Zolpidem Tartrate 10mg Tablets
Out of date information, search anotherProduct Summary
1. Trade Name of the Medicinal Product Zolpidem Tartrate 10mg Tablets
2. Qualitative and Quantitative Composition
Each tablet contains 10 mg of Zolpidem tartrate.
For excipients see 6.1.
3. Pharmaceutical Form
Film coated tablet.
White, oval, biconvex, film-coated tablets, embossed with “ZIM” on one side and “10” on the other.
Clinical Particulars
4.1 Therapeutic Indications
Zolpidem Tablets are used as a short-term treatment for patients who are suffering from incapacitating insomnia or where insomnia is causing severe distress.
4.2 Posology and Method of Administration
The dose should be taken at night not less than one hour after food. Zolpidem acts rapidly and therefore should be taken immediately before retiring, or in bed.
Adults:
Daily dose of 10mg Elderly or debilitated:
Daily dose of 5mg as these patients are likely to be more susceptible to the effects of zolpidem tablets.
Children:
Should not be used in children.
Hepatic impairment:
A dose of 5mg per day should be given as the clearance and metabolism of zolpidem is decreased in those with liver problems. Particular caution should be exercised in elderly patients with hepatic impairment. If an inadequate therapeutic effect has been observed and the drug is well tolerated in adults under the age of 65, the dose may be increased to 10mg.
The total recommended daily doses should not be exceeded.
Long term use is not recommended, as with all hypnotics, and the treatment schedule should therefore not last longer than 4 weeks. Treatment duration can vary from a few days to 2 weeks, with a maximum of 4 weeks to include gradual withdrawal where indicated.
Method of Administration Oral
4.3 Contra-indications
• Zolpidem tablets are contraindicated in the following circumstances:
• Hypersensitivity to zolpidem or any of the excipients in the tablet
• Obstructive sleep apnoea
• Myasthenia gravis
• Severe hepatic insufficiency
• Acute pulmonary insufficiency
• Respiratory depression
• Use in children
• Use in patients with psychotic illness
4.4 Special Warnings and Precautions for Use
Before using a hypnotic such as zolpidem tablets the underlying condition should be assessed, identified and treated where possible. If treatment has failed to alleviate the patient’s insomnia after 7 - 14 days this may be a sign that a primary psychiatric or physical disorder is present and the cause should therefore be investigated.
Use in Depression: If patients are showing depressive symptomology, zolpidem should be administered with caution. Due to possible suicidal ideation and the risk of intentional overdose by the patient, the quantity of zolpidem prescribed should be the smallest appropriate amount.
Use in patients with a history of drug or alcohol abuse: If patients have a history of drug, alcohol or substance abuse, great caution should be taken when prescribing zolpidem. Due to the high risk of habituation and psychological dependence, patients should be kept under close observation.
Use in Elderly: Caution is advised when prescribing for the elderly as they have increased sensitivity to zolpidem and are more likely to suffer from side effects.
When prescribing benzodiazepines or other hypnotic medications, the following information should be taken into account:
Tolerance: After continuous use for a few weeks there may be a loss of efficacy in the hypnotic effect of short acting drugs such as Zolpidem Tablets.
Dependence: There is a risk of physical and psychological dependence developing when benzodiazepines or benzodiazepine type drugs are used. The probability of dependence increases with the dose, the length of treatment and if the drug has a short duration of action. The risk is also increased in those people who have a history of substance abuse. If physical dependence has developed, withdrawal symptoms are likely if treatment is suddenly discontinued. These symptoms may include headache, depression, muscle pain, irritability, confusion, great anxiety and tension. Sometimes severe withdrawal effects are seen and these consist of derealisation, depersonalisation, hyperacusis, numbness and tingling of extremities, hypersensitivity to light, noise and physical contact, hallucinations and epileptic seizures.
Rebound Insomnia: On withdrawal of a benzodiazepine or benzodiazepinelike drug, the symptoms that originally prompted treatment may return in a heightened form. This recurrence, although transient, may also include other phenomena such as mood changes, anxiety and restlessness. It is important that the patient is informed about the possibility of this occurrence so their anxiety can be constrained if such symptoms arise. As abrupt cessation of the treatment is associated with withdrawal and rebound symptoms, if possible the dosage should be gradually reduced. It is thought that if a drug has a short duration of action these types of withdrawal symptoms can be seen between doses. This phenomenon is particularly observed in patients on high doses.
Amnesia: Patients should take the tablets at such a time as to ensure that they can sleep uninterrupted for 7-8 hours. This is because there is a risk of anterograde amnesia and this usually begins a few hours after the product has been ingested.
Psychiatric and ‘Paradoxical’ side-effects: There have been reports of behavioural side-effects that sometimes occur when patients, especially the elderly, take benzodiazepines or benzodiazepine type drugs. These adverse reactions include restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses and inappropriate behaviour. If such side-effects occur, Zolpidem Tablets should be discontinued.
4.5 Interactions with other Medicaments and other forms of Interaction
Alcohol should not be taken concurrently as the sedative effect of zolpidem may be increased.
Caution Advised:
Zolpidem should be used with caution when the patient is taking CNS depressants, as the depressant effect of the drugs may be magnified. Caution should therefore be taken when treating with
• Antipsychotics (neuroleptics)
• Hypnotics
• Anxiolytics/sedatives
• Antidepressant agents
• Narcotic analgesics
• Antiepileptics drugs
• Anaesthetics
• Sedative antihistamines
Concomitant use with narcotic analgesics may increase euphoria and therefore may contribute to an increase in psychological dependence.
The action of benzodiazepines and benzodiazepine type agents may be enhanced by drugs which inhibit certain hepatic enzymes, especially the cytochrome P450 enzyme.
4.6 Pregnancy and Lactation
Safety in pregnancy has not been established although no teratogenic or embryotoxic effects have been reported in animals. Zolpidem should be avoided in pregnancy, particularly during the first trimester.
Women of child bearing age should be informed that they should contact their doctor if they intend to become or suspect that they are pregnant.
If Zolpidem is used for urgent medical reasons during the late phase of pregnancy or during labour, the neonate may be effected by hypothermia, hypotonia and moderate respiratory depression as a result of the pharmacological action of the drug.
Mothers who take benzodiazepines or benzodiazepine like drugs persistently during pregnancy may give birth to babies that have developed physical dependence and so may develop withdrawal symptoms in the postnatal period.
Use of Zolpidem is not recommended for lactating mothers as Zolpidem appears in small quantities in the breast milk.
4.7 Effects on Ability to Drive and Use Machines
Simulated car driving tests have shown that on the day after taking the medicine driving was not affected. However due to the possible risk of drowsiness in the morning after treatment, those who drive vehicles and operate machines should be warned of the possible danger.
As the sedative effect of zolpidem may be increased with the concurrent intake of alcohol, which could then affect the patient’s ability to drive or use machinery, those who drive vehicles and operate machines should be warned of the possible danger.
4.8 Undesirable Effects
There is evidence of a dose-relationship for adverse effects associated with zolpidem use, particularly for certain CNS and gastrointestinal events. These adverse effects are seen more frequently in elderly patients.
The most frequently documented undesirable effects seen after taking Zolpidem are daytime drowsiness, dizziness, diarrhoea, headache, nausea, vomiting, weakness and vertigo.
More rare reactions that have been identified include memory disturbances (anterograde amnesia), nightmares, nocturnal restlessness, depressive syndrome, episodes of confusion, perceptual disturbances or diplopia, tremor, unsteady gait and falls. The likelihood of amnesia is not related to dose or age.
4.9 Overdose
When zolpidem is the sole drug taken, it has been found that consciousness is impaired and ranges from somnolence to light coma. Patients who have taken up to 40 times the daily dose, 400mg, have fully recovered.
Symptomatic and supportive measures should be taken, and where appropriate gastric lavage should be used and intravenous fluids should be given. If 100mg or more of zolpidem has been ingested, gastric lavage should be performed and the patient observed for at least 12 hours. Activated charcoal should be used to reduce absorption if emptying of the stomach is not appropriate. Sedating drugs should be withheld even if excitation occurs. Use of flumazenil may be considered where serious symptoms are observed.
As with all overdoses consideration needs to be given to the fact more than one drug may have been taken.
Pharmacological Properties
5.1 Pharmacodynamic Properties
Zolpidem is an imidazopyridine, and as such it is a GABA-A receptor agonist that selectively binds the omega-1 receptor subtype (also known as the benzodiazepine-1 subtype or BZ-1) which is the alpha unit of the GABA-A receptor complex. Benzodiazepines bind to all 3 omega receptor subtypes, but zolpidem selectively binds to the omega-1, the BZ1 receptor. It is thought that this selectivity is the reason that zolpidem is potent as a sedative as opposed to a muscle relaxant, anti-convulsant or minor anxiolytic. The sedative effect is gained by the modulation of the chloride anion channel via this receptor.
The effects of zolpidem are reversed by flumazenil, which is a benzodiazepine antagonist.
In animals: The myorelaxant and anticonvulsant properties that are usually seen in benzodiazepines are not present at hypnotic doses of zolpidem. It is believed that this is due to the selectivity for the omega-1 sites in the brain.
In humans: Deep sleep (stage 3 and 4 of slow wave sleep) is unchanged after treatment with Zolpidem. Again it is thought to be as a result of the selectivity to the omega 1 binding site.
5.2 Pharmacokinetic Properties
Zolpidem has both a rapid absorption and onset of hypnotic action. Bioavailability is 70% following oral administration and demonstrates linear kinetics in the therapeutic dose range. C max is reached at between 0.5 and 3 hours. A night-time food interaction study showed a 15% reduction in AUC and a 25% reduction in Cmax.
It is widely distributed throughout the body. The volume of distribution in adults is 0.54±0.02 L/kg and decreases to 0.34±0.05 L/kg in the elderly.
Protein binding amounts to 92.5%±0.1%. After repeated doses the drug does not accumulate and protein binding is unchanged.
Zolpidem undergoes first pass metabolism in the liver. The metabolites are not pharmacologically active.
The elimination half-life is short, with a mean of 2.4 hours (0.7-0.3.5) and a duration of action up to 6 hours. Zolpidem is almost entirely eliminated by the liver with 79-96% of the dose appearing as metabolites in the urine (56%) and faeces (37%). Less than 1% is excreted unchanged in the urine.
Zolpidem is not removed by haemodialysis.
In the elderly and patients with hepatic impairment, the plasma concentrations are increased, and the clearance and volume of distribution are reduced. In patients with renal problems there may be a moderate reduction in clearance, even after dialysis, although there is no need for dose adjustment. Other pharmacokinetic parameters are unaffected.
5.3 Preclinical Safety Data
Preclinical data revealed no special hazard to humans based on conventional studies of safety pharmacology, repeated dose toxicity, gentotoxicity, carcinogenic potential, toxicity to reproduction.
Pharmaceutical Particulars
6.1 List of Excipients
Tablet core:
Lactose monohydrate Microcrystalline cellulose Sodium starch glycollate Hypromellose Magnesium stearate
Film coat:
Hypromellose Titanium dioxide (E171) Macrogol 400
6.2 Incompatibilities
None Known
6.3 Shelf Life
36 months
6.4 Special Precautions for Storage
Store in the original package
6.5 Nature and Contents of Container
PVC/PE/PVDC/Al blister
HDPE containers sealed with an aluminium seal, and closed with a child resistant PP closure.
10, 28, 100
6.6 Instruction for Use/Handling
Not Applicable
7 MARKETING AUTHORISATION HOLDER
Sandoz Limited Frimley Business Park,
Frimley,
Camberley,
Surrey,
GU16 7SR,
United Kingdom.
8. MARKETING AUTHORISATION NUMBER(S)
PL 04416/0365
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
02/04/2009
10 DATE OF REVISION OF THE TEXT
08/02/2011