Madopar 50mg/12.5mg, 100mg/25mg Dispersible Tablets

  • Name:

    Madopar 50mg/12.5mg, 100mg/25mg Dispersible Tablets

  • Company:
    info
  • Active Ingredients:

    Benserazide Hydrochloride, Levodopa

  • Legal Category:

    Product subject to medical prescription which may be renewed (B)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 28/08/18

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Summary of Product Characteristics last updated on medicines.ie: 28/8/2018

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Roche Products (Ireland) Ltd

Roche Products (Ireland) Ltd

Company Products

Medicine NameActive Ingredients
Medicine Name Madopar 200mg/50mg Hard Capsules Active Ingredients Benserazide Hydrochloride, Levodopa
Medicine Name Madopar 50mg/12.5mg, 100mg/25mg Dispersible Tablets Active Ingredients Benserazide Hydrochloride, Levodopa
Medicine Name Pulmozyme 2500 U/2.5ml Nebuliser Solution Active Ingredients Dornase Alfa
Medicine Name Rivotril 0.5mg Tablets Active Ingredients Clonazepam
Medicine Name Roaccutane 10mg Soft Capsules Active Ingredients Isotretinoin
Medicine Name Roaccutane 20mg Soft Capsules Active Ingredients Isotretinoin
Medicine Name Rocephin 1g Powder and Solvent for IM Injection Only Active Ingredients Ceftriaxone sodium
Medicine Name Rocephin 1g Powder for Solution for Injection or Infusion Active Ingredients Ceftriaxone sodium
Medicine Name Valcyte 450 mg Film-coated Tablets Active Ingredients valganciclovir hydrochloride
Medicine Name Valcyte 50mg/ml Powder for Oral Solution Active Ingredients valganciclovir hydrochloride
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When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 28 August 2018 PIL

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Updated on 28 August 2018 SmPC

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Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 12 May 2018 SmPC

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Updated on 18 July 2016 SmPC

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Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 18 July 2016 SmPC

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  • Change to section 4.3 - Contraindications
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

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4.3    Contra-indications

Madopar must not be given to patients with a known hypersensitivity to levodopa or benserazide or any of the excipients.

[ ... ]


4.5    Interaction with other medicinal products and other forms of interaction


[ ... ]

Levodopa may affect the results of laboratory tests for catecholamines, ketone bodies, creatinine, uric acid and glucose. The urine test results may give a false positive for ketone bodies. Levodopa therapy has been reported to inhibit the response to protirelin in tests of thyroid function.  Coombs' tests may give a false-positive result in patients taking Madopar.


[ ... ]

10.    Date of Revision of the text

15 May 201512 July 2016





[ ... ]

Updated on 20 May 2015 PIL

Reasons for updating

  • New PIL for new product

Updated on 20 May 2015 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

4.5             Interaction with other medicinal products and other forms of interaction
[...]

Domperidone may increase the bioavailability of  levodopa by stimulation of gastric emptying.

[...]

Combination with other anti-parkinsonian agents such as anticholinergics, amantadine, selegiline, bromocriptine and dopamine agonists are permissible, though both the desired and undesired effects of treatment may be intensified.  It may be necessary to reduce the dosage of Madopar or the other substance.  When initiating an adjuvant treatment with a COMT inhibitor, a reduction of the dosage of Madopar may be necessary.  Anticholinergics should not be withdrawn abruptly when Madopar therapy is instituted, as levodopa does not begin to take effect for some time.

[...]

Concomitant administration of antipsychotics with dopamine-receptor blocking properties, particularly D2-receptor antagonists might antagonise the antiparkinsonian effects of levodopa-benserazide.  Levodopa may reduce antipsychotic effects of these drugs.  These drugs should be co-administered with caution.

[...]

4.8                  Undesirable effects
[...]
Other body fluids or tissues may also be discoloured or stained including saliva, the tongue, teeth or oral mucosa.

[...]

10                  DATE OF REVISION OF THE TEXT

15 May 2015

 

Updated on 20 May 2015 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to date of revision

Updated on 17 September 2014 PIL

Reasons for updating

  • Change to date of revision
  • Addition of information on reporting a side effect.

Updated on 7 July 2014 SmPC

Reasons for updating

  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Underlined text = new text

Strike-through text = deleted text                                                                                                                                                

4.3       Contra-indications

Madopar must not be given to patients with a known hypersensitivity to levodopa or benserazide.

 

Madopar is contra-indicated in narrow-angle glaucoma (it may be used in wide-angle glaucoma provided that the intra-ocular pressure remains under control); severe psychoneuroses or psychoses; severe endocrine, renal, hepatic or cardiac disorders.

 

It should not be given in conjunction with, or within two weeks of withdrawal of, monoamine oxidase (MAO) inhibitors except selective MAO-B inhibitors (e.g. selegiline) or selective MAO-A inhibitors (e.g. moclobemide) Madopar must not be given in conjunction with non-selective monoamine oxidase (MAO) inhibitors. However, selective MAO-B inhibitors, such as selegiline and rasagiline or selective MAO-A inhibitors, such as moclobemide, are not contraindicated. Combination of MAO-A and MAO-B inhibitors is equivalent to non-selective MAO inhibition, and hence this combination should not be given concomitantly with Madopar (see section 4.5).

 

Madopar must not be given to patients with decompensated endocrine (e.g. phaeochromocytoma, hyperthyroidism, Cushing syndrome), renal (except RLS patients on dialysis) or hepatic function, cardiac disorders (e.g. severe cardiac arrhythmias and cardiac failure), psychiatric diseases with a psychotic component or closed angle glaucoma (it may be used in wide-angle glaucoma provided that the intra-ocular pressure remains under control).

 

Madopar mustIt should not be given to patients less thanunder 25 years oldf age (skeletal development must be complete).

 

It shouldMadopar must not be given to pregnant women or to women of childbearing potential in the absence of adequate contraception.  If pregnancy occurs in a woman taking Madopar, the drug must be discontinued (as advised by the prescribing physician).

 

Suspicion has arisen that levodopa may activate a malignant melanoma.  Therefore, Madopar should not be used in persons who have a history of, or who may be suffering from, a malignant melanoma.

 

4.4       Special warnings and precautions for use

When other drugs must be given in conjunction with Madopar, the patient should be carefully observed for unusual side-effects or potentiating effects.

 

Hypersensitivity reactions may occur in susceptible individuals.

 

Regular measurement of intraocular pressure is advisable in patients with open-angle glaucoma, as levodopa theoretically has the potential to raise intraocular pressure.

 

Care should be taken when using Madopar in the following circumstances:  in endocrine, renal, pulmonary or cardiovascular disease, particularly where there is a history of myocardial infarction or arrhythmia; psychiatric disturbances (e.g. depression); hepatic disorder; peptic ulcer; osteomalacia; where sympathomimetic drugs may be required (e.g. bronchial asthma), due to possible potentiation of the cardiovascular effects of levodopa; where antihypertensive drugs are being used, due to possible increased hypotensive action.

 

Care should be exercised when Madopar is administered to patients with pre-existing coronary artery disorders, cardiac arrhythmias or cardiac failure (see also section 4.3). Cardiac function should be monitored with particular care in such patients during the period of treatment initiation and regularly thereafter throughout treatment.

 

Close monitoring of patients with risk factors for (e.g. elderly patients, concomitant antihypertensives or other medication with orthostatic potential) or a history of orthostatic hypotension is recommended especially at the beginning of treatment or at dose increases.

 

Madopar has been reported to induce decreases in blood count (e.g. haemolytic anaemia, thrombocytopenia and leukopenia). In a few instances agranulocytosis and pancytopenia have been reported in which the association with Madopar could neither be established, nor be completely ruled out. Therefore, periodical evaluation of blood count should be performed during treatment.

 

Depression can be part of the clinical picture in patients with Parkinson’s disease and RLS and may also occur in patients treated with Madopar. All patients should be carefully monitored for psychological changes and depression with or without suicidal ideation.

 

Madopar may induce dopamine dysregulation syndrome resulting in excessive use of the product. A small subgroup of PD patients suffer from cognitive and behavioural disturbance that can be directly attributed to taking increasing quantities of medication against medical advice and well beyond the doses required to treat their motor disabilities.

In the event of general anaesthesia being required, Madopar therapy may be continued as long as the patient is able to take fluids and medication by mouth.  If therapy is temporarily interrupted, the usual daily dosage may be administered as soon as the patient is able to take oral medication.  Whenever therapy has been interrupted for longer periods, dosage should again be adjusted gradually; however, in many cases the patient can rapidly be returned to his previous therapeutic dosage.

 

If a patient requires a general anaesthetic, the normal Madopar regimen should be continued as close to the surgery as possible, except in the case of halothane. In general anaesthesia with halothane Madopar should be discontinued 12 - 48 hours before surgical intervention as fluctuations in blood pressure and/or arrhythmias may occur in patients on Madopar therapy. Madopar therapy may be resumed following surgery; the dosage should be increased gradually to the preoperative level.

 

If a patient has to undergo emergency surgery, when Madopar has not been withdrawn, anaesthesia with halothane should be avoided.

 

There have been occasional reports of a neuroleptic malignant-like syndrome, involving hyperthermia, on abrupt withdrawal of levodopa preparations.  Sudden discontinuation of Madopar, without close supervision, or “drug holidays” should therefore be avoided. Madopar must not be withdrawn abruptly. Abrupt withdrawal of the preparation may result in a neuroleptic malignant-like syndrome (hyperpyrexia and muscular rigidity, possibly psychological changes and elevated serum creatinine phosphokinase, additional signs in severe cases may include myoglobinuria, rhabdomyolysis – and acute renal failure) which may be life-threatening. Should a combination of such symptoms and signs occur, the patient should be kept under medical surveillance, if necessary, hospitalized and rapid and appropriate symptomatic treatment given. This may include resumption of Madopar therapy after an appropriate evaluation.

 

Pyridoxine (vitamin B6) may be given with Madopar since the presence of a decarboxylase inhibitor protects against the peripheral levodopa transformation facilitated by pyridoxine.

 

Levodopa has been associated with somnolence and episodes of sudden sleep onset.  Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported very rarely.  Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with levodopa.  Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines.  Furthermore a reduction of dosage or termination or therapy may be considered (see section 4.7).

 

. 

Impulse control disorders

Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa, including Madopar. Review of treatment is recommended if such symptoms develop.

 

Care should be taken when using Madopar in the following circumstances:  In endocrine, renal, pulmonary or cardiovascular disease, particularly where there is a history of myocardial infarction or arrhythmia; psychiatric disturbances (e.g. depression); hepatic disorder; peptic ulcer; osteomalacia; where sympathomimetic drugs may be required (e.g. bronchial asthma), due to possible potentiation of the cardiovascular effects of levodopa; where antihypertensive drugs are being used, due to possible increased hypotensive action.

 

Periodical evaluation of hepatic, haemopoietic, renal and cardiovascular function and blood count should be performed during treatments is advised.

 

Patients with diabetes should undergo frequent blood sugar tests and the dosage of anti-diabetic agents should be adjusted to blood sugar levels.

Patients who improve on Madopar therapy should be advised to resume normal activities gradually as rapid mobilisation may increase the risk of injury.

 

Malignant melanoma

Epidemiological studies have shown that patients with Parkinson's disease have a higher risk of developing melanoma than the general population (approximately 2-6 fold higher). It is unclear whether the increased risk observed was due to Parkinson's disease, or other factors such as levodopa used to treat Parkinson's disease. Therefore patients and providers are advised to monitor for melanomas on a regular basis when using Madopar for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g. dermatologists).

 

4.5       Interaction with other medicinal products and other forms of interaction

Pharmacokinetic interactions

 

Co-administration of the anticholinergic drug trihexyphenidyl with standard dosage form of Madopar reduces the rate, but not the extent, of levodopa absorption. Trihexyphenidyl given concomitantly with Madopar CR formulation does not affect the pharmacokinetics of levodopa.

 

Ferrous sulfphate decreases maximum plasma concentration and the AUC of levodopa by 30 ‑ 50%.  The pharmacokinetic changes observed during co-treatment with ferrous sulfphate appear to be clinically significant in some but not all patients.

 

Opioids and drugs which interfere with central amine mechanisms, such as rauwolfia alkaloids (reserpine), tetrabenazine (Nitoman), metoclopramide, phenothiazines, thioxanthenes, butyrophenones, amphetamines and papaverine, should be avoided where possible. If, however, their administration is considered essential, extreme care should be exercised and a close watch kept for any signs of potentiation, antagonism or other interactions and for unusual side-effects.  Metoclopramide has been shown to increases the rate of levodopa absorption.

 

Pharmacodynamic interactions

 

Neuroleptics, opioids and antihypertensive medications containing reserpine inhibit the action of Madopar.

 

Concomitant administration of antipsychotics with dopamine-receptor blocking properties, particularly D2-receptor antagonists might antagonize the antiparkinsonian effects of  Madopar, therefore, should be carried out with caution, and the patient carefully observed for loss of antiparkinsonian effect and worsening of parkinsonian symptoms.

 

Symptomatic orthostatic hypotension occurred when combinations of levodopa and a decarboxylase inhibitor were added to the treatment of patients already receiving antihypertensives. Madopar needs to be introduced cautiously in patients receiving antihypertensive medication. Blood pressure needs to be monitored to allow for potential dosage adjustment of either of the drugs, if required.

 

Concomitant administration of Madopar with sympathomimetics (agents such as epinephrine, norepinephrine, isoproterenol or amphetamine which stimulate the sympathetic nervous system) may potentiate their effects, therefore these combinations are not recommended. Should concomitant administration prove necessary, close surveillance of the cardiovascular system is essential, and the dose of the sympathomimetic agents may need to be reduced.

 

If Madopar is to be administered to patients receiving irreversible non-selective MAO inhibitors, an interval of at least 2 weeks should be allowed between cessation of the MAO inhibitor and the start of Madopar therapy. Otherwise unwanted effects such as hypertensive crises are likely to occur (see 4.3 Contraindications). Selective MAO-B inhibitors, such as selegiline and rasagiline and selective MAO-A inhibitors, such as moclobemide, can be prescribed to patients on levodopa-benserazide. It is recommended to readjust the levodopa dose to the individual patient’s needs, in terms of both efficacy and tolerability. Combination of MAO-A and MAO-B inhibitors is equivalent to non-selective MAO inhibition, and hence this combination should not be given concomitantly with Madopar (see 4.3 Contraindications).

 

Combination with other anti-parkinsonian agents such as (anticholinergics, amantadine, and dopamine agonists) areis permissible, though both the desired and undesired effects of treatment may be intensified.  It may be necessary to reduce the dosage of Madopar or the other substance.  When initiating an adjuvant treatment with a COMT inhibitor, a reduction of the dosage of Madopar may be necessary.  Anticholinergics should not be withdrawn abruptly when Madopar therapy is instituted, as levodopa does not begin to take effect for some time.

 

Use with antihypertensive agents may increase the hypotensive response, while sympathomimetics may increase the cardiovascular side-effects of levodopa.

 

Levodopa may affect the results of laboratory tests interfere chemically with several diagnostic laboratory tests including those for catecholamines, ketone bodies, creatinine, uric acid and glucose, ketone bodies or catecholamines in urine and for glucose or uric acid in blood.  Levodopa therapy has been reported to inhibit the response to protirelin tests of thyroid function. 

 

Coombs’ tests may give a false-positive result in patients taking Madopar.

 

A diminution of effect is observed when the drug is taken with a protein-rich meal.

 

General anaesthesia with halothane: levodopa-benserazide should be discontinued 12-48 hours before surgical intervention requiring general anaesthesia with halothane as fluctuations in blood pressure and/or arrhythmias may occur. For general anesthesia with other anaesthetics see section 4.4.

 

 

4.6       Pregnancy and lactation

Madopar is contra-indicated in pregnancy and in women of child-bearing potential, in the absence of adequate contraception (see section 4.3 and section 5.3), since there is evidence of harmful effects in studies in pregnant rabbits and the benserazide component has been found to be associated with skeletal malformations in the rat.  If pregnancy occurs in a woman taking Madopar, the drug must be discontinued.  Patients taking Madopar should not breast-feed their infants.

Since it is not known whether benserazide passes into breast milk, mothers requiring Madopar treatment should not nurse their infants, since the occurrence of skeletal malformations in the infants cannot be excluded.

 

4.8       Undesirable effects

The following undesirable effects have been reported (frequency not known, cannot be estimated from the available data) to occur when levodopa- benserazide is administered:

 

Frequency categories are as follows:

Very common: ³1/10;

Common ³1/100 to <1/10;

Uncommon ³1/1,000 to <1/100

Rare (³1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

 

 

Blood and Lymphatic System Disorder

frequency not known

Haemolytic anaemia

Leukopenia

Thrombocytopenia

Metabolic and nutritional disorders

frequency not known

Decreased appetite

Psychiatric Disorders

frequency not known

Dopamine dysregulation syndrome

Confusional state

Depression

Agitation *

Anxiety*

Insomnia*

Hallucination*

Delusion*

Disorientation*

Pathological gambling

Increased libido

Hypersexuality

Compulsive shopping

Binge eating

Eating disorder symptom

Nervous System Disorders

frequency not known

Ageusia

Dysgeusia

Dyskinesia (choreiform and athetotic)

Fluctuations in therapeutic response

Freezing phenomenon

End-of-dose deterioration

On and off phenomenon

Somnolence

Sudden onset of sleep

Cardiac disorders

frequency not known

Arrhythmia

Vascular Disorders

frequency not known

Orthostatic hypotension

 

Gastrointestinal disorders

frequency not known

Nausea

Vomiting

Diarrhoea

Saliva discolouration

Tongue discolouration

Tooth discolouration

Oral mucosa discolouration

Liver and Biliary disorders

frequency not known

Transaminases increased

Alkaline phosphatase increased

Gamma-glutamyltransferase increased

Skin and subcutaneous tissue disorders

frequency not known

Pruritus

Rash

Musculoskeletal and connective tissue disorders

frequency not known

Restless legs syndrome

Renal and urinary disorders

frequency not known

Blood urea increased

 

 Chromaturia

 

*These events may occur particularly in elderly patients and in patients with a history of such disorders.

 

Impulse Control Disorders:

-          Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa including Madopar. (see section 4.4).

 

Nervous System Disorder:

Psychiatric disturbances are common in Parkinsonian patients, including those treated with levodopa, including mild elation, anxiety, agitation, insomnia, drowsiness, depression, aggression, delusions, hallucinations, temporal disorientation and “unmasking” of psychoses.

 

At later stages of the treatment, dyskinesia (e.g. choreiform or athetotic) may occur. These can usually be eliminated or be made tolerable by a reduction of dosage. With prolonged treatment, fluctuations in therapeutic response may also be encountered.

 

They include freezing episodes, end-of-dose deterioration and the “on-off” effect. These can usually be eliminated or made tolerable by adjusting the dosage and by giving smaller single doses more frequently. An attempt at increasing the dosage again can subsequently be made in order to intensify the therapeutic effect. Levodopa-benserazide is associated with somnolence and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes.

 

Gastrointestinal:

-          Undesirable gastrointestinal effects, which may occur mainly in the early stages of the treatment, can largely be Anorexia, nausea, vomiting, diarrhoea (less commonly than with levodopa) mainly occurring in the early stages of treatment.  May be controlled by taking Madopar with some food or liquid or by increasing the dose slowly.

-          Gastro-intestinal bleeding has been reported with levodopa therapy.

-          Isolated cases of loss or alterations of taste.

 

Vascular Disorders:

Orthostatic disorders commonly improve following reduction of the Madopar dosage.

 

Musculoskeletal and connective tissue disorders:

Restless Legs Syndrome: The development of augmentation (time shift of symptoms from the evening/night into the early afternoon and evening before taking the next nightly dose, is the most common adverse effect of dopaminergic long-term treatment.

Skin:

-            rarely allergic reactions such as pruritus and rash.

 

Cardiovascular:

-            Occasional reports of cardiac arrhythmias and orthostatic hypotension (less frequently than with levodopa alone).  Orthostatic disorders usually improve following dosage reduction.

Haematological:

-            Rare cases of haemolytic anaemia, transient leukopenia and thrombocytopenia.

 

Neuropsychiatric:

-            Psychiatric disturbances are common in Parkinsonian patients, including those treated with levodopa, including mild elation, anxiety, agitation, insomnia, drowsiness, depression, aggression, delusions, hallucinations, temporal disorientation and “unmasking” of psychoses.

-            Levodopa is associated with somnolence and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes.

-             

-            Involuntary movements (e.g. choreiform or athetotic, oral dyskinesias, “paddling” foot) are common, particularly on long-term administration.  These are usually dose-dependant and may disappear or become tolerable after dose adjustment.

 

Impulse control disorders:

Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa, including Madopar (see section 4.4 'Special warnings and precautions for use).

 

Laboratory abnormalities:

-            Transient rises in SGOT, SGPT and alkaline phosphatase values have been noted.

-            Increase of gamma-Glutamyltransferase has been reported.

-            Serum uric acid and blood urea nitrogen levels are occasionally increased.

 

Others:

-          Flushing and sweating have been reported with levodopa.

 

Investigations:

 

-          Urine passed during treatment may be altered in colour; usually acquiring a red-tinged, whichthis will turns dark on standing.  These changes are due to metabolites and is no cause for concern.

 

Tolerance to Madopar varies widely between patients and is often related to the rate of dosage increases.  With long-term administration, fluctuations in the therapeutic response may be encountered.  They include “freezing” episodes, end-of-dose deterioration and the so-called “on-off” effect.  Patients may be helped by dosage reduction or by giving smaller and more frequent doses.

 

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to the Pharmacovigilance Section, Irish Medicines Board, Kevin O’Malley House, Earlsfort Centre, Earlsfort Terrace, IRL-Dublin 2.  Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.imb.ie, e-mail: imbpharmacovigilance@imb.ie.

 

 

10.       DATE OF REVISION OF THE TEXT

February 201325 June 2014

Updated on 4 July 2014 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to storage instructions
  • Change to side-effects
  • Change to date of revision
  • Addition of information on reporting a side effect.

Updated on 7 March 2013 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Underlined text = New text

 

Strike through text = Deleted text                                                                                 

 

 

4.4       Special warnings and precautions for use

[ … ]

 

Pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists and/or levodopa for Parkinson’s disease. 

Impulse control disorders

Patients should be regularly monitored for the development of impulse control disorders. Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa, including Madopar. Review of treatment is recommended if such symptoms develop.

 

[ … ]

 

 

4.8       Undesirable effects

[ … ]

 

Neuropsychiatric:

-          Psychiatric disturbances are common in Parkinsonian patients, including those treated with levodopa, including mild elation, anxiety, agitation, insomnia, drowsiness, depression, aggression, delusions, hallucinations, temporal disorientation and “unmasking” of psychoses.

-          Levodopa is associated with somnolence and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes.

-          Patients treated with dopamine agonists and/or levodopa for treatment of Parkinson’s disease, especially at high doses, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality, generally reversible upon reduction of the dose  or treatment discontinuation. 

-          Involuntary movements (e.g. choreiform or athetotic, oral dyskinesias, “paddling” foot) are common, particularly on long-term administration.  These are usually dose-dependant and may disappear or become tolerable after dose adjustment.

 

Impulse control disorders:

Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa, including Madopar (see section 4.4 'Special warnings and precautions for use).

 

[ … ]

 

10.       DATE OF REVISION OF THE TEXT

December 2009February 2013

 

Updated on 4 March 2013 PIL

Reasons for updating

  • Change to date of revision
  • Change to warnings or special precautions for use
  • Change to side-effects

Updated on 14 April 2011 PIL

Reasons for updating

  • Change to further information section

Updated on 10 August 2010 PIL

Reasons for updating

  • Correction of spelling/typing errors

Updated on 15 December 2009 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may be renewed (B)

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Section 4.8 has been updated:

 

Laboratory abnormalities:

-          Transient rises in SGOT, SGPT and alkaline phosphatase values have been noted.

-          Increase of gamma-Glutamyltransferase has been reported.

-          Serum uric acid and blood urea nitrogen levels are occasionally increased.

Updated on 10 November 2009 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration

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underlined text has been deleted:

1.1                          Posology and method of administration

Dosage and administration are variable and no more than a guide can be given.

 

Adults

Patients not previously treated with levodopa

The recommended initial dose is one capsule or dispersible tablet of Madopar 50mg/12.5 mg three or four times daily.  If the disease is at an advanced stage, the starting dose should be one capsule or dispersible tablet of Madopar 100mg/25mg three times daily.

 

The daily dosage should then be increased by one capsule or dispersible tablet of Madopar 100mg/25mg, or their equivalent, once or twice weekly until a full therapeutic effect is obtained, or side-effects supervene.

 

In some elderly patients, it may suffice to initiate treatment with one capsule or dispersible tablet of Madopar 50mg/12.5mg once or twice daily, increasing by one capsule or dispersible tablet every third or fourth day.

 

The effective dose usually lies within the range of four to eight capsules or dispersible tablets of Madopar 100mg/25mg (two to four capsules of Madopar 200mg/50mg) daily in divided doses, most patients requiring no more than six capsules or dispersible tablets of Madopar 100mg/25mg daily.

 

Optimal improvement is usually seen in one to three weeks but the full therapeutic effect of Madopar may not be apparent for some time.  It is advisable, therefore, to allow several weeks to elapse before contemplating dosage increments above the average dose range.  If satisfactory improvement is still not achieved, the dose of Madopar may be increased but with caution.  It is rarely necessary to give more than ten capsules or dispersible tablets of Madopar 100mg/25mg (five capsules of Madopar 200mg/50mg) per day.

 

Treatment should be continued for at least six months before failure is concluded from the absence of a clinical response.

 

Madopar 50mg/12.5mg capsules or dispersible tablets may be used to facilitate adjustment of dosage to the needs of the individual patient.  Patients who experience fluctuations in response may be helped by dividing the dosage into smaller, more frequent doses with the aid of Madopar 50mg/12.5mg capsules or dispersible tablets without, however, altering the total daily dose.

 

Madopar 200mg/50mg capsules are only for maintenance therapy once the optimal dosage has been determined using Madopar 100mg/25mg capsules or dispersible tablets.

 

Patients previously treated with levodopa

The following procedure is recommended:  Levodopa alone should be discontinued and Madopar started on the following day.  The patient should be initiated on a total of one less Madopar 100mg/25mg capsule or dispersible tablet daily than the total number of 500mg levodopa tablets or capsules previously taken (for example, if the patient had previously taken 2g levodopa daily, then he should start on three capsules or dispersible tablets Madopar 100mg/25mg daily on the following day). Observe the patient for one week and then, if necessary, increase the dosage in the manner described for new patients.

 

Patients previously treated with other levodopa/decarboxylase inhibitor combinations

Previous therapy should be withdrawn for 12 hours.  In order to minimise the potential for any effects of levodopa withdrawal, it may be beneficial to discontinue previous therapy at night and institute Madopar therapy the following morning.

 

The initial Madopar dose should be one capsule or dispersible tablet of Madopar 50mg/12.5mg three or four times daily.  This dose may then be increased in the manner described for patients not previously treated with levodopa.

 

Other anti-Parkinsonian drugs may be given with Madopar.  Existing treatment with other anti-Parkinsonian drugs, e.g. anticholinergics or amantadine, should be continued during initiation of Madopar therapy.  However, as treatment with Madopar proceeds and the therapeutic effect becomes apparent, the dosage of the other drugs may need to be reduced or the drugs gradually withdrawn. 

 

Elderly

Although there may be an age-related decrease in tolerance to levodopa in the elderly, Madopar appears to be well-tolerated and side-effects are generally not troublesome. 

 

Children

Not to be given to patients under 25 years of age, therefore, no dosage recommendations are made for the administration of Madopar to children.

 

Madopar capsules and dispersible tablets are for oral administration.  They should be taken with, or immediately after, meals.

 

Madopar dispersible tablets may be swallowed whole or dispersed in at least 25ml water per tablet.  They may be taken in dilute orange squash (at least 25ml per tablet) if preferred.  However, orange juice should not be used.  Madopar dispersible tablets are particularly suitable for patients who dislike taking capsules or have difficulty in swallowing solid dosage forms.

Updated on 28 August 2009 SmPC

Reasons for updating

  • Change to section 9 - Date of renewal of authorisation

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

updated date of renewal of authorisation / date of revision of text

Updated on 24 August 2009 PIL

Reasons for updating

  • Change due to user-testing of patient information

Updated on 28 April 2008 SmPC

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  • Change to section 4.9 - Overdose

Legal category: Product subject to medical prescription which may be renewed (B)

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Overdose

Symptoms and signs

Symptoms and signs of overdosage are qualitatively similar to the side-effects of Madopar but may be of greater severitymagnitude.

 

Overdose may lead to cardiovascular side effects (e.g. cardiac arrhythmias), psychiatric disturbances (e.g. confusion and insomnia), gastro-intestinal effects (e.g. nausea and vomiting) and abnormal involuntary movements (see section 4.8).

 

Treatment

Monitor the patient’s vital signs and institute supportive measures as indicated by the patient’s clinical state.  In particular patients may require symptomatic treatment for cardiovascular effects (e.g. antiarrhythmics) or central nervous system effects (e.g. respiratory stimulants, neuroleptics).

 

Treatment should include gastric lavage, general supportive measures, intravenous fluids and the maintenance of an adequate airway.

 

Electrocardiographic monitoring should be instituted and the patient carefully observed for the possible development of arrhythmias.  If necessary, anti-arrhythmic therapy should be given and other symptoms treated as they arise.

 

Updated on 24 September 2007 PIL

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 22 August 2007 PIL

Reasons for updating

  • Change to side-effects

Updated on 22 August 2007 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

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4.4              Special warnings and precautions for use

 

Pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists and/or levodopa for Parkinson’s disease.  Madopar is not a dopamine agonist, however caution is advised as Madopar is a dopaminergic drug.

 

4.8              Undesirable effects

 

-          Patients treated with dopamine agonists and/or levodopa for treatment of Parkinson’s disease, especially at high doses, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality, generally reversible upon reduction of the dose of treatment discontinuation.  Madopar is not a dopamine agonist, however there is the possibility that these adverse effects may occur as Madopar is a dopaminergic drug.

 

Updated on 27 April 2006 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 6.1 - List of excipients
  • Change to section 4.2 - Posology and method of administration
  • Change to section 6.4 - Special precautions for storage
  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 27 April 2006 PIL

Reasons for updating

  • Change of active ingredient
  • Change to marketing authorisation holder
  • Change to date of revision

Updated on 8 March 2006 PIL

Reasons for updating

  • Change to marketing authorisation holder
  • Change to date of revision

Updated on 10 October 2005 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 18 May 2005 PIL

Reasons for updating

  • New PIL for medicines.ie

Updated on 24 June 2003 SmPC

Reasons for updating

  • New SPC for medicines.ie

Legal category: Product subject to medical prescription which may be renewed (B)