Levodopa and Benserazide (Systemic)


VA CLASSIFICATION
Primary: CN500

Commonly used brand name(s): Prolopa® 100–25; Prolopa® 200–50; Prolopa® 50–12.5.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antidyskinetic—

Indications

General considerations
The advantage of using combination levodopa therapy (i.e., levodopa and benserazide) is the reduced incidence of levodopa-induced peripheral side effects (e.g., nausea, vomiting, and cardiac arrhythmias). However, levodopa and benserazide combination therapy is only indicated for patients unable to tolerate an optimal daily dosage of levodopa. There is no clinical benefit to substituting combined therapy for levodopa in patients already on stable, effective and well-tolerated levodopa therapy.{01} The decision to place a patient on levodopa and benserazide combination therapy must balance efficacy with freedom from dyskinesias. Allow at least 3 to 6 weeks therapy before concluding levodopa and benserazide combination therapy is ineffective. {01}

Accepted

Parkinsonism (treatment)—levodopa and benserazide combinations indicated to alleviate symptoms and allow more normal body movements with improved muscle control in the treatment of Parkinson's disease. Levodopa and benserazide combination therapy is recommended in patients who previously were unable to tolerate an optimal daily dosage of levodopa.{01}

Unaccepted
levodopa and benserazide combination is not indicated to treat drug-induced parkinsonism. {01}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Levodopa is the metabolic precursor of dopamine. Benserazide is a decarboxylase inhibitor.{01}

Mechanism of action/Effect:

Levodopa—Normal motor function depends on the synthesis and release of dopamine by neurons projecting from substantia nigra to corpus striatum. The progressive degeneration of these neurons that occurs in Parkinson's disease disrupts the nigrostriatal pathway and results in diminished levels of the intrasynaptic neurotransmitter dopamine. Striatal dopaminergic neurotransmission may be enhanced by exogenous supplementation of dopamine through administration of dopamine's precursor, levodopa. A small percentage of each levodopa dose crosses the blood-brain barrier and is decarboxylated to dopamine. This newly formed dopamine then is available to stimulate dopaminergic receptors, thus compensating for the depleted supply of endogenous dopamine. Levodopa is rapidly converted to dopamine by aromatic acid decarboxylase at extracerebral sites. Due to the rapid metabolism of levodopa, greater doses of levodopa must be given for sufficient quanties of medication to reach the CNS. Large doses of levodopa, leading to excessive quantities of extracerebral dopamine, may be responsible for some of the side effects associated with levodopa therapy. Concomitant therapy with benserazide allows lower doses of levodopa to be administered to achieve adequate CNS dopamine concentrations without the added side effects{01}

Benserazide—Inhibits the peripheral decarboxylation of levodopa, thus decreasing its conversion to dopamine in peripheral tissues. Clinical studies have shown that the combination of levodopa and benserazide in a 4 to 1 ratio is effective in reducing peripheral adverse effects and the amount of levodopa required for therapeutic improvement.{01}

Absorption:

Levodopa—Levodopa is rapidly converted to dopamine by aromatic acid decarboxylase at extracerebral sites.

Benserazide—Approximately 66% to 74% of benserazide is absorbed from the gastrointestinal tract

Distribution:

Levodopa—Levodopa is widely distributed to most body tissues and does permeate the blood-brain barrier.{01}

Benserazide—Benserazide does not cross the blood-brain barrier.{01}

Biotransformation:

Levodopa—Levodopa is rapidly metabolized to dopamine by aromatic acid decarboxylase at extracerebral sites.{01}

Onset of action:

It may take 2 to 3 weeks before an accurate assessment of clinical efficacy can be made.{01}

Time to peak concentration:

Peak plasma concentrations are achieved 1 hour after oral administration.{01} {01}

Elimination:
    Renal—Approximately 53% to 64% of the oral benserazide dose is excreted in the urine.{01}
    Fecal—Approximately 30% of the oral benserazide dose is excreted in the feces. {01}


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done. Reproduction studies in rabbits have shown that levodopa can cause visceral and skeletal malformations. Healthcare providers should weigh the anticipated benefits of the drug against its possible hazards to the mother and to the fetus. {01}

Breast-feeding

It not known whether levodopa and benserazide combination is distributed into breast milk. the combination to nursing mothers. {01}

Pediatrics

Appropriate studies on the relationship of age to the effects of levodopa and benserazide combination have not been performed in children up to 18 years of age. Animal studies suggest that benserazide may cause skeletal abnormalities if administered before ossification is complete. {01}


Geriatrics


The safety and efficacy of levodopa and benserazide combination have not been established in the elderly. {01}

Surgical

If general anesthesia is required, the levodopa and benserazide combinatio can be discontinued the night before surgery and therapy restarted as soon as the patient is able to receive oral medication. {01}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Anesthetics    (for patients requiring general anesthesia, levodopa and benserazide combination should be discontinued the night before surgery then restarted as soon as the patient is able to receive oral medication{01})


» Antihypertensive agents    (postural hypotensive episodes have been reported with levodopa and benserazide combination therapy. For patient on concomitant antihypertensive agents, administer levodopa and benserazide combination with caution and monitor blood pressure{01})


» Monoamine oxidase (MAO) inhibitors
Reserpine
Phenothiazines
Tricyclic antidepressants    (sympathomimetics are contraindicated in patients on levodopa and benserazide combination therapy{01})

    (patients should be observed for signs of depression with suicidal tendencies or other serious behavior changes. Use extreme caution in patients with a history of psychotic disorders or who are receiving psychotherapeutic agents{01})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Coombs' (antiglobulin) test     (occasionally becomes positive after long-term levodopa and benserazide combination therapy{01})

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) and
Alkaline phosphatase and
Aspartate aminotransferase (AST [SGOT]) and
Bilirubin and
Lactate dehydrogenase (LDH) and
Protein-bound iodine (PBI)    (serum concentrations may be increased{01})


Blood urea nitrogen (BUN)    (concentrations may be increased{01})


Hematocrit and
Hemoglobin and
White blood cell counts    (values may be decreased{01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Cardiovascular disease, severe    (increased risk of cardiac arrhythmias{01})


Convulsive disorders, history of     (use of levodopa and benserazide combination may precipitate seizures{01})


Endocrine diseases    (use of levodopa and benserazide combination may adversely affect hypothalamus or pituitary function{01})


Glaucoma, wide-angle, chronic    (mydriatic effect may cause a slight increase in intraocular pressure; glaucoma therapy may need to be adjusted{01})


Hepatic function impairment
» Melanoma, history of or suspected    (use of levodopa and benserazide combination may activate a malignant melanoma{01})


» Mental depression or
» Psychosis    (increased risk of developing suicidal ideation and/or tendencies; also, conditions may be aggravated by neuropsychiatric effects of levodopa and benserazide combination{01})


» Myocardial infarction, history of, with residual atrial, nodal, or ventricular arrhythmias    (use of levodopa and benserazide combination may precipitate or aggravate condition{01})


» Peptic ulcer, history of    (increased risk of upper gastrointestinal hemorrhage{01})


» Renal function impairment    (use of levodopa and benserazide combination may lead to urinary retention{01})


Sensitivity to levodopa and benserazide combination {01}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood cell counts and
Hemoglobin determinations and
Hepatic function determinations and
Ophthalmologic examinations for glaucoma and monitoring of intraocular pressure in patients with wide-angle glaucoma and
Renal function determinations    (recommended at periodic intervals for patients on long-term levodopa and benserazide combination therapy{01})


Cardiovascular monitoring    (recommended at periodic intervals for patients on long-term therapy{01})




Side/Adverse Effects

Note: Complications to long-term levodopa and benserazide combination therapy appear commonly and include motor fluctuations, dyskinesias, neuropsychiatric problems, and cardiovascular effects.
Involuntary movements (e.g., choreiform or dystonic movements) are associated with levodopa and benserazide combination therapy. Muscle twitching may signify early signs of overdosage. The incidence of involuntary movements ranges from 30% to 40% in the first month and 50% to 60% or more by 6 to 9 months. Periodic oscillations in performance can occur after prolonged levodopa therapy and appear earlier after with levodopa and benserazide combination therapy. Oscillations in performance are either end dose akinesia, on-off phenomenon, or akinesia paradoxica.
End dose akinesia is an episodic re-emergence of Parkinsonian symptoms 3 or more hours after each dose of levodopa. Akinesia often follows a period of dyskinesia. During prolonged levodopa therapy, this type of akinesia tends to occur progressively earlier after each dose. The development of akinesia is likely due to a temporary insufficiency of dopamine at the appropriate receptor sites.{01}
The on-off phenomenon is also a result of a temporary insufficiency of dopamine at the appropriate receptor sites. This phenomenon is described as a rapid alteration between a state of satisfactory motility, usually with oral-facial dyskinesias, and a rigid akinetic state without dyskinesias. {01}
Akinesia paradoxica, also called hypnotic freezing, is thought to be associated with a severe temporary deficiency in norepinephrine in progressively depleted and damaged norepinephrine pathways. Hypnotic freezing manifests as irregular episodes of sudden freezing, usually of short duration, with the patient unable to move. The kind of muscle freezing is also accompanied by hypotonia and postural instability.{01}
Neuropsychiatric effects may occur in up to 20% of patients. These psychiatric disorders range from paranoid ideation, psychotic episodes, depression (with or without suicidal tendencies) and dementia. In some patients, levodopa may give rise to an improvement in mood. If levodopa is given to patients with bipolar depression, it tends to produce hypomania.{01}.
Intellectual function and autonomic functions may deteriorate, particularly in akinetic patients, during long-term prolonged levodopa therapy.{01}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Akinesia{01} (absence of or decrease in body movement)
    
blepharospasm {01} (increased blinking or twitching of eyelids)
    
choreiform movements{01} (involuntary movements of the limbs and facial muscles)
    
depression{01} (disorder marked especially by sadness, inactivity, difficulty with thinking and concentration, or feelings of dejection and hopelessness)
    
dyskinesia{01} (twitching, twisting, uncontrolled repetitive movements of tongue, lips, face, arms, or legs)
    
dystonic movements{01} (inability to move eyes increased blinking or spasms)
    
hypotonic freezing {01} (sudden freezing, hypotonia and postural instability)
    
muscle twitching{01}
    
paranoid ideation{01} (fearfulness, suspiciousness, or other mental changes)
    
psychotic episodes{01} (agitation, delusions, hallucinations)

Incidence less frequent
    
Agranulocytosis{01} ( chills, swollen neck, and sore throat sometimes with local ulceration )
    
angina pectoris{01} (chest pain; chest tightness; fast or irregular heartbeat; shortness of breath)
    
arrhythmias{01} (dizziness; fainting; fast, slow, or irregular heartbeat)
    
convulsions{01} ( seizures)
    
difficulty in swallowing{01}
    
duodenal ulcer{01} (stomach pain)
    
ECG changes{01}
    
flushing{01} ( to blush or become suddenly red in the face)
    
gastrointestinal bleeding{01} ( bloody or black, tarry stools; vomiting of blood or material that looks like coffee grounds; severe stomach pain)
    
hematuria{01} ( blood in urine; burning while urinating)
    
hemolytic anemia{01} ( bleeding gums ; dark urine; nosebleeds; pale skin)
    
muscle spasm, especially of neck and back
    
Horner's syndrome — activation{01} (a constricted pupil; drooping of the upper eyelid ; an absence of sweating over the affected side of the face )
    
hypertension{01} ( blurred vision; dizziness; pounding in the ears; slow or fast heartbeat)
    
leukopenia{01} (swollen glands ; unusual bleeding or bruising)
    
oculogyric crisis{01} (inability to move eyes)
    
orthostatic hypotension{01} ( confusion, dizziness, faintness, or light-headedness when getting up from lying or sitting position)
    
phlebitis{01} ( bluish color changes in skin color; pain or tenderness swelling of foot or leg)
    
torticollis{01} ( a twisting of the neck to one side)

{01}

Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent
    
Agitation or anxiety{01} ( nervousness; restlessness ; irritability; insomnia )
    
akinetic episodes{01} (absence of or decrease in body movement; loss or impairment of voluntary activity )
    
ataxia{01} ( shakiness and unsteady walk; clumsiness; trembling; problems with muscle control or coordination)
    
bitter taste{01}
    
bizarre breathing pattern{01} ( blurred vision)
    
bruxism{01} (clenching, gnashing, or grinding teeth)
    
burning sensation of the tongue{01} (change in urinary frequency; loss of bladder control ; a decrease in urine production)
    
confusion{01} ( mood or mental changes)
    
constipation{01}
    
cough{01}
    
dark sweat{01}
    
dark urine{01}
    
diarrhea{01} ( - increase in bowel movements; loose stools; soft stools)
    
dilated pupils{01}
    
diplopia{01} ( double vision )
    
dry mouth{01}
    
edema{01} (decreased urination; rapid weight gain; bloating or swelling of face, hands, lower legs, and/or feet)
    
epigastric distress or pain{01} ( stomach problems)
    
eructation{01} (belching )
    
euphoria{01} (false or unusual sense of well-being)
    
faintness{01}
    
fatigue and malaise{01} ( unusual tiredness or weakness; general feeling of discomfort or illness)
    
fever{01}
    
flatulence{01} (passing gas )
    
hair loss{01}
    
hallucinations and delusion{01} (seeing, hearing, or feeling things that are not there; false beliefs that cannot be changed by facts )
    
headache{01}
    
hiccups{01}
    
hoarseness{01}
    
impairment of gait{01} (change in walking and balance; clumsiness; unsteadiness)
    
increased hand tremor{01}
    
increased libido{01} ( increased in sexual ability or desire)
    
insomnia{01} (trouble sleeping)
    
low back pain{01}
    
muscle spasm and twitching{01}
    
musculoskeletal pain{01} ( muscle or bone pain)
    
nightmares{01}
    
numbness{01}
    
pallor{01} ( paleness of skin)
    
post-nasal drip{01} ( flow of mucous secretion from the nasal cavity onto the wall of the throat )
    
impairment of intellectual function{01} ( impairment in ability to think)
    
rash{01}
    
sedation{01} (drowsiness), sialorrhea{01} (excessive watering of mouth)
    
tightness of the mouth, lips or tongue{01}
    
trismus{01} (difficulty opening the mouth or lockjaw)
    
weight variation{01}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
    
Blepharospasm (increased blinking or spasms of eyelids)
    
Muscle twitching — possible early sign of overdose{01}


Treatment of overdose
Since there is no specific antidote for acute overdose with levodopa, treatment is symptomatic and supportive, with possible utilization of the following:



• To decrease absorption—Immediate gastric lavage.{01}The value of dialysis in the treatment of overdose is not known.{01}


• Monitoring—Electrocardiographic monitoring for development of arrhythmias.{01}


• Specific treatment—

• Antiarrhythmic medication, if necessary. {01}


• Pyridoxine is ineffective in reversing the effects of levodopa and benserazide combination.



• Supportive care—

• Judicious use of intravenous fluids. {01}


• Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.{01}



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Levodopa and Benserazide (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to levodopa or benserazide





Breast-feeding—Not recommended in nursing mothers




Use in children——The safety of levodopa and benserazide combination has not been established in children under 18 years of age.{01}






Use in the elderly—In patients with severe Parkinson's disease who improve on levodopa and benserazide combination therapy should resume normal activities gradually. Rapid mobilization may increase the risk of injury, especially in those patients with osteoporosis{01}

Surgical
If general anesthesia is required, levodopa and benserazide combination can be discontinued the night before surgery and therapy recommended as soon as the patient is able to receive oral medication.{01}
Other medications, especially anesthetics, antihypertensive agents, MAO inhibitors, reserpine, phenothiazines, psychotherapeutic agents, sympathomimetics, and tricyclic antidepressants; high-protein foods.
Other medical problems, especially severe cardiovascular disease, convulsive disorders, endocrine disorders, hepatic disease, hematologic disease, mental depression, peptic ulcer (history of), psychosis, severe pulmonary diseases, renal function impairment, or urinary retention.

Proper use of this medication
» Compliance with therapy; taking medication only as directed; not stopping medication unless ordered by physician

» Maximum effectiveness of medication may not occur for several weeks or months after therapy is initiated

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next scheduled dose; not doubling doses
If levodopa and benserazide combination therapy is interrupted for a brief period, the previous dosage may be administered as soon as the patient can take oral medication. If therapy is interrupted for a longer period of time, a lower dosage should be given and slowly titrated up to the appropriate dose.

Proper storage

Precautions while using this medication
Caution if any kind of surgery (including dental surgery) or emergency treatment is required

» Caution if drowsiness occurs

» Caution when getting up suddenly from lying or sitting position; dizziness and fainting may occur

» Caution in resuming normal physical activities when condition has improved, especially on patients with osteoporosis or phlebothrombosis.


Side/adverse effects
Agranulocytosis, akinesia, angina pectoris, arrhythmias, blepharospasm, choreiform movements, convulsions, depression, difficulty in swallowing, duodenal ulcer, dyskinesia, dystonic movements, ECG changes, flushing, gastrointestinal bleeding, hematuria, hemolytic, anemia, Horner's syndrome, hypertension, hypotonic freezing, leukopenia, muscle twitching, oculogyric crisis, orthostatic hypotension, paranoid ideation, phlebitis, psychotic episodes, or torticollis


General Dosing Information
Levodopa and benserazide combination therapy must be individualized and the dosage gradually titrated to the desired therapeutic level in order to reduce the high incidence of adverse reaction. Postencephalitic patients are more sensitive to levodopa and often require and tolerate lower dosage levels than other parkinsonism patients.{01}

With combination levodopa and benserazide combination therapy, more levodopa is available to the CNS. Under such conditions, titrations and dosage adjustments should be made in small steps to avoid adverse drug reactions.{01}

Any sign of involuntary movements should be regarded as an overdose of levodopa. Under such conditions, the dose of levodopa and benserazide combination should be reduced.{01}

Discontinue levodopa therapy for at least 12 hours before initiating levodopa and benserazide combination therapy.{01}

Provide at least 3 to 6 weeks of therapy before determining if levodopa and benserazide combination is ineffective for the patient.{01}

The limiting factor in treatment with levodopa and benserazide combination is the occurrence of involuntary movements. End-of-dose deterioration or “wearing off” periods usually have a close temporal relationship to the timing of levodopa administration. These effects may be alleviated for a time by shortening the dosing interval and reducing the size of individual doses. The threshold for dyskinetic manifestations may decrease and the incidence of oscillations in performance may increase sooner on levodopa and benserazide combination then on levodopa therapy alone.{01} A suggested technique for minimizing these manifestations include:

• After the initiation of therapy, daily maintenance of levodopa as combination therapy (i.e., levodopa and benserazide combination) should be reduced slowly (i.e., about 50 mg a month) over a period of a few months. The goal is give the lowest effective dose without dyskinesias.{01}


• After 1 year of therapy, patients should not receive more than 6 capsules of levodopa and benserazide combination 100–25 daily (600 mg of levodopa) divided into at least 4 to 6 doses.{01}


Diet/Nutrition
High-protein diets may decrease the effect of levodopa whereas a low protein diet tends to potentiate and stabilize the effects of levodopa.{01}

For treatment of adverse effects
If patients are experiencing abnormal involuntary movements, the dose should be reduced. However, the reduction in side effect may be at the expense of increasing parkinsonism.{01}


Parenteral Dosage Forms

LEVODOPA AND BENSERAZIDE CAPSULES

Usual Adult Dose
Parkinsonism—Patients not on levodopa


Initiation:
Oral, 100 mg of levodopa and 25 mg of benserazide twice a day.{01}


Note: Carefully increase initial doses of levodopa by 100 mg and benserazide by 25 mg every third or fourth day until an optimal therapeutic benefit is obtained without dyskinesia. Patients sensitive to levodopa therapy (e.g., postencephalitic Parkinson patients) may only tolerate a slower rate of dosage increase (e.g., weekly intervals). Towards the upper limits of dosage, the increments should be made more slowly (i.e., at 2- to 4-week intervals).{01}
The optimal daily dosage is usually 400 to 800 mg of levodopa and 100 to 200 mg of benserazide divided into 4 to 6 doses. Most patients will require no more than 600 mg of levodopa and 150 mg of benserazide per day. The goal of dosing frequency is to aim for at least 4 times daily taken with or immediately after meals{01}



Maintenance:
Oral, after optimal therapy has been determined, 200 mg of levodopa and 50 mg of benserazide. Patients should not receive more than 1000 to 1200 mg of levodopa during the first year of therapy.


Parkinsonism—Patients on levodopa


Initiation:
Start oral levodopa and benserazide at approximately 15% of the previous levodopa daily dosage. For example, if a patient is on a daily dose of 4000 mg levodopa, the levodopa and benserazide daily dosage should not exceed 600 mg of levodopa divided into 4 to 6 doses. {01}

Note: Allow at least 12 hours or more to elapse between the last dose of levodopa and the first dose of levodopa and benserazide.




Maintenance:
Oral, after optimal therapy has been determined, 200 mg of levodopa and 50 mg of benserazide. Patients should not receive more than 1000 to 1200 mg of levodopa and 250 to 300 mg of benserazide in combination daily during the first year of therapy.


Parkinsonism—All patients


Adjustments and Maintenance:
Oral, after the optimal therapy with levodopa and benserazide has been determined, use 200 mg of levodopa and 50 mg of benserazide. If frequent dosing is required to minimize adverse effects, use the levodopa 50 mg and benserazide 12.5 mg product{01}



Usual adult prescribing limits
Patients should not receive more than 1000 to 1200 mg of levodopa and 250 to 300 mg of benserazide in combination daily during the first year of therapy.{01}

Usual Pediatric Dose
Children up to 18 years of age: Safety and efficacy have not been established. {01}

Usual Geriatric Dose
See Usual adult dose.

Strength(s) usually available
U.S.—
Not commercially available

Canada—


50 mg levodopa/12.5 mg benserazide (Rx) [Prolopa® 50–12.5 (gelatin) (indigotine ) (iron oxide) (magnesium stearate) (mannitol) ( microcrystalline cellulose) (povidone) (talc) (titanium dioxide)]


100 mg levodopa/25 mg benserazide (Rx) [Prolopa® 100–25 (gelatin) (indigotine ) (iron oxide) (magnesium stearate) (mannitol) ( microcrystalline cellulose) (povidone) (talc) (titanium dioxide)]


200 mg levodopa/50 mg benserazide (Rx) [Prolopa® 200–50 (gelatin) (indigotine ) (iron oxide) (magnesium stearate) (mannitol) ( microcrystalline cellulose) (povidone) (talc) (titanium dioxide)]

Packaging and storage:
Store between 15 and 25 °C (59 and 77 °F), in a tight container. Protect from light.{01}

Auxiliary labeling:
   • Take with food.



Developed: 08/11/2000
Revised: 09/08/2000



References
  1. Product Information: Prolopa®, levodopa/benserazide. Hoffmann-La Roche Limited, Mississauga, ON, Canada, (PI revised 8/2000) reviewed 8/2000.
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