Home » Drug Information » FDA Approved Drugs » 2009
Medical Areas: Cardiology/Vascular Diseases | Pulmonary/Respiratory Diseases | Family Medicine
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Eli Lilly
Approval Status: Approved May 2009
Treatment Area: pulmonary arterial hypertension
Adcirca (tadalafil) is an oral inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Pulmonary hypertension is the result of upregulation of PDE5 gene expression, causing vasoconstriction in the lung. Inhibition of PDE5 by tadalafil increases the concentrations of cGMP resulting in elaxation of pulmonary vascular smooth muscle cells and vasodilation of the pulmonary vascular bed.
Adcirca is specifically indicated for the treatment of pulmonary arterial hypertension (WHO Group I) to improve exercise ability.
Adcirca is supplied as a 20 mg tablet for oral administration. The recommended initial dose of the drug is 40 mg (two 20 mg tablets) taken once daily with or without food. Dividing the dose (40 mg) over the course of the day is not recommended.
FDA approval of Adcirca for pulmonary hypertension was based on a randomized, double-blind, 16 week placebo-controlled study in 405 subjects (mean age 54 years), 341 of whom completed the study. The subjects were randomly assigned to 1 of 5 treatment groups (tadalafil 2.5, 10, 20, 40 mg, or placebo). The primary efficacy endpoint was the change from baseline at week 16 in 6-MWD. The mean baseline 6-minute walk distance (6-MWD) was 343 meters. In the Adcirca 40 mg treatment group, the placebo-adjusted mean change increase in 6-MWD was 33 meters (p=0.0004). The improvement in 6-MWD was apparent at 8 weeks of treatment and then maintained at week 12 and week 16. There was less clinical worsening (defined as death, lung transplantation, atrial septostomy, hospitalization because of worsening PAH, initiation of new PAH therapy or worsening WHO functional class) in the Adcirca 40 mg group compared to the placebo group and the groups that used lower doses of Adcirca.
A long-term extension study was conducted in 357 subjects from the placebo-controlled study. Of these, 311 subjects were treated with tadalafil for at least 6 months and 182 for 1 year (median exposure 356 days; range 2 days to 415 days). The survival rate in the extension study was 96.5 per 100 patient years.
Adverse events associated with the use of Adcirca may include, but are not limited to, the following:
- Back Pain
- Respiratory Tract Infection
- Pain in Extremity
Adverse reactions identified during post-approval use of tadalafil:
- Cardiovascular and cerebrovascular events
- Hypersensitivity reactions
- Nervous system reactions
- Ophthalmologic reactions
- Otologic reactions
Mechanism of Action
Adcirca (tadalafil) is an oral inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Pulmonary arterial hypertension is associated with impaired release of nitric oxide by the vascular endothelium and consequent reduction of cGMP concentrations in the pulmonary vascular smooth muscle. PDE5 is the predominant phosphodiesterase in the pulmonary vasculature. Inhibition of PDE5 by tadalafil increases the concentrations of cGMP resulting in elaxation of pulmonary vascular smooth muscle cells and vasodilation of the pulmonary vascular bed.
Galiè N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, Shapiro S, White RJ, Chan M, Beardsworth A, Frumkin L, Barst RJ; on behalf of the Pulmonary Arterial Hypertension and Response to Tadalafil (PHIRST) Study Group Tadalafil Therapy for Pulmonary Arterial Hypertension. Circulation 2009 May 26
Aggarwal P, Patial RK, Negi PC, Marwaha R Oral tadalafil in pulmonary artery hypertension: a prospective study. Indian Heart Journal 2007 Jul-Aug;59(4):329-35
Bharani A, Patel A, Saraf J, Jain A, Mehrotra S, Lunia B Efficacy and safety of PDE-5 inhibitor tadalafil in pulmonary arterial hypertension. Indian Heart Journal 2007 Jul-Aug;59(4):323-8
de Carvalho AC, Hovnanian AL, Fernandes CJ, Lapa M, Jardim C, Souza R Tadalafil as treatment for idiopathic pulmonary arterial hypertension. Arquivos brasileiros de cardiologia 2006 Nov;87(5):e195-7
For additional information regarding Adcirca or pulmonary arterial hypertension, please visit the Adcirca web page.