What is the half-life of tadalafil? The half-life of tadalafil is approximately 17.5 hours, making it one of the longest-acting phosphodiesterase type 5 (PDE5) inhibitors used to treat erectile dysfunction (ED) and benign prostatic hyperplasia (BPH). This extended half-life—the time taken for blood concentrations to reduce by half—distinguishes tadalafil from shorter-acting alternatives and allows therapeutic effects to persist for up to 36 hours. Understanding tadalafil's half-life is essential for safe dosing, managing drug interactions (particularly with nitrates), and choosing between on-demand or daily regimens tailored to individual needs and lifestyle.

What Is the Half-Life of Tadalafil?

The half-life of tadalafil is approximately 17.5 hours, making it one of the longest-acting phosphodiesterase type 5 (PDE5) inhibitors available for treating erectile dysfunction (ED) and benign prostatic hyperplasia (BPH). The half-life refers to the time it takes for the concentration of the drug in the bloodstream to reduce by half. This extended half-life distinguishes tadalafil from other medications in its class and contributes to its unique dosing flexibility.

Tadalafil works by inhibiting the PDE5 enzyme, which breaks down cyclic guanosine monophosphate (cGMP) in the smooth muscle cells lining blood vessels. By blocking this enzyme, tadalafil allows cGMP to accumulate, promoting smooth muscle relaxation and increased blood flow to the penis during sexual stimulation. This mechanism requires sexual arousal to be effective—tadalafil does not cause spontaneous erections.

The prolonged half-life means that tadalafil remains active in the body for a considerably longer period compared to shorter-acting alternatives. Following a single dose, therapeutic levels can persist for up to 36 hours, allowing for greater spontaneity in sexual activity, as patients do not need to time intercourse as precisely as with shorter-acting medications.

In the UK, tadalafil is available in two formulations: on-demand tablets (typically 10 mg or 20 mg taken before anticipated sexual activity, no more than once daily) and daily low-dose tablets (2.5 mg or 5 mg). Both regimens are approved by the Medicines and Healthcare products Regulatory Agency (MHRA) and supported by NICE Clinical Knowledge Summaries for appropriate patients. Important safety considerations include contraindications with nitrates (avoid for at least 48 hours after tadalafil) and riociguat, and caution with alpha-blockers due to potential blood pressure effects.

How Long Does Tadalafil Stay in Your System?

Tadalafil typically remains detectable in your system for approximately 3 to 5 days after a single dose, though this varies based on individual factors. While the half-life is 17.5 hours, it takes approximately five half-lives for a drug to be considered effectively eliminated from the body. This means that after taking a standard dose, measurable amounts of tadalafil can persist for 80–90 hours (roughly 3.5–4 days).

The duration tadalafil stays active in your system depends on several pharmacokinetic processes. After oral administration, tadalafil is rapidly absorbed, reaching peak plasma concentrations within 2 hours. Tadalafil may be taken with or without food, as food does not significantly affect its absorption. The drug is extensively metabolised in the liver, primarily by the cytochrome P450 enzyme CYP3A4. The resulting metabolites are then excreted through faeces (approximately 61%) and urine (approximately 36%).

For patients taking daily low-dose tadalafil (2.5 mg or 5 mg), steady-state plasma concentrations are achieved after approximately 5 days of consistent dosing. At steady state, the drug maintains a relatively constant level in the bloodstream, providing continuous therapeutic effect. This differs from on-demand dosing, where drug levels fluctuate more significantly between doses.

It is important to note that whilst tadalafil may remain detectable in the body for several days, its therapeutic effectiveness for erectile dysfunction is generally considered optimal within the first 36 hours after dosing. However, some patients may experience beneficial effects beyond this window. The extended presence of tadalafil in the system has important implications for drug interactions. Nitrates must be avoided for at least 48 hours after taking tadalafil; if urgent nitrate therapy is needed, it should be under close medical supervision. Tadalafil is also contraindicated with riociguat. For alpha-blockers, patients should be stable on alpha-blocker therapy before starting tadalafil, and combinations with doxazosin are not recommended due to increased hypotension risk.

Why Tadalafil's Half-Life Matters for Dosing

The extended half-life of tadalafil fundamentally influences dosing strategies and offers distinct advantages for treatment personalisation. Unlike shorter-acting PDE5 inhibitors that require precise timing before sexual activity, tadalafil's prolonged duration allows for two distinct dosing approaches, each suited to different patient needs and lifestyles.

On-demand dosing involves taking tadalafil (typically 10 mg or 20 mg) at least 30 minutes before anticipated sexual activity. This approach suits men who engage in sexual activity less frequently and prefer not to take daily medication. The long half-life means the effects may persist for up to 36 hours, potentially allowing for greater spontaneity. Importantly, on-demand tadalafil should not be taken more than once in 24 hours.

Daily dosing with lower-strength tablets (2.5 mg or 5 mg) leverages the half-life to maintain steady therapeutic levels. This regimen may be particularly appropriate for men who engage in sexual activity more frequently or who also require treatment for lower urinary tract symptoms associated with BPH. NICE Clinical Knowledge Summaries support daily tadalafil for men with both ED and BPH, as it addresses both conditions simultaneously. Daily dosing eliminates the need to plan sexual activity around medication timing, potentially reducing performance anxiety.

The half-life also has important safety implications. Because tadalafil remains in the system for several days, patients must avoid nitrate medications (used for angina) for at least 48 hours after taking tadalafil, as the combination can cause dangerous drops in blood pressure. Tadalafil is also contraindicated with riociguat. Similarly, caution is required with alpha-blockers, and dose adjustments may be necessary. Healthcare professionals must counsel patients about these interactions and ensure they understand that the effects of tadalafil persist well beyond a single day. Patients should never combine daily and on-demand tadalafil regimens.

Factors That Affect Tadalafil Half-Life

Several physiological and external factors can significantly influence how long tadalafil remains active in an individual's system, potentially altering both efficacy and side effect profiles. Understanding these variables helps clinicians personalise treatment and identify patients who may require dose adjustments.

Hepatic function is perhaps the most critical factor, as tadalafil is primarily metabolised by liver enzymes. In patients with mild to moderate hepatic impairment (Child-Pugh Class A or B), the half-life may be prolonged, and prescribing guidance recommends starting with lower doses (10 mg maximum for on-demand use). For those with severe hepatic impairment (Child-Pugh Class C), tadalafil is not recommended due to insufficient safety data and the risk of drug accumulation. The once-daily regimen is not recommended in severe hepatic impairment.

Renal function also affects tadalafil elimination. In patients with mild renal impairment (creatinine clearance 51–80 mL/min), standard dosing is generally appropriate. For moderate renal impairment (creatinine clearance 31–50 mL/min), reduced on-demand dosing (e.g., 10 mg) is advised. For those with severe renal impairment (creatinine clearance <30 mL/min) or on dialysis, the maximum dose should be 10 mg no more than once every 48 hours for on-demand use. The once-daily regimen is not recommended in severe renal impairment or dialysis patients.

Age influences tadalafil pharmacokinetics, with elderly patients (over 65 years) showing increased drug exposure compared to younger adults. This is partly due to age-related decline in hepatic and renal function. However, dose adjustment based solely on age is not routinely required unless accompanied by organ impairment.

Drug interactions can significantly alter tadalafil half-life. Strong CYP3A4 inhibitors such as ritonavir, ketoconazole, and itraconazole reduce tadalafil metabolism, substantially increasing plasma concentrations and prolonging half-life. Conversely, CYP3A4 inducers like rifampicin and carbamazepine may reduce tadalafil levels. Patients taking these medications require careful dose adjustment and monitoring. Additionally, grapefruit juice, a moderate CYP3A4 inhibitor, may modestly increase tadalafil exposure and should be consumed with caution. Excess alcohol consumption with tadalafil increases the risk of symptomatic hypotension and should be avoided.

Comparing Tadalafil Half-Life to Other ED Medications

When compared to other PDE5 inhibitors available in the UK, tadalafil's half-life stands out as exceptionally long, offering distinct advantages and considerations for patient selection. Understanding these differences helps clinicians and patients choose the most appropriate treatment based on individual circumstances and preferences.

Sildenafil (Viagra), the first PDE5 inhibitor introduced, has a half-life of approximately 3–5 hours. This shorter duration means sildenafil typically remains effective for 4–6 hours after administration. Patients must take sildenafil 30–60 minutes before sexual activity, requiring more precise timing. The shorter half-life may suit men who prefer medication that clears the system more quickly or who experience side effects, as these resolve faster. Sildenafil is available in 25 mg, 50 mg, and 100 mg doses for on-demand use.

Vardenafil (Levitra) has a similar half-life to sildenafil at approximately 4–5 hours, with an effective duration of 4–6 hours. Its pharmacokinetic profile closely resembles sildenafil, though some studies suggest slightly greater potency at equivalent doses. Like sildenafil, vardenafil requires planning around sexual activity and offers less spontaneity than tadalafil. Vardenafil is available in 5 mg, 10 mg, and 20 mg tablets.

Avanafil (Spedra), the newest PDE5 inhibitor available in the UK, has the shortest half-life at approximately 3–5 hours but the fastest onset of action, potentially working within 15–30 minutes. This rapid onset may appeal to patients seeking minimal delay between dosing and sexual activity, though the overall duration of effect remains shorter than tadalafil.

The key advantage of tadalafil's 17.5-hour half-life is the extended window of effectiveness (up to 36 hours) and the option for daily low-dose therapy. This makes tadalafil particularly suitable for men who value spontaneity, engage in frequent sexual activity, or have concurrent BPH. However, the prolonged presence in the system means side effects, if they occur, persist longer, and drug interaction risks extend over several days.

NICE Clinical Knowledge Summaries do not preferentially recommend one PDE5 inhibitor over another for ED, acknowledging that patient preference, tolerability, and individual response should guide selection. Sildenafil is commonly used as first-line treatment due to cost considerations and extensive evidence base, but tadalafil may be prescribed when clinically appropriate, particularly for patients with both ED and BPH. Patients should discuss their lifestyle, frequency of sexual activity, and any concerns about side effects with their healthcare provider to determine the most suitable option.

If you experience side effects from tadalafil or any medication, report them through the MHRA Yellow Card scheme (yellowcard.mhra.gov.uk or via the Yellow Card app). Seek urgent medical attention for priapism (erection lasting more than 4 hours), sudden vision or hearing loss, severe dizziness, or chest pain.

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