Xadago

What Is Xadago?

Xadago (safinamide) is a monoamine oxidase type B (MAO-B) inhibitor indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease (PD) experiencing “off” episodes.

What Are Side Effects of Xadago?

Common side effects of Xadago include:

• abnormal movements (dyskinesia),
• falls,
• nausea,
• insomnia,
• dizziness upon standing,
• anxiety,
• cough,
• indigestion,
• high blood pressure, or
• falling asleep during daily activities.

Dosage for Xadago

The initial dose of Xadago is 50 mg administered orally once daily at the same time of day; after two weeks, the dose may be increased to 100 mg once daily, based on individual need and tolerability.

What Drugs, Substances, or Supplements Interact with Xadago?

Xadago may interact with other MAO inhibitors, isoniazid, opioids, serotonin-norepinephrine reuptake inhibitors (SNRIs), triazolopyridine, tricyclic or tetracyclic antidepressants, cyclobenzaprine, St. John's wort, dextromethorphan, sympathomimetics, tyramine, selective serotonin reuptake inhibitors (SSRIs), substrates of breast cancer resistance protein (BCRP), antipsychotics, or metoclopramide. Tell your doctor all medications and supplements you use.

Xadago During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plant to become pregnant before using Xadago; it may harm a fetus. It is unknown if Xadago passes into breast milk. Because of the potential for adverse reactions in a nursing infant, breastfeeding while using Xadago is not recommended.

Additional Information

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

 

Xadago Consumer Information

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:

• vision changes;
• twitching or uncontrolled muscle movements;
• confusion, agitation, unusual thoughts or behavior;
• hallucinations (seeing or hearing things that are not real);
• a seizure;
• fever, sweating, fast heart rate, overactive reflexes;
• nausea, vomiting, diarrhea; or
• increased blood pressure--severe headache, blurred vision, pounding in your neck or ears, anxiety, nosebleed.

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:

• involuntary muscle movements;
• falls;
• nausea; or
• sleep problems (insomnia).

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 Xadago (Safinamide Tablets)

 

Xadago Professional Information

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of labeling:

• Hypertension [see WARNINGS AND PRECAUTIONS]
• Serotonin Syndrome [see WARNINGS AND PRECAUTIONS]
• Falling Asleep During Activities of Daily Living [see WARNINGS AND PRECAUTIONS]
• Dyskinesia [see WARNINGS AND PRECAUTIONS]
• Hallucinations / Psychotic Behavior [see WARNINGS AND PRECAUTIONS]
• Impulse Control / Compulsive Behaviors [see WARNINGS AND PRECAUTIONS]
• Withdrawal-Emergent Hyperpyrexia and Confusion [see WARNINGS AND PRECAUTIONS]
• Retinal Pathology [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Clinical trials are conducted under widely varying conditions; therefore, adverse reactions observed in the clinical trials of a drug cannot be directly compared to the incidence in the clinical trials of another drug and may not reflect the incidence observed in clinical practice.

Common Adverse Reactions In Placebo-Controlled PD Studies

Table 1 shows the incidence of adverse reactions with an incidence of at least 2% on XADAGO 100 mg/day and greater than placebo in controlled studies in PD (Study 1 and Study 2). The most common adverse reactions associated with XADAGO treatment in which the incidence for XADAGO 100 mg/day was at least 2% greater than the incidence for placebo were dyskinesia, fall, nausea, and insomnia.

Adverse Reactions Reported As Reason For Discontinuation From Study

In pooled placebo-controlled studies (Study 1 and Study 2) in patients with PD taking a stable dose of carbidopa/levodopa with or without other PD medications, there was an increase in the incidence of XADAGO-treated patients who discontinued from the study because of adverse reactions. The incidence of patients discontinuing from Study 1 and Study 2 for any adverse reaction was 5% for XADAGO 50 mg/day, 6% for XADAGO 100 mg/day, and 4% for placebo. The most frequently reported adverse reaction causing study discontinuation was dyskinesia (1% of patients treated with XADAGO 50 mg/day or XADAGO 100 mg/day vs. 0% for placebo).

Table 1: Percentage of Patients with Adverse Reactions with an Incidence ≥ 2% in the XADAGO 100 mg/day Group and Greater than Placebo in Studies 1 and 2.

	XADAGO 50 mg/day (N = 223)	XADAGO 100 mg/day (N = 498)	Placebo (N = 497)
Adverse Reaction	%	%	%
Dyskinesia	21	17	9
Fall	4	6	4
Nausea	3	6	4
Insomnia	1	4	2
Orthostatic hypotension	2	2	1
Anxiety	2	2	1
Cough	2	2	1
Dyspepsia	0	2	1

Abnormal Laboratory Changes

In Study 1 and Study 2, the proportion of patients who experienced a shift from normal to above the upper limit of normal for serum alanine aminotransferase (ALT) was 5% for XADAGO 50 mg, 7% for XADAGO 100 mg, and 3% for placebo. No patient treated with XADAGO experienced an increase in ALT that was 3 times the upper limit of normal or higher.

The proportion of patients with a shift from normal to above the upper limit of normal for serum aspartate aminotransferase (AST) was 7% for XADAGO 50 mg, 6% for XADAGO 100 mg, and 3% for placebo. The incidence of patients with an increase in AST to at least 3 times the upper limit of normal was similar for XADAGO and placebo.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of safinamide outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

A postmarketing report describes a patient who developed a hypersensitivity reaction consisting of swelling of the tongue and gingiva, dyspnea and skin rash. The symptoms resolved shortly after XADAGO was discontinued, but reappeared following rechallenge a month later.

DRUG INTERACTIONS

MAO Inhibitors (MAOIs)

XADAGO is contraindicated for use with other drugs in the MAOIs class or other drugs that are potent inhibitors of monoamine oxidase (e.g., linezolid, an oxazolidinone antibacterial, which also has reversible nonselective MAO inhibition activity). Co-administration increases the risk of nonselective MAO inhibition, which may lead to hypertensive crisis [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. At least 14 days should elapse between discontinuation of XADAGO and initiation of treatment with other MAOIs.

Isoniazid has some monoamine oxidase inhibiting activity. Monitor for hypertension and reaction to dietary tyramine in patients treated concomitantly with isoniazid and XADAGO.

Opioid Drugs

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

Serotonergic Drugs

Concomitant use of XADAGO with SNRIs; triazolopyridine, tricyclic or tetracyclic antidepressants; cyclobenzaprine (a skeletal muscle relaxant that is a tricyclic antidepressant derivative); or St. John's wort is contraindicated [see WARNINGS AND PRECAUTIONS]. At least 14 days should elapse between discontinuation of XADAGO and initiation of treatment with these drugs.

Monitor patients for symptoms of serotonin syndrome if SSRIs are used by patients treated with XADAGO [see WARNINGS AND PRECAUTIONS].

Dextromethorphan

The combination of MAOIs and dextromethorphan has been reported to cause episodes of psychosis or bizarre behavior. Therefore, in view of XADAGO's MAO inhibitory activity, dextromethorphan is contraindicated for use with XADAGO.

Sympathomimetic Medications

Severe hypertensive reactions have followed the administration of sympathomimetics and nonselective MAOIs. Hypertensive crisis has been reported in patients taking the recommended doses of selective MAO-B inhibitors and sympathomimetic medications. Concomitant use of XADAGO with methylphenidate, amphetamine, and their derivatives is contraindicated [see WARNINGS AND PRECAUTIONS].

Monitor patients for hypertension if XADAGO is prescribed concomitantly with prescription or nonprescription sympathomimetic medications, including nasal, oral, or ophthalmic decongestants and cold remedies [see WARNINGS AND PRECAUTIONS].

Tyramine

MAO in the gastrointestinal tract and liver (primarily type A) provides protection from exogenous amines (e.g., tyramine). If tyramine were absorbed intact, it could lead to severe hypertension, including hypertensive crisis. Aged, fermented, cured, smoked, and pickled foods containing large amounts of exogenous amines (e.g., aged cheese, pickled herring) may cause release of norepinephrine resulting in a rise in blood pressure (Tyramine Reaction). Patients should be advised to avoid foods containing a large amount of tyramine while taking recommended doses of XADAGO [see WARNINGS AND PRECAUTIONS].

Selectivity for inhibiting MAO-B decreases in a dose-related manner above the highest recommended daily dosage, which may increase the risk for hypertension [see CLINICAL PHARMACOLOGY] . In addition, isoniazid has some monoamine oxidase inhibiting activity. Monitor for hypertension and reaction to dietary tyramine in patients treated with isoniazid and XADAGO [see WARNINGS AND PRECAUTIONS].

Dopaminergic Antagonists

Dopamine antagonists, such as antipsychotics or metoclopramide, may decrease the effectiveness of XADAGO and exacerbate the symptoms of PD.

Read the entire FDA prescribing information for Xadago (Safinamide Tablets)