Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIG148MI0)
  Drug Name Propafenone Drug Info Lofexidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiarrhythmic Agents Antihypertensive Agents
  Structure

 Mechanism of Propafenone-Lofexidine Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Propafenone Lofexidine
      Mechanism 1 Hypotensive effects
Voltage-gated sodium channel  Blocker 		Hypotensive effects
Alpha-2 adrenergic receptor  Agonist
      Key Mechanism Factor 1
Factor Name Voltage-gated sodium channel Structure Sequence
Protein Family Sodium channel (TC 1.A.1.10) family
Protein Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:1309946, PubMed:21447824, PubMed:25370050, PubMed:23420830, PubMed:23085483, PubMed:26279430, PubMed:26392562, PubMed:26776555). It is a tetrodotoxin-resistant Na(+) channel isoform (PubMed:1309946). This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels (PubMed:19074138).
    Click to Show/Hide
      Key Mechanism Factor 2
Factor Name Adrenergic receptor alpha-2 Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
    Click to Show/Hide
      Mechanism Description
  • Additive hypotensive effects by the combination of Propafenone and Lofexidine 
     Increased risk of prolong QT interval Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Propafenone Lofexidine
      Mechanism 2 Prolong QT interval Prolong QT interval
      Key Mechanism Factor 3
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 Propafenone and Lofexidine 

Recommended Action
      Management Caution is recommended if lofexidine is used in combination with other drugs that can prolong the QT interval. Periodic monitoring with on-treatment electrocardiograms and serum electrolytes (magnesium, potassium) should be considered. 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.

References
1 Canadian Pharmacists Association.
2 Cerner Multum, Inc. "Australian Product Information.".
3 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4 Product Information. Lucemyra (lofexidine). US WorldMeds LLC, Louisville , KY.
5 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".