Voltarol 25mg, 50mg Rapid Tablets

VOLTAROL Rapid Tablets 25 and 50 mg

(diclofenac potassium)

What you need to know about Voltarol Rapid Tablets

Your doctor has decided that you need this medicine to help treat your condition.

Please read this leaflet carefully before you start to take your medicine. It contains important information. Keep the leaflet in a safe place because you may want to read it again.

If you have any other questions, or if there is something you don’t understand, please ask your doctor or pharmacist.

This medicine has been prescribed for you. Never give it to someone else. It may not be the right medicine for them even if their symptoms seem to be the same as yours.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

• 1. What Voltarol Rapid Tablets are, and what they are used for


• 2. Things to consider before you start to take Voltarol Rapid Tablets


• 3. How to take Voltarol Rapid Tablets


• 4. Possible side effects


• 5. How to store Voltarol Rapid Tablets


• 6. Further information

What Voltarol Rapid Tablets are and what they are used for

Diclofenac potassium, the active ingredient in Voltarol Rapid Tablets, is one of a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs reduce pain and inflammation.

Voltarol Rapid Tablets relieve pain, reduce swelling and ease inflammation in:

• Rheumatoid arthritis, osteoarthrosis, acute gout, low back pain, ankylosing spondylitis


• Migraine


• Conditions affecting the joints and muscles such as sprains and strains, soft tissue sports injuries, frozen shoulder, dislocations, and fractures


• Conditions affecting the tendons for example, tendonitis, tenosynovitis, bursitis.

They are also used to treat pain and inflammation associated with orthopaedic, dental and other minor surgery.

Things to consider before you start to take Voltarol Rapid Tablets

Some people MUST NOT take Voltarol Rapid Tablets. Talk to your doctor if:

• you think you may be allergic to diclofenac potassium, aspirin, ibuprofen or any other NSAID, or to any of the other ingredients of Voltarol Rapid Tablets. (These are listed at the end of the leaflet.) Signs of a hypersensitivity reaction include swelling of the face and mouth (angioedema), breathing problems, runny nose, skin rash or any other
  allergic type reaction


• you have now, or have ever had, a stomach (gastric) or duodenal (peptic) ulcer, or bleeding in the digestive tract (this can include blood in vomit, bleeding when emptying bowels, fresh blood in faeces or black, tarry faeces)


• you have had stomach or bowel problems after you have taken other NSAIDs


• you have severe heart, kidney or liver failure


• you are more than six months pregnant.

You should also ask yourself these questions before taking Voltarol Rapid Tablets:

• Do you suffer from any stomach or bowel disorders including ulcerative colitis or Crohn's disease?


• Do you have kidney or liver problems, or are you elderly?


• Do you have a condition called porphyria?


• Do you suffer from any blood or bleeding disorder? If you do, your doctor may ask you to go for regular check-ups while you are taking these tablets.


• Have you ever had asthma?


• Are you breast-feeding?


• Do you have heart problems, or have you had a stroke, or do you think you might be at risk of these conditions (for example, if you have high blood pressure, diabetes, or high cholesterol or are a smoker)?


• Do you have Lupus (SLE) or any similar condition?


• Do you have an intolerance to some sugars such as sucrose? (Voltarol Rapid Tablets contain sucrose.)

If the answer to any of these questions is YES, discuss your treatment with your doctor or pharmacist because Voltarol Rapid Tablets might not be the right medicine for you.

Are you taking other medicines?

Some medicines can interfere with your treatment. Tell your doctor or pharmacist if you are taking any of the following:

• Medicines to treat diabetes


• Anticoagulants (blood thinning tablets like warfarin)


• Diuretics (water tablets)


• Lithium (used to treat some mental problems)


• Methotrexate (for some inflammatory diseases and some cancers)


• Ciclosporin or tacrolimus (used to treat some inflammatory diseases and after transplants)


• Quinolone antibiotics (for infections)


• Any other NSAID or COX-2 (cyclo-oxgenase-2) inhibitor, for example aspirin or ibuprofen


• Mifepristone (a medicine used to terminate pregnancy)


• Cardiac glycosides (for example digoxin), used to treat heart problems


• Medicines known as SSRIs used to treat depression


• Oral steroids (an anti-inflammatory drug)


• Medicines used to treat heart conditions or high blood pressure, for example beta blockers or ACE inhibitors.

Always tell your doctor or pharmacist about all the medicines you are taking. This means medicines you have bought yourself as well as medicines on prescription from your doctor.

Pregnancy

• Are you pregnant or planning to become pregnant? Although not common, abnormalities have been reported in babies whose mothers have taken NSAIDs during pregnancy. You should not take Voltarol Rapid Tablets during the last 3 months of pregnancy as it may affect the baby’s circulation.


• Are you trying for a baby? Taking Voltarol Rapid Tablets may make it more difficult to conceive. You should talk to your doctor if you are planning to become pregnant, or if you have problems getting pregnant.

Will there be any problems with driving or using machinery?

Very occasionally people have reported that Voltarol Rapid Tablets have made them feel dizzy, tired or sleepy. Problems with eyesight have also been reported. If you are affected in this way, you should not drive or operate machinery.

Other special warnings

• You should take the lowest dose of Voltarol for the shortest possible time, particularly if you are underweight or elderly.


• There is a small increased risk of heart attack or stroke when you are taking any medicine like Voltarol. The risk is higher if you are taking high doses for a long time. Always follow the doctor’s instructions on how much to take and how long to take it for.


• Whilst you are taking these medicines your doctor may want to give you a check-up from time to time.


• If you have a history of stomach problems when you are taking NSAIDs, particularly if you are elderly, you must tell your doctor straight away if you notice any unusual symptoms.


• Because it is an anti-inflammatory medicine, Voltarol may reduce the symptoms of infection, for example, headache and high temperature. If you feel unwell and need to see a doctor, remember to tell him or her that you are taking Voltarol.

How to take Voltarol Rapid Tablets

The doctor will tell you how many Voltarol Rapid Tablets to take and when to take them. Always follow his/her instructions carefully. The dose will be on the pharmacist’s label. Check the label carefully. If you are not sure, ask your doctor or pharmacist. Keep taking your tablets for as long as you have been told, unless you have any problems. In that case, check with your doctor.

Take the tablets with or after food.

Voltarol Rapid Tablets are specially formulated to act quickly. Swallow the tablets whole with a drink of water. Do not crush or chew them.

The usual doses are:

Adults

75 mg to 150 mg daily divided into two or three doses. The number of tablets you take will depend on the strength the doctor has given you.

For the relief of migraine in adults:

Take 50 mg at the first signs of an attack. If the migraine has not gone after 2 hours, take another 50 mg. You can take further doses at intervals of 4 to 6 hours if necessary, but you must not take more than 200 mg in a day.

Elderly

Your doctor may advise you to take a dose that is lower than the usual adult dose if you are elderly. Your doctor may also want to check closely that the Voltarol Rapid Tablets are not affecting your stomach.

Children over 14

75 mg to 100 mg daily divided into two or three doses.

Voltarol Rapid Tablets are not recommended for children under 14. They are not recommended for the treatment of migraine in children of any age.

The doctor may also prescribe another drug to protect the stomach to be taken at the same time, particularly if you have had stomach problems before, or if you are elderly, or taking certain other drugs as well.

What if you forget to take a dose?

If you forget to take a dose, take one as soon as you remember. If it is nearly time for your next dose, though, just take the next dose and forget about the one you missed. Do not double up on the next dose to make up for the one missed. Do not take more than 150 mg (three 50 mg tablets or six 25 mg tablets) in 24 hours.

What if you take too many tablets?

If you, or anyone else, accidentally takes too much, tell your doctor or your nearest hospital casualty department. Take your medicine pack with you so that people can see what you have taken.

Possible side effects

Voltarol Rapid Tablets are suitable for most people, but, like all medicines, they can sometimes cause side effects.

Some side effects can be serious

Stop taking Voltarol Rapid Tablets and tell your doctor straight away if you notice:

• Stomach pain, indigestion, heartburn, wind, nausea (feeling sick) or vomiting (being sick)


• Any sign of bleeding in the stomach or intestine, for example, when emptying your bowels, blood in vomit or black, tarry faeces


• Allergic reactions which can include skin rash, itching, bruising, painful red areas, peeling or blistering


• Wheezing or shortness of breath (bronchospasm)


• Swollen face, lips, hands or fingers


• Yellowing of your skin or the whites of your eyes


• Persistent sore throat or high temperature


• An unexpected change in the amount of urine produced and/or its appearance.

If you notice that you are bruising more easily than usual or have frequent sore throats or infections, tell your doctor.

The side effects listed below have also been reported.

Up to 1 in 10 people have experienced:

• Stomach pain, heartburn, nausea, vomiting, diarrhoea, indigestion, wind, loss of appetite


• Headache, dizziness, vertigo


• Skin rash or spots


• Raised levels of liver enzymes in the blood.

Between 1 in 100,000 and 1 in 100 people have experienced:

• Stomach ulcers or bleeding (there have been very rare reported cases resulting in death, particularly in the elderly)


• Drowsiness, tiredness


• Hypotension (low blood pressure, symptoms of which may include faintness, giddiness or light headedness)


• Skin rash and itching


• Fluid retention, symptoms of which include swollen ankles


• Liver function disorders, including hepatitis and jaundice.

Isolated side-effects, reported in less than 1 in 100,000 people include:

Effects on the nervous system:

Tingling or numbness in the fingers, tremor, blurred or double vision, hearing loss or impairment, tinnitus (ringing in the ears), sleeplessness, nightmares, mood changes, depression, anxiety, mental disorders, confusion, hallucinations, malaise, disorientation and loss of memory, fits, headaches together with a dislike of bright lights, fever and a stiff neck, disturbances in sensation.

Effects on the stomach and digestive system:

Constipation, inflammation of the tongue, mouth ulcers, taste changes, lower gut disorders (including inflammation of the colon).

Effects on the heart, chest or blood:

Palpitations (fast or irregular heart beat), chest pain, hypertension (high blood pressure), inflammation of blood vessels (vasculitis), inflammation of the lung (pneumonitis), congestive heart failure, blood disorders (including anaemia), heart attack, stroke.

Effects on the liver or kidneys:

Kidney or liver disorders, presence of blood or protein in the urine.

Effects on skin or hair:

Serious skin rashes including Stevens-Johnson syndrome and Lyell’s syndrome and other skin rashes which may be made worse by exposure to sunlight.

Hair loss.

Other effects:

Inflammation of the pancreas, impotence.

Medicines such as diclofenac may be associated with a small increased risk of heart attack or stroke.

Do not be alarmed by this list - most people take Voltarol Rapid Tablets without any problems.

If any of the symptoms become troublesome, or if you notice anything else not mentioned here, please go and see your doctor. He/she may want to give you a different medicine.

How to store Voltarol Rapid Tablets

Store in a dry place, below 30°C. Keep the tablets in their original pack.

Keep out of the reach and sight of children.

Do not take Voltarol Rapid Tablets after the expiry date which is printed on the outside of the pack.

If your doctor tells you to stop taking the tablets, please take any unused tablets back to your pharmacist to be destroyed. Do not throw them away with your normal household water or waste. This will help to protect the environment.

Further information

The sugar-coated tablets come in two strengths containing either 25 mg or 50 mg of the active ingredient, diclofenac potassium.

The tablets also contain the inactive ingredients silica, calcium phosphate, magnesium stearate, maize starch, sodium starch glycollate, povidone, microcrystalline cellulose, red iron oxide (E172), macrogol, sucrose, talc and titanium dioxide (E171).

The tablets come in blister packs containing 2, 3, 28 or 30 tablets. Some of the pack sizes may not be marketed.

The Product licence holder is

Novartis Pharmaceuticals UK Limited

trading as Geigy Pharmaceuticals

Frimley Business Park

Frimley

Camberley

Surrey

GU16 7SR

England

Voltarol Rapid Tablets are released on to the market by

Novartis Pharmaceuticals UK Ltd

Wimblehurst Road

West Sussex

RH12 5AB

England

This leaflet was revised in March 2009.

If you would like any more information, or would like the leaflet in a different format, please contact Medical Information at Novartis Pharmaceuticals UK Ltd, telephone number 01276 698370.

VOLTAROL is a registered trade mark

Copyright Novartis Pharmaceuticals UK Limited

Flixotide Diskhaler 100 mcg

1. Name Of The Medicinal Product

Flixotide_TM Diskhaler_TM100 Micrograms

2. Qualitative And Quantitative Composition

Fluticasone Propionate (micronised) 100 micrograms

3. Pharmaceutical Form

Inhalation Powder.

4. Clinical Particulars

4.1 Therapeutic Indications

Fluticasone propionate given by inhalation offers preventative treatment for asthma. At recommended doses it has a potent glucocorticoid anti-inflammatory action within the lungs, with a lower incidence and severity of adverse effects than those observed when corticosteroids are administered systemically.

Prophylactic management in: -

Adults

Mild asthma:

Patients requiring intermittent symptomatic bronchodilator asthma medication on a regular daily basis.

Moderate asthma:

Patients with unstable or worsening asthma despite prophylactic therapy or bronchodilator alone.

Severe asthma:

Patients with severe chronic asthma and those who are dependent on systemic corticosteroids for adequate control of symptoms. On introduction of inhaled fluticasone propionate many of these patients may be able to reduce significantly, or to eliminate, their requirement for oral corticosteroids.

Children:

Any child who requires prophylactic medication, including patients not controlled on currently available prophylactic medication.

Route of administration: by inhalation.

4.2 Posology And Method Of Administration

The onset of therapeutic effect is within 4 to 7 days.

Adults and children over 16 years: 100 to 1,000 micrograms twice daily.

Patients should be given a starting dose of inhaled fluticasone propionate, which is appropriate to the severity of their disease.

Prescribers should be aware that fluticasone propionate is as effective as other inhaled steroids approximately at half the microgram daily dose. For example, a 100mcg of fluticasone propionate is approximately equivalent to 200mcg dose of beclometasone dipropionate (CFC containing) or budesonide

Due to the risk of systemic effects, doses above 500 micrograms twice daily should be prescribed only for adult patients with severe asthma where additional clinical benefit is expected, demonstrated by either an improvement in pulmonary function and/or symptom control, or by a reduction in oral corticosteroid therapy (see 4.4 Special Warnings and Precautions for Use and 4.8 Undesirable Effects).

Typical Adult Starting Doses:

For patients with mild asthma, a typical starting dose is 100 micrograms twice daily. In moderate and more severe asthma, starting doses may need to be 250 to 500 micrograms twice daily. Where additional clinical benefit is expected, doses of up to 1000 micrograms twice daily may be used. Initiation of such doses should be prescribed only by a specialist in the management of asthma (such as a consultant physician or general practitioner with appropriate experience).

The dose should be titrated down to the lowest dose at which effective control of asthma is maintained.

Typical starting doses for children over 4years of age:

50 to 100 micrograms twice daily .

Many children's asthma will be well controlled using the 50 to 100 microgram twice daily dosing regime. For those patients whose asthma is not sufficiently controlled, additional benefit may be obtained by increasing the dose up to 200 micrograms twice daily. The maximum licensed dose in children is 200 micrograms twice daily.

The starting dose should be appropriate to the severity of the disease. The dose should be titrated down to the lowest dose at which effective control of asthma is maintained.

Special patient groups:

There is no need to adjust the dose in elderly patients or those with hepatic or renal impairment.

4.3 Contraindications

Flixotide preparations are contra-indicated in patients with a history of hypersensitivity to any of their components.

4.4 Special Warnings And Precautions For Use

Flixotide Diskhalers are not designed to relieve acute symptoms for which an inhaled short acting bronchodilator is required. Patients should be advised to have such rescue medication available.

Severe asthma requires regular medical assessment, including lung-function testing, as patients are at risk of severe attacks and even death. Increasing use of short-acting inhaled β₂-agonists to relieve symptoms indicates deterioration of asthma control. If patients find that short-acting relief bronchodilator treatment becomes less effective, or they need more inhalations than usual, medical attention must be sought.

In this situation patients should be reassessed and consideration given to the need for increased anti-inflammatory therapy (e.g. higher doses of inhaled corticosteroids or a course of oral corticosteroids). Severe exacerbations of asthma must be treated in the normal way.

There have been very rare reports of increases in blood glucose levels, in patients with or without a history of diabetes mellitus (See 4.8 'Undesirable Effects'). This should be considered in particular when prescribing to patients with a history of diabetes mellitus.

As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. Flixotide Diskhaler should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.

Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). It is important therefore that the dose of inhaled corticosteroid is reviewed regularly and reduced to the lowest dose at which effective control of asthma is maintained.

Prolonged treatment with high doses of inhaled corticosteroids may result in adrenal suppression and acute adrenal crisis. Children aged < 16 years taking higher than licensed doses of fluticasone (typically

It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of inhaled corticosteroid, if possible, to the lowest dose at which effective control of asthma is maintained. In addition, consideration should be given to referring the patient to a paediatric respiratory specialist.

When changing from a dry powder inhaler to a metered dose inhaler, administration of high doses, above 1000 mcg daily, is recommended through a spacer to reduce side effects in the mouth and throat. However, this may increase drug delivery to the lungs. As systemic absorption is largely through the lungs, there may be an increase in the risk of systemic adverse effects. A lower dose may be required.

The benefits of inhaled fluticasone propionate should minimise the need for oral steroids. However, patients transferred from oral steroids, remain at risk of impaired adrenal reserve for a considerable time after transferring to inhaled fluticasone propionate. The possibility of adverse effects may persist for some time.

These patients may require specialised advice to determine the extent of adrenal impairment before elective procedures. The possibility of residual impaired adrenal response should always be considered in emergency (medical or surgical) and elective situations likely to produce stress, and appropriate corticosteroid treatment considered.

Lack of response or severe exacerbations of asthma should be treated by increasing the dose of inhaled fluticasone propionate and, if necessary, by giving a systemic steroid and/or an antibiotic if there is an infection.

For the transfer of patients being treated with oral corticosteroids:

The transfer of oral steroid-dependent patients to Flixotide and their subsequent management needs special care as recovery from impaired adrenocortical function, caused by prolonged systemic steroid therapy, may take a considerable time.

Patients who have been treated with systemic steroids for long periods of time or at a high dose may have adrenocortical suppression. With these patients adrenocortical function should be monitored regularly and their dose of systemic steroid reduced cautiously.

After approximately a week, gradual withdrawal of the systemic steroid is started by reducing the daily dose by one milligram prednisolone, or its equivalent. For maintenance doses of prednisolone in excess of 10mg daily, it may be appropriate to cautiously use larger reductions in dose at weekly intervals.

Some patients feel unwell in a non-specific way during the withdrawal phase despite maintenance or even improvement of the respiratory function. They should be encouraged to persevere with inhaled fluticasone propionate and to continue withdrawal of systemic steroid, unless there are objective signs of adrenal insufficiency.

Patients transferred from oral steroids whose adrenocortical function is still impaired should carry a steroid warning card indicating that they need supplementary systemic steroid during periods of stress, e.g. worsening asthma attacks, chest infections, major intercurrent illness, surgery, trauma, etc.

Replacement of systemic steroid treatment with inhaled therapy sometimes unmasks allergies such as allergic rhinitis or eczema previously controlled by the systemic drug. These allergies should be symptomatically treated with antihistamine and/or topical preparations, including topical steroids.

Treatment with Flixotide Diskhalers should not be stopped abruptly.

Special care is necessary in patients with active or quiescent pulmonary tuberculosis.

Ritonavir can greatly increase the concentration of fluticasone propionate in plasma. Therefore, concomitant use should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side-effects. There is also an increased risk of systemic side effects when combining fluticasone propionate with other potent CYP3A inhibitors (see 4.5 Interaction with Other Medicinal Products and Other Forms of Interaction).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after inhaled dosing, due to extensive first pass metabolism and high systemic clearance mediated by cytochrome P450 3A4 in the gut and liver. Hence, clinically significant drug interactions mediated by fluticasone propionate are unlikely.

In an interaction study in healthy subjects with intranasal fluticasone propionate, ritonavir (a highly potent cytochrome P450 3A4 inhibitor) 100 mg b.i.d. increased the fluticasone propionate plasma concentrations several hundred fold, resulting in markedly reduced serum cortisol concentrations. Information about this interaction is lacking for inhaled fluticasone propionate, but a marked increase in fluticasone propionate plasma levels is expected. Cases of Cushing's syndrome and adrenal suppression have been reported. The combination should be avoided unless the benefit outweighs the increased risk of systemic glucocorticoid side-effects.

In a small study in healthy volunteers, the slightly less potent CYP3A inhibitor ketoconazole increased the exposure of fluticasone propionate after a single inhalation by 150%. This resulted in a greater reduction of plasma cortisol as compared with fluticasone propionate alone. Co-treatment with other potent CYP3A inhibitors, such as itraconazole, is also expected to increase the systemic fluticasone propionate exposure and the risk of systemic side-effects. Caution is recommended and long-term treatment with such drugs should if possible be avoided.

4.6 Pregnancy And Lactation

There is inadequate evidence of safety of fluticasone propionate in human pregnancy. Administration of corticosteroids to pregnant animals can cause abnormalities of fetal development, including cleft palate and intra-uterine growth retardation. There may therefore be a very small risk of such effects in the human fetus. It should be noted, however, that the fetal changes in animals occur after relatively high systemic exposure. Because fluticasone propionate is delivered directly to the lungs by the inhaled route it avoids the high level of exposure that occurs when corticosteroids are given by systemic routes.

Administration of fluticasone propionate during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus.

The secretion of fluticasone propionate in human breast milk has not been investigated. Subcutaneous administration of fluticasone propionate to lactating laboratory rats produced measurable plasma levels and evidence of fluticasone propionate in the milk. However, plasma levels in humans after inhalation at recommended doses are likely to be low.

When fluticasone propionate is used in breast feeding mothers the therapeutic benefits must be weighed against the potential hazards to mother and baby.

4.7 Effects On Ability To Drive And Use Machines

Fluticasone propionate is unlikely to produce an effect.

4.8 Undesirable Effects

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (

System Organ Class	Adverse Event	Frequency
Infections & Infestations	Candidiasis of the mouth and throat Pneumonia (in COPD patients)	Very Common Common
Immune System Disorders	Hypersensitivity reactions with the following manifestations: Cutaneous hypersensitivity reactions Angioedema (mainly facial and oropharyngeal oedema), Respiratory symptoms (dyspnoea and/or bronchospasm), Anaphylactic reactions	Uncommon Very Rare Very Rare Very Rare
Endocrine Disorders	Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataract, glaucoma	Very Rare
Metabolism & Nutrition Disorders	Hyperglycaemia (see 4.4 'Special Warnings and Precautions for Use')	Very Rare
Gastrointestinal Disorders	Dyspepsia	Very Rare
Musculoskeletal & Connective Tissue Disorders	Arthralgia	Very Rare
Psychiatric Disorders	Anxiety, sleep disorders, behavioural changes, including hyperactivity and irritability (predominantly in children) Depression, aggression (predominantly in children)	Very Rare Not known
Respiratory, Thoracic & Mediastinal Disorders	Hoarseness/dysphonia Paradoxical bronchospasm	Common Very Rare
Skin & Subcutaneous Tissue Disorders	Contusions	Common

Hoarseness and candidiasis of the mouth and throat (thrush) occurs in some patients. Such patients may find it helpful to rinse out their mouth with water after using the Diskhaler. Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst still continuing with the Flixotide Diskhaler.

Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation, decreased bone mineral density, cataract, glaucoma.(see 4.4 Special Warnings and Special Precautions for Use).

As with other inhalation therapy, paradoxical bronchospasm may occur (see 4.4 'Special Warnings and Precautions for Use'). This should be treated immediately with a fast-acting inhaled bronchodilator. Flixotide Diskhaler should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted.

There was an increased reporting of pneumonia in studies of patients with COPD receiving FLIXOTIDE 500 micrograms. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbation frequently overlap.

4.9 Overdose

Acute: Inhalation of the drug in doses in excess of those recommended may lead to temporary suppression of adrenal function. This does not necessitate emergency action being taken.

In these patients treatment with fluticasone propionate by inhalation should be continued at a dose sufficient to control asthma adrenal function recovers in a few days and can be verified by measuring plasma cortisol.

Chronic: refer to section 4.4: risk of adrenal suppression.

Monitoring of adrenal reserve may be indicated. Treatment with inhaled fluticasone propionate should be continued at a dose sufficient to control asthma.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Fluticasone propionate given by inhalation at recommended doses has a potent glucocorticoid anti-inflammatory action within the lungs, with a lower incidence and severity of adverse effects than those observed when corticosteroids are administered systemically.

5.2 Pharmacokinetic Properties

Systemic absolute bioavailability of fluticasone propionate is estimated at 12-26% of an inhaled dose, dependent on presentation. Systemic absorption occurs mainly through the lungs and is initially rapid then prolonged. The remainder of the dose may be swallowed.

Absolute oral bioavailability is negligible (<1%) due to a combination of incomplete absorption from the GI tract and extensive first-pass metabolism. 87-100% of an oral dose is excreted in the faeces, up to 75% as parent compound. There is also a non-active major metabolite.

After an intravenous dose, fluticasone propionate is extensively distributed in the body. The very high clearance rate indicates extensive hepatic clearance.

5.3 Preclinical Safety Data

No clinically relevant findings were observed in preclinical studies.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose Ph Eur

6.2 Incompatibilities

None known

6.3 Shelf Life

24 months

6.4 Special Precautions For Storage

Whilst the disks provide good protection to the blister contents from the effects of the atmosphere, they should not be exposed to extremes of temperature and should not be stored above 30^oC. A disk may be kept in the diskhaler at all times but a blister should only be pierced immediately prior to use. Failure to observe this instruction will affect the operation of the diskhaler.

6.5 Nature And Contents Of Container

A circular double-foil (PVC/Aluminium) disk with four blisters, containing a mixture of fluticasone propionate and lactose. The foil disk is inserted into the Diskhaler device.

The following packs are registered: 5, 7, 10, 14 or 15 disks with or without a diskhaler. Refill packs of 5, 7, 10, 14 or 15 disks. A starter pack consisting of diskhaler pre-loaded with one disk (with or without a peak flow meter and diary card). A starter pack plus a spare disk (with or without a peak flow meter and diary card).

The following packs are marketed: cartons containing 14 disks (14x4 blisters), together with a Diskhaler inhaler. Cartons containing 5 disks (5x4 blisters) together with a Diskhaler inhaler (250 micrograms and 500 micrograms hospital packs only). Refill packs containing 14 disks (14x4 blisters).

6.6 Special Precautions For Disposal And Other Handling

See Patient Information Leaflet for detailed instructions.

Administrative Data

7. Marketing Authorisation Holder

Glaxo Wellcome UK Ltd

trading as Allen & Hanburys

Stockley Park West

Uxbridge,

Middlesex

UB11 1BT

8. Marketing Authorisation Number(S)

PL 10949/0006

9. Date Of First Authorisation/Renewal Of The Authorisation

25 February 1993

10. Date Of Revision Of The Text

23 August 2011

11. LEGAL STATUS

POM.

DOLPIN Haloperidol Oral Solution BP 5 mg / 5 ml

1. Name Of The Medicinal Product

DOLPIN Haloperidol Oral Solution BP 5 mg/5 ml

2. Qualitative And Quantitative Composition

Each 5 ml contains 5 mg of Haloperidol

3. Pharmaceutical Form

Oral Solution

4. Clinical Particulars

4.1 Therapeutic Indications

Psychotic disorders - schizophrenia, mania and hypomania, especially paranoid psychoses. Mental or behavioural problems such as aggression, hyperactivity and self - mutilation in the mentally retarded. As an adjunct to the short term management of moderate to severe psychomotor agitation, excitement, violent or dangerously impulsive behaviour. Gilles de la Tourette syndrome, intractable hiccup and severe tics. Childhood behaviour disorders, especially when associated with hyperactivity and aggression. Restlessness and agitation in the elderly. Nausea and vomiting.

4.2 Posology And Method Of Administration

For all indications dosage should be individually determined, depending on the patient's response. The initiation and titration of treatment should be under close clinical supervision.

The minimum clinically effective dose should be used.

The initial dose should be determined with consideration of the patient's age, severity of symptoms and previous response to neuroleptics. In the elderly and debilitated and those with previously reported adverse reactions to neuroleptic drugs, the recommended starting dose given below should be halved. This can be gradually titrated to achieve an optimal response.

Higher doses than those recommended should only be considered in patients who have responded poorly at a lower dose.

All patients should, once control has been achieved, have their doses gradually reduced and the minimal effective maintenance dose determined.

An oral syringe is included in the pack to assist with administering the correct dose.

IN ADULTS

For the treatment of; -Schizophrenia, mania and hypomania, as an adjunct to the short term management of moderate to severe psychomotor agitation, excitement, violent or dangerously impulsive behaviour, mental and behavioural problems, restlessness and agitation in the elderly.

Initial Dose;- Moderate Symptomatology - 1.5-3.0mg (1.5-3.0ml) bd or tds.

Severe Symptomatology- 3.0-5.0mg (3.0-5.0ml) bd or tds.

For elderly or debilitated patients half the initial adult dose is recommended.

Adolescents should receive the same doses though may in exceptional circumstance require up to a maximum of 30mg(30ml, 6 x 5ml spoonfuls) daily

Maintenance Dose;-

Once the control of symptoms has been achieved the dose should be gradually reduced to the lowest effective maintenance dose, typically 1-2mg (1-2ml) three to four times daily.

A rapid reduction in dose should be avoided.

For the treatment of;-

Gilles de la Tourette Syndrome, severe tic and intractable hiccup

Initial Dose:- 1.5mg (1.5ml) tds adjusted according to response

Maintenance Dose:-

Once the control of symptoms has been achieved the dose should be gradually reduced to the lowest effective maintenance dose. In Gilles de la Tourette Syndrome a daily maintenance dose of 10 ml may be required.

In general for all conditions the maximum daily dose is 30 mg.

IN CHILDREN

For the treatment of;-

Childhood behavioural disorders

A total daily maintenance dose of 0.025-0.05 mg/kg/day, up to a maximum of 10ml daily. Half the total dose should be given in the morning, the remaining half in the evening.

AGE	IDEAL BODY WEIGHT (kg)	DAILY DOSE (ml) 0.025 - 0.05 mg/kg body weight/day	TWICE DAILY DOSAGE (ml) Morning & Evening
New born	3.4	0.09 - 0.17	0.04 - 0.09
1 month	4.2	0.11 - 0.21	0.05 - 0.11
3 month	5.6	0.14 - 0.28	0.07 - 0.14
6 month	7.7	0.19 - 0.39	0.10 - 0.19
1 year	10	0.25 - 0.50	0.13 - 0.25
3 year	14	0.35 - 0.70	0.18 - 0.35
5 year	18	0.45 - 0.90	0.23 - 0.45
7 year	23	0.58 - 1.15	0.29 - 0.58
12 year	37	0.93 - 1.85	0.46 - 0.93

For the treatment of;-

Gilles de la Tourette Syndrome

Daily maintenance doses of up to 10 ml are required in most patients.

4.3 Contraindications

- Comatose states

- Patients with Parkinson's disease

- Patients with a known sensitivity to haloperidol or any of the product's ingredients

- Use during breast feeding

- CNS depression.

- Clinically significant cardiac disorders

- QTc interval prolongation

- History of ventricular arrhythmia or Torsades de pointes

- Bradycardia or 2/3° heart block

- Uncorrected hypokalemia

- Other QT prolonging drugs

4.4 Special Warnings And Precautions For Use

Please also refer to section 4.5 Interactions with other Medicaments and other forms of Interaction.

Caution is advised in patients with liver disease, renal failure and phaechromocytoma, prostatic hypertrophy, closed angle glaucoma, epilepsy and conditions predisposing to epilepsy or convulsions (e.g. alcohol withdrawl and brain damage). As severe neurotoxicity may result, haloperidol should only be used with great caution in patients with disturbed thyroid function. Antipsychotic therapy in these patients must always be accompanied by adequate management of the underlying thyroid dysfunction.

The risk-benefit of Haloperidol treatment should be fully assessed before treatment is commenced and patients with risk factors for ventricular arrhythmias such as cardiac disease, family history of sudden death and/or QT prolongation; uncorrected electrolyte disturbances; should be monitored carefully (ECGs and potassium levels), particularly during the initial phase of treatment to obtain steady plasma levels. Haloperidol should be used with caution in patients known to be slow metabolisers of CYP2D6, and during the use of cytochrome P450 inhbitors.

Baseline ECG recommended prior to treatment in all patients especially in the elderly and patients with a positive personal or family history of cardiac disease or abnormal findings on cardiac clinical examination. During therapy, the need for ECG monitoring e.g. at dose escalation should be assessed on an individual patient basis. Whilst on therapy, the dose should be reduced if QT is prolonged, and Haloperidol injection should be discontinued if the QTc exceeds 500 ms.

Periodic electrolyte monitoring is recommended, particularly if on diuretics or during inter-current illness.

For Patients at increased risk of arrhythmias, (those with hypokalaemia or a prolonged QT interval), and/or with severe cardiovascular disorders. The possibility of transient hypotension exists. Should hypotension occur and a vasopressor be required, adrenaline should not be used. Haloperidol may block adrenalin's vasopressor activity and cause a further paradoxical lowering of blood pressure.

Depression, unless psychotic or part of the effective component of schizophrenia. As with all antipyschotic agents, haloperidol should not be used alone where depression is predominant. Where depression and psychosis co-exist, haloperidol may be combined with an antidepressant.

Concomitant use of antipsychotics should be avoided.

Please note:-

Haloperidol may impair the metabolism of tricyclic antidepressants, (clinical significance unknown.)

-Parkinsonism, the syndrome is exacerbated by haloperidol's blockade of dopamine receptors.

-Caution should be taken in extremely hot or cold weather, the drug interfering with the crucial role of dopamine in hypothalamic thermoregulation.

Urinary retention may be exacerbated.

Haloperidol may impair alertness, especially at the start of treatment.

These effects may be potentiated by alcohol.

-Doses higher than those recommended, (an oral daily dose of 30 mg), should be considered carefully.

-A gradual reduction in dose is recommended. An acute withdrawal should be avoided.

Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Haloperidol and preventative measures undertaken.

Increased Mortality in Elderly people with Dementia

Data from two large observational studies showed that elderly people with dementia who are treated with antipsychotics are at a small increased risk of death compared with those who are not treated. There are insufficient data to give a firm estimate of the precise magnitude of the risk and the cause of the increased risk is not known.

Haloperidol is not licenced for the treatment of dementia-related behavioural disturbances.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Adrenaline: concurrent use may block the alpha-adrenergic effects of adrenaline, severe hypotension and tachycardia may result.

Alcohol: concurrent use may potentiate alcohol intoxication.

Amphetamines: concurrent use may decrease stimulant effects of amphetamines due to alpha-adrenergic blockade, the antipsychotic effects of haloperidol may be reduced.

Anticholinergics (or other medication with anticholinergic activity): concurrent use may intensify anticholinergic effects such as confusion, hallucinations, nightmares, and intraocular pressure. Paralytic ileus may also occur and the efficacy of haloperidol may be decreased because of reduced gastrointestinal absorption.

Anticonvulsants (including barbiturates and carbamazepine): concurrent use may cause a change in the pattern and/or frequency of epileptiform seizures. Dose adjustments of anticonvulsants may be necessary. Serum concentrations of haloperidol may be significantly reduced, (by up to 50% in the case of carbamazepine)

Antidepressants (including tricyclic antidepressants, 5HT reuptake inhibitors, MAO inhibitors, trazodone, maprotiline, Nefazodone): concurrent use may prolong and intensity the sedative and anticholinergic effects of these medications or of haloperidol.

Bromocriptine: haloperidol may increase serum prolactin concentrations and therefore concurrent use with bromocriptine may limit the effects of bromocriptine.

CNS depression producing medications (including sedatives, hypnotics, opiates): concurrent use may result in increased CNS and respiratory depression and increased hypotensive effects.

Diazoxide: concurrent use antagonises the inhibition of insulin release by diazoxide.

Dopamine: concurrent use may antagonise peripheral vasoconstriction produced by high doses of dopamine because of the alpha-adrenergic blocking action of haloperidol.

Ephedrine: concurrent use may decrease the pressor response to ephedrine.

Guanethidine and guanadrel: concurrent use may decrease the hypotensive effects of these agents because of displacement from and inhibition of uptake into alpha-adrenergic neurons.

Levodopa and pergolide: concurrent use may decrease the therapeutic effects of these drugs because of blockade of dopamine receptors by haloperidol

Lithium: at high doses of lithium concurrent use has been reported to be associated with irreversible neurological toxicity and brain damage, as well as neuromuscular symptoms and fever. If an unexplained pyrexia occurs in the presence of extrapyramidal side-effects, both lithium and haloperidol should be stopped immediately.

Methoxamine: prior administration of haloperidol may decrease the pressor effect and duration of action of methoxamine because of the alpha-adrenergic blocking action of haloperidol.

Methyldopa: concurrent use may cause unwanted mental effects such as disorientation and slowed or difficult thought processes.

Phenindione: concurrent use has been reported to interfere with the anticoagulant properties of phenindione in an isolated case. Caution is recommended for use with other anticoagulants.

Phenylephrine: prior administration of haloperidol may decrease the pressor effect of phenylephrine because of the alpha-adrenergic blocking action of haloperidol.

Use of haloperidol with concomitant QT prolonging drugs may result in additional QT prolongation and is not recommended (please refer to Section 4.3 – Contraindications).

Use of drugs that cause electrolyte imbalance may increase the risk of ventricular arrhythmias during concomitant use of haloperidol (please refer to Section 4.4 – Special Warnings and Special Precautions for Use).

Metabolic inhibitors of cytochrome P450, and specifically CYP2D6 may increase haloperidol levels.

4.6 Pregnancy And Lactation

Haloperidol's safe use in pregnancy and lactation has not been established. Reports exist of limb malformations in the first trimester, following the concurrent maternal use of haloperidol with other drugs of suspected teratogenicity. Animal studies have shown reduced fertility, delayed delivery, cleft palate and an increase in the number of stillbirths and newborn deaths at very high doses. Haloperidol is excreted in breast milk. Animal studies have shown that haloperidol in breast milk causes drowsiness and unusual muscle movements in nursing offspring. If the use of haloperidol is considered essential, breast feeding should be discontinued.

4.7 Effects On Ability To Drive And Use Machines

Haloperidol may impair alertness, especially at the start of treatment. The effects may be potentiated by alcohol. Patients should be warned of the risks of sedation and advised not to drive or operate machinery during treatment until their susceptibility is known.

4.8 Undesirable Effects

Extrapyramidal Effects (e.g. neuromuscular (extrapyramidal) effects such as Parkinson like symptoms, akathisia, dyskinesia, dystonia, hyperreflexia, rigidity, opisthotonus and occasionally oculogyric crisis). Rarely dystonia has been reported to produce laryngeal/pharyngeal spasm associated with gagging, respiratory distress and asphyxia. Anti-Parkinson agents should not be prescribed routinely, to prevent or reverse the neuromuscular reactions associated with haloperidol. If prescribed, the administration of anti-Parkinson drugs should be based on the likelihood of the patient developing extrapyramidal effects as well as the risk of adverse reactions resulting from the agents extended use. Frequent re-evaluation of anti-Parkinson therapy is recommended.

Tardive dyskinesias and tardive dystonia. Tardive dyskinesias may develop in some patients on long term therapy, possibly in relation to total cumulative dose or following the drug's withdrawal. The condition is characterised by rhythmical involuntary movements of the tongue, face or jaw, but such movements may be generalised. Its incidence in haloperidol users is reported as being approximately 15%, the elderly and those treated concurrently with anti-Parkinson drugs being at greatest risk. Symptoms may persist for several months to years, and in some patients appear permanent. On condition first being diagnosed consideration should be given to reducing or discontinuing antipyschotic medication. If withdrawal is undertaken this should be gradual, with gradual, with careful observation of both the dyskinesia and psychotic symptoms. In schizophrenia a recurrence of symptoms may not become apparent for several weeks or months.

Behavioural (e.g. motivational, emotional and behavioural changes, insomnia, depressive reactions and toxic confusional states, drowsiness, lethargy, stupor and catalepsy, confusion, restlessness, agitation, anxiety, euphoria and exacerbation of psychotic symptoms including hallucinations, alteration of sleep patterns).

Cardiovascular system: tachycardia and dose related hypotension are uncommon, but can occur, particularly in the elderly, who are more susceptible to the sedative and hypotensive effects. Less commonly, hypertension has been reported.

Cardiac effects such as QT-prolongation, Torsade de Pointes, ventricular arrhythmias, including ventricular fibrillation and ventricular tachycardia), and cardiac arrest have been reported rarely. Cases of sudden unexplained death have also occurred. These effects may occur more frequently with high doses, intravenous administration and in predisposed patients (see 4.4 Special Warnings and Special Precautions for Use).

Autonomic (e.g. nasal stuffiness, dry mouth, constipation, blurred vision, urinary retention and incontinence)

Endocrine (e.g. hyperprolactinaemia leading to oligo/amenorrhoea, gynaecomastia galactorrhoea, infertility (in the female) and impotence (in the male)

Gastrointestinal (e.g. heartburn, nausea, vomiting, weight loss, weight gain, constipation and diarrhoea).

Liver dysfunction with jaundice and eosinophilia. Additionally there may be a possible transient abnormality in liver function tests in the absence of jaundice.

Hyperpyrexia, heat stroke, headache, vertigo and cerebral seizures.

Dermatological (e.g. exfoliative dermatitis, erythema multiforme, and rarely photosensitisation.

Neuroleptic malignant syndrome (e.g. hyperthermia, muscle rigidity, autonomic instability, an altered level consciousness and coma.

i) Symptoms such as tachycardia, a labile arterial pressure and sweating may precede hyperthermia, and act as early warning of the condition.

ii) Recovery usually occurs within five to seven days of antipsychotic withdrawal.

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs – Frequency unknown

4.9 Overdose

In general haloperidol overdosage manifests as an extension of its pharmacological action, the most prominent of which are severe extrapyramidal symptoms, hypotension, respiratory difficulty and sedation possibility leading to impaired consciousness. A patient may appear comatose with respiratory depression and hypotension, possibly severe enough to produce a shock-like state. The risk of ECG changes associated with torsades de points should be considered. Unexpected reactions, such as bradycardia and an episode of severe delayed hypertension have been reported.

Haloperidol has no specific antidote. A patent airway should be established and mechanically assisted ventilation supplied if necessary. ECG monitoring is strongly advised in view of isolated reports of haloperidol's arrythmigenic action. Hypotension and circulatory collapse should be treated by plasma volume expansion and other appropriate measures.

ADRENALINE SHOULD NOT BE USED

Body temperature and adequate fluid intake should be maintained.

Severe extrapyramidal symptoms may merit the administration of appropriate anti-Parkinson medication.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Haloperidol is a butyrophenone derivative, it has antagonist action on a variety of receptors including muscarinic cholinergic, α-adrenergic and serotonin, (5HT1a/5HT2), and pronounced extrapyramidal reactions and a low incidence of autonomic side-effects result from the compound's pharmacological profile. Haloperidol is known to produce a selective effect on the central nervous system, by competitive blockade of postsynaptic dopamine (D2) receptors in the mesolimbic dopaminergic system and an increased turnover of brain dopamine to produce its tranquillizing effects.

5.2 Pharmacokinetic Properties

Steady state serum levels of haloperidol are normally achieved within 6 days on a fixed oral dosage. Total elimination takes approximately 28 days. Haloperidol is readily absorbed from the gastrointestinal tract. It is metabolised in the liver and is excreted in the urine, and via the bile, in the faeces: there is evidence of enterohepatic recycling. Haloperidol has been reported to have a plasma half life ranging from about 13 to 40 hours. Haloperidol is about 92% bound to plasma proteins. It is widely distributed in the body and crosses the blood brain barrier. Haloperidol is excreted in breast milk.

5.3 Preclinical Safety Data

There is no preclinical safety data of relevance to the prescriber.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactic acid

Methylhydroxybenzoate

Propylhydroxybenzoate

Propylene Glycol

Purified Water

6.2 Incompatibilities

None known

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

Do not store above 25°C. Store in the original container.

6.5 Nature And Contents Of Container

100 ml, 200 ml and 500 ml type III amber glass bottle with 28 x 18 ROPP LDPE plain white or aluminium cap with EPE (expanded polyethylene) wads and epoxy phenolic lacquer or child resistant closures with expanded polyethylene liners.

100 ml, 200 ml and 500 ml high density polyethylene bottle with 28 mm white polypropylene closure.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Pinewood Laboratories Limited, Ballymacarbry, Clonmel, Co. Tipperary, Ireland

8. Marketing Authorisation Number(S)

PL 04917/0023

9. Date Of First Authorisation/Renewal Of The Authorisation

27/02/2007

10. Date Of Revision Of The Text

25/02/2010

Trihexyphenidyl

Dosage Form: tablet
Trihexyphenidyl

HYDROCHLORIDE TABLETS, USP

Rx only

Trihexyphenidyl Description

Trihexyphenidyl HCl is a synthetic antispasmodic. Each tablet for oral administration, contains 2 mg or 5 mg Trihexyphenidyl HCl, each strength also containing as inactive ingredients: magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.

Trihexyphenidyl HCl is a white or slightly off white, crystalline powder, having not more than a very faint odor.

Trihexyphenidyl HCl is the substituted piperidine salt, 1-piperidinepropanol,α-cyclohexyl-α-phenyl-,hydrochloride,(±)-. The structural formula is:

Trihexyphenidyl - Clinical Pharmacology

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. Its therapeutic properties are similar to those of atropine, although undesirable side effects are ordinarily less frequent and severe than with the latter.

Indications and Usage for Trihexyphenidyl

Trihexyphenidyl HCl tablets are indicated as an adjunct in the treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic, and idiopathic). It is often useful as adjuvant therapy when treating these forms of parkinsonism with levodopa. Additionally, it is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as the dibenzoxazepines, phenothiazines, thioxanthenes, and butyrophenones.

Warnings

Patients to be treated with Trihexyphenidyl HCl should have a gonioscope evaluation and close monitoring of intraocular pressures at regular periodic intervals.

Precautions

Although Trihexyphenidyl HCl is not contraindicated for patients with cardiac, liver, or kidney disorders, or with hypertension, such patients should be maintained under close observation.

Since the use of Trihexyphenidyl HCl may, in some cases, continue indefinitely and since it has atropine-like properties, patients should be subjected to constant and careful long-term observation to avoid allergic and other untoward reactions. Inasmuch as Trihexyphenidyl HCl possesses some parasympatholytic activity, it 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. Geriatric patients, particularly over the age of 60, frequently develop increased sensitivity to the actions of drugs of this type, and hence, require strict dosage regulation. Incipient glaucoma may be precipitated by parasympatholytic drugs such as Trihexyphenidyl HCl.

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 coexist in patients receiving chronic neuroleptic treatment, and anticholinergic therapy with Trihexyphenidyl HCl may relieve some of these parkinsonism symptoms.

Adverse Reactions

Minor side effects, such as dryness of the mouth, blurring of vision, dizziness, mild nausea or nervousness, will be experienced by 30 to 50 percent of all patients. These sensations, however, are much less troublesome with Trihexyphenidyl HCl than with belladonna alkaloids and are usually less disturbing than unalleviated parkinsonism. 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.

Isolated instances of suppurative parotitis secondary to excessive dryness at the mouth, skin rashes, dilatation of the colon, paralytic ileus, and certain psychiatric manifestations such as delusions and hallucinations, plus one doubtful case of paranoia all of which may occur with any of the atropine-like drugs, have been reported rarely with Trihexyphenidyl hydrochloride.

Patients with arteriosclerosis or with a history of idiosyncrasy to other drugs may exhibit reactions of mental confusion, agitation, disturbed behavior, or nausea and vomiting. Such patients should be allowed to develop a tolerance through the initial administration of a small dose and 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 disturbances can result from indiscriminate use (leading to overdosage) to sustain continued euphoria.

Potential side effects associated with the use of any atropine-like drugs include constipation, drowsiness, urinary hesitancy or retention, tachycardia, dilation of the pupil, increased intraocular tension, weakness, vomiting, and headache.

The occurrence of angle-closure glaucoma due to long-term treatment with Trihexyphenidyl has been reported.

Trihexyphenidyl Dosage and Administration

Dosage should be individualized. The initial dose should be low and then increased gradually, especially in patients over 60 years of age. Whether Trihexyphenidyl HCl 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 Trihexyphenidyl HCl tends to dry the mouth excessively, it may be better to take it before meals, unless it causes nausea. If taken after meals, the thirst sometimes induced can be allayed by mint candies, chewing gum or water.

Trihexyphenidyl HCl in Idiopathic Parkinsonism

As initial therapy for parkinsonism, 1 mg of Trihexyphenidyl 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 this daily total of 6 to 10 mg, but some patients, chiefly those in the postencephalitic group, may require a total daily dose of 12 to 15 mg.

Trihexyphenidyl HCl in Drug-Induced Parkinsonism

The size and frequency of dose of Trihexyphenidyl HCl needed to control extrapyramidal reactions to commonly employed tranquilizers, notably the phenothiazines, thioxanthenes, and butyrophenones, 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 tranquilizer on instituting Trihexyphenidyl HCl 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 Trihexyphenidyl HCl 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 Trihexyphenidyl HCl therapy was discontinued.

Concomitant Use of Trihexyphenidyl HCl with Levodopa

When Trihexyphenidyl HCl is used concomitantly with levodopa, the usual dose of each may need to be reduced. Careful adjustment is necessary, depending on side effects and degree of symptom control. Trihexyphenidyl HCl dosage of 3 to 6 mg daily, in divided doses, is usually adequate.

Concomitant Use of Trihexyphenidyl HCl with Other Parasympathetic Inhibitors

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

The total daily intake of Trihexyphenidyl HCl tablets is tolerated best if divided into 3 doses and taken at mealtimes. High doses (>10 mg daily) may be divided into 4 parts, with 3 doses administered at mealtimes and the fourth at bedtime.

How is Trihexyphenidyl Supplied

Trihexyphenidyl HCl tablets are available as follows:

2 mg – round, flat, scored, white tablets; debossed "5971" above the score and "V" below the score. Available in bottles of 100, 500 and 1000.

5 mg – round, flat, scored, white tablets; debossed "5972" above the score and "V" below the score. Available in bottles of 100, 500, and 1000.

Dispense in a tight, light-resistant container as defined in the USP.

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Manufactured for:

QUALITEST PHARMACEUTICALS

Huntsville, AL 35811

8181446

R2/08-R2

PRINCIPAL DISPLAY PANEL

 

PRINCIPAL DISPALY PANEL

 

Trihexyphenidyl HYDROCHLORIDE  Trihexyphenidyl hydrochloride  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0603-6240 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Trihexyphenidyl HYDROCHLORIDE (Trihexyphenidyl) Trihexyphenidyl HYDROCHLORIDE 2 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE   CELLULOSE, MICROCRYSTALLINE   SODIUM STARCH GLYCOLATE TYPE A POTATO

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 8mm Flavor Imprint Code 5971;V Contains

Packaging # NDC Package Description Multilevel Packaging 1 0603-6240-21 100 TABLET In 1 BOTTLE, PLASTIC None 2 0603-6240-28 500 TABLET In 1 BOTTLE, PLASTIC None 3 0603-6240-32 1000 TABLET In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA040254	12/24/1998

Trihexyphenidyl HYDROCHLORIDE  Trihexyphenidyl hydrochloride  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0603-6241 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Trihexyphenidyl HYDROCHLORIDE (Trihexyphenidyl) Trihexyphenidyl HYDROCHLORIDE 5 mg

Inactive Ingredients Ingredient Name Strength MAGNESIUM STEARATE   CELLULOSE, MICROCRYSTALLINE   SODIUM STARCH GLYCOLATE TYPE A POTATO

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 10mm Flavor Imprint Code 5972;V Contains

Packaging # NDC Package Description Multilevel Packaging 1 0603-6241-21 100 TABLET In 1 BOTTLE, PLASTIC None 2 0603-6241-28 500 TABLET In 1 BOTTLE, PLASTIC None 3 0603-6241-32 1000 TABLET In 1 BOTTLE, PLASTIC None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA040254	12/24/1998

Labeler - Qualitest Pharmaceuticals (011103059)

Establishment
Name	Address	ID/FEI	Operations
Vintage Pharmaceuticals-Charlotte		151228897	MANUFACTURE

Establishment
Name	Address	ID/FEI	Operations
Vintage Pharmaceuticals-Huntsville		825839835	MANUFACTURE

Revised: 06/2011Qualitest Pharmaceuticals

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