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» Home » CAD » Neurology » Neurodegenerative Diseases » Parkinson’s Disease
Background
Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of nerve cells in the substantia nigra. PD generally develops in later life with at least one symptom of resting tremor or cogwheel rigidity and generalized slowing of movements (bradykinesia). A rapid rate of disease progression is observed in elderly patients.
Most cases of PD are of unknown cause and are referred to as ‘Idiopathic Parkinsonism’. Despite the availability of effective symptomatic treatments to improve quality of life and life expectancy, no cure exists, and disease is associated with increased morbidity and mortality. Death isn’t caused by PD but rather by the complications caused by immobility (Cardiovascular, Cerebrovascular, Aspiration Pneumonia).
Epidemiology
According to the Parkinson’s Disease Foundation, approximately 1 million Americans are affected by this condition currently. The incidence of PD in the United States estimates at 20 per 100,000 individuals per year, with a mean age of 60.
Most individuals with PD start developing symptoms in their late 50s. However, recent studies have shown that 1 in 400 individuals start developing symptoms after the age of 40. The incidence and prevalence rate of this disorder is associated with the advancing age of the patient.
Gender variations in Parkinson’s disease are represented in a 3:2 male-to-female ratio, with delayed onset in females due to estrogen’s neuroprotective effects on the nigrostriatal dopaminergic pathway.
Anatomy
Pathophysiology
PD is caused by the loss of nerve cells of the substantia nigra in the basal ganglia. The basal ganglia is a part of the extrapyramidal system of the brain, responsible for posture, rigidity, and muscle tone.
The loss of dopaminergic action results in diminished motor functions resulting in tremors, bradykinesia. The pathological features of PD include the loss of pigmented dopaminergic neurons and the existence of Lewy bodies.
Patients experience motor dysfunction after 50-80% loss of dopaminergic neurons, which indicates the involvement of compensatory mechanisms in the early stage of the disease. On examination of post-mortem basal ganglia, Lewy bodies are noted within the remaining dopaminergic cells of the substantia nigra.
Etiology
Parkinson’s disease is a condition of the basal ganglia composed of many nuclei. Different areas of the cortex send inhibitory and excitatory signals to the striatum. The pathology behind Parkinson’s Disease is the loss of dopaminergic neurons.
The depletion of dopamine causes a reduction in thalamus activation and increases cholinergic activity because of the loss of dopamine’s inhibitory action. The presence of Lewy bodies and the loss of pigmented dopaminergic neurons are histological characteristics of Parkinson’s disease.
Genetics
About 5-10% of PD patients have a genetic predisposition. Genes responsible for genetic cases of PD are Leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), and Superoxide dismutase 2 gene (SOD2).
Prognostic Factors
With advancing age and progression of the disease, patient with Parkinson’s disease has disability ranging from minimal disability to unilateral or bilateral involvement, which usually leads to immobility.
The condition causes disability in most patients within ten years. Patients with Parkinson’s disease have three times the mortality rate of the general population.
While medication might alleviate symptoms, the quality of life is often poor. The disease significantly impacts patients, families, and caregivers through its progressive degenerative effects on movement and muscular function.
Clinical History
Physical Examination
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
Medication
carbidopa-levodopa treatment with additional carbidopa:
Initial dose: 25 mg orally once a day
Maintenance dose: additionally, 12.5 mg or 25 mg once a day
The duration of therapy is 200 mg orally per day
titration of carbidopa and levodopa:
Initial dose: 25 mg orally 3 to 4 times a day, levodopa given at the same time
The duration of therapy is 200 mg orally per day
Initial dose:
1.25
mg
Orally
twice a day
dose can be increased up to 2.5 mg per day every 14 to 28 days
Maximum dosage: 100 mg once a day
100 mg orally 3 times a day as an adjunct to levodopa/carbidopa; and increased to 200 mg as tolerated orally 3 times a day
The Maximum dose per day is 600 mg
100
mg
Tablet
Oral
once a day
initially for 1 week, increase the dose to 200 mg once a day if well tolerated
Oral
Initial dose: 1.5 mg capsule orally every 12hr; increase it up to 1.5 mg/dose every 4 weeks
Maintenance: 1.5-6 mg capsule orally every 12 hours
Transdermal
Initial dose: Apply the patch 4.6 mg every 24 hours; increase it up to 9.5 mg every 24 hours minimum 4 weeks; further after additional 4 weeks increase dose up to 13.3 mg patch
84
mg
Orally inhaled as needed using the supplied inhaler
Do not exceed > 5 doses per day
Note:
Indicated for the treatment of OFF episodes in Parkinson's disease patients receiving carbidopa/levodopa
Begin when symptoms of the OFF period reappear
Individual titration is used to determine the optimal dosage:
All doses are given as carbidopa-levodopa
:
Oral disintegrating tablets and immediate release:
25 mg-100 mg every 8 hours a day or 10 mg-100 mg every 6-8 hours a day; may increase by 1 tablet daily or alternate day till it reached to 8 tablets; the optimum dose may be obtained by combining tablets from both ratios (1:4 or 1:10).
Conversion from LEVODOPA:
Levodopa must be stopped at least 12 hours before initiating carbidopa-levodopa; start with 25% of the previous levodopa dose.
<1500 mg/day levodopa: Start with 25 mg-100 mg carbidopa-levodopa orally every 6-8 hours a day
> 1500 mg/day levodopa: Start with 25 mg-250 mg carbidopa-levodopa orally every 6-8 hours a day
Sinemet
Immediate release and orally disintegrating tablets:
25 mg/100 mg 3 times daily or 10 mg/100 mg orally 3-4 times daily; levodopa 100 mg/day can be increased 1-2 days.
Carbidopa taken as 70-100 mg per day, with no > 200 mg per day, and levodopa with no > 800 mg per day
Sinemet CR: 50 mg/200 mg orally 2 times daily; next 1600 mg/day of levodopa; doses must be given at least 6 hours apart.
Rytary
IR and ER
Levodopa-naive: 23.75 mg/95 mg orally every 8 hours daily; on day 4, increase to 36.25 mg/145 mg
maximum dose recommended is 97.5 mg/390 mg every 8 hours daily
Dosing frequency:
Can be changed to 3 times to 5 times daily if required
maximum recommended daily dose 612.5 mg/2450 mg
Replacement an equal levodopa dose for Stalevo as the patient's dose at transfer:
Carbidopa should be 70-100 mg/day; maximum dose 200 mg/day
do not to exceed 8 tablets/day divided every 6-8 hours while awake
Extended-release capsule
137mg orally every night at bedtime
After one week, increase to the recommended dose of 274 mg orally every night at bedtime
Extended-release tablets
129mg orally daily in the morning can increase the dose weekly
Do not exceed 322mg/day
There is no equivalent dose or dosing schedule for extended-release tablets for people who can't take more than 100 mg/day of immediate-release amantadine
Immediate-release tablet or capsule
100mg/day orally initially
After one week, it may increase to 100 mg every 12 hours and escalate to 400 mg/day in divided doses
Indicated for Parkinson disease-related dyskinesia:
137mg orally at bedtime every day
After one week, increase the recommended night time oral dosage to 274 mg.
Extrapyramidal Effects Drug Induced
Extended-release tablets
129 mg orally at bedtime every day, can increase the dose weekly.
Do not exceed 322mg/day.
Immediate release tablets
100mg orally twice a day. Do not exceed 300 mg/day
Dose Adjustments
Renal Impairment
Immediate release tablets
CrCl 30-50 mL/min: 200 mg orally on the first day, followed by 100 mg/day orally
CrCl 15-29 mL/min: 200 mg orally on the initial day, followed by 100 mg orally on an alternate day
CrCl <15 mL/min or hemodialysis: 200 mg orally once per week
Extended-release capsule
Moderate (CrCl 60-89 ml/min/1.73 m2): No dose change is required
Moderate (CrCl 30-59 mL/min/1.73m2): 68.5 mg every night at bedtime; may increase to 137 mg qHS after one week if needed; not to exceed 137 mg qHS.
Severe (CrCl 15-29 mL/min/1.73m2): 68.5 mg every night at bedtime
renal failure (CrCl<15 mL/min/1.73m2): Contraindicated
Hemodialysis: removed ineffectively
Extended-release tablets
Mild (CrCl 60-89 mL/min/1.73 m2): Increase dosage weekly; take one dose every day
Moderate (CrCl 30-59 mL/min/1.73 m2): Increase dose every three weeks; take one dose every day
Severe (CrCl 15-29 mL/min/1.73 m2): Increase every four weeks; take one dosage every 96 hours.
Kidney failure (CrCl<15 mL/min/1.73 m2): Avoided in patients
Initial: 1 mg orally the first day, following may increase by 2 mg every 3-5 days till it reaches 6-10 mg/days
Maintenance: 5-15 mg per day orally divided every 6-8hours
Use the SR product once gets stabilized on the regular release medication; when treating with levodopa, take 3-6 mg per day in the divided doses
SR product should not be crushed
Monitor: Intraocular pressure
Monotherapy: 1mg orally every day
Adjunctive therapy without levodopa: 1mg orally every day
Adjunctive therapy with levodopa: Initial dose of 0.5 mg taken orally every day; this may be increased to 1 mg per day if necessary and acceptable
Consider lowering the dosage of levodopa
Dose Adjustments
Renal Impairment:
No dose change is needed for mild-to-moderate cases; severe cases have not been evaluated
Hepatic Impairment:
Moderate (Child-Pugh A): No more than 0.5 mg per day
Severe to moderate (Child-Pugh B/C): Do not use
10 gms orally every day
Initially: 50 mg orally every day
may increase the dosage to 100 mg orally every day after two weeks, depending on individual requirements and tolerance
Doses of more than 100 mg daily have not shown any additional benefit
Dose Adjustments
Dosage Modifications
Hepatic impairment
Moderate (Child-Pugh score B: 7 to 9): should not exceed more than 50 mg/day
Severe (Child-Pugh score C: 10 to 15): It is Contraindicated
Conventional-
5 mg orally at breakfast and 5 mg during lunch, hence; 10 mg/day
2-3 days later the selegiline therapy, taper the dose of levodopa by 10-30%, depending on the tolerance
Do not exceed the dose of more than 10 mg/day
If combined with levodopa, 1.25 mg orally each day
Orally-disintegrating-
Initially, 1.25 mg orally each day
If no adequate response is achieved, increase the dose after 6 weeks
Do not increase the dose to more than 2.5 mg/day
Don’t swallow
Take the medication in the morning without liquids
Dose Modifications
In the case of hepatic disease (mild to moderate), Child-Pugh class A & B- reduce the daily dose from 2.5 to 1.25 mg each day
Take 10-15 mg of medication orally once every other day or as directed by a physician
20 mg orally daily; with a maximum increase of 40 mg orally daily
Titration of the initial dosage is not necessary
Dose Adjustments
Dosage Modifications
Hepatic impairment
Mild (Child-Pugh score A): dose adjustment is not necessary
Moderate (Child-Pugh score B): should not exceed more than 20 mg orally daily
Severe (Child-Pugh score C): contraindicated
Renal impairment
Mild, moderate, or severe (CrCl 15 to 89 mL/min): dose adjustment is not necessary
End-stage renal disease (CrCl less than 15 mL/min) or ESRD that require hemodialysis: Not known
Coadministration along with strong CYP3A4 inhibitors
Should not exceed more than 20 mg orally daily
Tobacco smokers
Tobacco usage (above 20 cigarettes in a day or equal to tobacco product): 40 mg orally daily
Immediate release tablet- Initially, 0.25 mg orally every 8 hours for 1 week
Increase the dose weekly by 0.25 mg every 8 hours
If required, increase after 4 weeks
The dose may be increased each week by 1.5- 9 mg/day
Later increase it weekly by 3-24 mg/day
Extended-release tablet- Initially, 2 mg/day orally for 1-2 weeks
Increase the dose by 2 mg/day at a gap of more than 1 week
Do not exceed the dose of more than 24 mg/day
foscarbidopa/foslevodopa (FDA approval pending)
Pending FDA approval
Initial dose: Administer 100mg/25mg levodopa/benserazide once or twice a day.
As the high limits of the dosing range are reached, the frequency of dosage modifications should be reduced to every 2 to 4 weeks.
It should be added to the dosage every 3 to 4 days or more slowly (e.g., weekly) if there are tolerance issues.
Maintenance dose-Adminsiter 400mg/100mg levodopa/benserazide to 800mg/200mg levodopa/benserazide in four to six divided doses.
Maximum dose-Do not exceed 1000 -1200mg/day in the first year of treatment.
Intermittent restless leg syndrome (Off label)
Initial dose- Administer 100mg/25mg levodopa/benserazide whenever needed before bedtime.
The dosage can be increased to 200 mg/50 mg levodopa/benserazide based on response and tolerability.
Do not exceed 200mg of levodopa
Check combination drug levodopa/benserazide
In combination with levodopa
Initial dose: Administer 100mg/25mg levodopa/benserazide once or twice a day.
Do not exceed 12 capsules/day.
Indicated as monotherapy treatment
As hydrochloride: At the start, take 2.5 mg orally three times a day; adjust the dose incrementally based on clinical response up to a maximum of 15 to 60 mg a day, administered in divided doses
For monotherapy, administer 150–250 mg daily, divided into 3 to 5 doses. 50–150 mg per day in combination with levodopa treatment. The dosage must be increased gradually by 50 mg every three days. The dosage should be gradually decreased until the therapy has been completely discontinued.
Take an initial dose of 50 mcg orally in the evening on day 1, then raised up to 50 mcg two times a day on days 2 to 4
Raised dose by 100 to 250 mcg every 3 to 4 days in 3 divided doses up to a daily dose of 1.5 mg at day 28
After day 30, dose is raised up to max of 250 mcg two times day weekly
Take a maintenance dose of 2.1 to 2.5 mg orally daily in 3 divided doses
>65 years old: Treatment should depend on renal function
5-15 mg per day orally divided every 6-8hours
5 mg orally every with each breakfast and lunch
When combined with levodopa, keep the dose less than 5 mg each day
3 days later of selegiline therapy, taper the dose of levodopa by 10-30%
Continue to streamline the dose as per the patient’s response
Orally-disintegrating-
Initially, 1.25 mg orally each day
If no adequate response is achieved, increase the dose after 6 weeks
Do not increase the dose to more than 2.5 mg/day
foscarbidopa/foslevodopa (FDA approval pending)
Pending FDA approval
Future Trends
References
1. https://www.ncbi.nlm.nih.gov/books/NBK470193/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517533/
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» Home » CAD » Neurology » Neurodegenerative Diseases » Parkinson’s Disease
Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of nerve cells in the substantia nigra. PD generally develops in later life with at least one symptom of resting tremor or cogwheel rigidity and generalized slowing of movements (bradykinesia). A rapid rate of disease progression is observed in elderly patients.
Most cases of PD are of unknown cause and are referred to as ‘Idiopathic Parkinsonism’. Despite the availability of effective symptomatic treatments to improve quality of life and life expectancy, no cure exists, and disease is associated with increased morbidity and mortality. Death isn’t caused by PD but rather by the complications caused by immobility (Cardiovascular, Cerebrovascular, Aspiration Pneumonia).
According to the Parkinson’s Disease Foundation, approximately 1 million Americans are affected by this condition currently. The incidence of PD in the United States estimates at 20 per 100,000 individuals per year, with a mean age of 60.
Most individuals with PD start developing symptoms in their late 50s. However, recent studies have shown that 1 in 400 individuals start developing symptoms after the age of 40. The incidence and prevalence rate of this disorder is associated with the advancing age of the patient.
Gender variations in Parkinson’s disease are represented in a 3:2 male-to-female ratio, with delayed onset in females due to estrogen’s neuroprotective effects on the nigrostriatal dopaminergic pathway.
PD is caused by the loss of nerve cells of the substantia nigra in the basal ganglia. The basal ganglia is a part of the extrapyramidal system of the brain, responsible for posture, rigidity, and muscle tone.
The loss of dopaminergic action results in diminished motor functions resulting in tremors, bradykinesia. The pathological features of PD include the loss of pigmented dopaminergic neurons and the existence of Lewy bodies.
Patients experience motor dysfunction after 50-80% loss of dopaminergic neurons, which indicates the involvement of compensatory mechanisms in the early stage of the disease. On examination of post-mortem basal ganglia, Lewy bodies are noted within the remaining dopaminergic cells of the substantia nigra.
Parkinson’s disease is a condition of the basal ganglia composed of many nuclei. Different areas of the cortex send inhibitory and excitatory signals to the striatum. The pathology behind Parkinson’s Disease is the loss of dopaminergic neurons.
The depletion of dopamine causes a reduction in thalamus activation and increases cholinergic activity because of the loss of dopamine’s inhibitory action. The presence of Lewy bodies and the loss of pigmented dopaminergic neurons are histological characteristics of Parkinson’s disease.
About 5-10% of PD patients have a genetic predisposition. Genes responsible for genetic cases of PD are Leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), and Superoxide dismutase 2 gene (SOD2).
With advancing age and progression of the disease, patient with Parkinson’s disease has disability ranging from minimal disability to unilateral or bilateral involvement, which usually leads to immobility.
The condition causes disability in most patients within ten years. Patients with Parkinson’s disease have three times the mortality rate of the general population.
While medication might alleviate symptoms, the quality of life is often poor. The disease significantly impacts patients, families, and caregivers through its progressive degenerative effects on movement and muscular function.
carbidopa-levodopa treatment with additional carbidopa:
Initial dose: 25 mg orally once a day
Maintenance dose: additionally, 12.5 mg or 25 mg once a day
The duration of therapy is 200 mg orally per day
titration of carbidopa and levodopa:
Initial dose: 25 mg orally 3 to 4 times a day, levodopa given at the same time
The duration of therapy is 200 mg orally per day
Initial dose:
1.25
mg
Orally
twice a day
dose can be increased up to 2.5 mg per day every 14 to 28 days
Maximum dosage: 100 mg once a day
100 mg orally 3 times a day as an adjunct to levodopa/carbidopa; and increased to 200 mg as tolerated orally 3 times a day
The Maximum dose per day is 600 mg
100
mg
Tablet
Oral
once a day
initially for 1 week, increase the dose to 200 mg once a day if well tolerated
Oral
Initial dose: 1.5 mg capsule orally every 12hr; increase it up to 1.5 mg/dose every 4 weeks
Maintenance: 1.5-6 mg capsule orally every 12 hours
Transdermal
Initial dose: Apply the patch 4.6 mg every 24 hours; increase it up to 9.5 mg every 24 hours minimum 4 weeks; further after additional 4 weeks increase dose up to 13.3 mg patch
84
mg
Orally inhaled as needed using the supplied inhaler
Do not exceed > 5 doses per day
Note:
Indicated for the treatment of OFF episodes in Parkinson's disease patients receiving carbidopa/levodopa
Begin when symptoms of the OFF period reappear
Individual titration is used to determine the optimal dosage:
All doses are given as carbidopa-levodopa
:
Oral disintegrating tablets and immediate release:
25 mg-100 mg every 8 hours a day or 10 mg-100 mg every 6-8 hours a day; may increase by 1 tablet daily or alternate day till it reached to 8 tablets; the optimum dose may be obtained by combining tablets from both ratios (1:4 or 1:10).
Conversion from LEVODOPA:
Levodopa must be stopped at least 12 hours before initiating carbidopa-levodopa; start with 25% of the previous levodopa dose.
<1500 mg/day levodopa: Start with 25 mg-100 mg carbidopa-levodopa orally every 6-8 hours a day
> 1500 mg/day levodopa: Start with 25 mg-250 mg carbidopa-levodopa orally every 6-8 hours a day
Sinemet
Immediate release and orally disintegrating tablets:
25 mg/100 mg 3 times daily or 10 mg/100 mg orally 3-4 times daily; levodopa 100 mg/day can be increased 1-2 days.
Carbidopa taken as 70-100 mg per day, with no > 200 mg per day, and levodopa with no > 800 mg per day
Sinemet CR: 50 mg/200 mg orally 2 times daily; next 1600 mg/day of levodopa; doses must be given at least 6 hours apart.
Rytary
IR and ER
Levodopa-naive: 23.75 mg/95 mg orally every 8 hours daily; on day 4, increase to 36.25 mg/145 mg
maximum dose recommended is 97.5 mg/390 mg every 8 hours daily
Dosing frequency:
Can be changed to 3 times to 5 times daily if required
maximum recommended daily dose 612.5 mg/2450 mg
Replacement an equal levodopa dose for Stalevo as the patient's dose at transfer:
Carbidopa should be 70-100 mg/day; maximum dose 200 mg/day
do not to exceed 8 tablets/day divided every 6-8 hours while awake
Extended-release capsule
137mg orally every night at bedtime
After one week, increase to the recommended dose of 274 mg orally every night at bedtime
Extended-release tablets
129mg orally daily in the morning can increase the dose weekly
Do not exceed 322mg/day
There is no equivalent dose or dosing schedule for extended-release tablets for people who can't take more than 100 mg/day of immediate-release amantadine
Immediate-release tablet or capsule
100mg/day orally initially
After one week, it may increase to 100 mg every 12 hours and escalate to 400 mg/day in divided doses
Indicated for Parkinson disease-related dyskinesia:
137mg orally at bedtime every day
After one week, increase the recommended night time oral dosage to 274 mg.
Extrapyramidal Effects Drug Induced
Extended-release tablets
129 mg orally at bedtime every day, can increase the dose weekly.
Do not exceed 322mg/day.
Immediate release tablets
100mg orally twice a day. Do not exceed 300 mg/day
Dose Adjustments
Renal Impairment
Immediate release tablets
CrCl 30-50 mL/min: 200 mg orally on the first day, followed by 100 mg/day orally
CrCl 15-29 mL/min: 200 mg orally on the initial day, followed by 100 mg orally on an alternate day
CrCl <15 mL/min or hemodialysis: 200 mg orally once per week
Extended-release capsule
Moderate (CrCl 60-89 ml/min/1.73 m2): No dose change is required
Moderate (CrCl 30-59 mL/min/1.73m2): 68.5 mg every night at bedtime; may increase to 137 mg qHS after one week if needed; not to exceed 137 mg qHS.
Severe (CrCl 15-29 mL/min/1.73m2): 68.5 mg every night at bedtime
renal failure (CrCl<15 mL/min/1.73m2): Contraindicated
Hemodialysis: removed ineffectively
Extended-release tablets
Mild (CrCl 60-89 mL/min/1.73 m2): Increase dosage weekly; take one dose every day
Moderate (CrCl 30-59 mL/min/1.73 m2): Increase dose every three weeks; take one dose every day
Severe (CrCl 15-29 mL/min/1.73 m2): Increase every four weeks; take one dosage every 96 hours.
Kidney failure (CrCl<15 mL/min/1.73 m2): Avoided in patients
Initial: 1 mg orally the first day, following may increase by 2 mg every 3-5 days till it reaches 6-10 mg/days
Maintenance: 5-15 mg per day orally divided every 6-8hours
Use the SR product once gets stabilized on the regular release medication; when treating with levodopa, take 3-6 mg per day in the divided doses
SR product should not be crushed
Monitor: Intraocular pressure
Monotherapy: 1mg orally every day
Adjunctive therapy without levodopa: 1mg orally every day
Adjunctive therapy with levodopa: Initial dose of 0.5 mg taken orally every day; this may be increased to 1 mg per day if necessary and acceptable
Consider lowering the dosage of levodopa
Dose Adjustments
Renal Impairment:
No dose change is needed for mild-to-moderate cases; severe cases have not been evaluated
Hepatic Impairment:
Moderate (Child-Pugh A): No more than 0.5 mg per day
Severe to moderate (Child-Pugh B/C): Do not use
10 gms orally every day
Initially: 50 mg orally every day
may increase the dosage to 100 mg orally every day after two weeks, depending on individual requirements and tolerance
Doses of more than 100 mg daily have not shown any additional benefit
Dose Adjustments
Dosage Modifications
Hepatic impairment
Moderate (Child-Pugh score B: 7 to 9): should not exceed more than 50 mg/day
Severe (Child-Pugh score C: 10 to 15): It is Contraindicated
Conventional-
5 mg orally at breakfast and 5 mg during lunch, hence; 10 mg/day
2-3 days later the selegiline therapy, taper the dose of levodopa by 10-30%, depending on the tolerance
Do not exceed the dose of more than 10 mg/day
If combined with levodopa, 1.25 mg orally each day
Orally-disintegrating-
Initially, 1.25 mg orally each day
If no adequate response is achieved, increase the dose after 6 weeks
Do not increase the dose to more than 2.5 mg/day
Don’t swallow
Take the medication in the morning without liquids
Dose Modifications
In the case of hepatic disease (mild to moderate), Child-Pugh class A & B- reduce the daily dose from 2.5 to 1.25 mg each day
Take 10-15 mg of medication orally once every other day or as directed by a physician
20 mg orally daily; with a maximum increase of 40 mg orally daily
Titration of the initial dosage is not necessary
Dose Adjustments
Dosage Modifications
Hepatic impairment
Mild (Child-Pugh score A): dose adjustment is not necessary
Moderate (Child-Pugh score B): should not exceed more than 20 mg orally daily
Severe (Child-Pugh score C): contraindicated
Renal impairment
Mild, moderate, or severe (CrCl 15 to 89 mL/min): dose adjustment is not necessary
End-stage renal disease (CrCl less than 15 mL/min) or ESRD that require hemodialysis: Not known
Coadministration along with strong CYP3A4 inhibitors
Should not exceed more than 20 mg orally daily
Tobacco smokers
Tobacco usage (above 20 cigarettes in a day or equal to tobacco product): 40 mg orally daily
Immediate release tablet- Initially, 0.25 mg orally every 8 hours for 1 week
Increase the dose weekly by 0.25 mg every 8 hours
If required, increase after 4 weeks
The dose may be increased each week by 1.5- 9 mg/day
Later increase it weekly by 3-24 mg/day
Extended-release tablet- Initially, 2 mg/day orally for 1-2 weeks
Increase the dose by 2 mg/day at a gap of more than 1 week
Do not exceed the dose of more than 24 mg/day
foscarbidopa/foslevodopa (FDA approval pending)
Pending FDA approval
Initial dose: Administer 100mg/25mg levodopa/benserazide once or twice a day.
As the high limits of the dosing range are reached, the frequency of dosage modifications should be reduced to every 2 to 4 weeks.
It should be added to the dosage every 3 to 4 days or more slowly (e.g., weekly) if there are tolerance issues.
Maintenance dose-Adminsiter 400mg/100mg levodopa/benserazide to 800mg/200mg levodopa/benserazide in four to six divided doses.
Maximum dose-Do not exceed 1000 -1200mg/day in the first year of treatment.
Intermittent restless leg syndrome (Off label)
Initial dose- Administer 100mg/25mg levodopa/benserazide whenever needed before bedtime.
The dosage can be increased to 200 mg/50 mg levodopa/benserazide based on response and tolerability.
Do not exceed 200mg of levodopa
Check combination drug levodopa/benserazide
In combination with levodopa
Initial dose: Administer 100mg/25mg levodopa/benserazide once or twice a day.
Do not exceed 12 capsules/day.
Indicated as monotherapy treatment
As hydrochloride: At the start, take 2.5 mg orally three times a day; adjust the dose incrementally based on clinical response up to a maximum of 15 to 60 mg a day, administered in divided doses
For monotherapy, administer 150–250 mg daily, divided into 3 to 5 doses. 50–150 mg per day in combination with levodopa treatment. The dosage must be increased gradually by 50 mg every three days. The dosage should be gradually decreased until the therapy has been completely discontinued.
Take an initial dose of 50 mcg orally in the evening on day 1, then raised up to 50 mcg two times a day on days 2 to 4
Raised dose by 100 to 250 mcg every 3 to 4 days in 3 divided doses up to a daily dose of 1.5 mg at day 28
After day 30, dose is raised up to max of 250 mcg two times day weekly
Take a maintenance dose of 2.1 to 2.5 mg orally daily in 3 divided doses
>65 years old: Treatment should depend on renal function
5-15 mg per day orally divided every 6-8hours
5 mg orally every with each breakfast and lunch
When combined with levodopa, keep the dose less than 5 mg each day
3 days later of selegiline therapy, taper the dose of levodopa by 10-30%
Continue to streamline the dose as per the patient’s response
Orally-disintegrating-
Initially, 1.25 mg orally each day
If no adequate response is achieved, increase the dose after 6 weeks
Do not increase the dose to more than 2.5 mg/day
foscarbidopa/foslevodopa (FDA approval pending)
Pending FDA approval
1. https://www.ncbi.nlm.nih.gov/books/NBK470193/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517533/
Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of nerve cells in the substantia nigra. PD generally develops in later life with at least one symptom of resting tremor or cogwheel rigidity and generalized slowing of movements (bradykinesia). A rapid rate of disease progression is observed in elderly patients.
Most cases of PD are of unknown cause and are referred to as ‘Idiopathic Parkinsonism’. Despite the availability of effective symptomatic treatments to improve quality of life and life expectancy, no cure exists, and disease is associated with increased morbidity and mortality. Death isn’t caused by PD but rather by the complications caused by immobility (Cardiovascular, Cerebrovascular, Aspiration Pneumonia).
According to the Parkinson’s Disease Foundation, approximately 1 million Americans are affected by this condition currently. The incidence of PD in the United States estimates at 20 per 100,000 individuals per year, with a mean age of 60.
Most individuals with PD start developing symptoms in their late 50s. However, recent studies have shown that 1 in 400 individuals start developing symptoms after the age of 40. The incidence and prevalence rate of this disorder is associated with the advancing age of the patient.
Gender variations in Parkinson’s disease are represented in a 3:2 male-to-female ratio, with delayed onset in females due to estrogen’s neuroprotective effects on the nigrostriatal dopaminergic pathway.
PD is caused by the loss of nerve cells of the substantia nigra in the basal ganglia. The basal ganglia is a part of the extrapyramidal system of the brain, responsible for posture, rigidity, and muscle tone.
The loss of dopaminergic action results in diminished motor functions resulting in tremors, bradykinesia. The pathological features of PD include the loss of pigmented dopaminergic neurons and the existence of Lewy bodies.
Patients experience motor dysfunction after 50-80% loss of dopaminergic neurons, which indicates the involvement of compensatory mechanisms in the early stage of the disease. On examination of post-mortem basal ganglia, Lewy bodies are noted within the remaining dopaminergic cells of the substantia nigra.
Parkinson’s disease is a condition of the basal ganglia composed of many nuclei. Different areas of the cortex send inhibitory and excitatory signals to the striatum. The pathology behind Parkinson’s Disease is the loss of dopaminergic neurons.
The depletion of dopamine causes a reduction in thalamus activation and increases cholinergic activity because of the loss of dopamine’s inhibitory action. The presence of Lewy bodies and the loss of pigmented dopaminergic neurons are histological characteristics of Parkinson’s disease.
About 5-10% of PD patients have a genetic predisposition. Genes responsible for genetic cases of PD are Leucine-rich repeat kinase 2 (LRRK2), PTEN-induced putative kinase 1 (PINK1), and Superoxide dismutase 2 gene (SOD2).
With advancing age and progression of the disease, patient with Parkinson’s disease has disability ranging from minimal disability to unilateral or bilateral involvement, which usually leads to immobility.
The condition causes disability in most patients within ten years. Patients with Parkinson’s disease have three times the mortality rate of the general population.
While medication might alleviate symptoms, the quality of life is often poor. The disease significantly impacts patients, families, and caregivers through its progressive degenerative effects on movement and muscular function.
1. https://www.ncbi.nlm.nih.gov/books/NBK470193/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517533/
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