Tadalafil: a long-acting phosphodiesterase-5 inhibitor for the treatment of pulmonary arterial hypertension

Clin Ther. 2011 Aug;33(8):993-1004. doi: 10.1016/j.clinthera.2011.06.008. Epub 2011 Jul 16.


Background: Tadalafil is a phosphodiesterase-5 (PDE-5) inhibitor that was approved by the US Food and Drug Administration (FDA) in 2009 for the treatment of pulmonary arterial hypertension (PAH).

Objective: The purpose of this review is to evaluate the pharmacology, pharmacokinetic properties, clinical efficacy, adverse effects, drug interactions, and dosage and administration of tadalafil in patients with PAH.

Methods: A literature search of MEDLINE and International Pharmaceutical Abstracts (1960 through September 5, 2010) was conducted with the search terms tadalafil, pulmonary arterial hypertension, and phosphodiesterase-5 inhibitor. Data found from orignial research and case series published in English were screened for relevancy to pharmacology, pharmacokinetics, clinical efficacy and safety, and tolerability. Relevant articles from the bibliographies of the identified published articles were also obtained. Unpublished data and posters were obtained from the manufacturer of tadalafil and the FDA Web site.

Results: By selectively inhibiting PDE-5, tadalafil causes nitric oxide-mediated vasodilation in the pulmonary vasculature. Tadalafil has a greater affinity (10,000-fold) for PDE-5 compared with the other PDE inhibitors and has a t(½) of 17.5 hours. In a controlled clinical study in patients with PAH, patients receiving tadalafil in a total daily dose of 40 mg had significant improvements in their 6-minute walk distance (33 m from baseline) and time to clinical worsening compared with those receiving placebo (both, P < 0.05). Tadalafil had adverse effects similar to placebo, with headache being the most commonly reported (42%).

Conclusions: In the small number of studies available, tadalafil was effective and well tolerated when used to treat patients with PAH. Compared with placebo, tadalafil was associated with significant improvements in exercise capacity and reduced time to clinical worsening (68% relative risk reduction; P = 0.038). There is limited evidence comparing tadalafil with sildenafil and vardenafil, and the studies are limited by short treatment durations.

Publication types

  • Review

MeSH terms

  • Carbolines / adverse effects
  • Carbolines / pharmacology
  • Carbolines / therapeutic use*
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / drug effects
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism
  • Drug Interactions
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Nitric Oxide / metabolism
  • Phosphodiesterase 5 Inhibitors / adverse effects
  • Phosphodiesterase 5 Inhibitors / pharmacology
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Tadalafil
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use


  • Carbolines
  • Phosphodiesterase 5 Inhibitors
  • Vasodilator Agents
  • Nitric Oxide
  • Tadalafil
  • Cyclic Nucleotide Phosphodiesterases, Type 5