Co-beneldopa (benserazide and levodopa) oral
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulations of levodopa and benserazide
Co-beneldopa is a mixture of benserazide and levodopa in mass proportions corresponding to 1 part benserazide and 4 parts of levodopa.
Parkinson's disease (not drug induced)
Dosage and administration are very variable and must be titrated to the needs of the individual patient.
Patients with fluctuations related to levodopa plasma concentrations or timings of dose e.g. end of dose deterioration or wearing off effects, are more likely to benefit from modified release co-beneldopa.
Standard release capsules and dispersible tablets
Patients not previously treated with levodopa:
The recommended initial dose is one capsule or dispersible tablet of co-beneldopa 12.5/50 mg three or four times daily. If the disease is at an advanced stage, the starting dose should be co-beneldopa 25/100 mg three times daily.
The daily dosage should then be increased by co-beneldopa 25/100 mg once or twice daily until a full therapeutic effect is obtained or side effects supervene.
The effective dose usually lies within the range of 4 to 8 capsules or dispersible tablets of co-beneldopa 25/100 mg (400 to 800 mg levodopa) daily in divided doses, most patients requiring no more than 600 mg of levodopa daily.
Optimal improvement is usually seen in one to three weeks but the full therapeutic effect may not be apparent for some time. It is therefore advisable to allow several weeks to elapse before contemplating dosage increments above the average dosage range. If satisfactory improvement is still not achieved, the dose should be increased with caution. It is rarely necessary to give more than ten capsules or dispersible tablets of co-beneldopa 25/100 mg (1000 mg levodopa) per day.
Treatment should be continued for at least six months before failure is concluded from the absence of clinical response.
Patients already receiving levodopa therapy:
Levodopa alone should be discontinued and co-beneldopa started on the following day. The patient should be initiated on a total of one less co-beneldopa 25/100 mg capsule or dispersible tablet daily than the total number of 500 mg levodopa tablets or capsules previously taken. For example if the patient had previously taken 2 g levodopa daily then he should start on three capsules or dispersible tablets of co-beneldopa 25/100 mg on the following day. Observe the patient for one week then if necessary increase the dosage in the manner described for new patients.
Patients already receiving 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 co-beneldopa therapy the following morning. The initial dose of co-beneldopa should be one capsule or dispersible tablet of co-beneldopa 12.5/50 mg three or four times a day. 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 co-beneldopa. Existing treatment with other anti-parkinsonian drugs e.g. anticholinergics or amantadine, should be continued during initiation of co-beneldopa therapy. However as treatment with co-beneldopa proceeds and the therapeutic effect becomes apparent, the dosage of the other drugs may need to be reduced or the drugs gradually withdrawn.
Modified release capsules
In patients with nocturnal immobility, positive effects have been reported after gradually increasing the last evening dose to two co-beneldopa modified release capsules on retiring.
Patients not previously treated with levodopa:
In patients with mild to moderate disease, the initial recommended dose is one co-beneldopa modified release capsule three times a day.
Higher doses, in general, of co-beneldopa modified release capsules will be required than with conventional levodopa-decarboxylase inhibitor combinations as a result of the reduced bioavailability.
The initial dosage should not exceed 600 mg per day of levodopa.
Some patients may require a supplementary dose of conventional co-beneldopa capsules or dispersible tablets together with the first morning dose of co-beneldopa modified release capsules to compensate for the more gradual onset of the modified release formulation.
In cases of poor response to co-beneldopa modified release capsules at a total daily doses of co-beneldopa modified release capsules plus any supplementary co-beneldopa corresponding to 1200 mg levodopa, administration of co-beneldopa modified release capsules should be discontinued and alternative therapy considered.
Patients already receiving levodopa therapy:
Co-beneldopa modified release capsules should be substituted for the standard levodopa-decarboxylase inhibitor preparation by one capsule co-beneldopa modified release capsule per 100 mg levodopa. For example where a patient previously received daily doses of 200 mg levodopa with decarboxylase inhibitor, then therapy should be initiated with two capsules of co-beneldopa modified release capsules. Therapy should continue with the same frequency of doses as previously.
With co-beneldopa modified release capsules, on average, a 50% increase in daily levodopa dosage compared with previous therapy has been found to be appropriate. The dosage should be titrated every 2 to 3 days using dosage increments of co-beneldopa modified release capsules and a period of up to 4 weeks should be allowed for optimisation of dosage.
Patients already on levodopa therapy should be informed that their condition may deteriorate initially until the optimal dosage regimen has been found. Close medical supervision of the patient is advisable during the initial period whilst adjusting the dosage.
(See Dosage; Adult)
Additional Dosage Information
Switching from modified release capsules to dispersible tablets.
Co-beneldopa dispersible tablets have a higher bioavailability, faster onset of action and shorter duration of action than the modified release capsules. As such, alternative sources suggest a 30% reduction in dose when switching from modified release capsules to dispersible tablets. Adjustments to dose frequency may also be required.
Patients under 25 years
Within 2 weeks of discontinuing MAOIs
History of malignant melanoma
Narrow angle glaucoma
Severe cardiac disorder
Severe endocrine disease
Severe hepatic disorder
Severe psychiatric disorder
Severe renal disorder
Precautions and Warnings
Females of childbearing potential
History of cardiac arrhythmias
History of myocardial infarction
History of peptic ulcer
History of postural hypotension
Open angle glaucoma
Advise patient ability to drive or operate machinery may be impaired
Advise patient that sudden onset sleep episodes may affect ability to drive
Some products may contain soya or soya derivative
Different formulations are not bioequivalent
Advise patient to take 30 minutes before or 1 hour after meals
Take at a different time from iron supplement
Diabetic control may need adjustment
Exclude pregnancy before issuing each prescription
Monitor blood glucose closely in patients with diabetes mellitus
Monitor cardiac function in patients with cardiac disease
Monitor for melanoma regularly
Monitor patient for signs and symptoms of depression
Monitor patients at risk of glaucoma for increases in intraocular pressure
Monitor patients for impulse control disorders
Monitor renal, hepatic and haematological parameters
Review treatment if impulse control disorders symptoms occur
Advise patient that postural hypotension may occur
Advise patient that red discolouration of body fluids may occur
Advise patient to report any new or worsening depression/suicidal ideation
Dopamine agonists have been associated with pathological gambling
May affect results of some laboratory tests
May colour urine red
Avoid abrupt withdrawal: May cause signs of neuroleptic malignant syndrome
Discontinue prior to surgery
Pregnancy confirmed: Discontinue this medication
Reduce dose or discontinue if sudden onset of sleep during daily activities
Female: Ensure adequate contraception during treatment
Advise patient to resume normal activities gradually
Advise patient/carer about symptoms of impulse control disorders
Monitor patients for unusual side effects or potentiating effects when given concurrently with other drugs.
Co-beneldopa may induce dopamine dysregulation syndrome resulting in excessive use of the product.
If a patient requires a general anaesthesia, the normal co-beneldopa regimen should be continued as close to the surgery as possible, except in the case of halothane. In general anaesthesia with halothane co-beneldopa should be discontinued 12 to 48 hours before surgical intervention as fluctuations in blood pressure and/or arrhythmias may occur in patients on co-beneldopa therapy. Co-beneldopa therapy may be resumed following surgery; the dosage should be increased gradually to the preoperative level.
If a patient has to undergo surgery when co-beneldopa has not been withdrawn, anaesthesia with halothane should be avoided.
Co-beneldopa has been reported to induce decreases in blood cell count (e.g. haemolytic anaemia, thrombocytopenia and leukopenia). In a few instances agranulocytosis and pancytopenia have been reported in which the association with co-beneldopa could neither be established, nor be completely ruled out. Therefore, periodical evaluation of blood cell count should be performed during treatment.
Pregnancy and Lactation
Co-beneldopa is contraindicated during pregnancy and in women of child bearing potential in the absence of adequate contraception.
The manufacturer does not recommend taking co-beneldopa during pregnancy.
Co-beneldopa is contraindicated during breastfeeding.
The manufacturer suggests not breastfeeding whilst taking co-beneldopa. It is unknown if co-beneldopa is expressed in breast milk, therefore the risks like skeletal malformations cannot be excluded.
'Unmasking' of psychoses
Activation of latent Horner's syndrome
Decrease in mental acuity
Discolouration of urine
False positive Coombs test
Fine tremor (usually hands)
Gamma glutamyl transferase (GGT) increased
Glaucoma (closed angle)
Impulse control disorders
Increase in alkaline phosphatase
Increase in blood urea nitrogen
Increase in serum ALT/AST
Increased uric acid level
Involuntary movement disorders
Neuroleptic malignant syndrome
Sudden sleep onset episodes
Effects on Laboratory Tests
Levodopa may affect the results of laboratory tests for catecholamines, ketone bodies, creatinine, uric acid and glycosuria. 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 co-beneldopa.
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: August 2014
Summary of Product Characteristics: Madopar CR capsules 125. Roche Products Ltd. Revised December 2020.
Summary of Product Characteristics: Madopar 200mg/50mg capsules. Roche Products Ltd. Revised March 2020.
Summary of Product Characteristics: Madopar 100mg/25mg capsules. Roche Products Ltd. Revised March 2020.
Summary of Product Characteristics: Madopar 50mg/12.5mg capsules. Roche Products Ltd. Revised March 2020.
Summary of Product Characteristics: Madopar Dispersible tablets. Roche Products Ltd. Revised August 2015.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 26 November 2018
UKMi medicines Q&A October 2018
How do you convert from co-beneldopa (madopar) prolonged-release capsules to dispersible tablets?
Available at: www.sps.nhs.uk
Last accessed: 26 November 2018
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