levodopa and benserazide

Action and Spectrum

Actions and Spectrum: 

• levodopa is a precursor of dopamine, a neurotransmitter that plays a crucial role in regulating movement and other functions in the brain. In Parkinson’s disease, there is a deficiency of dopamine due to the progressive degeneration of dopaminergic neurons in the substantia nigra, a region of the brain. levodopa is converted into dopamine by enzymes in the brain, which helps replenish the depleted dopamine levels and alleviate the motor symptoms of Parkinson’s disease. 
• benserazide is a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor. AADC is an enzyme that converts levodopa into dopamine in the brain and peripheral tissues. By inhibiting AADC outside the brain, benserazide ensures that more levodopa is available to enter the brain, which can be converted into dopamine to alleviate Parkinson’s symptoms. 
• levodopa is highly effective in treating the motor symptoms of Parkinson’s disease, such as bradykinesia (slowness of movement), rigidity, and resting tremors.  
• benserazide does not have a therapeutic effect on its own; instead, it enhances the effectiveness of levodopa by preventing its premature conversion to dopamine in peripheral tissues. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Involuntary body movements 

Psychiatric disturbance 

Paranoid ideation 

Post-marketing reports 

Cardiac arrhythmias 

Alopecia 

Diaphoresis 

Nocturia 

Dyskinesia 

Abnormal gait 

Akinesia 

Blepharospasm 

Angina pectoris 

Dark sweat 

Hematuria 

Urinary frequency 

Lower back pain 

Agitation 

Blurred vision 

ECG changes 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity or Allergy: Individuals with known hypersensitivity or allergy to levodopa, benserazide, or other medication components should not use this combination. 
• Narrow-Angle Glaucoma: levodopa may increase intraocular pressure, potentially worsening narrow-angle glaucoma.  
• Non-Controlled Psychiatric Disorders: Patients with severe psychiatric disorders, such as schizophrenia or psychosis, should avoid using levodopa and benserazide as they may exacerbate their condition. 
• History of Melanoma: Evidence suggests a possible link between levodopa use and an increased risk of melanoma, a type of skin cancer.  

Caution: 

• Gastrointestinal Disorders: levodopa can cause nausea, vomiting, and other gastrointestinal disturbances, especially when starting the treatment.  
• Cardiovascular Conditions: levodopa can cause fluctuations in blood pressure, leading to episodes of orthostatic hypotension and increased heart rate.  
• Psychiatric Disorders: levodopa can have effects on mood and behavior. Patients with a history of depression or other psychiatric disorders should be closely monitored for changes in mood or symptoms of psychosis during treatment. 
• Dyskinesias: Long-term use of levodopa can lead to involuntary movements, known as dyskinesias. The risk of dyskinesias increases with higher doses and prolonged use.

Pregnancy / Lactation

Pregnancy consideration: It is contraindicated during pregnancy 

Lactation: Excretion of the drug in human breast milk is known 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

• levodopa is a naturally occurring amino acid and precursor of dopamine, a neurotransmitter in the brain that plays a crucial role in controlling movement and coordination.  
• benserazide is an aromatic L-amino acid decarboxylase (AADC) inhibitor. 
• Combining levodopa with benserazide helps to address the challenges associated with levodopa’s peripheral metabolism and its limited ability to cross the blood-brain barrier. By working together, these medications allow more levodopa to reach the brain, which can be converted into dopamine and alleviate the motor symptoms of Parkinson’s disease. 

Pharmacodynamics:  

By combining levodopa with benserazide, the peripheral metabolism of levodopa is reduced, leading to higher levels of levodopa available for conversion to dopamine in the brain. This helps to enhance the therapeutic effect of levodopa on motor symptoms in Parkinson’s disease while reducing peripheral side effects. 

Pharmacokinetics: 

Absorption 

levodopa has a high bioavailability of 98% (74% to 112%) after oral administration. benserazide is absorbed to 66% to 74% after oral administration. 

Distribution 

levodopa has a distribution volume of 57 L. It readily crosses the blood-brain barrier, allowing it to reach the brain, where it exerts its therapeutic effects. benserazide does not cross the blood-brain barrier and is mainly concentrated in the kidneys, liver, lungs, and small intestine. 

Metabolism 

levodopa is metabolized by several pathways, with the major ones being decarboxylation to dopamine and O-methylation to 3-O-methyldopa. Minor pathways include transamination and oxidation. benserazide is hydroxylated in the intestine and liver to form trihydroxybenzylhydrazine, a potent decarboxylase inhibitor. 

Elimination and Excretion 

benserazide is primarily excreted in the urine (64%) and, to a lesser extent, in feces (24%). The half-life of levodopa is approximately 1.5 hours, while its major metabolite, 3-O-methyldopa, has a longer half-life of about 15 hours. levodopa and its metabolites are primarily excreted in the urine. 

Adminstartion

Administration: 

Oral administration 

Take this medication after a low- or no-protein food (such as fruit, applesauce, or biscuits) to reduce GI side effects. Avoid crushing, chewing, opening, or dissolving capsules in liquid; consume them whole. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: levodopa and benserazide 

Why do we use levodopa and benserazide? 

Combining levodopa and benserazide is an effective therapeutic option to manage the motor symptoms associated with Parkinson’s disease.  

• Improved Motor Function: The main goal of levodopa/benserazide therapy is to improve motor function in individuals with Parkinson’s disease. levodopa is a dopamine precursor and can cross the blood-brain barrier to replenish the depleted dopamine levels in the brain. Increasing dopamine levels help alleviate motor symptoms such as tremors, rigidity, bradykinesia (slowness of movement), and postural instability. 
• Reduction of “Off” Periods: Parkinson’s disease patients often experience fluctuations in their response to medication, leading to “off” periods when their symptoms are not well controlled. The levodopa/benserazide combination can help reduce these “off” periods and provide a more stable and continuous improvement in motor function. 
• Enhanced Efficacy: benserazide, a peripheral decarboxylase inhibitor (PDI), is combined with levodopa to prevent its breakdown into dopamine in peripheral tissues. By inhibiting the enzyme aromatic L-amino acid decarboxylase (AADC) outside the brain, benserazide increases the amount of levodopa that reaches the brain. This enhances the therapeutic effect of levodopa on Parkinson’s motor symptoms. 
• Symptom Relief: levodopa/benserazide can significantly improve the quality of life for individuals with Parkinson’s disease by relieving debilitating motor symptoms and improving mobility and function.