SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Benzhexol 5mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 5 mg of Trihexyphenidyl hydrochloride.

For excipients, see section 6.1

3 PHARMACEUTICAL FORM

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:

Drug induced parkinsonism:

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.

Benzhexol 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    Contraindications

Known hypersensitivity to trihexyphenidyl hydrochloride or any of the ingredients.

4.4    Special warnings and precautions for use

Since the use of trihexyphenidyl may, in some cases, continue indefinitely, the patient should be under careful observation over the long term. It should be administered with care to avoid allergic or other untoward reactions.

Except in the case of vital complications, abrupt discontinuation of the drug should be avoided.

Incipient glaucoma may be precipitated by para-sympatholytic drugs such as trihexyphenidyl.

Hypertension, cardiac, liver or kidney disorders are not contraindicated, but such patients should be followed closely.

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

Trihexyphenidyl should be used with caution in patients with glaucoma, obstructive disease of the gastro-intestinal or genito-urinary tracts, and in elderly males with possible prostatic hypertrophy.

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.

Since certain psychiatric manifestations such as confusion, delusions and hallucinations, all of which may occur with any of the atropine-like drugs, have been reported rarely with trihexyphenidyl, it should be used with extreme caution in elderly patients (see Dosage and Administration).

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

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 may be the subject of abuse due to its euphoric or hallucinogenic properties.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsoprtion or sucrase-maltase insufficiency should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Concurrent use of trihexyphenidyl hydrochloride with drugs possessing antimuscarinic effects increases the side-effects such as dry mouth, urine retention and constipation; concomitant use can also lead to confusion in the elderly. Interactions to 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.

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    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 the 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.

4.6 Fertility, 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. Trihexyphenidyl should not be used during pregnancy unless clearly necessary.

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 breast feeding.

4.7    Effects on ability to drive and use machines

Trihexyphenidyl hydrochloride may affect the performance of skilled tasks such as driving and operating machinery as it can cause blurring of vision, dizziness and mild nausea. Also mental confusion in some cases.

4.8    Undesirable effects

Modern clinical data required to determine the frequency of undesirable effects are lacking for trihexyphenidyl. Minor side effects such as dryness of mouth, constipation, blurring of vision, dizziness, mild nausea or nervousness will be experienced by 30-50% of all patients. These reactions tend to become less pronounced as treatment continues. Patients should be allowed to develop a tolerance using the smaller initial dose until an effective level is reached.

Immune system disorders: Hypersensitivity.

Psychiatric disorders: Nervousness, restlessness, confusional states, agitation, delusions, hallucinations, insomnia, especially in the elderly and patients with arteriosclerosis. The development of psychiatric disturbances may necessitate discontinuation of treatment.

Euphoria may occur. There have been reports of abuse of trihexyphenidyl due to its euphoric and hallucinogenic properties.

Nervous system disorders: Dizziness.

Impairment of immediate and short-term memory function has been reported.

Worsening of myasthenia gravis may occur (see section 4.4).

Eye disorders: Dilatation of the pupils with loss of accommodation and photophobia, raised intraocular pressure (see section 4.4).

Cardiac disorders: Tachycardia.

Respiratory, thoracic and mediastinal disorders: Decreased bronchial secretions.

Gastrointestinal disorders: Dry mouth with difficulty swallowing, constipation, nausea, vomiting.

Skin and subcutaneous tissue disorders: Flushing and dryness of skin, skin rashes.

Renal and urinary disorders: Urinary retention, difficulty in micturition. General disorders: Thirst, pyrexia.

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

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. A rash may appear on the face or upper trunk. Symptoms of CNS stimulation include restlessness, confusion, hallucinations, paranoid and psychotic reactions, incoordination, delirium and occasionally convulsions. In severe overdose, CNS depression may occur with coma, circulatory and respiratory failure and death.

Treatment

Treatment should always be supportive. 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.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: anti-cholinergic agents ATC code: NO4A A 01

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 preclinical data of relevance to the presciber which are additional to that already included in other sections of the SPC.

6 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

Plastic Containers: Keep the container tightly closed Blister Packs: Store in the original package

6.5 Nature and contents of container

Trihexyphenidyl tablets 5 mg 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.

6.6 Special precautions for disposal

No special instructions for use/handling.

7    MARKETING AUTHORISATION HOLDER

Ennogen Pharma Limited Unit G4,

Riverside Industrial Estate, Riverside Way,

Dartford DA1 5BS UK

MARKETING AUTHORISATION NUMBER(S)

PL 40147/0012

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

30/01/2009

DATE OF REVISION OF THE TEXT

15/12/2014