Medical Editor: John P. Cunha, DO, FACOEP Last updated on RxList: 10/15/2021
Zelapar Side Effects Center

What Is Zelapar?

Zelapar (selegiline hydrochloride) is an enzyme blocker (MAO inhibitor) that works by slowing the breakdown of certain natural substances in the brain (neurotransmitters such as dopamine, norepinephrine, and serotonin) used together with other medicines to treat symptoms of Parkinson's disease.

What Are Side Effects of Zelapar?

Common side effects of Zelapar include:

Tell your doctor if you have serious side effects of Zelapar including:

Dosage for Zelapar

Treatment with Zelapar should be initiated with a 1.25 mg dose given once a day for at least 6 weeks. After 6 weeks, the dose may be escalated to 2.5 mg given once a day if prescribed.

What Drugs, Substances, or Supplements Interact with Zelapar?

Zelapar may interact with arbamazepine, diet pills or cold medicines that contain ephedrine, pseudoephedrine, or phenylephrine, nafcillin, phenobarbital, rifampin, or antidepressants. Many other medicines can cause serious medical problems if taken together with Zelapar. Tell your doctor all medications and supplements you use.

Zelapar During Pregnancy and Breastfeeding

During pregnancy, Zelapar should be used only when prescribed. It is unknown if this drug passes into breast milk, but it may have undesirable effects on a nursing infant. Consult your doctor before breastfeeding.

Additional Information

Our Zelapar (selegiline hydrochloride) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.


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Zelapar Consumer Information

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Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • a light-headed feeling, like you might pass out;
  • trouble breathing;
  • confusion, hallucinations, unusual thoughts or behavior;
  • increased tremors or uncontrolled muscle movements;
  • worsening side effects of your other medications;
  • high levels of serotonin in the body (when taken with an antidepressant)--agitation, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting; or
  • dangerously high blood pressure--severe headache, blurred vision, pounding in your neck or ears, anxiety, nausea, vomiting, severe chest pain, shortness of breath, pounding heartbeats, or seizure (convulsions).

You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking this medicine. Talk with your doctor if this occurs.

Common side effects may include:

  • dizziness;
  • nausea, stomach pain, constipation;
  • skin rash or other irritation;
  • sleep problems (insomnia); or
  • mouth sores or ulcers, pain with swallowing (while using selegiline orally disintegrating tablets).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Zelapar (Selegiline Hydrochloride)


Parkinson's disease is only seen in people of advanced age. See Answer
Zelapar Professional Information


The following adverse reactions are discussed in more detail in the Warnings and Precautions section of labeling:

  • Risk for Hypertension [see WARNINGS AND PRECAUTIONS]
  • Risk of Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]
  • Falling Asleep During Activities of Daily Living and Somnolence [see WARNINGS AND PRECAUTIONS]
  • Hypotension/Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]
  • Hallucinations/Psychotic-Like Behavior [see WARNINGS AND PRECAUTIONS]
  • Impulse Control/Compulsive Behaviors [see WARNINGS AND PRECAUTIONS]
  • Withdrawal Emergent Hyperpyrexia and Confusion [see WARNINGS AND PRECAUTIONS]
  • Irritation of the Buccal Mucosa [see WARNINGS AND PRECAUTIONS]
  • Risk for Patients with Phenylketonuria [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction per total number of patients treated) observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the incidence of adverse reactions observed in clinical practice.

Because the controlled trials performed during premarketing development both used a titration design (1.25 mg per day for 6 weeks, followed by 2.5 mg per day for 6 weeks), with a resultant confounding of time and dose, it was impossible to adequately evaluate the effects of dose on the incidence of adverse reactions.

The most common adverse reactions (treatment difference incidence at least 3% greater than placebo incidence) reported in the double-blind, placebo-controlled trials during ZELAPAR treatment were constipation, skin disorders, vomiting, dizziness, dyskinesia, insomnia, dyspnea, myalgia, and rash (see Table 1).

Of the 194 patients treated with ZELAPAR in the double-blind, placebo-controlled trials, 5% discontinued due to adverse reactions compared to 1% of the 98 patients who received placebo. Most common adverse reactions causing discontinuation of treatment included dizziness, chest pain, accidental injury, and myasthenia.

Incidence In Controlled Clinical Trials

Table 1 lists the adverse reactions reported in the placebo-controlled trials after at least one dose of ZELAPAR (incidence 2% or greater).

Table 1: Adverse Reactions* in Double-Blind, Placebo-Controlled Trials with an Incidence ≥2% of Patients Treated with ZELAPAR and More Frequent than the Placebo Group

Body System/
Adverse Event
1.25/2.5 mg
Body as a Whole
Pain 8 7
Back Pain 5 3
Chest Pain 2 0
Cardiovascular System
Hypertension 3 2
Digestive System
Nausea 11 9
Stomatitis 5 4
Dyspepsia 5 3
Constipation 4 0
Vomiting 3 0
Diarrhea 2 1
Dysphagia 2 1
Flatulence 2 1
Tooth Disorder 2 1
Hemic and Lymphatic System
Ecchymosis 2 0
Metabolic and Nutritional Disorders
Hypokalemia 2 0
Musculoskeletal System
Leg Cramps 3 1
Myalgia 3 0
Nervous System
Dizziness 11 8
Headache 7 6
Insomnia 7 4
Dyskinesia 6 3
Dry Mouth 4 2
Hallucinations 4 2
Somnolence 3 2
Tremor 3 1
Ataxia 3 1
Depression 2 1
Respiratory System
Pharyngitis 4 2
Rhinitis 7 6
Dyspnea 3 0
Skin and Appendages
Rash 4 1
Skin Disorders** 6 2
* Patients may have reported multiple adverse experiences during the study or at discontinuation; thus patients may be included in more than one category.
** Skin disorders represent any new skin abnormality that would not be characterized as rash or neoplastic lesion. These include events such as skin ulcer, fungal dermatitis, skin hypertrophy, contact dermatitis, herpes simplex, dry skin, sweating, urticaria, and pruritus.

Certain adverse reactions were reported at a higher frequency by patients ≥65 years of age compared to patients <65 years [see Use In Specific Populations].

No consistent differences in the incidences of adverse reactions were observed between male and female patients.

There were insufficient data to assess the impact of race on the incidence of adverse reactions.


Opioid Drugs

Because serious, sometimes fatal reactions have been precipitated with concomitant use of opioid drugs (e.g., meperidine and its derivatives, methadone, or tramadol) and MAOIs, including selective MAO-B inhibitors, concomitant use of these drugs with ZELAPAR is contraindicated [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. At least 14 days should elapse between discontinuation of ZELAPAR and initiation of treatment with these drugs.


The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior. Therefore, in view of ZELAPAR’s MAO inhibitory activity, dextromethorphan should not be used concomitantly with ZELAPAR [see CONTRAINDICATIONS].

MAO Inhibitors

ZELAPAR is contraindicated for concomitant use with other drugs in the MAOI class or other drugs that are potent inhibitors of monoamine oxidase (including linezolid, an oxazolidinone antibacterial, which also has reversible nonselective MAO inhibition activity) because of the increased risk for hypertensive crisis [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. At least 14 days should elapse between discontinuation of ZELAPAR and initiation of treatment with other MAOIs.

Sympathomimetic Medications

Uncontrolled hypertension, including hypertensive crisis, has been reported when taking the recommended dose of swallowed selegiline and a sympathomimetic medication (ephedrine).

Tyramine/Selegiline Interaction

The enzyme, monoamine oxidase (MAO) (primarily type A), in the gastrointestinal tract and liver provides protection from ingested amines (e.g., tyramine) that, if absorbed, have the capacity to cause uncontrolled hypertension (tyramine reaction). If MAO is inhibited in the gastrointestinal tract and liver, ingestion of exogenous amines contained in some foods such as fermented cheese, herring, or over-the-counter cough/cold medicines may be absorbed systemically causing release of norepinephrine and a rise in systemic blood pressure with the potential for uncontrolled hypertension. Selective MAO-B inhibitors lose their selectivity for MAO-B when taken in doses higher than recommended. Non-selective MAOA inhibitors or MAO-B inhibitors in higher than recommended doses may result in MAO-A inhibition in the gastrointestinal tract and liver.

Results of a tyramine challenge study indicate that ZELAPAR is relatively selective for MAO-B at the recommended dose. In most cases, there is no need for dietary tyramine restriction in patients prescribed ZELAPAR [see CLINICAL PHARMACOLOGY] at the recommended dose. Because the selectivity for inhibiting MAO-B diminishes as the dose of ZELAPAR is increased above the recommended daily dose, patients should not take more than 2.5 mg of ZELAPAR daily.

Reports of hypertensive reactions have occurred in patients who ingested tyramine-containing consumables (i.e., food or drink) while receiving swallowed selegiline at the recommended dose (a dose believed to be relatively selective for MAOB). Hypertensive crisis has also been reported with ZELAPAR use that was not above the recommended dosing.

Uncontrolled hypertension has been reported when taking the recommended dose of swallowed selegiline and a sympathomimetic medication (ephedrine).

Tricyclic Antidepressants And Selective Serotonin Reuptake Inhibitors

Severe toxicity has also been reported in patients receiving the combination of tricyclic antidepressants and swallowed selegiline, or selective serotonin reuptake inhibitors and swallowed selegiline [see WARNINGS AND PRECAUTIONS].

Drugs That Induce CYP450

Adequate studies have not been done investigating the effect of CYP3A4 inducers on selegiline. Drugs that induce CYP3A4 (e.g., phenytoin, carbamazepine, nafcillin, phenobarbital, and rifampin) should be used with caution.

Dopaminergic Antagonists

It is possible that dopamine antagonists, such as antipsychotics or metoclopramide, could diminish the effectiveness of ZELAPAR.

Read the entire FDA prescribing information for Zelapar (Selegiline Hydrochloride)

© Zelapar Patient Information is supplied by Cerner Multum, Inc. and Zelapar Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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