Medications & Marijuana

Understanding PD medications and more

Dear Ratna Prasad,

Whether you are new to Parkinson’s disease (PD) or have been living with it for years, you’re likely aware
of the many medications that can be part of a PD treatment plan. Of course, it will differ from person to
person, but medication management in PD can be very tricky. With so many medications available, it can
be difficult to understand the differences between them; and the timing of when to take your meds can be
complicated. Some people also wonder if non-medical options, like marijuana and CBD products, could
supplement their treatment plan. APDA is here to help with some useful resources about PD medications
and more.  

 The Many Forms of Carbidopa/Levodopa: The most effective medication for people with PD,
carbidopa/levodopa, is available in various strengths and delivery systems which makes
understanding all the available options very confusing. This article will help you make sense of the
different options and the rationale for using each one.

 Approved Medications: Take a look at this helpful list of medications used to treat the motor and
non-motor symptoms of Parkinson’s disease. This list is also available in Spanish.

 Medications to Avoid: Equally, if not more important, is knowing which medications to avoid.

Familiarize yourself with this list and keep it handy. Of course, every patient is different, and you may
need to take one of these medications despite caution against it. Always discuss your particular
situation with your physician and do not stop any medication that you are currently taking without
first seeking medical advice. This list is also available in Spanish.
  Medical Marijuana & PD: Learn about the difference between THC and CBD, the potential benefits
and cautions, clinical trials for medical marijuana, availability in your state, and more.

 Understanding CBD & PD: Learn more about what CBD is and its possible use for symptoms of PD.
Find out whether or not it’s legal, the regulation (or lack of) CBD products, the evidence surrounding
CBD for use in PD, and much more.

 APDA Symptom Tracker App: Not only does APDA’s free Symptom Tracker App help you keep track
of your symptoms and create a report to share with your healthcare team, but it also features
an interactive medication tracker where you can enter the specific medications/doses and the time of
day you take them and receive reminder notifications. It’s available in English and Spanish and you
can start using it right now – just download the free APDA Symptom Tracker app from the App Store
or Google Play.

We hope these resources help you better manage your PD medications. It’s not always easy to get your
meds “just right,” but it can make a big difference when you do.

As always, we’ve got many great exercise classes and educational programs planned for you. Don’t forget
to check out our Virtual Events Calendar to see what's coming up soon. Here are two that you won't want
to miss:

 January 26, 3:30 pm ET: Sing Loud for PD is back! Exercise your voice while having fun during this
popular program. No singing experience (or talent!) required. The theme for this week’s class is
“Seasons & Weather”

 February 14, 12 pm ET: Dr. Gilbert Hosts: Taking Research From the Lab to our Lives   Spend
your Valentine’s Day with APDA as we welcome some brilliant guests to talk about how PD research
that is being done now in a lab will benefit people with PD in “real life”
Remember, APDA is here for you every step of the way. Please do not hesitate to reach out via our APDA
helpline at (800-223-2732)  or email us at apda@apdaparkinson.org.

Have a great day,

Leslie A. Chambers
President & CEO

 The many variations of carbidopa/levodopa – the mainstay of Parkinson’s disease treatment

Posted on March 9, 2021 by Dr. Rebecca Gilbert

HOW CARBIDOPA/LEVODOPA IS USED TO TREAT PARKINSON’S DISEASE SYMPTOMS

Loss of neurons in the brain that use dopamine to communicate is one of the hallmark features of
Parkinson’s disease (PD), causing slowness, stiffness, tremor and balance problems. Replacing the brain’s
dopamine is therefore one of the key treatment strategies to help improve the motor symptoms of PD.
Dopamine itself does not cross the blood-brain barrier and therefore can’t be used to treat PD. Instead,
levodopa, a precursor of dopamine, which does cross the blood-brain barrier is used. If levodopa is
ingested by itself however, it breaks down in the bloodstream before it crosses into the brain, so levodopa
is typically ingested with another medication that stops it from breaking down. In the US, the combination
of carbidopa/levodopa is used.
Carbidopa/levodopa is the mainstay of treatment for PD and is the most effective medication currently
available for PD. APDA research support played a role in the discovery of levodopa for PD treatment when
we funded the work of Dr. George C. Cotzias back in the 1960s.

This previous blog answers common questions regarding carbidopa/levodopa.

While carbidopa/levodopa remains the most effective medication for people with PD, it is available in
various strengths and delivery systems which makes understanding all the available levodopa options very
confusing. To help you make sense of the many options, I will describe the various levodopa formulations
and the rationale for using each one.

Carbidopa/levodopa immediate release (brand name Sinemet) is the original formulation and the one that
is most frequently used.
This is typically the first formulation to be tried when someone is started on levodopa treatment. This
medication comes in three dosages 10/100, 25/100 and 25/250. The first number refers to the milligrams
of carbidopa in the pill. The second number refers to the milligrams of levodopa in the pill.

Early on in PD, a dose can last six hours or longer, but often, as PD progresses, a levodopa dose tends to
relieve symptoms for shorter and shorter amounts of time. A person may take a dose of levodopa and
have good symptom relief for a period of time, referred to as ON time. Then the effects of levodopa may
start to wear off and symptoms of PD return for a period of time, referred to as OFF time. This
phenomenon of alternating between ON and OFF time is known as motor fluctuations. There are many
strategies that your doctor can try to smooth out your response to medication throughout the day and
these are summarized in a recent APDA webinar.

If this is happening, one strategy is to try a different formulation of levodopa that is designed to last
longer than carbidopa/levodopa immediate release. Another strategy is to try a formulation of levodopa
that can be used as needed if the medication effect wears off between oral doses of medication.

CARBIDOPA/LEVODOPA FORMULATIONS THAT MAY LAST LONGER THAN CARBIDOPA/LEVODOPA

IMMEDIATE RELEASE

Carbidopa/levodopa extended release (brand name Sinemet CR)

This is a formulation of carbidopa/levodopa that was originally designed to be extended or controlled
release. For some people it works well as an option to extend the life of a dose of carbidopa/levodopa.
Sometimes, this medication is prescribed at bedtime to help with nighttime symptoms and to try to
prevent OFF time in the morning. The brand-name version of this medication  is no longer being
manufactured, although a number of generics are available. The dosages of this medication are 25/100
and 50/200. Again, the first number refers to the milligrams of carbidopa in the pill and the second
number refers to the milligrams of levodopa in the pill.

Despite its “extended release” formulaton, for many people this formulation does not last longer than
carbidopa/levodopa immediate release. Other formulations were therefore designed to achieve this goal.

Carbidopa/levodopa/entacapone (brand name Stalevo)

This is a combination medication of carbidopa/levodopa and entacapone, designed to last longer than
carbidopa/levodopa alone. Entacapone is a COMT (cathechol-O-methyltransferase) inhibitor which, in a
manner similar to carbidopa, inhibits the breakdown of levodopa in the periphery and allows more
levodopa to cross the blood brain barrier and get converted into dopamine in the brain. This medication
comes in a number of dosages as follows:
 carbidopa Levodopa entacapone

Stalevo 50 12.5 mg 50 mg 200 mg

Stalevo 75 18.75 mg 75 mg 200 mg

Stalevo 100 25 mg 100 mg 200 mg

Stalevo 125 31.25 mg 125 mg 200 mg

Stalevo 150 37.5 mg 150 mg 200 mg

Stalevo 200 50 mg 200 mg 200 mg

Carbidopa/levodopa extended-release capsules (brand name Rytary ®)
In this formulation of carbidopa/levodopa, the medication exists in varying sized beads within a capsule.
The different sized beads dissolve at different rates, allowing for a more prolonged release of the
medication from the stomach. Four strengths are available: 23.75/95, 36.25/145, 48.75/195, 61.25/245
(with the first number again referring to the milligrams of carbidopa in the pill and the second number
refers to the milligrams of levodopa in the pill.) A typical dose of medication is three capsules, three to
four times a day. Capsules can be opened and the beads can be added to food without losing their
extended release properties. This can be useful for someone with swallowing difficulties.

Carbidopa/levodopa enteral suspension (brand name Duopa TM)

Instead of taking carbidopa/levodopa in a pill form, people with PD can receive carbidopa-levodopa in a
gel form infused directly into the small intestine where levodopa is known to be absorbed. This system can
be useful for those with advancing PD who have motor fluctuations that are no longer controlled by oral
medications alone. The system can be particularly helpful for those who have gastroparesis, or delayed
gastric emptying, which is a common non-motor symptom of PD and can keep oral medications stuck in
the stomach and therefore unable to be absorbed readily by the small intestine.

This is how the system works (diagram above). In a minor surgical procedure, a gastroenterologist inserts
a PEG/J (percutaneous endoscopic gastrostomy with jejunal) tube with one end in the small intestine and
the other end emerging from a stoma or hole in the abdominal wall. The tubing that emerges from the
abdomen is then attached to a small portable pump, which can be worn in a carrying case over the
shoulder or around the waist. The pump is in turn connected to a cassette of carbidopa/levodopa gel.

After the system is inserted, the person with PD works with his/her neurologist to find the right
settings for the pump. There are three doses of medication (also called a bolus) that need to be optimized

The amount of levodopa that is infused into the small intestine

Morning bolus when the system is started in the morning
This bolus allows the person to turn “ON” in the morning

The rate at which the gel is infused into the small intestine over
Infusion rate
the course of 16 hours of the day

The amount of levodopa that is infused into the small intestine on

an “as needed” basis when the pump is activated by the person
As-needed bolus
with PD
Used for unexpected OFF times during the day

Your doctor will show you how to properly care for the stoma and explain any potential issues to be
mindful of.

For someone with Duopa in place, the daily routine may be as follows:
 A set of carbidopa/levodopa enteral suspension cassettes (each containing 2,000 mg of levodopa – a
person with high levodopa requirements may need two cassettes over the course of a day) are stored in
the refrigerator.
 In the morning, a cassette is removed from the refrigerator 20 minutes prior to use and attached to the
pump once it reaches room temperature.
 The cassette tubing is attached to the tubing that emerges from the abdomen
 The pump is turned on and activated to give the morning bolus
 Then the pump automatically starts delivering the gel at the predetermined continuous rate
 The pump can be inserted into its carrying case so that it is portable as the person with PD performs
their daily activities
 The person with PD can activate the pump to deliver pre-programmed extra doses throughout the day if
necessary
 At the end of the day, the pump is removed from the carrying case and shut off.
 The cassette tubing and the abdominal tubing are disconnected. The tubing that emerges from the
abdomen is flushed with saline and capped for the night.
 If medication is needed during the night, the person may be given oral doses of carbidopa/levodopa to
take.

CARBIDOPA/LEVODOPA FORMULATIONS TO BE USED AS NEEDED

Carbidopa/levodopa orally disintegrating tablets (brand name Parcopa ®)

This formulation of carbidopa/levodopa dissolves in the mouth. Although it is absorbed in the gut, the fact
that it does not have to be broken down in the stomach means that onset of action of the medication is
somewhat quicker than regular Sinemet. It is also useful for those who have difficulty swallowing pills.

Levodopa inhalation powder (brand name Inbrija ®)

This is an inhalation formulation (containing only levodopa) designed for quicker onset of action, to be
used as needed if medication effects wear off between oral doses of carbidopa-levodopa. The dose is
taken when PD symptoms start to return. Absorption of the medication takes place through the lungs
which bypass absorption through the gastrointestinal tract. When a person is experiencing return of
his/her symptoms, he or she breaks a blister pack containing a 42 mg levodopa capsule and inserts it into
the Inbrija inhaler device and inhales through the device. Then a second capsule is inserted into the
device and inhaled (one dose is two capsules). This can be done one time during each OFF period, up to
five times a day.  The inhaler cannot be preloaded with the capsules which must stay in their blister
package until immediately before use. Only an Inbrija inhaler can be used with the levodopa capsules. 

FORMULATIONS OF CARBIDOPA/LEVODOPA THAT ARE IN THE RESEARCH PIPELINE FOR POTENTIAL USE
IN TREATING PARKINSON’S DISEASE
While we already have quite a few options, researchers are constantly looking for new and better
formulations of carbidopa/levodopa. Everyone experiences PD differently, so the more medication options
your doctor has to choose from, the better he/she can find one that works best for your specific needs.
There are a number of carbidopa/levodopa formulations in the research pipeline now which I’ll explain
below. We’ve also put together an overview of additional medications (beyond carbidopa/levodopa) in the
research pipeline.

IPX203

This new carbidopa/levodopa formulation is being investigated in a phase 3 clinical trial (NCT03670953).
Thirteen weeks of the trial is double-blinded and placebo controlled and compares the efficacy of this
formulation to that of carbidopa/levodopa immediate release.  This investigational formulation is being
developed by the same company that manufactures Rytary. IPX203 is also made of different sized beads
of carbidopa/levodopa and it is designed to cause a quick rise in levodopa absorption after the pill is
ingested, followed by steady, continuous absorption.

Accordion pill carbidopa/levodopa

This is a pill with an innovative design, which involves loading the medication onto thin films which are
then folded into a wavy shape and placed within a capsule. The pill enters the stomach and releases the
medication more slowly than a regular pill as the films containing the medication unfurl. The Accordion pill
was studied in a phase 3 multi-centered double-blind, randomized trial that included 320 patients.
Unfortunately, the trial did not demonstrate a statistically significant reduction in OFF time as compared to
immediate release carbidopa/levodopa. However, the data continues to be analyzed and further trials may
be planned.
Subcutaneous infusions that are being researched as treatments for PD
ABBV-951

This is a carbidopa/levodopa subcutaneous infusion system which is under investigation in a phase 3

clinical trial. (NCT04380142) The medication is delivered via a small implantable device that infuses the
novel formulation of carbidopa/levodopa under the skin. The study compares the efficacy, safety and
tolerability of a continuous infusion to that of orally ingested medication.

ND0612

This is a second carbidopa/levodopa subcutaneous infusion system which is under investigation in a phase
3 clinical trial (NCT04006210), with the effects of the subcutaneous infusion being compared to that of
oral medication.

Infudopa SubC

This is a third subcutaneous formulation of carbidopa/levodopa currently under investigation. A phase 1

clinical trial (NCT03419806) was recently completed which demonstrated safety and showed that
adequate levodopa concentrations were reached.

While some of these will not end up being approved for use, the research is still important because we
learn from it. As the trials progress, we hope that several of these medications will be approved and added
to the arsenal with which we fight PD.

Tips and Takeaways

 Carbidopa/levodopa is the mainstay of PD treatment medications

 Carbidopa/levodopa comes in a variety of formulations and doses and seeks to replenish the dopamine
in the brain that is lost due to PD
 Some formulations help to smooth out motor fluctuations
 Other formulations are used “as needed” if PD symptoms return between doses
 Additional formulations are in the research pipeline
 Consult your neurologist if your current dosage is no longer working as effectively as before, and/or to
determine whether there is a new formulation that may benefit you

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