Levodopa + Benserazide

Indications

Levodopa + Benserazide is used for: Parkinson's disease

Adult Dose

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

Child Dose

Renal Dose

Administration

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 1 hr 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 ½ hr of dissolving the tab.

Contra Indications

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.

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.

Pregnancy-Lactation

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.

Adverse Effects

Side effects of Levodopa + Benserazide : 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.

Mechanism of Action

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.