Does tadalafil increase creatinine levels? This is a common concern for patients prescribed this phosphodiesterase type 5 (PDE5) inhibitor for erectile dysfunction, benign prostatic hyperplasia, or pulmonary arterial hypertension. Creatinine is a waste product filtered by the kidneys, and elevated levels may indicate impaired renal function. Understanding the relationship between tadalafil and kidney function tests is important for safe medication use. Clinical evidence shows that tadalafil does not cause clinically significant kidney damage in most patients, though dose adjustments are recommended for those with pre-existing renal impairment. This article examines the evidence, explains when monitoring is needed, and clarifies when to seek medical advice.

What Is Tadalafil and How Does It Work?

Tadalafil is a prescription medication primarily used to treat erectile dysfunction (ED) and the urinary symptoms of benign prostatic hyperplasia (BPH). It belongs to a class of drugs called phosphodiesterase type 5 (PDE5) inhibitors, which also includes sildenafil and vardenafil. In the UK, tadalafil is available under brand names such as Cialis, as well as generic formulations approved by the MHRA.

The mechanism of action involves selective inhibition of the PDE5 enzyme, which is found in the smooth muscle of blood vessels. When sexual stimulation occurs, nitric oxide is released in the erectile tissue of the penis, activating an enzyme that produces cyclic guanosine monophosphate (cGMP). This chemical messenger relaxes smooth muscle and increases blood flow to the penis, facilitating an erection. PDE5 normally breaks down cGMP, so by inhibiting this enzyme, tadalafil helps maintain higher levels of cGMP, prolonging smooth muscle relaxation and improving erectile function.

Tadalafil is also licensed for treating pulmonary arterial hypertension (PAH) under the brand name Adcirca, where it works by relaxing blood vessels in the lungs to improve exercise capacity. The drug has a notably long half-life of approximately 17.5 hours, which allows for once-daily dosing or 'on-demand' use with efficacy for up to 36 hours after taking a dose.

Common side effects include headache, indigestion, back pain, muscle aches, flushing, and nasal congestion. These effects are generally mild to moderate and reflect the drug's vasodilatory properties. Serious adverse effects are rare but can include sudden vision or hearing loss, priapism (prolonged erection), and cardiovascular events in susceptible individuals.

Tadalafil is contraindicated with nitrates and guanylate cyclase stimulators (such as riociguat) due to potentially dangerous blood pressure drops. Caution is needed with alpha-blockers, strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir), CYP3A4 inducers (e.g., rifampicin), and grapefruit juice. Patients should report suspected side effects via the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk).

Understanding Creatinine and Kidney Function Tests

Creatinine is a waste product generated from the normal breakdown of muscle tissue and the metabolism of creatine, a molecule important for energy production in muscles. It is produced at a relatively constant rate and is filtered out of the blood by the kidneys, then excreted in urine. Measuring creatinine levels in the blood provides valuable information about kidney function.

In clinical practice, serum creatinine is one of the most commonly used markers to assess renal function. Reference ranges typically fall between approximately 60–110 micromoles per litre (µmol/L) for men and 45–90 µmol/L for women, though these can vary between laboratories. Always refer to the specific reference ranges provided by your local laboratory. Elevated creatinine levels may indicate that the kidneys are not filtering waste effectively, which could suggest acute kidney injury, chronic kidney disease, or other renal impairment.

However, creatinine alone does not provide a complete picture. The estimated glomerular filtration rate (eGFR) is calculated using serum creatinine along with age and sex. The eGFR gives a more accurate assessment of kidney function and is expressed in mL/min/1.73m². According to NICE guidance (NG203), an eGFR below 60 mL/min/1.73m² for more than three months indicates chronic kidney disease. Alongside eGFR, the urine albumin-to-creatinine ratio (uACR) is an important marker used to diagnose and stage chronic kidney disease.

Several factors can influence creatinine levels beyond kidney function, including:

• Muscle mass: Individuals with greater muscle mass naturally produce more creatinine

• Diet: High meat consumption can temporarily raise levels

• Medications: Certain drugs can affect creatinine production or secretion

• Hydration status: Dehydration can concentrate creatinine in the blood

• Age: Creatinine production decreases with age as muscle mass declines

Understanding these variables is essential when interpreting kidney function tests and considering potential drug effects.

Does Tadalafil Increase Creatinine Levels?

The relationship between tadalafil and creatinine levels requires careful interpretation. Clinical trials and post-marketing surveillance have not identified kidney toxicity as a significant concern with tadalafil use. The Summary of Product Characteristics (SmPC) approved by the MHRA does not list renal impairment as a common adverse effect.

While some studies have reported small changes in creatinine levels in certain patients taking PDE5 inhibitors, there is no established consistent evidence or mechanism by which tadalafil causes true kidney damage or significantly impairs renal function in patients with normal kidney health. Any observed increases are generally modest and clinically insignificant in most individuals.

For patients with pre-existing kidney disease, dose adjustments are recommended as a precautionary measure. According to the UK SmPC and BNF guidance:

• Mild to moderate renal impairment (eGFR 30-80 mL/min/1.73m²):
• For on-demand use: Initial maximum dose of 10 mg, not more than once every 48 hours

• For once-daily use: Start with 2.5 mg once daily, may increase to 5 mg based on individual response and tolerability

• Severe renal impairment (eGFR less than 30 mL/min/1.73m²):

• For on-demand use: Maximum 10 mg, not more than once every 72 hours
• Once-daily regimens are not recommended

In patients requiring dialysis, tadalafil is highly protein-bound and not significantly cleared by haemodialysis. The SmPC notes limited data in this population, and specialist advice should be sought.

Key points to remember:

• There is no established evidence that tadalafil causes clinically significant kidney damage

• Routine monitoring of kidney function is not required for most patients on tadalafil

• Patients with existing kidney disease should inform their prescriber

• Any significant or persistent changes in kidney function tests warrant medical review

When to Seek Medical Advice About Tadalafil and Kidney Health

While tadalafil is generally well-tolerated, certain situations warrant prompt medical attention. Patients should contact their GP or healthcare professional if they experience symptoms that might suggest kidney problems or other serious adverse effects whilst taking tadalafil.

Symptoms that may indicate kidney issues include:

• Significant changes in urination patterns (frequency, volume, or colour)

• Persistent swelling in the legs, ankles, or feet (oedema)

• Unexplained fatigue or weakness

• Nausea or loss of appetite

• Confusion or difficulty concentrating

• Shortness of breath

• Blood in the urine

Patients with pre-existing medical conditions should discuss tadalafil use with their doctor before starting treatment. This is particularly important for those with known chronic kidney disease, cardiovascular disease, liver impairment, or those taking multiple medications. Drug interactions can occur, especially with nitrates and riociguat (both absolutely contraindicated), alpha-blockers, antihypertensive medications, potent CYP3A4 inhibitors or inducers, and grapefruit juice.

If you are scheduled for routine blood tests that include kidney function, inform your healthcare professional that you are taking tadalafil. This allows proper interpretation of results, particularly if a small change in creatinine is noted. In most cases, this will not require stopping the medication but may prompt further assessment to rule out other causes.

Seek immediate medical attention (call 999 or go to A&E) if you experience:

• Chest pain or irregular heartbeat (do not take nitrates if you have recently taken tadalafil)

• Sudden vision or hearing loss

• An erection lasting more than four hours (priapism)

• Severe allergic reactions (difficulty breathing, swelling of face or throat)

For urgent but non-emergency advice, contact NHS 111.

Regular medication reviews with your GP or prescriber are advisable, particularly if you have multiple health conditions or take several medications. NICE recommends that patients on long-term treatment for chronic conditions should have periodic assessments to ensure ongoing appropriateness and safety of their medication regimen. Open communication with healthcare professionals ensures that tadalafil continues to be both effective and safe for your individual circumstances.

Frequently Asked Questions