ZOLPIDEM TARTRATE

Posology The treatment should be taken in a single intake and not be re-administered during the same night. The recommended daily dose for adults is 10 mg to be taken immediately at bedtime. The lowest effective daily dose of zolpidem tartrate should be used and must not exceed 10 mg.

4). Treatment should be given for the shortest possible duration. If this medicine is being used for the treatment of epilepsy this medicine should be used for as long as the prescriber considers it necessary. The duration of treatment should usually vary from a few days to two weeks with a maximum of four weeks including tapering off where clinically appropriate.

Treatment should be as short as possible. It should not exceed four weeks including the period of tapering off. 4). Special Population Paediatric population Zolpidem 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.

1. Elderly Elderly or debilitated patients may be especially sensitive to the effects of zolpidem tartrate therefore a 5mg dose is recommended. These recommended doses should not be exceeded. Hepatic impairment Mild to Moderate Hepatic Impairment As clearance and metabolism of zolpidem tartrate 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. 3) Method of administration Oral administration.

8.

Important information regarding the ingredients of this medicine Lactose:

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Sodium:

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’. 5 Interaction with other medicinal products and other forms of interaction Not recommended: Alcohol Concomitant intake with alcohol The sedative effect may be enhanced when the product 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 agents, narcotic analgesics, antiepileptic drugs, anaesthetics and sedative antihistamines.

7). Also, isolated cases of visual hallucinations were reported in patients taking zolpidem with antidepressants including bupropion, desipramine, fluoxetine, sertraline and venlafaxine. Co- administration of fluvoxamine may increase blood levels of zolpidem tartrate, concurrent use is not recommended.

In the case of narcotic analgesics enhancement of euphoria may also occur leading to an increase in psychological dependence.

CYP450 inhibitors and inducers:

Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of some hypnotics like zolpidem. Zolpidem tartrate is metabolised via several hepatic cytochrome P450 enzymes, the main enzyme being CYP3A4 with the contribution of CYP1A2.

The pharmacodynamic effect of zolpidem tartrate is decreased when it is administered with a CYP3A4 inducer such as rifampicin and St. John's Wort. Co-administration of St. John's Wort may decrease blood levels of zolpidem, concurrent use is not recommended.

However when zolpidem tartrate was administered with itraconazole (a CYP3A4 inhibitor) its pharmacokinetics and pharmacodynamics were not significantly modified. The clinical relevance of these results is unknown. Co-administration of zolpidem with ketoconazole (200mg twice daily), a potent CYP3A4 inhibitor, prolonged zolpidem elimination half-life, increased total AUC, and decreased apparent oral clearance when compared to zolpidem plus placebo.

83 when compared to zolpidem alone. A routine dosage adjustment of zolpidem is not considered necessary, but patients, should be advised that use of zolpidem with ketoconazole may enhance the sedative effects. Co-administration ciprofloxacin may increase blood levels of zolpidem, concurrent use is not recommended.

Since CYP3A4 plays an important role in zolpidem tartrate metabolism, possible interactions with drugs that are substrates or inducers of CYP3A4 should be considered.

Opioids:

The concomitant use of sedative medicines such as benzodiazepines or related drugs such as zolpidem with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. 4). 6 Fertility, pregnancy and lactation Pregnancy The use of zolpidem is not recommended during pregnancy.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Zolpidem crosses the placenta. A large amount of data on pregnant women (more than 1000 pregnancy outcomes) collected from cohort studies has not demonstrated evidence of the occurrence of malformations following exposure to benzodiazepines or benzodiazepine-like substances during the first trimester of pregnancy.

However, certain case-control studies reported an increased incidence of cleft lip and palate associated with use of benzodiazepines during pregnancy. Cases of reduced foetal movement and foetal heart rate variability have been described after administration of benzodiazepines or benzodiazepine-like substances during the second and/or third trimester of pregnancy.

Administration of zolpidem during the late phase of pregnancy or during labour has been associated with effects on the neonate, such as hypothermia, hypotonia, feeding difficulties (‘floppy infant syndrome’) and respiratory depression due to the pharmacological action of the product.

Cases of severe neonatal respiratory depression have been reported. Moreover, infants born to mothers who took sedative/hypnotics 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.

Appropriate monitoring of the newborn in the postnatal period is recommended. If zolpidem 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.

Breast-feeding Small quantities of zolpidem tartrate appear in breast milk. The use of zolpidem tartrate in nursing mothers is therefore not recommended. 7. 8). In order to minimise this risk a resting period of at least 8 hours is recommended between taking zolpidem […]

4 In the absence of data, zolpidem tartrate should not be prescribed for children or patients with psychotic illness. 4 Special warnings and precautions for use Zolpidem should be used with caution in patients with sleep apnoea syndrome, and myasthenia gravis.

Next-day psychomotor impairment Like other sedative/hypnotic drugs, zolpidem tartrate has CNS-depressant effects. 5). Zolpidem tartrate 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 is prescribed to patients with compromised respiratory function. 2 dose recommendations. Due to the myorelaxant effect, there is a risk of falls and consequent injury, particularly when they get up at night.

Risk from concomitant use of opioids:

Concomitant use of zolpidem and opioids may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing of sedative medicines such as benzodiazepines or related drugs such as zolpidem with opioids should be reserved for patients for whom alternative treatment options are not possible.

2). The patients should be followed closely for signs and symptoms of respiratory depression and sedation. 5).

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 tartrate or any other hypnotic, since they are at risk of habituation and psychological dependence.

Psychotic illness:

Hypnotics such as Zolpidem are not recommended for the primary treatment of psychotic illness. Paediatric Patients Safety and effectiveness of zolpidem have not been established in patients below the age of 18 years. 4% vs. 0%). 2 Posology and method of Administration).

Suicidal ideation, suicide attempt, suicide and depression:

Some epidemiological studies suggest an increased incidence of suicidal ideation, suicide attempt and suicide in patients with or without depression, and treated with benzodiazepines and other hypnotics, including zolpidem. However, a causal relationship has not been established.

Although no clinically significant pharmacokinetic and pharmacodynamic interactions with SSRIs have been demonstrated (see section

1. • Severe hepatic insufficiency • Acute and/or severe respiratory depression. • Known to have previously experienced complex sleep behaviours after taking zolpidem, see section