From the FDA Drug Label
Nonselective monoamine oxidase (MAO) inhibitors are contraindicated for use with carbidopa and levodopa orally disintegrating tablets. Carbidopa and levodopa orally disintegrating tablets are contraindicated in patients with known hypersensitivity to any component of this drug, and in patients with narrow-angle glaucoma. Dopamine D2 receptor antagonists (e. g., phenothiazines, butyrophenones, risperidone) and isoniazid may reduce the therapeutic effects of levodopa. In addition, the beneficial effects of levodopa in Parkinson’s disease have been reported to be reversed by phenytoin and papaverine. Use of carbidopa and levodopa orally disintegrating tablets with dopamine-depleting agents (e. g., reserpine and tetrabenazine) or other drugs known to deplete monoamine stores is not recommended.
The medications that are contraindicated in a patient with Parkinson's disease who is on Sinemet (carbidopa-levodopa) include:
- Nonselective monoamine oxidase (MAO) inhibitors
- Medications to which the patient has a known hypersensitivity
- Medications for narrow-angle glaucoma The following medications may have adverse interactions:
- Dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone)
- Isoniazid
- Phenytoin
- Papaverine
- Dopamine-depleting agents (e.g., reserpine and tetrabenazine) 1 1
From the Research
Patients with Parkinson's disease taking Sinemet (carbidopa-levodopa) should avoid certain medications that can worsen their symptoms or cause dangerous interactions, including antipsychotics, antiemetics, certain antihypertensives, monoamine oxidase inhibitors (MAOIs), and high-dose pyridoxine supplements. When considering medication interactions, it's crucial to prioritize those that directly impact the efficacy and safety of Sinemet.
- Antipsychotics, particularly typical antipsychotics like haloperidol, chlorpromazine, and fluphenazine, should be avoided due to their dopamine-blocking properties, which can exacerbate Parkinson's symptoms or lead to neuroleptic malignant syndrome 2.
- Antiemetics such as metoclopramide, prochlorperazine, and promethazine are also contraindicated because they can block dopamine receptors, worsening Parkinson's symptoms 3.
- Certain antihypertensives, like reserpine and methyldopa, can deplete dopamine stores, leading to symptom worsening.
- MAOIs, such as phenelzine and tranylcypromine, can cause hypertensive crises when combined with levodopa, although selective MAO-B inhibitors are often used as adjunctive therapy 4.
- High-dose pyridoxine (vitamin B6) supplements can reduce levodopa effectiveness by promoting its peripheral conversion to dopamine before reaching the brain, though this is less problematic with carbidopa-levodopa combinations. These medications are contraindicated because they either block dopamine receptors, deplete dopamine stores, or interfere with levodopa's mechanism of action, all of which can worsen Parkinson's symptoms or cause dangerous drug interactions, as highlighted in recent guidelines and reviews on the treatment of Parkinson's disease 2, 4.