Phosphodiesterase type 5 (PDE-5) inhibitor
Brand names: Cialis, Adcirca, Alyq
Updated · Methodology
Second line
Used in symptomatic benign prostatic hyperplasia in patients with concomitant erectile dysfunction per EAU 2024. Dose 5 mg once daily. Effect on IPSS and Qmax is comparable to tamsulosin, with less retrograde ejaculation. Dual benefit in coexisting conditions makes tadalafil a preferred choice in this group.
Sources
ICD-10: N40 · ICD-11: GA90
First line
Tadalafil is first-line PDE-5 inhibitor for erectile dysfunction. AEMPS approved two regimens: on-demand (10–20 mg 30 minutes before intercourse) and daily (2.5–5 mg). Long half-life is the main advantage over sildenafil – effect up to 36 hours (the 'weekend pill'). Also approved for pulmonary arterial hypertension (Adcirca 40 mg/day).
Sources
ICD-10: N52.9 · ICD-11: HA01.1
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Tadalafil is a long-acting phosphodiesterase-5 (PDE5) inhibitor. It is prescribed for erectile dysfunction, benign prostatic hyperplasia, and pulmonary arterial hypertension (AEMPS Ficha Técnica). In sports circles, tadalafil is promoted to improve pulmonary gas exchange and physical endurance in healthy athletes. Clinical studies in healthy athletes are small and conflicting. The drug has specific risks: headache, facial flushing, nasal congestion, dyspepsia, muscle pain, visual disturbances (bluish tint), rarely non-arteritic anterior ischemic optic neuropathy (vision loss risk), and sudden hearing loss. It is dangerous combined with nitrates (sharp blood pressure drop). If tadalafil is used for training, consider seeking a second opinion.
Selectively inhibits PDE-5, the enzyme that degrades cGMP in smooth muscle of corpora cavernosa and pulmonary vessels. cGMP accumulation via NO signalling produces vasodilation and erection or reduces pulmonary artery pressure. Metabolised by CYP3A4. Half-life is 17 hours, the longest among PDE-5 inhibitors, requiring a 48-hour washout with any nitrate.
Not used for erectile dysfunction in women. For pulmonary hypertension in women, specialist discussion needed.
No milk excretion data.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
The Cialis SmPC names grapefruit juice among CYP3A4 inhibitors to be used with caution, because they can raise tadalafil levels. No specific grapefruit studies exist. If levels rise, tadalafil's own adverse effects increase: headache, flushing, back and muscle pain, nasal congestion.
Source: EMA: Ficha técnica de Cialis 10 mg comprimidos recubiertos con película (tadalafilo) (2023)
6 pairs found. Sorted from critical to minor.
Mechanism
Synergistic systemic vasodilation.
Symptoms
Fatal hypotension.
Management
Combination contraindicated.
Sources
Mechanism
Both activate cGMP pathway. Synergistic systemic vasodilation – fatal hypotension with MI. Tadalafil's long T1/2 requires 48-hour washout.
Symptoms
Sudden hypotension, MI.
Management
Combination contraindicated. 48 hours between tadalafil and nitrate.
Sources
Mechanism
Both raise cGMP in vascular smooth muscle. Synergistic systemic vasodilation – fatal hypotension with MI. Tadalafil's long T1/2 requires 48-hour washout.
Symptoms
Sudden hypotension, syncope, MI.
Management
Combination contraindicated. 48 hours between tadalafil and nitrate.
Sources
Mechanism
Both raise cGMP. Synergistic systemic hypotension. Adempas Section 4.3 strict contraindication.
Symptoms
Severe hypotension, syncope.
Management
Combination contraindicated.
Sources
Mechanism
Ritonavir inhibits CYP3A4, the enzyme that clears tadalafil. Ritonavir 200 mg twice daily doubled tadalafil exposure (AUC) after a single 20 mg dose, and 500–600 mg twice daily raised it by 32% (tadalafil and ritonavir SmPCs). Later ritonavir also induces the same enzyme, and after about one week tadalafil exposure is close to normal (US tadalafil label for pulmonary arterial hypertension, ).
Symptoms
Hypotension, headache, priapism.
Management
The combination is not contraindicated, but the tadalafil dose is limited and the plan depends on the indication. For erectile dysfunction taken as needed, use no more than 10 mg of tadalafil once every 72 hours and watch more closely for adverse reactions (ritonavir SmPC). For once-daily use in erectile dysfunction or benign prostatic hyperplasia, the maximum is 2.5 mg a day (US tadalafil label, ). In pulmonary arterial hypertension, the European tadalafil SmPC () does not recommend use with ritonavir. If the pair cannot be avoided, the US label gives this plan: in a patient on ritonavir for at least one week, start tadalafil at 20 mg once daily and increase to 40 mg as tolerated; when ritonavir is added to tadalafil, stop tadalafil at least 24 hours before ritonavir starts and resume at 20 mg after at least one week (US tadalafil label, FDA).
Sources
Mechanism
Tadalafil is a phosphodiesterase type 5 (PDE5) inhibitor with vasodilator properties: on its own it causes a slight and transient fall in blood pressure (tadalafil SmPC, ). Losartan lowers blood pressure by blocking angiotensin II receptors, and other substances with a hypotensive effect add to its action (losartan SmPC). In studies with angiotensin II receptor blockers tadalafil 20 mg produced a small additional fall in blood pressure without a clinically significant interaction; in people with uncontrolled hypertension the fall was larger, but in most of them without symptoms of hypotension (tadalafil SmPC, EMA). The interaction is pharmacodynamic: two blood-pressure-lowering effects add up (Cialis label, ).
Symptoms
Usually none: the fall in blood pressure is small and not clinically relevant (tadalafil SmPC, ). Dizziness, weakness or light-headedness on standing can signal a drop in blood pressure; the risk is higher with uncontrolled hypertension and with volume or sodium depletion from diuretics, diarrhoea, vomiting or a salt-restricted diet, when losartan itself can cause symptomatic hypotension (tadalafil and losartan SmPCs).
Management
By the SmPCs the combination is acceptable and no dose change of losartan or tadalafil is needed: no clinically significant interaction with angiotensin II receptor blockers was found (tadalafil SmPC, ). The patient is told that blood pressure may fall slightly in addition to antihypertensive treatment (tadalafil SmPC, EMA). Before tadalafil is prescribed, cardiovascular status is assessed, because sexual activity itself carries some cardiac risk (tadalafil SmPC, EMA); with uncontrolled hypertension or blood pressure below 90/50 mm Hg tadalafil is not recommended, and in people with uncontrolled hypertension the fall in pressure was larger (Cialis label, ; tadalafil SmPC, EMA). Volume or sodium depletion after diuretics, diarrhoea or vomiting is corrected before losartan starts, or losartan is started at a lower dose (losartan SmPC).
Sources
Verbatim lines from the interaction sections, in the language of the label
«CONTRAINDICATIONS: Administration of tadalafil tablets to patients using any form of organic nitrate is contraindicated. Tadalafil was shown to potentiate the hypotensive effect of nitrates ( 4.1 ).»FDA, section 4 · Open on DailyMed
«Durante los ensayos clínicos, se observó que tadalafilo incrementaba el efecto hipotensor de los nitratos, lo que se piensa que es debido a la combinación de los efectos de tadalafilo y los nitratos…»AEMPS, section 4.3 · Open on CIMA
«La administración conjunta de inhibidores de la fosfodiesterasa tipo 5 (PDE5), incluyendo tadalafilo, con estimuladores de la guanilato ciclasa, como riociguat, está contraindicada ya que puede…»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Administration with guanylate cyclase (GC) stimulators, such as riociguat ( 4.3 ).»FDA, section 4 · Open on DailyMed
«Antihipertensivos (incluyendo bloqueantes de los canales del calcio): La administración conjunta de doxazosina (4 y 8 mg diarios) y tadalafilo (dosis diaria de 5 mg, y dosis única de 20 mg) aumenta…»AEMPS, section 4.5 · Open on CIMA
«Uso con inductores o inhibidores del CYP3A4: No se recomienda el uso de tadalafilo en pacientes que estén tomando de manera concomitante inhibidores potentes del CYP3A4, como ketoconazol o ritonavir…»AEMPS, section 4.4 · Open on CIMA
«Uso con inductores o inhibidores del CYP3A4: No se recomienda el uso de tadalafilo en pacientes que estén tomando de forma crónica inductores potentes del CYP3A4, tales como rifampicina (ver sección…»AEMPS, section 4.4 · Open on CIMA
«Uso con inductores o inhibidores del CYP3A4: No se recomienda el uso de tadalafilo en pacientes que estén tomando de manera concomitante inhibidores potentes del CYP3A4, como ketoconazol o ritonavir…»AEMPS, section 4.4 · Open on CIMA
«DRUG INTERACTIONS: CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) increase tadalafil exposure ( 2.7 , 5.10 , 7.2 ) requiring dose adjustment: Tadalafil tablets for use as needed: no more than 10 mg…»FDA, section 7 · Open on DailyMed
«Potential for Pharmacodynamic Interactions with Tadalafil Tablets: Alpha-Blockers — Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. PDE5 inhibitors, including…»FDA, section 7 · Open on DailyMed
«Uso con inductores o inhibidores del CYP3A4: No se recomienda el uso de tadalafilo en pacientes que estén tomando de forma crónica inductores potentes del CYP3A4, tales como rifampicina (ver sección…»AEMPS, section 4.4 · Open on CIMA
«DRUG INTERACTIONS: CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) increase tadalafil exposure ( 2.7 , 5.10 , 7.2 ) requiring dose adjustment: Tadalafil tablets for use as needed: no more than 10 mg…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) increase tadalafil exposure ( 2.7 , 5.10 , 7.2 ) requiring dose adjustment: Tadalafil tablets for use as needed: no more than 10 mg…»FDA, section 7 · Open on DailyMed
«Potential for Pharmacodynamic Interactions with Tadalafil Tablets: Alpha-Blockers — Caution is advised when PDE5 inhibitors are coadministered with alpha-blockers. PDE5 inhibitors, including…»FDA, section 7 · Open on DailyMed
«Potential for Pharmacodynamic Interactions with Tadalafil Tablets: Antihypertensives — PDE5 inhibitors, including tadalafil are mild systemic vasodilators. Clinical pharmacology studies were…»FDA, section 7 · Open on DailyMed
«Acido acetilsalicílico: Tadalafilo (10 mg y 20 mg) no potenció el aumento del tiempo de hemorragia causado por ácido acetilsalicílico.»AEMPS, section 4.5 · Open on CIMA
«Potential for Pharmacodynamic Interactions with Tadalafil Tablets: Antihypertensives — PDE5 inhibitors, including tadalafil are mild systemic vasodilators. Clinical pharmacology studies were…»FDA, section 7 · Open on DailyMed
«Potential for Other Drugs to Affect Tadalafil Tablets: Antacids — Simultaneous administration of an antacid (magnesium hydroxide/FDA, section 7 · Open on DailyMed
«Anticonceptivos orales: En el estado estacionario, tadalafilo (40 mg una vez al día) incrementó la exposición (AUC) al etinilestradiol en un 26 % así como el valor de C max en un 70 %, en relación…»AEMPS, section 4.5 · Open on CIMA
«Potential for Other Drugs to Affect Tadalafil Tablets: CYP3A4 (e.g., Rifampin) — Rifampin (600 mg daily), a CYP3A4 inducer, reduced tadalafil 10-mg single-dose exposure (AUC) by 88% and C max by 46%…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: CYP3A4 inducers (e.g. rifampin) decrease tadalafil exposure ( 7.2 ).»FDA, section 7 · Open on DailyMed
«Sustratos de la p-glicoproteína (por ejemplo digoxina): Tadalafilo (40 mg una vez al día) no tuvo un efecto clínicamente significativo sobre la farmacocinética de la digoxina.»AEMPS, section 4.5 · Open on CIMA
«Potential for Tadalafil Tablets to Affect Other Drugs: P-glycoprotein (e.g. Digoxin) — Coadministration of tadalafil (40 mg once per day) for 10 days did not have a significant effect on the…»FDA, section 7 · Open on DailyMed
«CONTRAINDICATIONS: Do not use isosorbide dinitrate in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil…»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Do not use isosorbide mononitrate in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil…»FDA, section 4 · Open on DailyMed
«Uso concomitante de inhibidores de la fosfodiesterasa tipo 5 (PDE5), como el sildenafilo, tadalafilo, vardenafilo,ya que pueden potenciar el efecto vasodilatador de Cordiplast, provocando una…»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Use of phosphodiesterase type 5 (PDE-5) inhibitors, such as avanafil, sildenafil, tadalafil, or vardenafil, or soluble guanylate cyclase (sGC) stimulators. ( 4.1 , 7.1 )»FDA, section 4 · Open on DailyMed
«Phosphodiesterase Inhibitors: Concomitant administration of Adempas with specific PDE-5 inhibitors (such as sildenafil, tadalafil, or vardenafil) or nonspecific PDE-5 inhibitors (such as dipyridamole…»FDA, section 4 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: PDE5 inhibitors: sildenafil, tadalafil, vardenafil ↑ sildenafil ↑ tadalafil ↑ vardenafil Coadministration with atazanavir has not been…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Sildenafil Tadalafil Vardenafil Use With Caution Sildenafil, Tadalafil, Vardenafil: Each of these phosphodiesterase inhibitors is primarily metabolized by CYP3A, and CYP3A will be…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Interactions: Phosphodiesterase-5 (PDE-5) Inhibitors: avanafil sildenafil tadalafil vardenafil ↑ PDE-5 inhibitors Coadministration with avanafil is not…»FDA, section 7 · Open on DailyMed
«INHIBIDORES DE LA FOSFODIESTERASA 5 (PDE-5): La combinación de avanafilo y darunavir potenciado está contraindicada (ver sección 4.3). La administración simultánea de otros inhibidores de PDE-5 para…»AEMPS, section 4.5 · Open on CIMA
«Established and Other Potentially Significant Drug Interactions: PDE-5 inhibitors : e.g. avanafil, sildenafil, tadalafil, vardenafil PDE-5 inhibitors (only the use of sildenafil at doses used for…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: PDE5 Inhibitors: avanafil sildenafil, tadalafil, vardenafil ↑ avanafil ↑ sildenafil ↑ tadalafil ↑ vardenafil Sildenafil when used for…»FDA, section 7 · Open on DailyMed
«Sildenafilo, tadalafilo y vardenafilo: Cada uno de estos inhibidores de fosfodiestearasa es metabolizado, al menos en parte, por CYP3A, y CYP3A se puede inhibir con la administración concomitante con…»AEMPS, section 4.5 · Open on CIMA
«Uso con inhibidores de la PDE-5 : La administración concomitante de doxazosina con inhibidores de la fosfodiesterasa-5 (p.ej. sildenafilo, tadalafilo y vardenafilo) debe realizarse con precaución…»AEMPS, section 4.4 · Open on CIMA
«Inhibidores de la fosfodiesterasa: Se debe tener cuidado con el uso concomitante de tadalafilo y ritonavir para el tratamiento de la disfunción erectil dosificado como agente antirretroviral o como…»AEMPS, section 4.5 · Open on CIMA
«Inhibidores de la PDE-5: Se han observado mínimas interacciones farmacodinámicas entre la silodosina y dosis máximas de sildenafilo o tadalafilo. En un ensayo controlado con placebo en el que…»AEMPS, section 4.5 · Open on CIMA
«PDE5 Inhibitors: Co-administration of silodosin with a single dose of 100 mg sildenafil or 20 mg tadalafil was evaluated in a placebo-controlled clinical study that included 24 healthy male subjects…»FDA, section 7 · Open on DailyMed
«Fármacos que pueden disminuir los niveles plasmáticos de carbamazepina: Medicamentos utilizados para la disfunción eréctil : tadalafilo.»AEMPS, section 4.5 · Open on CIMA
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Tadalafil is evaluated for the following indications with varying evidence strength: Benign prostatic hyperplasia (evidence tier A), Erectile dysfunction (evidence tier A), Athletic endurance (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Tadalafil (≥ 1 in 100): Headache, Facial flushing, Nasal congestion, Back pain, Dyspepsia. See the Safety section for uncommon and serious reactions.
Not used for erectile dysfunction in women. For pulmonary hypertension in women, specialist discussion needed.
No milk excretion data.
Tadalafil is contraindicated in: Combination with any nitrate or NO donor (48 h washout); Combination with riociguat; Severe heart failure; MI within last 90 days; Stroke within last 6 months. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Tamsulosin, Tolterodine, Trospium, Vardenafil, Dutasteride + Tamsulosin, Mirabegron, Pygeum africanum, Dutasteride