Safinamide, known by its brand name Xadago, is an oral prescription medication used to manage Parkinson’s disease symptoms. Approved by the U.S. Food and Drug Administration (FDA) in 2017, it helps individuals better control their condition.
Mechanism of Action
Safinamide works within the brain through a dual mechanism, primarily as a selective and reversible inhibitor of monoamine oxidase B (MAO-B). MAO-B is an enzyme that breaks down dopamine, a neurotransmitter crucial for smooth motor control. By inhibiting this enzyme, safinamide increases available dopamine levels in the brain. This action helps to alleviate motor symptoms that arise from dopamine deficiency in Parkinson’s disease.
Safinamide also modulates glutamate release. Glutamate is the central nervous system’s main excitatory neurotransmitter, and its dysregulation is implicated in neurodegenerative conditions like Parkinson’s disease. Safinamide achieves this modulation by inhibiting voltage-dependent sodium channels and influencing calcium channels, which leads to a reduction in abnormal glutamate release. This secondary mechanism distinguishes safinamide from other MAO-B inhibitors.
Role in Parkinson’s Disease Therapy
Safinamide is not typically prescribed as a standalone or initial treatment for Parkinson’s disease. Instead, it serves as an “add-on” therapy for patients already receiving levodopa/carbidopa, a common medication combination for Parkinson’s. This approach aims to enhance the overall effectiveness of the existing treatment regimen. Safinamide is specifically indicated for adults who experience “off” episodes.
“Off” episodes refer to periods when the effects of levodopa medication wear off, leading to a return or worsening of Parkinson’s symptoms such as increased slowness, stiffness, or tremor. Clinical trials have shown that safinamide can reduce “off” time by approximately 0.6 to 1.37 hours per day, while also increasing “on” time (periods of good symptom control) without worsening troublesome involuntary movements.
Common and Serious Side Effects
Patients taking safinamide may experience common side effects. These include uncontrolled involuntary movements, known as dyskinesia, which can sometimes worsen. Other frequently reported effects are falls, nausea, difficulty sleeping, headaches, and dizziness.
More serious side effects require immediate medical attention. Safinamide can cause or worsen high blood pressure (hypertension). Serotonin syndrome, a potentially severe reaction, can occur, particularly when safinamide is combined with other medications that increase serotonin levels. Symptoms include agitation, confusion, rapid heart rate, high blood pressure, muscle rigidity, and fever. Hallucinations, other psychotic-like behaviors, and unusual urges or an inability to control impulses (like compulsive gambling or increased sexual urges) have also been reported.
Drug and Food Interactions
Safinamide should not be taken with other monoamine oxidase (MAO) inhibitor drugs, including non-selective MAOIs or other MAO-B inhibitors. Combining safinamide with certain antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants, is also generally avoided due to the heightened risk of serotonin syndrome. A period of at least 14 days is typically recommended between discontinuing safinamide and starting these other medications to prevent adverse reactions.
Over-the-counter products containing dextromethorphan, often found in cough and cold medicines, should also be avoided due to the potential for psychosis or unusual behavior. The herbal supplement St. John’s Wort also poses a risk of serotonin syndrome when combined with safinamide. Regarding food, while safinamide is less likely to cause the “cheese effect” seen with older MAOIs due to its selective MAO-B inhibition, caution is still advised with foods high in tyramine. Consuming large amounts of high-tyramine foods, such as aged cheeses, cured meats (e.g., salami, pepperoni), and fermented products (e.g., sauerkraut, soy sauce), can potentially lead to a dangerous spike in blood pressure, known as a hypertensive crisis.