Sinemet (levodopa, carbidopa) is a combination antiparkinsonian medication used to treat Parkinson's disease and similar symptoms, such as shakiness and stiffness, when caused by disorders or damage to the central nervous system.

Parkinson's disease is thought to be caused by low dopamine levels in the brain. Most treatments consist of raising dopamine levels in the brain, which Sinemet also does. To better understand how Sinemet works we'll need to look at its two active ingredients:

• Levodopa, also called L-DOPA, is widely regarded as the best treatment for Parkinson's. In the brain it converts to dopamine, which helps patients with movement issues. However, when used on its own, much of levodopa is converted before it reaches the brain, resulting in higher doses, greater risk of side effects, and reduced benefit.
• Carbidopa inhibits conversion of levodopa before it reaches the brain. Including this medication with levodopa means patients receive greater benefit with lower doses and reduced risk/severity of side effects.

Levodopa and carbidopa may be taken as separate tablets, but most patients find Sinemet's combination tablet much more convenient.

It's important to note that patients taking Sinemet should not also take levodopa separately; this is far too much levodopa and side effects are likely to be experienced.

Before Taking Sinemet

While Sinemet produces positive benefits faster than levodopa alone, it also causes adverse reactions quicker. Note that not every patient will experience adverse effects, and they can often be resolved by reducing dosage if they are experienced. Any concerning symptom should be brought to the attention of a doctor.

Patients starting treatment, following dosage adjustments, or abruptly ending treatment should be alert for warning signs.

Though Sinemet is meant to help resolve movement issues, ironically it's a little more likely than levodopa alone to cause different versions of them. An early symptom of these movement disorders is often blepharospam---involuntary blinking or closing of eyelids---but this does not always occur.

Other concerning side effects involve changing mood or behaviors; decreased impulse control and increased sex drive are common. If these become powerful enough to be concerning or cause disruption, consult a doctor.

Sinemet can cause urine, saliva, or sweat to become discolored, even dark red or black. While this may appear alarming it is not cause for concern.

Other medications can interact with Sinemet; be sure the prescribing doctor is aware if taking:

• Blood pressure medications
• Antidepressants or antipsychotics
• Any supplement containing iron
• Risperidone
• Isoniazid
• Metoclopramide
• Reserpine
• Phenytoin
• Papaverine
• Any medication that ends in -azine, such as tetrabenazine, perphaenazine, chlorpromazine, and so forth

Sinemet can cause drowsiness; some patients fall asleep with little warning. Use caution performing dangerous tasks---such as driving or operating machinery---until effects of Sinemet are known.

Dosage & Administration

Sinemet comes in tablets, available in several strengths:

• 10/100 mg carbidopa/levodopa
• 25/100 mg carbidopa/levodopa
• 25/250 mg carbidopa/levodopa

Tablets can be taken with food, but high-fat or high-protein meals will delay effectiveness. If in doubt, take one or two hours before or after a meal. A full glass of fluid is recommended with each dose.

Patients are typically started on lower doses, which is increased only if needed and if no disruptive side effects develop. Treatment is typically:

• Start with 25/100 mg carbidopa/levodopa, taken three times per day (total dose of 75/300 mg carbidopa/levodopa)
• If needed, dosage may be gradually increased. Tablets may be split if needed for accurate dosing.
• Do not exceed 200 mg carbidopa per day; that's 8 25/100 or 25/250 mg tablets per day.

Other medications and other medical conditions can also influence dosage, usually calling for it to be lower; patients with other conditions or taking other medications may be started on 10/100 mg carbidopa/levodopa.

Treatment really is individualized. Ideally patients will work closely with a doctor, who can evaluate results and monitor for side effects.

Treatment with Sinemet should not end abruptly; dosage should be gradually reduced if treatment ends. A doctor can help come up with a discontinuation plan.

Sinemet CR (levodopa, carbidopa) is a combination antiparkinsonian medication, predominantly used to help resolve movement disorders associated with Parkinson's disease or Parkinson's syndrome. It may also be used off-label to help with other conditions, such as restless leg syndrome.

The CR in this product's name indicates it is controlled release, compared to the fast-acting version of regular Sinemet. Some patients find the CR version works better, though others find the fast-acting version is more effective. Note that CR tablets cannot be crushed, chewed, or otherwise damaged; doing so will destroy their CR properties and may result in too much medication at once.

Sinemet and Sinemet CR are the first-line, gold standard treatment for Parkinson's.

How it Works

Like many Parkinson's medications, Sinemet CR works by increasing the level of dopamine in the brain. It contains two active ingredients, which work together to provide benefit:

• Levodopa, also called L-DOPA, is widely regarded as the best treatment for Parkinson's. In the brain it converts to dopamine, which helps patients with movement issues. However, when used on its own, much of levodopa is converted before it reaches the brain, resulting in higher doses, greater risk of side effects, and reduced benefit.
• Carbidopa inhibits conversion of levodopa before it reaches the brain. Including this medication with levodopa means patients receive greater benefit with lower doses and reduced risk/severity of side effects.

Sinemet CR definitely provides significant benefit in the majority of patients who take it; it alleviates symptoms of slow movements, stiff muscles, tremors, and so forth. However, it is not a cure and it will not slow progression of the disease.

There will come a time when Sinemet CR's benefit begins to wane; the medication will be less effective, on-off syndrome may become more pronounced, resistance to the medication may develop, and there is some evidence that long-term use contributes to dopamine dysregulation. Long-term use is also associated with increased risk of dyskinesia, spontaneous, involuntary movements.

At some point, when the medication no longer provides benefit or negative side effects outweigh its benefit, treatment may end.

Benefits of the CR Version

The biggest benefit of Sinemet CR versus the fast-acting version has to do with keeping levels of the drug consistent in the body, which can provide greater benefit both in helping with muscle stiffness and preventing side effects.

On-off syndrome describes the fluctuation between feeling good and feeling bad; as levels of the drug increase and peak in the body the patient feels good, as they wane away the patients feels bad. This happens relatively rapidly with fast-acting versions; it is considerably slower with Sinemet CR.

At peak levels dyskinesia symptoms may also develop. Patients taking Sinemet CR are often able to avoid these symptoms when they are experienced with regular Sinemet, as more regular levels of the drug reduce both highs and lows.

There are always exceptions; Sinemet CR may not alleviate these effects in all patients, particularly at higher doses or if the disease has progressed for some time.

Dosage & Administration

Sinemet CR is available in tablets for most patients. Those unable to swallow whole tablets may be able to get this medication in a gel or as orally-dissolving tablets.

Treatment is highly individualized, and thus highly variable. Patients are strongly advised to consult a doctor about dosage, frequency of administration, and discontinuing treatment.

Dosage is typically limited by amount of levodopa, rather than carbidopa. Most patients take somewhere between 400 to 1600 mg of levodopa per day, which is divided into smaller doses that may be taken as frequently as every 4 hours throughout the day.

Treatment usually begins with low doses, increased if needed. Dosage should not be increased more frequently than every three days. It's not unusual for dosage to gradually increase over time as the disease progresses.

Sinemet CR should not be discontinued abruptly; speak with a doctor about a discontinuation plan.

There are numerous other medications that can help with Parkinson's; sometimes one or more will be given along with Sinemet CR. This may affect dosage of one or more of the medications involved; do not start taking additional medications without first clearing them with a doctor.

Precautions

Sinemet CR can cause drowsiness; some patients fall asleep with little warning. Use caution performing dangerous tasks---such as driving or operating machinery---until effects of Sinemet CR are known.

Sinemet CR can cause urine, saliva, or sweat to become discolored, even dark red or black. While this may appear alarming it is not cause for concern.

Other medications can interact with Sinemet; be sure the prescribing doctor is aware if taking:

• Blood pressure medications
• Antidepressants or antipsychotics
• Any supplement containing iron
• Risperidone
• Isoniazid
• Metoclopramide
• Reserpine
• Phenytoin
• Papaverine
• Any medication that ends in -azine, such as tetrabenazine, perphaenazine, chlorpromazine, and so forth

Other conditions that may influence dosage include:

• Kidney or liver impairment
• Breathing difficulties, such as asthma
• Heart or blood vessel issues
• Irregularities in heart rhythm
• Endocrine disorders
• Sleep disorders, such as narcolepsy
• History of stomach ulcers
• History of heart attack
• Wide-angle glaucoma

Speak with a doctor before taking Sinemet or Sinemet CR if trying to get pregnant, pregnant, or breastfeeding.