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Ask the MD: Choosing the Right Therapy for "Off" Time

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Inbrija (inhaled levodopa), a new therapy for "off" time — when Parkinson's disease (PD) symptoms re-emerge — is now available by prescription through a network of specialty pharmacies. Under-the-tongue apomorphine, also for "off" time, is currently under review with the U.S. Food and Drug Administration (FDA). For many people, these medications may offer a different and, in some ways, easier route to manage symptoms. But it can be hard to know if and when to add a new drug and what you should ask your doctor. Here, we discuss the new and existing treatments for "off" and tips for thinking about newer medications.

What is "off" time? 
"Off" time is when PD symptoms return between medication doses. Not everyone experiences "off" time, but it's more common the longer you have Parkinson's and the longer you take levodopa. "Off" time may involve movement problems (tremor, slowness and stiffness) as well as non-movement symptoms (anxiety, sweating, or cloudy or fuzzy thinking). Because each person's Parkinson's is unique, everyone's "off" time is unique. "Off" time can happen at different times: in the morning, before the first dose of medication; between medication doses or after meals throughout the day; or suddenly and unpredictably.

What is the new "off" treatment?
Acorda's Inbrija is an inhaled form of levodopa, which is the most commonly prescribed Parkinson's drug. In the brain, levodopa turns into the chemical dopamine, which decreases in PD and causes abnormal and uncoordinated movement. Inbrija is absorbed through the lungs, so it is absorbed more quickly than a pill taken by mouth.

Inbrija is to be used as needed, up to five times per day, to rapidly reverse "off" symptoms. You take it in addition to regularly scheduled Parkinson's medications. This is similar to asthma treatment, where a person may take a daily medication to control breathing and use a rescue inhaler if sudden problems arise. 


In clinical trials, Inbrija started to work in as little as 10 minutes and lasted up to an hour. The most common potential side effects of Inbrija include nausea, cough, upper respiratory infection, or changes in saliva or spit color.

Learn more about Inbrija.

Should I take Inbrija? 
If you have recurring or sporadic "off" times, you may want to consider Inbrija. But because this is an add-on medication, it may be helpful to first ensure your current treatment is working as well as it can. Adjustments to how and when you take your medications could lessen "off" time.

For some people, separating levodopa from high-protein meals (meat, fish, nuts or beans, for example) by 30 to 60 minutes may ease symptoms. Levodopa and dietary protein are absorbed in the same part of the gut. When you take medication and protein at the same time, less medication may be absorbed, potentially leading to "off" time.

Changing your medication's dose or timing also may help. If your symptoms start to return gradually about an hour before every levodopa dose, for example, your doctor may recommend you take it more often or increase the dose, or add a longer-acting PD drug to prevent "wearing off."

If you still have "off" time despite dietary and medication adjustments, Inbrija may be an option. Even for those whose symptoms are fairly well controlled, it may be good to have a rescue therapy on hand just in case "off" time comes on at an unpredictable or inconvenient moment.

Isn't Apokyn already available for "off" time? 
Apokyn, injectable apomorphine, has been available since 2004 to use as needed for Parkinson's "off" time. Apomorphine mimics the brain chemical dopamine, which decreases in PD. When prescribing Apokyn, doctors typically add medication to prevent nausea and observe your first dose to make sure blood pressure doesn't drop too low. The main side effects are nausea, low blood pressure or dizziness, and sleepiness as well as redness and bruising from the injections. The FDA currently is reviewing a reformulation of this medication — a strip that dissolves under the tongue, similar to a Listerine breath strip.

How do my doctor and I choose the right therapy?
When thinking about a new therapy (whether it's new to the market or just new to you), consider which of your symptoms are most bothersome and how they interfere with what you want and need to do. Will the new medication treat these better than your current therapies? Always weigh the potential benefits (such as quick relief of "off" time) against the possible side effects (different for each drug) and costs. Other considerations include:

  • Success or difficulty with similar drugs.
    Have you had a good or bad response to a drug that works in the same way? You might have a similar effect with a new drug. For example, if other dopamine agonists caused intolerable nausea or sleepiness, you may want to avoid the Apokyn injection.
  • Other medications.
    How might the drug impact your other prescription or over-the-counter medications? Inbrija should not be taken with certain antidepressants and anti-anxiety medications called non-selective MAO-B inhibitors. (These are different than Parkinson's MAO-B inhibitors such as Azilect and selegiline.) Always review medications with your doctor and pharmacist to avoid possible drug interactions.
  • Medical conditions.
    How might the drug affect diseases you live with or risk factors you have? Inbrija was not tested in people with asthma or COPD (chronic obstructive pulmonary disease), so you may want to exercise caution or choose another therapy if you have one of these respiratory diseases. (Clinical trials did not find evidence of significant lung problems with the drug.) Many people also worry about dyskinesia (involuntary, uncontrolled movement), which is a potential risk with higher levodopa doses over longer periods. If you take large doses of levodopa in daily Sinemet or Rytary, for example, talk with your doctor about the benefits and risks of adding more.
  • Delivery method.
    How do you prefer to take medication? Inbrija is like an asthma inhaler; you breathe the medication into the lungs. Apokyn is like an insulin shot; it's injected under the skin. For some, taking medication through an inhaler is challenging or uncomfortable. Others have a hard time managing injections because their hands are stiff and slow during "off" time. Think about what fits your symptoms and your lifestyle and what's most practical for you. If you can't or won't use it, no drug will do you any good at all. 

What's the bottom line? 
People respond differently to different medications, and treating Parkinson's can be a bit of trial and error. Talk with your doctor about your symptoms, diet and current medications, new medications, and what's on the horizon so that together you can make an informed decision about your care. Read a movement disorder specialist's tips for considering new therapies.

Listen to a webinar about "off" time.

Watch a short video about "off" time.

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