Tadalafil Dosing for Pulmonary Arterial Hypertension in Adults
The FDA-approved dose of tadalafil for adults with pulmonary arterial hypertension is 40 mg once daily. 1
Standard Dosing Regimen
Tadalafil 40 mg once daily is the recommended dose for treatment of PAH in adults, as this was the only dose that met the primary efficacy endpoint in the pivotal PHIRST trial 2
Do not exceed 40 mg once daily - treatment with more than the recommended dose has not been studied and is not recommended 2
No dose titration is required - patients should be started directly at 40 mg once daily, unlike some other PAH medications that require gradual uptitration 2
Clinical Efficacy Data Supporting This Dose
The 40 mg daily dose demonstrated:
Mean placebo-corrected increase in 6-minute walk distance of 33 meters in the combined patient population (with and without background endothelin receptor antagonist therapy) 2
44-meter improvement in treatment-naive patients receiving tadalafil 40 mg as monotherapy 3
Reduction in clinical worsening events, defined as death, transplantation, atrial septostomy, hospitalization for PAH, or initiation of new PAH therapy 2
Improvements maintained for up to 52 weeks in extension studies 4
Use as Monotherapy vs. Combination Therapy
For treatment-naive WHO Functional Class II-III patients, tadalafil 40 mg daily can be used as monotherapy or in initial combination therapy with ambrisentan 10 mg daily 1
As add-on to bosentan, tadalafil 40 mg showed a 23-meter improvement in 6-minute walk distance, though this was not statistically significant in the subgroup analysis 3
Important Safety Considerations
Absolutely contraindicated with nitrates - patients must avoid nitrates for at least 48 hours after tadalafil use due to severe hypotension risk 5
Do not combine with riociguat - coadministration with PDE5 inhibitors causes systemic hypotension 2
Common adverse effects include headache, nasal congestion, flushing, dyspepsia, back pain, and myalgia, which are typically transient and mild to moderate 6
Dosing Across WHO Functional Classes
WHO FC II patients: 40 mg daily resulted in 24-meter mean increase in 6-minute walk distance from baseline 2
WHO FC III-IV patients: 40 mg daily resulted in 36-meter mean increase in 6-minute walk distance from baseline 2
Both functional classes benefit from the same 40 mg daily dose - no dose adjustment based on functional class is needed 2
Key Clinical Pitfall to Avoid
Do not use lower doses (2.5,10, or 20 mg) for PAH treatment - only the 40 mg dose met the pre-specified primary endpoint (P < .01 difference in placebo-adjusted 6-minute walk distance) in the pivotal trial 2. Lower doses showed numerically smaller improvements that did not reach statistical significance for the primary outcome.