title: Interaction between the phosphodiesterase 5 inhibitor, tadalafil and 2 alpha-blockers, doxazosin and tamsulosin in healthy normotensive men.
abstract: OBJECTIVE
  Tadalafil, a phosphodiesterase type 5 inhibitor, is effective therapy for erectile dysfunction (ED). Men with ED have a high incidence of comorbid conditions including cardiovascular disease, diabetes mellitus and benign prostatic hyperplasia. Although phosphodiesterase type 5 inhibitors are safe when administered with most medications, sildenafil given with doxazosin and vardenafil given with terazosin evoke orthostatic hypotension in some patients. We examined the hemodynamic interactions of tadalafil with the alpha-blockers doxazosin and tamsulosin.
  
  
  METHODS
  In separate double-blind, placebo controlled, randomized crossover studies (18 patients in each study) we evaluated the hemodynamic effects of doxazosin 8 mg with tadalafil 20 mg, and tamsulosin 0.4 mg with tadalafil 10 and 20 mg. Blood pressure (BP) and heart rate were recorded before dosing and for 24 hours after dosing.
  
  
  RESULTS
  Tadalafil 20 mg augmented the hypotensive effect of doxazosin by producing a mean maximal decrease in standing systolic BP (SBP) that was significantly greater than placebo (a mean difference of 9.8 mm Hg). Analysis of BP outliers showed that the number of subjects with a standing SBP of less than 85 mm Hg was greater after doxazosin plus tadalafil (28%) versus doxazosin plus placebo (6%). In subjects on tamsulosin, tadalafil 10 and 20 mg produced mean maximal decreases in standing SBP that were similar to placebo (mean difference of 1.7 and 2.3 mm Hg, respectively). No subject taking tamsulosin had a decrease in standing SBP less than 85 mm Hg.
  
  
  CONCLUSIONS
  Tadalafil augmented the hypotensive effects of doxazosin but had little hemodynamic interaction with tamsulosin. In patients taking tadalafil for ED, tamsulosin 0.4 mg may be given for the treatment of benign prostatic hyperplasia.
authors.affiliation: The Heart Institute, Good Samaritan Hospital, Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90017, USA. rkloner@goodsam.org
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kloner
authors.forename: Graham
authors.initials: G
authors.lastname: Jackson
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Emmick
authors.forename: Malcolm I
authors.initials: MI
authors.lastname: Mitchell
authors.forename: Alun
authors.initials: A
authors.lastname: Bedding
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Warner
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pereira
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000368:Aged; D002243:Carbolines / Q000494:pharmacology*; D018592:Cross-Over Studies; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004311:Double-Blind Method; D017292:Doxazosin / Q000494:pharmacology*; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases; D013449:Sulfonamides / Q000494:pharmacology*; D000068581:Tadalafil; D000077409:Tamsulosin
chemical_list: D000317:Adrenergic alpha-Antagonists; D002243:Carbolines; D013449:Sulfonamides; D000068581:Tadalafil; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D000077409:Tamsulosin; D017292:Doxazosin