SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Trihexyphenidyl 2mg Tablets BP

2.    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 2 mg of trihexyphenidyl hydrochloride BP.

For excipients, see section 6.1.

3.    PHARMACEUTICAL FORM

Tablet

White, flat bevel edged tablets with a breakline.

4.    CLINICAL PARTICULARS

4.1.    Therapeutic indications

1.    Treatment of parkinsonism

2.    Prevention and control of drug-induced extrapyramidal symptoms (excluding tardive dyskinesia)

4.2.    Posology and method of administration

Route of administration: Oral

Dosage Adults (only)

All forms of parkinsonism

Initial dose: 1 - 2 mg gradually increased by 1 - 2 mg increment to 6 - 10 mg

daily according to the patient’s response. Some patients may require 12 - 15 mg daily or more. The maximum daily dose is 20 mg. Postencephalitic patients tolerate and require larger doses.

Drug-induced parkinsonism

Usual dose: 5 - 10 mg daily

Some cases may be controlled with 1 mg daily.

Elderly:    Patients over 65 years of age may require a reduced

dosage.

The above dosage should be administered in 3 - 4 divided doses daily before or with meals.

Antimuscarinic treatment of parkinsonism should never be terminated suddenly.

When changing from one drug to another, withdraw the one in small amounts while gradually increasing the dose of the other.

Trihexyphenidyl tablets may be given with other drugs employed for the relief of parkinsonism e.g. other antimuscarinic drugs, levodopa and amantadine. Dose reduction may be required.

4.3 Contra-indications

Known hypersensitivity to trihexyphenidyl hydrochloride or any of the ingredients. Incipient glaucoma may be precipitated.

The following are not absolute contraindications, nevertheless caution must be observed in patients with hypertension,cardiac, liver or kidney dysfunction, obstructive disease of the gastrointestinal or genitourinary tracts, glaucoma, and in males with a prostatic hypertrophy.

4.4 Special warnings and precautions for use

Anticholinergic medications, including trihexyphenidyl, should not be withdrawn abruptly in patients on long-term therapy, to avoid recurrence of the original symptoms and possible anticholinergic rebound. Prescribers should be aware that Trihexyphenidyl hydrochloride is liable to abuse as it may produce euphoric effects or hallucinogenic properties.

Since atropine-like drugs may cause psychiatric symptoms such as confusion, delusion and hallucinations, trihexyphenidyl should be used with extreme caution in elderly patients.

As trihexyphenidyl may provoke or exacerbate tardive dyskinesia, it is not recommended for use in patients with this condition.

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

Patients with arteriosclerosis or those with a history of idiosyncrasy to other drugs may be more likely to develop severe mental reactions to trihexyphenidyl.

Since the treatment is to be continued for an indefinite period the patient should be carefully supervised over the long term.

Avoid sudden discontinuation of treatment.

Patients with rare hereditary problems of galactose intolerance, the LAPP lactase deficiency, glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interactions

Concurrent use of trihexyphenidyl hydrochloride with drugs possessing antimuscarinic effects such as antihistamines increases the side-effects such as blurred vision, dry mouth, urine retention and constipation; concomitant use can also lead to confusion in the elderly. Interactions do not generally apply to antimuscarinics used by inhalation.

Concurrent use of trihexyphenidyl hydrochloride with nefopam increases antimuscarinic effects.

Concurrent use of tricyclic anti-depressants and monoamine oxidase inhibitors with trihexyphenidyl hydrochloride increases the antimuscarinic side-effects and may also cause excitation, confusion and hallucination.

Concurrent use of trihexyphenidyl hydrochloride with ketoconazole reduces the absorption of the latter.

Concurrent use of trihexyphenidyl with anti-histamine increases the antimuscarinic side-effects.

Concurrent use of trihexyphenidyl hydrochloride with disopyramide increases the antimuscarinic effects.

Concurrent use of trihexyphenidyl hydrochloride with phenothiazines increases the antimuscarinic effect (but reduces plasma concentrations).

Increased antimuscarinic side-effects are observed with amantadine and absorption of levodopa is possibly reduced.

Concurrent use of trihexyphenidyl hydrochloride with metoclopramide and domperidone antagonises gastro-intestinal effects.

Antimuscarinics reduce the effects of sublingual nitrates due to failure to dissolve under the tongue owing to dry mouth.

Parasympathomimetics antagonise the effects of antimuscarinics.

Use during pregnancy and lactation

Pregnancy

There is inadequate information regarding the use of trihexyphenidyl in pregnancy. Animal studies are insufficient with regard to effects on pregnancy, embryonal/foetal development, parturition and postnatal development. The potential risk for humans is unknown, As with other medication trihexyphenidyl hydrochloride tablets should only be used during pregnancy if considered essential by the physician.

Lactation

It is unknown whether trihexyphenidyl is excreted in human breast milk. The excretion of trihexyphenidyl in milk has not been studied in animals. Infants may be very sensitive to the effects of antimuscarinic medications. Trihexyphenidyl should not be used during breastfeeding.

4.7 Effects on ability to drive and use machines

Patients should be warned of the potential hazards of driving or operating machinery if they experience blurred vision or a reduction in alertness. Trihexyphenidyl hydrochloride may affect the performance of skilled tasks such as driving and using machinery.

4.8 Undesirable effects

Minor adverse effects include dry mouth, constipation, blurred vision, dizziness and gastro-intestinal disturbances and will be experienced by 30 - 50% of all patients treated. This is more frequent in the elderly but reduces with tolerance. Less commonly urinary retention, tachycardia, hypersensitivity, nervousness and with high doses in susceptible patients, mental confusion, excitement or euphoria, agitation, hallucinations, insomnia, restlessness and very occasionally paranoid delusions have been reported. There have been reports of abuse of trihexiphenidyl due to its euphoric and hallucinogenic properties and psychiatric disturbances which may necessitate discontinuation of treatment; impaired memory (immediate and short-term memory functions) has also been reported.

Reporting of suspected adverse reactions:

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose symptoms, emergency procedures, antidotes

Symptoms of overdose with antimuscarinic agents include flushing and dryness of the skin, dilated pupils, dry mouth and tongue, tachycardia, rapid respiration, hyperpyrexia, hypertension, nausea, vomiting. Symptoms of CNS stimulation include marked restlessness, confusion, excitement, paranoid and psychotic reactions, incoordination, hallucination and delirium and occasionally seizures or convulsions. A rash may appear on the face and upper trunk. In severe intoxication central stimulation may give way to CNS depression, coma, circulatory and respiratory failure and death.

Treatment entails gastric lavage as there is no specific antidote. General supportive treatment should be carried out. Cold compresses and forcing of fluid are mandatory. Atropine antagonists may be useful. An adequate airway should be maintained. Diazepam may be administered to control excitement and convulsions but the risk of central nervous system depression should be considered. Hypoxia and acidosis should be corrected. Antiarrhythmic drugs are not recommended if dysrhythmias occur.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Anticholinergic agents; tertiary amines ATC code: N04A A01

Trihexyphenidyl hydrochloride is an antimuscarinic agent with both central and peripheral actions. The stimulation of the CNS is followed by depression. It is also an antispasmodic agent exerting a direct inhibitory effect on the parasympathetic nervous system and also has a relaxing effect on the smooth muscles and reduces secretions especially the salivary and the bronchial. It also reduces perspiration. The biliary and pancreatic secretions are little affected.

5.2. Pharmacokinetic properties

Trihexyphenidyl hydrochloride is well absorbed from the gastro-intestinal tract. The onset of action occurs within 1 hour of oral administration.

5.3. Preclinical safety data

There are no pre-clinical data of relevance to the prescriber that are additional to that already included in other sections of the SPC.

PHARMACEUTICAL PARTICULARS

6.1. List of excipients

Magnesium stearate Maize starch

Pregelatinised maize starch Lactose

6.2. Incompatibilities

None.

6.3. Shelf life

5 years for opaque plastic containers.

2 years for aluminium/opaque PVC blister packs.

6.4. Special precautions for storage

Store in a cool dry place.

Keep out of the reach of children.

6.5. Nature and contents of container

Trihexyphenidyl 2mg Tablets BP are packed in the following containers and closures.

Opaque plastic containers (securitainers) with plastic caps for all pack sizes.

Opaque plastic container composed of either high density polypropylene or high density polyethylene with a tamper-evident or child resistant tamper evident closure composed of high density polyethylene for all pack sizes (28, 30, 42, 50, 56, 60, 84, 90, 100, 112, 250, 500 and 1000) and packaging inclusion of standard polyether foam or polyethylene or polypropylene made filler.

Blister packs of aluminium/opaque PVC. It is subsequently packed in printed boxboard cartons in pack sizes of 28, 30, 42, 56, 60, 84, 90 and 112.

Not all pack sizes may be marketed.

6.6. Instructions for use/handling

No special instructions for use/handling.

7. MARKETING AUTHORISATION HOLDER

Crescent Pharma Limited.

Units 3 and 4

Quidhampton Business Units Polhampton Lane Overton

Hants RG25 3ED, UK

8. MARKETING AUTHORISATION NUMBER(S)

PL 20416/0029

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

13 February 2004

10 DATE OF REVISION OF THE TEXT

15/07/2015