Zoltab 5mg & 10mg Tablet

ZOLTAB is indicated for the short-term treatment of insomnia. ZOLTAB is a short-acting hypnotic, is only indicated when the disorder is severe, debilitating or is causing severe distress for the patient.

Posology: Treatment should be as short as possible. The duration of treatment ranges from a few days to two weeks, with a maximum of four weeks (includes the tapering off period). 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. The recommended daily dose for adults is 10 mg to be taken immediately before bedtime. The lowest effective daily dose of ZOLTAB should be used and must not exceed 10 mg.

Special populations: Elderly patients: Elderly or debilitated patients may be especially sensitive to the effects of ZOLTAB therefore a 5 mg dose is recommended in these patients. The total dose should not exceed 10 mg in these patients. Patients with hepatic impairment: In hepatic impairment patients, the recommended dosage of ZOLTAB is 5 mg with particular caution being exercised in elderly patients. Paediatric patients: Safety and effectiveness of ZOLTAB in paediatric patients under the age of 18 years have not been established. ZOLTAB should not be prescribed in this population (see section 4.3).

Method of administration: ZOLTAB is for once-daily oral administration.

• Hypersensitivity to zolpidem or to any of the excipients listed in section 6.1.
• Obstructive sleep apnoea.
• Myasthenia gravis.
• Severe hepatic insufficiency (see section 4.4).
• Acute and/or severe respiratory depression.
• Children under the age of 18.
• Safety in Pregnancy and lactation has not been established (see section 4.6).

The cause of insomnia should be identified wherever possible and the underlying factors treated before ZOLTAB 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.

Severe hepatic insufficiency: ZOLTAB is contraindicated in patients with severe hepatic insufficiency as it may precipitate encephalopathy (see section 4.3).

Respiratory insufficiency: As hypnotics have the capacity to depress respiratory drive, precautions should be observed if ZOLTAB is prescribed to patients with compromised respiratory function.

Risks from concomitant use with opioids: Concomitant use of ZOLTAB 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 medicines such as zolpidem with opioids should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe ZOLTAB concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible (see also general dose recommendation in section 4.2). The patients should be followed closely for signs and symptoms of respiratory depression and sedation.

Paediatric patients: ZOLTAB is contraindicated in patients under the age of 18 years due to increased occurrence of adverse effects including dizziness, headache and hallucinations.

Elderly patients: See section 4.2 for dose recommendations.

Psychomotor impairment: ZOLTAB has CNS-depressant effects. The risk of next-day psychomotor impairment, including impaired driving ability, is increased if:

• ZOLTAB 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;
• ZOLTAB is co-administered with other CNS depressants or with other medicines that increase the blood levels of zolpidem, or with alcohol or illicit medicines (see section 4.5).

History of medicine or alcohol abuse: ZOLTAB should not be used in patients with a history of medicine or alcohol abuse.

Psychotic illness: ZOLTAB is not recommended for the primary treatment of psychotic illness.

Suicidality and depression: Increased incidence of suicide and suicide attempt in patients with or without depression, treated with benzodiazepines and other hypnotics, including ZOLTAB were observed. ZOLTAB should not be used as the primary treatment depressive syndromes. ZOLTAB should be administered with caution in patients exhibiting symptoms of depression. Suicidal tendencies may be present therefore the least amount of ZOLTAB 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 ZOLTAB. Since insomnia may be a symptom of depression, the patient should be re-evaluated if insomnia persists.

Alcohol: Concomitant intake with alcohol is not recommended. The sedative effects may be enhanced when ZOLTAB 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. Therefore, concomitant use of ZOLTAB with these medicines may increase drowsiness and following day psychomotor impairment, including impaired driving ability (see sections 4.4 and 4.7).

Cases of visual hallucinations were reported in patients taking ZOLTAB with antidepressants including bupropion, desipramine, fluoxetine, sertraline and venlafaxine. Co-administration of fluvoxamine may increase blood levels of zolpidem as in ZOLTAB, concomitant 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 medicines such as ZOLTAB with 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 certain hepatic enzymes (particularly cytochrome P450) may enhance the activity of benzodiazepines and benzodiazepine-like medicines such as ZOLTAB. ZOLTAB is metabolised via several hepatic cytochrome P450 enzymes, the main enzyme being CYP3A4 with the contribution of CYP1A2. The pharmacodynamic effect of ZOLTAB 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 ZOLTAB, concurrent use is not recommended. However when ZOLTAB 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 ZOLTAB with ketoconazole (200 mg twice daily), a potent CYP3A4 inhibitor, prolonged ZOLTAB elimination half-life, increased total AUC, and decreased apparent oral clearance when compared to ZOLTAB plus placebo). The total AUC for ZOLTAB, when co-administered with ketoconazole, increased by a factor of 1.83 when compared to ZOLTAB alone. A routine dosage adjustment of zolpidem is not considered necessary, but patients should be advised that use of ZOLTAB with ketoconazole may enhance the sedative effects.

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 ZOLTAB, concurrent use is not recommended. Co-administration of ciprofloxacin may increase blood levels of ZOLTAB, concurrent use is not recommended. Other medicines: When ZOLTAB was administered with warfarin, digoxin, ranitidine or cimetidine, no significant pharmacokinetic interactions were observed.

Women of child-bearing potential: If ZOLTAB is prescribed to a woman of childbearing potential, she should be warned to contact her medical doctor about stopping the ZOLTAB if she intends to become or suspects that she is pregnant.

Pregnancy: The use of ZOLTAB is not recommended during pregnancy. ZOLTAB crosses the placenta. Administration of ZOLTAB during the late phase of pregnancy, or during labour has been associated with effects on the neonate, such as hypothermia, hypotonia, feeding difficulties (which may result in poor weight gain), and respiratory depression, sometimes severe, due to the pharmacological action of the medicine. Infants born to mothers who took sedative/hypnotic medicines as in ZOLTAB chronically during the latter stages of pregnancy may develop physical dependence and may be at risk of developing withdrawal symptoms in the postnatal period.

Lactation: Small quantities of zolpidem as in ZOLTAB appear in breast milk. The use of ZOLTAB in nursing mothers is therefore contra-indicated.

ZOLTAB has major influence on the ability to drive and use machines. Vehicle drivers and machine operators should be warned that there may be a possible risk of adverse reactions including drowsiness, prolonged reaction time, dizziness and vertigo, sleepiness, blurred/double vision, reduced alertness and impaired driving the morning after therapy. If insufficient sleep duration occurs, the likelihood of impaired alertness may increase. In order to minimise this risk a full night of sleep (7 u2013 8 hours) is recommended. The co-administration of ZOLTAB 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 ZOLTAB.

Adverse drug reactions are listed below by system organ class and frequency. Frequencies are defined as: Frequent, less frequent, frequency unknown.

Infections and infestations: Frequent: upper respiratory tract infection, lower respiratory tract infection.

Psychiatric disorders: Frequent: hallucination, agitation, nightmare. Less frequent: confusional state, irritability. Frequency unknown: restlessness, aggression, anger, delusion, abnormal behaviour, somnambulism (see section 4.4), dependence (withdrawal symptoms, or rebound effects may occur after treatment discontinuation); euphoric mood, libido disorder, depression, and psychosis. Most of these psychiatric undesirable effects are related to paradoxical reactions.

Nervous system disorders: Frequent: somnolence, headache, dizziness, exacerbated insomnia, cognitive disorders such as anterograde amnesia (amnesic effects may be associated with inappropriate behaviour). Less frequent: paraesthesia, tremor. Frequency unknown: disturbance in attention, speech disorder, depressed level of consciousness.

General disorders and administrative site conditions: Frequent: fatigue. Frequency unknown: gait disturbances, medicine tolerance and fall.

Eye disorders: Less frequent: diplopia, vision blurred and visual impairment.

Metabolism and nutrition disorders: Less frequent: appetite disorder.

Respiratory, thoracic and mediastinal disorders: Frequency unknown: respiratory depression (see section 4.4).

Gastrointestinal disorders: Frequent: diarrhoea, nausea, vomiting and abdominal pain.

Hepatobiliary disorders: Frequency unknown: liver enzymes elevated, hepatocellular, cholestatic or mixed liver injury (see sections 4.2, 4.3 and 4.4).

Skin and subcutaneous tissue disorders: Frequency unknown: rash, pruritus, angioneurotic oedema, hyperhidrosis and urticaria.

Musculoskeletal, connective tissue and bone disorders: Frequent: back pain. Less frequent: arthralgia; myalgia, muscle spasms, neck pain. Frequency unknown: muscular weakness.

In cases of overdose, involving ZOLTAB alone or with other CNS-depressant medicines (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. 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 appearance of neurological symptoms (convulsions). In the management of overdose with any medicine, it should be borne in mind that multiple medicines may have been taken. ZOLTAB is not dialysable.