Tadalafil: Contraindications, Interactions, and Red-Flag Symptoms

Absolute Contraindications: Nitrates & Riociguat

Some medication combinations with tadalafil are never safe, regardless of dose or timing. Chief among these are nitrates and riociguat. The reason is pharmacological: tadalafil inhibits phosphodiesterase type 5 (PDE5), increasing cyclic guanosine monophosphate (cGMP) levels in smooth muscle. Nitrates and riociguat also boost cGMP — nitrates by releasing nitric oxide, and riociguat by stimulating soluble guanylate cyclase. When combined, the result is excessive vasodilation and potentially catastrophic hypotension.

Nitrates come in many forms:

• Short-acting: nitroglycerin sublingual tablets or sprays, often used for acute angina.
• Long-acting: isosorbide mononitrate/dinitrate tablets, patches, or ointments.
• Recreational: inhaled nitrites (“poppers”), sometimes used in club settings.

Riociguat is prescribed for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The combination with tadalafil or any PDE5 inhibitor is explicitly contraindicated in both drugs’ prescribing information.

Importantly, “waiting a few hours” is not enough. Tadalafil’s long half-life (~17.5 hours) means it can remain active for over 36 hours. Patients on nitrates or riociguat should never be started on tadalafil, and those already using tadalafil should avoid initiating these drugs until the PDE5 inhibitor is fully cleared.

Clear documentation of this counseling is critical. Patients must be reminded that using emergency nitrates while tadalafil is in their system could drop blood pressure to dangerous levels, causing syncope, myocardial infarction, or stroke.

Cardiovascular Precautions & Princeton IV Consensus

Before starting tadalafil, it’s important to determine whether a patient’s cardiac status allows for safe sexual activity. Sexual activity naturally increases heart rate and blood pressure; in some men with significant cardiovascular disease, that strain can be risky even without the drug’s vasodilating effects.

The Princeton IV Consensus (2024) provides a three-tier framework:

• High risk: unstable angina, uncontrolled hypertension, recent myocardial infarction (<2 weeks), recent stroke (<6 weeks), severe heart failure (NYHA IV), or high-risk arrhythmias. These men should avoid sexual activity and PDE5 inhibitors until stabilized.
• Intermediate risk: stable angina with limited exercise tolerance, recent revascularization, or NYHA class II heart failure. Additional evaluation — often including stress testing — is advised before starting treatment.
• Low risk: well-controlled hypertension, mild stable angina, or prior successful revascularization with good exercise capacity. PDE5 inhibitors are generally considered safe here.

Functional capacity often predicts risk better than diagnosis alone; for example, being able to climb two flights of stairs without symptoms suggests low cardiovascular risk.

Alpha-Blockers & BP-Lowering Agents

Tadalafil has a vasodilatory effect that can become additive when taken alongside medications designed to lower blood pressure. This is particularly important with alpha-blockers, which are frequently prescribed for hypertension or for relieving lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). When tadalafil and an alpha-blocker are combined, especially at treatment initiation or during dose adjustments, the result can be a significant drop in blood pressure, leading to dizziness, lightheadedness, or even fainting.

Not all alpha-blockers carry the same level of risk. Selective α1A-blockers such as tamsulosin tend to be better tolerated in combination with tadalafil, particularly when the alpha-blocker dose has been stable before adding the PDE5 inhibitor. In contrast, non-selective alpha-blockers like doxazosin or terazosin can cause more pronounced blood pressure reductions when combined with tadalafil, and the risk is greatest if both drugs are started close together.

The safest approach is to first ensure that the patient is stable on their alpha-blocker regimen before introducing tadalafil, beginning with the lowest effective dose. Close monitoring during the first several days is important to identify signs of hypotension early. In some cases, taking one or both medications in the evening can help reduce the likelihood of daytime dizziness, though this should be tailored to the patient’s routine and tolerance.

Other classes of antihypertensive drugs, such as calcium channel blockers, ACE inhibitors, and diuretics, can also add to the blood pressure–lowering effect, though typically to a lesser extent. Patients who are on multiple BP-lowering agents should still be monitored more closely, particularly when first combining them with tadalafil. Practical patient counseling should reinforce the importance of rising slowly from sitting or lying positions, maintaining adequate hydration, and seeking medical attention promptly if severe dizziness or fainting occurs.

Hepatic & Renal Impairment: Dose Adjustments

Tadalafil is metabolized predominantly by the liver through the CYP3A4 pathway and excreted partly via the kidneys, which means both hepatic and renal function directly influence its clearance. In patients with mild to moderate hepatic impairment (Child-Pugh class A or B), tadalafil can be used with caution, but the starting dose should be conservative. For on-demand use in erectile dysfunction, 10 mg may be appropriate, but daily dosing should generally not exceed 5 mg — and some patients may benefit from starting as low as 2.5 mg. In severe hepatic impairment (Child-Pugh class C), tadalafil is not recommended, as impaired metabolism can lead to significantly increased drug exposure and a higher risk of adverse effects.

Renal impairment is equally important. In mild to moderate renal impairment (creatinine clearance 30–80 mL/min), dose reductions are advised, especially for once-daily regimens. For severe renal impairment (CrCl <30 mL/min), tadalafil should generally be avoided for daily use, and on-demand doses should not exceed 10 mg every 48 hours. In patients on hemodialysis, exposure to tadalafil can be markedly increased, and use is often discouraged. These restrictions are not simply theoretical. Reduced clearance leads to higher plasma concentrations, which in turn heightens the risk of headaches, hypotension, dyspepsia, and, in extreme cases, cardiovascular instability. Before prescribing, clinicians should always review recent liver function tests and estimated glomerular filtration rate (eGFR). If organ function declines during treatment, doses must be reassessed promptly.

In both hepatic and renal impairment, a “start low, go slow” approach allows for careful titration and minimizes the chance of adverse reactions. Patient counseling should include clear guidance on recognizing side effects early and reporting them before they escalate. This is particularly important in individuals whose drug elimination is compromised, as even small increases in plasma tadalafil can have a disproportionate physiological impact.

Vision/Hearing Changes & Priapism: When to Seek Immediate Care

Although uncommon, certain adverse effects of tadalafil require urgent medical attention. One is non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition that can cause sudden, painless vision loss in one eye. Patients with a history of NAION, crowded optic disc anatomy, diabetes, or hypertension may be at higher risk. Any abrupt visual disturbance while on tadalafil warrants immediate discontinuation and ophthalmologic evaluation.

Another red flag is sudden hearing loss, sometimes accompanied by tinnitus or dizziness. The onset can be rapid, and prompt ENT assessment is essential to maximize recovery chances.

Priapism, an erection lasting more than four hours, is an urologic emergency. Untreated, it can cause permanent erectile dysfunction due to ischemic tissue injury.

Patients should be instructed clearly on these red-flag symptoms before starting therapy. Rapid recognition and emergency care can mean the difference between full recovery and irreversible harm, making patient education as vital as the prescription itself.

Conclusion

Tadalafil remains a safe and effective therapy for most men with ED or BPH — provided its use follows established safety guidelines. Screening for absolute contraindications, assessing cardiovascular readiness, adjusting doses for hepatic or renal impairment, and anticipating drug interactions all reduce avoidable risks. Equally important is preparing patients to recognize and act on red-flag symptoms such as sudden vision or hearing loss or priapism. With careful prescribing, thorough monitoring, and informed shared decision-making, clinicians can help patients gain the full benefits of tadalafil while minimizing the potential for serious adverse events. Safety must always come first.

References

1. American Urological Association. (2023). Benign prostatic hyperplasia (BPH) guideline. https://www.auanet.org/guidelines-and-quality/guidelines/benign-prostatic-hyperplasia-(bph)-guideline
2. European Medicines Agency. (2023). Cialis: EPAR – product information. https://www.ema.europa.eu/en/documents/product-information/cialis-epar-product-information_en.pdf
3. Food and Drug Administration. (2018). Cialis (tadalafil) [Prescribing information]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021368s030lbl.pdf
4. Food and Drug Administration. (2023). Adcirca (tadalafil) [Prescribing information]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022332s022lbl.pdf
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