Zolpidem

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of zolpidem there are no specific foods that you must exclude from your diet when receiving zolpidem.

Before receiving zolpidem, tell your doctor about all of your medical conditions, including if you:

• have a history of depression, mental illness, or suicidal thoughts
• have a history of drug or alcohol abuse or addiction
• have kidney or liver disease
• have a lung disease or breathing problems
• are pregnant, planning to become pregnant, or breastfeeding

Tell your doctor about all of the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category C. In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. Therefore, this medication may be used if the potential benefits to the mother outweigh the potential risks to the unborn child.

Take zolpidem exactly as prescribed. Do not take more zolpidem than prescribed for you.

• Take zolpidem right before you get into bed.
• Do not take zolpidem unless you are able to stay in bed a full night (7–8 hours) before you must be active again.
• Zolpidem should be taken without food.
• Call your doctor if your insomnia worsens or is not better within 7 to 10 days. This may mean that there is another condition causing your sleep problem.
• If you take too much zolpidem or overdose, call your doctor or poison control center right away, or get emergency treatment.

In January 2013, the Food and Drug Administration (FDA) lowered the recommended dose for Ambien, Edluar, and Zolpimist. If you have taken zolpidem in the past, your doctor may direct you to take a lower dose of this medicine than you did before.

Follow all directions on your prescription label. Never take zolpidem in larger amounts, or for longer than prescribed.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Zolpidem may be habit-forming. Never share zolpidem with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it. Selling or giving away this medicine is against the law.

The recommended doses of zolpidem are not the same in men and women, and this drug is not approved for use in children. Misuse of this medication can result in dangerous side effects.

Never take Ambien, Edluar, or Zolpimist if you do not have a full 7 to 8 hours to sleep before being active again.

Do not take Intermezzo for middle-of-the-night insomnia unless you have 4 hours of sleep time left before being active.

Zolpidem is for short-term use only. Tell your doctor if your insomnia symptoms do not improve, or if they get worse after using this medication for 7 to 10 nights in a row. Do not take zolpidem for longer than 4 or 5 weeks without your doctor's advice.

Do not stop using zolpidem suddenly after long-term use, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using zolpidem.

Insomnia symptoms may also return after you stop taking zolpidem. These symptoms may seem to be even worse than before you started taking the medicine. Call your doctor if you still have worsened insomnia after the first few nights without taking zolpidem.

Do not crush, chew, or break an Ambien CR tablet. Swallow the pill whole.

Do not swallow the Edluar or Intermezzo tablet whole. Place the tablet under your tongue and allow it to dissolve in your mouth without water.

Spray Zolpimist directly into your mouth over your tongue. Prime the spray before the first use by pumping 5 test sprays into the air, away from your face. Prime the spray with 1 test spray if it has not been used for longer than 14 days.

Store at room temperature away from moisture and heat. Do not freeze. Keep the Zolpimist bottle upright when not in use.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of zolpidem can be fatal, especially when it is taken together with other medications that can cause drowsiness.

Overdose symptoms may include sleepiness, confusion, shallow breathing, feeling light-headed, fainting, or coma.

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

• CNS-depressant effects and next-day impairment [see Warnings and Precautions (5.1)]
• Serious anaphylactic and anaphylactoid reactions [see Warnings and Precautions (5.3)]
• Abnormal thinking and behavior changes, and complex behaviors [see Warnings and Precautions (5.4)]
• Withdrawal effects [see Warnings and Precautions (5.8)]

Clinical Trials Experience

Associated with discontinuation of treatment: Approximately 4% of 1,701 patients who received Zolpidem at all doses (1.25 to 90 mg) in U.S. premarketing clinical trials discontinued treatment because of an adverse reaction. Reactions most commonly associated with discontinuation from U.S. trials were daytime drowsiness (0.5%), dizziness (0.4%), headache (0.5%), nausea (0.6%), and vomiting (0.5%).

Approximately 4% of 1,959 patients who received Zolpidem at all doses (1 to 50 mg) in similar foreign trials discontinued treatment because of an adverse reaction. Reactions most commonly associated with discontinuation from these trials were daytime drowsiness (1.1%), dizziness/vertigo (0.8%), amnesia (0.5%), nausea (0.5%), headache (0.4%), and falls (0.4%).

Data from a clinical study in which selective serotonin reuptake inhibitor (SSRI)-treated patients were given Zolpidem revealed that four of the seven discontinuations during double-blind treatment with Zolpidem (n=95) were associated with impaired concentration, continuing or aggravated depression, and manic reaction; one patient treated with placebo (n=97) was discontinued after an attempted suicide.

Most commonly observed adverse reactions in controlled trials: During short-term treatment (up to 10 nights) with Zolpidem tartrate at doses up to 10 mg, the most commonly observed adverse reactions associated with the use of Zolpidem and seen at statistically significant differences from placebo-treated patients were drowsiness (reported by 2% of Zolpidem patients), dizziness (1%), and diarrhea (1%). During longer-term treatment (28 to 35 nights) with Zolpidem at doses up to 10 mg, the most commonly observed adverse reactions associated with the use of Zolpidem and seen at statistically significant differences from placebo-treated patients were dizziness (5%) and drugged feelings (3%).

Adverse reactions observed at an incidence of ≥ 1% in controlled trials: The following tables enumerate treatment-emergent adverse reactions frequencies that were observed at an incidence equal to 1% or greater among patients with insomnia who received Zolpidem tartrate and at a greater incidence than placebo in U.S. placebo-controlled trials. Events reported by investigators were classified utilizing a modified World Health Organization (WHO) dictionary of preferred terms for the purpose of establishing event frequencies. The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice, in which patient characteristics and other factors differ from those that prevailed in these clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigators involving related drug products and uses, since each group of drug trials is conducted under a different set of conditions. However, the cited figures provide the physician with a basis for estimating the relative contribution of drug and nondrug factors to the incidence of side effects in the population studied.

The following table was derived from results of 11 placebo-controlled short-term U.S. efficacy trials involving Zolpidem in doses ranging from 1.25 to 20 mg. The table is limited to data from doses up to and including 10 mg, the highest dose recommended for use.

The following table was derived from results of three placebo-controlled long-term efficacy trials involving Zolpidem tartrate. These trials involved patients with chronic insomnia who were treated for 28 to 35 nights with Zolpidem at doses of 5, 10, or 15 mg. The table is limited to data from doses up to and including 10 mg, the highest dose recommended for use. The table includes only adverse events occurring at an incidence of at least 1% for Zolpidem patients. 

Dose relationship for adverse reactions: There is evidence from dose comparison trials suggesting a dose relationship for many of the adverse reactions associated with Zolpidem use, particularly for certain CNS and gastrointestinal adverse events.

Adverse event incidence across the entire preapproval database: Zolpidem tartrate was administered to 3,660 subjects in clinical trials throughout the U.S., Canada, and Europe. Treatment-emergent adverse events associated with clinical trial participation were recorded by clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals experiencing treatment-emergent adverse events, similar types of untoward events were grouped into a smaller number of standardized event categories and classified utilizing a modified World Health Organization (WHO) dictionary of preferred terms.

The frequencies presented, therefore, represent the proportions of the 3,660 individuals exposed to Zolpidem, at all doses, who experienced an event of the type cited on at least one occasion while receiving Zolpidem. All reported treatment-emergent adverse events are included, except those already listed in the table above of adverse events in placebo-controlled studies, those coding terms that are so general as to be uninformative, and those events where a drug cause was remote. It is important to emphasize that, although the events reported did occur during treatment with Zolpidem tartrate, they were not necessarily caused by it.

Adverse events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in greater than 1/100 subjects; infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in less than 1/1,000 patients.

Autonomic nervous system: Infrequent: increased sweating, pallor, postural hypotension, syncope. Rare: abnormal accommodation, altered saliva, flushing, glaucoma, hypotension, impotence, increased saliva, tenesmus.

Body as a whole: Frequent: asthenia. Infrequent: edema, falling, fatigue, fever, malaise, trauma. Rare: allergic reaction, allergy aggravated, anaphylactic shock, face edema, hot flashes, increased ESR, pain, restless legs, rigors, tolerance increased, weight decrease.

Cardiovascular system: Infrequent: cerebrovascular disorder, hypertension, tachycardia. Rare: angina pectoris, arrhythmia, arteritis, circulatory failure, extrasystoles, hypertension aggravated, myocardial infarction, phlebitis, pulmonary embolism, pulmonary edema, varicose veins, ventricular tachycardia.

Central and peripheral nervous system: Frequent: ataxia, confusion, euphoria, headache, insomnia, vertigo Infrequent: agitation, anxiety, decreased cognition, detached, difficulty concentrating, dysarthria, emotional lability, hallucination, hypoesthesia, illusion, leg cramps, migraine, nervousness, paresthesia, sleeping (after daytime dosing), speech disorder, stupor, tremor. Rare: abnormal gait, abnormal thinking, aggressive reaction, apathy, appetite increased, decreased libido, delusion, dementia, depersonalization, dysphasia, feeling strange, hypokinesia, hypotonia, hysteria, intoxicated feeling, manic reaction, neuralgia, neuritis, neuropathy, neurosis, panic attacks, paresis, personality disorder, somnambulism, suicide attempts, tetany, yawning.

Gastrointestinal system: Frequent: dyspepsia, hiccup, nausea. Infrequent: anorexia, constipation, dysphagia, flatulence, gastroenteritis, vomiting. Rare: enteritis, eructation, esophagospasm, gastritis, hemorrhoids, intestinal obstruction, rectal hemorrhage, tooth caries.

Hematologic and lymphatic system: Rare: anemia, hyperhemoglobinemia, leukopenia, lymphadenopathy, macrocytic anemia, purpura, thrombosis.

Immunologic system: Infrequent: infection. Rare: abscess herpes simplex herpes zoster, otitis externa, otitis media.

Liver and biliary system: Infrequent: abnormal hepatic function, increased SGPT. Rare: bilirubinemia, increased SGOT.

Metabolic and nutritional: Infrequent: hyperglycemia, thirst. Rare: gout, hypercholesteremia, hyperlipidemia, increased alkaline phosphatase, increased BUN, periorbital edema.

Musculoskeletal system: Frequent: arthralgia, myalgia. Infrequent: arthritis. Rare: arthrosis, muscle weakness, sciatica, tendinitis.

Reproductive system: Infrequent: menstrual disorder, vaginitis. Rare: breast fibroadenosis, breast neoplasm, breast pain.

Respiratory system:  Frequent: upper respiratory infection, lower respiratory infection. Infrequent: bronchitis, coughing, dyspnea, rhinitis. Rare: bronchospasm, respiratory depression, epistaxis, hypoxia, laryngitis, pneumonia.

Skin and appendages: Infrequent: pruritus. Rare: acne, bullous eruption, dermatitis, furunculosis, injection-site inflammation, photosensitivity reaction, urticaria.

Special senses: Frequent: diplopia, vision abnormal. Infrequent: eye irritation, eye pain, scleritis, taste perversion, tinnitus. Rare: conjunctivitis, corneal ulceration, lacrimation abnormal, parosmia, photopsia.

Urogenital system: Frequent: urinary tract infection. Infrequent: cystitis, urinary incontinence. Rare: acute renal failure, dysuria, micturition frequency, nocturia, polyuria, pyelonephritis, renal pain, urinary retention.

Postmarketing Experience

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

Liver and biliary system: acute hepatocellular, cholestatic or mixed liver injury with or without jaundice (i.e., bilirubin >2x ULN, alkaline phosphatase ≥2x ULN, transaminase ≥5x ULN).

Zolpidem tartrate USP is a gamma-aminobutyric acid (GABA) A agonist of the imidazopyridine class and is available in 5 mg and 10 mg strength tablets for oral administration.

Chemically, Zolpidem is N,N,6-trimethyl-2-p-tolylimidazo[1,2-a] pyridine-3-acetamide L-(+)-tartrate (2:1). It has the following structure:

Zolpidem tartrate USP is a white to off-white crystalline powder that is sparingly soluble in water, alcohol, and propylene glycol. It has a molecular weight of 764.88.

Each Zolpidem tartrate tablet, USP includes the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, hypromellose, polyethylene glycol, and titanium dioxide.

Meets USP Dissolution Test-3.

Mechanism of Action

Zolpidem, the active moiety of Zolpidem tartrate, is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties. It interacts with a GABA-BZ receptor complex and shares some of the pharmacological properties of the benzodiazepines. In contrast to the benzodiazepines, which non-selectively bind to and activate all BZ receptor subtypes, Zolpidem in vitro binds the BZ1 receptor preferentially with a high affinity ratio of the α1/α5 subunits. This selective binding of Zolpidem on the BZ1 receptor is not absolute, but it may explain the relative absence of myorelaxant and anticonvulsant effects in animal studies as well as the preservation of deep sleep (stages 3 and 4) in human studies of Zolpidem tartrate at hypnotic doses.

Pharmacokinetics

The pharmacokinetic profile of Zolpidem tartrate is characterized by rapid absorption from the gastrointestinal tract and a short elimination half-life (T1/2) in healthy subjects.

In a single-dose crossover study in 45 healthy subjects administered 5 and 10 mg Zolpidem tartrate tablets, the mean peak concentrations (Cmax) were 59 (range: 29 to 113) and 121 (range: 58 to 272) ng/mL, respectively, occurring at a mean time (Tmax) of 1.6 hours for both. The mean Zolpidem tartrate elimination half-life was 2.6 (range: 1.4 to 4.5) and 2.5 (range: 1.4 to 3.8) hours, for the 5 and 10 mg tablets, respectively. Zolpidem tartrate is converted to inactive metabolites that are eliminated primarily by renal excretion. Zolpidem tartrate demonstrated linear kinetics in the dose range of 5 to 20 mg. Total protein binding was found to be 92.5 ± 0.1% and remained constant, independent of concentration between 40 and 790 ng/mL. Zolpidem did not accumulate in young adults following nightly dosing with 20 mg Zolpidem tartrate tablets for 2 weeks.

A food-effect study in 30 healthy male subjects compared the pharmacokinetics of Zolpidem tartrate 10 mg when administered while fasting or 20 minutes after a meal. Results demonstrated that with food, mean AUC and Cmax were decreased by 15% and 25%, respectively, while mean Tmax was prolonged by 60% (from 1.4 to 2.2 hr). The half-life remained unchanged. These results suggest that, for faster sleep onset, Zolpidem tartrate should not be administered with or immediately after a meal.

Special Populations

Elderly:

In the elderly, the dose for Zolpidem tartrate should be 5 mg [see Warnings and Precautions (5) and Dosage and Administration (2)]. This recommendation is based on several studies in which the mean Cmax, T1/2, and AUC were significantly increased when compared to results in young adults. In one study of eight elderly subjects (> 70 years), the means for Cmax, T1/2, and AUC significantly increased by 50% (255 vs. 384 ng/mL), 32% (2.2 vs. 2.9 hr), and 64% (955 vs. 1,562 ng•hr/mL), respectively, as compared to younger adults (20 to 40 years) following a single 20 mg oral dose. Zolpidem tartrate did not accumulate in elderly subjects following nightly oral dosing of 10 mg for 1 week.

Hepatic Impairment:

The pharmacokinetics of Zolpidem tartrate in eight patients with chronic hepatic insufficiency were compared to results in healthy subjects. Following a single 20 mg oral Zolpidem tartrate dose, mean Cmax and AUC were found to be two times (250 vs. 499 ng/mL) and five times (788 vs. 4,203 ng•hr/mL) higher, respectively, in hepatically -compromised patients. Tmax did not change. The mean half-life in cirrhotic patients of 9.9 hr (range: 4.1 to 25.8 hr) was greater than that observed in normal subjects of 2.2 hr (range: 1.6 to 2.4 hr). [see Dosage and Administration (2.2), Warnings and Precautions (5.7), Use in Specific Populations (8.7)].

Renal Impairment:

The pharmacokinetics of Zolpidem tartrate were studied in 11 patients with end-stage renal failure (mean ClCr = 6.5 ± 1.5 mL/min) undergoing hemodialysis three times a week, who were dosed with Zolpidem tartrate 10 mg orally each day for 14 or 21 days. No statistically significant differences were observed for Cmax, Tmax, half-life, and AUC between the first and last day of drug administration when baseline concentration adjustments were made. Zolpidem was not hemodialyzable. No accumulation of unchanged drug appeared after 14 or 21 days. Zolpidem pharmacokinetics were not significantly different in renally impaired patients. No dosage adjustment is necessary in patients with compromised renal function. 

Drug Interactions

CNS-depressants

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

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.

An additive adverse effect on psychomotor performance between alcohol and oral Zolpidem was demonstrated [see Warnings and Precautions (5.1)].

Following five consecutive nightly doses at bedtime of oral Zolpidem tartrate 10 mg in the presence of sertraline 50 mg (17 consecutive daily doses, at 7:00 am, in healthy female volunteers), Zolpidem Cmax was significantly higher (43%) and Tmax was significantly decreased (-53%). Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by Zolpidem.

A single-dose interaction study with Zolpidem tartrate 10 mg and fluoxetine 20 mg at steady-state levels in male volunteers did not demonstrate any clinically significant pharmacokinetic or pharmacodynamic interactions. When multiple doses of Zolpidem and fluoxetine were given at steady state and the concentrations evaluated in healthy females, 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 inhibitors of other P450 enzymes on the pharmacokinetics of Zolpidem is unknown.

A single-dose interaction study with Zolpidem tartrate 10 mg and itraconazole 200 mg at steady-state levels in male volunteers resulted in a 34% increase in AUC0-∞ of Zolpidem tartrate. There were no pharmacodynamic effects of Zolpidem detected on subjective drowsiness, postural sway, or psychomotor performance.

A single-dose interaction study with Zolpidem tartrate 10 mg and rifampin 600 mg at steady-state levels in female subjects showed significant reductions of the AUC (-73%), Cmax (-58%), and T1/2 (-36 %) of Zolpidem together with significant reductions in the pharmacodynamic effects of Zolpidem tartrate. Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of Zolpidem [see Drug Interactions (7.2)].

Similarly, St. John's Wort, a CYP3A4 inducer, may also decrease the blood levels of Zolpidem.  

A single-dose interaction study with Zolpidem tartrate 5 mg and ketoconazole, a potent CYP3A4 inhibitor, given as 200 mg twice daily for 2 days increased Cmax of Zolpidem (30%) and the total AUC of Zolpidem (70%) compared to Zolpidem alone and prolonged the elimination half-life (30 %) along with an increase in the pharmacodynamic effects of Zolpidem [see Drug Interactions (7.2)].  

Additionally, fluvoxamine (a strong inhibitor of CYP1A2 and a weak inhibitor of CYP3A4 and CYP2C9) and ciprofloxacin (a strong inhibitor of CYP1A2 and a moderate inhibitor of CYP3A4) are also likely to inhibit Zolpidem’s metabolic pathways, potentially leading to an increase in Zolpidem exposure.

Other Drugs with No Interactions with Zolpidem

A study involving cimetidine/Zolpidem tartrate and ranitidine/Zolpidem tartrate combinations revealed no effect of either drug on the pharmacokinetics or pharmacodynamics of Zolpidem.

Zolpidem tartrate had no effect on digoxin pharmacokinetics and did not affect prothrombin time when given with warfarin in healthy subjects.

Zolpidem Tartrate Tablets USP, 5 mg are white to off-white, circular, biconvex, film-coated tablets, debossed with “E” on one side and “78” on the other side.

                     Bottles of 100                                   NDC 16714-621-01
                     Bottles of 500                                   NDC 16714-621-02
                     10 x 10 Unit-dose Tablets                 NDC 16714-621-11

Zolpidem Tartrate Tablets USP, 10 mg are white to off-white, oval shaped, biconvex, film-coated tablets, debossed with “E” on one side and “79” on the other side.

                       Bottles of 100                                   NDC 16714-622-01
                       Bottles of 500                                   NDC 16714-622-02
                       10 x 10 Unit-dose Tablets                 NDC 16714-622-11

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

See FDA-approved patient labeling (Medication Guide).

Inform patients and their families about the benefits and risks of treatment with Zolpidem tartrate. Inform patients of the availability of a Medication Guide and instruct them to read the Medication Guide prior to initiating treatment with Zolpidem tartrate and with each prescription refill. Review the Zolpidem tartrate Medication Guide with every patient prior to initiation of treatment. Instruct patients or caregivers that Zolpidem tartrate should be taken only as prescribed.

CNS Depressant Effects and Next-Day Impairment

Tell patients that Zolpidem tartrate has the potential to cause next-day impairment, and that this risk is increased if dosing instructions are not carefully followed. Tell patients to wait for at least 8 hours after dosing before driving or engaging in other activities requiring full mental alertness. Inform patients that impairment can be present despite feeling fully awake.

Severe Anaphylactic and Anaphylactoid Reactions

Inform patients that severe anaphylactic and anaphylactoid reactions have occurred with Zolpidem. Describe the signs/symptoms of these reactions and advise patients to seek medical attention immediately if any of them occur.

Sleep-driving and Other Complex Behaviors

Instruct patients and their families that sedative hypnotics can cause abnormal thinking and behavior change, including “sleep driving” and other complex behaviors while not being fully awake (preparing and eating food, making phone calls, or having sex). Tell patients to call you immediately if they develop any of these symptoms.

Suicide

Tell patients to immediately report any suicidal thoughts.

Alcohol and Other Drugs

Ask patients about alcohol consumption, medicines they are taking, and drugs they may be taking without a prescription. Advise patients not to use Zolpidem tartrate if they drank alcohol that evening or before bed.

Tolerance, Abuse, and Dependence

Tell patients not to increase the dose of Zolpidem tartrate on their own, and to inform you if they believe the drug “does not work”.

Administration Instructions

Patients should be counseled to take Zolpidem tartrate right before they get into bed and only when they are able to stay in bed a full night (7 to 8 hours) before being active again. Zolpidem tartrate tablets should not be taken with or immediately after a meal. Advise patients NOT to take Zolpidem tartrate if they drank alcohol that evening.

Medication Guides available at www.northstarrxllc.com/products or call 1-800-206-7821.

Revised: 06/2017

Rx only
NDC 16714-621-01
Zolpidem Tartrate
Tablets, USP 5 mg CIV
PHARMACIST: PLEASE DISPENSE WITH
MEDICATION GUIDE PROVIDED SEPARATELY.
100 Tablets
Northstar Rx LLC

• Hypnotic, Miscellaneous

Insomnia: Oral: Note: The lowest effective dose should be used; higher doses may be more likely to impair next morning activities.

Immediate release tablet, spray: 5 mg (females) or 5 to 10 mg (males) immediately before bedtime; maximum dose: 10 mg daily

Extended release tablet: 6.25 mg (females) or 6.25 to 12.5 mg (males) immediately before bedtime; maximum dose: 12.5 mg daily

Sublingual tablet:

Edluar, Sublinox [Canadian product]: 5 mg (females) or 5 to 10 mg (males) immediately before bedtime; if 5 mg dose is ineffective may increase to 10 mg (maximum dose: 10 mg daily)

Intermezzo: Note: Take in bed only if ≥4 hours left before waking and there is difficulty in returning to sleep

Females: 1.75 mg once per night as needed (maximum: 1.75 mg/night)

Males: 3.5 mg once per night as needed (maximum: 3.5 mg/night)

Dosage adjustment with concomitant CNS depressants: Females and males: 1.75 mg once per night as needed; dose adjustment of concomitant CNS depressant(s) may be necessary.

Debilitated:

Immediate release tablet, spray: 5 mg immediately before bedtime

Sublingual tablet:

Edluar, Sublinox [Canadian product]: 5 mg immediately before bedtime

Extended release tablet: 6.25 mg immediately before bedtime

Immediate release tablet:

Mild to moderate impairment: 5 mg immediately before bedtime

Severe impairment: Avoid use

Extended release tablet:

Mild to moderate impairment: 6.25 mg immediately before bedtime

Severe impairment: Avoid use

Oral spray: 5 mg immediately before bedtime

Sublingual tablet:

Edluar: 5 mg immediately before bedtime

Intermezzo: Females and males: 1.75 mg once per night as needed. Note: Take in bed only if ≥4 hours left before waking and there is difficulty in returning to sleep.

Sublinox [Canadian product]:

Mild to moderate impairment: 5 mg immediately before bedtime

Severe impairment: Use is contraindicated.

Commonly reported side effects of zolpidem include: dizziness and drowsiness. Other side effects include: myalgia, visual hallucination, anxiety, hallucination, and nausea. See below for a comprehensive list of adverse effects.

No adjustment recommended; however, closely monitor patients as a general precaution.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule IV

This drug is not dialyzable.

• Food delays the onset of effect so zolpidem will work faster if not taken with food. Take tablets immediately before going to bed, not sooner.
• Sublingual tablets should be placed under the tongue and allowed to disintegrate. Do not swallow whole. Protect from light and moisture. Edluar should not be taken with water.
• Zolpimist should be sprayed directly into the mouth over the tongue. Prime pump prior to initial use or if not used for at least 14 days.
• The extended-release form of zolpidem may help with staying asleep, as well as sleep initiation. Do not cut, crush, or chew extended-release forms.
• Higher dosages and extended-release forms may impair next-day alertness and ability to drive.
• One dosage form of zolpidem (Intermezzo) should only be taken by people who awaken in the middle of the night with more than four hours of sleep remaining; do not take if less than four hours sleep remaining. Other forms of zolpidem (Ambien, Edluar, Zolpimist, Ambien CR) should only be taken if there are 7 to 8 hours that can be devoted to sleep before awakening.
• Be cautious about driving or operating machinery the next day if you are still feeling sleepy after taking zolpidem the night before.
• If your mood changes or you experience depression or a worsening of depression, talk with your doctor.
• Zolpidem may make you feel dizzy, increasing your risk of falls. Be careful when sitting or standing up after lying down.
• The safety and effectiveness of zolpidem in children has not been demonstrated.

• Time to peak effect varies depending on formulation but ranges from just over half an hour to 1.5 hours. Food delays time to peak.
• Duration of effect also varies depending on formulation but immediate-release tablets last 6-8 hours.
• Immediate-release forms of zolpidem are Ambien, Intermezzo, Edluar, and Zolpimist. These help a person to fall asleep. Intermezzo may also be used if a person awakens in the middle of the night and has trouble falling back to sleep (although at least four hours of potential sleep time should still remain).
• Ambien CR is an extended-release form of zolpidem. It consists of an outer layer that dissolves quickly to help a person fall asleep and a second layer that dissolves slowly to help a person stay asleep.

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