Consumer medicine information

Paxam

Clonazepam

BRAND INFORMATION

Brand name

Paxam

Active ingredient

Clonazepam

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Paxam.

SUMMARY CMI

PAXAM®

Consumer Medicine Information (CMI) summary

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

1. Why am I taking PAXAM?

PAXAM contains the active ingredient clonazepam. PAXAM is used to treat epilepsy in adults and children aged 2 years and over.

For more information, see Section 1. Why am I taking PAXAM? in the full CMI.

2. What should I know before I take PAXAM?

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

Do not take if you have severe and chronic lung disease or severe liver disease.

Do not take if you have an addiction to drugs or alcohol. This medicine may be addictive.

Talk to your doctor if you have any other medical conditions, 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 PAXAM? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with PAXAM 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 PAXAM?

  • Take PAXAM exactly as your doctor has prescribed.
  • PAXAM tablets can be broken in half or quarters if your doctor has prescribed half or quarter of a tablet.

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

5. What should I know while taking PAXAM?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are taking PAXAM.
  • Do not take any other medicines whether they require a prescription or not without first telling your doctor.
  • Tell your doctor if you become pregnant while taking PAXAM.
  • Tell your doctor if, for any reason, you have not taken your medicine exactly as prescribed.
Things you should not do
  • Do not stop taking or lower the dose of this medicine suddenly.
  • Do not take PAXAM for a longer time than your doctor has prescribed.
  • Do not take PAXAM while taking sedatives, tranquillisers or hypnotics.
Driving or using machines
  • Do not drive or use any machines or tools until you know how PAXAM affects you.
Drinking alcohol
  • You should not drink alcohol while taking PAXAM. Alcohol may increase the effects of PAXAM and lead to serious side effects.
Looking after your medicine
  • Keep your tablets in the bottle until it is time to take them.
  • Keep your tablets in a cool dry place where the temperature stays below 25°C.

For more information, see Section 5. What should I know while taking PAXAM? in the full CMI.

6. Are there any side effects?

Mild side effects: drowsiness, tiredness, dizziness, unsteadiness, muscle weakness, tremor, loss of memory, inattentiveness, confusion, lack of concentration, headache, hangover feeling in the morning, slurred speech, unpleasant dreams, palpitations, vomiting. Serious side effects: aggression, agitation, depression, restlessness, nervousness, hostility, anxiety, excitation, hallucinations or delusions, severe sleep disturbances, severe withdrawal symptoms following discontinuation of PAXAM. Very serious side effects: difficulty breathing, thoughts of self-harm. This is not a complete list of all possible side effects.

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.



FULL CMI

PAXAM®

Active ingredient(s): clonazepam

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I taking PAXAM?

PAXAM contains the active ingredient clonazepam. PAXAM belongs to a group of medicines called benzodiazepines. They are thought to work by their action on brain chemicals.

PAXAM is used for the treatment of epilepsy in adults and children aged 2 years and over.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

The use of benzodiazepines may lead to dependence on the medicine. If you have any concerns, you should discuss this with your doctor.

2. What should I know before I take PAXAM?

Warnings

Do not take PAXAM if:

  • you are allergic to clonazepam or have had an allergic reaction to PAXAM, any other benzodiazepine medicine or any ingredients listed at the end of this leaflet.
    Some symptoms of an allergic reaction may include:
    - shortness of breath
    - wheezing or difficulty in breathing
    - swelling of the face, lips, tongue or other parts of the body
    - rash, itching or hives on the skin.
  • you have severe and chronic lung disease.
  • you have severe liver disease.
  • you have an addiction to drugs or alcohol.
  • you have galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption.
    People with these rare hereditary problems should not take this medicine as it contains lactose.
  • the package is torn or shows signs of tampering.
  • the expiry date (EXP) printed on the pack has passed. If you take this medicine after the expiry date has passed it may not work as well.
  • Always check the ingredients to make sure you can take this medicine.
  • If you are not sure whether you should start taking this medicine, talk to your doctor.

This medicine may be addictive. The risks are greater for patients on higher doses or on long term treatment, or patients who have a history of alcohol or drug abuse.

Check with your doctor if you:

  • are pregnant or plan to become pregnant.
  • are breastfeeding or plan to breastfeed.
  • have any other medical conditions including:
    - liver, kidney or lung disease
    - high or low blood pressure
    - myasthenia gravis (severe muscle weakness)
    - sleep apnoea (a condition where you have temporary stops in breathing during sleep)
    PAXAM is not recommended for use in patients with sleep apnoea due to possible additive effects on respiratory depression.
    - glaucoma (a condition where you have high pressure in the eye)
    - depression, psychosis or schizophrenia and /or you have had depression or suicidal thoughts in the past
    - spinal or cerebellar ataxia, condition of clumsiness or in coordination of the muscles
    - porphyria (a rare blood pigment disorder)
    - a history of addiction, alcohol or drug abuse/dependence.
  • drink alcohol.
  • are lactose intolerant.
  • are allergic to any other medicines, foods, dyes or preservatives.
  • take any medicines for any other condition.

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 or intend to become pregnant.

It is not known whether PAXAM is safe to use during pregnancy. There have been reports of unwanted effects occurring in the newborn with the use of medicines of this class when used during pregnancy.

Mothers taking more than one medicine to treat their epilepsy may be a greater risk of having a baby with malformation than mothers taking only one medicine for epilepsy. Your baby may develop withdrawal symptoms such as a low body temperature, floppy limbs, feeding problems and breathing difficulties. If there is a need to take PAXAM when you are pregnant, your doctor will discuss the risks and benefits to you and the unborn baby.

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

PAXAM may pass into the breast milk and cause drowsiness and/or feeding difficulties in the baby. PAXAM is not recommended for use while breastfeeding.

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 PAXAM and affect how it works.

  • sleeping tablets, sedatives or tranquillisers
  • some medicines for depression such as tricyclic antidepressants, monoamine oxidase inhibitors
  • other medicines to control epilepsy such as phenytoin, carbamazepine, sodium valproate
  • medicines for mental illness
  • medicines for allergies or colds such as antihistamines
  • pain relievers
  • muscle relaxants
  • anaesthetics
  • cimetidine - a medicine used to treat reflux and stomach ulcers
  • disulfiram - a medicine used to deter alcohol consumption in alcohol abuse
  • lithium - a medicine used to treat mood swings and some types of depression
  • Fluconazole - an antifungal medication used for a number of fungal infections

These medicines may be affected by PAXAM or may affect how well PAXAM works. Your doctor or pharmacist can tell you what to do if you are taking any of these medicines. They also have a more complete list of medicines to be careful with or avoid while taking PAXAM.

Taking central nervous system depressants/ sedatives

You should not take central nervous system depressants, such as sedatives, tranquillisers, and hypnotics, while taking PAXAM. These medicines have the potential to increase the effects of PAXAM resulting in severe effects including coma and death.

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

4. How do I take PAXAM?

How much to take

  • Take PAXAM exactly as your doctor has prescribed.
  • Your doctor will tell you how much PAXAM to take each day and when to take them.
  • The dose varies from person to person depending on age, the condition being treated and whether or not you are taking any other medicines.
  • PAXAM is usually started using a low dose. Your doctor may gradually increase this dose to the lowest amount needed to control your condition depending on how well you respond to and tolerate the medicine.
  • The usual adult maintenance dose is between 4 mg and 8 mg a day.
  • Children, the elderly and people with liver or kidney problems may need smaller doses.
  • Follow the instructions provided and continue taking PAXAM until your doctor tells you to stop.
    This medicine helps to control your condition but does not cure it. It is important to keep taking your medicine even if you feel well.

When to take PAXAM

  • PAXAM is usually taken twice a day (in the morning and evening). However, depending on your dose, your doctor may recommend you take it three or four times a day.
  • PAXAM may be taken with or without food.
  • Take your medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How to take PAXAM

  • Swallow the PAXAM tablets with a glass of water.
  • PAXAM tablets can be broken in half or quarters if your doctor has prescribed half or quarter of a tablet.

If you forget to take PAXAM

PAXAM should be taken regularly at the same time each day. If you miss your dose at the usual time, take it as soon as you remember and then go back to taking it as you would normally.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

If you are not sure whether to skip the dose, talk to your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much PAXAM

If you think that you or anyone else have taken too much PAXAM, urgent medical attention may be needed.

You should immediately:

  • phone the Poisons Information Centre
    (telephone 13 11 26) for advice, 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.

If you have taken too much PAXAM, you may feel drowsy, tired, confused, dizzy, have difficulty breathing, feel weak or become unconscious.

Keep telephone numbers for these places handy.

If you are not sure what to do, contact your doctor or pharmacist.

5. What should I know while taking PAXAM?

Things you should do

  • Tell all doctors, dentists and pharmacists who are treating you that you are taking PAXAM.
  • Do not take any other medicines whether they require a prescription or not without first telling your doctor.
  • If you are going to have surgery, including dental surgery, tell the surgeon, anaesthetist or dentist that you are taking this medicine.
    It may affect other medicines used during surgery.
  • Tell your doctor if you become pregnant while taking PAXAM.
  • If you continue to have seizures (fits) your doctor may need to adjust or review your treatment.
  • Tell your doctor if, for any reason, you have not taken your medicine exactly as prescribed.
    Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.
  • Tell your doctor if you feel PAXAM is not helping your condition.
  • Be sure to keep all of your appointments with your doctor so that your progress can be checked.
    Your doctor may want to do some blood and other tests from time to time to check on your progress and detect any unwanted side effects.

All mentions of suicide or violence must be taken seriously. Tell your doctor or a mental health professional immediately if you have any suicidal thoughts or other mental/mood changes such as restlessness, aggression, rage, hallucinations or any adverse behavioural effects or unusual behaviour.

Things you should not do

  • Do not stop taking PAXAM or lower the dose without first checking with your doctor.
    Stopping this medicine suddenly may cause some unwanted effects. Your doctor will explain how you should slowly reduce your dose of PAXAM before you can stop taking it completely.
  • Do not take PAXAM for a longer time than your doctor has prescribed.
  • Do not let yourself run out of medicine over the weekend or on holidays.
  • Do not give PAXAM to anyone else even if they have the same condition as you.
  • Do not take PAXAM to treat other complaints unless your doctor says to.

Things to be careful of

  • Be careful if you are elderly, unwell, or taking other medicines.
    Some people may experience side effects such as drowsiness, confusion, dizziness and unsteadiness which may increase the risk of a fall.
  • If PAXAM is being given to a young child, you should be especially careful that they are breathing freely.
    PAXAM may increase the amount of saliva and fluid in the airways.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how PAXAM affects you.

PAXAM may cause drowsiness or dizziness in some people and therefore may affect alertness.

Make sure you know how you react to PAXAM before you drive a car or operate machinery or do anything else that could be dangerous if you are drowsy, dizzy or not alert.

Children should not ride a bike, climb trees or do anything else that could be dangerous if they are feeling drowsy or sleepy.

Drinking alcohol

Tell your doctor if you drink alcohol.

Do not drink alcohol while taking PAXAM.

Combining PAXAM and alcohol can make you more sleepy or dizzy. Alcohol can also affect how well PAXAM works and may even cause more seizures (fits).

Alcohol may increase the effects of PAXAM and lead to serious side effects, resulting in coma or death.

Looking after your medicine

  • Keep your tablets in the bottle until it is time to take them.
    If you take the tablets out of the bottle they will not keep well.
  • Keep your tablets in a cool dry place where the temperature stays below 25°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.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

When to discard your medicine

If your doctor tells you to stop taking PAXAM, or the medicine has passed its expiry date, ask your pharmacist what to do with any tablets that are left over.

Getting rid of any unwanted medicine

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

Do not take 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.

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking PAXAM.

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

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Less serious side effects

Less serious side effectsWhat to do
  • drowsiness, tiredness
  • dizziness, light-headedness, unsteadiness
  • muscle weakness
  • tremor
  • loss of memory, inattentiveness, confusion, lack of concentration, slowed reactions
  • headache, hangover feeling in the morning
  • slurred speech
  • unpleasant dreams
  • palpitations
  • vomiting
  • increased saliva
  • chest congestion
Speak to your doctor if you have any of these less serious side effects and they worry you.
This list includes the more common side effects of your medicine. Some side effects may disappear with continued treatment.

Serious side effects

Serious side effectsWhat to do
  • hallucinations or delusions
  • severe sleep disturbances, nightmares, vivid dreams
  • behaviour changes such as aggression, agitation, irritability, depression, restlessness, nervousness, hostility, anxiety, excitation, sudden feelings of rage
  • bleeding or bruising more easily than normal
  • signs of frequent infections such as fever, severe chills, sore throat, mouth ulcers
  • severe withdrawal symptoms following discontinuation of PAXAM (including psychological disturbances such as delusional beliefs, feeling outside oneself, confusion, delirium, psychosis)
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.
This list includes serious side effects which may require medical attention.
Some of these side effects are rare.

Very serious side effects

Very serious side effectsWhat to do
  • swelling of the face, lips, mouth, throat or neck, which may cause difficulty swallowing or breathing
  • fainting
  • more fits than usual
  • difficulty breathing, shortness of breath
  • chest pain
  • thoughts of self-harm
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these very serious side effects.
You may need urgent medical attention or hospitalisation.

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.

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 PAXAM contains

Active ingredient
(main ingredient)		Clonazepam
Other ingredients
(inactive ingredients)
  • lactose monohydrate
  • maize starch
  • microcrystalline cellulose
  • magnesium stearate
  • sunset yellow FCF aluminium lake [PAXAM 0.5 tablet only]
Potential allergensSugars as lactose and sulfites

Do not take this medicine if you are allergic to any of these ingredients.

What PAXAM looks like

PAXAM 0.5 mg: 8 mm, flat bevel edged, peach tablet, debossed "CN" over "0.5" on one side, and cross scored on the other (AUST R 54846).

PAXAM 2 mg: 8 mm, flat bevel edged, white tablet, debossed marked "CN" over "2" on one side, and cross scored on the other (AUST R 54847).

Each bottle contains 100 tablets.

Who distributes PAXAM

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in April 2024.

PAXAM® is a Viatris company trade mark

PAXAM_cmi\Apr24/00

Published by MIMS June 2024

BRAND INFORMATION

Brand name

Paxam

Active ingredient

Clonazepam

Schedule

S4

 

1 Name of Medicine

Clonazepam.

2 Qualitative and Quantitative Composition

Each tablet contains 0.5 mg or 2 mg of clonazepam as the active ingredient.

Excipients of known effect.

Sugars as lactose and trace quantities of sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Paxam 0.5.

8 mm, flat bevel edged, peach tablet, debossed ''CN'' over ''0.5'' on one side and cross scored on the other.

Paxam 2.

8 mm, flat bevel edged, white tablet, debossed ''CN'' over ''2'' on one side and cross scored on the other.

4 Clinical Particulars

4.1 Therapeutic Indications

Most types of epilepsy in children, especially absences (petit mal), myoclonic seizures and tonic-clonic fits, whether due to primary generalised epilepsy, or to secondary generalisation of partial epilepsy.
In adults, all varieties of generalised epilepsy (including myoclonic, akinetic, tonic and tonic-clonic seizures), and in partial epilepsy (including psychomotor seizures).

4.2 Dose and Method of Administration

Dosage of clonazepam is essentially individualised and depends in the first instance on the age of the patient. It will be determined in each patient according to clinical response and tolerance. In order to minimise initial adverse effects, it is essential to commence with low doses and increase the daily dose progressively until a maintenance dose suited to the individual patient has been reached. Some degree of tolerance may be observed to both the adverse and therapeutic effects. If epilepsy is not adequately controlled at the maximum recommended dosage level, alternative or combination therapy should be considered (see Section 4.4 Special Warnings and Precautions for Use).
Before adding clonazepam to an existing anticonvulsant regimen, it should be considered that the use of multiple anticonvulsants may result in an increase of undesirable effects.
As with all antiepileptic agents, treatment with clonazepam must not be stopped abruptly, but must be reduced in a stepwise fashion (see Section 4.4 Special Warnings and Precautions for Use).

Dosage for initiation of therapy.

Children.

2 to 5 years: 0.5 mg/day (half a 0.5 mg tablet morning and evening); 6 to 12 years: 0.75 mg/day (half a 0.5 mg tablet in the morning, one 0.5 mg tablet in the evening).

Adults.

1 mg/day (one 0.5 mg tablet morning and evening). See Table 1.
The daily quota should, if possible, be divided into three or four doses spread over the day.
The maintenance dose should be attained after 2 to 4 weeks of treatment. To obtain optimum adjustment of the dose in children, the 0.5 mg tablets should be used.

Use in the elderly.

Elderly patients are usually more sensitive to the effects of benzodiazepines. Particular care should be taken during up-titration in elderly patients. The lowest possible dose should be used in the elderly. The maintenance dose will usually be in the lower range of adult dosage (see Section 4.4 Special Warnings and Precautions for Use).

Impaired hepatic function.

Patients with severe hepatic impairment should not be treated with clonazepam (see Section 4.3 Contraindications). Patients with mild to moderate hepatic impairment should be given the lowest dose possible.

Impaired renal function.

The safety and efficacy of clonazepam in patients with renal impairment has not been studied. Based on pharmacokinetic considerations no dose adjustment is required in these patients, however the pharmacodynamics of the probable accumulated clonazepam metabolites may necessitate dosage review in these patients (see Section 5.2 Pharmacokinetic Properties, Pharmacokinetics in special populations).

4.3 Contraindications

Clonazepam is contraindicated in patients with:
known hypersensitivity to benzodiazepines;
known hypersensitivity to any of the excipients in Paxam;
chronic obstructive airways disease with incipient respiratory failure;
dependence on drugs of abuse and CNS depressants including alcohol;
severe hepatic impairment as benzodiazepines may precipitate hepatic encephalopathy.

4.4 Special Warnings and Precautions for Use

Some loss of effect may occur during the course of clonazepam treatment.

Lactose intolerance.

Since Paxam contains lactose, patients with rare hereditary problems of galactose intolerance (the Lapp lactase deficiency or glucose-galactose malabsorption) should not take this medicine.

Porphyria.

Clonazepam should be used with care in patients with porphyria because it may have a porphyrogenic effect.

Concomitant use of alcohol and CNS depressants.

The concomitant use of clonazepam with alcohol and/or CNS depressants has the potential to increase the clinical effects of clonazepam; possibly including severe sedation that could result in coma or death, clinically relevant respiratory and/or cardiovascular depression (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.9 Overdose).
Since alcohol can provoke epileptic seizures irrespective of therapy and may potentiate the CNS depressant effects of clonazepam, it is imperative that patients should abstain from drinking alcohol while under treatment with clonazepam. Patients should be advised that their tolerance for alcohol and other CNS depressants will be diminished and that these medications should either be eliminated or given in reduced dosage in the presence of Paxam.
Paxam should be used with particular care in patients with ataxia; in the event of acute intoxication with alcohol or drugs, other anti-epileptic medicines, hypnotics, analgesics, neuroleptic agents, antidepressants or lithium; or if the patient suffers from sleep apnoea.
As up to 70% of clonazepam metabolites are excreted via the kidneys, the pharmacodynamics of clonazepam and its metabolites might be altered.

Hypotension.

Although hypotension has occurred rarely, Paxam should be administered with caution to patients in whom a drop in blood pressure might lead to cardiac or cerebral complications. This is particularly important in elderly patients.

Amnesia.

Transient amnesia or memory impairment has been reported in association with the use of benzodiazepines. The risk increases with higher doses.

Sleep apnoea.

Benzodiazepines are not recommended for use in patients with sleep apnoea due to possible additive effects on respiratory depression. Sleep apnoea appears to be more common in patients with epilepsy and the relationship between sleep apnoea, seizure occurrence and post-ictal hypoxia needs to be considered in light of benzodiazepine-induced sedation and respiratory depression. Therefore, clonazepam should only be used in epileptic patients with sleep apnoea when the expected benefit exceeds the potential risk.

Myasthenia gravis.

As with any substance with CNS depressant and/or muscle relaxant properties, clonazepam could increase the muscle weakness in myasthenia gravis and should be used with caution in this condition.

Acute narrow-angle glaucoma.

Caution should be used in the treatment of patients with acute narrow angle glaucoma (because of atropine-like side effects).

Psychiatric and paradoxical reactions.

Paradoxical reactions such as restlessness, agitation, irritability, aggressiveness, nervousness, hostility, anxiety, delusion, sleep disturbances, nightmares, hallucinations, psychoses, vivid dreams, acute rage, stimulation or excitement, inappropriate behaviour and other adverse behavioural effects may occur. Should such reactions occur Paxam should be discontinued.

Impaired respiratory function.

Caution in the use of Paxam is recommended in patients with respiratory depression. In patients with chronic obstructive pulmonary disease (COPD), benzodiazepines can cause increased arterial carbon dioxide tension and decreased oxygen tension. The dosage of Paxam must be carefully adjusted to individual requirements in patients with pre-existing disease of the respiratory system.

Depression, psychosis and schizophrenia.

Paxam is not recommended as primary therapy in patients with depression and/or psychosis. In such conditions, psychiatric assessment and supervision are necessary if benzodiazepines are indicated. Benzodiazepines may increase depression in some patients, and may contribute to deterioration in severely disturbed schizophrenics with confusion and withdrawal. Suicidal tendencies may be present or uncovered and protective measures may be required. Patients with a history of depression and/or suicide attempts should be kept under close supervision.

Epilepsy.

The dosage of Paxam must be carefully adjusted to individual requirements in patients undergoing treatment with other centrally acting medications or anticonvulsant (antiepileptic) agents (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
When clonazepam is administered to persons with convulsive disorders, an increase in the frequency and/or severity of grand mal seizures may occur, necessitating increased anticonvulsant medication. Abrupt withdrawal of benzodiazepines in persons with convulsive disorders may be associated with a temporary increase in the frequency and/or severity of seizures. When in the judgement of the clinician, the need for dosage reduction or discontinuation arises, this should be done gradually.

Abuse.

Caution must be exercised in administering Paxam 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.

Dependence.

The use of benzodiazepines may lead to development of physical and psychological dependence, as defined by the presence of a withdrawal syndrome on discontinuation of the medicine. The risk of dependence increases with dose and duration of treatment. It is also greater in patients with a medical history of alcohol and/or drug abuse. Abuse has been reported in poly-drug users. Tolerance, as defined by a need to increase the dose in order to achieve the same therapeutic effect, seldom occurs in patients receiving recommended doses under medical supervision. Tolerance to sedation may occur with benzodiazepines, especially in those with drug seeking behaviour.
Withdrawal symptoms similar in character to those noted with barbiturates and alcohol have occurred following abrupt discontinuation of benzodiazepines. These symptoms range from insomnia, anxiety, agitation, sleep disturbances, headaches, diarrhoea, irritability, dysphoria, palpitations, panic attacks, vertigo, myoclonus, akinesia, hypersensitivity to light, sound and touch, abnormal body sensations (e.g. feeling of motion, metallic taste), depersonalisation, derealisation, delusional beliefs, hyperreflexia and loss of short-term memory, to a major syndrome which may include convulsions, tremor, abdominal and muscle cramps, confusional state, delirium, hallucinations, hyperthermia, psychosis, vomiting and sweating. Such manifestations of withdrawal, especially the more serious ones, are more common in patients who have received excessive doses over a prolonged period. However, withdrawal symptoms have been reported following abrupt discontinuation of benzodiazepines taken continuously at therapeutic levels. Accordingly, Paxam should be terminated by tapering the dose to minimise the occurrence of withdrawal symptoms. Patients should be advised to consult with their physician before either increasing the dose or abruptly discontinuing the medication.
Rebound phenomena have been described in the context of benzodiazepine use. Rebound insomnia and anxiety mean an increase in the severity of these symptoms beyond pre-treatment levels following cessation of benzodiazepines. Rebound phenomena, in general, possibly reflect re-emergence of pre-existing symptoms combined with withdrawal symptoms described earlier. Some patients prescribed benzodiazepines with very short half-lives (in the order of 2 - 4 hours) may experience relatively mild rebound symptoms in between their regular doses. Withdrawal/rebound symptoms may follow high doses for relatively short periods.

Use in hepatic impairment.

Benzodiazepines may have a contributory role in precipitating episodes of hepatic encephalopathy in severe hepatic impairment (see Section 4.3 Contraindications). Special caution should be exercised when administering clonazepam to patients with mild to moderate hepatic impairment. In patients in whom benzodiazepine therapy for periods longer than 4 weeks is deemed necessary, periodic liver function tests are recommended.
Following the prolonged use of clonazepam at therapeutic doses, withdrawal from the medication should be gradual. An individualised withdrawal timetable needs to be planned for each patient in whom dependence is known or suspected. Periods from 4 weeks to 4 months have been suggested. As with other benzodiazepines, when treatment is suddenly withdrawn, a temporary increase in sleep disturbance can occur after the use of clonazepam (see Dependence below).
Only a small minority of patients with the common seizure types achieves a lasting remission with clonazepam. Tolerance to the anticonvulsant effect of clonazepam may occur after 4 weeks to 6 months of continuous treatment of patients, leading to increased seizure frequency. Increasing the dose in this situation is rarely worthwhile. If seizures are no longer being adequately controlled, the medicine should be discontinued, and alternative treatment implemented.

Use in renal impairment and blood dyscrasias.

Patients with impaired renal function should use benzodiazepine medication with caution and dosage reduction may be advisable. In rare instances, patients on benzodiazepines have developed blood dyscrasias, and some have had elevations of liver enzymes. In patients in whom benzodiazepine therapy for periods longer than 4 weeks is deemed necessary, periodic blood counts are recommended.

Use in the elderly.

There have been reports of falls and fractures in benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcoholic beverages) and in the elderly.
Elderly or debilitated patients may be particularly susceptible to the pharmacologic effects of benzodiazepines such as giddiness, ataxia and confusion, which may increase the risk of a fall.
Elderly patients, patients with pre-existing disease of the respiratory system (e.g. chronic obstructive lung disease), liver or kidney disease, or those who are receiving treatment with other centrally acting medications or anticonvulsant agents, require very careful dosage adjustment.

Paediatric use.

Salivary and bronchial hypersecretion can occur in infants and small children, and supervision is required to ensure that airways remain free, especially on commencing therapy or in the event of respiratory infection.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Clonazepam can be administered concurrently with one or more other anti-epileptic medicines, in which case the dosage of each medicine must be adjusted to achieve the optimum effect. Interactions have been reported between some benzodiazepines and other anticonvulsants, with changes in the serum concentration of the benzodiazepine or anticonvulsant. It is recommended that patients be observed for altered responses when benzodiazepines and anticonvulsants are prescribed together, and that serum level monitoring of the other anticonvulsant is performed more frequently.

Pharmacokinetic interactions.

The anti-epileptic medicines phenytoin, phenobarbital (phenobarbitone), carbamazepine, lamotrigine and valproate may increase the clearance of clonazepam, thereby decreasing the plasma concentrations of the latter during combined treatment.

Phenytoin.

The effect of clonazepam on phenytoin plasma levels is not clear as the latter may increase or decrease according to study reports depending on dosing and patient factors.

Carbamazepine.

Levels may be lowered by clonazepam.
Clonazepam itself does not appear to induce the enzymes responsible for its own metabolism. The enzymes involved in the metabolism of clonazepam have not been clearly identified but include CYP3A4. Inhibitors of CYP3A4 (e.g. fluconazole) may impair the metabolism of clonazepam and lead to exaggerated concentration and effects.
The selective serotonin reuptake inhibitors (SSRIs) sertraline and fluoxetine do not significantly affect the pharmacokinetics of clonazepam when administered concomitantly.

Pharmacodynamic interactions.

Benzodiazepines, including clonazepam, produce additive CNS depressant effects when co-administered with other medications which themselves produce CNS depression, e.g. other anticonvulsant (anti-epileptic) agents, lithium, barbiturates, sedatives, tricyclic antidepressants, non-selective MAO inhibitors, phenothiazines and other antipsychotics, skeletal muscle relaxants, antihistamines, narcotic analgesics and anaesthetics. This is especially true in the presence of alcohol (see Section 4.4 Special Warnings and Precautions for Use).
Clonazepam undergoes oxidative metabolism and, consequently, may interact with disulfiram or cimetidine resulting in increased plasma levels of clonazepam. Patients should be observed closely for evidence of enhanced benzodiazepine response during concomitant treatment with either disulfiram or cimetidine; some patients may require a reduction in benzodiazepine dosage.
The anticholinergic effects of atropine and similar medicines, antihistamines and antidepressants may be potentiated.
Minor EEG changes, usually low voltage fast activity, of no known clinical significance, has been reported with benzodiazepine administration.
Some specific interactions noted with clonazepam are:

Alcohol.

Epileptic patients should not under any circumstances consume alcohol while being treated with clonazepam, since alcohol may alter the effect of the medicine, reduce the efficacy of treatment or produce unexpected side effects (see Section 4.4 Special Warnings and Precautions for Use).

Sodium valproate.

Reports of sodium valproate causing petit mal status epilepticus with clonazepam exist.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Dietary administration of clonazepam to male and female rats was associated with a reduced pregnancy rate and impaired pup survival at doses of 60 mg/m2/day or greater (4-fold the maximal recommended human dose [MRHD]); the no effect dose was 6 mg/m2/day (less than clinical exposure).
(Category B3)
The risk of a mother with epilepsy and taking anticonvulsants giving birth to a baby with an abnormality is about three times that of the normal population. Some of this risk is due to the anticonvulsant medicines taken. Mothers taking more than one anticonvulsant medicine might have a higher risk of having a baby with a malformation than mothers taking one medicine.
Overall the risk of having an abnormal child is far outweighed by the dangers to the mother and foetus of uncontrolled convulsions. It is, therefore, recommended that:
women on anticonvulsant medicines receive pre-pregnancy counselling with regard to the risk of foetal abnormalities;
anticonvulsants should be continued during pregnancy and monotherapy should be used if possible at the lowest effective dose;
folic acid supplement (5 mg daily) should be commenced four weeks prior to and continue for twelve weeks after conception;
specialist prenatal diagnosis including detailed mid-trimester ultrasound should be offered.
Clonazepam is a benzodiazepine. These medicines cross the placenta and appear in the foetus and may, after continuous administration during a large part of pregnancy, give rise to hypotonia, reduced respiratory function and hypothermia in the newborn child. Withdrawal symptoms in newborn infants have occasionally been reported with this class of medicines.
Oral administration of clonazepam during the period of organogenesis has elicited a low, non-dose-related incidence of a similar pattern of malformations in rabbits (cleft palate, open eyelids, fused sternebrae, limb defects) and mice (exencephaly, central nervous system defects) at doses less than MRHD. These effects were not observed in rats at oral doses more than 20-fold MRHD. The clinical significance of these findings is unknown.
Withdrawal symptoms in newborn infants have been reported with benzodiazepines.
Studies in animals have shown evidence of an increased occurrence of foetal damage, the significance of which is considered uncertain in humans.
 Paxam must not be given to breastfeeding women. Clonazepam is excreted in human breast milk, and may cause drowsiness and feeding difficulties in the infant.
If there is a compelling reason for use of clonazepam, breast feeding should be discontinued.

4.7 Effects on Ability to Drive and Use Machines

As with all patients taking CNS depressant medications, patients receiving Paxam should be warned not to operate dangerous machinery or motor vehicles until it is known that they do not become drowsy or dizzy from clonazepam therapy. Abilities may be impaired on the day following use (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.8 Adverse Effects (Undesirable Effects)

Adverse effects to clonazepam occur in about 50% of patients, depending on dose and they are usually referable to its sedative and muscle relaxant effects and are also usually transitory (however, they can continue in up to 10% of patients and may result in withdrawal of the medicine) (see Table 2). Adverse effects can, to a certain extent, be avoided by a low initial dose, which is gradually increased in the absence of side effects.

More common adverse effects.

Drowsiness or somnolence (50%), ataxia (30%), behaviour problems (25%), hypersalivation (10%), fatigue (8%), muscle weakness (5%), vertigo (5%) and light-headedness, tiredness, sleepiness, lassitude and dizziness.
These effects are generally temporary and usually disappear during treatment either spontaneously or by dose reduction.

Less common adverse effects.

Agitation (1.5%), excitability (0.7%), irritability (1.5%), aggressive behaviour (1.4%), disturbances of concentration, depression (1%), confusion (1.9%), bronchial hypersecretion (1.4%), slowed reactions and antero-grade amnesia, restlessness and disorientation have been observed.
With certain forms of epilepsy, an increase in the frequency of seizures during long-term treatment is possible.
Even if taken as directed, clonazepam can slow reactions to such an extent that the ability to drive a vehicle or operate machinery is seriously impaired. The effect is increased if the patient has also taken alcohol (see Section 4.4 Special Warnings and Precautions for Use; Section 4.7 Effects on Ability to Drive and Use Machines).
Other adverse events which have been reported and may be related to clonazepam administration are presented in Table 3.

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

Symptoms.

Overdosage of benzodiazepines is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion and lethargy. In more serious cases, symptoms may include ataxia, dysarthria, nystagmus, hypotonia, hypotension, respiratory depression, coma, and very rarely, death. Coma may be more protracted and cyclical, particularly in elderly patients. Increased frequency of seizures may occur in patients at supratherapeutic plasma concentrations. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease.
Benzodiazepines increase the effects of other central nervous system depressants, including alcohol. When combined with other CNS depressants, the effects of overdosage are likely to be severe and may prove fatal.

Treatment.

Treatment of overdose is symptomatic; institute supportive measures as indicated by the patient's clinical state. If the overdosage is known to be small, observation of the patient and monitoring of their vital signs only may be appropriate. In adults or children who have taken an overdose of benzodiazepines within 1 - 2 hours, consider activated charcoal with airway protection if indicated.
If CNS depression is severe consider the use of flumazenil (Anexate), a benzodiazepine antagonist. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore, patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil may precipitate seizures and is to be used with extreme caution in the presence of medicines that reduce seizure threshold (e.g. tricyclic antidepressants) and epileptic patients who have been treated with benzodiazepines. Refer to the prescribing information for flumazenil (Anexate), for further information on the correct use of this medicine.
Haemoperfusion and haemodialysis are not useful in benzodiazepine intoxication.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Clonazepam is an anticonvulsant, which exhibits several pharmacological properties characteristic of the benzodiazepine class of medicines.
The exact site and mode of action of the anticonvulsant action of clonazepam is unknown.
Benzodiazepines enhance the polysynaptic inhibitory processes at all levels of the central nervous system. Clonazepam is more effective in blocking spread of electrical activity in the lesion itself.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption and bioavailability.

Clonazepam is rapidly and almost completely (82 - 98%) absorbed after oral administration, with peak serum levels being reached between 2 to 3 hours. The absorption half-life is 24 min. With continuous therapy, accumulation occurs, and although values differ in different reports, the therapeutic serum level appears to be between 10 and 80 nanogram/mL. In one study with increase in dosage to 5 mg/day, the average level of clonazepam after 15 days was 54 nanogram/mL. A steady state is usually reached within 2 to 3 weeks.
Plasma concentrations of clonazepam at steady states for once daily dosage regimens are 3-fold higher than those after single oral doses. Following multiple oral doses of 2 mg three times daily, steady-state pre-dose plasma concentrations of clonazepam ranged from 30 - 80 nanogram/mL. The plasma concentration-dose relationship of clonazepam is linear.
The absolute bioavailability is 90%.

Distribution.

Clonazepam enters the cerebral tissues rapidly.
The distribution half-life is approximately between 0.5 - 1 hour. The apparent volume of distribution (3 L/kg) suggests concentration in some tissues.
The plasma protein binding of clonazepam ranges from 82 - 86%.

Metabolism.

Clonazepam is metabolised in the liver. The metabolic pathways include hydroxylation, reduction of the nitro groups to an amine and addition of acetate to the amino grouping. Clonazepam is extensively metabolised by reduction to 7-amino-clonazepam and by N-acetylation to 7-acetamido-clonazepam. Hydroxylation at the C-3 position also occurs. Hepatic cytochrome P-450 3A4 is implicated in the nitroreduction of clonazepam to pharmacologically inactive metabolites.

Excretion.

The mean elimination half-life is 39.0 ± 8.3 hours. The mean clearance ± SD is 55.1 ± 8.2 mL/min following a single dose of 2 mg clonazepam given intravenously.
50 - 70% of the dose is excreted in the urine and 10 - 30% in the faeces as metabolites. The urinary excretion of unchanged clonazepam is usually less than 2% of the administered dose. The metabolites are present in urine both as free and conjugated (glucuronide and sulphate) compounds.

Clinical significance of pharmacokinetics.

With chronic dosing, accumulation occurs. However, there is a wide variation in therapeutic plasma levels and a correlation between adverse effects with plasma levels or the rate of increase in plasma concentration of clonazepam and its metabolites has not been established. Consequently, monitoring of plasma levels, as is often done with some anticonvulsants, would be valuable.
It should be emphasised that because of the effect of clonazepam on plasma levels of other anticonvulsants administered concomitantly (and vice versa) the patient should be monitored carefully in the initial stages for clinical response and occurrence of side effects.

Pharmacokinetics in special populations.

Renal impairment.

Renal impairment does not affect the pharmacokinetics of clonazepam. Therefore, based on pharmacokinetic considerations, no dosage adjustment may be required in patients with renal impairment. The pharmacodynamics of probable accumulated clonazepam metabolites may necessitate dosage review in these patients.

Hepatic impairment.

The influence of hepatic disease on clonazepam pharmacokinetics has not been investigated. However, due to the sole hepatic metabolism of clonazepam, the pharmacokinetics of clonazepam are expected to be affected on theoretical grounds.

Elderly patients.

The pharmacokinetics of clonazepam in the elderly has not been established.

Neonates.

Although the elimination half-life (41.9 ± 29.8 hours) and clearance values in neonates pre-treated with phenobarbital are the same order of magnitude as those reported in non-pretreated adults, post-natal age does, however, affect the clearance of clonazepam under normal conditions.

5.3 Preclinical Safety Data

Genotoxicity.

Clonazepam and five of its metabolites were negative in bacterial gene mutation assays. Chromosomal damage assays have not been conducted with clonazepam.

Carcinogenicity.

No 2-year carcinogenicity studies have been conducted with clonazepam. An 18-month chronic study in rats showed no treatment-related histopathological changes at dietary doses up to 1800 mg/m2/day (greater than 100-fold MRHD).

6 Pharmaceutical Particulars

6.1 List of Excipients

Paxam 0.5 tablets contain lactose monohydrate, microcrystalline cellulose, maize starch, magnesium stearate and sunset yellow FCF aluminium lake.
Paxam 2 tablets contain lactose monohydrate, microcrystalline cellulose, maize starch and magnesium stearate.

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 25°C.

6.5 Nature and Contents of Container

Container type: bottle (HDPE) with a child resistant closure.
Pack sizes: 100, 200 tablets.
Some strengths, pack sizes and/or pack types may not be marketed.

Australian Register of Therapeutic Goods (ARTG).

AUST R 54846 - Paxam 0.5 clonazepam 0.5 mg tablet bottle.
AUST R 54847 - Paxam 2 clonazepam 2 mg tablet bottle.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.


Clonazepam is a light yellow powder which is practically insoluble in water.
Chemical name: 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one.
Molecular formula: C15H10ClN3O3.
Molecular weight: 315.7.

CAS number.

1622-61-3.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes