Consumer medicine information

Stilnox CR

Zolpidem tartrate

BRAND INFORMATION

Brand name

Stilnox CR

Active ingredient

Zolpidem tartrate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Stilnox CR.

SUMMARY CMI

STILNOX CR®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I taking STILNOX CR?

STILNOX CR contains the active ingredient zolpidem tartrate. STILNOX CR is used to initiate and maintain sleep in those with sleeping difficulties, also called insomnia in patients over 18 years of age. For more information, see Section 1. Why am I taking STILNOX CR? in the full CMI.

2. What should I know before I take STILNOX CR?

Do not use if you have ever had an allergic reaction to STILNOX CR or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, have been drinking alcohol, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before I take STILNOX CR? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with STILNOX CR and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take STILNOX CR?

  • In Adults: Usual dose is one 12.5 mg tablet taken just before bedtime.
  • In people over 65 years of age: The dose is one 6.25 mg tablet taken just before bedtime.

More instructions can be found in Section 4. How do I take STILNOX CR? in the full CMI.

5. What should I know while taking STILNOX CR?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using STILNOX CR.
  • If you become pregnant or suspect that you are pregnant while you are taking this medicine, stop taking it and tell your doctor or pharmacist immediately.
Things you should not do
  • Do not take STILNOX CR if you have sleep apnoea, myasthenia gravis, severe liver problems, acute and / or severe lung problems or if you have previously experienced complex sleep behaviours such as sleep walking.
  • Do not give STILNOX CR to a child or adolescent
Driving or using machines
  • You should not operate dangerous machinery or drive motor vehicles for 8 hours after you take it. You should also be careful the next morning when you wake up.
Drinking alcohol
  • You should not drink alcohol while you are taking STILNOX CR.
Looking after your medicine
  • Keep the medicine in a cool, dry place where the temperature stays below 30°C.

For more information, see Section 5. What should I know while using STILNOX CR? in the full CMI.

6. Are there any side effects?

Common side effects are: drowsiness, sleepiness, dizziness, headache, fatigue, anxiety, disorientation, slowness in thinking and movement, poor attention and concentration, loss of memory, diarrhoea, nausea, constipation, muscle cramps or aching, muscle tenderness or weakness not caused by exercise, neck and back pain, influenza or flu-like symptoms and visual disturbances.

If any of the following happen, stop taking this medicine and tell your doctor immediately, or go to Accident and Emergency at your nearest hospital: swelling of the face, lips, mouth or throat, which may cause difficulty in swallowing or breathing, hives, fainting.

Sleep walking, driving motor vehicles and other unusual, and on some occasions dangerous, behaviours whilst apparently asleep may also occur. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

WARNING: ZOLPIDEM MAY BE ASSOCIATED WITH UNUSUAL AND POTENTIALLY DANGEROUS BEHAVIOURS WHILST APPARENTLY ASLEEP. THESE HAVE INCLUDED SLEEP WALKING, DRIVING MOTOR VEHICLES AND OTHER BIZARRE BEHAVIOURS. SOME MEDICINES MAY INTERACT WITH ZOLPIDEM AND PARTICULAR CAUTION IS NEEDED WITH OTHER DRUGS THAT MAY ALSO ACT ON THE BRAIN; BEFORE YOU TAKE ZOLPIDEM REFER TO THE "TAKING OTHER MEDICINES" SECTION BELOW OR ASK YOUR DOCTOR OR PHARMACIST. YOU MUST NOT DRINK ALCOHOL WHEN YOU TAKE ZOLPIDEM. DO NOT TAKE ZOLPIDEM FOR MORE THAN 4 WEEKS. IF YOUR SLEEP PROBLEMS CONTINUE, CONSULT YOUR DOCTOR.



FULL CMI

STILNOX CR®

Active ingredient: zolpidem tartrate


Consumer Medicine Information (CMI)

This leaflet provides important information about using STILNOX CR. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about STILNOX CR.

Where to find information in this leaflet:

1. Why am I taking STILNOX CR?
2. What should I know before I take STILNOX CR?
3. What if I am taking other medicines?
4. How do I take STILNOX CR?
5. What should I know while taking STILNOX CR?
6. Are there any side effects?
7. Product details

1. Why am I taking STILNOX CR?

STILNOX CR contains the active ingredient zolpidem tartrate. STILNOX CR is used to initiate and maintain sleep in those with sleeping difficulties, also called insomnia in patients over 18 years of age. It is not recommended for use for more than 4 weeks at a time.

STILNOX CR has a different chemical structure to other sleeping tablets. STILNOX CR works by binding to special sites in the brain which produce sleep.Your doctor, however, may prescribe STILNOX CR for another purpose.

2. What should I know before I take STILNOX CR?

Warnings

Do not take STILNOX CR if:

  • you are allergic to zolpidem tartrate, or any of the ingredients listed at the end of this leaflet.
Always check the ingredients to make sure you can use this medicine.
  • you have been drinking alcohol or you believe that you may have alcohol in your bloodstream.
  • you have sleep apnoea (a condition where you temporarily stop breathing while you sleep).
  • you have myasthenia gravis (a condition in which the muscles become weak and tire easily).
  • you have severe liver problems
  • you have acute and/or severe lung problems
  • you have previously experienced complex sleep behaviours after taking this medicine including sleepwalking, sleep-driving, and/or engaging in other activities while not fully awake.

Do not give STILNOX CR to a child or adolescent under 18 years of age.

There is no experience with its use in children or adolescents under 18 years of age.

Check with your doctor if you:

  • have any problems with your breathing or if you often snore while you are asleep.
  • have ever been addicted to alcohol or any drug or medicine or if you have ever suffered from a mental illness. If you have, you may be at risk of getting into a regular pattern or habit of taking STILNOX CR.
  • have or have had any other medical conditions especially the following: problems with your heart, liver, kidneys or lungs, epilepsy, depression, mental illness, for example, schizophrenia.
  • plan to have surgery.
  • have allergies to any of the ingredients listed at the end of this leaflet
  • take any medicines for any other condition.

Talk to your doctor or pharmacist if you have ever had a mental disorder or have abused or have been dependent on alcohol or drugs.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant, suspect that you are pregnant, or intend to become pregnant.

Like most medicines of this kind, STILNOX CR is not recommended to be used during pregnancy. Your doctor will discuss the risks and benefits of taking it if you are pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

STILNOX CR can pass into breast milk. Your doctor will discuss the risks and benefits of using it if you are breast-feeding or planning to breast-feed.

Do not take it after the expiry date (EXP) printed on the pack.

Do not take it if the packaging is damaged or shows signs of tampering.

Contains sugars (as lactose).

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with STILNOX CR and affect how it works.

Medicines that may increase the effect of STILNOX CR include:

  • alcohol
  • medicines to treat depression, anxiety and mental illness
  • medicine used to produce calmness or to help you sleep
  • medicines to treat epilepsy
  • pain relievers
  • muscle relaxants
  • antihistamines
  • ciprofloxacin a medicine used to treat infections
  • ketoconazole, a medicine to treat antifungal infections
  • opioids

These medicines may increase drowsiness. This may affect your ability to drive a car or operate dangerous machinery. You may need to use different amounts of your medicine, or take different medicines. Your doctor will advise you.

Medicines that may reduce the effect of STILNOX CR include:

  • St John's Wort (also known as Hypericum), a herbal remedy used to treat depression
  • rifampicin a medicine used to treat infection

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect STILNOX CR.

4. How do I take STILNOX CR?

How much to take

  • The usual adult dose of STILNOX CR is one 12.5 mg tablet taken just before you go to bed.
  • If you are over 65 years of age the dose is one STILNOX CR 6.25 mg tablet taken just before you go to bed.
  • If you have a liver problem, the usual recommended dose is one STILNOX CR 6.25 mg tablet.
Do not take STILNOX CR if you have a severe liver problem.
  • Your doctor may have prescribed a different dose. Follow the instructions provided and use STILNOX CR until your doctor tells you to stop.
  • If you take the wrong dose, STILNOX CR may not work as well.
  • If you take too much your consciousness may be impaired (see 'If you take too much STILNOX CR' below).
  • Ask your doctor if you are unsure of the correct dose for you. They will tell you exactly how much to take.

When to take STILNOX CR

  • Take STILNOX CR immediately before you go to bed or while you are in bed
  • STILNOX CR should only be taken when you are able to get a full night's sleep (7 to 8 hours) before you need to be active again. It should be taken in one dose and not be re-administered during the same night.

How long to take it

  • Usually, STILNOX CR or any other medicines to treat sleeping disorders should only be used for short periods (e.g. 2 to 4 weeks). Continuous long term use is not recommended unless advised by your doctor.

Ask your doctor or pharmacist if you are not sure how long to take the medicine for.

How to take STILNOX CR

  • Swallow the tablet whole with a full glass of water
  • Do not crush or chew the tablet: Each STILNOX CR tablet has been especially designed to release the right dose of medicine while you sleep. If you crush, chew or divide STILNOX CR tablets they will not work properly.
  • If you take STILNOX CR on an empty stomach it may work more quickly

If you forget to take STILNOX CR

If you forget to take the tablet before you go to bed, and you wake up late in the night or very early in the morning, do not take it. You may have trouble waking at your normal time.

If you are not sure what to do, ask your doctor.

If you take too much STILNOX CR

If you think that you have used too much STILNOX CR, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

If you take too much your consciousness may be impaired ranging from drowsiness to light coma.

5. What should I know while taking STILNOX CR?

Things you should do

Tell all the doctors, dentists and pharmacists who are treating you that you are taking STILNOX CR.

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking STILNOX CR.

If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are taking this medicine.

If you become pregnant or suspect that you are pregnant while you are taking this medicine, stop taking it and tell your doctor or pharmacist immediately.

Call your doctor straight away if you:

  • have any of the serious side effects listed in section 6

Remind any doctor, dentist or pharmacist you visit that you are taking STILNOX CR.

Things you must not do

  • Do not take more than the recommended dose unless your doctor tells you to. This can increase the risk of side effects.
  • Do not give this medicine to anyone else, even if they have the same condition as you.
  • Do not use this medicine to treat any other complaints unless your doctor tells you to.
  • Do not drink alcohol before or after taking this medicine. This can increase the risk of side effects or the effects of alcohol could be made worse while taking STILNOX CR.

Things to be careful of:

  • If you are over 65 and unwell or taking other medicines. You may be more sensitive to some of the side effects of STILNOX CR. Some patients may be particularly susceptible to the sedative effects of the medication, which may increase the possibility of a fall.

After taking STILNOX CR

  • Sleep medicines should in most cases, be used only for short periods of time. If your sleep problems continue, consult your doctor.
  • Some medicines can cause dependence, especially when they are used regularly for longer than a few weeks. People who have been dependent on alcohol or other drugs in the past may have a higher chance of becoming addicted to sleep medicines. If you have been addicted to alcohol or drugs in the past, it is important to tell your doctor before starting STILNOX CR.
  • Sometimes when medicines are stopped suddenly, after being used for a long time, withdrawal symptoms may occur. Symptoms of withdrawal may include abdominal and muscle cramps, vomiting and sweating. In some cases your insomnia may appear worse for a short time which may be accompanied with other reactions including mood changes, anxiety and restlessness; speak to your doctor if this occurs. Patients taking part in trials have not had any problems when they stopped taking STILNOX CR. However, let your doctor know if you have any problems when you stop taking STILNOX CR.

Driving or using machines

Because STILNOX CR will make you sleepy, you should not operate dangerous machinery or drive motor vehicles for 8 hours after you take it. You should also be careful the next morning when you wake up.

Make sure you know how you react to STILNOX CR before you drive a car or operate machinery. This is very important if you are taking other drugs that also make you drowsy.

Drinking alcohol

You should not drink alcohol while you are taking STILNOX CR.

Tell your doctor if you drink alcohol.

Alcohol may increase the risk of side effects or the effects of alcohol could be made worse while taking STILNOX CR.

Looking after your medicine

  • Keep your tablets in the blister pack until it is time to take them. If you take the tablets out of the box or the blister pack they may not keep well.
  • Keep the medicine in a cool, dry place where the temperature stays below 30°C.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Tell your doctor as soon as possible if you do not feel well while you are taking STILNOX CR.

Less serious side effects

Less serious side effectsWhat to do
Head and neurology related:
  • drowsiness
  • dizziness
  • headache
  • fatigue
  • anxiety
  • disorientation
  • hallucinations
  • nightmares
  • slowness in thinking and movement
  • poor attention and concentration
  • memory impairment and loss
  • unexpected changes in behaviour. These have included rage reactions, worsened insomnia, confusion, agitation, hallucinations, delirium, and other forms of unwanted behaviour.
Gastrointestinal related:
  • stomach discomfort, indigestion, wind, frequent bowel movements
  • diarrhoea, nausea and vomiting
  • constipation
  • changes in appetite
Musculoskeletal related
  • aching muscle, muscle weakness or tenderness not caused by exercise
  • muscle cramps
  • neck and back pain
Infection related:
  • influenza or flu-like symptoms, such as high temperature, sore throat, runny nose, cough and chills
Eye related:
  • visual disturbances

Although these side effects can occur at the usual recommended doses, the risk of these behaviours occurring may also be increased if you take more than the recommended dose.

Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Allergic reactions:
  • swelling of the face, lips, mouth or throat, which may cause difficulty in swallowing or breathing
  • hives
  • fainting
Sleepwalking and associated behaviours:
  • sleep walking, driving motor vehicles and other unusual, and on some occasions dangerous, behaviours whilst apparently asleep. These have also included preparing and eating food, making phone calls or having sexual intercourse. People experiencing these effects have had no memory of the events.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Alcohol can increase the risk of sleep walking and other related behaviours. These side effects can also occur without the presence of alcohol. Although these side effects can occur at the usual recommended doses, the risk of these behaviours occurring may also be increased if you take more than the recommended dose.

Some sleep medicines may cause a short-term memory loss. When this occurs, a person may not remember what has happened for several hours after taking the medicine. This is usually not a problem since most people fall asleep after taking the medicine.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Do not be alarmed by this list of possible side effects.

You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What STILNOX CR contains

Active ingredient
(main ingredient)
Each STILNOX CR 6.25 mg tablet contains zolpidem tartrate 6.25 mg as the active ingredient.
Each STILNOX CR 12.5 mg tablet contains zolpidem tartrate 12.5 mg as the active ingredient.
Other ingredients
(inactive ingredients)
colloidal anhydrous silica
hypromellose
indigo carmine
iron oxide yellow (STILNOX CR 12.5 mg)
iron oxide red (STILNOX CR 6.25 mg)
macrogol 3350
magnesium stearate
microcrystalline cellulose
potassium hydrogen tartrate
sodium starch glycollate type A
titanium dioxide
Potential allergenslactose monohydrate

STILNOX CR does not contain gluten.

What STILNOX CR looks like

STILNOX CR 6.25 mg tablets are pink, bi-convex two-layer tablets engraved with ZMR on one side (Aust R 120707).

STILNOX CR 6.25 mg tablets are available in boxes of 14 tablets.

STILNOX CR 12.5 mg tablets are blue, bi-convex two-layer tablets engraved with ZMR on one side (Aust R 120713).

STILNOX CR 12.5 mg tablets are available in boxes of 14 tablets.

Who distributes STILNOX CR

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Email: [email protected]
Tel: 1800 818 806

This leaflet was prepared in October 2020.

® Registered Trademark
stilnox-cr-ccdsv17-cmiv16-30oct20

Published by MIMS January 2021

BRAND INFORMATION

Brand name

Stilnox CR

Active ingredient

Zolpidem tartrate

Schedule

S4

 

1 Name of Medicine

Zolpidem tartrate.

2 Qualitative and Quantitative Composition

Each tablet contains zolpidem tartrate 6.25 mg or 12.5 mg.

Excipient with known effect.

Lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Stilnox CR 6.25 mg tablets are pink, bi-convex two-layer tablets engraved with ZMR on one side.
Stilnox CR 12.5 mg tablets are blue, bi-convex two-layer tablets engraved with ZMR on one side.

4 Clinical Particulars

4.1 Therapeutic Indications

Stilnox CR is indicated for the short-term treatment of insomnia in adults (see Section 4.2 Dose and Method of Administration).

4.2 Dose and Method of Administration

Stilnox CR acts rapidly and should therefore be taken immediately before retiring, or in bed. Stilnox CR should be taken in a single intake and not be re-administered during the same night. As with all hypnotics, long-term use of zolpidem is not recommended. Treatment should be as short as possible and should not exceed four weeks.
For oral use only.

Discontinuation of treatment.

See Section 4.8 Adverse Effects (Undesirable Effects).

Withdrawal effects.

See Section 4.4 Special Warnings and Precautions for Use.

Recommended dosage.

Tablets should not be divided, crushed or chewed.

Adults.

The recommended daily dose is 12.5 mg. The lowest effective daily dose of zolpidem should be used and not exceed 12.5 mg.

Elderly or debilitated patients.

Elderly or debilitated patients may be especially sensitive to the effects of zolpidem. The recommended daily dose is 6.25 mg.

Hepatic impairment.

As clearance and metabolism of zolpidem is reduced in hepatic impairment, caution should be exercised in these patients with particular caution being exercised in elderly patients. The recommended daily dose is 6.25 mg and these patients should be closely monitored. Stilnox CR should not be used in patients with severe hepatic impairment (see Section 4.3 Contraindications).

Renal impairment.

No dosage adjustment is necessary in these patients, although they should be closely monitored.

Children.

As the safety and efficacy of Stilnox CR has not yet been established, the use of Stilnox CR in children under 18 years of age is contra-indicated.

4.3 Contraindications

Sleep apnoea.
Known hypersensitivity to zolpidem or other ingredients in the tablet.
Myasthenia gravis.
Severe hepatic insufficiency.
Acute and/or severe pulmonary insufficiency.
Prior or concomitant intake with alcohol.
Stilnox CR should not be prescribed for children under 18 years of age.
Patients who have previously experienced complex sleep behaviours after taking Stilnox CR.

4.4 Special Warnings 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.

Withdrawal, rebound, dependence and tolerance.

Tolerance.

Continuous long-term use of Stilnox CR is not recommended and should not exceed four weeks.
Some loss of efficacy to the hypnotic effects of sedative/ hypnotic agents may develop after repeated use for a few weeks.

Dependence.

Use of zolpidem may lead to the development of abuse and/or 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. Stilnox CR should be used with extreme caution in patients with current or a history of 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, delirium or epileptic seizures. Dependence has been very rarely reported with zolpidem.

Rebound insomnia.

Rebound insomnia, a transient syndrome whereby the symptoms that led to treatment with sedative/ hypnotic agents 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.
There are indications that, in the case of sedative/ hypnotic agents with a short duration of action, withdrawal phenomena can become manifest within the dosage interval, especially when the dosage is high.
When Stilnox CR is used in accordance with the recommendations for dosage, duration of treatment and warnings, the risk of withdrawal symptoms or rebound phenomena occurring is minimal.

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.

Patients with long QT syndrome.

An in vitro cardiac electrophysiological test showed that under experimental conditions, using very high concentration and pluripotent stem cells, zolpidem may reduce the hERG related potassium currents. As a precaution, the benefit/ risk ratio of zolpidem treatment in patients with known congenital long QT syndrome should be carefully considered.

CNS effects.

As with all patients taking CNS depressant medications, patients receiving Stilnox CR should be warned not to operate dangerous machinery or motor vehicles until it is known that they do not become drowsy or dizzy from Stilnox CR therapy. Patients should be advised that their tolerance for other CNS depressants will be diminished and that these medications should either be eliminated or given in reduced dosage in the presence of Stilnox CR. Prior or concomitant intake with alcohol is contraindicated (see Section 4.3 Contraindications).

Respiratory function.

Both animal and human pharmacology studies performed with Stilnox CR have not observed any effect on the respiratory centre. However, as other sedative/ hypnotics have the capacity to depress respiratory drive, caution is advised when Stilnox CR is administered to patients with respiratory insufficiency (see Section 4.3 Contraindications).

Use in hepatic impairment.

As clearance and metabolism of zolpidem is reduced in hepatic impairment, dosage should begin at 6.25 mg with particular caution being exercised in elderly patients. In adults (under 65 years) dosage may be increased to 12.5 mg only where the clinical response is inadequate and the drug is well tolerated. (See Section 4.4 Special Warnings and Precautions for Use, Use in the elderly or debilitated patient; Section 4.2 Dose and Method of Administration). Zolpidem must not be used in patients with severe hepatic impairment as it may contribute to encephalopathy.

Use in renal impairment.

Dosage reduction is not necessary in patients with renal impairment, however, as a general precaution, these patients should be monitored closely (see Section 4.2 Dose and Method of Administration).

Use in the elderly or debilitated patient.

Elderly and debilitated patients may be particularly sensitive to the effects of Stilnox CR, therefore a 6.25 mg dose is recommended. This dose should not be exceeded in these patients (see Section 4.2 Dose and Method of Administration).
Such patients may be particularly susceptible to the sedative effects of the medication and associated giddiness, ataxias and confusion, which may increase the possibility of a fall.

Memory impairment.

Sedative/ hypnotic agents may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 7-8 hours.

Suicidality, depression, psychosis and schizophrenia.

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 zolpidem. Stilnox CR should be administered with caution in patients exhibiting symptoms of depression. Stilnox CR is not recommended as primary therapy in patients with psychotic illness, including depression and psychosis. In such conditions, psychiatric assessment and supervision are necessary as depression may increase in some patients and may contribute to deterioration in severely disturbed schizophrenics with confusion and withdrawal. Pre-existing depression may be unmasked during the use of Stilnox CR. Suicidal tendencies may be present or uncovered and protective measures may be required. Intentional overdosage is more common in this group of patients; therefore, the least amount of drug that is feasible should be prescribed for the patient at any one time.

Other psychiatric and paradoxical reactions.

Other psychiatric and paradoxical reactions such as acute rage, restlessness, insomnia exacerbated, agitation, irritability, aggression, delusions, anger, nightmares, hallucinations, stimulation or excitement, abnormal behaviour, delirium and other adverse behavioural effects, are known to occur when using sedative/ hypnotic agents like Stilnox CR. Should such reactions occur, Stilnox CR should be discontinued. These reactions are more likely to occur in the elderly.

Somnambulism and associated behaviours.

Complex sleep behaviours, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake, may occur following the first or any subsequent use of Stilnox CR. Patients can be seriously injured or injure others during complex sleep behaviours. Such injuries may result in a fatal outcome. Other complex sleep behaviours (e.g. preparing and eating food, making phone calls, or having sex) have also been reported. Patients usually do not remember these events. Postmarketing reports have shown that complex sleep behaviours may occur with Stilnox CR alone at recommended doses, with or without the concomitant use of alcohol or other central nervous system (CNS) depressants (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Discontinue Stilnox CR immediately if a patient experiences a complex sleep behaviour (see Section 4.3 Contraindications). The use of alcohol and other CNS depressants with zolpidem appears to increase the risk of such behaviours, as does the use of Stilnox CR at doses exceeding the maximum recommended dose (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)). These events can occur in sedative-hypnotic naive as well as sedative-hypnotic experienced patients.

Psychomotor impairment.

Zolpidem has CNS-depressant effects. The risk of psychomotor impairment, including impaired driving ability, is increased if zolpidem is taken within less than 7-8 hours before performing activities that require mental alertness, a dose higher than the recommended dose is taken, or zolpidem is co-administered with other CNS depressants, alcohol, or with other drugs that increase the blood levels of zolpidem.

Interactions with alcohol.

Prior or concomitant intake with alcohol is contraindicated (see Section 4.3 Contraindications). Patients should be advised that their tolerance for alcohol and other CNS depressants might be reduced and have an additive effect on psychomotor performance (see Section 4.4 Special Warnings and Precautions for Use, Somnambulism and associated behaviours, above).

Risks from concomitant use with opioids.

Concomitant use of sedative-hypnotic drugs, including zolpidem, with opioids may result in sedation, respiratory depression, coma and death. Because of these risks, reserve concomitant prescribing of opioids and zolpidem for use in patients for whom alternative treatment options are inadequate.
If a decision is made to prescribe zolpidem concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Severe anaphylactic and anaphylactoid reactions.

Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including zolpidem. Some patients have had additional symptoms such as dyspnoea, throat closing or nausea and vomiting, that suggest anaphylaxis. Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with zolpidem should not be rechallenged with the drug.

Epilepsy.

Abrupt withdrawal of CNS depressant drugs in persons with convulsive disorders has been associated with a temporary increase in the frequency and/or severity of seizures.
As with other sedative/ hypnotics, caution is advised when Stilnox CR is used in these patients.

Abuse.

Caution must be exercised in administering Stilnox CR to individuals known to be addiction prone or those whose history suggests they may increase the dosage on their own initiative. It is desirable to limit repeat prescription without adequate medical supervision.

Paediatric use.

See Section 4.2 Dose and Method of Administration.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

CNS depressants.

Co-administration of Stilnox CR with other CNS depressants should be exercised with caution since the central depressant effect may be additive. CNS depressants include alcohol, benzodiazepines, barbiturates, sedative/ hypnotics, anxiolytics, antidepressant agents (including tricyclic antidepressants, MAOIs), antipsychotics (neuroleptics), phenothiazines, skeletal muscle relaxants, antihistamines, neuroleptics, antiepileptic drugs, narcotic analgesics or anaesthetics. Concomitant use of zolpidem with these drugs may increase drowsiness and psychomotor impairment, including impaired driving ability. In the case of narcotic analgesics, enhancement of euphoria may also occur.

Opioids.

The concomitant use of sedative-hypnotic drugs, including zolpidem, and opioids increases the risk of sedation, respiratory depression, coma and death because of additive CNS depressant effect. Limit dosage and duration of concomitant use of zolpidem and opioids (see Section 4.4 Special Warnings and Precautions for Use, Risks from concomitant use with opioids).

Alcohol.

Prior or concomitant intake with alcohol is contraindicated (see Section 4.3 Contraindications). Patients should be advised that their tolerance for alcohol and other CNS depressants might be reduced and have an additive effect on psychomotor performance. The use of alcohol and other CNS depressants with zolpidem appears to increase the risk of somnambulism and associated behaviours (see Section 4.4 Special Warnings and Precautions for Use, Somnambulism and associated behaviours).

Imipramine.

The sedative effects of imipramine 75 mg and zolpidem 20 mg were shown to be additive when the two compounds were given concomitantly in healthy volunteers. No pharmacokinetic interaction was shown between zolpidem and imipramine or its metabolite, desipramine.

Chlorpromazine.

The combination of zolpidem 10 mg and chlorpromazine 50 mg in healthy volunteers produced an addition of effects seen in psychometric tests and decreased alertness and psychomotor performance. No pharmacokinetic interaction was observed.

Haloperidol.

No evidence of pharmacokinetic interaction between zolpidem 20 mg and haloperidol 2 mg was seen when they were given concurrently to healthy volunteers.

Caffeine.

No change in the sleep inducing effect of zolpidem was seen when 300 mg caffeine was given in the evening 45 minutes before administration of zolpidem 20 mg to 8 healthy volunteers.

Warfarin.

Prothrombin times were not prolonged in healthy adults when zolpidem 20 mg was administered for 4 consecutive nights concomitantly with warfarin. Warfarin had been given for at least 10 days previously to produce a 1.5 times prolongation of baseline prothrombin time in the volunteers. Zolpidem does not appear to modify the anticoagulant activity of warfarin.

Digoxin.

The concurrent administration of zolpidem 10 mg once daily and digoxin 0.25 mg in healthy volunteers did not show any alteration of the pharmacokinetic or pharmacodynamic profile of digoxin.

H2-antagonists.

Simultaneous administration of zolpidem 20 mg and cimetidine 200 mg tds and 400 mg at night or ranitidine 150 mg bd did not cause any significant change in psychometric tests from those produced by zolpidem alone. No change in the pharmacokinetics of zolpidem were caused by concomitant administration of either cimetidine or ranitidine.

Hepatic enzyme inhibitors and inducers.

Zolpidem is metabolized via several hepatic cytochrome P450 enzymes, the main enzyme being CYP3A4 with the contribution of CYP1A2. Compounds which inhibit or enhance certain hepatic enzymes (particularly cytochrome P450) may increase or decrease the activity of some hypnotics like zolpidem. The pharmacodynamic effect of zolpidem 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 zolpidem, therefore concurrent use is not recommended.
Ketoconazole has a significant but only quantitatively modest reduction in zolpidem clearance, with an increase in its pharmacodynamic effects. Patients should be advised that use of zolpidem with ketoconazole may enhance the sedative effects of zolpidem. However, when zolpidem is administered with itraconazole (a CYP3A4 inhibitor) its pharmacokinetics and pharmacodynamics were not significantly modified. The clinical relevance of these results is unknown.
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 zolpidem, 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 zolpidem, concurrent use is not recommended.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
This drug has been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have shown evidence of an increased occurrence of foetal damage, the significance of which is uncertain in humans. The use of zolpidem is not recommended during pregnancy.
Cases of reduced fetal movement and fetal heart rate variability have been described after administration of benzodiazepines or other sedative-hypnotic drugs such as zolpidem during pregnancy.
Administration of zolpidem during the late phase of pregnancy or during labor has been associated with effects on the neonate, such as hypothermia, hypotonia, feeding difficulties, and respiratory depression.
If zolpidem 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.

Teratogenic effects.

In reproductive toxicity studies, rats treated with oral zolpidem with estimated exposures (AUC) to zolpidem and its major metabolite of 41 and 15 times, respectively, the anticipated clinical exposure did not exhibit teratogenic effects but post-implantation survival index and postpartum viability of the offspring were significantly reduced. In rats, delayed ossification of foetal skull bones occurred at zolpidem and metabolite exposure levels of 8 and 3 times, respectively, the anticipated clinical exposure.
Rabbits treated with oral zolpidem with estimated exposure to zolpidem of 0.6-2.6 times the anticipated clinical exposure did not exhibit teratogenic effects, but there was increased post-implantation loss.
Although animal studies have not shown any teratogenic effects with zolpidem, the safety of zolpidem in human pregnancy has not been established.

Nonteratogenic effects.

Cases of severe neonatal respiratory depression have been reported when zolpidem was used with other CNS depressants at the end of pregnancy.
Infants born to mothers who took hypnotics chronically during the latter stages of pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period. Appropriate monitoring of the newborn in the postnatal period is recommended.
The use of Stilnox CR in nursing women is not recommended as small quantities of zolpidem are excreted into breast milk.

4.7 Effects on Ability to Drive and Use Machines

This preparation is to aid sleep. Patients should not drive or operate machinery for 8 hours after taking Stilnox CR.
Adverse effects including drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/ double vision, reduced alertness and/or impaired driving may continue the following day. In order to minimise this risk a full night of sleep (7-8 hours) is recommended. After ingesting the medicine, patients should be cautioned against engaging in hazardous occupations requiring complete mental alertness or motor coordination such as operating machinery or driving a motor vehicle, including potential impairment of the performance of such activities that may occur the day following ingestion of Stilnox CR. Furthermore, the co-administration of zolpidem 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 zolpidem.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials data.

There is evidence of a dose relationship for adverse effects associated with Stilnox CR use, particularly for certain CNS events. These occur most frequently in elderly patients.
Associated with discontinuation of treatment. Approximately 4% of 1,701 patients who received zolpidem at all doses (1.25 to 90 mg) in US premarketing clinical trials discontinued treatment because of an adverse clinical event. Events most commonly associated with discontinuation from US trials were daytime drowsiness (0.5%), dizziness (0.4%), headache (0.5%), nausea (0.6%) and vomiting (0.5%).
Approximately 6% of 1,320 patients who received zolpidem at all doses (5 to 50 mg) in similar European trials discontinued treatment because of an adverse event. Events most commonly associated with discontinuation from these trials were daytime drowsiness (1.6%), amnesia (0.6%), dizziness (0.6%), headache (0.6%) and nausea (0.6%).
In clinical trials with Stilnox CR, 3.5% of 201 patients receiving 6.25 mg or 12.5 mg of Stilnox CR discontinued treatment because of an adverse event. Events most commonly associated with discontinuation were somnolence (1.0%) and dizziness (1.0%).
Incidence in controlled clinical trials.

Most commonly observed adverse events in controlled trials.

During short-term treatment (up to 10 nights) with zolpidem at doses up to 10 mg, the most commonly observed adverse events associated with the use of zolpidem and seen at statistically significant differences from placebo treated patients were drowsiness (reported by 2% of zolpidem patients), dizziness (1%) and diarrhoea (1%). During longer-term treatment (28 to 35 nights) with zolpidem at doses up to 10 mg, the most commonly observed adverse events associated with the use of zolpidem and seen at statistically significant differences from placebo treated patients were dizziness (5%) and drugged feelings (3%).
During longer-term treatment (3 weeks) with zolpidem at doses up to 12.5 mg, the most commonly observed adverse events associated with the use of zolpidem were headache (16%), somnolence (10%) and dizziness (10%).

Adverse events observed at an incidence of ≥ 1% in controlled trials.

Tables 1, 2 and 3 enumerate treatment emergent adverse event frequencies that were observed at an incidence equal to 1% or greater among patients with insomnia who received Stilnox in US placebo controlled trials or modified-release Stilnox CR in placebo-controlled trials. Events reported by investigators were classified utilising a modified World Health Organisation (WHO) dictionary of preferred terms in Stilnox studies or MedDRA dictionary in modified release Stilnox CR studies for the purpose of establishing event frequencies.
Table 1 was derived from a pool of 11 placebo-controlled short-term US efficacy trials involving zolpidem in doses ranging from 1.25 to 20 mg. Table 1 is limited to data from doses up to and including 10 mg, the highest dose recommended for use.
Table 2 was derived from a pool of three placebo-controlled long-term efficacy trials involving Stilnox (zolpidem tartrate). These trials involved patients with chronic insomnia who were treated for 28 to 35 nights with zolpidem at doses of 5, 10 or 15 mg. Table 2 is limited to data from doses up to and including 10 mg, the highest dose recommended for use. Table 2 includes only adverse events occurring at an incidence of at least 1% for Stilnox patients.
Table 3 was derived from pooled results of two placebo-controlled efficacy trials involving modified-release zolpidem. These trials involved patients with primary insomnia who were treated for 3 weeks with modified-release zolpidem at doses of 6.25 or 12.5 mg. Table 3 includes only adverse events occurring at an incidence of at least 1% for modified-release zolpidem patients.

Stilnox CR postmarketing data.

See Table 4.
Elevated liver enzymes, rash, pruritus and urticaria have also been reported.
The treatment-emergent adverse events associated with participation in modified-release Stilnox CR studies were not different in nature or frequency to that seen in studies with Stilnox.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Signs and symptoms.

In reports of overdose with immediate-release zolpidem alone or with other CNS depressant agents (including alcohol), impairment of consciousness has ranged from somnolence to coma, and more severe symptomatology, including fatal outcomes have been reported. Fatalities have occurred when overdoses of multi-CNS depressants were taken. No differences were identified with reports of overdose with controlled release zolpidem.

Management.

General symptomatic and supportive measures should be used, along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. Sedative drugs should be withheld, even if excitation occurs.
Zolpidem has been shown in trials to be non-dialysable.
Use of flumazenil may be considered when serious symptoms are observed. However, flumazenil administration may contribute to the appearance of neurological symptoms, such as convulsions, since zolpidem does not exhibit the anticonvulsant effects of benzodiazepines.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Zolpidem belongs to the imidazopyridine group of compounds and is structurally unrelated to other hypnotic agents. Zolpidem selectively binds the omega-1 receptor subtype (also known as the benzodiazepine-1 subtype) which is the alpha unit of the GABA-A receptor complex. Whereas benzodiazepines non-selectively bind all three omega receptor subtypes, zolpidem preferentially binds the omega-1 subtype. The modulation of the chloride anion channel via this receptor leads to the specific sedative effects demonstrated by zolpidem, i.e. the preservation of deep sleep (stage 3 and 4 slow wave sleep).
These effects are reversed by the benzodiazepine antagonist flumazenil.

In animals.

The selective binding of zolpidem to omega-1 receptors may explain the virtual absence at hypnotic doses of myorelaxant and anti-convulsant effects in animals which are normally exhibited by benzodiazepines which are not selective for omega-1 sites.

In humans.

The preservation of deep sleep (stages 3 and 4 slow-wave sleep) may be explained by the selective omega-1 binding by zolpidem. All identified effects of zolpidem are reversed by the benzodiazepine antagonist flumazenil.

Clinical trials.

Stilnox CR was evaluated in two placebo-controlled studies for the treatment of patients with chronic primary insomnia (as defined in the APA Diagnostic and Statistical Manual of Mental Disorders, DSM IV).
Adult outpatients (18-64 years) with primary insomnia (n = 212) were evaluated in a double-blind, randomised, parallel-group, three-week trial comparing Stilnox CR 12.5 mg and placebo. Stilnox CR 12.5 mg was superior to placebo on objective measures (polysomnography recordings) of sleep maintenance (by decreasing wake time after sleep onset (WASO) (mean ± SD) by 30 ± 28 minutes during the first two nights and by 27 ± 27 min after two weeks of treatment), sleep induction (by decreasing latency to persistent sleep (LPS) (mean ± SD) by 23 ± 28 min during the first two nights and by 20 ± 28 min after two weeks of treatment) and sleep duration (by increasing total sleep time (TST) (mean ± SD) by 58 ± 46 min during the first two nights and by 41 ± 52 min after two weeks of treatment), during the first two nights and after two weeks of treatment in adult and elderly patients, respectively. Stilnox CR 12.5 mg was also superior to placebo on the patient-reported global impression regarding the aid to sleep, after the first two nights and after three weeks of treatment.
Elderly outpatients (≥ 65 years) with primary insomnia (N = 205) were evaluated in a double-blind, randomised, parallel-group, three-week trial comparing Stilnox CR 6.25 mg and placebo. Stilnox CR 6.25 mg was superior to placebo on objective measures (polysomnography recordings) of sleep maintenance (by decreasing WASO mean ± SD by 32 ± 26 min during the first two nights and by 18 ± 31 min after two weeks of treatment), sleep induction (by decreasing LPS mean ± SD by 17 ± 21 min during the first two nights and by 15 ± 25 min after two weeks of treatment) and sleep duration (by increasing TST mean ± SD by 49 ± 39 min during the first two nights and by 28 ± 44 min after two weeks of treatment). Stilnox CR 6.25 mg was also superior to placebo on the patient's reported global impression regarding the aid to sleep, after the first two nights and after three weeks of treatment. The hypnotic efficacy and safety of Stilnox CR has not been assessed in children under 18 years of age and pregnant women.

Next-day residual effects.

The potential next-day residual effects associated with Stilnox CR were evaluated in 5 clinical studies; 3 controlled studies in adults (18-64 years) and 2 controlled studies in the elderly (≥ 65 years). In these studies using neurocognitive tests assessing vigilance, memory or motor function, no significant decrease in performance was observed with Stilnox CR 8 hours after administration. In addition, no evidence of next-day residual effects were detected with zolpidem 12.5 mg and 6.25 mg using self ratings of sedation.

Rebound effects.

In the two placebo-controlled studies in patients with primary insomnia, a rebound effect was only observed on the first night after abrupt discontinuation of Stilnox CR. On the second night, there was no worsening compared to baseline in the Stilnox CR group.

Effects on sleep stages.

In studies that measured the percentage of sleep time spent in each sleep stage, Stilnox CR has generally been shown to preserve sleep stages.

5.2 Pharmacokinetic Properties

Absorption.

The pharmacokinetic profile of Stilnox CR is characterised by rapid and almost complete absorption from the GI tract. Stilnox CR exhibits biphasic absorption characteristics, which result in rapid initial absorption and provide extended plasma concentrations beyond 3 hours after administration. Thereafter, the zolpidem plasma concentration rapidly drops with a terminal half-life of 2.8 hours.
The absolute bioavailability is around 70% and the peak plasma concentration is reached at between 1.5 and 2.5 hours. The interindividual variability (CV) is around 40-60% for AUC and 30-40% for Cmax. The pharmacokinetics of zolpidem is linear within the therapeutic dosage. Administration after food decreases Cmax and AUC by 30 and 23% and delays the time to maximal plasma concentrations by 2 hours.

Distribution.

The in vitro plasma protein binding is around 92%. The distribution volume in adults is 0.54 L/kg following intravenous administration.

Metabolism.

The main cytochrome P450 enzyme involved in the hepatic biotransformation of zolpidem is CYP3A4. Other P450 isoenzymes such as CYP1A2, CYP2C9, CYP2C19 and CYP2D6 contribute minimally to the metabolism of zolpidem (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Zolpidem itself is not a significant inhibitor or inducer of human CYP isoforms.

Excretion.

All metabolites are pharmacologically inactive and are eliminated in the urine (56%) and in the faeces (37%). Furthermore, they do not interfere with zolpidem plasma binding. Clearance is around 212 mL/min. Reduced clearance of 100 mL/min has been noticed in elderly patients.

Special populations.

In adult and elderly patients who were treated for 3 weeks with Stilnox CR at 12.5 mg and 6.25 mg, respectively, zolpidem plasma concentrations after wake up (approximately 9 hours post-dose) were measured on day 1 and day 15. Zolpidem concentrations did not change upon repeated dosing, indicating no evidence of accumulation with Stilnox CR.
In the elderly, after a single dose of Stilnox CR 6.25 mg, maximal plasma concentration increased by 18 to 56% and the AUC by 7 to 82% as compared to young subjects after Stilnox CR 6.25 mg, without any change in the terminal half-life (around 3 hours). Therefore, the dose of modified release Stilnox CR should be reduced by half in the elderly (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use).
In patients with hepatic impairment, the clearance of zolpidem is decreased and the elimination half-life is extended (around 10 hours). In the case of liver cirrhosis a 5-fold increase of AUC and a 3-fold increase of half-life have been observed.
In patients with renal insufficiency, whether dialysed or not, there is a moderate increase (around 30%) of the volume of distribution compared to healthy subjects. Other pharmacokinetic parameters, such as clearance, AUC and elimination half-life are not affected. Therefore, no dose adjustment is necessary in patients with renal impairment.

5.3 Preclinical Safety Data

Genotoxicity.

Zolpidem was not genotoxic in assays for gene mutations (Salmonella typhimurium histidine reversion assay, L5178Y mouse lymphoma assay), for chromosomal aberrations (human lymphocytes, mouse micronucleus assay) and for DNA repair assays (in human fibroblasts and rat hepatocytes). The mutagenic activity of zolpidem and/or its metabolites was equivocal in a Chinese hamster V79/HRPT gene mutation assay in the presence of metabolic activation.

Carcinogenicity.

Two year dietary carcinogenicity studies on zolpidem were conducted in rats and mice. No evidence of carcinogenic potential was observed in mice at plasma concentrations (AUC) of zolpidem and its major human metabolite of about 2 and 7-12 times, respectively, the anticipated clinical exposure at the maximum recommended clinical dose. An increased incidence of renal liposarcomas was observed in male rats (6% cf. 0 in controls) at plasma concentrations (AUC) of zolpidem and its major metabolite of at least 22 and 9 times, respectively, the anticipated human exposure.

6 Pharmaceutical Particulars

6.1 List of Excipients

Lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycollate type A, magnesium stearate, colloidal anhydrous silica, iron oxide yellow (Stilnox CR 12.5 mg), iron oxide red (Stilnox CR 6.25 mg tablets), titanium dioxide, macrogol 3350, potassium hydrogen tartrate and indigo carmine.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C.

6.5 Nature and Contents of Container

Stilnox CR 6.25 mg and 12.5 mg tablets are available in blister packs of 2 (sample), 7#, 10#, and 14, 20#, 21#, 28# and 100# tablets.
#Not Marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Zolpidem tartrate is a white to off white colourless, crystalline powder, sparingly soluble in water.

Chemical structure.


Its chemical name is 2-(4-methylphenyl)- N,N,6-trimethylimidazo [1,2,a] pyridine-3-acetamide hemitartrate.
Its molecular formula is (C19H21N3O)2, C4H6O6. MW is 764.9.

CAS number.

99294-93-6 (zolpidem tartrate) and 82626-48-0 (zolpidem).

7 Medicine Schedule (Poisons Standard)

Prescription Medicine (Schedule 4).

Summary Table of Changes