Madopar DR Uses

• Madopar DR indications
• Madopar DR description
• Madopar DR dosage
• Madopar DR interactions
• Madopar DR side effects
• Madopar DR contraindications

Madopar DR indications

Treatment of Parkinson's disease.

Madopar DR dispersible is a formulation which is suitable for patients with dysphagia (difficulties in swallowing) or who require a formulation with a more rapid onset of action eg, patients suffering from early morning and afternoon akinesia, or who exhibit "delayed on" or "wearing off" phenomena.

Madopar DR HBS is indicated for patients presenting with all types of fluctuations (eg, "peak-dose dyskinesia" and "end of dose deterioration" eg, nocturnal immobility).

Madopar DR description

Madopar DR is a combination of Levodopa (Madopar DR) and the decarboxylase inhibitor besnerazide (as hydrochloride) in a ratio of 4:1 for the treatment of Parkinson's disease..

Madopar DR 62.5 is Levodopa (Madopar DR) 50 mg and Benserazide (Madopar DR) 12.5 mg; 125 is Levodopa (Madopar DR) 100 mg and Benserazide (Madopar DR) 25 mg; 250 is Levodopa (Madopar DR) 200 mg and besenrazide 50 mg.

Madopar DR 250: Each capsule contains Levodopa (Madopar DR) 200 mg and Benserazide (Madopar DR) HCl 50 mg.

Madopar DR HBS (Hydrodynamically Balanced System): Each capsule contains Levodopa (Madopar DR) 100 mg and Benserazide (Madopar DR) HCl 25 mg.

Madopar DR dosage

Standard

Dosage: Treatment with Madopar DR should be introduced gradually, dosage should be assessed individually and titrated for optimal effect. The following dosage instructions should therefore be regarded as guidelines.

Initial Therapy: In the early stages of Parkinson's disease it is advisable to start treatment with 1 capsule of Madopar DR '62.5' or half a tablet of Madopar DR '125' 3-4 times daily. As soon as tolerability of the initial dosing schedule is confirmed, the dosage should be increased slowly in accordance with the patient's response.

An optimal effect is generally achieved with a daily dosage of Madopar DR corresponding to Levodopa (Madopar DR) 300-800 mg + Benserazide (Madopar DR) 75-200 mg, to be divided into ≥3 doses. Between 4 and 6 weeks may be needed to achieve the optimal effect. If it proves necessary to further increase the daily dosage, this should be done on a monthly basis.

Maintenance Therapy: The average maintenance dosage is 1 capsule or tablet of Madopar DR '125' 3-6 times daily. The number of individual doses (not <3) and their distribution throughout the day must be titrated for optimal effect. Madopar DR HBS and Madopar DR dispersible may substitute standard Madopar DR to achieve an optimal effect.

Special Dosage Instructions: Dosage must be carefully titrated in all patients. Patients on other antiparkinsonian agents may receive Madopar DR. However, as treatment with Madopar DR proceeds and the therapeutic effect becomes apparent, the dosage of the other drugs may need to be reduced or these drugs gradually withdrawn.

Madopar DR dispersible tablets are particularly suitable for patients with dysphagia (difficulties in swallowing) or in situations where a more rapid onset of action is required eg, in patients suffering from early morning and afternoon akinesia or who exhibit "delayed on" or "wearing off" phenomena.

Patients who experience large fluctuations in the drug's effect in the course of the day (on-off phenomena) should receive smaller, more frequent single doses or be switched to Madopar DR HBS.

The switch from standard Madopar DR to Madopar DR HBS is preferably made from 1 day to the next, beginning with the morning dose. The daily dose and dosing interval should initially be the same as with standard Madopar DR.

After 2-3 days, the dosage should be gradually increased by about 50%. Patients should be informed that their condition may temporarily deteriorate.

Due to the pharmacokinetic properties of Madopar DR HBS, the onset of action is delayed. The clinical effect may be achieved more rapidly by administering Madopar DR HBS together with standard Madopar DR or Madopar DR dispersible. This may prove especially useful for the 1st morning dose, which should preferably be higher than the subsequent daily doses. The individual titration for Madopar DR HBS must be carried out slowly and carefully, allowing intervals of at least 2-3 days between dose changes.

In patients with nocturnal immobility, positive effects have been reported after gradually increasing the last evening dose to Madopar DR HBS 250 mg on retiring.

Excessive responses to Madopar DR HBS (dyskinesia) can be controlled by increasing the interval between doses rather than reducing the single doses.

Treatment with standard Madopar DR or Madopar DR dispersible should be resumed if the response to Madopar DR HBS is inadequate.

Patients should be carefully observed for possible undesirable psychiatric symptoms.

Administration: When taking standard Madopar DR capsules or Madopar DR HBS, patients must always ensure to swallow the whole capsule without chewing it.

Standard Madopar DR tablets are breakable to facilitate swallowing.

Madopar DR dispersible tablets are to be dispersed in a quarter of a glass of water (approximately 25-50 mL). The tablets disintegrate completely, producing a milky-white dispersion within a few minutes. Because of rapid sedimentation, it is advisable to stir the dispersion before drinking. Madopar DR dispersible tablets should be taken within ½ an hr of preparing the dispersion.

Madopar DR should be taken 30 min before or 1 hr after meals where possible. Undesirable gastrointestinal effects, which may occur mainly in the early stages of the treatment, can largely be controlled by taking Madopar DR with a small snack (eg, biscuits) or liquid or by increasing the dose slowly.

Madopar DR interactions

Pharmacokinetic Interactions: Co-administration of the anticholinergic drug trihexyphenidyl with standard Madopar DR reduces the rate, but not the extent of Levodopa (Madopar DR) absorption. Trihexyphenidyl given concomitantly with Madopar DR HBS does not affect the pharmacokinetics of Levodopa (Madopar DR).

Co-administration of antacids with Madopar DR HBS reduces the extent of Levodopa (Madopar DR) absorption by 32%.

Ferrous sulphate decreases the maximum plasma concentration and the AUC of Levodopa (Madopar DR) by 30-50%. The pharmacokinetic changes observed during co-treatment with ferrous sulphate appear to be clinically significant in some but not all patients.

Metoclopramide increases the rate of Levodopa (Madopar DR) absorption.

Domperidone may increase the bioavailability of Levodopa (Madopar DR) by stimulation of gastric emptying.

Pharmacodynamic Interactions: Neuroleptics, opioids and antihypertensive medications containing reserpine inhibit the action of Madopar DR.

If Madopar DR is to be administered to patients receiving irreversible nonselective MAO inhibitors, an interval of at least 2 weeks should be allowed between cessation of the MAO inhibitor and the start of Madopar DR therapy. Otherwise unwanted effects eg, hypertensive crises are likely to occur. Selective MAO-B inhibitors eg, selegiline and rasagiline and selective MAO-A inhibitors eg, moclobemide, can be prescribed to patients on Madopar DR therapy; it is recommended to readjust the Levodopa (Madopar DR) 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 nonselective MAO inhibition and hence this combination should not be given concomitantly with Madopar DR.

Madopar DR should not be administered concomitantly with sympathomimetics (agents eg, epinephrine, norepinephrine, isoproterenol or amphetamine which stimulate the sympathetic nervous system) as Levodopa (Madopar DR) may potentiate their effects. 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.

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

Levodopa (Madopar DR) may affect the results of laboratory tests for catecholamines, creatinine, uric acid and glucose.

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

Concomitant administration of antipsychotics with dopamine-receptor blocking properties, particularly D₂-receptor antagonists might antagonize the antiparkinsonian effects of Levodopa (Madopar DR)-Benserazide (Madopar DR). Levodopa (Madopar DR) may reduce antipsychotic effects of these drugs. These drugs should be co-administration with caution.

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

General Anesthesia with Halothane: Madopar DR should be discontinued 12-48 hrs before surgical intervention requiring general anesthesia with halothane as fluctuations in blood pressure and/or arrhythmias may occur.

For general anesthesia with other anesthetics see Precautions.

Madopar DR side effects

Post-Marketing: Blood and Lymphatic System Disorders: Hemolytic anemia, transient leukopenia and thrombocytopenia have been reported in rare cases. Therefore, as in any long-term Levodopa (Madopar DR)-containing treatment, blood count and liver and kidney function should be monitored periodically.

Metabolic and Nutritional Disorders: Anorexia has been reported.

Psychiatric Disorders: Depression can be part of the clinical picture in patients with Parkinson's disease and may also occur in patients treated with Madopar DR. Agitation, anxiety, insomnia, hallucinations, delusions and temporal disorientation may occur particularly in elderly patients and in patients with a history of such disorders.

Nervous System Disorder: Isolated cases of ageusia or dysgeusia have been reported. At later stages of the treatment, dyskinesia (eg, 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. Madopar DR is associated with somnolence and has been associated very rarely with excessive daytime somnolence and sudden sleep onset episodes.

Cardiac Disorders: Cardiac arrhythmias may occur occasionally.

Vascular Disorders: Orthostatic hypotension may occur occasionally. Orthostatic disorders commonly improve following reduction of the Madopar DR dosage.

Gastrointestinal Disorders: Nausea, vomiting and diarrhea have been reported with Madopar DR. Undesirable gastrointestinal effects, which may occur mainly in the early stages of the treatment, can largely be controlled by taking Madopar DR with some food or liquid or by increasing the dose slowly.

Skin and Subcutaneous Tissue Disorders: Allergic skin reactions eg, pruritus and rash may occur in rare cases.

Investigations: Transient elevation of liver transaminase and alkaline phosphatase may occur. Increase of γ-glutamyltransferase has been reported.

Rises in blood urea nitrogen have been noted with Madopar DR.

Urine may be altered in color, usually acquiring a red tinge which turns dark on standing. Other body fluids or tissues may also be discoloured or stained including saliva, the tongue, teeth or oral mucosa.

Laboratory Abnoramlities: See Post-Marketing as previously mentioned.

Madopar DR contraindications

Hypersensitivity to Levodopa (Madopar DR) or Benserazide (Madopar DR).

In conjunction with nonselective monoamine oxidase (MAO) inhibitors. However, selective MAO-B inhibitors eg, selegiline and rasagiline or selective MAO-A inhibitors eg, moclobemide are not contraindicated. Combination of MAO-A and MAO-B inhibitors is equivalent to nonselective MAO inhibition and hence, this combination should not be given concomitantly with Madopar DR.

Patients with decompensated endocrine, renal (except patients on dialysis) or hepatic function, cardiac disorders, psychiatric diseases with a psychotic component or closed angle glaucoma.

Pregnant women or to women of childbearing potential in the absence of adequate contraception. If pregnancy occurs in a woman taking Madopar DR, the drug must be discontinued (as advised by the prescribing physician).

Patients <25 years (skeletal development must be complete).

Use in pregnancy: Madopar DR is contraindicated during pregnancy and in women of childbearing potential in the absence of adequate contraception.

Active ingredient matches for Madopar DR:

Benserazide/Levodopa in Switzerland.

References

1. DailyMed. "CARBIDOPA; ENTACAPONE; LEVODOPA: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
2. PubChem. "levodopa". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
3. PubChem. "benserazide". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).

Reviews

User reports

Consumer reviews

Information checked by Dr. Sachin Kumar, MD Pharmacology