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 10mg to be taken immediately at bedtime. The lowest effective daily dose of zolpidem tartrate should be used and must not exceed 10mg.

Treatment should be as short as possible. It should not exceed four weeks including the period of tapering off. 4). 4). Treatment should be given for the shortest possible duration. Special populations Paediatric population Zolpidem tartrate 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 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. Excipients Zolpidem tartrate contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine. This medicine contains less than 1 mmol sodium (23mg) per tablet, that is to say essentially ‘sodium-free’.

5 Interaction with other medicinal products and other forms of interaction Not recommended 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.

Take into account Combination with 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 tartrate 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. Opioids The concomitant use of sedative medicines such as benzodiazepines or related drugs such as zolpidem tartrate with opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect.

4). CYP450 inhibitors and inducers Co-administration of ciprofloxacin may increase blood levels of zolpidem, concurrent use is not recommended. Compounds which inhibit certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines and benzodiazepine-like agents.

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. St. John’s Wort has been shown to have a pharmacokinetic interaction with zolpidem tartrate. 0% lower, respectively) for zolpidem administered with St. John’s Wort compared to zolpidem administered alone. Co-administration of St.

John’s Wort may decrease blood levels of zolpidem tartrate, 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 tartrate with ketoconazole (200mg twice daily), a potent CYP3A4 inhibitor, prolonged zolpidem tartrate elimination half-life, increased total AUC, and decreased apparent oral clearance when compared to zolpidem tartrate plus placebo.

83 when compared to zolpidem tartrate alone. A routine dosage adjustment of zolpidem tartrate is not considered necessary, but patients should be advised that use of zolpidem tartrate with ketoconazole may enhance the sedative effects.

Since CYP3A4 plays an important role in zolpidem metabolism, possible interactions with drugs that are substrates or inducers of CYP3A4 should be considered. Other drugs When zolpidem tartrate was administered with ranitidine, no significant pharmacokinetic interactions were observed.

6 Fertility, pregnancy and lactation Pregnancy The use of zolpidem tartrate is not recommended during pregnancy. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Zolpidem tartrate 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 the 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 tartrate 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/hypnotic agents 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.

Appropriate monitoring of the newborn in the postnatal period is recommended. If zolpidem tartrate 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 Effects on ability to drive and use machines Zolpidem tartrate has major influence on the ability to drive and use machines.

[…]

4 Special warning 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 Like other sedative/hypnotic drugs, zolpidem 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 tartrate is prescribed to patients with compromised respiratory function. 2. 2 for dose recommendations.

Risk from concomitant use of opioids Concomitant use of zolpidem tartrate 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 tartrate 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 tartrate are not recommended for the primary treatment of psychotic illness.

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 tartrate.

However, a causal relationship has not been established. As with other sedative/hypnotic drugs, zolpidem tartrate should be administered with caution in patients exhibiting symptoms of depression. Suicidal tendencies may be present therefore the least amount of zolpidem tartrate that is feasible should be supplied to these patients to avoid the possibility of intentional overdose by the patient.

Pre-existing depression may be unmasked during use of zolpidem tartrate. 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.

Drug dependence, tolerance and potential for abuse Drug addiction comprises behavioural, cognitive and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use and possible tolerance or physical dependence.

Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, which manifests as withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.

Addiction and dependence are related but distinct presentations and in discussing these themes, terminology that apportion blame to the individual should be avoided. For all patients, prolonged use of this product may lead to drug dependence and addiction but can occur with short-term use at recommended therapeutic doses.

, major depression). Additional support and monitoring may be necessary when prescribing for patients at risk of drug misuse. A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions.

Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of symptom control as initially experienced. Patients may also supplement their treatment with additional medications to achieve the same effect.

These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient. Overuse or misuse may result in overdose and/or death. It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else.

Patients should be closely monitored for signs of misuse, abuse, or addiction. The clinical need for treatment with zolpidem tartrate should be reviewed regularly, with frequent assessments of patients being undertaken during the course of their […]

1 • Obstructive sleep apnoea • Myasthenia gravis • Severe hepatic insufficiency • Acute and/or severe respiratory depression In the absence of data, zolpidem tartrate should not be prescribed for children or patients with psychotic illness.