Madopar: Everything You Need to Know

Madopar ® is a drug used to alleviate the motor symptoms of Parkinson's disease. It has two different active ingredients that maximize its effectiveness.

Written and verified by el biólogo Samuel Antonio Sánchez Amador.

Last update: 16 January, 2023

Madopar ® is a drug that contains two active substances: levodopa (L-DOPA) and benserazide. Benserazide allows more levodopa to reach the brain, but it’s the latter that does the bulk of the compound’s pharmacological work.

The purpose of the drug is to increase the amount of dopamine in the nervous system, in order to treat conditions such as Parkinson’s disease. Although here we’re going to focus on the drug Madopar®, it should be noted that there are others that contain the levodopa/benserazide duo, such as Madopar Retard®.

In addition, more drugs are conceived to treat parkinsonian conditions, such as Apodespan PR ®, Caramet CR ® and Lecado ®, among others.

What is Madopar ®?

As the National Library of Medicine states in the United States, Parkinson’s disease causes the death of certain brain cells. In this condition, the neurons responsible for producing dopamine disappear. Without dopamine, the cells in charge of controlling movement can’t send nerve messages correctly to the muscles.

This neural damage worsens over time, although the cause of neurodegeneration still isn’t fully understood. Be that as it may, the disease manifests with bradykinesia (slow movement), stiffness (increased muscle tone), tremors, and loss of posture control. It also leads to depression and impaired cognitive function.

Madopar ® increases the concentration of dopamine in the nervous system, because after all, levodopa (L-DOPA) is the precursor of dopamine, epinephrine, and norepinephrine. Let’s have a look at the pharmacological action of each of its active principles separately.

Levodopa (L-DOPA)

You might think that the injection or oral administration of dopamine would be more useful, as it’s the neurotransmitter that fails. As indicated by the Statpearls medical portal, this is not the case, as dopamine doesn’t cross the blood-brain barrier, a highly selective structure that separates circulating blood from the extracellular fluid of the brain in the central nervous system (CNS).

In contrast, levodopa (L-DOPA) does cross the blood-brain barrier. In addition, it’s capable of converting into dopamine in the central nervous system, and also in the peripheral one. Thanks to this work, it reduces the bradykinesia typical of Parkinson’s disease.

Recent studies have shown that the administration of L-DOPA could reduce the progression of Parkinson’s disease and have long-term beneficial effects, in addition to reporting possible benefits in other pathologies.

Benserazide

Benserazide, also called serazide or Ro 4-4602, is a DOPA-decarboxylase inhibitor. In a normal situation, this lyase enzyme is responsible for transforming levodopa into dopamine, something that should be positive. However, DOPA-decarboxylase causes decarboxylation of L-Dopa to dopamine before it reaches the brain, preventing it from crossing the blood-brain barrier.

Bensezaride inhibits the previously named decarboxylation. For this reason, levodopa reaches the brain, crosses the blood-brain barrier, and is transformed into dopamine in the nervous system. Since bensezaride can’t cross this barrier, dopamine can accumulate properly in the brain.

How is Madopar ® administered?

Although the drug can also be found in the Madopar Retard ® form, we’re going to refer to the prospectus of the conventional variant. First of all, it should be noted that Madopar ® is designed as a pill for oral intake and each unit has 200 milligrams of levodopa and 50 milligrams of benserazide.

The usual dose varies between patients and depends a lot on the symptoms. However, a conservative initial approach is usually taken, starting with 1/4 pill, 2 to 4 times a day. After a week of treatment, the specialist can increase the dose in order to improve well-being.

If we look at the dosage of levodopa or L-DOPA separately, we’ll see that the minimum dose is 300 milligrams and up to 1200 milligrams can be taken per day —even more if it’s tolerated—, divided into 3 to 12 doses every 24 hours. The general rule of thumb is to increase the dosage by 100 milligrams every 3-4 days.

These figures allow us to estimate the general dosage of Madopar ®, but we must bear in mind that this drug has another active principle (benserazide). For this reason, the information provided is only an estimate and the specific dose should always be accompanied by a prescription.

As indicated in the package insert, it may take several weeks for the effect of the drug to become apparent and the patient can experience sporadic worsening at first. In addition, it’s recommended to take the tablets half an hour before eating or one hour after meals.

Who should not take Madopar ®?

Madopar ® has many contraindications. In the following list, we’ll show you the most important ones:

• This medicine cannot be taken by anyone who has shown allergic reactions to the active substances levodopa and benserazide. You also have to be careful with the rest of the compounds that the pills contain.
• Madopar ® cannot be combined with monoamine oxidase inhibitor antidepressant drugs (MAOIs), with few exceptions.
• It isn’t recommended in patients with acute high intraocular pressure, i.e. closed-angle glaucoma.
• It shouldn’t be prescribed in patients with severe kidney, liver, and heart problems. However, it can be administered in normal doses in people with mild kidney failure.
• Its use is reserved in people with severe psychiatric disorders with a psychotic component. This includes those patients with personality disorders and dissociations.

In pregnancy

As indicated by medical sources, this drug is completely contraindicated in pregnant women and in those who don’t take contraceptive precautions. It has been shown to cause skeletal changes in fetuses and children during development.

During lactation

This drug is transmitted through the milk from mother to child. Therefore, a lady who is being treated with Madopar ® should not breastfeed her child.

What are the possible side effects of Madopar ®?

Like all existing drugs, Madopar ® can report certain side effects in the patient in the short and long term. However, this is a special case, as all the possible side effects are of unknown frequency. This means that symptoms have been detected in those who take the drug, but the percentage of those affected is not known.

As we don’t have verified data, we’re going to show you the side effects based on the affected organs and systems in the following list:

• Circulatory system disorders: Hemolytic anemia, leukopenia, and thrombocytopenia.
• Nutritional problems: Decreased appetite.
• Psychiatric disorders: Dopamine dysregulation syndrome, confusion, depression, agitation, anxiety, insomnia, hallucinations, hypersexuality, and delusions.
• Nervous system disorders: A loss of the sense of taste, fluctuations in therapeutic response, freezing phenomena, drowsiness, sudden episodes of sleep, and dyskinesia – abnormal movements of the orofacial muscles.
• Heart problems: Arrhythmias.
• Vascular disorders: Orthostatic hypotension.
• Gastrointestinal disorders: Nausea, vomiting, diarrhea, discoloration of saliva, tongue, teeth, and oral mucosa.
• Skin problems: Itching and skin rashes.
• Renal and urinary disorders: Increased blood urea and urine color changes.

The most common side effects of taking levodopa drugs are dizziness, nausea, headaches, and drowsiness. To avoid gastrointestinal symptoms, it can be prescribed together with domperidone.

What happens if I miss a dose?

It can be often difficult to keep track of all the daily doses, as some patients need to take either a part or the whole drug in 2, 3, 4, or more doses every 24 hours. Therefore, in these cases, it’s especially advisable to make use of alarms and other reminders.

In these specific cases, it’s best that you skip the forgotten dose and continue with the treatment as if nothing had happened throughout the day. This applies when doses are spread over 3 or more doses a day, because you should never compensate for missed doses by taking two tablets very close together

What should I do in cases of an overdose?

If you have taken more Madopar ® than you should, urgently consult your pharmacist, doctor or call the Toxicology Information Service in your region. If you can, make your own way to a hospital, but if you are incapacitated, call an ambulance and find someone to stay with you.

Madopar ® overdose can lead to adverse effects such as cardiac arrhythmias, confusion and insomnia, nausea, and involuntary movements.

How to store or dispose of this medicine?

This medicine should be kept in its original container, closed, and out of the reach of children. It’s also recommended not to store it above 30 degrees Celsius. Don’t take it once it’s past its expiry date.

Finally, if you want to get rid of this medicine because it has expired, don’t throw it away or throw it down the toilet. Contact the relevant organization in your country to dispose of it correctly.

Final notes

Madopar ® is one of the drugs par excellence to treat Parkinson’s disease, as it somewhat solves the lack of dopamine in the nervous system that characterizes the pathology. The aforementioned studies are optimistic regarding this drug, as it appears to slow down the pathological process.

However, it also has many contraindications and can cause several very unpleasant side effects, the frequency of which is unknown. If you have any questions or feel that the treatment is giving you problems, discuss possible scenarios with your doctor.