Tylenol PM With Carbidopa/Levodopa Interaction

There is a possible interaction between the two drugs.

Aug 19, 2018

Elf asked

Can I take Tylenol PM with carbidopa/levodopa?

At a glance

  • Diphenhydramine, the antihistamine in Tylenol PM, has an interaction with levodopa.
  • It can decrease levodopa absorption by delaying stomach emptying and slowing down the movement of the gastrointestinal tract. Since levodopa is broken down in the stomach, increasing the time it stays there will decrease absorption of the drug.

Answer

There is a potential interaction between Tylenol PM and carbidopa/levodopa, but it is generally considered to be minor. Specifically, it is the diphenhydramine in Tylenol PM that can cause the following issues:

  • Although typically very sedating, diphenhydramine can rarely cause paradoxical CNS (central nervous stem) excitation, potentially worsening movement disorders.
  • Diphenhydramine has anticholinergic effects. They can decrease the rate and absorption of levodopa, making it less effective.

Prior to any discussion on the potential negatives of diphenhydramine, it is important to note that anticholinergic drugs (diphenhydramine has anticholinergic effects) are recommended and indicated for the treatment of Parkinson's disease in certain individuals since they can reduce muscle tremors.

Below, I discuss diphenhydramine in more detail and potential interactions.

What Is Diphenhydramine?

Diphenhydramine is a sedating, 'first-generation' antihistamine and is the active ingredient in Benadryl. Diphenhydramine is known to have 'anticholinergic' effects, which can cause:

  • Sedation
  • Dry mouth
  • Dry eyes
  • Constipation
  • Urinary retention
  • Cognitive impairment

Anticholinergics have a place in therapy for individuals with Parkinson's Disease and are recommended by various guidelines for some. Drugs include:

These drugs can reduce symptoms of tremor but aren't often used due to their side effect profile and generally are only recommended in individuals under 60.

Diphenhydramine CNS Excitation

Although diphenhydramine is often taken for its sedative effects (which is why it is in Tylenol PM), it can rarely cause CNS excitation in certain individuals. Symptoms include:

  • Agitation
  • Insomnia
  • Muscle spasms
  • Nervousness
  • Irritability

These are rare side effects and generally, aren't seen in most individuals but are important to be aware of, especially if it makes any Parkinson's symptoms worse.

Diphenhydramine Interaction With Levodopa

Anticholinergic medications decrease movement of the GI tract and therefore, increase the length of time drugs stay there. Levodopa breaks down in the stomach and GI tract, and therefore, when taken with an anticholinergic, may show decreased absorption. Per one study:

"It is well recognized that selected anticholinergic drugs have modest antiparkinsonian effects. However, in certain parkinsonian patients, these drugs will markedly delay gastric emptying and thus perhaps minimize or negate the therapeutic benefit from levodopa."

Anticholinergics, however, can certainly be used with levodopa drugs, but sometimes dosage adjustment needs to be made. Per the prescribing information for Sinemet CR (carbidopa/levodopa):

References
  1. Sinemet CR Prescribing Information. Merck
  2. Interactions Between Levodopa and Other Drugs: Significance in the Treatment of Parkinson’s Disease. Springer Link
  3. Anti-cholinergics. Parkinson's Foundation
  4. Parkinson’s Disease and Its Management. PubMed
  5. Absorption and metabolism of L-dopa by the human stomach. PubMed
  6. Paradoxical excitation on diphenhydramine may be associated with being a CYP2D6 ultrarapid metabolizer: three case reports. PubMed

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