Stilnox 12.5 mg MR Tablet

Short-term treatment of insomnia. STILNOX MR 12,5 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 S5 STILNOX MR 12,5 acts rapidly and therefore should be taken immediately before bedtime, or in bed. For a faster sleep onset, STILNOX MR 12,5 should not be administered with or immediately after a meal (see section 5.2, Pharmacokinetic properties). STILNOX MR 12,5 should be taken in a single intake and not be readministered 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 STILNOX MR 12,5 should be used and must not exceed 12,5 mg. Special populations Hepatic impairment: STILNOX MR 12,5 should not be used in patients with severe hepatic impairment (see section 4.3 and section 4.4). Renal impairment: No dosage adjustment is required. Children: Safety and effectiveness of STILNOX MR 12,5 in paediatric patients under the age of 18 years have not been established. Therefore, STILNOX MR 12,5 should not be prescribed in this population (see section 4.3). Elderly: As STILNOX MR 12,5 has not been evaluated in elderly patients (u2265 65 years), STILNOX MR 12,5 is not recommended in this population. Method of administration: Oral administration. Tablets should not be halved, crushed or chewed.

• A 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: As hypnotics have the capacity to depress respiratory drive, precautions should be observed if STILNOX MR 12,5 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 STILNOX MR 12,5, 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 STILNOX MR 12,5 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. Paediatric patients: STILNOX MR 12,5 is contraindicated in patients under the age of 18 years because the safety and effectiveness of STILNOX MR 12,5 have not been established (see section 4.3). In an 8-week study in paediatric patients (aged 6 u2013 17 years) with insomnia associated with attention-deficit/hyperactivity disorder (ADHD), psychiatric and nervous system disorders comprised the most frequent treatment emergent adverse events observed with zolpidem versus placebo and included dizziness (23,5 % vs. 1,5 %), headache (12,5 % vs. 9,2 %), and hallucinations (7,4 % vs. 0 %). Elderly patients: See section 4.2 for dose recommendations. Amnesia: STILNOX MR 12,5 may induce anterograde amnesia. The condition occurs most often several hours after ingesting STILNOX MR 12,5 and therefore, to reduce the risk, patients should ensure that they get a full nightu2019s sleep (7 - 8 hours) before being active. Other psychiatric and u201cparadoxicalu201d 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 STILNOX MR 12,5. Should this occur, use of STILNOX MR 12,5 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 STILNOX MR 12,5 and were not fully awake. Isolated cases of self-harming behaviour have also been reported. The use of alcohol and other CNS-depressants, or medicines which act on the central nervous system, with STILNOX MR 12,5 appears to increase the risk of such behaviours, as does the use of STILNOX MR 12,5 at doses exceeding the maximum recommended dose. Discontinuation of STILNOX MR 12,5 should be strongly considered for patients who report such behaviours, due to the risk to the patient and others. Psychomotor impairment: The risk of psychomotor impairment, including impaired driving ability, is increased if: STILNOX MR 12,5 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 STILNOX MR 12,5 is co-administered with other CNS depressants, alcohol, or with other medicines that increase the blood levels of STILNOX MR 12,5. Tolerance: Some loss of efficacy to the hypnotic effects of STILNOX MR 12,5 may develop after repeated use for a few weeks. Dependence: Use of STILNOX MR 12,5 may lead to the development of abuse and/or physical and psychological dependence. The risk of dependence increases with dose and duration of treatment, or in predisposed patients. Cases of dependence have been reported more frequently in patients treated with STILNOX MR 12,5 for longer than 4 weeks. The risk of abuse and dependence is also greater in patients with a history of psychiatric disorders and/or alcohol or medicine abuse. STILNOX MR 12,5 should be used with extreme caution in patients with current or a history of alcohol or medicine abuse. Patients with a history of alcohol or drug abuse u2013 see Patients with a history of alcohol and drug abuse. 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. Dependence has been reported with STILNOX MR 12,5 (see section 4.8). Withdrawal symptoms occur after abrupt termination and are limited, in the mildest cases, to tremors, restlessness, sleep disturbances, anxiety, headaches and impaired concentration. However, other symptoms such as sweating, muscle and abdominal cramps, perception disturbances, and rarely, delusions and epileptic seizures may occur. Depending on the duration of action of zolpidem, as in STILNOX MR 12,5, withdrawal symptoms develop a few hours to one week or more after discontinuation of treatment. To minimise the risk of dependence, STILNOX MR 12,5 should only be prescribed after carefully reviewing the indication and should be taken for the shortest time possible (generally not longer than 4 weeks). The need to continue treatment should be reviewed periodically. Prolonged treatment is only indicated in some patients. To avoid withdrawal symptoms, a tapering-off period, during which doses are reduced gradually, is advised. If withdrawal symptoms develop, very close medical supervision and patient management are essential. Rebound insomnia: A transient syndrome, whereby the symptoms that led to treatment with STILNOX MR 12,5 recur in an enhanced form, may occur on withdrawal of STILNOX MR 12,5 treatment. It may be accompanied by other reactions including mood changes, anxiety and restlessness. There are indications that, in the case of STILNOX MR 12,5 with a short duration of action, withdrawal phenomenon can become manifest within the dosage interval, especially when the dosage is high. The rebound phenomenon, if it occurs with STILNOX MR 12,5, was limited to the first night after the medicine discontinuation in clinical studies (see Pharmacodynamic properties). It is important that the patient should be aware of the possibility of rebound phenomenon, thereby minimising anxiety over such symptoms should they occur when STILNOX MR 12,5 is discontinued. Patients with a history of alcohol or drug abuse: STILNOX MR 12,5 should not be used in patients with a history of alcohol or medicine abuse. Hepatic impairment: STILNOX MR 12,5 should be used with caution in patients with mild to moderate hepatic impairment. STILNOX MR 12,5 must not be used in patients with severe hepatic impairment as it may contribute to encephalopathy. (see section 4.3 and section 5.2, Hepatic impairment). Psychotic illness: STILNOX MR 12,5 is not recommended for the primary treatment of psychotic illness. Suicidality and depression: Several epidemiological studies show an increased incidence of suicide and suicide attempt in patients with or without depression, treated with benzodiazepines and other hypnotics, including STILNOX MR 12,5. A causal relationship has not been established. STILNOX MR 12,5 should not be used alone to treat depression or anxiety associated with depression (suicide may be precipitated in such patients). As suicidal tendencies may be present, the least amount of STILNOX MR 12,5 that is feasible, should be supplied to these patients because of the possibility of intentional overdosage by the patient. A pre-existing depression may be unmasked during the use of STILNOX MR 12,5. Since insomnia may be a symptom of depression, the patient should be re-evaluated if insomnia persists. Drowsiness: Due to its pharmacological properties, STILNOX MR 12,5 can cause drowsiness and a decreased level of consciousness, which may lead to falls and consequently to severe injuries. It may be accompanied by other reactions including mood changes, anxiety and restlessness. Patients with long QT syndrome: An in vitro cardiac electrophysiological study showed that under experimental conditions using very high concentration and pluripotent stem cells STILNOX MR 12,5 may reduce the hERG (human ether-a-go-go-related gene) related potassium currents. The potential consequence in patients with congenital long QT syndrome is unknown. As a precaution, the benefit/risk ratio of STILNOX MR 12,5 treatment in patients with known congenital long QT syndrome should be carefully considered. Lactose intolerance: Since STILNOX MR 12,5 tablets contain lactose monohydrate, patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption, should not take STILNOX MR 12,5.

Alcohol: Concomitant use with alcohol is not recommended. The sedative effect may be enhanced when STILNOX MR 12,5 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, opioids (analgesics and antitussives), narcotic analgesics, antiepileptic medicines, anaesthetics and sedative antihistamines. Concomitant use of STILNOX MR 12,5 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. Combination of STILNOX MR 12,5 with fluoxetine or sertraline, SSRI (selective serotonin reuptake inhibitors) antidepressants, it should be noted that: u2022 with fluoxetine, no clinically significant interaction, either for pharmacokinetics or pharmacodynamics, has been observed u2022 with sertraline, the maximum concentration of zolpidem is significantly elevated and the T max is decreased. Although it has not been demonstrated clinically, these changes could theoretically accelerate the hypnotic effect of zolpidem. Opioids: The concomitant use of benzodiazepines and other sedative-hypnotic medicines, including STILNOX MR 12,5, 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 STILNOX MR 12,5. STILNOX MR 12,5 is metabolised via several hepatic cytochrome P450 enzymes, the main enzyme being CYP3A4 with the contribution of CYP1A2. Co-administration of STILNOX MR 12,5 with ketoconazole (200 mg twice daily), a potent CYP3A4 inhibitor, produced a 64 % increase in STILNOX MR 12,5 plasma levels. A routine dosage adjustment of STILNOX MR 12,5 is not necessary, but patients should be advised that the sedative effects might be enhanced. However, co-administration of STILNOX MR 12,5 with itraconazole or fluconazole did not produce any significant changes in STILNOX MR 12,5 pharmacokinetics and pharmacodynamics. It is not necessary to change the dose of STILNOX MR 12,5 with itraconazole use. 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 STILNOX MR 12,5; 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 STILNOX MR 12,5; concurrent use is not recommended. The pharmacodynamic effect of STILNOX MR 12,5 is decreased when it is administered with a CYP3A4 inducer such as rifampicin due to an increase in liver metabolism. The pharmacodynamic effect of STILNOX MR 12,5 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 STILNOX MR 12,5; concurrent use is not recommended. Other: No significant pharmacokinetic interactions were observed, when STILNOX MR 12,5 was administered with warfarin, digoxin, ranitidine or cimetidine.

Safety in pregnancy and lactation has not been established (see section 4.3). Pregnancy: The use of STILNOX MR 12,5 during pregnancy should be avoided. Zolpidem, as in STILNOX MR 12,5 crosses the placenta. Cases of reduced fetal movement and fetal heart rate variability have been described after administration of benzodiazepines during the second and/or third trimester of pregnancy. The data collected from cohort studies has not demonstrated evidence of the occurrence of malformations following exposure to benzodiazepines (like zolpidem) during the first trimester of pregnancy. However, in certain epidemiological case-control studies, an increased incidence of cleft lip and palate was observed with benzodiazepines. Administration of STILNOX MR 12,5 during the late phase of pregnancy or during labour, has been associated with effects on the neonate, such as hypothermia, hypotonia, feeding difficulties and moderate respiratory depression, can be expected due to the pharmacological action of STILNOX MR 12,5. Cases of severe neonatal respiratory depression have been reported. Infants born to mothers who took hypnotics, including STILNOX MR 12,5, 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. If STILNOX MR 12,5 is prescribed to a woman of childbearing potential, she should be warned to contact her medical practitioner about stopping STILNOX MR 12,5 if she intends to become, or suspects that she is pregnant. Lactation: Small quantities of zolpidem is excreted in breast milk, the use of STILNOX MR 12,5 in breastfeeding mothers is not recommended (see section 4.3).

Vehicle drivers and machine operators should be warned that there may be a possible risk of adverse reactions including drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/double vision, reduced alertness and impaired driving the morning after therapy. In order to minimise this risk, a full night of sleep (7 - 8 hours) is recommended. Furthermore, the co-administration of STILNOX MR 12,5 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 STILNOX MR 12,5 (see section 4.4 and section 4.5). The risk related to anterograde amnesia should also be taken into consideration.

Adverse reactions have been ranked under headings of system-organ class and frequency using the following: very common (u2265 10 %); common (u2265 1 and < 10 %); uncommon (u2265 0,1 % and < 1 %); rare (u2265 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 STILNOX MR 12,5 use, particularly for certain CNS events. They occur most frequently in elderly patients. Infections and Infestations Common: influenza Uncommon: gastroenteritis, labyrinthitis, lower respiratory tract infection, otitis externa, upper respiratory tract infection Immune system disorders Not known: angioneurotic oedema Metabolism and nutrition disorders Uncommon: appetite disorder Psychiatric disorders Common: anxiety, psychomotor retardation, disorientation Uncommon: restlessness, aggression, depression, hallucination, including visual and hypnagogic hallucination, apathy, binge eating, confusional state, depersonalisation, depressed mood, disinhibition, euphoric mood, mood swings, nightmares, stress symptoms, somnambulism (see section 4.4, Somnambulism and associated behaviours) Rare: libido disorder Very rare: delusion, dependence (withdrawal symptoms, or rebound effects may occur after treatment discontinuation) Not known: anger, abnormal behaviour Most of these psychiatric undesirable effects are related to paradoxical reactions. Nervous system disorders Very common: headache, somnolence Common: dizziness, cognitive disorders such as memory disorders (memory impairment, amnesia, anterograde amnesia), disturbance in attention Uncommon: balance disorder, hypoaesthesia, paraesthesia, ataxia, burning sensation, postural dizziness, dysgeusia, involuntary muscle contractions, tremor Rare: depressed level of consciousness, speech disorder Eye disorders Common: visual disturbance Uncommon: eye redness, blurred vision, altered visual depth perception, asthenopia Ear and labyrinth disorders Uncommon: vertigo, tinnitus Cardiac disorders Uncommon: palpitations Respiratory, thoracic and mediastinal disorders Uncommon: cough, dry throat, throat irritation Very rare: respiratory depression Gastrointestinal disorders Common: nausea, constipation Uncommon: vomiting, abdominal discomfort, flatulence, frequent bowel movements, gastro-oesophageal reflux disease Hepato-biliary disorders: Rare: bilirubinaemia, severe hepatitis with jaundice, raised liver enzymes, hepatocellular, cholestatic or mixed liver injury Skin and subcutaneous tissue disorders Uncommon: rash, urticaria, contact dermatitis, skin wrinkling Musculoskeletal and connective tissue disorders Common: myalgia, muscle cramp, neck pain, back pain Uncommon: arthralgia, muscular weakness Renal and urinary disorders Uncommon: dysuria Reproductive system and breast disorders Uncommon: dysmenorrhoea, menorrhagia, vulvovaginal dryness General disorders and administration site conditions Common: fatigue Uncommon: asthenia, chest discomfort, feeling drunk, influenza-like illness, lethargy, pain, pyrexia Rare: gait disturbances, fall (predominantly in elderly patients and when STILNOX MR 12,5 was not taken in accordance with prescribing recommendation) Not known: drug tolerance Investigations Uncommon: increased blood pressure, increased body temperature, increased heart rate

Signs and symptoms: In cases of overdose involving STILNOX MR 12,5 alone or with other CNS-depressant agents (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. If there is no advantage in emptying the stomach, 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. It may be useful for diagnosis and/or treatment of an intentional or accidental STILNOX MR 12,5 overdose. However, flumazenil administration may contribute to the appearance of neurological symptoms (convulsions). STILNOX MR 12,5 is not dialysable.