Nurofen 200mg Caplets

1. Name Of The Medicinal Product

Nurofen 200 mg Caplets

2. Qualitative And Quantitative Composition

Ibuprofen 200 mg

For excipients, see 6.1.

3. Pharmaceutical Form

Coated Tablet

A white to off-white, biconvex, round, sugar coated tablet printed 'Nurofen' in black on one face.

4. Clinical Particulars

4.1 Therapeutic Indications

For the relief of migraine-headaches, backache, dental pain, neuralgia and period pains as well as rheumatic and muscular pains.

Nurofen relieves pain and reduces inflammation and temperature as well as relieving headaches and other types of pain. It also relieves cold and flu symptoms.

4.2 Posology And Method Of Administration

For oral administration and short-term use only.

During short-term use, if symptoms persist or worsen the patient should be advised to consult a doctor.

Adults and children over 12 years:

The minimum effective dose should be used for the shortest time necessary to relieve symptoms. If the product is required for more than 10 days, or if the symptoms worsen the patient should consult a doctor.

Take 1 or 2 caplets with water, up to three times a day as required.

Leave at least four hours between doses.

Do not take more than 6 caplets in any 24 hour period.

Not for use by children under 12 years of age.

4.3 Contraindications

Hypersensitivity to ibuprofen or any of the excipients in the product.

Patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema, or urticaria) in response to aspirin or other non-steroidal anti-inflammatory drugs.

Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

Severe heart failure, renal failure or hepatic failure (see section 4.4)

Last trimester of pregnancy

4.4 Special Warnings And Precautions For Use

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see GI and cardiovascular risks below).

The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.

Respiratory:

Bronchospasm may be precipitated in patients suffering from, or with a previous history of, bronchial asthma or allergic disease.

Other NSAIDs:

The use of Ibuprofen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided (see section 4.5).

SLE and mixed connective tissue disease:

systemic lupus erythematosus as well as those with mixed connective tissue disease – increased risk of aseptic meningitis (see section 4.8)

Renal:

Renal impairment as renal function may further deteriorate (see sections 4.3 and 4.8).

Hepatic:

Hepatic dysfunction (see sections 4.3 and 4.8)

Cardiovascular and cerebrovascular effects:

Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of ibuprofen, particularly at high doses (2400mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Overall, epidemiological studies do not suggest that low dose ibuprofen (e.g.

Impaired female fertility:

There is limited evidence that drugs which inhibit cyclo-oxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible upon withdrawal of treatment.

Gastrointestinal:

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8).

GI bleeding, ulceration or perforation, which can be fatal has been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of GI events.

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available.

Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).

When GI bleeding or ulceration occurs in patients receiving ibuprofen, the treatment should be withdrawn.

Dermatological:

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Ibuprofen should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

The label will include:

Read the enclosed leaflet before taking this product

Do not take if you:

• have (or have had two or more episodes of ) a stomach ulcer, perforation or bleeding

• are allergic to ibuprofen, to any of the ingredients, or to aspirin or other related painkillers

• are taking other NSAID pain killers or aspirin with a daily dose above 75mg

Speak to a pharmacist or your doctor before taking if you:

• have or have had asthma, diabetes, high cholesterol, high blood pressure, a stroke, heart, liver, kidney or bowel problems

• Are a smoker

• Are pregnant

If symptoms persist or worsen, or if new symptoms occur, consult your doctor or pharmacist.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Ibuprofen (like other NSAIDs) should be avoided in combination with:

Aspirin unless low-dose aspirin (not above 75mg daily) has been advised by a doctor as this may increase the risk of adverse reactions (see Section 4.4).

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).

Other NSAIDs including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs as this may increase the risk of adverse effects (see section 4.4)

Ibuprofen should be used in caution in combination with:

Corticosteroids: as these may increase the risk of gastrointestinal ulceration or bleeding (see Section 4.4)

Antihypertensives and diuretics: since NSAIDs may diminish the effects of these drugs. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Anticoagulants. NSAIDs may enhance the effects of anti-coagulants, such as warfarin (See section 4.4).

Ant-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).

Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Lithium: There is evidence for potential increase in plasma levels of lithium.

Methotrexate.: There is evidence for the potential increase in plasma levels of methotrexate.

Ciclosporin: Increased risk of nephrotoxicity.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk haemarthroses and haematoma in HIV (+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

4.6 Pregnancy And Lactation

Whilst no teratogenic effects have been demonstrated in animal experiments, the use of Nurofen should, if possible, be avoided during the first 6 months of pregnancy.

During the 3^rd trimester, ibuprofen is contraindicated as there is a risk of premature closure of the foetal ductus arteriosus with possible persistent pulmonary hypertension. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child. (See section 4.3 Contraindications).

In limited studies, ibuprofen appears in the breast milk in very low concentration and is unlikely to affect the breast-fed infant adversely.

See section 4.4 regarding female fertility.

4.7 Effects On Ability To Drive And Use Machines

None expected at recommended dose and duration of therapy.

4.8 Undesirable Effects

Hypersensitivity reactions have been reported following treatment with ibuprofen. These may consist of (a) non-specific allergic reaction and anaphylaxis, (b) respiratory tract activity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritis, urticaria, purpura, angioedema and, more rarely, exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

The list of the following adverse effects relates to those experienced with ibuprofen at doses available over the counter for short-term use. In the treatment of chronic conditions, under long-term treatment, additional adverse effects may occur.

Hypersensitivity reactions:

Uncommon: Hypersensitivity reactions with urticaria and pruritis

Very rare: severe hypersensitivity reactions. Symptoms could be facial, tongue and laryngeal swelling, dyspnoea, tachycardia, hypotension, (anaphylaxis, angioedema or severe shock).

Exacerbation of asthma and bronchospasm.

Gastrointestinal:

The most commonly observed adverse events are gastrointestinal in nature.

Uncommon: abdominal pain, nausea, dyspepsia

Rare: Diarrhoea, flatulence, constipation and vomiting

Very rare: peptic ulcer, perforation or gastrointestinal haemorrhage, melaena, haematemesis, sometimes fatal, particularly in the elderly. Ulcerative stomatitis, gastritis.

Exacerbation of colitis and Crohn's disease (section 4.4).

Nervous System:

Uncommon: Headache

Very rare: Aseptic meningitis – single cases have been reported very rarely.

Renal:

Very rare: Acute renal failure, papillary necrosis, especially in long-term use, associated with increased serum and oedema.

Hepatic:

Very rare: liver disorders.

Haematological:

Very rare: Haematopoietic disorders (anaemia, leucopenia, thrombocytopenia, pancytopenia, agranulocytosis). First signs are fever, sore throat, superficial mouth ulcers, flu-like symptoms, severe exhaustion, unexplained bleeding and bruising.

Dermatological:

Uncommon: Various skin rashes

Very rare: Severe forms of skin reactions such as bullous reactions including Stevens-Johnson syndrome, erythema multiforme and toxic epidermal necrolysis can occur.

Immune System:

In patients with existing auto-immune disorders (such as systemic lupus erythematosus, mixed connective tissue disease) during treatment with ibuprofen, single cases of symptoms of aseptic meningitis, such as stiff neck, headache, nausea, vomiting, fever or disorientation have been observed (see section 4.4).

Cardiovascular and Cerebrovascular

Oedema, hypertension and cardiac failure, have been reported in association with NSAID treatment.

Clinical trial and epidemiological data suggest that the use of ibuprofen (particularly at high doses 2400 mg daily) and in long-term treatment may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

4.9 Overdose

In children ingestion of more than 400 mg/kg may cause symptoms. In adults the dose response effect is less clear cut. The half-life in overdose is 1.5-3 hours.

Symptoms

Most patients who have ingested clinically important amounts of NSAIDs will develop no more than nausea, vomiting, epigastric pain, or more rarely diarrhoea. Tinnitus, headache and gastrointestinal bleeding are also possible. In more serious poisoning, toxicity is seen in the central nervous system, manifesting as drowsiness, occasionally excitation and disorientation or coma. Occasionally patients develop convulsions. In serious poisoning metabolic acidosis may occur and the prothrombin time/ INR may be prolonged, probably due to interference with the actions of circulating clotting factors. Acute renal failure and liver damage may occur. Exacerbation of asthma is possible in asthmatics.

Management

Management should be symptomatic and supportive and include the maintenance of a clear airway and monitoring of cardiac and vital signs until stable. Consider oral administration of activated charcoal if the patient presents within 1 hour of ingestion of a potentially toxic amount. If frequent or prolonged, convulsions should be treated with intravenous diazepam or lorazepam. Give bronchodilators for asthma.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Ibuprofen is a propionic acid derivative NSAID that has demonstrated its efficacy by inhibition of prostaglandin synthesis. In humans, ibuprofen reduces inflammatory pain, swellings and fever. Furthermore, ibuprofen reversibly inhibits platelet aggregation.

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400mg was taken within 8 h before or within 30 min after immediate release aspirin dosing (81mg), a decreased effect of ASA on the formation of thromboxane or platelet aggregation occurred. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.

5.2 Pharmacokinetic Properties

Ibuprofen is rabidly absorbed following administration and is rapidly distributed throughout the whole body. The excretion is rapid and complete via the kidneys.

Maximum plasma concentrations are reached 45 minutes after ingestion if taken on an empty stomach. When taken with food, peak levels are observed after 1 to 2 hours. These times may vary with different dosage forms.

Elimination half-life is approximately 2 hours.

In limited studies, ibuprofen appears in the breast milk in very low concentrations.

5.3 Preclinical Safety Data

No relevant information, additional to that contained elsewhere in the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Tablet Core

Croscarmellose Sodium

Sodium Laurilsulfate

Sodium Citrate

Stearic Acid

Colloidal Anhydrous Silica

Sugar coat ingredients

Carmellose Sodium

French Chalk for Tablets (Talc)

Acacia Spray Dried

Sucrose

Titanium Dioxide

Macrogol 6000

Tablet printing

Opacode S-1-8152 HV Black (solids)1

¹ Opacode S-1-8152 HV black contains the following residual materials after application

Shellac USNF 53.504%

Iron oxide black (E172) 44.699%

Soya lecithin 1.788%

Antifoam DC1510 0.009%

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

24 months.

6.4 Special Precautions For Storage

Do not store above 25°C.

Store in the original pack.

6.5 Nature And Contents Of Container

The tablets will be packed in blisters consisting of:

Push through laminate consisting of opaque, white 250 micron PVC heat-sealed to 20 micron aluminium foil

or

Push through laminate consisting of opaque, white 250 micron PVC with 40 gsm PVdC, heat-sealed to 20 micron aluminium foil.

The blisters are contained in a cardboard carton

2, 3, 4, 5, 6, 8, 10, 12, 15, 16 tablets.

Not all packs will be marketed.

6.6 Special Precautions For Disposal And Other Handling

Not applicable

7. Marketing Authorisation Holder

Crookes Healthcare Limited

1 Thane Road West

Nottingham NG2 3AA

8. Marketing Authorisation Number(S)

PL 00327/0145

9. Date Of First Authorisation/Renewal Of The Authorisation

15^th July 2004

10. Date Of Revision Of The Text

25/03/2009

Bladder Cancer Medications

Definition of Bladder Cancer:

A malignant tumor growth within the bladder. Bladder cancers usually arise from the transitional cells of the bladder (the cells lining the bladder).

These tumors may be classified based on their growth pattern as either papillary tumors (meaning they have a wart-like lesion attached to a stalk) or nonpapillary tumors. Nonpapillary tumors are much less common, but they are more invasive and have a poorer prognosis.

Drugs associated with Bladder Cancer

The following drugs and medications are in some way related to, or used in the treatment of Bladder Cancer. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Learn more about Bladder Cancer

Medical Encyclopedia:

• Bladder cancer

Harvard Health Guide:

• Symptoms and treatment for Bladder Cancer

Drug List:

Adriamycin

Cytoxan

Cytoxan-Lyophilized-Oral-Injection

Mutamycin

Neosar

Platinol

Platinol-Aq

Thioplex

Trexall

Risperdal Tablets, Liquid & Quicklet

1. Name Of The Medicinal Product

RISPERDAL

RISPERDAL LIQUID

RISPERDAL Quicklet

*Intensive monitoring is requested only when used for the recently licensed indications of short-term treatment of persistent aggression in Alzheimer's dementia and conduct disorder in children

2. Qualitative And Quantitative Composition

Film-coated Tablets:

Each film-coated tablet contains 0.5,1, 2, 3, 4 or 6 mg of risperidone

Excipients:

Each 0.5 mg film-coated tablet contains 91 mg lactose

Each 1 mg film-coated tablet contains 131 mg lactose

Each 2 mg film-coated tablet contains 130 mg lactose and 0.05 mg sunset yellow (E110)

Each 3 mg film-coated tablet contains 195 mg lactose

Each 4 mg film-coated tablet contains 260 mg lactose

Each 6 mg film-coated tablet contains 115 mg lactose and 0.01 mg sunset yellow (E110)

Oral Solution:

1 ml oral solution contains 1 mg of risperidone

Orodispersible Tablets:

Each orodispersible tablet contains 0.5,1,2,3 or 4 mg of risperidone

Excipients:

Each 0.5 mg orodispersible tablet contains 0.25 mg aspartame (E951)

Each 1 mg orodispersible tablet contains 0.5 mg aspartame (E951)

Each 2 mg orodispersible tablet contains 0.75 mg aspartame (E951)

Each 3 mg orodispersible tablet contains 1.125 mg aspartame (E951)

Each 4 mg orodispersible tablet contains 1.5 mg aspartame (E951)

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Film-coated tablet

0.5 mg risperidone as brownish-red half-scored oblong biconvex tablets.

1 mg risperidone as white half-scored oblong tablets.

2 mg risperidone as orange half-scored oblong tablets.

3 mg risperidone as yellow half-scored oblong tablets

4 mg risperidone as green half-scored oblong tablets.

6 mg risperidone as yellow circular biconvex tablets.

The score line is only to facilitate breaking for ease of swallowing and not to divide into equal doses.

Oral solution.

The solution is clear and colourless

Orodispersible tablet

0.5 mg risperidone as light coral, round, biconvex tablets

1 mg risperidone as light coral, square, biconvex tablets

2 mg risperidone as coral, square, biconvex tablets

3 mg risperidone as coral, round, biconvex tablets

4 mg risperidone as coral, round, biconvex tablets

Oro-dispersible tablets are etched on one side with R 0.5, R1, R2, R3, and R4 respectively.

4. Clinical Particulars

4.1 Therapeutic Indications

RISPERDAL is indicated for the treatment of schizophrenia.

RISPERDAL is indicated for the treatment of moderate to severe manic episodes associated with bipolar disorders.

RISPERDAL is indicated for the short-term treatment (up to 6 weeks) of persistent aggression in patients with moderate to severe Alzheimer's dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self or others.

RISPERDAL is indicated for the short-term symptomatic treatment (up to 6 weeks) of persistent aggression in conduct disorder in children from the age of 5 years and adolescents with subaverage intellectual functioning or mental retardation diagnosed according to DSM-IV criteria, in whom the severity of aggressive or other disruptive behaviours require pharmacologic treatment. Pharmacological treatment should be an integral part of a more comprehensive treatment programme, including psychosocial and educational intervention. It is recommended that risperidone be prescribed by a specialist in child neurology and child and adolescent psychiatry or physicians well familiar with the treatment of conduct disorder of children and adolescents.

4.2 Posology And Method Of Administration

Schizophrenia

Adults

RISPERDAL may be given once daily or twice daily.

Patients should start with 2 mg/day risperidone. The dosage may be increased on the second day to 4 mg. Subsequently, the dosage can be maintained unchanged, or further individualised, if needed. Most patients will benefit from daily doses between 4 and 6 mg. In some patients, a slower titration phase and a lower starting and maintenance dose may be appropriate.

Doses above 10 mg/day have not demonstrated superior efficacy to lower doses and may cause increased incidence of extrapyramidal symptoms. Safety of doses above 16 mg/day has not been evaluated, and are therefore not recommended.

Elderly

A starting dose of 0.5 mg twice daily is recommended. This dosage can be individually adjusted with 0.5 mg twice daily increments to 1 to 2 mg twice daily.

Paediatric population

Risperidone is not recommended for use in children below age 18 with schizophrenia due to a lack of data on efficacy.

Manic episodes in bipolar disorder

Adults

RISPERDAL should be administered on a once daily schedule, starting with 2 mg risperidone. Dosage adjustments, if indicated, should occur at intervals of not less than 24 hours and in dosage increments of 1 mg per day. Risperidone can be administered in flexible doses over a range of 1 to 6 mg per day to optimize each patient's level of efficacy and tolerability. Daily doses over 6 mg risperidone have not been investigated in patients with manic episodes.

As with all symptomatic treatments, the continued use of RISPERDAL must be evaluated and justified on an ongoing basis.

Elderly

A starting dose of 0.5 mg twice daily is recommended. This dosage can be individually adjusted with 0.5 mg twice daily increments to 1 to 2 mg twice daily. Since clinical experience in elderly is limited, caution should be exercised.

Paediatric population

Risperidone is not recommended for use in children below age 18 with bipolar mania due to a lack of data on efficacy.

Persistent aggression in patients with moderate to severe Alzheimer's dementia

A starting dose of 0.25 mg twice daily is recommended. This dosage can be individually adjusted by increments of 0.25 mg twice daily, not more frequently than every other day, if needed. The optimum dose is 0.5 mg twice daily for most patients. Some patients, however, may benefit from doses up to 1 mg twice daily.

RISPERDAL should not be used more than 6 weeks in patients with persistent aggression in Alzheimer's dementia. During treatment, patients must be evaluated frequently and regularly, and the need for continuing treatment reassessed.

Conduct disorder

Children and adolescents from 5 to 18 years of age

For subjects

As with all symptomatic treatments, the continued use of RISPERDAL must be evaluated and justified on an ongoing basis.

RISPERDAL is not recommended in children less than 5 years of age, as there is no experience in children less than 5 years of age with this disorder.

Renal and hepatic impairment

Patients with renal impairment have less ability to eliminate the active antipsychotic fraction than in adults with normal renal function. Patients with impaired hepatic function have increases in plasma concentration of the free fraction of risperidone.

Irrespective of the indication, starting and consecutive dosing should be halved, and dose titration should be slower for patients with renal or hepatic impairment.

RISPERDAL should be used with caution in these groups of patients.

Method of administration

RISPERDAL is for oral use. Food does not affect the absorption of RISPERDAL.

Upon discontinuation, gradual withdrawal is advised. Acute withdrawal symptoms, including nausea, vomiting, sweating, and insomnia have very rarely been described after abrupt cessation of high doses of antipsychotic medicines (see section 4.8). Recurrence of psychotic symptoms may also occur, and the emergence of involuntary movement disorders (such as akathisia, dystonia and dyskinesia) has been reported.

Switching from other antipsychotics.

When medically appropriate, gradual discontinuation of the previous treatment while RISPERDAL therapy is initiated is recommended. Also, if medically appropriate, when switching patients from depot antipsychotics, initiate RISPERDAL therapy in place of the next scheduled injection. The need for continuing existing anti-Parkinson medicines should be re-evaluated periodically.

RISPERDAL oral solution:

For instructions on handling RISPERDAL oral solution see section 6.6.

RISPERDAL orodispersible tablets:

Do not open the blister until ready to administer. Peel open the blister to expose the tablet. Do not push the tablet through the foil because it may break. Remove the tablet from the blister with dry hands.

Immediately place the tablet on the tongue. The tablet will begin disintegrating within seconds. Water may be used if desired.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

4.4 Special Warnings And Precautions For Use

Elderly patients with dementia

Increased mortality in elderly people with dementia

In a meta-analysis of 17 controlled trials of atypical antipsychotic drugs, including RISPERDAL, elderly patients with dementia treated with atypical antipsychotics have an increased mortality compared to placebo. In placebo-controlled trials with oral RISPERDAL in this population, the incidence of mortality was 4.0% for RISPERDAL-treated patients compared to 3.1% for placebo-treated patients. The odds ratio (95% exact confidence interval) was 1.21 (0.7, 2.1). The mean age (range) of patients who died was 86 years (range 67-100). Data from two large observational studies showed that elderly people with dementia who are treated with conventional antipsychotics are also 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. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.

Concomitant use with furosemide

In the RISPERDAL placebo-controlled trials in elderly patients with dementia, a higher incidence of mortality was observed in patients treated with furosemide plus risperidone (7.3%; mean age 89 years, range 75-97) when compared to patients treated with risperidone alone (3.1%; mean age 84 years, range 70-96) or furosemide alone (4.1%; mean age 80 years, range 67-90). The increase in mortality in patients treated with furosemide plus risperidone was observed in two of the four clinical trials. Concomitant use of risperidone with other diuretics (mainly thiazide diuretics used in low dose) was not associated with similar findings.

No pathophysiological mechanism has been identified to explain this finding, and no consistent pattern for cause of death observed. Nevertheless, caution should be exercised and the risks and benefits of this combination or co-treatment with other potent diuretics should be considered prior to the decision to use. There was no increased incidence of mortality among patients taking other diuretics as concomitant treatment with risperidone. Irrespective of treatment, dehydration was an overall risk factor for mortality and should therefore be carefully avoided in elderly patients with dementia.

Cerebrovascular Adverse Events (CVAE)

An approximately 3-fold increased risk of cerebrovascular adverse events have been seen in randomised placebo controlled clinical trials in the dementia population with some atypical antipsychotics. The pooled data from six placebo-controlled studies with RISPERDAL in mainly elderly patients (>65 years of age) with dementia showed that CVAEs (serious and non-serious, combined) occurred in 3.3% (33/1009) of patients treated with risperidone and 1.2% (8/712) of patients treated with placebo. The odds ratio (95% exact confidence interval) was 2.96 (1.34, 7.50). The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. RISPERDAL should be used with caution in patients with risk factors for stroke.

The risk of CVAEs was significantly higher in patients with mixed or vascular type of dementia when compared to Alzheimer's dementia. Therefore, patients with other types of dementias than Alzheimer's should not be treated with risperidone.

Physicians are advised to assess the risks and benefits of the use of RISPERDAL in elderly patients with dementia, taking into account risk predictors for stroke in the individual patient. Patients/caregivers should be cautioned to immediately report signs and symptoms of potential CVAEs such as sudden weakness or numbness in the face, arms or legs, and speech or vision problems. All treatment options should be considered without delay, including discontinuation of risperidone.

RISPERDAL should only be used short term for persistent aggression in patients with moderate to severe Alzheimer's dementia to supplement non-pharmacological approaches which have had limited or no efficacy and when there is potential risk of harm to self or others.

Patients should be reassessed regularly, and the need for continuing treatment reassessed.

Orthostatic hypotension

Due to the alpha-blocking activity of risperidone, (orthostatic) hypotension can occur, especially during the initial dose-titration period. Clinically significant hypotension has been observed postmarketing with concomitant use of risperidone and antihypertensive treatment. RISPERDAL should be used with caution in patients with known cardiovascular disease (e.g., heart failure, myocardial infarction, conduction abnormalities, dehydration, hypovolemia, or cerebrovascular disease), and the dosage should be gradually titrated as recommended (see section 4.2). A dose reduction should be considered if hypotension occurs.

Tardive dyskinesia/extrapyramidal symptoms (TD/EPS)

Medicines with dopamine receptor antagonistic properties have been associated with the induction of tardive dyskinesia characterised by rhythmical involuntary movements, predominantly of the tongue and/or face. The onset of extrapyramidal symptoms is a risk factor for tardive dyskinesia. If signs and symptoms of tardive dyskinesia appear, the discontinuation of all antipsychotics should be considered.

Neuroleptic malignant syndrome (NMS)

Neuroleptic Malignant Syndrome, characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinase levels has been reported to occur with antipsychotics. Additional signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. In this event, all antipsychotics, including RISPERDAL, should be discontinued.

Parkinson's disease and dementia with Lewy bodies

Physicians should weigh the risks versus the benefits when prescribing antipsychotics, including RISPERDAL, to patients with Parkinson's Disease or Dementia with Lewy Bodies (DLB). Parkinson's Disease may worsen with risperidone. Both groups may be at increased risk of Neuroleptic Malignant Syndrome as well as having an increased sensitivity to antipsychotic medicinal products; these patients were excluded from clinical trials. Manifestation of this increased sensitivity can include confusion, obtundation, postural instability with frequent falls, in addition to extrapyramidal symptoms.

Hyperglycaemia and diabetes mellitus

Hyperglycaemia, diabetes mellitus and exacerbation of pre-existing diabetes have been reported during treatment with RISPERDAL. In some cases, a prior increase in body weight has been reported which may be a predisposing factor. Association with ketoacidosis has been reported very rarely, and rarely with diabetic coma. Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines. Patients treated with any atypical antipsychotic, including RISPERDAL should be monitored for symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and weakness) and patients with diabetes mellitus should be monitored regularly for worsening of glucose control.

Weight gain

Significant weight gain has been reported with RISPERDAL use. Weight should be monitored regularly.

Hyperprolactinaemia

Tissue culture studies suggest that cell growth in human breast tumours may be stimulated by prolactin. Although no clear association with the administration of antipsychotics has so far been demonstrated in clinical and epidemiological studies, caution is recommended in patients with relevant medical history. RISPERDAL should be used with caution in patients with pre-existing hyperprolactinaemia and in patients with possible prolactin-dependent tumours.

QT prolongation

QT prolongation has very rarely been reported postmarketing. As with other antipsychotics, caution should be exercised when risperidone is prescribed in patients with known cardiovascular disease, family history of QT prolongation, bradycardia, or electrolyte disturbances (hypokalaemia, hypomagnesaemia), as it may increase the risk of arrhythmogenic effects, and in concomitant use with medicines known to prolong the QT interval.

Seizures

RISPERDAL should be used cautiously in patients with a history of seizures or other conditions that potentially lower the seizure threshold.

Priapism

Priapism may occur with RISPERDAL treatment due to its alpha-adrenergic blocking effects.

Body temperature regulation

Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic medicines. Appropriate care is advised when prescribing RISPERDAL to patients who will be experiencing conditions which may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant treatment with anticholinergic activity, or being subject to dehydration.

Venous thromboembolism

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 RISPERDAL and preventative measures undertaken.

Children and adolescents

Before risperidone is prescribed to a child or adolescent with conduct disorder they should be fully assessed for physical and social causes of the aggressive behaviour such as pain or inappropriate environmental demands.

The sedative effect of risperidone should be closely monitored in this population because of possible consequences on learning ability. A change in the time of administration of risperidone could improve the impact of the sedation on attention faculties of children and adolescents.

Risperidone was associated with mean increases in body weight and body mass index (BMI). Changes in height in the long-term open-label extension studies were within expected age-appropriate norms. The effect of long-term risperidone treatment on sexual maturation and height have not been adequately studied.

Because of the potential effects of prolonged hyperprolactinemia on growth and sexual maturation in children and adolescents, regular clinical evaluation of endocrinological status should be considered, including measurements of height, weight, sexual maturation, monitoring of menstrual functioning, and other potential prolactin-related effects.

During treatment with risperidone regular examination for extrapyramidal symptoms and other movement disorders should also be conducted.

For specific posology recommendations in children and adolescents see Section 4.2.

Excipients

The film-coated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

The 2 mg and 6 mg film-coated tablets contain sunset yellow (E110). May cause allergic reactions.

The orodispersible tablets contain aspartame. Aspartame is a source of phenylalanine which may be harmful for people with phenylketonuria.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

As with other antipsychotics, caution is advised when prescribing risperidone with medicinal products known to prolong the QT interval, e.g., class Ia antiarrhythmics (e.g., quinidine, dysopiramide, procainamide), class III antiarrhythmics (e.g., amiodarone, sotalol), tricyclic antidepressant (i.e., amitriptyline), tetracyclic antidepressants (i.e., maprotiline), some antihistaminics, other antipsychotics, some antimalarials (i.e., chinice and mefloquine), and with medicines causing electrolyte imbalance (hypokalaemia, hypomagnesiaemia), bradycardia, or those which inhibit the hepatic metabolism of risperidone. This list is indicative and not exhaustive.

Potential for RISPERDAL to affect other medicinal products

Risperidone should be used with caution in combination with other centrally-acting substances notably including alcohol, opiates, antihistamines and benzodiazepines due to the increased risk of sedation.

RISPERDAL may antagonise the effect of levodopa and other dopamine agonists. If this combination is deemed necessary, particularly in end-stage Parkinson's disease, the lowest effective dose of each treatment should be prescribed.

Clinically significant hypotension has been observed postmarketing with concomitant use of risperidone and antihypertensive treatment.

RISPERDAL does not show a clinically relevant effect on the pharmacokinetics of lithium, valproate, digoxin or topiramate.

Potential for other medicinal products to affect RISPERDAL

Carbamazepine has been shown to decrease the plasma concentrations of the active antipsychotic fraction of risperidone. Similar effects may be observed with e.g. rifampicin, phenytoin and phenobarbital which also induce CYP 3A4 hepatic enzyme as well as P-glycoprotein. When carbamazepine or other CYP 3A4 hepatic enzyme/P-glycoprotein (P-gp) inducers are initiated or discontinued, the physician should re-evaluate the dosing of RISPERDAL.

Fluoxetine and paroxetine, CYP 2D6 inhibitors, increase the plasma concentration of risperidone, but less so of the active antipsychotic fraction. It is expected that other CYP 2D6 inhibitors, such as quinidine, may affect the plasma concentrations of risperidone in a similar way. When concomitant fluoxetine or paroxetine is initiated or discontinued, the physician should re-evaluate the dosing of RISPERDAL.

Verapamil, an inhibitor of CYP 3A4 and P-gp, increases the plasma concentration of risperidone.

Galantamine and donepezil do not show a clinically relevant effect on the pharmacokinetics of risperidone and on the active antipsychotic fraction.

Phenothiazines, tricyclic antidepressants, and some beta-blockers may increase the plasma concentrations of risperidone but not those of the active antipsychotic fraction. Amitriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction. Cimetidine and ranitidine increase the bioavailability of risperidone, but only marginally that of the active antipsychotic fraction. Erythromycin, a CYP 3A4 inhibitor, does not change the pharmacokinetics of risperidone and the active antipsychotic fraction.

The combined use of psychostimulants (e.g., methylphenidate) with RISPERDAL in children and adolescents did not alter the pharmacokinetics and efficacy of RISPERDAL.

See section 4.4 regarding increased mortality in elderly patients with dementia concomitantly receiving furosemide.

Concomitant use of oral RISPERDAL with paliperidone is not recommended as paliperidone is the active metabolite of risperidone and the combination of the two may lead to additive active antipsychotic fraction exposure.

4.6 Pregnancy And Lactation

Pregnancy

There are no adequate data from the use of risperidone in pregnant women. According to postmarketing data reversible extrapyramidal symptoms in the neonate were observed following the use of risperidone during the last trimester of pregnancy. Consequently newborns should be monitored carefully. Risperidone was not teratogenic in animal studies but other types of reproductive toxicity were seen (see section 5.3). The potential risk for humans is unknown. Therefore, RISPERDAL should not be used during pregnancy unless clearly necessary. If discontinuation during pregnancy is necessary, it should not be done abruptly.

Lactation

In animal studies, risperidone and 9-hydroxy-risperidone are excreted in the milk. It has been demonstrated that risperidone and 9-hydroxy-risperidone are also excreted in human breast milk in small quantities. There are no data available on adverse reactions in breast-feeding infants. Therefore, the advantage of breast-feeding should be weighed against the potential risks for the child.

4.7 Effects On Ability To Drive And Use Machines

RISPERDAL can have minor or moderate influence on the ability to drive and use machines due to potential nervous system and visual effects (see section 4.8). Therefore, patients should be advised not to drive or operate machinery until their individual susceptibility is known.

4.8 Undesirable Effects

The most frequently reported adverse drug reactions (ADRs) (incidence

The following are all the ADRs that were reported in clinical trials and postmarketing. The following terms and frequencies are applied: very common (

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Adverse Drug Reactions by System Organ Class and Frequency
Investigations
Common	Blood prolactin increaseda, Weight increased
Uncommon	Electrocardiogram QT prolonged, Electrocardiogram abnormal, Transaminases increased, White blood cell count decreased Body temperature increased, Eosinophil count increased, Haemoglobin decreased, Blood creatine phosphokinase increased
Rare	Body temperature decreased
Cardiac disorders
Common	Tachycardia
Uncommon	Atrioventricular block, Bundle branch block, Atrial fibrillation, Sinus bradycardia, Palpitations
Blood and lymphatic system disorders
Uncommon	Anaemia, Thrombocytopenia
Rare	Granulocytopenia
Not known	Agranulocytosis
Nervous system disorders
Very common	Parkinsonismb, Headache
Common	Akathisiab, Dizziness, Tremorb, Dystoniab, Somnolence, Sedation, Lethargy, Dyskinesiab
Uncommon	Unresponsive to stimuli, Loss of consciousness, Syncope, Depressed level of consciousness, Cerebrovascular accident, Transient ischaemic attack, Dysarthria, Disturbance in attention, Hypersomnia, Dizziness postural, Balance disorder, Tardive dyskinesia, Speech disorder, Coordination abnormal, Hypoaesthesia
Rare	Neuroleptic malignant syndrome, Diabetic coma, Cerebrovascular disorder, Cerebral ischaemia, Movement disorder
Eye disorders
Common	Vision blurred
Uncommon	Conjunctivitis, Ocular hyperaemia, Eye discharge, Eye swelling, Dry eye, Lacrimation increased, Photophobia
Rare	Visual acuity reduced, Eye rolling, Glaucoma
Ear and labyrinth disorders
Uncommon	Ear pain, Tinnitus
Respiratory, thoracic and mediastinal disorders
Common	Dyspnoea, Epistaxis, Cough, Nasal congestion, Pharyngolaryngeal pain
Uncommon	Wheezing, Pneumonia aspiration, Pulmonary congestion, Respiratory disorder, Rales, Respiratory tract congestion, Dysphonia
Rare	Sleep apnea syndrome, Hyperventilation
Gastrointestinal disorders
Common	Vomiting, Diarrhoea, Constipation, Nausea, Abdominal pain, Dyspepsia, Dry mouth, Stomach discomfort
Uncommon	Dysphagia, Gastritis, Faecal incontinence, Faecaloma
Rare	Intestinal obstruction, Pancreatitis, Lip swelling, Cheilitis
Renal and urinary disorders
Common	Enuresis
Uncommon	Urinary retention, Dysuria, Urinary incontinence, Pollakiuria
Skin and subcutaneous tissue disorders
Common	Rash, Erythema
Uncommon	Angioedema, Skin lesion, Skin disorder, Pruritus, Acne, Skin discolouration, Alopecia, Seborrhoeic dermatitis, Dry skin, Hyperkeratosis
Rare	Dandruff
Musculoskeletal and connective tissue disorders
Common	Arthralgia, Back pain, Pain in extremity
Uncommon	Muscular weakness, Myalgia, Neck pain, Joint swelling, Posture abnormal, Joint stiffness, Musculoskeletal chest pain
Rare	Rhabdomyolysis
Endocrine disorders
Rare	Inappropriate antidiuretic hormone secretion
Metabolism and nutrition disorders
Common	Increased appetite, Decreased appetite
Uncommon	Diabetes mellitusc, Anorexia, Polydipsia, Hyperglycaemia
Rare	Hypoglycaemia
Very rare	Diabetic ketoacidosis
Not known	Water intoxication
Infections and infestations
Common	Pneumonia, Influenza, Bronchitis, Upper respiratory tract infection, Urinary tract infection
Uncommon	Sinusitis, Viral infection, Ear infection, Tonsillitis, Cellulitis, Otitis media, Eye infection, Localised infection, Acarodermatitis, Respiratory tract infection, Cystitis, Onychomycosis
Rare	Otitis media chronic
Vascular disorders
Uncommon	Hypotension, Orthostatic hypotension, Flushing
General disorders and administration site conditions
Common	Pyrexia, Fatigue, Peripheral oedema, Asthenia, Chest pain
Uncommon	Face oedema, Gait disturbance, Feeling abnormal, Sluggishness, Influenza like illness, Thirst, Chest discomfort, Chills
Rare	Generalised oedema, Hypothermia, Drug withdrawal syndrome, Peripheral coldness
Immune system disorders
Uncommon	Hypersensitivity
Rare	Drug hypersensitivity
Not known	Anaphylactic reaction
Hepatobiliary disorders
Rare	Jaundice
Reproductive system and breast disorders
Uncommon	Amenorrhoea, Sexual dysfunction, Erectile dysfunction, Ejaculation disorder, Galactorrhoea, Gynaecomastia, Menstrual disorder, Vaginal discharge,
Not known	Priapism
Psychiatric disorders
Very common	Insomnia
Common	Anxiety, Agitation, Sleep disorder
Uncommon	Confusional state, Mania, Libido decreased, Listless, Nervousness
Rare	Anorgasmia, Blunted affect

^a Hyperprolactinemia can in some cases lead to gynaecomastia, menstrual disturbances, amenorrhoea, galactorrhea.

^b Extrapyramidal disorder may occur: Parkinsonism (salivary hypersecretion, musculoskeletal stiffness, parkinsonism, drooling, cogwheel rigidity, bradykinesia, hypokinesia, masked facies, muscle tightness, akinesia, nuchal rigidity, muscle rigidity, parkinsonian gait, and glabellar reflex abnormal),akathisia ( akathisia, restlessness, hyperkinesia, and restless leg syndrome), tremor, dyskinesia (dyskinesia, muscle twitching, choreoathetosis, athetosis, and myoclonus), dystonia.

Dystonia includes dystonia, muscle spasms, hypertonia, torticollis, muscle contractions involuntary, muscle contracture, blepharospasm, oculogyration, tongue paralysis, facial spasm, laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurothotonus, tongue spasm, and trismus. Tremor includes tremor and parkinsonian rest tremor. It should be noted that a broader spectrum of symptoms are included, that do not necessarily have an extrapyramidal origin.

^cIn placebo-controlled trials diabetes mellitus was reported in 0.18%

Co-Amilofruse 40 / 5mg Tablets

1. Name Of The Medicinal Product

Co-Amilofruse 5/40mg Tablets

2. Qualitative And Quantitative Composition

Furosemide 40.00mg

Amiloride Hydrochloride (dihydrate) 5.68mg

For excipients, see 6.1.

3. Pharmaceutical Form

Tablet for oral use.

Pale orange circular, flat faced beveled edge tablets debossed with 'ARD' '|' 40 on one side and plain on the other side.

.

4. Clinical Particulars

4.1 Therapeutic Indications

Co-amilofruse is indicated where a prompt diuresis is required especially in conditions where potassium conservation is important: congestive cardiac failure, nephrosis, fluid retention due to corticosteroid or oestrogen therapy and ascites associated with cirrhosis.

4.2 Posology And Method Of Administration

The starting dose is usually 5/40mg, subsequent dosage being adjusted to suit the needs of the patient.

Adults:

One to two tablets to be taken in the morning.

Children:

Not indicated for children.

Elderly:

The dosage should be adjusted according to diuretic response. Serum electrolytes and urea should be carefully monitored.

4.3 Contraindications

Known hypersensitivity to the active ingredients or any of the excipients. Hyperkalaemia (serum potassium> 5.5 mmol/litre), Addison's disease, acute renal failure, anuria, severe progressive renal disease, precomatose states associated with cirrhosis, concomitant potassium supplements or potassium sparing diuretics, electrolyte imbalance.

Co-amilofruse is contraindicated in children, as safety in this age group has not been established.

4.4 Special Warnings And Precautions For Use

Hyperkalaemia has been observed in patients receiving amiloride hydrochloride. Clinical condition and serum electrolytes must be carefully and continuously monitored if combination with an ACE inhibitor is deemed essential (see Interactions).

Serum uric acid levels may rise during treatment with Co-amilofruse and acute attacks of gout may be precipitated. Furosemide may cause latent diabetes to become manifest.

Patients with prostatic hypertrophy or impairment of micturition have an increased risk of developing acute urinary retention during diuretic therapy.

Patients who are being treated with this preparation require regular supervision, with monitoring of electrolyte status and fluid status to avoid excessive loss of fluid.

Co-amilofruse should be used with caution in elderly or those with potential obstruction of the urinary tract or disorders rendering electrolyte balance precarious.

Hyponatraemia, hypochloremia and raised blood urea nitrogen may occur during vigorous diuresis, especially in seriously ill patients. Careful monitoring of serum electrolytes and urea should therefore be undertaken in these patients. The haematopoietic state should be monitored regularly during treatment.

Co-amilofruse should be discontinued before a glucose tolerance test.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

ACE inhibitors may elevate serum potassium levels especially in the presence of renal impairment, and combination with Co-amilofruse is best avoided in elderly patients or in any others in whom renal function may be compromised. The dosage of concurrently administered antihypertensive agents, cardiac glycosides, lithium or non-depolarising muscle relaxants may require adjustment. It may be necessary to increase the dose of hypoglycaemic agents in diabetic patients. Concomitant use of Co-amilofruse with cephaloridine may increase cephaloridine-induced nephrotoxicity. Likewise, use with aminoglycoside antibiotics may increase the associated ototoxicity. Some NSAIDs e.g. indometacin, may antagonise the action of Furosemide.

4.6 Pregnancy And Lactation

There is no evidence of safety in either human pregnancy or lactation.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Nausea, vomiting, malaise, gastric upset, diarrhoea and constipation may occur. If skin rashes or pruritus occurs, treatment should be withdrawn.

Rare complications may include disturbances in liver function tests, ototoxicity and minor psychiatric disturbances. Bone marrow depression occasionally complicates treatment, necessitating withdrawal of the product.

4.9 Overdose

Treatment should be aimed at reversing dehydration and correcting electrolyte imbalance, particularly hyperkalaemia. If hyperkalaemia is seen, appropriate measures to reduce serum potassium must be instituted. Emesis should be induced or gastric lavage performed. Treatment is symptomatic and supportive.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Furosemide is a potent loop diuretic with a rapid action. Its effects are evident within one hour when administered orally, lasting four to six hours, and onset five minutes after intravenous injection, persisting for up to two hours. It has been reported to exert inhibiting effects on electrolyte reabsorption in the proximal and distal renal tubules, and in the ascending loop of Henle. Excretion of sodium, potassium and chloride ions is increased and water excretion enhanced.

Amiloride hydrochloride is a mild diuretic, which appears to act mainly on the distal renal tubules. It takes effect about two hours after oral administration and persists for up to 24 hours. The full effect may be delayed until after several days of treatment. It increases the excretion of sodium and chloride and reduces the excretion of potassium. Amiloride adds to the natriuretic but diminishes the kaliuretic effects of other diuretics and is used as an adjunct to Furosemide to conserve potassium.

5.2 Pharmacokinetic Properties

Furosemide is incompletely but fairly rapidly absorbed from the gastrointestinal tract. It has a biphasic half-life in the plasma with a terminal elimination phase that has been estimated to range up to one and a half-hours. It is up to 99% bound to plasma proteins, and is mainly excreted in the urine, largely unchanged, but also in the form of the glucuronide and free amine metabolites. Variable amounts are also excreted in bile, non-renal elimination being considerably increased in renal failure. Furosemide crosses the placental barrier and is excreted in milk.

Amiloride is incompletely absorbed from the gastrointestinal tract; peak serum concentrations are achieved about three to four hours after oral administration. It is excreted unchanged in the urine, and animal studies have shown little evidence of any biliary excretion. Amiloride has been estimated to have a serum half-life of about six hours.

5.3 Preclinical Safety Data

There are no pre-clinical data of any relevance to the prescriber, which are additional to those already included in other sections.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose monohydrate

Microcrystalline Cellulose

15005 Dispersed Sunset Yellow FCF Lake

Povidone K30

Sodium Starch Glycollate

Magnesium Stearate

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.

6.5 Nature And Contents Of Container

Opaque white blister packs manufactured from UPVC and aluminium foil containing 28,30, 56, or 60 tablets.

Polypropylene or polyethylene tablet containers with a lid containing 100 or 500 tablets.

6.6 Special Precautions For Disposal And Other Handling

None

7. Marketing Authorisation Holder

Aurobindo Pharma Limited

Ares Block, Odyssey Business Park

West End Road

South Ruislip

HA4 6QD

United Kingdom

8. Marketing Authorisation Number(S)

PL 20532/0084

9. Date Of First Authorisation/Renewal Of The Authorisation

27/03/2009

10. Date Of Revision Of The Text

27/03/2009

Jimrost

Jimrost may be available in the countries listed below.

Ingredient matches for Jimrost

Manidipine

Manidipine dihydrochloride (a derivative of Manidipine) is reported as an ingredient of Jimrost in the following countries:

• Japan

International Drug Name Search

Geodon

Pronunciation: zi-PRAS-i-done
Generic Name: Ziprasidone
Brand Name: Geodon

Geodon is an atypical antipsychotic. It may increase the risk of death when used to treat mental problems caused by dementia in elderly patients. Most of the deaths were linked to heart problems or infection. Geodon is not approved to treat mental problems caused by dementia. Discuss any questions or concerns with your doctor.

Geodon is used for:

Treating acute agitation in patients with schizophrenia who require an injectable medicine. It may also be used for other conditions as determined by your doctor.

Geodon is an antipsychotic. It may work by altering the balance of certain chemicals that occur naturally in the brain, which are responsible for thinking and behavior.

Do NOT use Geodon if:

• you are allergic to any ingredient in Geodon


• you have recently had a heart attack, have severe heart failure, or have a history of certain types of irregular heartbeat (eg, long QT syndrome)


• you are taking astemizole, cisapride, dofetilide, droperidol, halofantrine, levomethadyl, a macrolide immunosuppressive (eg, tacrolimus), mefloquine, methadone, nilotinib, pentamidine, certain phenothiazines (eg, thioridazine), pimozide, probucol, procainamide, quinidine, certain quinolone antibiotics (eg, moxifloxacin), a serotonin receptor antagonist antiemetic (eg, dolasetron), sotalol, sparfloxacin, terfenadine, or tetrabenazine

Contact your doctor or health care provider right away if any of these apply to you.

Before using Geodon:

Some medical conditions may interact with Geodon. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have considered or attempted suicide


• if you have had any problems with fainting or dizziness


• if you have a history of heart problems (eg, heart failure, slow or irregular heartbeat), low blood potassium or magnesium levels, low blood volume, low white blood cell counts, a drug-induced movement disorder, diabetes, kidney or liver problems, stroke, heart attack, low blood pressure, seizures, difficulty swallowing, neuroleptic malignant syndrome (NMS), Alzheimer disease, or dementia


• if you have diabetes or a family history of diabetes or if you are very overweight


• if you have had high blood prolactin levels or a history of certain types of cancer (eg, breast, pancreas, pituitary), or if you are at risk for breast cancer


• if you are dehydrated, drink alcohol, or will be exposed to high temperatures

Some MEDICINES MAY INTERACT with Geodon. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Arsenic, astemizole, bepridil, chloroquine, cisapride, class III antiarrhythmics (eg, amiodarone, sotalol), dofetilide, domperidone, droperidol, halofantrine, haloperidol, IA and IC antiarrhythmics (eg, flecainide, procainamide, propafenone, quinidine), kinase inhibitors (eg, lapatinib, nilotinib), levomethadyl , macrolide immunosuppressives (eg, tacrolimus), macrolides and ketolides (eg, azithromycin, erythromycin), maprotiline, mefloquine, methadone, pentamidine, phenothiazines (eg, thioridazine), pimozide, probucol, quinolones (eg, ciprofloxacin, moxifloxacin), serotonin receptor antagonist antiemetics (eg, dolasetron), sparfloxacin, streptogramins (eg, mitomycin, pristinamycin), terfenadine, or tetrabenazine because the risk of side effects such as abnormal heart rhythms may be increased


• Tramadol because the risk of seizures may be increased


• Ketoconazole because it may increase the risk of Geodon's side effects


• Carbamazepine because it may decrease Geodon's effectiveness

This may not be a complete list of all interactions that may occur. Ask your health care provider if Geodon may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Geodon:

Use Geodon as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Geodon is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Geodon at home, a health care provider will teach you how to use it. Be sure you understand how to use Geodon. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.


• Do not use Geodon if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.


• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.


• If you miss a dose of Geodon, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Geodon.

Important safety information:

• Geodon may cause drowsiness, dizziness, or lightheadedness. These effects may be worse if you take it with alcohol or certain medicines. Use Geodon with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not drink alcohol or use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Geodon; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Geodon may cause dizziness, lightheadedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.


• Do not become overheated in hot weather or while you are being active; heatstroke may occur.


• Geodon may rarely cause a prolonged, painful erection. This could happen even when you are not having sex. If this is not treated right away, it could lead to permanent sexual problems such as impotence. Contact your doctor right away if this happens.


• Geodon is intended for short-term control of acute agitation symptoms. If you require continuous treatment for your condition, your doctor may switch you to an oral medicine.


• Geodon may lower the ability of your body to fight infection. Avoid contact with people who have colds or infections. Tell your doctor if you notice signs of infection like fever, sore throat, rash, or chills.


• Geodon may raise your blood sugar. High blood sugar may make you feel confused, drowsy, or thirsty. It can also make you flush, breathe faster, or have a fruit-like breath odor. If these symptoms occur, tell your doctor right away.


• Diabetes patients - Geodon may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Serotonin syndrome is a possibly fatal syndrome that can be caused by Geodon. Your risk may be greater if you take Geodon with certain other medicines (eg, "triptans," monoamine oxidase inhibitors [MAOIs]). Symptoms may include agitation; confusion; hallucinations; coma; fever; fast or irregular heartbeat; tremor; excessive sweating; and nausea, vomiting, or diarrhea. Contact your doctor at once if you have any of these symptoms.


• NMS is a possibly fatal syndrome that can be caused by Geodon. Symptoms may include fever; stiff muscles; confusion; abnormal thinking; fast or irregular heartbeat; and sweating. Contact your doctor at once if you have any of these symptoms.


• Geodon may increase the amount of a certain hormone (prolactin) in your blood. Symptoms may include enlarged breast, missed menstrual period, decreased sexual ability, or nipple discharge. Contact your doctor right away if you experience any of these symptoms.


• Some patients who take Geodon may develop muscle movements that they cannot control. This is more likely to happen in elderly patients, especially women. The chance that this will happen or that it will become permanent is greater in those who take Geodon in higher doses or for a long time. Muscle problems may also occur after short-term treatment with low doses. Tell your doctor at once if you have muscle problems with your arms; legs; or your tongue, face, mouth, or jaw (eg, tongue sticking out, puffing of cheeks, mouth puckering, chewing movements) while taking Geodon.


• Lab tests, including electrolyte levels, complete blood cell counts (CBC), or fasting blood sugar levels, may be performed while you use Geodon. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Geodon with caution in the ELDERLY; they may be more sensitive to its effects, especially dizziness and lightheadedness upon sitting or standing up and uncontrolled muscle movements.


• Geodon should not be used in CHILDREN; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of taking Geodon while you are pregnant. Using Geodon during the third trimester may result in uncontrolled muscle movements or withdrawal symptoms in the newborn. Discuss any questions or concerns with your doctor. It is not known if Geodon is found in breast milk. Do not breast-feed while taking Geodon.

Possible side effects of Geodon:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Anxiety; constipation; diarrhea; dizziness; drowsiness; dry mouth; feeling unusually tired or sleepy; headache; increased cough or runny nose; loss of appetite; nausea; pain at the injection site; restlessness; upset stomach; vomiting; weakness; weight gain.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thoughts; change in amount of urine produced; confusion; decreased sexual ability; difficulty speaking or swallowing; enlarged breasts; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; inability to move; missed menstrual period; muscle rigidity; muscle spasms or twitching; nipple discharge; pounding in the chest; prolonged or painful erection; seizures; shortness of breath; suicidal thoughts or attempts; sweating; symptoms of high blood sugar (increased thirst, increased urination, confusion, flushing, rapid breathing, or fruity breath odor); tremor; uncontrolled movements (eg, arm or leg movements, twitching of the face or tongue, jerking or twisting); unusual mood or mental changes; vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Geodon side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include fainting; irregular heartbeat; seizure; slurring of speech; uncontrolled movement of the head and neck.

Proper storage of Geodon:

Geodon is usually handled and stored by a health care provider. If you are using Geodon at home, store Geodon as directed by your pharmacist or health care provider. Keep Geodon, as well as needles and syringes, out of the reach of children and away from pets.

General information:

• If you have any questions about Geodon, please talk with your doctor, pharmacist, or other health care provider.


• Geodon is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Geodon. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Geodon resources

• Geodon Side Effects (in more detail)
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• Geodon Support Group
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• Geodon Prescribing Information (FDA)


• Geodon Consumer Overview


• Geodon Monograph (AHFS DI)


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