Consumer medicine information

Artane

Trihexyphenidyl (benzhexol) hydrochloride

BRAND INFORMATION

Brand name

Artane

Active ingredient

Trihexyphenidyl (benzhexol) hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Artane.

SUMMARY CMI

ARTANE®

Consumer Medicine Information (CMI) summary

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

1. Why am I using ARTANE?

ARTANE contains the active ingredient Trihexyphenidyl (benzhexol) hydrochloride. ARTANE is used along with other medicines to help treat Parkinson's disease. ARTANE is also used after illnesses, which have after-effects like Parkinson's disease. ARTANE can also be used to help prevent tremor or shaking, which have been caused by tranquillisers such as reserpine and phenothiazines.

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

2. What should I know before I use ARTANE?

Do not use if you have ever had an allergic reaction to Trihexyphenidyl (benzhexol) hydrochloride medicine or any of the ingredients listed at the end of the CMI.

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 use ARTANE? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with ARTANE 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 use ARTANE?

  • The dose of ARTANE may be different for each person. Your doctor will decide the right dose for you.
  • If you are over 60, your starting dose will be low and then increased gradually.

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

5. What should I know while using ARTANE?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using ARTANE.
Things you should not do
  • Do not stop taking ARTANE or change the dose, without first checking with your doctor.
  • Do not use this medicine to treat any other complaints unless your doctor says to.
  • Do not give ARTANE to anyone else, even if their symptoms seem similar to yours.
Driving or using machines
  • Be careful driving or operating machinery until you know how ARTANE affects you. ARTANE may cause drowsiness or dizziness in some people and therefore may affect alertness.
Drinking alcohol
  • Be careful when drinking alcohol while you are taking this medicine.
Looking after your medicine
  • Keep ARTANE in a cool dry place where the temperature stays below 25°C.
  • Keep ARTANE where children cannot reach it.

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

6. Are there any side effects?

Common side effects: dryness of mouth, blurred vision, dizziness, feeling sick or nausea, nervousness, and worsening of muscle weakness (myasthenia gravis). Rare side effects: swelling of your salivary glands, rash, bowel problems, confusion, agitation, delusions, or disturbed behaviour, seeing, feeling or hearing things that are not there. Other side effects that have been reported in medicines that work the same way as ARTANE includes constipation, drowsiness, difficulty passing urine, fast hear rate, enlarged pupils, increased pressure in the eye, weakness, vomiting, and headache.

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

ARTANE®

Active ingredient(s): Trihexyphenidyl (benzhexol) hydrochloride

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I using ARTANE?

ARTANE contains the active ingredient Trihexyphenidyl (benzhexol) hydrochloride. ARTANE belongs to a group of medicines known as antidyskinetics. It works by relaxing muscle tissue and by acting on the nerves, which control the working of muscles.

ARTANE is used along with other medicines to help treat Parkinson's disease.

Parkinson's disease is a brain disorder, which affects movement. The symptoms of Parkinson's disease include trembling, rigid posture, slow movements and a shuffling unbalanced walk.

ARTANE is also used after illnesses, which have after-effects like Parkinson's disease.

ARTANE can also be used to help prevent tremor or shaking, which have been caused by tranquillizers such as reserpine and phenothiazines.

Ask your doctor if you have any questions about why ARTANE has been prescribed for you. Your doctor may have prescribed this medicine for another purpose.

ARTANE is not habit forming.

2. What should I know before I use ARTANE?

Warnings

Do not use ARTANE if:

  • you are allergic to ingredient Trihexyphenidyl (benzhexol) hydrochloride
  • or any of the ingredients listed at the end of this leaflet
  • any other similar medicines
  • always check the ingredients to make sure you can use this medicine.
  • Some symptoms of an allergic reaction include rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or troubled breathing.
  • Do not take ARTANE if you have narrow angle glaucoma, a condition often associated with an increase in pressure of the eye.
  • Do not give this medicine to children unless advised by the child's doctor. The safety and effectiveness of ARTANE in children have not been established.
  • If you are not sure whether you should start taking this medicine, talk to your doctor.

Check with your doctor if you:

  • have any allergies to any other medicines, foods, preservatives or dyes
  • have any other medical conditions including
    - liver, kidney or heart disease
    - high blood pressure
    - glaucoma (high pressure in the eye)
    - problems with your stomach or bowel
    - difficulty urinating
    - prostate problems
    - an inability to sweat normally
    - myasthenia gravis
    If you have not told your doctor about any of the above, tell them before you take any ARTANE.
  • 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. Your doctor will discuss the risks and benefits of taking ARTANE during pregnancy.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Your doctor will discuss the risks and benefits of taking ARTANE when 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 ARTANE. These include:

  • medicines used to treat depression (e.g. barbiturates, opiates, monoamine oxidase inhibitors, tricyclic antidepressants)
  • other medicines used to treat Parkinson's disease, movement disorders or muscle spasms (e.g. levodopa, anticholinergics)
  • medicines used to treat certain nerve disorders
  • medicines used to control epilepsy
  • medicines used to relieve nausea (e.g. metoclopramide)
  • medicines used to treat glaucoma (e.g. acetazolamide)
  • magnesium hydroxide (e.g. antacids)

These medicines may be affected by ARTANE or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines. Your doctor or pharmacist may have more information on medicines to be careful with or avoid while taking ARTANE.

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

4. How do I use ARTANE?

How much to take

  • The dose of ARTANE may be different for each person. Your doctor will decide the right dose for you.
  • If you are over 60, your starting dose will be low and then increased gradually.
  • The starting dose is usually 1mg on the first day. The dose may then be increased by 2 mg at a time every three to five days until a total dose of 6 to 10 mg is taken daily.
  • Some people may need to take a daily dose of 12 to 15 mg.
  • If you are taking ARTANE for tremor or shaking caused by other medicines, the usual daily dose is between 5 and 15 mg.

How to take ARTANE

  • Swallow ARTANE with a glass of water.

When to take ARTANE

  • ARTANE may be taken with or without food. ARTANE makes some people feel very thirsty. How you react will determine if it is better for you to take ARTANE before or after meals.
  • If you salivate a lot, take it after meals.
  • If you find it makes your mouth very dry, take it before meals unless it makes you feel sick.
  • If you take it after meals, mint candies, chewing gum or water can help lessen the thirst.
  • Take ARTANE three times a day at mealtimes, if you are on a lower dose.
  • Take ARTANE four times daily, with three doses at mealtimes and the fourth dose at bedtime, if you are on a higher dose.

How long to take ARTANE

  • Continue taking this medicine as long as your doctor recommends it.
  • You may need to take ARTANE indefinitely.

If you forget to use ARTANE

If 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 it as soon as you remember, and then go back to taking it as you would normally

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

If you are unsure about whether to take your next dose, speak to your doctor or pharmacist.

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

If you use too much ARTANE

If you think that you have used too much ARTANE, 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.

5. What should I know while using ARTANE?

Things you should do

Use ARTANE exactly as your doctor has prescribed.

Call your doctor straight away if you:

  • develop an allergy to ARTANE.
    ARTANE can cause allergies unexpectedly, even if you have been taking it for a long time.
  • become pregnant while you are taking ARTANE.
  • feel ARTANE is not helping your condition.
    Visit your doctor regularly.

Your doctor needs to check your progress and see whether you need to keep taking ARTANE. Your doctor will also want to check the pressure in your eyes regularly as ARTANE may affect your vision.

Always discuss with your doctor any problems or difficulties during or after taking ARTANE.

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.

Keep enough medicine to last weekends and holidays.

Remind any doctor, dentist or pharmacist you visit that you are using ARTANE.

Things you should not do

  • Do not stop taking ARTANE or change the dose, without first checking with your doctor.
    Especially if you are over 60 years, the dose of ARTANE must be strictly adhered to, as you are more likely to become sensitive to its effects.
  • Do not use this medicine to treat any other complaints unless your doctor says to.
  • Do not give ARTANE to anyone else, even if their symptoms seem similar to yours.
  • Do not use ARTANE if the packaging is torn or shows

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 or dizziness, which may increase the risk of a fall.

Driving or using machines

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

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

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

Drinking alcohol

Be careful when drinking alcohol while you are taking this medicine.

If you drink alcohol, drowsiness and dizziness may be worse. Alcohol may also decrease the affect of ARTANE.

Looking after your medicine

  • Keep your tablets in their bottle until it is time to take them. If you take the tablets out of the bottle they may not keep well.
  • Keep ARTANE 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.

Getting rid of any unwanted medicine

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

Do not use this medicine after the expiry date.

6. Are there any side effects?

ARTANE helps most people with Parkinson's disease, but it may have unwanted side effects in some people.

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.

Common side effects

Common side effectsWhat to do
  • dryness of mouth
  • blurred vision
  • dizziness
  • feeling sick or nausea
  • nervousness
  • worsening of muscle weakness (myasthenia gravis)
Speak to your doctor if you have any of these less serious side effects and they worry you.

These are the more common side effects of ARTANE. These side effects usually go away with time. If they persist you may need to have your dose changed.

Rare effects

Rare side effectsWhat to do
  • swelling of your salivary glands
  • rash
  • bowel problems
  • confusion
  • agitation
  • delusions, or disturbed behaviour
  • seeing, feeling or hearing things that are not there

Other side effects that have been reported in medicines that work the same way as ARTANE include:

  • constipation
  • drowsiness
  • difficulty passing urine
  • fast hear rate
  • enlarged pupils
  • increased pressure in the eye
  • weakness
  • vomiting
  • headache
Speak to your doctor if you have any of these less serious side effects and they worry you.

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 ARTANE contains

Active ingredient
(main ingredient)		2 mg or 5 mg of trihexyphenidyl hydrochloride
Other ingredients
(inactive ingredients)
  • calcium hydrogen phosphate
  • maize starch
  • pregelatinised maize starch
  • magnesium stearate
Potential allergensN/A

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

ARTANE does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

What ARTANE looks like

ARTANE 2 mg tablets are white, round, flat-faced, bevelled edge tablet with break bar on one side and plain on the other. (Aust R 15125)

ARTANE 5 mg tablets are white, round, flat-faced, bevelled edge tablet with break bar on one side and plain on the other. (Aust R 15126)

Both ARTANE 2 mg and 5 mg tablets come in bottles of 200 tablets.

Who distributes ARTANE

Arrotex Pharmaceuticals Pty Ltd
15 - 17 Chapel Street
Cremorne VIC 3121
Australia
www.arrotex.com.au

This leaflet was prepared in January 2025.

Published by MIMS April 2025

BRAND INFORMATION

Brand name

Artane

Active ingredient

Trihexyphenidyl (benzhexol) hydrochloride

Schedule

S4

 

1 Name of Medicine

Trihexyphenidyl (benzhexol) hydrochloride.

2 Qualitative and Quantitative Composition

Artane is supplied in two tablet strengths containing 2 mg and 5 mg trihexyphenidyl hydrochloride.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Artane 2 mg and Artane 5 mg.

White, round, flat-faced, bevelled edge tablet with break bar on one side and plain on the other.

4 Clinical Particulars

4.1 Therapeutic Indications

As an adjunct in the therapy of all forms of parkinsonism (postencephalitis, arteriosclerotic and idiopathic). It is useful in the prevention or control of extrapyramidal disorders due to CNS drugs such as phenothiazines.

4.2 Dose and Method of Administration

Parkinsonism.

Dosage should be individualised. The initial dose should be low and then increased gradually, especially in patients over 60. Whether Artane may best be given before or after meals should be determined by the way the patient reacts. Postencephalitic patients, who are usually more prone to excessive salivation, may prefer to take it after meals and may, in addition, require small amounts of atropine which under such circumstances is sometimes an effective adjuvant. If Artane tends to dry the mouth excessively, it may be better to take it before meals, unless it causes nausea. If taken after meals, mints, chewing gum or water can allay the thirst sometimes induced.
As initial therapy for parkinsonism, 1 mg of Artane in tablet form may be administered the first day. The dose may then be increased by 2 mg increments at intervals of three to five days, until a total of 6 to 10 mg is given daily. The total daily dose will depend upon what is found to be the optimal level. Many patients derive maximum benefit from a daily total of 6 to 10 mg. A daily intake at this dosage level is tolerated best if divided into 3 doses and taken at mealtimes. Some patients, chiefly those in the post-encephalitic group, may require a total daily dose of 12 to 15 mg. High doses (> 10 mg daily) may be divided into 4 parts, with 3 doses administered at mealtimes and the fourth at bedtime.

Concomitant use with other parasympathetic inhibitors.

Artane may be substituted, in whole or part, for other parasympathetic inhibitors. The usual technique is partial substitution initially, with progressive reduction in the other medication as the dose of Artane is increased.

Drug induced parkinsonism.

The size and frequency of dose of Artane needed to control extrapyramidal reactions to commonly employed tranquillisers, notably phenothiazine derivatives, must be determined empirically. The total daily dosage usually ranges between 5 and 15 mg although, in some cases, these reactions have been satisfactorily controlled on as little as 1 mg daily. It may be advisable to commence therapy with a single 1 mg dose. If the extrapyramidal manifestations are not controlled in a few hours, the subsequent doses may be progressively increased until satisfactory control is achieved. Satisfactory control may sometimes be more rapidly achieved by temporarily reducing the dosage of the tranquilliser on instituting Artane therapy and then adjusting dosage of both drugs until the desired ataractic effect is retained without onset of extrapyramidal reactions.
It is sometimes possible to maintain the patient on a reduced Artane dosage after the reactions have remained under control for several days. Instances have been reported in which these reactions have remained in remission for long periods after therapy was discontinued.

4.3 Contraindications

Artane is contraindicated in patients with:
Hypersensitivity to trihexyphenidyl or any other ingredients of the preparation.
Narrow angle glaucoma. Blindness after long-term use due to narrow angle glaucoma has been reported.

4.4 Special Warnings and Precautions for Use

Visual disturbances.

Trihexyphenidyl can induce cycloplegia and mydriasis, resulting in increased intraocular pressure.
Patients to be treated with Artane should have a gonioscopic evaluation and close monitoring of intraocular pressures at regular intervals. The use of anticholinergic drugs may precipitate angle closure with an increase in intraocular pressure. If blurring of vision occurs during therapy, the possibility of narrow angle glaucoma should be considered. Blindness has been reported due to aggravation of narrow angle glaucoma (see Section 4.3 Contraindications; Section 4.8 Adverse Effects (Undesirable Effects)). The anticholinergic effects of trihexyphenidyl may make the eyes dry. This can cause an increased lens awareness, or blurred vision for wearers of contact lenses. The use of lubricating drops may be necessary or, in severe cases, discontinued use of contact lenses while taking Artane.

Anhidrosis.

Artane should be administered with caution in the presence of fever, high environmental temperature and/or during physical exercise, especially when given concomitantly with other atropine-like drugs to the chronically ill, alcoholics, those who have central nervous system disease, or those who do manual labour in a hot environment. Anhidrosis may occur more readily when some disturbance of sweating already exists. If there is evidence of anhidrosis, the possibility of hyperthermia should be considered. Dosage should be decreased so that the ability to maintain body heat equilibrium via perspiration is not impaired. Severe anhidrosis and fatal hyperthermia have occurred with the use of anticholinergics under the conditions described above.

Neuroleptic malignant syndrome.

A potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS) has been reported in association with dose reduction or discontinuation of Artane (see Section 4.4 Special Warnings and Precautions for Use, Abrupt withdrawal of treatment for parkinsonism). Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias).
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g. pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system pathology.

Tardive dyskinesia.

Tardive dyskinesia may appear in some patients on long-term therapy with antipsychotic drugs or may occur after therapy with these drugs has been discontinued. Antiparkinsonism agents do not alleviate the symptoms of tardive dyskinesia and, in some instances, may aggravate them. However, parkinsonism and tardive dyskinesia often co-exist in patients receiving chronic neuroleptic treatment, and anticholinergic therapy with Artane may relieve some of these parkinsonism symptoms. Artane is not recommended for use in patients with tardive dyskinesia unless they have concomitant Parkinson's disease.

Cardiac effects.

Artane has anticholinergic properties; as a result, existing hypertension may be aggravated and tachycardia may occur. Patients at risk (arrhythmia, heart failure, coronary heart disease, mitral stenosis) should be monitored carefully over a prolonged period.
Artane should be used with caution in patients with cardiac disease such as ischaemic heart disease, or with atherosclerosis and hypertension because of its positive chronotropic effect that could cause tachycardia and/or coronary ischaemia.

Patients with arteriosclerosis or with a history of idiosyncrasy to other drugs.

Patients with arteriosclerosis or with a history of idiosyncrasy to other drugs may exhibit reactions of mental confusion, agitation, disturbed behaviour or nausea and vomiting. Such patients should be allowed to develop a tolerance through the initial administration of a small dose with gradual increase in dose until an effective level is reached. If a severe reaction should occur, administration of the drug should be discontinued for a few days and then resumed at a lower dosage.

Psychiatric adverse effects.

The development of psychiatric disturbances may necessitate discontinuation of treatment. See Section 4.8 Adverse Effects (Undesirable Effects).

Drug abuse.

It has been reported that trihexyphenidyl may be deliberately abused for its stimulating and euphoriant effects. Trihexyphenidyl has also been reported to induce vivid visual hallucinations, confusion and delusions. The precise psychopharmacological mechanisms for the euphoria and hallucinations are unclear. It is possible that the drug produces a form of anticholinergic delirium. Euphoric effects may be mediated via catecholamines.

Abrupt withdrawal of treatment for parkinsonism.

Abrupt withdrawal of treatment for parkinsonism may result in acute exacerbation of parkinsonism symptoms. Withdrawal syndrome, characterised by anxiety, tachycardia, orthostatic hypotension and apparent deterioration of sleep quality, may follow discontinuation of long-term trihexyphenidyl therapy. NMS during abrupt treatment withdrawal has also been reported. Therefore, Artane should be slowly titrated down when discontinuing therapy to avoid NMS and other withdrawal adverse events.

Anticholinergic properties.

Since Artane has atropine-like properties, patients should be subjected to constant and careful long-term observation to avoid allergic and other untoward reactions. Early glaucoma may be precipitated by the administration of anticholinergic agents. Artane should be used with caution in patients with glaucoma, obstructive disease of the gastrointestinal or genitourinary tracts and in elderly males with possible prostatic hypertrophy (see Use in the elderly).

Patients with myasthenia gravis.

Since trihexyphenidyl has been associated with the clinical worsening of myasthenia gravis, the drug should be avoided or used with great caution in patients with this condition.

Use in hepatic or renal impairment.

Patients with impaired hepatic or renal function should be maintained under close observation since side effects may be aggravated or increased by any reduction in the metabolism of trihexyphenidyl.

Use in the elderly.

Elderly patients, particularly over the age of 60 years, frequently develop increased sensitivity to the actions of anticholinergic drugs and hence require strict dosage regulation. Elderly patients generally should be started on low doses of Artane and observed closely.
Incipient glaucoma may be precipitated. Artane has been shown to cause some cognitive dysfunctions in the elderly, including confusion, delusions and hallucinations and memory impairment.
Since elderly males are more likely to develop prostatic hypertrophy, they are predisposed to developing urinary retention. The addition of anticholinergic agents in this population may increase this risk.

Paediatric use.

Safety and effectiveness in paediatric patients have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

CNS depressants.

Cannabinoids, barbiturates, opiates and alcohol may have additive effects with Artane, and thus, an abuse potential exists. Alcohol use should be avoided as increased trihexyphenidyl metabolism may occur, which may lead to lower blood concentrations and decreased therapeutic effects.

Anticholinergics.

The concomitant use of Artane with other anticholinergic drugs may produce increased or additive peripheral anticholinergic effects. Monoamine oxidase inhibitors and tricyclic antidepressants possessing significant anticholinergic activity may intensify the anticholinergic effects of antidyskinetic agents including trihexyphenidyl because of the secondary anticholinergic activities of these medications. It should be noted that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye and temperature regulation. This can cause dry mouth, blurred vision, urinary hesitancy, urinary retention and constipation. Additive drowsiness may also occur, depending on the interacting agent.
In general, anticholinergic agents should be used with caution in patients who are receiving tricyclic antidepressants or monoamine oxidase inhibitors. In patients who are already on antidepressant therapy the dose of trihexyphenidyl should be initially reduced and the patient reviewed regularly.

Neuroleptics.

Prophylactic administration of anticholinergic agents, such as Artane, as a prevention of drug induced parkinsonism during neuroleptic therapy is not recommended. There may be an increased risk for the development of tardive dyskinesia during concomitant administration of anticholinergics and neuroleptics. (See Section 4.4 Special Warnings and Precautions for Use, Tardive dyskinesia).

Levodopa.

The usual dose of either Artane or levodopa may need to be reduced during concomitant therapy, since concomitant administration may increase drug induced involuntary movements.

Anticonvulsants.

Exacerbation of seizures in patients with adequately controlled epilepsy has been suggested during initiation of anticholinergic agents such as Artane.

Parasympathomimetics.

The muscarinic actions of parasympathomimetic drugs, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonise the antimuscarinic actions of trihexyphenidyl.

Prokinetic drugs.

The antimuscarinic properties of trihexyphenidyl may pharmacodynamically oppose the effects of prokinetic agents such as metoclopramide, tegaserod and domperidone on gastrointestinal function.

Carbonic anhydrase inhibitors.

Acetazolamide can decrease excretion and enhance the effects of antimuscarinics. Carbonic anhydrase inhibitors increase the alkalinity of the urine, thereby increasing the amount of non-ionised drug available for renal tubular reabsorption. Use caution if carbonic anhydrase inhibitors are administered with Artane and monitor for excessive anticholinergic adverse effects. Through an additive effect, the use of topiramate (a weak carbonic anhydrase inhibitor) with Artane may lead to oligohidrosis, hyperthermia and/or heat stroke.

Magnesium hydroxide.

Magnesium hydroxide inhibits the absorption of trihexyphenidyl. Simultaneous administration should be avoided; separate dosing by at least 2 hours to limit an interaction.

Memantine.

The adverse effects of trihexyphenidyl such as dry mouth, urinary hesitancy or blurred vision may be enhanced with use of memantine; dosage adjustments of Artane may be required when memantine is co-administered.

Foods.

The use of acidic foods such as citrus and fruit juices may decrease the effect of an Artane dose. Large amounts of coffee with Artane use may lead to a euphoric effect.

Other medicines.

Extra care should be taken when trihexyphenidyl is given concomitantly with phenothiazines, clozapine, antihistamines, disopyramide, nefopam and amantadine because of the possibility of increased antimuscarinic side-effects.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B1)
Animal reproduction studies to evaluate teratogenic and embryotoxic potential have not been conducted with Artane. It is also not known whether Artane can cause foetal harm when administered to a pregnant woman or can affect reproduction capacity. In general, Artane should be used during pregnancy only if the potential benefit to the mother justifies the unknown risk to the foetus.
 It is not known whether trihexyphenidyl is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Artane is administered to a nursing woman. As with other anticholinergics, Artane may cause suppression of lactation. Therefore, Artane should only be used if the expected benefit to the mother outweighs the potential risk to the infant.

4.7 Effects on Ability to Drive and Use Machines

Artane may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle. Patients should be cautioned about operating machinery, including motor vehicles, until they are reasonably certain that Artane therapy does not adversely affect their ability to engage in such activities.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions to trihexyphenidyl are mainly extensions of its anticholinergic effects. Adverse side effects, such as dryness of the mouth, blurring of vision, dizziness, mild nausea or nervousness, will be experienced by 30 to 50% of patients. Such reactions tend to become less pronounced and even to disappear as treatment continues. Even before these reactions have remitted spontaneously, they may often be controlled by careful adjustment of dosage form, amount of drug or interval between doses. See Table 1.
In addition to adverse events seen in adults, the following adverse events have been reported in the literature in paediatric patients: hyperkinesia, psychosis, forgetfulness, weight loss, restlessness, chorea, and sleep alterations.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Signs and symptoms.

Overdosage with Artane produces typical central symptoms of atropine intoxication (the central anticholinergic syndrome). Correct diagnosis depends upon recognition of the peripheral signs of parasympathetic blockade, including fever. The most common cardiovascular effects of overdose are tachycardia and hypertension, although with increasing doses cutaneous vasodilation and hypotension may occur. Other reported effects include lip smacking and tasting movements. The condition can progress to stupor, coma, paralysis, cardiac and respiratory arrest and death.

Treatment.

Treatment of acute overdose involves symptomatic and supportive therapy. Activated charcoal may reduce absorption of the drug if given within one to two hours of ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube once the airway is protected. A small dose of diazepam or a short acting barbiturate may be administered if CNS excitation is observed. Phenothiazines are contraindicated because the toxicity may be intensified due to their antimuscarinic action, causing coma. Respiratory support, artificial respiration, or vasopressor agents may be necessary. Hyperpyrexia must be reversed, fluid volume replaced and acid-base balance maintained. Urinary catheterisation may be necessary. It is not known if trihexyphenidyl is dialysable.
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.

Trihexyphenidyl exerts a direct inhibitory effect upon the parasympathetic nervous system. It also has a relaxing effect on smooth musculature, exerted both directly upon the muscle tissue itself and indirectly through an inhibitory effect upon the parasympathetic nervous system. In small doses, trihexyphenidyl has CNS depressant effects, but in larger doses, CNS stimulatory effects similar to those seen with atropine toxicity can occur. Tolerance to the effects of trihexyphenidyl can occur with prolonged use.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Ingredients are calcium hydrogen phosphate, starch-maize, starch - pregelatinised maize 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 30°C.

6.5 Nature and Contents of Container

HDPE bottle of 200 tablets.

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

Chemical structure.

Trihexyphenidyl hydrochloride is chemically defined as 1-cyclohexyl-1-phenyl-3-piperidino-propan-1-ol hydrochloride with a molecular weight of 337.9.
It is a white or creamy-white crystalline powder; odourless or almost odourless and slightly soluble in water.
Molecular formula: C20H31NO, HCl.

CAS number.

52-49-3.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes