Zolpidem 12,5 mg XR tablets

Short-term treatment of insomnia. ZOLPIDEM XR 12,5 ADCO is indicated in adults below the age of 65 years, and only when the disorder is severe, disabling or subjecting the individual to extreme distress.

Posology
ZOLPIDEM XR 12,5 ADCO acts rapidly and therefore should be taken immediately before bedtime, or in bed. For a faster sleep onset, ZOLPIDEM XR 12,5 ADCO should not be administered with or immediately after a meal (see section 5.2). ZOLPIDEM XR 12,5 ADCO should be taken in a single intake and not be re-administered during the same night. Treatment should be as short as possible. Generally, the duration of treatment varies from four days to two weeks with a maximum, including the tapering off process, of four weeks. In certain cases, extension beyond the maximum treatment period may be necessary; if so, it should not take place without re-evaluation of the patientu2019s status. Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded.
Adults (< 65 years): The recommended daily dose is 12,5 mg. The lowest effective daily dose of ZOLPIDEM XR 12,5 ADCO should be used and must not exceed 12,5 mg.
Special populations
Hepatic impairment: ZOLPIDEM XR 12,5 ADCO should not be used in patients with severe hepatic impairment (see sections 4.3. and 4.4).
Renal impairment: No dosage adjustment is required.
Elderly patients: As ZOLPIDEM XR 12,5 ADCO has not been evaluated in elderly patients (u2265 65 years), ZOLPIDEM XR 12,5 ADCO is not recommended in this population.
Children: Safety and effectiveness of ZOLPIDEM XR 12,5 ADCO in paediatric patients under the age of 18 years have not been established. Therefore, ZOLPIDEM XR 12,5 ADCO should not be prescribed in this population (see section 4.3).
Method of administration
Oral administration. Tablets should not be halved, crushed or chewed.

• Hypersensitivity to the active substance zolpidem tartrate or any of the excipients listed in section 6.1.
• Children under the age of 18 years.
• Sleep apnoea syndrome.
• Myasthenia gravis.
• Severe hepatic impairment.
• Acute and/or severe respiratory impairment.
• Pregnancy and lactation (see section 4.6).

General information related to effects seen following administration of hypnotics, which should be considered by the prescribing medical practitioner are described below. 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 u2013 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.
Respiratory impairment
Hypnotics have the capacity to depress respiratory drive, precautions should be observed if ZOLPIDEM XR 12,5 ADCO is prescribed to patients with mild to moderate compromised respiratory function.
Risks from concomitant use with opioids
Concomitant use of opioids with benzodiazepines or other sedative-hypnotic medicines, including ZOLPIDEM XR 12,5 ADCO, may result in sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of opioids and benzodiazepines for use in patients for whom alternative treatment options are inadequate. If a decision is made to prescribe ZOLPIDEM XR 12,5 ADCO concomitantly with opioids, prescribe the lowest effective dosages and minimum duration of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation.
Amnesia
ZOLPIDEM XR 12,5 ADCO may induce anterograde amnesia. The condition occurs most often several hours after ingesting ZOLPIDEM XR 12,5 ADCO and therefore, to reduce the risk, patients should ensure that they get a full nightu2019s sleep (7 u2013 8 hours) before being active.
Other psychiatric and paradoxical reactions
Other psychiatric and paradoxical reactions like restlessness, exacerbated insomnia, agitation, irritability, aggression, delusion, anger, nightmares, hallucinations, abnormal behaviour and other behavioural effects are known to occur when using ZOLPIDEM XR 12,5 ADCO. Should this occur, use of ZOLPIDEM XR 12,5 ADCO 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 u201csleep drivingu201d, preparing and eating food, making phone calls or having sex, with amnesia for the event have been reported in patients who have taken ZOLPIDEM XR 12,5 ADCO and were not fully awake. The use of alcohol and other central nervous system (CNS) depressants with ZOLPIDEM XR 12,5 ADCO appears to increase the risk of such behaviours, as does the use of ZOLPIDEM XR 12,5 ADCO at doses exceeding the maximum recommended dose. Discontinuation of ZOLPIDEM XR 12,5 ADCO should be strongly considered for patients who report such behaviours.
Psychomotor impairment
The risk of psychomotor impairment, including impaired driving ability, is increased if: ZOLPIDEM XR 12,5 ADCO is taken within less than 7 u2013 8 hours before performing activities that require mental alertness, a dose higher than the recommended dose is taken, or ZOLPIDEM XR 12,5 ADCO is co-administered with other CNS depressants, alcohol, or with other medicines that increase the blood levels of ZOLPIDEM XR 12,5 ADCO.

Alcohol
Concomitant use with alcohol is not recommended. The sedative effect may be enhanced when ZOLPIDEM XR 12,5 ADCO is used in combination with alcohol. This affects the ability to drive or use machines.
CNS depressants
Enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant medicines, narcotic analgesics, antiepileptic medicines, anaesthetics and sedative antihistamines. Concomitant use of ZOLPIDEM XR 12,5 ADCO with these medicines may increase drowsiness and psychomotor impairment, including impaired driving ability.
Concomitant use with hypnotics may enhance the euphoric effect of narcotic analgesics, which may lead to an increase in psychological dependence.
Co-administration of fluvoxamine may increase blood levels of ZOLPIDEM XR 12,5 ADCO; concurrent use is not recommended (see CYP450 inhibitors and inducers).
Opioids
The concomitant use of benzodiazepines and other sedative-hypnotic medicines, including ZOLPIDEM XR 12,5 ADCO, and opioids increases the risk of sedation, respiratory depression, coma, and death because of additive CNS depressant effect. The dosage and duration of concomitant use should be limited (see section 4.4).
CYP450 inhibitors and inducers
Compounds which inhibit cytochrome P450 may enhance the activity of ZOLPIDEM XR 12,5 ADCO. Co-administration of ZOLPIDEM XR 12,5 ADCO with ketoconazole (200 mg twice daily), a potent CYP3A4 inhibitor, produced a 64 % increase in ZOLPIDEM XR 12,5 ADCO plasma levels. A routine dosage adjustment of ZOLPIDEM XR 12,5 ADCO is not necessary, but patients should be advised that the sedative effects might be enhanced. However, co-administration of ZOLPIDEM XR 12,5 ADCO with itraconazole or fluconazole did not produce any significant changes in ZOLPIDEM XR 12,5 ADCO pharmacokinetics and pharmacodynamics. Fluvoxamine is a strong inhibitor of CYP1A2 and a moderate to weak inhibitor of CYP2C9 and CYP3A4. Co-administration of fluvoxamine may increase blood levels of ZOLPIDEM XR 12,5 ADCO; concurrent use is not recommended. Ciprofloxacin has been shown to be a moderate inhibitor of CYP1A2 and CYP3A4. Co-administration of ciprofloxacin may increase blood levels of ZOLPIDEM XR 12,5 ADCO; concurrent use is not recommended. The pharmacodynamic effect of ZOLPIDEM XR 12,5 ADCO is decreased when it is administered with a CYP3A4 inducer such as rifampicin due to an increase in liver metabolism. The pharmacodynamics effect of ZOLPIDEM XR 12,5 ADCO is decreased when it is administered with a CYP3A4 inducer, such as St. Johnu2019s Wort. Co-administration of St. Johnu2019s Wort may decrease blood levels of ZOLPIDEM XR 12,5 ADCO; concurrent use is not recommended.
Antiretrovirals
HIV-protease inhibitors such as ritonavir may increase plasma concentrations of zolpidem with a risk of extreme sedation and respiratory depression; use together is possible provided the patient is carefully monitored for excessive sedative effects.
Other
No significant pharmacokinetic interactions were observed when ZOLPIDEM XR 12,5 ADCO was administered with warfarin, digoxin, ranitidine or cimetidine.

Women of childbearing potential
If ZOLPIDEM XR 12,5 ADCO is prescribed to a woman of childbearing potential, she should be warned to contact her medical practitioner about stopping ZOLPIDEM XR 12,5 ADCO if she intends to become, or suspects that she is pregnant.
Pregnancy
Safety in pregnancy has not been established. The use of ZOLPIDEM XR 12,5 ADCO during pregnancy should be avoided (see section 4.3). If for compelling medical reasons ZOLPIDEM XR 12,5 ADCO 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 zolpidem. Infants born to mothers who took hypnotics, including ZOLPIDEM XR 12,5 ADCO, chronically during the latter stages of pregnancy may have developed physical dependence and may be at risk of developing withdrawal symptoms in the postnatal period.
Breastfeeding
As zolpidem is excreted in breast milk, the use of ZOLPIDEM XR 12,5 ADCO in breastfeeding mothers should be avoided (see section 4.3).
Fertility
There is no data on fertility.

Patients should be warned that there may be a possible risk of adverse reactions including drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/double vision, and reduced alertness and impaired driving the morning after therapy. In order to minimise this risk, a full night of sleep (7 u2013 8 hours) is recommended. Furthermore, the co-administration of ZOLPIDEM XR 12,5 ADCO with alcohol and other CNS depressants increases the risk of such effects. Patients should be warned not to use alcohol or other psychoactive substances when taking ZOLPIDEM XR 12,5 ADCO (see sections 4.4. and 4.5).

a) Summary of the safety profile
The reaction most commonly associated with discontinuation in a 3-week study was somnolence, whilst in a 6-month study, anxiety, restlessness or agitation, (depression, major depression or depressed mood) were the most common adverse effects that resulted after discontinuation of treatment. Short-term studies indicate the most common adverse effects to be headache, next-day somnolence and dizziness. A six month study revealed the most common adverse effects to be the same as those indicated in short-term use, with the addition of higher incidence of anxiety. There is evidence of a dose-relationship for adverse effects associated with ZOLPIDEM XR 12,5 ADCO use, particularly for certain CNS events. They occur most frequently in elderly patients.
b) Tabulated list of adverse reactions

Signs and symptoms
In cases of overdose involving ZOLPIDEM XR 12,5 ADCO alone or with other CNS-depressant medicines (including alcohol), impairment of consciousness up to coma, and more severe symptomatology, including fatal outcomes have been reported.
Management
General symptomatic and supportive measures should be used. Activated charcoal should be given to reduce absorption. Sedating medicines should be withheld even if excitation occurs. Use of flumazenil may be considered where serious symptoms are observed. However, flumazenil administration may contribute to the appearance of neurological symptoms (convulsions). ZOLPIDEM XR 12,5 ADCO is not dialysable.