Levodopa/ Benserazide

Registered South African indications:

• Parkinsonism

Contraindications

• Known hypersensitivity to levodopa or benserazide or to any of the excipients
• Patients receiving monoamine oxidase (MAO) inhibitors due to the risk of hypertensive crisis. The same contraindications apply to sympathomimetic medicines (such as epinephrine (adrenaline) and norepinephrine (noradrenaline) and their derivatives)
• Patients with decompensated endocrine, renal, or hepatic function
• Cardiac disorders
• Glaucoma
• Psychoses
• Highly pronounced psychoneuroses
• Patients under 25 years of age (skeletal development must be complete prior to administration)
• Pregnancy
• Lactation

Cautions

• Elderly
• Open angle glaucoma
• Endocrine disease 
• Pulmonary disease 
• Cardiovascular disease
• Psychiatric disease
• History of myocardial infarction or arrhythmia
• History of orthostatic hypotension
• Peptic ulcer
• Osteomalacia
• Coronary artery disorders
• Cardiac failure
• Abrupt withdrawal
• May impairment ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: cap, tab

Parkinsonism
-Excluding drug-induced Parkinsonism

Levodopa/ Benserazide
200/50 (mg)

• Oral (tab): Initial: 1/2 tab, 8hrly; Titrate by 1/2 tab at 1 week intervals; Maintenance: 2-4 tab/day, in 3-4 divided doses

Do not take within 30mins before or 60mins after meals

See additional prescribing points

Not established for use in children

Recommendations for this combination product as per highest risk category when comparing individual active ingredients

Pregnancy

• Contraindicated

Breastfeeding

• Contraindicated

Renal Impairment

• Decompensated renal function: Contraindicated

Hepatic Impairment

• Decompensated hepatic function: Contraindicated

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Hallucinations
• Mania
• Agitation
• Confusion 
• Fainting
• Dyskinesia
• Hyperkinesia
• Involuntary jerks
• Hiccups
• Insomnia
• Depression
• Nocturnal excitation
• Diurnal excitation
• Somnolence
• Dizziness
• Abnormal involuntary movements

Cardiovascular Disorders

• Palpitations
• Angina pectoris
• Rhythm disturbances
• Orthostatic hypotension

Gastrointestinal Disorders

• Nausea and vomiting
• Anorexia
• Constipation
• Weight gain
• Oedema
• Diarrhoea
• Sialorrhoea
• Dyspnoea

Genitourinary Disorders

• Altered colour of urine 
• Changes in libido

Musculoskeletal Disorders

• Muscle cramps
• Hypotonia
• Leg pain
• Torsion 
• Dystonia

Skin and Subcutaneous Tissue Disorders

• Pruritius
• Rash

Immune, Blood and Lymphatic System Disorders

• Haemolytic anaemia
• Transient leukopenia
• Thrombocytopenia

Sensory Disorders

• Loss or change of taste

• Halothane
• Trihexyphenidyl
• Ferrous sulphate
• Opioids 
• Tetrabenazine
• Metoclopramide
• Phenothiazines
• Thioxanthenes
• Butyrophenones
• Amphetamines
• Papaverine
• Domperidone
• Antipsychotics
• Antihypertensives
• Sympathomimetic agents
• Epinephrine (adrenaline)
• Norepinephrine (noradrenaline)
• Monoamine oxidase inhibitors
• Anticholinergic agents
• Amantadine
• Selegiline
• Bromocriptine
• Dopamine agonists
• Catechol-O-methyl transferase inhibitors

• Hepatic function
• Renal function
• Full blood count

Specific cases may require

• Blood glucose

Starting patients on combination treatment

Patients previously treated with levodopa:

• Levodopa should be discontinued and the combination started on the following day
• The patient should be initiated on a total of 1/2 tab or 1 cap, less than the total number of 500mg levodopa tabs or caps previously taken

Patients previously treated with other levodopa/decarboxylase inhibitor combinations

• Previous therapy should be withdrawn for 12hrs
• It may be beneficial to discontinue previous therapy at night and institute the Levodopa/ Benserazide the following morning

Levodopa
Levodopa is the metabolic precursor of dopamine. The latter is severely depleted in the striatum, pallidum and substantia nigra of Parkinsonian patients and it is considered that administration of levodopa raises the level of available dopamine in these centres. However, conversion of levodopa into dopamine by the enzyme dopa decarboxylase also takes place in extracerebral tissues. As a consequence the full therapeutic effect may not be obtained and side-effects occur.

Benserazide
Administration of a peripheral decarboxylase inhibitor, which blocks the extracerebral decarboxylation of levodopa, in conjunction with levodopa has significant advantages; these include reduced gastrointestinal side-effects, a more rapid response at the initiation of therapy and a simpler dosage regimen. 

COMBINATION PREPARATIONS

Benserazide/ Levodopa

Capsule 25mg/100mg

• Madopar hbs (Roche) originator

Tablet 50mg/200mg

• Madopar (Roche) originator