Save up to 80% by drug discount in your pharmacy with "Pharmacy Near Me - National Drug Discount Card"
You can scan QR Code(just open camera on your phone/scan by application) from the image on prescription drug discount card to save it to your mobile phone. Or just click on image if you're on mobile phone.
| Product NDC Code | 55700-357 | ||||||
|---|---|---|---|---|---|---|---|
| Drug Name | Zolpidem tartrate |
||||||
| Type | Generic | ||||||
| Pharm Class | Central Nervous System Depression [PE], GABA A Receptor Positive Modulators [MoA], gamma-Aminobutyric Acid A Receptor Positive Modulator [EPC] |
||||||
| Active Ingredients |
|
||||||
| Route | ORAL | ||||||
| Dosage Form | TABLET | ||||||
| RxCUI drug identifier | 854873 | ||||||
| Application Number | ANDA077903 | ||||||
| Labeler Name | Lake Erie Medical DBA Quality Care Products LLC | ||||||
| Packages |
|
||||||
| Check if available Online | Get Medication Prices online with Discount |
Abuse
Information about the types of abuse that can occur with the drug and adverse reactions pertinent to those types of abuse, primarily based on human data. May include descriptions of particularly susceptible patient populations.9.2 Abuse Abuse and addiction are separate and distinct from physical dependence and tolerance. 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 a diminution of one or more of the drug effects over time. Tolerance may occur to both desired and undesired effects of drugs and may develop at different rates for different effects. Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. Its characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, using a multidisciplinary approach, but relapse is common. Studies of abuse potential in former drug abusers found that the effects of single doses of zolpidem tartrate 40 mg were similar, but not identical, to diazepam 20 mg, while zolpidem tartrate 10 mg was difficult to distinguish from placebo. Because persons with a history of addiction to, or abuse of, drugs or alcohol are at increased risk for misuse, abuse and addiction of zolpidem, they should be monitored carefully when receiving zolpidem or any other hypnotic.
Controlled substance
Information about the schedule in which the drug is controlled by the Drug Enforcement Administration, if applicable.9.1 Controlled Substance Zolpidem tartrate is classified as a Schedule IV controlled substance by federal regulation.
Dependence
Information about characteristic effects resulting from both psychological and physical dependence that occur with the drug, the quantity of drug over a period of time that may lead to tolerance or dependence, details of adverse effects related to chronic abuse and the effects of abrupt withdrawl, procedures necessary to diagnose the dependent state, and principles of treating the effects of abrupt withdrawal.9.3 Dependence Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. 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. The following adverse events which are considered to meet the DSM-III-R criteria for uncomplicated sedative/hypnotic withdrawal were reported during U.S. clinical trials following placebo substitution occurring within 48 hours following last zolpidem treatment: fatigue, nausea, flushing, lightheadedness, uncontrolled crying, emesis, stomach cramps, panic attack, nervousness and abdominal discomfort. These reported adverse events occurred at an incidence of 1% or less. However, available data cannot provide a reliable estimate of the incidence, if any, of dependence during treatment at recommended doses. Post-marketing reports of abuse, dependence and withdrawal have been received.
Drug abuse and dependence
Information about whether the drug is a controlled substance, the types of abuse that can occur with the drug, and adverse reactions pertinent to those types of abuse.9. DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance Zolpidem tartrate is classified as a Schedule IV controlled substance by federal regulation. 9.2 Abuse Abuse and addiction are separate and distinct from physical dependence and tolerance. 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 a diminution of one or more of the drug effects over time. Tolerance may occur to both desired and undesired effects of drugs and may develop at different rates for different effects. Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. Its characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, using a multidisciplinary approach, but relapse is common. Studies of abuse potential in former drug abusers found that the effects of single doses of zolpidem tartrate 40 mg were similar, but not identical, to diazepam 20 mg, while zolpidem tartrate 10 mg was difficult to distinguish from placebo. Because persons with a history of addiction to, or abuse of, drugs or alcohol are at increased risk for misuse, abuse and addiction of zolpidem, they should be monitored carefully when receiving zolpidem or any other hypnotic. 9.3 Dependence Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. 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. The following adverse events which are considered to meet the DSM-III-R criteria for uncomplicated sedative/hypnotic withdrawal were reported during U.S. clinical trials following placebo substitution occurring within 48 hours following last zolpidem treatment: fatigue, nausea, flushing, lightheadedness, uncontrolled crying, emesis, stomach cramps, panic attack, nervousness and abdominal discomfort. These reported adverse events occurred at an incidence of 1% or less. However, available data cannot provide a reliable estimate of the incidence, if any, of dependence during treatment at recommended doses. Post-marketing reports of abuse, dependence and withdrawal have been received.
Overdosage of zolpidem tartrate
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10. OVERDOSAGE 10.1 Signs and Symptoms In postmarketing experience of overdose with zolpidem tartrate alone, or in combination with CNS-depressant agents, impairment of consciousness ranging from somnolence to coma, cardiovascular and/or respiratory compromise, and fatal outcomes have been reported. 10.2 Recommended Treatment General symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. Zolpidem’s sedative hypnotic effect was shown to be reduced by flumazenil and therefore may be useful; however, flumazenil administration may contribute to the appearance of neurological symptoms (convulsions). As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention. Sedating drugs should be withheld following zolpidem overdosage, even if excitation occurs. The value of dialysis in the treatment of overdosage has not been determined, although hemodialysis studies in patients with renal failure receiving therapeutic doses have demonstrated that zolpidem is not dialyzable. As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. The physician may wish to consider contacting a poison control center for up-to-date information on the management of hypnotic drug product overdosage.
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6. ADVERSE REACTIONS Most commonly observed adverse reactions were: Short-term (< 10 nights): Drowsiness, dizziness, and diarrhea Long-term (28 - 35 nights): Dizziness and drugged feelings ( ) 6.1 To report SUSPECTED ADVERSE REACTIONS, contact Torrent Pharma Inc. at 1-269-544-2299 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following serious 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 (5.7)] 6.1 Clinical Trials Experience 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%). Associated with discontinuation of treatment: 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. During short-term treatment (up to 10 nights) with zolpidem tartrate tablets 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%). Most commonly observed adverse reactions 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. Adverse reactions observed at an incidence of 1% in controlled trials: 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. Incidence of Treatment-Emergent Adverse Experiences in Placebo-Controlled Clinical Trials Lasting up to 10 Nights (Percentage of patients reporting) Zolpidem Body System/ (≤10 mg) Placebo Adverse Event Reactions reported by at least 1% of patients treated with zolpidem tartrate tablets and at a greater frequency than placebo. (N=685) (N=473) Central and Peripheral Nervous System Headache 7 6 Drowsiness 2 - Dizziness 1 - Gastrointestinal System Diarrhea 1 - The following table was derived from results of three placebo-controlled long-term efficacy trials involving zolpidem tartrate tablets. 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. Incidence of Treatment-Emergent Adverse Experiences in Placebo-Controlled Clinical Trials Lasting up to 35 Nights (Percentage of patients reporting) Zolpidem Body System/ (≤10 mg) Placebo Adverse Event Reactions reported by at least 1% of patients treated with zolpidem tartrate tablets and at a greater frequency than placebo. (N=152) (N=161) Autonomic Nervous System Dry mouth 3 1 Body as a Whole Allergy 4 1 Back Pain 3 2 Influenza-like symptoms 2 - Chest pain 1 - Cardiovascular System Palpitation 2 - Central and Peripheral Nervous System Drowsiness 8 5 Dizziness 5 1 Lethargy 3 1 Drugged feeling 3 - Lightheadedness 2 1 Depression 2 1 Abnormal dreams 1 - Amnesia 1 - Sleep disorder 1 - Gastrointestinal System Diarrhea 3 2 Abdominal pain 2 2 Constipation 2 1 Respiratory System Sinusitis 4 2 Pharyngitis 3 1 Skin and Appendages Rash 2 1 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. Dose relationship for adverse reactions: Zolpidem tartrate tablets were 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. Adverse event incidence across the entire preapproval database: 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 tablets, 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. Infrequent: increased sweating, pallor, postural hypotension, syncope. Rare: abnormal accommodation, altered saliva, flushing, glaucoma, hypotension, impotence, increased saliva, tenesmus. Autonomic nervous system: 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. Body as a whole: 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. Cardiovascular 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. Central and peripheral nervous system: Frequent: dyspepsia, hiccup, nausea. Infrequent: anorexia, constipation, dysphagia, flatulence, gastroenteritis, vomiting. Rare: enteritis, eructation, esophagospasm, gastritis, hemorrhoids, intestinal obstruction, rectal hemorrhage, tooth caries. Gastrointestinal system: Rare: anemia, hyperhemoglobinemia, leukopenia, lymphadenopathy, macrocytic anemia, purpura, thrombosis. Hematologic and lymphatic system: Infrequent: infection. Rare: abscess, herpes simplex, herpes zoster, otitis externa, otitis media. Immunologic system: Infrequent: abnormal hepatic function, increased SGPT. Rare: bilirubinemia, increased SGOT. Liver and biliary system: Infrequent: hyperglycemia, thirst. Rare: gout, hypercholesteremia, hyperlipidemia, increased alkaline phosphatase, increased BUN, periorbital edema. Metabolic and nutritional: Frequent: arthralgia, myalgia. Infrequent: arthritis. Rare: arthrosis, muscle weakness, sciatica, tendinitis. Musculoskeletal system: Infrequent: menstrual disorder, vaginitis. Rare: breast fibroadenosis, breast neoplasm, breast pain. Reproductive system: Frequent: upper respiratory infection, lower respiratory infection. Infrequent: bronchitis, coughing, dyspnea, rhinitis. Rare: bronchospasm, respiratory depression, epistaxis, hypoxia, laryngitis, pneumonia. Respiratory system: Infrequent: pruritus. Rare: acne, bullous eruption, dermatitis, furunculosis, injection-site inflammation, photosensitivity reaction, urticaria. Skin and appendages: Frequent: diplopia, vision abnormal. Infrequent: eye irritation, eye pain, scleritis, taste perversion, tinnitus. Rare: conjunctivitis, corneal ulceration, lacrimation abnormal, parosmia, photopsia. Special senses: Frequent: urinary tract infection. Infrequent: cystitis, urinary incontinence. Rare: acute renal failure, dysuria, micturition frequency, nocturia, polyuria, pyelonephritis, renal pain, urinary retention. Urogenital system:
| Zolpidem | ||
| Body System/ | (≤10 mg) | Placebo |
| Adverse Event | (N=685) | (N=473) |
| Central and Peripheral Nervous System | ||
| Headache | 7 | 6 |
| Drowsiness | 2 | - |
| Dizziness | 1 | - |
| Gastrointestinal System | ||
| Diarrhea | 1 | - |
| Zolpidem | ||
| Body System/ | (≤10 mg) | Placebo |
| Adverse Event | (N=152) | (N=161) |
| Autonomic Nervous System | ||
| Dry mouth | 3 | 1 |
| Body as a Whole | ||
| Allergy | 4 | 1 |
| Back Pain | 3 | 2 |
| Influenza-like symptoms | 2 | - |
| Chest pain | 1 | - |
| Cardiovascular System | ||
| Palpitation | 2 | - |
| Central and Peripheral Nervous System | ||
| Drowsiness | 8 | 5 |
| Dizziness | 5 | 1 |
| Lethargy | 3 | 1 |
| Drugged feeling | 3 | - |
| Lightheadedness | 2 | 1 |
| Depression | 2 | 1 |
| Abnormal dreams | 1 | - |
| Amnesia | 1 | - |
| Sleep disorder | 1 | - |
| Gastrointestinal System | ||
| Diarrhea | 3 | 2 |
| Abdominal pain | 2 | 2 |
| Constipation | 2 | 1 |
| Respiratory System | ||
| Sinusitis | 4 | 2 |
| Pharyngitis | 3 | 1 |
| Skin and Appendages | ||
| Rash | 2 | 1 |
zolpidem tartrate Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7. DRUG 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 effect (7.2) 7.1 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 for several CNS drugs. [see Warnings and Precautions (5.1)]. Imipramine, Chlorpromazine 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 . [see Clinical Pharmacology (12.3)] 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 . [see Clinical Pharmacology (12.3)] Alcohol An additive adverse effect on psychomotor performance between alcohol and oral zolpidem was demonstrated . [see Warnings and Precautions (5.1)] Sertraline Concomitant administration of zolpidem and sertraline increases exposure to zolpidem . [see Clinical Pharmacology (12.3)] 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 drugs on 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.
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12. CLINICAL PHARMACOLOGY 12.1 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 binds the BZ receptor preferentially with a high affinity ratio of the α /α subunits. This selective binding of zolpidem on the BZ 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. in vitro 1 1 5 1 12.3 Pharmacokinetics The pharmacokinetic profile of zolpidem tartrate tablets is characterized by rapid absorption from the gastrointestinal tract and a short elimination half-life (T ) in healthy subjects. 1/2 In a single-dose crossover study in 45 healthy subjects administered 5 and 10 mg zolpidem tartrate tablets, the mean peak concentrations (C ) were 59 (range: 29 to 113) and 121 (range: 58 to 272) ng/mL, respectively, occurring at a mean time (T ) of 1.6 hours for both. The mean zolpidem tartrate tablets 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 tablets are converted to inactive metabolites that are eliminated primarily by renal excretion. Zolpidem tartrate tablets 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. max max A food-effect study in 30 healthy male subjects compared the pharmacokinetics of zolpidem tartrate tablets 10 mg when administered while fasting or 20 minutes after a meal. Results demonstrated that with food, mean AUC and C were decreased by 15% and 25%, respectively, while mean T 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 tablets should not be administered with or immediately after a meal. max max Special Populations Elderly: In the elderly, the dose for zolpidem tartrate tablets should be 5 mg This recommendation is based on several studies in which the mean C , T , and AUC were significantly increased when compared to results in young adults. In one study of eight elderly subjects (>70 years), the means for C , T , 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 tablets did not accumulate in elderly subjects following nightly oral dosing of 10 mg for 1 week. [see and ]. Warnings and Precautions (5) Dosage and Administration (2) max 1/2 max 1/2 Hepatic Impairment: The pharmacokinetics of zolpidem tartrate tablets in eight patients with chronic hepatic insufficiency were compared to results in healthy subjects. Following a single 20 mg oral zolpidem tartrate dose, mean C 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. T 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). Dosing should be modified accordingly in patients with hepatic insufficiency . max max [see Dosage and Administration (2.2)] Renal Impairment: The pharmacokinetics of zolpidem tartrate were studied in 11 patients with end-stage renal failure (mean Cl = 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 C , T , 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. Cr max max Drug Interactions CNS-depressants 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 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. [see Warnings and Precautions (5.1)]. 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 C was significantly higher (43%) and T was significantly decreased (-53%). Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem. max max 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 AUC of zolpidem tartrate. There were no pharmacodynamic effects of zolpidem detected on subjective drowsiness, postural sway, or psychomotor performance. 0-∞ 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%), C (-58%), and T (-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. max 1/2 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 C 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. Consideration should be given to using a lower dose of zolpidem when ketoconazole and zolpidem are given together. max 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.
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 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 binds the BZ receptor preferentially with a high affinity ratio of the α /α subunits. This selective binding of zolpidem on the BZ 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. in vitro 1 1 5 1
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics The pharmacokinetic profile of zolpidem tartrate tablets is characterized by rapid absorption from the gastrointestinal tract and a short elimination half-life (T ) in healthy subjects. 1/2 In a single-dose crossover study in 45 healthy subjects administered 5 and 10 mg zolpidem tartrate tablets, the mean peak concentrations (C ) were 59 (range: 29 to 113) and 121 (range: 58 to 272) ng/mL, respectively, occurring at a mean time (T ) of 1.6 hours for both. The mean zolpidem tartrate tablets 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 tablets are converted to inactive metabolites that are eliminated primarily by renal excretion. Zolpidem tartrate tablets 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. max max A food-effect study in 30 healthy male subjects compared the pharmacokinetics of zolpidem tartrate tablets 10 mg when administered while fasting or 20 minutes after a meal. Results demonstrated that with food, mean AUC and C were decreased by 15% and 25%, respectively, while mean T 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 tablets should not be administered with or immediately after a meal. max max Special Populations Elderly: In the elderly, the dose for zolpidem tartrate tablets should be 5 mg This recommendation is based on several studies in which the mean C , T , and AUC were significantly increased when compared to results in young adults. In one study of eight elderly subjects (>70 years), the means for C , T , 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 tablets did not accumulate in elderly subjects following nightly oral dosing of 10 mg for 1 week. [see and ]. Warnings and Precautions (5) Dosage and Administration (2) max 1/2 max 1/2 Hepatic Impairment: The pharmacokinetics of zolpidem tartrate tablets in eight patients with chronic hepatic insufficiency were compared to results in healthy subjects. Following a single 20 mg oral zolpidem tartrate dose, mean C 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. T 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). Dosing should be modified accordingly in patients with hepatic insufficiency . max max [see Dosage and Administration (2.2)] Renal Impairment: The pharmacokinetics of zolpidem tartrate were studied in 11 patients with end-stage renal failure (mean Cl = 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 C , T , 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. Cr max max Drug Interactions CNS-depressants 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 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. [see Warnings and Precautions (5.1)]. 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 C was significantly higher (43%) and T was significantly decreased (-53%). Pharmacokinetics of sertraline and N-desmethylsertraline were unaffected by zolpidem. max max 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 AUC of zolpidem tartrate. There were no pharmacodynamic effects of zolpidem detected on subjective drowsiness, postural sway, or psychomotor performance. 0-∞ 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%), C (-58%), and T (-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. max 1/2 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 C 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. Consideration should be given to using a lower dose of zolpidem when ketoconazole and zolpidem are given together. max 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.
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4. CONTRAINDICATIONS Known hypersensitivity to zolpidem (4) Zolpidem tartrate tablets are contraindicated in patients with known hypersensitivity to zolpidem. Observed reactions include anaphylaxis and angioedema . [see Warnings and Precautions (5.3)]
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11. DESCRIPTION Zolpidem tartrate 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: hypromellose, lactose monohydrate, microcrystalline cellulose, magnesium stearate, polyethylene glycol, sodium starch glycolate, titanium dioxide and ferric oxide red; the 10 mg tablet also contains ferric oxide yellow. Image 1
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2. DOSAGE AND ADMINISTRATION Use the lowest dose effective for the patient (2.1) Recommended initial dose is 5 mg for women and 5 or 10 mg for men, immediately before bedtime with at least 7-8 hours remaining before the planned time of awakening (2.1) Geriatric patients and patients with hepatic impairment: Recommended dose is 5 mg for men and women (2.2) Lower doses of CNS depressants may be necessary when taken concomitantly with zolpidem tartrate tablets (2.3) The effect of zolpidem tartrate tablets may be slowed if taken with or immediately after a meal (2.4) 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 7-8 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 . The total dose of zolpidem tartrate tablets should not exceed 10 mg once daily immediately before bedtime. [see Warnings and Precautions (5.1)] 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. Patients with hepatic insufficiency do not clear the drug as rapidly as normal subjects. The recommended dose of zolpidem tartrate in both of these patient populations is 5 mg once daily immediately before bedtime [see Warnings and Precautions (5.1); Use in Specific Populations (8.5)]. 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.
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3. DOSAGE FORMS AND STRENGTHS 5 mg and 10 mg tablets. Tablets scored. ( ) not 3 Zolpidem tartrate tablets are available in 5 mg and 10 mg strength tablets for oral administration. Tablets are not scored. Zolpidem tartrate 5 mg tablets are red colored, capsule shaped tablets with the Torrent logo debossed on one side and '5 MG' debossed on the other side. Zolpidem tartrate 10 mg tablets are peach-yellow colored, capsule shaped tablets with the Torrent logo debossed on one side and '10 MG' debossed on the other side.
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1. INDICATIONS AND USAGE Zolpidem tartrate tablets, USP are gamma-amino butyric acid (GABA) A agonist, are indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. Zolpidem tartrate tablets, USP have been shown to decrease sleep latency for up to 35 days in controlled clinical studies. ( 1) Zolpidem tartrate tablets, USP are indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. Zolpidem tartrate tablets, USP 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 4-5 weeks in duration with the final formal assessments of sleep latency performed at the end of treatment.
Spl product data elements
Usually a list of ingredients in a drug product.ZOLPIDEM TARTRATE zolpidem tartrate ZOLPIDEM TARTRATE ZOLPIDEM FERRIC OXIDE RED peach-yellow Capsule 10MG
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Zolpidem was administered to mice and rats for 2 years at oral dosages of 4, 18, and 80 mg base/kg. In mice, these doses are approximately 2.5, 10, and 50 times the maximum recommended human dose (MRHD) of 10 mg/day (8 mg zolpidem base) on mg/m basis. In rats, these doses are approximately 5, 20, and 100 times the MRHD on a mg/m basis. No evidence of carcinogenic potential was observed in mice. In rats, renal tumors (lipoma, liposarcoma) were seen at the mid- and high doses. Carcinogenesis: 2 2 Zolpidem was negative in (bacterial reverse mutation, mouse lymphoma, and chromosomal aberration) and (mouse micronucleus) genetic toxicology assays. Mutagenesis: in vitro in vivo : Oral administration of zolpidem (doses of 4, 20, and 100 mg base/kg/day) to rats prior to and during mating, and continuing in females through postpartum day 25, resulted in irregular estrus cycles and prolonged precoital intervals at the highest dose tested. The no-effect dose for these findings is approximately 24 times the MRHD on a mg/m basis. There was no impairment of fertility at any dose tested. Impairment of fertility 2
Nonclinical toxicology
Information about toxicology in non-human subjects.13. NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Zolpidem was administered to mice and rats for 2 years at oral dosages of 4, 18, and 80 mg base/kg. In mice, these doses are approximately 2.5, 10, and 50 times the maximum recommended human dose (MRHD) of 10 mg/day (8 mg zolpidem base) on mg/m basis. In rats, these doses are approximately 5, 20, and 100 times the MRHD on a mg/m basis. No evidence of carcinogenic potential was observed in mice. In rats, renal tumors (lipoma, liposarcoma) were seen at the mid- and high doses. Carcinogenesis: 2 2 Zolpidem was negative in (bacterial reverse mutation, mouse lymphoma, and chromosomal aberration) and (mouse micronucleus) genetic toxicology assays. Mutagenesis: in vitro in vivo : Oral administration of zolpidem (doses of 4, 20, and 100 mg base/kg/day) to rats prior to and during mating, and continuing in females through postpartum day 25, resulted in irregular estrus cycles and prolonged precoital intervals at the highest dose tested. The no-effect dose for these findings is approximately 24 times the MRHD on a mg/m basis. There was no impairment of fertility at any dose tested. Impairment of fertility 2
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.image description
Recent major changes
A list of the section(s) that contain substantive changes that have been approved by FDA in the product labeling. The headings and subheadings, if appropriate, affected by the change are listed together with each section’s identifying number and the month and year on which the change was incorporated in the labeling.Warnings and Precautions, Severe Injuries (5.8) 10/2014
zolpidem tartrate: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17. PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Medication Guide). Inform patients and their families about the benefits and risks of treatment with zolpidem. Inform patients of the availability of a Medication Guide and instruct them to read the Medication Guide prior to initiating treatment with zolpidem and with each prescription refill. Review the zolpidem tartrate tablets Medication Guide with every patient prior to initiation of treatment. Instruct patients or caregivers that zolpidem tartrate tablets should be taken only as prescribed. CNS Depressant Effects and Next-Day Impairment Tell patients that zolpidem 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 if they drank alcohol that evening or before bed. Tolerance, Abuse, and Dependence Tell patients not to increase the dose of zolpidem on their own, and to inform you if they believe the drug "does not work". Administration Instructions Patients should be counseled to take zolpidem right before they get into bed and only when they are able to stay in bed a full night (7-8 hours) before being active again. Zolpidem tablets should not be taken with or immediately after a meal. Advise patients NOT to take zolpidem if they drank alcohol that evening. Manufactured by: TORRENT PHARMACEUTICALS LTD., Indrad-382 721, Dist. Mehsana, INDIA. For: TORRENT PHARMA INC., 150 Allen Road, Suite 102, Basking Ridge, NJ 07920. 8052216 Revised November 2014 image
Spl medguide
Information about the patient medication guide that accompanies the drug product. Certain drugs must be dispensed with an accompanying medication guide. This field may contain information about when to consult the medication guide and the contents of the medication guide.MEDICATION GUIDE Z olpidem Tartrate (zole-PI-dem TAR-trate) Tablets, USP C-IV Read the Medication Guide that comes with zolpidem tartrate tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. What is the most important information I should know about zolpidem tartrate tablets? • Do not take more zolpidem tartrate tablets than prescribed. • Do not take zolpidem tartrate tablets unless you are able to stay in bed a full night (7 to 8 hours) before you must be active again. • Take zolpidem tartrate tablets right before you get in bed, not sooner. Zolpidem tartrate tablets may cause serious side effects, including: You have a higher chance for doing these activities if you drink alcohol or take other medicines that make you sleepy with zolpidem tartrate tablets. Reported activities include: After taking zolpidem tartrate tablets, you may get up out of bed while not being fully awake and do an activity that you do not know you are doing. The next morning, you may not remember that you did anything during the night. ○ driving a car ("sleep-driving") ○ making and eating food ○ talking on the phone ○ having sex ○ sleep-walking Call your healthcare provider right away if you find out that you have done any of the above activities after taking zolpidem tartrate tablets. Do not take zolpidem tartrate tablets if you: drank alcohol that evening or before bed took another medicine to help you sleep. What are zolpidem tartrate tablets? Zolpidem tartrate tablets are sedative-hypnotic (sleep) medicine. Zolpidem tartrate tablets are used in adults for the short-term treatment of a sleep problem called insomnia (trouble falling asleep). It is not known if zolpidem tartrate tablets are safe and effective in children under the age of 18 years. Zolpidem tartrate is a federally controlled substance (C-IV) because it can be abused or lead to dependence. Keep zolpidem tartrate tablets in a safe place to prevent misuse and abuse. Selling or giving away zolpidem tartrate tablets may harm others, and is against the law. Tell your healthcare provider if you have ever abused or have been dependent on alcohol, prescription medicines or street drugs. Who should not take zolpidem tartrate tablets? • Do not take zolpidem tartrate tablets if you are allergic to zolpidem or any other ingredients in zolpidem tartrate tablets. See the end of this Medication Guide for a complete list of ingredients in zolpidem tartrate tablets. • Do not take zolpidem tartrate tablets if you have had an allergic reaction to drugs containing zolpidem, such as zolpidem tartrate CR tablets, Edluar, Zolpimist, or Intermezzo. Symptoms of a serious allergic reaction to zolpidem can include: • swelling of your face, lips, and throat that may cause difficulty breathing or swallowing What should I tell my healthcare provider before taking zolpidem tartrate tablets? Zolpidem tartrate tablets may not be right for you. Before starting zolpidem tartrate tablets, tell your healthcare provider about all of your health 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. It is not known if zolpidem tartrate tablets will harm your unborn baby. are breastfeeding or plan to breastfeed. Zolpidem tartrate tablets can pass into your breast milk. It is not known if zolpidem tartrate tablets will harm your baby. Talk to your healthcare provider about the best way to feed your baby while you take zolpidem tartrate tablets. Tell your healthcare provider about all of the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. Medicines can interact with each other, sometimes causing serious side effects. Do not take zolpidem tartrate tablets with other medicines that can make you sleepy unless your healthcare provider tells you to unless your healthcare provider tells you to. Know the medicines you take. Keep a list of your medicines with you to show your healthcare provider and pharmacist each time you get a new medicine. How should I take zolpidem tartrate tablets? See "What is the most important information I should know about zolpidem tartrate tablets?" Take zolpidem tartrate tablets exactly as prescribed. Only take 1 zolpidem tartrate tablet a night if needed. Do not take zolpidem tartrate tablets if you drank alcohol that evening or before bed. You should not take zolpidem tartrate tablets with or right after a meal. Zolpidem tartrate tablets may help you fall asleep faster if you take it on an empty stomach. Call your healthcare provider 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 tartrate tablets or overdose, or get emergency treatment. What are the possible side effects of zolpidem tartrate tablets? Zolpidem tartrate tablets may cause serious side effects, including: See " " getting out of bed while not being fully awake and do an activity that you do not know you are doing. What is the most important information I should know about zolpidem tartrate tablets? Symptoms include more outgoing or aggressive behavior than normal, confusion, agitation, hallucinations, worsening of depression, and suicidal thoughts or actions. abnormal thoughts and behavior. memory loss anxiety Symptoms include swelling of the tongue or throat, and trouble breathing. Get emergency medical help if you get these symptoms after taking zolpidem tartrate tablets. severe allergic reactions. falls, which may lead to severe injuries Call your healthcare provider right away if you have any of the above side effects or any other side effects that worry you while using zolpidem tartrate tablets. The most common side effects of zolpidem tartrate tablets are: drowsiness dizziness diarrhea grogginess or feeling as if you have been drugged you may have symptoms for 1 to 2 days such as: After you stop taking a sleep medicine, • trouble sleeping • nausea • flushing • lightheadedness • uncontrolled crying • vomiting • stomach cramps • panic attack • nervousness • stomach area pain These are not all the side effects of zolpidem tartrate tablets. Ask your healthcare provider or pharmacist for more information. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1–800–FDA–1088. How should I store zolpidem tartrate tablets? 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]. Keep zolpidem tartrate tablets and all medicines out of reach of children. General Information about the safe and effective use of zolpidem tartrate tablets Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use zolpidem tartrate tablets for a condition for which it was not prescribed. Do not share zolpidem tartrate tablets with other people, even if you think they have the same symptoms that you have. It may harm them and it is against the law. This Medication Guide summarizes the most important information about zolpidem tartrate tablets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about zolpidem tartrate tablets that is written for healthcare professionals. For more information, call 1-269-544-2299. What are the ingredients in zolpidem tartrate tablets? Zolpidem tartrate, USP Active Ingredient: hypromellose, lactose monohydrate, microcrystalline cellulose, magnesium stearate, polyethylene glycol, sodium starch glycolate, titanium dioxide and ferric oxide red; the 10 mg tablet also contains ferric oxide yellow. Inactive Ingredients: This Medication Guide has been approved by the U.S. Food and Drug Administration. Trademarks are the property of their respective owners. Manufactured by: TORRENT PHARMACEUTICALS LTD., Indrad-382 721, Dist. Mehsana, INDIA. For: TORRENT PHARMA INC., 150 Allen Road, Suite 102, Basking Ridge, NJ 07920. 8052217 Revised November 2014 Logo
| Zolpidem tartrate is a federally controlled substance (C-IV) because it can be abused or lead to dependence. Keep zolpidem tartrate tablets in a safe place to prevent misuse and abuse. Selling or giving away zolpidem tartrate tablets may harm others, and is against the law. Tell your healthcare provider if you have ever abused or have been dependent on alcohol, prescription medicines or street drugs. |
Clinical studies
This field may contain references to clinical studies in place of detailed discussion in other sections of the labeling.14. CLINICAL STUDIES 14.1 Transient Insomnia Normal adults experiencing transient insomnia (n = 462) during the first night in a sleep laboratory were evaluated in a double-blind, parallel group, single-night trial comparing two doses of zolpidem (7.5 and 10 mg) and placebo. Both zolpidem doses were superior to placebo on objective (polysomnographic) measures of sleep latency, sleep duration, and number of awakenings. Normal elderly adults (mean age 68) experiencing transient insomnia (n = 35) during the first two nights in a sleep laboratory were evaluated in a double-blind, crossover, 2-night trial comparing four doses of zolpidem (5, 10, 15 and 20 mg) and placebo. All zolpidem doses were superior to placebo on the two primary PSG parameters (sleep latency and efficiency) and all four subjective outcome measures (sleep duration, sleep latency, number of awakenings, and sleep quality). 14.2 Chronic Insomnia Zolpidem was evaluated in two controlled studies for the treatment of patients with chronic insomnia (most closely resembling primary insomnia, as defined in the APA Diagnostic and Statistical Manual of Mental Disorders, DSM-IV™). Adult outpatients with chronic insomnia (n = 75) were evaluated in a double-blind, parallel group, 5-week trial comparing two doses of zolpidem tartrate and placebo. On objective (polysomnographic) measures of sleep latency and sleep efficiency, zolpidem 10 mg was superior to placebo on sleep latency for the first 4 weeks and on sleep efficiency for weeks 2 and 4. Zolpidem was comparable to placebo on number of awakenings at both doses studied. Adult outpatients (n=141) with chronic insomnia were also evaluated, in a double-blind, parallel group, 4-week trial comparing two doses of zolpidem and placebo. Zolpidem 10 mg was superior to placebo on a subjective measure of sleep latency for all 4 weeks, and on subjective measures of total sleep time, number of awakenings, and sleep quality for the first treatment week. Increased wakefulness during the last third of the night as measured by polysomnography has not been observed in clinical trials with zolpidem tartrate tablets. 14.3 Studies Pertinent to Safety Concerns for Sedative/Hypnotic Drugs Next-day residual effects of zolpidem tartrate tablets were evaluated in seven studies involving normal subjects. In three studies in adults (including one study in a phase advance model of transient insomnia) and in one study in elderly subjects, a small but statistically significant decrease in performance was observed in the Digit Symbol Substitution Test (DSST) when compared to placebo. Studies of zolpidem tartrate tablets in non-elderly patients with insomnia did not detect evidence of next-day residual effects using the DSST, the Multiple Sleep Latency Test (MSLT), and patient ratings of alertness. Next-day residual effects: There was no objective (polysomnographic) evidence of rebound insomnia at recommended doses seen in studies evaluating sleep on the nights following discontinuation of zolpidem tartrate tablets. There was subjective evidence of impaired sleep in the elderly on the first post-treatment night at doses above the recommended elderly dose of 5 mg. Rebound effects: Controlled studies in adults utilizing objective measures of memory yielded no consistent evidence of next-day memory impairment following the administration of zolpidem tartrate tablets. However, in one study involving zolpidem doses of 10 and 20 mg, there was a significant decrease in next-morning recall of information presented to subjects during peak drug effect (90 minutes post-dose), i.e., these subjects experienced anterograde amnesia. There was also subjective evidence from adverse event data for anterograde amnesia occurring in association with the administration of zolpidem tartrate tablets, predominantly at doses above 10 mg. Memory impairment: In studies that measured the percentage of sleep time spent in each sleep stage, zolpidem tartrate tablets have generally been shown to preserve sleep stages. Sleep time spent in stages 3 and 4 (deep sleep) was found comparable to placebo with only inconsistent, minor changes in REM (paradoxical) sleep at the recommended dose. Effects on sleep stages:
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use A total of 154 patients in U.S. controlled clinical trials and 897 patients in non-U.S. clinical trials who received zolpidem were ≥60 years of age. For a pool of U.S. patients receiving zolpidem at doses of ≤10 mg or placebo, there were three adverse reactions occurring at an incidence of at least 3% for zolpidem and for which the zolpidem incidence was at least twice the placebo incidence (i.e., they could be considered drug related). Adverse Event Zolpidem Placebo Dizziness 3% 0% Drowsiness 5% 2% Diarrhea 3% 1% A total of 30/1,959 (1.5%) non-U.S. patients receiving zolpidem reported falls, including 28/30 (93%) who were ≥70 years of age. Of these 28 patients, 23 (82%) were receiving zolpidem doses >10 mg. A total of 24/1,959 (1.2%) non-U.S. patients receiving zolpidem reported confusion, including 18/24 (75%) who were ≥70 years of age. Of these 18 patients, 14 (78%) were receiving zolpidem doses >10 mg. The dose of zolpidem tartrate tablets in elderly patients is 5 mg to minimize adverse effects related to impaired motor and/or cognitive performance and unusual sensitivity to sedative/hypnotic drugs [see ]. Warnings and Precautions (5.1)
| Dizziness | 3% | 0% |
| Drowsiness | 5% | 2% |
| Diarrhea | 3% | 1% |
Labor and delivery
Information about the drug’s use during labor or delivery, whether or not the use is stated in the indications section of the labeling, including the effect of the drug on the mother and fetus, on the duration of labor or delivery, on the possibility of delivery-related interventions, and the effect of the drug on the later growth, development, and functional maturation of the child.8.2 Labor and Delivery Zolpidem tartrate tablets have no established use in labor and delivery [see ]. Pregnancy (8.1)
Nursing mothers
Information about excretion of the drug in human milk and effects on the nursing infant, including pertinent adverse effects observed in animal offspring.8.3 Nursing Mothers Zolpidem is excreted in human milk. Caution should be exercised when zolpidem is administered to a nursing woman.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use Zolpidem is not recommended for use in children. Safety and effectiveness of zolpidem in pediatric patients below the age of 18 years have not been established. In an 8-week study, in pediatric patients (aged 6-17 years) with insomnia associated with attention-deficit/hyperactivity disorder (ADHD) an oral solution of zolpidem tartrate dosed at 0.25 mg/kg at bedtime did not decrease sleep latency compared to placebo. Psychiatric and nervous system disorders comprised the most frequent (> 5%) treatment emergent adverse reactions observed with zolpidem versus placebo and included dizziness (23.5% vs. 1.5%), headache (12.5% vs. 9.2%), and hallucinations were reported in 7% of the pediatric patients who received zolpidem; none of the pediatric patients who received placebo reported hallucinations . Ten patients on zolpidem (7.4%) discontinued treatment due to an adverse reaction. [see Warnings and Precautions(5.4)]
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies of zolpidem tartrate tablets in pregnant women. Studies in children to assess the effects of prenatal exposure to zolpidem have not been conducted; however, cases of severe neonatal respiratory depression have been reported when zolpidem was used at the end of pregnancy, especially when taken with other CNS-depressants. Children born to mothers taking sedative-hypnotic drugs may be at risk for withdrawal symptoms during the postnatal period. Neonatal flaccidity has also been reported in infants born to mothers who received sedative-hypnotic drugs during pregnancy. Zolpidem should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Administration of zolpidem to pregnant rats and rabbits resulted in adverse effects on offspring development at doses greater than the zolpidem tartrate tablets maximum recommended human dose (MRHD) of 10 mg/day (approximately 8 mg/day zolpidem base); however, teratogenicity was not observed. When zolpidem was administered at oral doses of 4, 20, and 100 mg base/kg/day to pregnant rats during the period of organogenesis, dose-related decreases in fetal skull ossification occurred at all but the lowest dose, which is approximately 5 times the MRHD on a mg/m basis. In rabbits treated during organogenesis with zolpidem at oral doses of 1, 4, and 16 mg base/kg/ day increased embryo-fetal death and incomplete fetal skeletal ossification occurred at the highest dose tested. The no-effect dose for embryo-fetal toxicity in rabbits is approximately 10 times the MRHD on a mg/m basis. Administration of zolpidem to rats at oral doses of 4, 20, and 100 mg base/kg/day during the latter part of pregnancy and throughout lactation produced decreased offspring growth and survival at all but the lowest dose, which is approximately 5 times the MRHD on a mg/m basis. 2 2 2
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8. USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm (8.1) 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) 8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies of zolpidem tartrate tablets in pregnant women. Studies in children to assess the effects of prenatal exposure to zolpidem have not been conducted; however, cases of severe neonatal respiratory depression have been reported when zolpidem was used at the end of pregnancy, especially when taken with other CNS-depressants. Children born to mothers taking sedative-hypnotic drugs may be at risk for withdrawal symptoms during the postnatal period. Neonatal flaccidity has also been reported in infants born to mothers who received sedative-hypnotic drugs during pregnancy. Zolpidem should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Administration of zolpidem to pregnant rats and rabbits resulted in adverse effects on offspring development at doses greater than the zolpidem tartrate tablets maximum recommended human dose (MRHD) of 10 mg/day (approximately 8 mg/day zolpidem base); however, teratogenicity was not observed. When zolpidem was administered at oral doses of 4, 20, and 100 mg base/kg/day to pregnant rats during the period of organogenesis, dose-related decreases in fetal skull ossification occurred at all but the lowest dose, which is approximately 5 times the MRHD on a mg/m basis. In rabbits treated during organogenesis with zolpidem at oral doses of 1, 4, and 16 mg base/kg/ day increased embryo-fetal death and incomplete fetal skeletal ossification occurred at the highest dose tested. The no-effect dose for embryo-fetal toxicity in rabbits is approximately 10 times the MRHD on a mg/m basis. Administration of zolpidem to rats at oral doses of 4, 20, and 100 mg base/kg/day during the latter part of pregnancy and throughout lactation produced decreased offspring growth and survival at all but the lowest dose, which is approximately 5 times the MRHD on a mg/m basis. 2 2 2 8.2 Labor and Delivery Zolpidem tartrate tablets have no established use in labor and delivery [see ]. Pregnancy (8.1) 8.3 Nursing Mothers Zolpidem is excreted in human milk. Caution should be exercised when zolpidem is administered to a nursing woman. 8.4 Pediatric Use Zolpidem is not recommended for use in children. Safety and effectiveness of zolpidem in pediatric patients below the age of 18 years have not been established. In an 8-week study, in pediatric patients (aged 6-17 years) with insomnia associated with attention-deficit/hyperactivity disorder (ADHD) an oral solution of zolpidem tartrate dosed at 0.25 mg/kg at bedtime did not decrease sleep latency compared to placebo. Psychiatric and nervous system disorders comprised the most frequent (> 5%) treatment emergent adverse reactions observed with zolpidem versus placebo and included dizziness (23.5% vs. 1.5%), headache (12.5% vs. 9.2%), and hallucinations were reported in 7% of the pediatric patients who received zolpidem; none of the pediatric patients who received placebo reported hallucinations . Ten patients on zolpidem (7.4%) discontinued treatment due to an adverse reaction. [see Warnings and Precautions(5.4)] 8.5 Geriatric Use A total of 154 patients in U.S. controlled clinical trials and 897 patients in non-U.S. clinical trials who received zolpidem were ≥60 years of age. For a pool of U.S. patients receiving zolpidem at doses of ≤10 mg or placebo, there were three adverse reactions occurring at an incidence of at least 3% for zolpidem and for which the zolpidem incidence was at least twice the placebo incidence (i.e., they could be considered drug related). Adverse Event Zolpidem Placebo Dizziness 3% 0% Drowsiness 5% 2% Diarrhea 3% 1% A total of 30/1,959 (1.5%) non-U.S. patients receiving zolpidem reported falls, including 28/30 (93%) who were ≥70 years of age. Of these 28 patients, 23 (82%) were receiving zolpidem doses >10 mg. A total of 24/1,959 (1.2%) non-U.S. patients receiving zolpidem reported confusion, including 18/24 (75%) who were ≥70 years of age. Of these 18 patients, 14 (78%) were receiving zolpidem doses >10 mg. The dose of zolpidem tartrate tablets in elderly patients is 5 mg to minimize adverse effects related to impaired motor and/or cognitive performance and unusual sensitivity to sedative/hypnotic drugs [see ]. Warnings and Precautions (5.1) 8.6 Gender Difference in Pharmacokinetics Women clear zolpidem tartrate from the body at a lower rate than men. C and AUC parameters of zolpidem were approximately 45% higher at the same dose in female subjects compared with male subjects. Given the higher blood levels of zolpidem tartrate in women compared to men at a given dose, the recommended initial dose of zolpidem for adult women is 5 mg, and the recommended dose for adult men is 5 or 10 mg. max In geriatric patients, clearance of zolpidem is similar in men and women. The recommended dose of zolpidem in geriatric patients is 5 mg regardless of gender.
| Dizziness | 3% | 0% |
| Drowsiness | 5% | 2% |
| Diarrhea | 3% | 1% |
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16. HOW SUPPLIED/STORAGE AND HANDLING NDC:55700-357-15 in a BOTTLE of 15 TABLETS NDC:55700-357-30 in a BOTTLE of 30 TABLETS NDC:55700-357-60 in a BOTTLE of 60 TABLETS
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API