Tadalafil is chemically a phosphodiesterase-5 (PDE5) inhibitor, aimed at blocking the degradative action of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels in the pulmonary arterial wall, which is responsible for excessive vasoconstriction and a rise in blood pressure.
Marketed under the name Adcirca by Lung Biotechnology in the U.S. and Eli Lilly, the therapy’s developer, elsewhere, tadalafil is used to treat patients with pulmonary arterial hypertension (PAH) and improve exercising ability. Because of its chemical nature and mechanism of action, it has also been approved for treatment of erectile dysfunction (ED) and benign prostate hyperplasia (BPH) by the U.S. FDA. It is an oral formulation available in the form of 20 mg tablets.
How Adcirca (tadalafil) Works
PAH is mostly associated with PDE5 upregulation, which impairs release of nitric oxide (NO) by the vascular endothelium and reduction of cGMP concentrations in the pulmonary vascular smooth muscle as a consequence. PDE5 is the most abundantly available phosphodiesterase in the vascular endothelium, so inhibiting this enzyme normalizes the NO concentration by increasing cGMP levels, which causes the release of calcium ions in cellular cytoplasm resulting in relaxation of pulmonary smooth muscle cells and vasodilation.
FDA Approval for Adcirca (tadalafil)
The FDA approval for Adcirca came in May 2009 after promising results shown by the drug in both short-term and long-term clinical trials with PAH patients. The short-term trial was a randomized, double-blind, 16-week placebo-controlled study in 405 subjects (mean age 54 years). Of these participants, 341 — who were divided into five treatment groups with varying doses of the drug (2.5, 10, 20, 40 mg, or placebo) — completed the study with positive results as measured with reference to the six-minute walk distance (6-MWD). The best results and least clinical worsening of conditions were observed in the treatment group receiving 40 mg of Adcirca. The long-term trial enrolled 357 patients from the previous study, with 311 being treated with Adcirca for at least six months and 182 for one year. The survival rate was 96.5 per 100 patient years.
Adcirca (tadalafil) Dosing
Normal dosage for Adcirca is 40 mg once daily by prescription. Co-administration along with drugs like CYP3A4 inhibitors should be avoided, and if necessary, long-term therapy is advisable. For people already taking both drugs, doses for both need to be consulted from specialists for best results, depending on the patient’s tolerability. Patients having cardiac complications or a history of heart attack within the past 90 days; a stroke or congestive heart failure within the past six months; pulmonary or renal co-morbidites; or bleeding problems like hemophilia, should consult their specialists before taking the drug.
The most common side effects include back pain, nausea, headache, flushing, pain in extremities, respiratory tract infections and myalgia. Some of the severe adverse effects during the use of Adcirca include hypersensitivity reactions, nervous system reactions, ophthalmologic and otologic reactions.
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