HIGHLIGHTS OF PRESCRIBING INFORMATION Depression ...

1 HIGHLIGHTS OF PRESCRIBING INFORMATIONT hese HIGHLIGHTS do not include all the INFORMATION needed to use ambien safely andeffectively. See full PRESCRIBING INFORMATION for (zolpidem tartrate) tablets, for oral use, C-IVInitial Approval: 1992 WARNING: COMPLEX SLEEP BEHAVIORSSee full PRESCRIBING INFORMATION for complete boxed sleep behaviors including sleep-walking, sleep-driving, and engaging inother activities while not fully awake may occur following use of ambien . Some ofthese events may result in serious injuries, including death. Discontinue ambien immediately if a patient experiences a complex sleep behavior. (4, ) RECENT MAJOR CHANGES Boxed Warning08/2019 Contraindications (4)08/2019 Warnings and Precautions, Complex Sleep Behaviors ( )08/2019 Warnings and Precautions, CNS-Depressant Effects and Next-DayImpairment ( )02/2019 INDICATIONS AND USAGE ambien , a gamma-aminobutyric acid (GABA) A receptor positive modulator, is indicated for theshort-term treatment of insomnia characterized by difficulties with sleep initiation.

2 (1) DOSAGE AND ADMINISTRATION Use the lowest dose effective for the patient and must not exceed a total of 10 mg daily ( ) Recommended initial dose is a single dose of 5 mg for women and a single dose of 5 or 10mg for men, immediately before bedtime with at least 7 8 hours remaining before the plannedtime of awakening ( ) Geriatric patients and patients with mild to moderate hepatic impairment: Recommended doseis 5 mg for men and women ( ) Lower doses of CNS depressants may be necessary when taken concomitantly with ambien ( ) The effect of ambien may be slowed if taken with or immediately after a meal ( ) DOSAGE FORMS AND STRENGTHS 5 mg and 10 mg tablets.

3 Tablets not scored. (3) CONTRAINDICATIONS Patients who have experienced complex sleep behaviors after taking ambien (4) Known hypersensitivity to zolpidem (4) WARNINGS AND PRECAUTIONS CNS-Depressant Effects: Impairs alertness and motor coordination including risk of morningimpairment. Risk increases with dose and use with other CNS depressants and patients on correct use. ( ) Need to Evaluate for Comorbid Diagnoses: Re-evaluate if insomnia persists after 7 to 10 daysof use. ( ) Severe Anaphylactic/Anaphylactoid Reactions: Angioedema and anaphylaxis have beenreported.

4 Do not rechallenge if such reactions occur. ( ) Abnormal Thinking and Behavioral Changes: Changes including decreased inhibition, bizarrebehavior, agitation, and depersonalization have been reported. Immediately evaluate any newonset behavioral changes. ( ) Depression : Worsening of Depression or suicidal thinking may occur. Prescribe the leastamount of tablets feasible to avoid intentional overdose. ( ) Respiratory Depression : Consider this risk before PRESCRIBING in patients with compromisedrespiratory function. ( ) Hepatic Impairment: Avoid ambien use in patients with severe hepatic impairment. ( ) Withdrawal Effects: Symptoms may occur with rapid dose reduction or discontinuation.

5 ( , ) ADVERSE REACTIONS Most commonly observed adverse reactions were:Short-term (<10 nights): Drowsiness, dizziness, and diarrheaLong-term (28 35 nights): Dizziness and drugged feelings ( )To report SUSPECTED ADVERSE REACTIONS, contact sanofi-aventis LLC at 1-800-633-1610 or FDA at 1-800-FDA-1088 or DRUG INTERACTIONS CNS depressants, including alcohol: Possible adverse additive CNS-depressant effects ( , ) Imipramine: Decreased alertness observed ( ) Chlorpromazine: Impaired alertness and psychomotor performance observed ( ) CYP3A4 inducers (rifampin or St.)

6 John s wort): Combination use may decrease effect ( ) Ketoconazole: Combination use may increase effect ( ) USE IN SPECIFIC POPULATIONS Pregnancy: May cause respiratory Depression and sedation in neonates with exposure late inthe third trimester. ( ) Lactation: A lactating woman may pump and discard breast milk during treatment and for 23hours after ambien administration. ( ) Pediatric use: Safety and effectiveness not established. Hallucinations (incidence rate 7%) andother psychiatric and/or nervous system adverse reactions were observed frequently in a studyof pediatric patients with Attention-Deficit/Hyperactivity Disorder.

7 ( , )See 17 for PATIENT COUNSELING INFORMATION and Medication GuideRevised: 08/2019 FULL PRESCRIBING INFORMATION : CONTENTS*WARNING: COMPLEX SLEEP BEHAVIORS1 INDICATIONS AND USAGE2 DOSAGE AND in with CNS DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND Sleep Effects and Next-Day to Evaluate for Comorbid Anaphylactic and Anaphylactoid Thinking and Behavioral in Patients with of Hepatic Effects6 ADVERSE Trials Experience7 DRUG that Affect Drug Metabolism via Cytochrome P4508 USE IN SPECIFIC Difference in Impairment9 DRUG ABUSE AND Signs and Recommended Treatment11 DESCRIPTION12 CLINICAL Mechanism of Pharmacokinetics13 NONCLINICAL Carcinogenesis.

8 Mutagenesis, Impairment of Fertility14 CLINICAL Transient Chronic Studies Pertinent to Safety Concerns for Sedative/Hypnotic Drugs16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION *Sections or subsections omitted from the full PRESCRIBING INFORMATION are not listed1 FULL PRESCRIBING INFORMATIONWARNING: COMPLEX SLEEP BEHAVIORSC omplex sleep behaviors including sleep-walking, sleep-driving, and engaging in otheractivities while not fully awake may occur following use of ambien . Some of these eventsmay result in serious injuries, including death. Discontinue ambien immediately if apatient experiences a complex sleep behavior[see Contraindications (4) and Warningsand Precautions ( )].

9 1 INDICATIONS AND USAGEAMBIEN (zolpidem tartrate) is indicated for the short-term treatment of insomnia characterized bydifficulties with sleep initiation. ambien has been shown to decrease sleep latency for up to 35 daysin controlled clinical studies[see Clinical Studies (14)].The clinical trials performed in support of efficacy were 4 5 weeks in duration with the final formalassessments of sleep latency performed at the end of DOSAGE AND Dosage in AdultsUse the lowest effective dose for the patient. The recommended initial dose is 5 mg for women andeither 5 or 10 mg for men, taken only once per night immediately before bedtime with at least 7 8 hoursremaining before the planned time of awakening.

10 If the 5 mg dose is not effective, the dose can beincreased to 10 mg. In some patients, the higher morning blood levels following use of the 10 mg doseincrease the risk of next-day impairment of driving and other activities that require full alertness[seeWarnings and Precautions ( )]. The total dose of ambien should not exceed 10 mg once dailyimmediately before bedtime. ambien should be taken as a single dose and should not bereadministered during the same recommended initial doses for women and men are different because zolpidem clearance is lowerin Special PopulationsElderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate.