.1)
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Chlorpromazine: Impaired alertness and psychomotor performance observed ( 7.1)
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CYP3A4 inducers (rifampin or St. John’s wort): Combination use may decrease effect ( 7.2)
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Ketoconazole: Combination use may increase effect ( 7.2)

USE IN SPECIFIC POPULATIONS

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Pregnancy: Based on animal data, may cause fetal harm ( 8.1)
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Pediatric use: Safety and effectiveness not established. Hallucinations (incidence rate 7%) and other psychiatric and/or nervous system adverse reactions were observed frequently in a study of pediatric patients with Attention-Deficit/Hyperactivity Disorder ( 5.4, 8.4)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 3/2017

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Dosage in Adults
2.2 Special Populations
2.3 Use with CNS Depressants
2.4 Administration
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 CNS Depressant Effects and Next-Day Impairment
5.2 Need to Evaluate for Co-Morbid Diagnoses
5.3 Severe Anaphylactic and Anaphylactoid Reactions
5.4 Abnormal Thinking and Behavioral Changes
5.5 Use in Patients with Depression
5.6 Respiratory Depression
5.7 Precipitation of Hepatic Encephalopathy
5.8 Withdrawal Effects
5.9 Severe Injuries
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
7 DRUG INTERACTIONS
7.1 CNS-active Drugs
7.2 Drugs That Affect Drug Metabolism via Cytochrome P450
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Labor and Delivery
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Gender Difference in Pharmacokinetics
8.7 Hepatic Impairment
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
9.2 Abuse
9.3 Dependence
10 OVERDOSAGE
10.1 Signs and Symptoms
10.2 Recommended Treatment
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14.1 Transient Insomnia
14.2 Chronic Insomnia
14.3 Studies Pertinent to Safety Concerns for Sedative/Hypnotic Drugs
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
Zolpidem Tartrate Tablets USP 5 mg CIV 100s Label Text
Zolpidem Tartrate Tablets USP 10 mg CIV 100s Label Text

*
Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS AND USAGE

Zolpidem tartrate tablets are indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. Zolpidem tartrate tablets have been shown to decrease sleep latency for up to 35 days in controlled clinical studies [see Clinical Studies (14)].

The clinical trials performed in support of efficacy were 4 to 5 weeks in duration with the final formal assessments of sleep latency performed at the end of treatment.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage in Adults

Use the lowest effective dose for the patient. The recommended initial dose is 5 mg for women and either 5 or 10 mg for men, taken only once per night immediately before bedtime with at least 7 to 8 hours remaining before the planned time of awakening. If the 5 mg dose is not effective, the dose can be increased to 10 mg. In some patients, the higher morning blood levels following use of the 10 mg dose increase the risk of next day impairment of driving and other activities that require full alertness [see Warnings and Precautions (5.1)]. The total dose of zolpidem tartrate tablets should not exceed 10 mg once daily immediately before bedtime. Zolpidem tartrate tablets should be taken as a single dose and should not be readministered during the same night.

The recommended initial doses for women and men are different because zolpidem clearance is lower in women.

2.2 Special Populations

Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate. The recommended dose of zolpidem tartrate in these patients is 5 mg once daily immediately before bedtime [see Warnings and Precautions (5.1), Use in Specific Populations (8.5)].

Patients with mild to moderate hepatic impairment do not clear the drug as rapidly as normal subjects. The recommended dose of zolpidem tartrate in these patients is 5 mg once daily immediately before bedtime. Avoid zolpidem tartrate use in patients with severe hepatic impairment as it may contribute to encephalopathy [see Warnings and Precautions (5.7), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

2.3 Use with CNS Depressants

Dosage adjustment may be necessary when zolpidem tartrate tablets are combined with other CNS depressant drugs because of the potentially additive effects [see Warnings and Precautions (5.1)].

2.4 Administration

The effect of zolpidem tartrate tablets may be slowed by ingestion with or immediately after a meal.

3 DOSAGE FORMS AND STRENGTHS

Zolpidem tartrate tablets USP are available in 5 mg and 10 mg strength tablets for oral administration. Tablets are not scored.

Zolpidem tartrate tablets USP, 5 mg are pink, film-coated, round tablets; debossed “TEVA” on one side and “73” on the other.

Zolpidem tartrate tablets USP, 10 mg are white to off-white, film-coated, round tablets; debossed “TEVA” on one side and “74” on the other.