New FDA-approved Therapies Can Help Prevent Carbidopa/Levodopa Complications
Parkinson’s disease (PD) is a neurodegenerative disease that results from the loss of dopamine in the brain. It is a complicated disease that results in many symptoms, the hallmark of which is slowness of movement. There are several medications used to treat PD with new therapies entering the market. The gold standard is levodopa, which is given in conjunction with carbidopa for entry into the brain. There have been various formulations of this including immediate release carbidopa/levodopa (Sinemet®) and controlled release carbidopa/levodopa (Sinemet® CR).
Since the first clinical trial in 1961, levodopa remains the most effective treatment for PD, but after chronic use of the medication, complications can develop. One of these complications is that the medication wears off, and the therapeutic effect no longer lasts as long. Patients may end up having to take the medication many times a day, which can be frustrating. Another complication is dyskinesia, or involuntary movement of the body.
Studies have shown that the intermittent nature of oral levodopa replacement contributes to these complications. This occurs for several reasons: Erratic gastric emptying, variable jejunal absorption, and the short half-life of the drug lead to fluctuating levels. This pulsating stimulation of dopamine receptors in the brain is thought to cause gene and molecular changes that lead to these motor complications.
Two new therapies
In 2015, two therapies were approved by the FDA that attempt to overcome this problem. Rytary™ is a capsule that contains both immediate and extended release carbidopa/levodopa. As opposed to the prior sustained release formulation (Sinemet CR), this formulation has fast onset (similar to immediate release carbidopa/levodopa), as well as extended release action. It was studied as a medication to be taken three times daily. In some cases, this needs to be adjusted to dosing more often during the day, but it can simplify a previously complicated levodopa regimen. It also can be used in the beginning of the disease in an attempt to prevent complications, although this effect has not been proven.
The second new therapy is called Duopa™. This is an intestinal infusion of a carbidopa/levodopa gel. Similar to a feeding tube, patients have a procedure to place a tube in the small intestine so there can be a direct infusion of the medication that bypasses the stomach. This helps prevent absorption problems that can occur in the stomach. The pump is attached to a cartridge filled with the medication, providing a continuous infusion so patients do not have to take pills throughout the day. It often replaces adjunctive medications as well. It is another therapy that improves the motor complications of wearing off and dyskinesia.
Research is ongoing to find innovative treatments for Parkinson’s disease. Part of this effort has been these new formulations of levodopa. If you or a loved one suffers from the complications of treating PD, it may be worth asking your neurologist about these new therapies.
Susan M. Sifers, M.D., M.S., is a neurologist at Saint Luke’s Marion Bloch Neuroscience Institute who is fellowship trained in movement disorders. She also has her master’s degree in neuroscience.