Benserazide + Levodopa


Concise Prescribing Info
Indications/Uses
Parkinson's disease
Dosage/Direction for Use
Adult : PO Parkinson's disease As standard forms or dispersible forms in Levodopa (mg)/Benserazide (mg) 50/12.5, 100/25, 200/50. Doses expressed as Levodopa: Initially 50 mg 3-4 times/day (100 mg 3 times/day in advance stage disease); increase by 100 mg/day once or twice wkly. Effective dose range: 400-800 mg/day in divided doses. Patients previously on levodopa monotherapy: Initiate with 10-15% of the usual dose previously taken. Patient previously on other levodopa/dopa-decarboxylase combination therapy: Withdraw previous therapy for 12 hr before initiating therapy at 50 mg 3-4 times/day. As controlled release cap of Levodopa 100 mg/Benserazide 25 mg: Initially 1 cap 3 times/day; max initial dose: 6 caps/day. Patients previously on immediate-release Levodopa/Benserazide preparations: Initial dose should substitute every 100 mg of Levodopa with 1 controlled-release cap, given at same dosage frequency as before. Increase every 2-3 days according to response.
Dosage Details
Oral
Parkinson's disease
Adult: Standard forms or Dispersible form Available in Levodopa (mg)/Benserazide (mg) formulations 50/12.5, 100/25, 200/50. Doses expressed as Levodopa: Initially 50 mg 3 or 4 times daily (100 mg tid in advance stage disease); gradually increase by 100 mg daily once or twice wkly. Effective dose range: 400-800 mg daily in divided doses; most require < 600 mg daily. Patients previously on levodopa monotherapy: Initiate with 10-15% of the usual dose previously taken. Patient previously on other levodopa/dopa-decarboxylase combination therapy: Withdraw previous therapy for 12 hr before initiating therapy at 50 mg 3 or 4 times daily. Controlled-release form As Levodopa (mg)/Benserazide (mg) 100/25 cap: Initially 1 cap tid. Max initial dose: 6 caps/day. Patients previously on immediate-release Levodopa/Benserazide preparations: Initially dose should substitute every 100 mg of Levodopa with 1 controlled-release cap, given at same dosage frequency as before. Increase every 2-3 day
Elderly: Standard forms or Dispersible form Doses expressed as Levodopa: Initially 50 mg once or twice daily, gradually increase by 50 mg every 3-4 days according to response.
Administration
Standard Cap &Amp; Hbs Cap: Should be taken on an empty stomach. Best taken at least 30 min before or 1 hr after meals, whenever possible. GI discomfort which occurs mainly in the early stages of treatment may be controlled by taking w/ food or liqd or by increasing the dose slowly. Swallow whole, do not chew/crush.
Dispersible Tab: Should be taken on an empty stomach. Best taken at least 30 min before or 1 hr after meals, whenever possible. GI discomfort which occurs mainly in the early stages of treatment may be controlled by taking w/ food or liqd or by increasing the dose slowly. Disperse in ¼ glass of water (approx 25-50 mL). Stir before drinking. Consume entire amount w/in 30 min of dissolving the tab.
Contraindications
Concurrent use or within 2 wk of withdrawal of non-selective monoamine oxidase (MAO) inhibitors. Severe psychoneuroses or psychoses; severe endocrine, renal, hepatic or cardiac disorders; narrow-angle glaucoma; malignant melanoma; in patients < 25 yr, and pregnancy.
Special Precautions
CV disease, liver or renal disease, pulmonary disease, endocrine disorders, seizure disorders, psychiatric disturbances (e.g. depression); open-angle glaucoma, osteomalacia, history of peptic ulcer. Monitor hepatic, psychiatric, haematological, renal and CV functions periodically. Levodopa has been associated with somnolence and sudden onset of sleep; patients should not drive or operate machine if experienced such effects. Neuroleptic malignant-like syndrome has been reported on abrupt withdrawal. Long term use of Levodopa and/or dopamine agonists has been associated with behavioural disturbances such as hypersexuality, excessive gambling or shopping, punding. Should not be used in women of child-bearing potential without adequate contraception. Breast-feeding is not recommended.
Adverse Reactions
GI disturbances e.g. nausea, vomiting, anorexia, diarrhoea, taste disturbances. GI bleeding in peptic ulcer patients. Orthostatic hypotension, cardiac arrhythmias. Psychiatric disturbances e.g. mild elation, anxiety, agitation, insomnia, drowsiness, depression, aggression, hallucination. Somnolence, sudden onset of sleep episodes. Abnormal involuntary movements e.g. dyskinesia, dystonia, chorea. Haemolytic anemia, transient leucopenia and thrombocytopenia. Transient elevations of liver enzymes; increased BUN and uric acid.
Overdosage
Signs and symptoms may include nausea, vomiting, insomnia, confusion, cardiac arrhythmia and abnormal involuntary movements. Monitor vital signs and provide supportive and symptomatic treatment.
Drug Interactions
Increased postural hypotension and possible reduced absorption of Levodopa with TCAs. Reduced effects with phenothiazines, butyrophenones, thioxanthenes and other antipsychotic agents; reserpine, papaverine, phenytoin and isoniazid. Reduced absorption with ferrous sulphate. Pyridoxine (10-25 mg) may reverse antiparkinsonian effect of Levodopa in the absence of concurrent dopa-decarboxylase inhibitor. Exacerbation of abnormal involuntary movements and possibly delayed absorption when used with anticholinergics. Additive hypotensive effects with antihypertensive agents. Increased CNS toxicity with methyldopa. Exacerbation of parkinsonian symptoms with metoclopramide due to its antagonistic effects on dopamine receptor.
Potentially Fatal: Increased risk of hypertensive crises with nonselective MAOIs. Increased risk of cardiac arrhythmias with cyclopropane and halothane.
Food Interaction
A high protein diet may reduce therapeutic effect of Levodopa. Absorption is reduced and delayed by food, though it is usually administered with meal to reduce nausea and vomiting.
Lab Interference
May give a false-positive result in Coombs' tests.
Action
Description: Levodopa is the metabolic precursor of dopamine. Only a small amount of administered Levodopa enters blood-brain barrier unaltered and the remainder is converted peripherally to dopamine by dopa-decarboxylase. Benserazide is a peripheral decarboxylase inhibitor that reduces the peripheral conversion of Levodopa; concurrent admin enables dosage of Levodopa to be reduced and may diminish peripheral side effects such as nausea and vomiting.
Pharmacokinetics:
Absorption: Mainly from upper region of small intestine; Benserazide may enhance absorption of Levodopa. Standard forms and Dispersible form: Levodopa: Tmax: About 1 hr, shorter with dispersible form; absolute bioavailability: About 98%. Absorption reduced and delayed by food. Controlled-release form Tmax (Levodopa): About 3 hr (5 hr if administered after meal). Bioavailability and Cmax are lower than that of standard forms; but are not affected by food. Lesser fluctuation in plasma concentrations between doses.
Distribution: Levodopa: Crosses the blood-brain barrier (saturable transport system); not bound to plasma proteins. Vd: 57 L. Benserazide: Concentrates in kidney, lung, small intestine and liver; does not cross the blood-brain barrier at therapeutic doses.
Metabolism: Levodopa: Mostly decarboxylated in the gut, liver and kidney, to dopamine via aromatic L-amino acid decarboxylase; which in turn is further metabolised to dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Also metabolised by 0-methylation to form 3-O-methyldopa (elimination half-life: 15 hr). Other minor metabolism pathways: Transamination, oxidation. Benserazide: Hydroxylated in the intestinal mucosa and liver to trihydroxybenzylhydrazine, which is a potent inhibitor of aromatic amino acid decarboxylase.
Excretion: Levodopa: Elimination half-life: About 1.5 hr (in the presence of Benserazide); may prolong with controlled-release form. About 80% of oral dose eliminated in urine as DOPAC and HVA; minimal is excreted unchanged in faeces. Benserazide: Almost entirely eliminated by metabolism.
Storage
Store at 15-30°C (59-86°F) in a well closed and light-resistant container.
Disclaimer: This information is independently developed by MIMS based on Benserazide + Levodopa from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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