Levodopa increases dopamine levels in the brain leading to the stimulation of dopamine receptors.

Absorption
Rapidly absorbed from the GI tract (oral); absorption reduced and delayed by food. Peak plasma concentrations within 2 hours.

Distribution
Protein-binding: 10-30%. Penetrates the blood-brain barrier; crosses the placenta; distributed into breast milk.

Metabolism
Metabolised in the gut, liver and kidney; decarboxylated by L-aminodecarboxylase to dihydrophenylacetic acid (DOPAC) and homovanillic acid (HVA). Other routes: O-methylation, transamination, oxidation.

Excretion
Via urine within 24 hours (80% as metabolites); via faeces (minimal amounts). 30-60 minutes (elimination half-life).

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GI disturbances e.g. nausea, vomiting, anorexia. GI bleeding in peptic ulcer patients. Orthostatic hypotension, cardiac arrhythmias. Psychiatric symptoms (especially the elderly), depression with or without suicidal tendency. Abnormal involuntary movements or dyskinesias, delirium, hallucinations. Slight elevation of liver enzymes, BUN and uric acid. Transient leucopenia and thrombocytopenia.

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Heart disease, liver or renal disease, pulmonary disease, endocrine disorders, seizure disorders, dementia or psychosis; open-angle glaucoma, osteomalacia, history of peptic ulcer. Monitor hepatic, psychiatric, haematological, renal and CV functions periodically. May impair ability to drive or operate machinery. Elderly. Avoid abrupt withdrawal. Pregnancy and lactation.

Increased postural hypotension and possible reduced absorption with TCAs. Reduced effects with phenothiazines, butyrophenones, thioxanthenes and other antipsychotic agents; reserpine, papaverine, phenytoin, isoniazid. Reversal of effects of levodopa monotherapy with pyridoxine. Exacerbation of abnormal involuntary movements and possibly delayed absorption with anticholinergics. Additive hypotensive effects with antihypertensive agents. Increased CNS toxicity with methyldopa. Exacerbation of parkinsonian symptoms with metoclopramide.

Potentially Fatal: Increased risk of hypertensive crises with nonselective MAOIs. Increased risk of cardiac arrhythmias with cyclopropane or halogenated anaesthetics.

Food Interaction
Food reduces and delays absorption of levodopa. Effects of levodopa reduced by beans, liver, skimmed milk, yeast and wheat germ. Large neutral amino acids reduce absorption and passage across blood-brain barrier. Recommended to be taken after a light meal to slow absorption and reduce central emetic effect.

Oral
Parkinsonism
Adult: Initially, 125 mg bid; increase gradually every 3-7 days according to response. Max dose: 8 g daily in divided doses.

Oral
Parkinsonism in conjunction with benserazide
Adult: Patients not previously on levodopa therapy: Initially, 50 mg 3 or 4 times daily; gradually increase in increments of 100 mg once or twice wkly. Increase initial dose to 100 mg tid for advanced disease stages. Maintenance dose: 400-800 mg daily in divided doses; most require <600 mg daily. Patients previously on levodopa monotherapy: 10-15% of the usual dose previously taken. Patient previously on other levodopa/dopa-decarboxylase combination therapy: Initially, 50 mg 3 or 4 times daily.
Elderly: Initially, 50 mg once or bid, then increase by 50 mg every 3rd or 4th day.

Oral
Parkinsonism in conjunction with carbidopa
Adult: Patients not previously on levodopa therapy: Initially, 25 mg carbidopa with 100 mg levodopa tid; gradually increase in increments of 12.5 mg carbidopa with 50 mg levodopa or 25 mg carbidopa with 100 mg levodopa every day or on alternate days. Maintenance dose: 75-200 mg carbidopa with 750 mg to 2 g levodopa daily in divided doses. Max carbidopa dose: 200 mg daily. Patients previously on levodopa monotherapy: 20-25% of the dose previously taken 3 or 4 times daily. Patient previously on other levodopa/dopa-decarboxylase combination therapy: Initial dose should provide the same daily levodopa dose.

Should be taken with food. (GI discomfort may be reduced by increasing the dose of l-dopa gradually, &/or by taking w/ or after meals. However, taking l-dopa on a full stomach may lead to lower plasma conc. In later disease, it may be preferable to admin on an empty stomach if the patient can tolerate it. Keep a consistent diet. A change in diet to foods high in protein may delay l-dopa absorption & reduce amt taken up in circulation.)

Caution when used during pregnancy

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Caution when used during lactation

Safety and efficacy in children younger than 12 years of age not established.

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Angle-closure glaucoma; malignant melanoma.

Oral
Store at 20-25°C (68-77°F).

False-positive Coombs' test. Interferes with serum tests for bilirubin, catecholamines, creatinine, glucose and uric acid and urine tests for creatinine, glucose, ketone and vanillyl mandelic acid (VMA).

Levobunolol, a nonselective β-adrenergic blocking agent, decreases IOP by reducing aqueous humour production.

Onset
Within 1 hour (ophthalmic).

Duration
Up to 24 hours (ophthalmic).

Absorption
Rapidly and almost completely absorbed from the GI tract (oral).

Metabolism
Extensively hepatic.

Excretion
Via urine as metabolites and unchanged drug.

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Ocular stinging, burning, blepharoconjunctivitis, decreased heart rate, decreased BP, iridocyclitis, headache, transient ataxia, dizziness, lethargy, decreased corneal sensitivity, tearing, visual disturbances, urticaria and pruritus.

Levobunolol HCl ophthalmic solution USP sterile should be used with caution in patients with known hypersensitivity to other beta-adrenoceptor blocking agents.Use with caution in patients with known diminished pulmonary function.

Levobunolol HCl ophthalmic solution should be used with caution in patients who are receiving a beta-adrenergic blocking agent orally, because of the potential for additive effects on systemic beta-blockade or on intraocular pressure. Patients should not typically use two or more topical ophthalmic beta-adrenergic blocking agents simultaneously.

Because of the potential effects of beta-adrenergic blocking agents on blood pressure and pulse rates, these medications must be used cautiously in patients with cerebrovascular insufficiency. Should signs or symptoms develop that suggest reduced cerebral blood flow while using Levobunolol HCl ophthalmic solution, alternative therapy should be considered.

In patients with angle-closure glaucoma, the immediate objective of treatment is to reopen the angle. This requires, in most cases, constricting the pupil with a miotic. Levobunolol HCl ophthalmic solution has little or no effect on the pupil. When Levobunolol HCl is used to reduce elevated intraocular pressure in angle-closure glaucoma, it should be followed with a miotic and not alone.

Muscle Weakness: Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis and generalized weakness).

Patients at risk of developing hypoglycaemia. DM. Thyrotoxicosis. Known diminished pulmonary function. Cerebrovascular insufficiency. Do not drive or operate machinery until vision is clear. Pregnancy and lactation.

Mydriasis may occur when used with epinephrine. Additive effects with catecholamine-depleting drugs e.g. reserpine. Possible AV conduction disturbances, LVF and hypotension with IV calcium antagonists. Additive prolongation of AV conduction time with digitalis and calcium antagonists. Additive hypotensive effects with phenothiazine-related agents. Additive effect with systemic β-blockers.

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Ophthalmic
Open-angle glaucoma, Ocular hypertension
Adult: As hydrochloride: 0.5% solution: 1-2 drops of in the affected eye(s) once daily; may be given bid for more severe or uncontrolled glaucoma. 0.25% solution: 1-2 drops bid.

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Caution when used during pregnancy

Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Caution when used during lactation

Safety and efficacy not established

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Bronchial asthma, severe COPD; sinus bradycardia; 2nd and 3rd degree heart block; overt cardiac failure; cardiogenic shock.

Ophthalmic
Store at 15-30°C (59-86°F).

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