Benserazide

BRAND NAMES

Madopar: A combination of levodopa and benserazide used for Parkinson's disease, sold by Roche in the UK and other countries. 

Prolopa: Also a levodopa and benserazide combination made by Roche and used for Parkinson's disease, sold in Canada and other regions. 

Levodopa/ Benserazide ratiopharm: A generic brand available in some markets. 

Benspar: Another brand name for the combination. 

Levopar: Another brand name for the combination. 

MECHANISM OF ACTION

Benserazide's mechanism of action involves inhibiting the enzyme aromatic-L-amino acid decarboxylase (AADC) in the peripheral nervous system. This enzyme is responsible for converting levodopa into dopamine outside the brain. By blocking this conversion in the periphery, benserazide ensures that more levodopa remains available to cross the blood-brain barrier, where it can then be converted into dopamine in the brain to help alleviate the motor symptoms of Parkinson’s disease. Importantly, benserazide itself does not cross the blood-brain barrier and has no therapeutic effect on its own.

PHARMACOKINETICS

Absorption

Benserazide is efficiently absorbed from the gastrointestinal tract, with a substantial amount of the oral dose reaching the bloodstream. After absorption, it undergoes rapid metabolism in the intestinal lining and the liver.

Distribution

The volume of distribution (Vd) of benserazide is not well-defined in publicly available clinical data, likely due to its rapid metabolism and limited systemic distribution, as it acts primarily in the peripheral tissues and does not cross the blood-brain barrier.

Metabolism

Benserazide is rapidly metabolized after oral administration, primarily in the intestinal mucosa and the liver. It is converted into several inactive metabolites, as it does not cross the blood-brain barrier and is intended to act only in the peripheral nervous system. The rapid metabolism limits its systemic activity and ensures its effect remains peripheral, allowing levodopa to reach the brain without being prematurely converted to dopamine in the body.

Elimination

Benserazide is primarily eliminated through urinary excretion. Following intravenous administration, approximately 86–90% of benserazide is excreted in the urine. After oral administration, about 53–64% of the dose is recovered in urine. Benserazide is almost completely eliminated through metabolism, with its primary metabolites excreted mainly in the urine (around 64%) and to a lesser extent in the feces (about 24%).

PHARMACODYNAMICS

Benserazide is a decarboxylase inhibitor that does not cross the blood-brain barrier. Its primary pharmacodynamic action is to enhance the delivery of levodopa to the central nervous system (CNS) by inhibiting its conversion to dopamine in the peripheral tissues. On its own, benserazide has no significant antiparkinsonian effects and is only used in combination with levodopa.

ADMINISTRATION

Benserazide is given orally in combination with levodopa, typically as a fixed-dose tablet or capsule. It’s usually taken 30 minutes before or 1 hour after meals to improve absorption. It is not used alone or given by injection.

DOSAGE AND STRENGTH

Benserazide is not administered alone but always in combination with levodopa in fixed-dose formulations. Common strengths include levodopa 100 mg with benserazide 25 mg, and levodopa 200 mg with benserazide 50 mg. The typical starting dose is levodopa 50–100 mg combined with benserazide 12.5–25 mg, taken two to three times daily. Maintenance doses are adjusted according to the patient’s response and can range up to levodopa 400–800 mg with benserazide 100–200 mg daily, divided into multiple doses. It is essential to follow the prescribing healthcare provider’s instructions for dosing and adjustments.

FOOD INTERACTIONS

Benserazide, given in combination with levodopa, can be affected by food intake. High-protein meals may reduce the absorption of levodopa, potentially decreasing its effectiveness. Therefore, it is generally recommended to take the medication 30 minutes before or 1 hour after meals to improve absorption. Aside from this, there are no significant food interactions specific to benserazide itself.

DRUG INTERACTIONS

Benserazide, particularly when used with levodopa, can interact with several medications. Notably, combining it with monoamine oxidase (MAO) inhibitors may lead to a hypertensive crisis. Additionally, drugs that block dopamine receptors (D2 antagonists) can decrease the effectiveness of levodopa, including some antipsychotic medications. Patients with narrow-angle glaucoma should use benserazide cautiously, as it may raise intraocular pressure. It is also important to be aware of potential interactions with other dopamine agonists such as selegiline, pergolide, and ropinirole.

CONTRAINDICATIONS

Benserazide is contraindicated in patients who are allergic to benserazide or any components of the medication. It should not be used in individuals with pheochromocytoma, a type of adrenal gland tumor, as it may cause dangerous increases in blood pressure. Additionally, benserazide is contraindicated in patients with narrow-angle glaucoma unless carefully monitored, due to the risk of increased intraocular pressure. Use with caution or avoid in patients with a history of severe cardiac, hepatic, or renal disease. Since benserazide is always combined with levodopa, contraindications related to levodopa should also be considered.

SIDE EFFECTS

• Gastrointestinal issues.

• Dizziness.

• Involuntary movements (dyskinesia).

• Sleep problems.

• Mental changes.

• Sudden onset of sleep.

• Hallucinations.

• Impulse control disorders.

• Neuroleptic malignant syndrome (NMS).

• Heart problems.

• Severe diarrhea.

OVERDOSE

1. Central Nervous System:

• Agitation, confusion, hallucinations

• Insomnia, restlessness

• Sedation or drowsiness (less common)

2. Cardiovascular:

• Tachycardia, arrhythmias

• Fluctuations in blood pressure (hypotension or hypertension)

3. Gastrointestinal:

• Nausea, vomiting, diarrhea, abdominal discomfort

4. Other Possible Effects:

• Sweating, flushing

• Ataxia (loss of coordination)

• Involuntary movements (dyskinesia)

TOXICITY

Benserazide can cause nausea, vomiting, agitation, confusion, insomnia, abnormal movements (dyskinesias), and cardiovascular effects such as irregular heartbeat or blood pressure changes. Severe cases may lead to hallucinations or loss of coordination. There is no specific antidote; treatment is supportive, focusing on stabilizing vital signs and managing symptoms.