Drug General Information (ID: DDITV5XGSB)
Drug Name			Tramadol		Drug Info		Pimavanserin		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Analgesics				Atypical Antipsychotics
Structure

Mechanism of Tramadol-Pimavanserin Interaction (Severity Level: Major)
Additive CNS depression effects Click to Show/Hide Mechanism Graph
Drug Name		Tramadol				Pimavanserin
Mechanism 1		CNS depression effects				CNS depression effects
Key Mechanism Factor 1
		Factor Name		CNS depression effects
		Factor Description		CNS depressants are drugs that inhibit or suppress brain activity and can reduce mental and physical processes. Excessive CNS depression can lead to decreased heart rate, slow breathing (less than 10 breaths per minute), extreme confusion or loss of memory, nausea and vomiting, poor judgment, blue lips or fingertips, irritability and aggression, and clammy or cold skin.
Mechanism Description		Additive CNS depression effects by the combination of Tramadol and Pimavanserin
Increased risk of prolong QT interval Click to Show/Hide Mechanism Graph
Drug Name		Tramadol				Pimavanserin
Mechanism 2		Prolong QT interval				Prolong QT interval
Key Mechanism Factor 2
		Factor Name		QT interval
		Factor Description		Long QT syndrome is a heart signaling disorder that can cause a fast, chaotic heartbeat (arrhythmia). Many people may not exhibit symptoms, and usually the condition is detected during routine medical tests. In others, the most common symptoms include: sudden fainting, palpitations, dizziness, seizures, sudden death.
Mechanism Description		Increased risk of prolong QT interval by the combination of Tramadol and Pimavanserin

Recommended Action
Management		Coadministration of pimavanserin with tramadol should generally be avoided. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve the desired clinical effect. Patients should have regular ECGs and be monitored for arrhythmias when the QT interval is prolonged. Persistent QTc measurements exceeding 500 msec will require suspension of pimavanserin therapy and immediate action to correct any concomitant risk factors before resuming treatment. Particular care should be exercised in patients suspected to be at an increased risk of torsade de pointes. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. In addition, patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them.

References
1	US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines requires its strongest warning.".
2	Product Information. Nuplazid (pimavanserin). Accelis Pharma, East Windsor, NJ.