Cardiac complications & contraindications

High plasma concentrations of the non-sedative antihistamines may be achieved by several means:

• simple overdose
  
  
• slowing the rate of hepatic excretion:
  • by competing for the specific cytochrome P450 isoenzyme in the liver e.g. erythromycin and the antifungal imidazoles
  • as a result of hepatic failure

High doses of non-sedative antihistamines prolong the cardiac QT interval and predispose to arrythmias such as ventricular fibrillation and torsade de pointes.

Thus, the following precautions should be observed when prescribing non-sedative antihistamines:

• do not exceed the recommended dose
  
  
• avoid simultaneous administration of:
  • antifungal imidazoles e.g. ketoconazole
  • macrolide antibiotics e.g. erythromycin
    
    
• avoid simultaneous administration of drugs which prolong the QT interval, including amiodarone, bretylium, disopyramide, procainamide, quinidine, sotalol, neuroleptic drugs and tricyclic antidepressants
  
  
• potassium or magnesium depletion is a contraindication
  
  
• symptomatic liver disease is a contraindication
  
  
• pre-existing QT prolongation (> 450 ms) is a contraindication