Xadago (Safinamide) - Oral

What Is Xadago?

Xadago (safinamide) is a monoamine oxidase type B (MAO-B) inhibitor used along with the drugs levodopa and carbidopa in Parkinson’s disease “off” episodes.

In Parkinson’s disease, brain cells that produce dopamine gradually die. Dopamine is a necessary chemical messenger that facilitates many neurologic functions. Xadago reversibly targets and inhibits the enzyme MAO-B. MAO-B naturally breaks down dopamine in the brain. By blocking its activity, safinamide helps prevent the breakdown of dopamine. This allows dopamine to remain in the brain for longer before breaking down.

Xadago is available by prescription as an oral tablet.

What Is Xadago Used For?

The Food and Drug Administration (FDA) approved Xadago for use in addition to levodopa/carbidopa treatment to treat "off" episodes in Parkinson's disease (PD). Carbidopa/levodopa is a combination oral medication commonly used to treat symptoms of PD or Parkinson's-like symptoms. Brand names for carbidopa/levodopa include Sinemet, Duopa, and Rytary.

An "off" episode occurs during the time when the effects of the primary medication wear off before you're due for another dose, allowing symptoms to resurface. Then, you feel better once the new dose of your medication starts to take effect. This is known as the "on" period. As Parkinson's disease progresses, standard treatments such as levodopa may not work as well, which triggers this "on-off" phenomenon.

Xadago is not effective as a monotherapy (single therapy) for treating Parkinson’s disease.

How to Take Xadago

Take Xadago at the same time each day, with or without food. Avoid eating foods high in tyramine (containing more than 150 milligrams), as high amounts of tyramine can cause high blood pressure in people using this medication.

What Are the Side Effects of Xadago?

This is not a complete list of side effects, and others may occur. A healthcare provider can advise you on side effects. If you experience other effects, contact your healthcare provider. You may report side effects to the FDA at fda.gov/medwatch or 1-800-FDA-1088.

Common Side Effects

Common side effects of Xadago include:

• Nausea
• Dyskinesia (abnormal, uncontrolled muscle movements)
• Insomnia (trouble sleeping)
• Falls

Severe Side Effects

Call your healthcare provider immediately if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and symptoms can include the following:

• Hypertension (high blood pressure): Hypertension may not cause any noticeable symptoms. You may need to monitor your blood pressure. If you have consistently elevated blood pressure, your healthcare provider may adjust your medication.
• Hallucinations, which may involve hearing, seeing, feeling, smelling, or tasting things that are not there.
• Impulse control disorder, which may include difficulty controlling emotions or behaviors and commonly involve pathological gambling, excessive spending, hypersexuality, or over-eating.
• Serotonin syndrome (serotonin toxicity), a potentially dangerous condition associated with increased serotonergic activity in the central nervous system: Symptoms may include mental status changes, tachycardia (fast heart rate), muscle tremor or rigidity, and/or gastrointestinal issues such as nausea, vomiting, or diarrhea.

Dosage: How Much Xadago Should I Take?

Modifications

Safe use of Xadago in pregnancy has not been established. In animal studies, developmental toxicity including teratogenic effects (developmental malformations) was observed at clinically relevant doses when administered to pregnant animals.

It is not known if Xadago is excreted in human breast milk. There is no published human experience of lactation with Xadago. Animal lactation studies suggest potential liver harm to nursing rat pups.

The safety and effectiveness of Xadago in children have not been established. 

In clinical trials of Xadago’s effectiveness, approximately 40% of participants were aged 65 and older. There was no observed difference in safety or efficacy in older adults compared with younger adults.

Missed Dose

If you miss a dose of Xadago, take the next dose at your usual time the next day. Do not double up on the medication to make up for a missed dose.

Overdose: What Happens If I Take Too Much Xadago?

There is no published data on human overdose with Xadago. Overdoses of Xadago should be treated symptomatically. Following an overdose with Xadago, you may need to follow dietary tyramine restrictions for several weeks.

Precautions

What Are Reasons I Shouldn’t Take Xadago?

Do not take Xadago if:

• You are taking another monoamine oxidase inhibitor (MAOI) or other potent inhibitors of MAO, including Zyvox (linezolid). 
• You are taking opioid drugs (e.g., Demerol (meperidine), Methadose (methadone)); serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g., Effexor (venlafaxine)); Amrix (cyclobenzaprine); Ritalin (methylphenidate), Adzenys (amphetamine), and derivatives; or St. John’s wort. These combined with Xadago could result in life-threatening serotonin syndrome. 
• You are taking other antidepressants, such as tricyclic (e.g., Elavil (amitriptyline), Pamelor (nortriptyline)), tetracyclic (e.g., Remeron (mirtazapine)), or triazolopyridine (e.g., trazodone) antidepressants. This combination can also cause serotonin syndrome.
• You are taking dextromethorphan. The combination has resulted in episodes of psychosis. 
• You have a hypersensitivity to safinamide or any of its components. 
• You have severe liver impairment.

What Other Medications Interact With Xadago?

Xadago can interact with the following drugs:

• MAO inhibitors: Coadministration of Xadago with other MAOIs or drugs that are potent inhibitors of monoamine oxidase (e.g., linezolid) may lead to dangerously high blood pressure (hypertensive crisis). Wait at least 14 days between stopping Xadago and starting another MAOI. 
• Opioids: Using Xadago with opioids can result in serious, sometimes fatal, reactions; therefore, this combination should be avoided. Wait at least 14 days between taking Xadago and opioid drugs.
• Serotonergic drugs: Monitor for symptoms of serotonin syndrome when taking Xadago with a selective serotonin reuptake inhibitor (SSRI). 
• Dextromethorphan: Combining Xadago and dextromethorphan has resulted in episodes of psychosis and bizarre behavior. Avoid this combination. 
• Sympathomimetic drugs: Combining Xadago with sympathomimetics such as methylphenidate and amphetamine can result in a hypertensive crisis. Monitor for high blood pressure when combining Xadago with nonprescription oral, nasal, and ophthalmic decongestants and cold remedies (e.g., pseudoephedrine (such as Sudafed or Zyrtec)).
• Substrates of breast cancer resistance protein (BCRP) (e.g., methotrexate, mitoxantrone, imatinib, rosuvastatin, sulfasalazine): Xadago may increase the plasma concentrations of these drugs. Monitor for increased pharmacologic effects and increased side effects. 
• Dopaminergic antagonists (e.g., antipsychotics, metoclopramide): These drugs may decrease the effectiveness of Xadago and worsen Parkinson’s symptoms.
  

What Medications Are Similar?

Xadago is a monoamine oxidase type B (MAO-B) inhibitor. Other MAO-B inhibitors include:

• Azilect (rasagiline)
• Zelapar (selegiline)

People generally take only one MAO-B inhibitor at a time but may combine this with other classes of medications to treat Parkinson’s disease.

How Can I Stay Healthy While Taking Xadago?

It is important to keep in mind that Xadago and other MAOIs have many drug interactions, including some common over-the-counter (OTC) medications, like pseudoephedrine and dextromethorphan. Talk to your healthcare provider or pharmacist before starting a new medication.

Although tyramine is linked to high blood pressure in people taking Xadago, you don't need to avoid all foods that contain tyramine. Instead, be aware of foods with more than 150 milligrams (mg) of tyramine and stay away from those. You can do this by avoiding or limiting foods known to be high in tyramine content. Foods to avoid include:

• Meat, fish, poultry, or egg products that are aged, dried, fermented, salted, smoked, or pickled
• Non-fresh meat or liver
• Aged cheese
• Fermented vegetable or soy products
• Nuts

The National Headache Foundation offers a guide on tyramine-containing foods and how to follow a low-tyramine eating plan. Talk to your healthcare team about nutritional and dietary needs, or consult a registered dietitian and nutritionist (RDN), who can help you find the right eating plan.

Consult with your healthcare provider before stopping Xadago, as the dose may need to decrease slowly. Stopping this medication suddenly can cause serious health problems.