What are the approved clinical uses of tadalafil?

Clinical Uses of Tadalafil

Tadalafil is FDA-approved for three distinct indications: erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension (PAH). 1, 2, 3

Primary FDA-Approved Indications

Erectile Dysfunction

• Tadalafil received FDA approval in 2009 for group 1 pulmonary arterial hypertension in adults, and is also approved for erectile dysfunction with two dosing regimens: as-needed dosing (2.5-20 mg taken at least 30 minutes before sexual activity, effective for up to 36 hours) and once-daily dosing (2.5-5 mg taken at approximately the same time each day). 1, 2
• Placebo-controlled trials demonstrate that tadalafil improves exercise capacity, time to clinical worsening, and health-related quality of life in adult patients with idiopathic PAH or associated PAH. 1
• In clinical trials, approximately 69% of men using tadalafil reported successful sexual intercourse attempts compared to 33% with placebo. 1, 4, 2
• The medication works by inhibiting phosphodiesterase type-5, which increases smooth muscle cell cGMP levels and promotes pulmonary vascular dilation. 1, 5

Benign Prostatic Hyperplasia

• Tadalafil 5 mg once daily is FDA-approved to treat signs and symptoms of BPH in adult males, and uniquely can address both BPH and ED simultaneously when these conditions coexist. 6, 7, 3, 8
• The medication improves International Prostate Symptom Score (IPSS), voiding and storage subscores, IPSS Quality of Life, and BPH Impact Index. 6, 9
• The mechanism for improved lower urinary tract symptoms is thought to involve alterations in nitric oxide levels, Rho-associated protein kinase deactivation, and reductions in pelvic atherosclerosis. 8
• Unlike 5-alpha-reductase inhibitors, tadalafil does not lower PSA levels, avoiding the need for PSA adjustment during monitoring. 7

Pulmonary Arterial Hypertension

• Tadalafil, a long-acting PDE5 inhibitor, received FDA approval in 2009 in adults with group 1 PAH. 1
• A placebo-controlled study demonstrated that tadalafil improved exercise capacity, time to clinical worsening, and health-related quality of life in adult patients with IPAH or associated PAH. 1
• Open-label use has suggested benefit in Eisenmenger syndrome and in combination with prostacyclin analogs. 1
• A retrospective study in 33 pediatric patients with PAH demonstrated safety and potential efficacy, with 14 of 29 children transitioned from sildenafil to tadalafil showing significant improvements in mean pulmonary artery pressure and pulmonary vascular resistance index on repeat cardiac catheterization. 1

Emerging and Off-Label Uses

Chronic Prostatitis/Chronic Pelvic Pain Syndrome

• Tadalafil 5 mg once daily is appropriate for patients with moderate-to-severe CPPS pain (NIH-CPSI pain subscore ≥4) who have not responded adequately to first-line antibiotics or alpha-blockers, with clinical benefit observed after a minimum of 4 weeks. 7
• The mechanism involves reducing collagen deposition and increasing apoptosis in pelvic tissues, potentially mitigating fibrotic and inflammatory components. 7

Critical Safety Considerations Before Prescribing

Absolute Contraindications

• Tadalafil is absolutely contraindicated with any form of nitrate use due to risk of potentially fatal hypotension. 4, 7, 2
• Patients must be explicitly asked about all forms of nitrate use, including sublingual, oral, transdermal, and recreational (e.g., "poppers"). 4

Cardiovascular Risk Assessment

• Before prescribing tadalafil, assess cardiovascular fitness by asking if the patient can walk 1 mile in 20 minutes or climb 2 flights of stairs without symptoms; refer to cardiology if unable to perform this level of activity. 4, 7
• High-risk patients who should defer treatment include those with unstable angina, uncontrolled hypertension, recent MI, NYHA Class II-IV heart failure, or severe valvular disease. 4
• The majority of ED patients fall into the low-risk category and can safely receive PDE5 inhibitors, including those with asymptomatic coronary artery disease with <3 risk factors, controlled hypertension, mild stable angina, successful coronary revascularization, uncomplicated past MI, mild valvular disease, and CHF (NYHA class I). 4

Drug Interactions

• Co-administration of riociguat (a soluble guanylate cyclase stimulator) with tadalafil is contraindicated because it can cause severe hypotension. 4
• Before administration, assess concomitant use of nonselective α-adrenergic antagonists (particularly doxazosin, which augments hypotensive effects), nitrates, and cytochrome P450 inhibitors for possible drug interactions. 10, 8
• Tadalafil had little hemodynamic interaction with tamsulosin 0.4 mg, making it a safer alpha-blocker choice for patients requiring both medications. 10

Hepatic and Renal Impairment

• Tadalafil should not be used in patients with significant hepatic or renal impairment. 7
• For severe hepatic impairment, use of PDE5 inhibitors is generally not recommended. 4

Common Adverse Effects

• The most common adverse events include headache, dyspepsia, back pain, myalgia, nasal congestion, and flushing. 4, 6, 7
• Tadalafil has lower rates of flushing compared to sildenafil, potentially improving tolerability. 4, 7
• Gastroesophageal reflux occurs more frequently with tadalafil than with other PDE5 inhibitors. 7

Rare but Serious Adverse Events

• Patients should be advised to seek emergency medical attention for erections lasting greater than 4 hours, as priapism can result in irreversible damage to erectile tissue if not treated promptly. 2
• Patients should stop tadalafil and seek medical attention immediately for sudden loss of vision in one or both eyes, which may be a sign of non-arteritic anterior ischemic optic neuropathy (NAION). 2
• Patients should stop tadalafil and seek prompt medical attention for sudden decrease or loss of hearing, which may be accompanied by tinnitus and dizziness. 2

Pharmacokinetic Advantages

• The half-life of tadalafil is 17.5 hours, with clinical studies suggesting significant activity 24 hours post-dosing and efficacy for up to 36 hours. 2, 5
• This extended duration allows for spontaneous sexual activity without precise timing, eliminating the need to schedule medication with sexual activity. 4, 6