- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Special PopulationsPaediatric populationStilnoct 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 5.1.
ElderlyElderly 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 impairmentAs 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.
Next-day psychomotor impairmentThe risk of next-day psychomotor impairment, including impaired driving ability, is increased if: • zolpidem tartrate is taken within less than 8 hours before performing activities that require mental alertness (see section 4.7); • a dose higher than the recommended dose is taken; • zolpidem tartrate is co-administered with other CNS depressants or with other drugs that increase the blood levels of zolpidem tartrate, or with alcohol or illicit drugs (see section 4.5). 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 Stilnoct is prescribed to patients with compromised respiratory function.
Hepatic Insufficiency:See section 4.2.
Elderly:See section 4.2 dose recommendations.
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 Stilnoct are not recommended for the primary treatment of psychotic illness.
Depression: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 Stilnoct 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 Stilnoct. 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 Stilnoct may develop after repeated use for a few weeks
Dependence:Use of benzodiazepines or benzodiazepine-like agents like Stilnoct 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, 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 Stilnoct 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 4.8).
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 Stilnoct and were not fully awake. The use of alcohol and other CNS-depressants with Stilnoct appears to increase the risk of such behaviours, as does the use of Stilnoct at doses exceeding the maximum recommended dose. Discontinuation of Stilnoct 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 4.5 Interactions with other medicinal products and other forms of interaction; and Section 4.8 Undesirable effects).
Severe injuries:Due to its pharmacological properties, zolpidem can cause drowsiness and a decreased level of consciousness, which may lead to falls and consequently to severe injuries.
Not recommendedConcomitant 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 accountCombination 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. Therefore, concomitant use of Stilnoct with these drugs may increase drowsiness and next-day psychomotor impairment, including impaired driving ability (see section 4.4 and section 4.7). Also, isolated cases of visual hallucinations were reported in patients taking Stilnoct 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:Co- administration of ciprofloxacin may increase blood levels of zolpidem tartrate, 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 rifampicin (a CYP3A4 inducer). 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 Stilnoct with ketoconazole (200mg twice daily), a potent CYP3A4 inhibitor, prolonged Stilnoct elimination half-life, increased total AUC, and decreased apparent oral clearance when compared to Stilnoct plus placebo. The total AUC for Stilnoct, when co-administered with ketoconazole, increased by a factor of 1.83 when compared to Stilnoct alone. A routine dosage adjustment of Stilnoct is not considered necessary, but patients, should be advised that use of Stilnoct with ketoconazole may enhance the sedative effects. Since CYP3A4 plays an important role in zolpidem tartrate 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.
PregnancyFor Zolpidem tartrate, no or very limited amount of data on pregnant patients are available. Although animal studies have shown no teratogenic or embryotoxic effects, safety in pregnancy has not been established. As with all drugs zolpidem tartrate 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 tartrate 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 tartrate 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.
LactationSmall quantities of zolpidem tartrate appear in breast milk. The use of zolpidem tartrate in nursing mothers is therefore not recommended.
Immune system disordersNot known: angioneurotic oedema
Psychiatric disordersCommon: hallucination, agitation, nightmareUncommon: confusional state, irritabilityNot known: restlessness, aggression, delusion, anger, psychosis, abnormal behaviour, somnambulism (see section 4.4), dependence (withdrawal symptoms, or rebound effects may occur after treatment discontinuation), libido disorder, depression (see section 4.4)Most of these psychiatric undesirable effects are related to paradoxical reactions
Nervous system disordersCommon: somnolence, headache, dizziness, exacerbated insomnia, anterograde amnesia: (amnestic effects may be associated with inappropriate behaviour)Not known: depressed level of consciousness
Eye disordersUncommon: diplopia
Respiratory, thoracic and mediastinal disordersNot Known: respiratory depression (see section 4.4)
Gastro-intestinal disordersCommon: diarrhoea, nausea, vomiting, abdominal pain Hepatobiliary disordersNot known: Liver enzymes elevated
Skin and subcutaneous tissue disordersNot known: rash, pruritus, urticaria, hyperhidrosis
Musculoskeletal and connective tissue disordersCommon: back painNot known: muscular weakness Infections and infestationsCommon: upper respiratory tract infection, lower respiratory tract infection
General disorders and administration site conditionsCommon: 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 4.4).
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
Signs and Symptoms:In cases of overdose involving zolpidem tartrate 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 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.
|Tablet core:||Lactose monohydrate, Microcrystalline cellulose, Hypromellose, Sodium starch glycollate, Magnesium stearate.|
|Film coating:||Hypromellose, Titanium dioxide (E171), Macrogol 400.|
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