- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Patients who have never before received Levodopa therapyLecado 100/25 mg is designed for use in patients, who have not previously had levodopa treatment or to aid titration in patients who receive Lecado 200/50 mg. The recommended starting dose is one tablet 100/25 mg two times per day. In patients who need more levodopa a daily dose of three to four tablets of Lecado 100/25 mg is usually well tolerated.For Lecado 200/500 mg the recommended starting dose is one tablet two times per day.The starting dose should not be higher than 600 mg levodopa per day and the doses should be administered with minimum intervals of six hours.Dose adjustments should occur with intervals of at least two to four days.Depending of the severity of the disease, six months of treatment may be required to achieve optimal disease control.
A guide to substitution for patients who are treated with the immediate-release combination of levodopa and decarboxylase inhibitorTransferring to Lecado 100/25 mg should initially occur in a dose that supplies at most about 10% more levodopa per day when higher doses are indicated (more than 900 mg daily). Levodopa and decarboxylase inhibitor should be discontinued at least 12 hours before the administration of Lecado. The dose interval should be prolonged by 30 % to 50% at intervals of ranging from 4 12 hours. If the divided doses are not equal it is recommended to administer the lowest dose at the end of the day. The dose should be adjusted depending on the clinical reaction, as indicated below in Dose Adjustment. It could be that doses which supply maximally 30% more levodopa per day are necessary.A guide for the substitution of Lecado prolonged-release treatment for immediate-release levodopa/carbidopa combinations is shown in the table below:
|Levodopa/carbidopa||Lecado 100/25 mg|
|Daily dose||Daily dose||Dose schedule|
|Levodopa (mg)||Levodopa (mg)|
|100 - 200||200||1 tablet, twice daily|
|300 - 400||400||4 tablets divided in 3 or more doses|
|Levodopa/carbidopa||Lecado 200/50 mg|
|Daily dose||Daily dose||Dose schedule|
|Levodopa (mg)||Levodopa (mg)|
|300-400||400||1 tablet, twice daily|
|500-600||600||1 tablet, 3 times per day|
Patients who are currently treated with just levodopaLevodopa must be discontinued at least twelve hours before therapy with levodopa/carbidopa tablet is started. In patients with a mild to moderate form of the disease the recommended starting dose is 200 mg levodopa / 50 mg carbidopa twice daily.• Dose AdjustmentAfter the treatment is established the doses and the dose frequency can be increased or decreased depending on the therapeutic response. Most patients are adequately treated with 400 mg levodopa / 100 mg carbidopa to 1600 mg levodopa / 400 mg carbidopa per day, administered in divided doses at intervals ranging from four to twelve hours during the waking day. Higher doses (up to 2400 mg levodopa / 600 mg carbidopa) and shorter intervals (less than four hours) have been used, but are generally not recommended.When doses of Lecado are given at intervals of less than four hours or if the divided doses are not equal, it is recommended to administer the lowest dose at the end of the day.The effect of the first morning dose can be delayed in some patients for up to one hour compared to the usual reaction of the first morning dose of immediate-release Levodopa/Carbidopa.Adjustments of the dosage should occur in intervals of at least three days.• Maintenance doseBecause Parkinson's Disease is progressive, periodic clinical check-ups are recommended and an adjustment of the dose schedule of Lecado may be needed. • Addition of other anti-Parkinson medicationsAnti-cholinergics, dopamine agonists and amantadine can be administered concomitantly with Lecado. It might be necessary to adjust the dose Lecado when these medications are added to an ongoing treatment of Lecado.• Interruption of the therapyPatients should be carefully observed in case of a sudden reduction of the dose or if it is necessary to discontinue treatment with Lecado, particularly in the patient who is receiving anti-psychotics. (see section 4.4).If anaesthetic is necessary, the administration of Lecado can be continued as long as the patient is allowed to take oral medications. In case of a temporary interruption of the therapy, the usual dose can be administered as soon as the patient is able to take the oral medications.• Use in ChildrenThe safety in patients under 18 years of age has not been established.• Use in the elderlyThere is a wide experience in the use of combinations of levodopa and carbidopa in elderly patients. The recommendations set out above reflect the clinical data derived from this experience.• Use in renal/hepatic impairmentNo dose adjustment is necessary.
Impulse control disordersPatients 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 eatingcan occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa, including Lecado 100/25 mg. Review of treatment is recommended if such symptoms develop.Patients with Parkinson's disease show a possible increased risk of melanoma, but no confirmed association with levodopa therapy has been established. Therefore caution should be exercised during treatment.Laboratory testsCarbidopa/levodopa preparations had given rise to abnormalities in several laboratory tests and these can also occur with Lecado. These include elevations of liver function tests, such as alkaline phosphatase, SGOT, SGPT, lactic acid dehydrogenase, bilirubin, blood urea nitrogen and a positive Coombs test.Decreased haemoglobin and haematocrit, elevated serum glucose and white blood cells, bacteria and blood in the urine have also been reported with Levodopa/Carbidopa.When a test strip is used to determine ketonuria, carbidopa/levodopa preparations can show a false positive result for urinary ketone bodies. This reaction is not altered by boiling the urine sample. False negative results can also occur in the examination of glycosuria with the use of glucose oxidase methods.
Anti-hypertensivesSymptomatic orthostatic dysregulation has occurred when levodopa is added with a decarboxylase inhibitor to certain antihypertensives. Dose adjustment of antihypertensives may be necessary during the titration phase of treatment with Lecado 100/25 mg.
Anti-depressivesThere have been rare reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant administration of tricyclic anti-depressants and carbidopa/levodopa preparations. (See section 4.3 for patients receiving mono-amine oxidase inhibitors).
Anti-cholinergicsAnti-cholinergics may act synergistically with levodopa to decrease tremor. However combined use may exacerbate abnormal involuntary movements. Anticholinergics may decrease the effects of levodopa by delaying its absorption. An adjustment of the dose of Levodopa/Carbidopa may be needed.
Other medicinesDopamine-D2-receptor antagonists (for instance phenothiazines, butyrophenons, risperidone), benzodiazepines and isoniazide can reduce the therapeutic effect of levodopa. The beneficial effects of levodopa in Parkinson's disease may be reduced by phenytoin and papaverine. Patients taking these medications together with Lecado, should be observed carefully for loss of therapeutic response.Concomitant use of selegiline and levodopa-carbidopa may be associated with severe orthostatic hypotension. (See also section 4.3)
COMT inhibitors (tolcapone, entacapone)Concomitant use of COMT (Catechol-O-Methyl Transferase) inhibitors and levodopa/carbidopa can increase the bioavailability of levodopa. The dose of levodopa/ carbidopa may possibly need adjusting.Amantadine has a synergistic effect with levodopa and may increase levodopa-related side events. An adjustment of the dose of levodopa/carbidopa may be needed.Metoclopramide increases gastric emptying and may increase the bioavailability of Lecado.Sympathomimetics may increase cardiovascular side events related to levodopaConcomitant use of ferrous sulphate and levodopa-carbidopa can lead to a reduction in the bioavailabillity of levodopa.As levodopa competes with certain amino acids, the absorption of levodopa can be impaired in some patients who are on a protein rich diet.The effect of administration of antacids and Lecado on the bioavailability of levodopa has not been studied.
PregnancyInsufficient data on the use of levodopa/carbidopa in pregnant women. The results of animal studies have shown reproduction toxicity. (see section 5.3). The potential human risk to the embryo or the foetus is not known.Lecado should not be used during pregnancy. Any woman of childbearing potential who is receiving Lecado 100/25 mg must practise effective contraception.
LactationLevodopa is secreted in breast milk in significant quantities. While using Lecado 100/25mg women should not breast-feed.
Blood and lymphatic system disordersRare (≥1/10,000 to <1/1,000): Leukopenia, haemolytic and non-haemolytic anaemia, thrombocytopeniaVery rare (<1/10,000): Agranulocytosis
Metabolism and nutrition disordersCommon (≥1/100 to < 1/10): AnorexiaUncommon (≥1/1,000 to <1/100): Loss of weight, increased weight
Psychiatric disordersCommon (≥1/100 to < 1/10): Hallucinations, confusion, dizziness, nightmares, sleepiness, fatigue, sleeplessness, depression with very rare suicide attempts, euphoria, dementia, psychotic episodes, feeling of stimulationRare (≥1/10,000 to <1/1,000): Agitation, fear, reduced thinking capacity, disorientation, headache, increased libido, numbness, convulsionsUnknown frequency: Impulse control disordersPathological 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 Levodopa/Carbidopa retard (see section 4.4).
Nervous system disordersCommon (≥1/100 to < 1/10): Dyskinesia (a higher frequency of dyskinesia was seen with Lecado than with the immediate-release formulation of Levodopa/Carbidopa), chorea, dystonia, extrapyramidal and movement disorders, the on-off-appearanceBradykinesia (on-off episodes) may appear some months to years after the beginning of treatment with levodopa and is probably related to the progression of the disease. The adaptation of dose schedule and dose intervals may be required.Uncommon (≥1/1,000 to <1/100): Ataxia, increased tremor of the handsRare (≥1/10,000 to <1/1,000): Malignant neuroleptic syndrome, paraesthesia, falling, walking defects, trismus
Eye disordersRare (≥1/10,000 to <1/1,000): Hazy vision, blepharospasm, activation of a latent Horner's syndrome, double vision, dilated pupils, oculogyric crisesBlepharospasm can be an early sign of overdosage.
Cardiac disordersCommon (≥1/100 to < 1/10): Palpitations, irregular heartbeat
Vascular disordersCommon (≥1/100 to < 1/10): Orthostatic hypotension, inclination to faint, syncopeUncommon (≥1/1,000 to <1/100): HypertensionRare (≥1/10,000 to <1/1,000): Phlebitis
Respiratory, thoracic and mediastinal disordersUncommon (≥1/1,000 to <1/100): Hoarseness, chest painRare (≥1/10,000 to <1/1,000): Dyspnoea, abnormal breathing pattern
Gastrointestinal disordersCommon (≥1/100 to < 1/10): Nausea, vomiting, dry mouth, bitter tasteUncommon (≥1/1,000 to <1/100): Constipation, diarrhoea, sialorrhoea, dysphagia, flatulenceRare (≥1/10,000 to <1/1,000): Dyspepsia, gastro-intestinal pain, dark saliva, bruxism, hiccups, gastrointestinal bleeding, burning sensation of the tongue, duodenal ulceration
Skin and subcutaneous tissue disordersUncommon (≥1/1,000 to <1/100): OedemaRare (≥1/10,000 to <1/1,000): Angioedema, urticaria, pruritus, facial redness, hair loss, exanthema, increased perspiration, dark perspiration fluid, Schönlein-Henoch purpura
Musculoskeletal, connective tissue and bone disordersUncommon (≥1/1,000 to <1/100): Muscle spasms
Renal and urinary disordersUncommon (≥1/1,000 to <1/100): Dark urineRare (≥1/10,000 to <1/1,000): Urinary retention, urinary incontinence, priapism
General disorders and administration site conditionsUncommon (≥1/1,000 to <1/100): Weakness, malaise, flare ups
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