Each Uncoated Orally Disintegrating Tablet contains:
Zolpidem Tartrate I.P. 5mg
Excipients q.s.

Each Uncoated Orally Disintegrating Tablet contains:
Zolpidem Tartrate I.P 10 mg
Excipients q.s.

Orally Disintegrating Tablets
5mg/10mg

4.1 THERAPEUTIC INDICATION
It is indicated for insomnia.

4.2 POSOLOGY AND METHOD OF ADMINISTRATION
Route of administration: Oral
Zolpidem has been shown to decrease sleep latency for up to 35 days in controlled clinical studies.
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.
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 ODT should not exceed 10 mg once daily immediately before bedtime. Zolpidem ODT should be taken as a single dose and should not be re-administered during the same night.
Place the Zolpidem ODT tablet in the mouth where it disintegrates in seconds and can then be swallowed. The tablet may be taken with or without water. Do NOT chew, break, or split the tablet.
Zolpidem ODT should not be administered with or immediately after a meal.
The recommended initial doses for women and men are different because zolpidem ODT clearance is lower in women.
Special Populations
Paediatric population Zolpidem ODT is not recommended for use in children and adolescents below 18 years of age, due to a lack of data to support use in this age group. The available evidence from placebo-controlled clinical trials is presented in section Pharmacodynamic properties.
Elderly
Elderly or debilitated patients may be especially sensitive to the effects of Zolpidem ODT therefore a minimum 5mg dose once daily is recommended. These recommended doses should not be exceeded.
Hepatic impairment
As clearance and metabolism of Zolpidem ODT is reduced in hepatic impairment, dosage should begin at 5mg in these patients with particular caution being exercised in elderly patients. In adults (under 65 years) dosage may be increased to 10mg only where the clinical response is inadequate and the drug is well tolerated

4.3 CONTRAINDICATIONS
Zolpidem ODT is contraindicated in patients with a hypersensitivity to Zolpidem ODT or any of the inactive ingredients Observed hypersensitivity reactions include anaphylaxis and angioedema, obstructive sleep apnoea, myasthenia gravis, severe hepatic insufficiency, acute and/or severe respiratory depression. In the absence of data, Zolpidem ODT should not be prescribed for children or patients with psychotic illness.

4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE
The cause of insomnia should be identified wherever possible and the underlying factors treated before a hypnotic is prescribed. The failure of insomnia to remit after a 7-14 day course of treatment may indicate the presence of a primary psychiatric or physical disorder, and the patient should be carefully re-evaluated at regular intervals.
Next-day psychomotor impairment The risk of next-day psychomotor impairment, including impaired driving ability, is increased if:
• Zolpidem ODT is taken within less than 8 hours before performing activities that require mental alertness (see section Effects on ability to drive and use machines)
• a dose higher than the recommended dose is taken
• Zolpidem ODT is co-administered with other CNS depressants or with other drugs that increase the blood levels of Zolpidem ODT, or with alcohol or illicit drugs (see section Drug Interactions). Zolpidem ODT should be taken in a single intake immediately at bedtime and not be re-administered during the same night.
Specific Patient groups
Respiratory Insufficiency: As hypnotics have the capacity to depress respiratory drive,precautions should be observed if Zolpidem ODT is prescribed to patients with compromised respiratory function. Although studies with 10 mg olpidem ODT did not reveal respiratory depressant effects at hypnotic doses in healthy subjects or in patients with mild-to moderate chronic obstructive pulmonary disease (COPD), a reduction in the Total Arousal Index.
Use in patients with a history of drug or alcohol abuse: Extreme caution should be exercised when prescribing for patients with a history of drug or alcohol abuse. These patients should be under careful surveillance when receiving Zolpidem ODT or any other hypnotic, since they are at risk of habituation and psychological dependence.

Psychotic illness: Hypnotics such as Zolpidem ODT are not recommended for the primary treatment of psychotic illness.
Depression: As with other sedative/hypnotic drugs, Zolpidem ODT should be administered with caution in patients exhibiting symptoms of depression. Suicidal tendencies may be present.

therefore the least amount of Zolpidem ODT that is feasible should be supplied to these patients to avoid the possibility of intentional overdosage by the patient. Pre existing depression may be unmasked during use of Zolpidem ODT. Since insomnia may be a symptom of depression, the patient should be re-evaluated if insomnia persists. General information relating to effects seen following administration of benzodiazepines and other hypnotic agents which should be taken into account by the prescribing physician are described below.
Tolerance: Some loss of efficacy to the hypnotic effects of short acting benzodiazepines and benzodiazepine like agents like Zolpidem ODT may develop after repeated use for a few weeks.
Dependence: Use of benzodiazepines or benzodiazepine-like agents like Zolpidem ODT may lead to the development of physical and psychological dependence. The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a history of psychiatric disorders and/or alcohol or drug abuse. These patients should be under careful surveillance when receiving hypnotics. Once physical dependence has developed, rapid dose decrease or abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches or muscle pain, extreme anxiety and tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures.
Rebound insomnia: A transient syndrome whereby the symptoms that led to treatment with a benzodiazepine or benzodiazepine-like agent recur in an enhanced form may occur on withdrawal of hypnotic treatment. It may be accompanied by other reactions including mood changes, anxiety and restlessness. It is important that the patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms should they occur when the medicinal product is discontinued. Since the risk of withdrawal phenomena or rebound has been shown to be greater after abrupt discontinuation of treatment, it is recommended that the dosage is decreased gradually where clinically appropriate. There are indications that, in the case of benzodiazepines and benzodiazepine like agents with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high.
Amnesia: Benzodiazepines or benzodiazepine-like agents such as Zolpidem ODT may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product. In order to reduce the risk, patients should ensure that they will be able to have an uninterrupted sleep of 8 hours (see section Adverse Effects).

Other psychiatric and "paradoxical" reactions: Other psychiatric and paradoxical reactions like restlessness, exacerbated insomnia, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, psychosis, abnormal behaviour and other adverse behavioural effects are known to occur when using benzodiazepines or benzodiazepine like agents. Should this occur, use of the product should be discontinued. These reactions are more likely to occur in the elderly.
Somnambulism and associated behaviours: Sleep walking and other associated behaviours such as “sleep driving”, preparing and eating food, making phone calls or having sex, with amnesia for the event, have been reported in patients who had taken Zolpidem ODT and were not fully awake. The use of alcohol and other CNS depressants with Zolpidem ODT appears to increase the risk of such behaviours, as does the use of Zolpidem ODT at doses exceeding the maximum recommended dose. Discontinuation of Zolpidem ODT should be strongly considered for patients who report such behaviours (for example, sleep driving), due to the risk to the patient and others (See Section Drug Interactions and Adverse effects).
Severe injuries: Due to its pharmacological properties, Zolpidem ODT can cause drowsiness and a decreased level of consciousness, which may lead to falls and consequently to severe injuries. Severe injuries such as hip fractures and intracranial hemorrhage have been reported.

4.5 DRUGS INTERACTIONS
CNS-Active Drugs
Co-administration of zolpidem with other CNS depressants increases the risk of CNS depression. Concomitant use of zolpidem with these drugs may increase drowsiness and psychomotor impairment, including impaired driving ability.
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 ODT produced no pharmacokinetic interaction, but there was an additive effect of decreased alertness and psychomotor performance
Haloperidol
A study involving haloperidol and zolpidem revealed no effect of haloperidol on the pharmacokinetics or pharmacodynamics of zolpidem. The lack of a drug interaction following single-dose administration does not predict the absence of an effect following chronic administration
Alcohol
An additive adverse effect on psychomotor performance between alcohol and oral zolpidem was demonstrated. The sedative effect may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.
Sertraline
Concomitant administration of zolpidem and sertraline increases exposure to zolpidem
Fluoxetine
After multiple doses of Zolpidem ODT and fluoxetine 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 induce or inhibit CYP3A may affect exposure to zolpidem. The effect of drugs that induce or inhibit other P450 enzymes on the exposure to zolpidem is not known.
CYP3A4 Inducers
Rifampin, a CYP3A4 inducer, significantly reduced the exposure to and the pharmacodynamic effects of zolpidem. Use of CYP3A4 inducers in combination with zolpidem may decrease the efficacy of zolpidem

4.6 USE IN SPECIAL POPULATIONS (SUCH AS PREGNANT WOMEN, LACTATING WOMEN, PAEDIATRIC PATIENTS, GERIATRIC PATIENTS ETC.)
PREGNANCY AND LACTATION

For Pediatric and Geriatric patients refer section 4.2

Pregnancy for Zolpidem ODT,

The use of zolpidem is not recommended during pregnancy.

Zolpidem crosses the placenta.

Although animal studies have shown no teratogenic or embryotoxic effects, safety in pregnancy has not been established. As with all drugs Zolpidem ODT should be avoided in pregnancy particularly during the first trimester. If the product is prescribed to a woman of childbearing potential, she should be warned to contact her physician about stopping the product if she intends to become or suspects that she is pregnant. If, for compelling medical reasons, Zolpidem ODT is administered during the late phase of pregnancy, or during labour, effects on the neonate, such as hypothermia, hypotonia and moderate respiratory depression, can be expected due to the pharmacological action of the product. Cases of severe neonatal respiratory depression have been reported when Zolpidem ODT was used with other CNS depressants at the end of pregnancy. Infants born to mothers who took benzodiazepines or benzodiazepine-like agents chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk of developing withdrawal symptoms in the postnatal period.
Lactation Small quantities of Zolpidem ODT appear in breast milk. The use of Zolpidem ODT in nursing mothers is therefore not recommended.

4.7 EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Zolpidem ODT has major influence on theability to drive and use machines. Vehicle drivers and machine operators should be warned that, as with other hypnotics, there may be a possible risk of drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/double vision and reduced alertness and impaired driving the morning after therapy (see section Adverse Effects). In order to minimise this risk a resting period of at least 8 hours is recommended between taking Zolpidem ODT and driving, using machinery and working at heights. Driving ability impairment and behaviours such as ‘sleep-driving’ have occurred with Zolpidem ODT alone at therapeutic doses. Furthermore, the co-administration of Zolpidem ODT with alcohol and other CNS depressants increases the risk of such behaviours (see section warnings and precautions and Drug Interactions). Patients should be warned not to use alcohol or other psychoactive substances when taking Zolpidem ODT.

4.8 UNDESIRABLE EFFECTS
The following CIOMS frequency rating is used, when applicable: Very common ≥10% Common ≥ 1 and < 10% Uncommon ≥ 0.1 and < 1% Rare ≥0.01 and < 0.1% Very rare < 0.01% Not known: cannot be estimated based on available data.
There is evidence of a dose-relationship for adverse effects associated with Zolpidem ODT use, particularly for certain CNS and gastrointestinal events. As recommended in section Dosage & Administration, they should in theory be less if Zolpidem ODT is taken immediately before retiring, or in bed. They occur most frequently in elderly patients.
Immune system disorders
Not known: angioneurotic oedema

Psychiatric disorders
Common: hallucination, agitation, nightmare Uncommon: confusional state, irritability Not known: restlessness, aggression, delusion, anger, psychosis, abnormal behaviour, somnambulism (see section warnings and precautions), dependence (withdrawal symptoms, or rebound effects may occur after treatment discontinuation), libido disorder, depression (see section warnings and precautions). Most of these psychiatric undesirable effects are related to paradoxical reactions
Nervous system disorders Common: somnolence, headache, dizziness, exacerbated insomnia, anterograde amnesia: (amnestic effects may be associated with inappropriate behaviour) Not known: depressed level of consciousness
Eye disorders: Uncommon: diplopia
Respiratory, thoracic and mediastinal disorders: Not Known: respiratory depression
Gastro-intestinal disorders Common: diarrhoea, nausea, vomiting, abdominal pain
Hepatobiliary disorders Not known: Liver enzymes elevated
Skin and subcutaneous tissue disorders Not known: rash, pruritus, urticaria, hyperhidrosis
Musculoskeletal and connective tissue disorders Common: back pain Not known: muscular weakness
Infections and infestations Common: upper respiratory tract infection, lower respiratory tract infection
General disorders and administration site conditions Common: fatigue Not known: gait disturbance, drug tolerance, fall (predominantly in elderly patients and when zolpidem was not taken in accordance with prescribing recommendation) (see section warnings and precautions).

DRUG ABUSE AND DEPENDENCE
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. It is 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.

Dependence
Use of Zolpidem may lead to the development of physical and/or psychological dependence. The risk of dependence increases with dose and duration of treatment. The risk of abuse and dependence is also greater in patients with a history of alcohol or drug abuse. AMBIEN should be used with extreme caution in patients with current or past alcohol or drug abuse 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, convulsions, and delirium.
The following adverse events, which are considered to meet the DSM-III-R criteria for uncomplicated sedative/hypnotic withdrawal, were reported during clinical trials with Zolpidem 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. There have been postmarketing reports of abuse, dependence and withdrawal with zolpidem.

4.9 OVERDOSE
Signs and Symptoms: In cases of overdose involving Zolpidem ODT alone or with other CNS-depressant agents (including alcohol), impairment of consciousness ranging from somnolence to coma, and more severe symptomatology, including fatal outcomes have been reported.
Management: General symptomatic and supportive measures should be used. If there is no advantage in emptying the stomach, activated charcoal should be given to reduce absorption. Sedating drugs should be withheld even if excitation occurs. Use of flumazenil may be considered where serious symptoms are observed. Flumazenil is reported to have an elimination half-life of about 40 to 80 minutes. Patients should be kept under close observation because of this short duration of action; further doses of flumazenil may be necessary. However, flumazenil administration may contribute to the appearance of neurological symptoms (convulsions). Zolpidem ODT is not dialyzable. The value of dialysis in the treatment of an overdose has not been determined. Dialysis in patients with renal failure receiving therapeutic doses of zolpidem have demonstrated no reduction in levels of zolpidem. In the management of overdose with any medicinal product, it should be borne in mind that multiple agents may have been taken.

5.1 MECHANISM OF ACTION
Zolpidem ODT is a GABAA receptor positive modulator presumed to exert its therapeutic effects in insomnia through binding to the benzodiazepine site of α1 subunit containing GABA A receptors, increasing the frequency of chloride channel opening resulting in the inhibition of neuronal excitation

5.2 PHARMACODYNAMIC PROPERTIES
Zolpidem ODT binds to GABA A receptors with greater affinity for α1 subunit relative to α2 and α3 subunit containing receptors. Zolpidem has no appreciable binding affinity for α5 subunit containing GABAA receptors.This binding profile may explainthe relative absenc of myorelaxant effects in animal studies. Zolpidem has no appreciable binding affinity for dopaminergic D2, serotonergic 5HT2, adrenergic, histaminergic or muscarinic receptors.

5.3 PHARMACOKINETIC PROPERTIES
ZOLPIDEM ODT(zolpidem tartrate-Orally Disintegrating Tablets) are bioequivalent to Zolpidem tablets.
Absorption: Zolpidem is absorbed from the gastrointestinal tract. Following a single 10 mg dose of ZOLPIDEM ODTin 35 healthy volunteers under fasting conditions, a mean zolpidem Cmax of 101.68 ± 32.68 ng/mL was attained at about 1.75 hours. The bioavailability of ZOLPIDEM ODT relative to the conventional immediate-release formulation is 103%. The pharmacokinetics of zolpidem are linear in the 5 – 10 mg dose range.
Food Effect: The pharmacokinetics of zolpidem after concomitant food intake were similar between ZOLPIDEM ODT and Zolpidem tablets. Since food decreases AUC and Cmax of zolpidem and delays time to peak zolpidem concentrations (by 60%), for faster sleep onset.
ZOLPIDEM ODT should not be administered with or immediately after a meal.
ZOLPIDEM ODT can be administered with or without water.
Distribution: Total protein binding of zolpidem is 92.5 ± 0.1% and remains constant independent of concentration between 40 and 790 ng/mL.
Metabolism and Excretion: The mean zolpidem elimination half-life is approximately 3.5 hours, following night time dosing.
Zolpidem is converted to inactive metabolites that are eliminated primarily by renal excretion.

6.1 ANIMAL TOXICOLOGY OR PHARMACOLOGY
Carcinogenesis, mutagenesis, impairment of fertility
Carcinogenesis:
Zolpidem was administered to mice and rats for 2 years at oral doses of 4, 18, and 80 mg base/kg/day. In mice, these doses are approximately 2.5, 10, and 50 times the MRHD of 10 mg/day (8 mg zolpidem base) based on mg/m2 body surface area and in rats, these doses are approximately 5, 20, and 100 times the MRHD based on mg/m2 body surface area. No evidence of carcinogenic potential was observed in mice. In rats, renal tumors (lipoma, liposarcoma) were seen at the mid and high doses.

Mutagenesis:
Zolpidem was negative in in vitro (bacterial reverse mutation, mouse lymphoma, and chromosomal aberration) and in vivo (mouse micronucleus) genetic toxicology assays.

Impairment of Fertility:
Zolpidem was administered to rats at 4, 20, and 100 mg base/kg/day, which are approximately 5,25, and 120 times the MRHD of 10 mg/day (8 mg zolpidem base) based on mg/m2 body surface area, prior to and during mating, and continuing in females through postpartum day 25.
Zolpidem caused irregular estrus cycles and prolonged precoital intervals at the highest dose tested, which is approximately 120 times the MRHD based on mg/m2 body surface area. The NOAEL for these effects is 25 times the MRHD based on a mg/m2 body surface area. There was no impairment of fertility at any dose tested.

5mg – White to off-white, round shaped tablets debossed with “Abbott logo” on one side and plain on other side.
10 mg – white to off-white, capsule shaped tablets debossed with “Abbott logo” on one side and plain on other side.

8.1 INCOMPATIBILITIES
Not Applicable

8.2 SHELF-LIFE
Refer pack

8.3 PACKAGING INFORMATION
Sales Pack: 15’s Blister (Cold form Alu alu pack)
PS Pack: 2’s Blister (Cold form Alu alu pack)

8.4 STORAGE AND HANDING INSTRUCTIONS
Store protected from light and moisture, at a temperature not exceeding 30°C.

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

Complex Sleep Behaviors
Instruct patients and their families that Zolpidem ODT may cause complex sleep behaviors, including sleep-walking, sleep driving, preparing and eating food, making phone calls, or having sex while not being fully awake. Serious injuries and death have occurred during complex sleep behaviour episodes. Tell patients to discontinue Zolpidem ODT and notify their healthcare provider immediately if they develop any of these symptoms

CNS-Depressant Effects and Next-Day Impairment
Tell patients that Zolpidem ODT 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. Advise patients that increased drowsiness and decreased consciousness may increase the risk of falls in some patients.

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

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 ODT if they drank alcohol that evening or before bed.

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

Administration Instructions
Patients should be counseled to take Zolpidem ODT 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 ODT tablets should not be taken with or immediately after a meal. Advise patients NOT to take Zolpidem ODT if they drank alcohol that evening.
Place the Zolpidem ODT tablet in the mouth where it disintegrates in seconds and can then be swallowed. The tablet may be taken with or without water. Do NOT chew, break, or split the tablet.
Zolpidem ODT should not be administered with or immediately after a meal.

Manufactured by: Abbott India Limited
At; 26A, 27-30, Sector 8A, IIE, SIDCUL, Ranipur,
Haridwar-249 403, Uttarakhand, India.
®Regd. Trademark of Abbott GMBH.

15/UA/LL/2015 dated 02.01.2023

Version No. 2.0, dated 19.04.23
For Product complaints/Adverse events or Queries please write to webmasterindia@abbott.com