Consumer medicine information

Symmetrel

Amantadine hydrochloride

BRAND INFORMATION

Brand name

Symmetrel

Active ingredient

Amantadine hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Symmetrel.

SUMMARY CMI

SYMMETREL®

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 SYMMETREL?

SYMMETREL contains the active ingredient amantadine hydrochloride. SYMMETREL is used to treat Parkinson's disease and to prevent infection from Influenza Type A ("the flu"). For more information, see Section 1. Why am I taking SYMMETREL? in the full CMI.

2. What should I know before I take SYMMETREL?

Do not take if you have ever had an allergic reaction to SYMMETREL or any of the ingredients listed at the end of the CMI. Tell your doctor if you are allergic to any other medicines, foods, dyes, or preservatives.
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. You must not take SYMMETREL if you are pregnant or plan to become pregnant.
For more information, see Section 2. What should I know before I take SYMMETREL? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with SYMMETREL 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 SYMMETREL?

  • Take the capsule after a meal or snack.
  • Swallow the capsule whole with a full glass of water. Do not chew, break, or crush the capsule.
  • Your doctor will tell you how much SYMMETREL to take as it depends on factors like your condition, age, and overall health.

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

5. What should I know while taking SYMMETREL?

Things you should do
  • Remind any doctor, dentist, surgeon, or pharmacist you visit that you are taking SYMMETREL.
  • Tell your doctor if your skin is burning more easily.
  • Keep all your appointments.
Things you should not do
  • Do not stop taking this medicine suddenly or take more than your doctor tells you to.
  • Do not give this medicine to someone else or allow yourself to run out of capsules.
Driving or using machines
  • SYMMETREL may cause dizziness, confusion, difficulty concentrating, impair your reactions, or cause blurred vision in some people. Be careful when undertaking any task that requires your attention.
  • Children should avoid doing things like riding bicycles or climbing trees.
Drinking alcohol
  • Do not drink alcohol while you are on treatment with SYMMETREL.
Looking after your medicine
  • Store it in a cool dry place (below 30°C) away from moisture, heat, or sunlight.
  • Do not store in the bathroom or near a sink, in the car or on a windowsill.

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

6. Are there any side effects?

More common side effects: Skin changes (redness, itching, blotchy fishnet type pattern), feeling/being sick, more sweating, difficulty passing urine, tummy discomfort, appetite changes, dry mouth, nightmares, feeling sad, tired, anxious, light-headed, dizzy, or agitated; trouble focusing/sitting still, decreased impulse control, trouble sleeping. More serious side effects: wheezing, difficulty breathing, spreading rash or blisters on face, lips or hands, swelling of tongue or face (signs of an allergic reaction); experiencing things that are not there (hallucinations), uncontrollable movement (fits, seizures), stiff muscles/limbs; yellow skin/eyes (signs of liver problem), constantly sick with flu-like symptoms: chills/fever; vision loss, heart problems like rapid heart rate, feeling faint or disoriented/confused and difficulty speaking or slurred speech (possible signs of stroke).
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

SYMMETREL® (Sym-me-trel)

Active ingredient(s): amantadine hydrochloride (A-MAN-ta-deen Hi-droh-clor-ride)

Consumer Medicine Information (CMI)

This leaflet provides important information about taking SYMMETREL. 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 SYMMETREL.

Where to find information in this leaflet:

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

1. Why am I taking SYMMETREL?

SYMMETREL contains the active ingredient amantadine hydrochloride. SYMMETREL is both an "antiparkinsonian agent" (treats the symptoms of "Parkinson's disease) and an "anti-influenzal virostatic" (stops the activity) of Influenza Type A; the virus that causes "the flu" in your body.

SYMMETREL is used to treat adults with Parkinson's Disease. This occurs when chemicals in your brain responsible for sending messages ('neurotransmitters') are not in the right balance. Parkinson's disease causes shaking, trembling and uncontrolled movement because you may have too little "dopamine" and/or too much "acetylcholine" which makes it difficult to perform day-to-day tasks. SYMMETREL is either taken alone, or with other medicines to relieve these symptoms but is not a cure for this disease.

SYMMETREL is also used to prevent serious cases of only influenza Type A ("the flu") in patients aged 5 years or older where they may become very sick if they were to catch it and may or may not have been vaccinated. It does this by stopping the virus from creating new copies of itself. This medicine does not prevent or treat a cold or other types of flu.

2. What should I know before I take SYMMETREL?

Warnings

Do not take SYMMETREL if:

  • You are allergic to amantadine, hydroxbenzoates, sulfites, or any of the ingredients listed at the end of this leaflet.
  • You are pregnant or breastfeeding.
  • The expiry date on the packaging has passed or if the packaging is damaged/shows signs of tampering.

Always check the ingredients to make sure you can take this medicine. You should talk to your doctor if you are prone to allergies including other medicines, food, dyes, and preservatives.

Check with your doctor if you have:

  • problems with your kidneys or liver
  • seizures (uncontrollable fits)
  • diagnosed mental illness or suicidal thoughts
  • heart or circulation problems
  • stomach ulcers (sores)
  • low blood pressure
  • glaucoma (increased pressure in the eyes)
  • prostate problems (in men)
  • persistent dry skin in the form of eczema
  • have a history of addiction to gambling, sex or shopping

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?

Monitoring

Your doctor will monitor your health and your behaviour closely throughout treatment. If you develop blurred vision for example, your doctor may refer you to an ophthalmologist (eye doctor) and they may recommend you stop taking it. It is important that you do not alter your dose or stop taking SYMMETREL unless your doctor tells you to as this could increase the chance of having unwanted effects.

Changes to behaviour

SYMMETREL may make you unable to resist acting on impulses (urges) that you may or may not ordinarily do. This type of behaviour can include addictive gambling, excessive eating or spending, or heightened sex drive even if you have no prior history of these behaviours. Your doctor will want to monitor this.

Increased sensitivity of skin

SYMMETREL may cause your skin to be more sensitive than it normally is to the sun. For this reason, you should also avoid tanning beds and sunlamps.

When you are outside, ensure that you wear protective clothing that covers your skin and that you use a sunscreen of at least SPF 15+ to help prevent your skin from becoming red and blistered from sunburn.

Pregnancy and breastfeeding

You must not take SYMMETREL if you are pregnant or breastfeeding as it may harm your unborn baby. Check with your doctor if you are pregnant, think you may be pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed. The active ingredient in SYMMETREL (amantadine) passes into breast milk.

Contraception

If you are a woman and you may become pregnant you must use an effective form of contraception (birth control) during treatment and for five days after your last dose of SYMMETREL.

Children and adolescents

Children under the age of five should not take SYMMETREL as there is not enough information that it is safe or effective in these patients.

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 SYMMETREL and affect how it works. This may include:

  • other medicines for Parkinson's disease
  • medicines used for mental conditions such depression, schizophrenia
  • medicines that affect the nervous system (including those that make you calmer, relieve pain, or substances like alcohol)
  • medicines for tummy cramps or spasms
  • medicines used to treat high blood pressure (such as (hydrochlorothiazide and triamterene)

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

4. How do I take SYMMETREL?

  • Take the capsule after a meal or snack.
  • Swallow the capsule whole with a full glass of water.
  • Do not chew or crush the capsule.

How much to take

  • Your doctor will tell you how many SYMMETREL capsules you need to take based on the condition that you have, your age, your overall health (in particular your kidney function) and what other medicines you may be taking.
  • Follow the instructions provided and take SYMMETREL until your doctor tells you to stop.

Parkinson's Disease

  • If you are taking SYMMETREL capsules because you have Parkinson's Disease, treatment is usually one capsule (100 mg) taken once a day.
  • Your doctor may increase this to one capsule (100mg) taken twice a day, or higher doses depending on how you respond to treatment.
  • You must not take more capsules than your doctor tells you to or stop taking this medicine suddenly regardless of how well you feel.

Type A Influenza

If you are taking SYMMETREL capsules because you have Type A influenza, treatment depends on your age and overall health.

Children aged 5 to 9 years:

Take only one capsule (100 mg) each day.

Children aged 10 or older:

Take one capsule (100 mg) twice daily.

Adolescents and adults up to age 65 years:

Take one capsule (100 mg) twice daily.

Adults over 65 years:

Take only one capsule (100 mg) each day.

In elderly patients with impaired kidney function:

If you are over 65 years of age or have reduced kidney function, your doctor may reduce your dose or ask you to take SYMMETREL capsules less frequently than patients with normal kidney function.

In elderly patients WITHOUT impaired kidney function:

Do not take more than 100 mg daily unless prescribed by your doctor.

You must not take more capsules than your doctor tells you to regardless of how well you feel or whether you think it is working.

When to take SYMMETREL

SYMMETREL should be taken at about the same time every day, as directed by your doctor. This will have the best effect and helps you remember to take it.

Parkinson's Disease

  • Adults up to the age of 65 years old: For the first week, take your medicine (one 100 mg capsule) once daily. After the first week of treatment, depending on how you respond, your doctor may suggest you take one capsule (100 mg) twice daily.
  • Adult over 65 years old: Take only one capsule (100 mg) per day.

Type A influenza

SYMMETREL capsules should be taken soon as possible after exposure to the flu virus in accordance with the below:

  • Children aged 5-9: Take only one capsule (100 mg) daily.
  • Children aged 10 and older & adults to 65 years: Take one capsule (100 mg) twice each day
  • Adults over 65 years old: Take only one capsule (100 mg) daily.
  • People with reduced kidney function due to increasing age or kidney disease: Take as directed by your doctor as you may be reduced to one capsule (100 mg) every 2 to 7 days to help prevent side effects.
  • If side effects occur: your doctor may reduce your dose to one capsule (100 mg) daily.

How long to take SYMMETREL

Parkinson's Disease

  • You may need to take SYMMETREL for a long time to control your symptoms.
  • You must not change your dose or stop taking SYMMETREL unless you doctor tells you to.
  • If your doctor tells you to stop taking SYMMETREL then they may gradually reduce your dose before taking you off treatment completely.

Type A Influenza

  • Keep taking Symmetrel for at least 10 days, ideally as soon as you are exposed to the virus.
  • Sometimes it may be necessary to keep taking it until the outbreak of influenza is over.

If you forget to take SYMMETREL

  • SYMMETREL should be taken regularly at about the same time each day.
  • If you miss your dose at the usual time and it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take the dose as soon you remember and then go back to taking it as you normally would.
  • Do not take a double dose to make up for the dose you missed. This may increase the chance of you getting an unwanted side effect.

If you take too much SYMMETREL

If you think that you have taken too much SYMMETREL 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. Patients over the age of 65 years or patients who have a problem with their kidneys are at a higher risk of this.

Some of the symptoms of an overdose may include stiffness or unusual muscle movements, seizures (fits), vomiting, difficulty breathing, fast or irregular heartbeat, seeing or hearing things that are not there and losing consciousness.

5. What should I know while taking SYMMETREL?

Things you should do

  • Keep all your doctor's appointments so that your progress and overall health can be checked.
  • Take SYMMETREL exactly as your doctor tells you to.
  • Be careful when getting up from a sitting or lying position. You can help manage the light-headed/dizzy feelings by getting up slowly and flexing leg muscles and wiggling your toes to get the blood flowing. When getting out of bed, dangle your legs over the side for a minute or two before standing up.
  • Tell your doctor if your skin becomes red or blistered (like a sunburn).
  • Tell your doctor if you have been having urges to gamble, shop or are experiencing a higher than normal sex drive (libido) that is difficult to resist.
  • Remind any doctor, dentist, surgeon, or pharmacist you visit that you are taking SYMMETREL.

Call your doctor straight away if you:

  • Become pregnant or think you may become pregnant
  • Experience vision loss or blurred vision. Your doctor may refer you to an eye doctor (ophthalmologist) who may recommend you stop taking SYMMETREL.
  • Experience confusion, disorientation, hallucinations, nausea, vomiting, accelerated breathing, irregular heartbeat, movement disorders, or seizures

Things you should not do

  • Do not take more SYMMETREL than your doctor has told you to take.
  • Do not stop taking this medicine suddenly without talking to your doctor.
  • Do not allow yourself to run out of capsules where you may not have access to a pharmacy (such as weekends, public holidays or while on holidays)
  • Do not give this medicine to someone else.

Driving or using machines

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

SYMMETREL may cause dizziness, confusion, difficulty concentrating, impair your reactions, or cause blurred vision in some people. Be careful when doing something that requires your attention.

Children should avoid doing things like riding bicycles or climbing trees.

Drinking alcohol

Do not drink alcohol while you are on treatment with SYMMETREL.

Taking SYMMETREL with alcohol could make you more dizzy or lightheaded than usual. If this medicine makes you feel light-headed, dizzy, or faint, be careful when getting up from a sitting or lying position.

Looking after your medicine

Keep your medicine in the container it came in until it is time to take it. Follow the instructions on the carton on how to take care of your medicine properly.

Store it in a cool dry place (below 30°C) 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 windowsills.

Keep it where young children cannot reach it.

When to discard your medicine

You may discard your medicine when it is empty, your doctor tells you that you do not need to take it anymore, or if it is out of date.

Getting rid of any unwanted medicine

If your doctor tells you that 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.

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

Less serious side effects

Less serious side effectsWhat to do
Changes to behaviour or mood
  • Desire to gamble a lot
  • Increased sex drive/interest
  • Uncontrollable shopping/spending
  • Binge eating or compulsive overeating.
  • Feeling anxious, nervous, agitated, or depressed (sad)
Tummy problems
  • Constipation
  • Diarrhoea
  • Vomiting (being sick)
  • Indigestion
  • Nausea (feeling sick)
General well-being
  • Sweating a lot
  • Feeling weak or shaky
  • Feeling restless or tired
  • Problems paying attention
  • Poor sleep, nightmares
  • Hair loss
  • Feeling dizzy/light-headed
  • Dry mouth
Skin problems
  • Skin that looks like sunburn - redness, itching, blistering
  • Purple or blotchy skin that looks like a fishnet pattern.
Kidney problems
  • Difficulty passing urine or unable to stop passing urine.
  • Swelling of feet or lower legs due to fluid buildup
Eye problems
  • Blurred vision
Speak to your doctor if you have any of these less serious side effects and they worry you.
If you are over 65 years old, you should be especially careful while taking this medicine. Report any side effects promptly to your doctor.
SYMMETREL can cause confusion or disorientation, especially in older people. Your family or carer should be made aware of this.

Serious side effects

Serious side effectsWhat to do
Signs of an allergic reaction
  • Sudden and spreading skin changes including an angry, itchy, or red rash, hives, swelling/blisters on the lips, mouth, or tongue
  • Shortness of breath, wheezing, trouble breathing
Heart and circulation problems
  • Fast or irregular heartbeat
  • Feeling disoriented, confused, fainting and sudden drop in body temperature.
  • Difficulty speaking, slurred speech (possible signs of stroke).
Liver problems
  • Yellow skin or eyes
General well-being
  • Hallucinations (seeing, hearing, or feeling things that are not there)
  • Abnormally high-level of energy, erratic behaviour (mania)
Movement problems
  • Stiff or rigid muscles
  • Uncontrollable movement (fits, seizures)
Eye problems
  • Sudden vision loss
Infections
  • Being sick constantly with flu-like symptoms (chills, fever, sore throats, aching joints, swollen glands, or sores in the mouth.
  • Very low body temperature (below 35°C); especially in children
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.

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.

Symmetrel capsules contain 100 mg of amantadine hydrochloride.

What SYMMETREL contains

Active ingredient
(main ingredient)		amantadine hydrochloride.
Other ingredients
(inactive ingredients)
  • rape seed oil
  • lecithin
  • a wax blend composed of yellow beeswax, hydrogenated, and partially hydrogenated soya oils
  • sodium ethyl hydroxybenzoate
  • sodium propyl hydroxybenzoate
  • gelatin
  • glycerol
  • iron oxide red
  • Karion 83 (a mixture of sorbitol, mannitol, and hydrolysed starch in water)
  • titanium dioxide
  • white, edible branding ink
Potential allergensSYMMETREL contains hydroxbenzoates and sulfites. It does not contain sucrose, gluten, tartrazine, or any other azo dyes.

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

What SYMMETREL looks like

SYMMETREL capsules are soft brown gelatin capsules, marked "GEIGY" on one side and "GB" on the other. Each bottle contains 100 capsules (AUST R 11057).

Who distributes SYMMETREL

NOVARTIS Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone: 1 800 671 203
®= Registered Trademark
This leaflet was prepared in March 2024.

(CMI sym080420c_v2 is based on the PI sym080420i).

Published by MIMS April 2024

BRAND INFORMATION

Brand name

Symmetrel

Active ingredient

Amantadine hydrochloride

Schedule

S4

 

1 Name of Medicine

Amantadine hydrochloride.

2 Qualitative and Quantitative Composition

Each capsule contains amantadine hydrochloride 100 mg.
Excipients with known effect: contains hydroxybenzoates and sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

100 mg capsules: brown, soft gelatin, marked "GEIGY" on one side and "GB" on reverse.

4 Clinical Particulars

4.1 Therapeutic Indications

Parkinson's disease.

Idiopathic Parkinson's disease; post-encephalitic parkinsonism; symptomatic parkinsonism (e.g. following CNS injury from carbon monoxide poisoning); arteriosclerotic parkinsonism; drug-induced extrapyramidal reactions.
Symmetrel can be given alone for initial therapy or combined with anticholinergic drugs or L-dopa (see Section 4.2 Dose and Method of Administration).

Note.

Symmetrel is not indicated for the treatment of tardive dyskinesia.

Type A viral influenza.

Prophylaxis of respiratory tract illness caused by influenza type A.
Prophylaxis in non-immunised individuals (including children) for whom influenza may have serious consequences (e.g. persons with chronic respiratory disease or diabetes mellitus).

4.2 Dose and Method of Administration

Before use in elderly patients or those with impaired liver or kidney function, see Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties. In patients over 65 years of age, both age and renal function should be taken into consideration. By age 65, renal function will typically have declined to a level at which reduced doses of Symmetrel or increased dosing interval are appropriate. Specific dosage schedules for patients over 65 years of age and those with impaired renal function are shown below.

Recommended dosages. Parkinson's disease.

Adults to 65 years.

When used alone, 100 mg daily for the first week of treatment, increasing in the second week to 100 mg twice daily. The dose can be titrated against signs and symptoms. Amounts exceeding 200 mg daily may provide some additional relief but may also be associated with increasing toxicity. In these cases the dose should be raised gradually, at intervals of not less than 1 week.

Adults over 65 years.

Since patients in this age group tend to have lower renal clearance and consequently higher plasma concentrations (see Section 5.2 Pharmacokinetic Properties), the recommended dose is 100 mg daily. If the patient has, or develops, any renal impairment, the dosing interval should be adjusted (see Section 4.2 Dose and Method of Administration, Dosage in renal impairment).

Note.

Patients deriving benefit initially from Symmetrel not uncommonly experience a reduction in effectiveness after a few weeks. Temporary discontinuation of Symmetrel for several weeks, followed by re-introduction of therapy, may result in regaining of benefit in some patients. The use of other anti-Parkinson drugs may be necessary. Treatment with Symmetrel must be reduced gradually because abrupt discontinuation may exacerbate Parkinson's syndrome, regardless of the patient's response to therapy (see Section 4.4 Special Warnings and Precautions for Use).
Combined treatment. Any anti-Parkinson drug with which the patient is already being treated should be continued during the first stage of treatment with Symmetrel. In many cases it is then possible to gradually reduce the dosage of the other drug without prejudicing the treatment response. If increased side effects occur, however, its dosage should be reduced more quickly. In patients receiving high doses of L-dopa or anticholinergic drugs, the initial period of low dosage with Symmetrel should be extended to two weeks.
Drug induced extrapyramidal reactions.

Adults.

The most appropriate treatment is to reduce the dosage of the drug inducing the reactions. Where this is not practical, the usual dose of Symmetrel is 100 mg twice daily. Occasionally, a patient may require 100 mg three times daily in order to obtain an optimal response.
As drug-induced extra-pyramidal reactions may decrease or disappear without treatment, an attempt should be made to discontinue treatment with Symmetrel when the reactions have been controlled for a period.

Type A virus influenza.

Children aged 5-9 years.

100 mg once daily.

Children and adults aged 10-65 years.

100 mg twice daily. Effective prevention of influenza A has been reported with a dosage of 100 mg daily. This dosage may be indicated for persons who have demonstrated intolerance to 200 mg daily.

Adults over 65 years.

100 mg daily.
Dosage with Symmetrel should start immediately after suspected exposure and continue for at least 10 days. When exposure to infection is recurrent or prolonged, treatment throughout the epidemic may be indicated. Symmetrel is effective for prophylaxis only during the period of its administration. The recommended dosage should not be exceeded.

Dosage in renal impairment.

In patients with compromised renal function and in those on haemodialysis, the elimination half-life of amantadine is substantially prolonged, resulting in elevated plasma concentrations (see Section 5.2 Pharmacokinetic Properties). Careful adjustment of the dose of Symmetrel by increasing the dosing interval according to the creatinine clearance (see Table 1) is required in these patients. Ideally, amantadine plasma concentrations should be monitored. Careful surveillance of the patient is recommended (see Section 5.2 Pharmacokinetic Properties, Renal failure, Haemodialysis).

Loading dose on the first day of treatment with Symmetrel.

Starting dose as recommended for patients without renal impairment (see Section 4.2 Dose and Method of Administration, Parkinson's disease, Type A virus influenza).

Dose thereafter.

100 mg at interval shown in Table 1.
When it is not possible to measure creatinine clearance, the value may be estimated in patients with stable renal function using the formula of Cockcroft and Gault (see Equation 1).
This formula should only be used if the patient is in a steady state with respect to serum creatinine concentration.

4.3 Contraindications

Pregnancy, lactation; hypersensitivity to amantadine or to any of the excipients in Symmetrel.

4.4 Special Warnings and Precautions for Use

Medical supervision during treatment with Symmetrel is essential. The margin between the therapeutically effective dose and that producing toxic manifestations may be only 100 to 200 mg per day. The usual daily dose should, therefore, not be exceeded.

Use with caution in the following circumstances.

Patients with pre-existing seizure disorders have been reported to develop an increased frequency of major motor seizures during amantadine ingestion. A reduction in dosage may minimise this risk. These patients should be closely monitored.
Those patients with confusional, hallucinatory or psychotic states should receive Symmetrel with caution as an increase in confusion, hallucinations and nightmares may occur in patients with underlying psychiatric disorders.
Because of the possibility of serious adverse effects, caution should be observed when prescribing Symmetrel to patients being treated with drugs having CNS effects or for whom the potential risks outweigh the benefit of treatment. Because some patients have attempted suicide by using an overdose of amantadine, prescriptions should be written for the smallest quantity consistent with good patient management.
Particular care is called for in patients suffering from or with a history of recurrent eczema, gastric ulceration or cardiovascular disorders.
Peripheral oedema, probably due to local vascular disturbance, may occur in some patients during treatment with Symmetrel capsules. This should be considered if Symmetrel is prescribed for patients with a history of heart failure.
The dosage of Symmetrel may need careful adjustment in patients with orthostatic hypotension.
The possible occurrence of anticholinergic effects should be borne in mind particularly when treating patients with glaucoma or prostatic enlargement.
Symmetrel should be used with care in patients suffering from or with a history of recurrent eczematoid rash, and should be withdrawn if allergic skin reactions occur.
Isolated cases of corneal lesions have been reported, e.g. punctate sub-epithelial opacities which might be associated with superficial punctate keratitis, corneal epithelial oedema and markedly reduced visual acuity.
Because amantadine has anticholinergic effects, it should not be given to patients with untreated angle closure glaucoma.
If blurred vision or other visual problems occur an ophthalmologist should be contacted to exclude corneal oedema. In case that corneal oedema is diagnosed treatment with amantadine should be discontinued.

Discontinuation of Symmetrel in Parkinson's disease.

Abrupt discontinuation of anti-parkinsonian drugs, including Symmetrel, may result in worsening of the symptoms of Parkinson's disease or in symptoms resembling neuroleptic malignant syndrome (NMS), catatonia as well as in cognitive manifestations (e.g. confusion, disorientation, worsening of mental status, delirium). There have been isolated reports on a possible association between the aggravation of NMS or neuroleptic-induced catatonia and the withdrawal of amantadine in patients treated concurrently with neuroleptic agents and amantadine, following abrupt cessation of the latter. Therefore, treatment with amantadine should not be stopped abruptly.

Development of resistance during use for influenza A.

Resistance to amantadine is readily achieved by serial passage of influenza virus strains in vitro or in vivo in the presence of the drug. Influenza A viruses cross resistant to amantadine can emerge when this drug is used to treat influenza infections. Apparent transmission of drug-resistant viruses may have been the reason for failure of prophylaxis and treatment in household contacts and in nursing home patients. However, there is no evidence to date that the resistant virus produces a disease that is in any way different from that produced by sensitive viruses.

Impulse control disorders.

Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including Symmetrel. Dose reduction/ tapered discontinuation should be considered if such symptoms develop.

Use in renal or liver impairment.

Symmetrel should be used cautiously in patients with renal or liver disorders. In cases of impaired renal function the dosage should be adjusted according to the creatinine clearance of the individual patient and, ideally, amantadine plasma concentrations should be monitored. Since only small amounts of amantadine are eliminated by patients undergoing haemodialysis for renal failure, these patients should have their dosage carefully adjusted in order to avoid adverse reactions (see Section 5.2 Pharmacokinetic Properties; Section 4.2 Dose and Method of Administration).

Use in the elderly.

Elderly patients are often especially susceptible to adverse reactions or exacerbation of pre-existing central nervous system symptoms (see Section 5.2 Pharmacokinetic Properties; Section 4.2 Dose and Method of Administration).
Plasma amantadine concentrations are influenced by renal function. In the elderly, the elimination half-life tends to be longer and renal clearance lower than in younger subjects. A dose not exceeding 100 mg daily is recommended in elderly patients without renal disease. If the patient has any renal function impairment, the dosing interval should be adjusted (see Section 4.2 Dose and Method of Administration, Adults over 65 years, Dosage in renal impairment).

Paediatric use.

Symmetrel is not recommended for use in patients below the age of 5 years. Hypothermia has been observed in children. Caution should be exercised when prescribing Symmetrel to children for the prevention and treatment of influenza type A virus (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

Observed interactions resulting in concomitant use not being recommended.

Concomitant administration of amantadine and anticholinergic agents may increase confusion, hallucinations, nightmares, gastrointestinal disturbances or other atropine-like side effects (also see Section 4.9 Overdose).
In isolated cases psychotic decompensation has been reported in patients receiving amantadine and concomitant antipsychotic drugs or levodopa.
Concomitant administration of amantadine with fixed dose combination of hydrochlorothiazide and triamterene may reduce the systemic clearance of the drug leading to increased plasma concentrations and toxic effects (confusion, hallucinations, ataxia, and myoclonus).

Anticipated interactions to be considered.

Drugs acting on the central nervous system.

Concomitant administration of amantadine and drugs or substances (e.g. alcohol) acting on the central nervous system may result in additive CNS toxicity. Close observation is recommended (also see Section 4.9 Overdose).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Symmetrel administered to both male and female rats at a dose equivalent to the maximum recommended human dose on a mg/m2 basis impaired fertility.
(Category B3)
Amantadine-related complications during pregnancy have been reported. Symmetrel is contraindicated during pregnancy. Women of child-bearing potential must use highly effective contraception during treatment, and for 5 days after their last dose of amantadine.
 Amantadine passes into breast milk. Adverse drug reactions have been reported in breast-fed infants. Nursing mothers should not take Symmetrel.

4.7 Effects on Ability to Drive and Use Machines

Patients receiving treatment with Symmetrel should be warned that dizziness, blurred vision and other central nervous symptoms may occur and impair the patient's reactions, in which case they should not drive, operate potentially dangerous machinery or engage in other activities that may become hazardous because of decreased alertness (see Section 4.8 Adverse Effects (Undesirable Effects), Nervous system disorders).

4.8 Adverse Effects (Undesirable Effects)

The undesirable effects of amantadine usually appear within the first 1-4 days of treatment and promptly disappear in 24-48 hours after discontinuation of amantadine.
A direct relationship between dose and incidence of side effects has not been demonstrated. However, there seems to be a tendency towards more common adverse drug reactions, particularly affecting the central nervous system, with increasing doses.
The adverse reactions (Table 2) are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. In addition, the corresponding frequency category for each adverse drug reaction is based on the following convention (CIOMS III): very common: ≥ 1/10 (≥ 10%); common: ≥ 1/100 to < 1/10 (≥ 1% to < 10%); uncommon: ≥ 1/1,000 to < 1/100 (≥ 0.1% to < 1%); rare: ≥ 1/10,000 to < 1/1,000 (≥ 0.01% to < 0.1%); very rare: < 1/10,000 (< 0.01%); not known: frequency has not been assessed.

Impulse control disorders.

Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including Symmetrel (see Section 4.4 Special Warnings and Precautions for Use).

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

Overdose (acute overdose with multiples of the maximum recommended dose or overexposure due to high dosages for elderly and/or renally impaired patients) with Symmetrel capsules can lead to a fatal outcome (see Section 4.4 Special Warnings and Precautions for Use).

Signs and symptoms.

Neuromuscular disturbances and symptoms of acute psychosis are prominent features of acute poisoning with amantadine.

Central nervous system.

Hyper-reflexia, motor restlessness, convulsions; extrapyramidal signs: torsion spasms, dystonic posturing; confusion, disorientation, delirium, visual hallucinations, dilated pupils, dysphagia and myoclonus, aggression/ hostility, depressed level of consciousness and coma.

Respiratory system.

Hyperventilation, pulmonary oedema, respiratory distress including adult respiratory distress syndrome.

Cardiovascular system.

Disturbances of fluid, electrolyte and acid/ base balance, sinus tachycardia, arrhythmia and hypertension. Cardiac arrest and sudden cardiac death have been reported.

Gastrointestinal system.

Nausea, vomiting, dry mouth.

Renal function.

Urinary retention, renal dysfunction including increase in blood urea nitrogen (BUN) and decreased creatinine clearance.

Overdose from combined drug treatment.

The peripheral and central adverse effects of anticholinergic drugs are increased by the concomitant use of amantadine, and acute psychotic reactions (which may be identical to those caused by atropine poisoning) may occur, especially when large doses of anticholinergic agents are used (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). When overdosage of amantadine has occurred in conjunction with the use of alcohol or central nervous system stimulants, the signs and symptoms of acute poisoning with Symmetrel may be aggravated or otherwise modified.

Treatment.

There is no specific amantadine hydrochloride antidote.

Removal and/or inactivation of poisoning agent(s).

Induction of vomiting and/or gastric aspiration and lavage if patient is conscious, activated charcoal, saline cathartic, if judged appropriate. Since amantadine is largely excreted unchanged in the urine, maintenance of renal excretory function, copious diuresis, and forced diuresis, if necessary, are effective in removing it from the blood stream. Acidification of the urine favours the excretion of amantadine in the urine. Haemodialysis does not remove significant amounts of amantadine.
Monitoring of blood pressure, heart rate, ECG, respiration, body temperature, and treatment for possible hypotension and cardiac arrhythmias, as necessary. Caution is required when administering adrenergic substances in case of cardiac arrhythmias and hypotension as the clinical status may deteriorate due to arrhythmogenic nature of the adrenergic drugs.

Convulsions and excessive motor restlessness.

Administer anticonvulsants such as diazepam I.V., paraldehyde I.M. or per rectum, or phenobarbital I.M.

Acute psychotic symptoms, delirium, dystonic posturing, myoclonic manifestations.

Physostigmine by slow I.V. infusion (1 mg doses in adults, 0.5 mg in children) in repeated administration according to initial response and subsequent need has been reported.

Retention of urine.

The bladder should be catheterized; an indwelling catheter can be left in place for the time required.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Therapeutic/ pharmacological group: antiparkinsonian agent and anti-influenzal virostatic (ATC code N04B B01).

Mechanism of action.

As antiparkinsonian agent.

The mechanism of action of amantadine is not fully understood. There is evidence to suggest that amantadine acts as an indirect dopamine receptor agonist by enhancing the synthesis and release of dopamine from central neurons and delaying the reuptake into synaptic vesicles. Other evidence suggests an alteration of striatal D2 receptors towards a high affinity state. Amantadine may also exert some anticholinergic activity. When administered either alone or in combination with other drugs, amantadine produces an improvement in the cardinal signs and symptoms of parkinsonism and improves functional capacity. In Parkinson's disease, the clinical response usually occurs within 24 to 48 hours or, at the most, one week. An optimal effect is obtained during a period extending from several days to a few weeks.

As anti-influenzal virostatic.

Amantadine specifically inhibits the replication of influenza A viruses at low concentrations. Using a sensitive plaque-reduction assay, human influenza viruses, including H1N1, H1N2, H2N2, H3N2 subtypes, are inhibited by 0.2 to 0.7 microgram/mL or less of amantadine. It is recognised, however, that not all strains susceptible under in vitro conditions will be similarly affected in clinical practice. The exact mechanism of action of amantadine is unclear.
Amantadine does not completely prevent the host immune response to influenza A infection. Individuals who take this drug may still develop immune responses to natural disease or vaccination and may be protected when later exposed to antigenically related viruses.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Symmetrel is completely absorbed from the gastrointestinal tract after oral administration, producing a peak concentration of amantadine in plasma 1 to 4 hours after ingestion. Peak plasma concentrations of approximately 250 nanogram/mL and 500 nanogram/mL are attained after single oral administration of 100 mg and 200 mg amantadine, respectively. Following repeated administration of 200 mg daily, the trough steady-state plasma concentration is approximately 300 nanogram/mL within 3 days.

Distribution.

67% of amantadine is bound to plasma proteins in vitro. A substantial amount of amantadine is bound to red blood cells. The erythrocyte amantadine concentration in normal healthy volunteers is 2.66 times the plasma concentration. The apparent volume of distribution of the drug is approximately 5-10 L/kg, suggesting extensive tissue binding. It declines with increasing doses. The concentration of amantadine in the lung, heart, kidney, liver and spleen is higher than in the blood. The drug accumulates after several hours in nasal secretions, is found in saliva in concentrations similar to those in plasma, and in CSF in concentrations about 60% of those in plasma.

Metabolism.

Amantadine is metabolised to a minor extent, principally by N-acetylation. Whether this metabolic pathway is affected by acetylator phenotype remains to be determined.

Excretion.

Amantadine is eliminated in healthy young adults with a mean plasma elimination half-life of approximately 15 hours (10-31 hours). The total plasma clearance is about the same as renal clearance (250 mL/min). Renal clearance of amantadine is much higher than the creatinine clearance, suggesting renal tubular secretion.
A single dose of amantadine is excreted over 72 hours as follows: 65-85% unchanged, 5-15% as the acetyl metabolite in urine and 1% in the stool. After 4-5 days, approximately 90% of the dose appears unchanged in the urine. The rate is considerably influenced by urinary pH, a rise in pH bringing about a fall in excretion.

Effect of age and disease on pharmacokinetics.

Elderly patients.

Compared with data from healthy young adults, the elimination half-life is doubled and renal clearance is diminished. The renal/ creatinine clearance ratio in elderly subjects is smaller than in young people. Tubular secretion diminishes more than glomerular filtration. In elderly patients, repeated administration of 100 mg amantadine daily may raise the plasma concentration into the toxic range.

Renal failure.

Accumulation of amantadine may occur in renal failure, causing severe adverse reactions. A creatinine clearance of less than 40 mL/min/1.73 m2 causes a 3 to 5-fold increase in elimination half-life and a 5-fold decrease in total and renal clearance. Renal elimination is dominant even in cases of renal failure.
Renal function declines steadily after early adulthood (at about 10% per decade from the fourth decade on). By age 65, renal function will typically have declined to a level at which reduced doses of Symmetrel (or increased dosing interval) are appropriate. Elderly patients or patients with renal failure should receive an adequately reduced dosage in accordance with the individual creatinine clearance (see Section 4.2 Dose and Method of Administration). The target plasma amantadine concentration should not exceed a maximum of 300 nanogram/mL.

Haemodialysis.

Little amantadine is removed by haemodialysis. This inefficiency may be related to its extensive tissue binding. Less than 5% (7-15 mg) of a single 300 mg dose is eliminated after a 4-hour haemodialysis. The mean elimination half-life reaches 24 dialysis hours.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Symmetrel soft capsules also contain the inactive ingredients: rape seed oil, lecithin, beeswax-yellow, soya oil-hydrogenated and soya oil-partially hydrogenated. The capsule shell contains: sodium ethyl hydroxybenzoate, sodium propyl hydroxybenzoate, gelatin, glycerol, iron oxide red, Karion 83 (sorbitol, mannitol and starch-hydrolysed maize as 70% aqueous solution), titanium dioxide, edible ink-white.

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. Protect from moisture.

6.5 Nature and Contents of Container

White plastic bottles of 100 capsules, fitted with a push and turn closure.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Amantadine, the active ingredient of Symmetrel, is a stable, white, crystalline powder with a bitter taste, readily soluble in water and soluble in ethanol and chloroform.

Chemical structure.

Chemical name: 1-adamantanamine hydrochloride.
Molecular weight: 187.71.
Molecular formula: C10H18NCl.

CAS number.

665-67-7.

7 Medicine Schedule (Poisons Standard)

(S4) Prescription Only Medicine.

Summary Table of Changes