Benserazide + Levodopa

Oral
Parkinson's disease

standard cap & 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.

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.

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.

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.

Signs and symptoms may include nausea, vomiting, insomnia, confusion, cardiac arrhythmia and abnormal involuntary movements. Monitor vital signs and provide supportive and symptomatic treatment.

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.

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.

May give a false-positive result in Coombs' tests.

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.

Store at 15-30°C (59-86°F) in a well closed and light-resistant container.

Antiparkinsonian Drugs