Tadalafil is a medicine used to treat erectile dysfunction and the symptoms of an enlarged prostate (benign prostatic hyperplasia). Its effect can last up to 36 hours. It must not be taken with nitrates (such as nitroglycerin).
Also known as: Cialis
Nitrate + PDE5 inhibitor: CONTRAINDICATED — potentially fatal severe hypotension.
Both cause potent vasodilation. The combination can cause severe and potentially fatal hypotension. CONTRAINDICATED — minimum 24-hour interval.
DailyMed/FDA (NIH/NLM) — approved Isosorbide Dinitrate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=44ede034-1fa1-4993-9aa5-49e04fada541
Never take tadalafil with nitrates (such as nitroglycerin). The combination can cause a sudden, dangerous drop in blood pressure, with a risk of fainting or heart attack.
Tadalafil potentiates the hypotensive effect of nitrates: both act on the nitric oxide/cGMP pathway, and their combined action causes marked arterial and venous vasodilation with a pronounced and potentially severe fall in blood pressure (symptomatic hypotension, syncope and, in extreme cases, ischaemic events). The contraindication is absolute with any nitrate form, including intermittent use for angina. Because tadalafil has a long half-life (about 17.5 h; effect up to 36 h), the safety window before giving a nitrate is longer than with sildenafil — no safe interval is documented, so the combination should simply be avoided. If chest pain occurs, the patient should seek immediate medical help and report tadalafil use.
PDE5 + nitrate: absolute contraindication. Both raise cGMP in vascular smooth muscle — additive vasodilation with potentially fatal profound hypotension. Do not co-administer; respect the 48–72 h window (long tadalafil half-life).
Both raise cGMP in vascular smooth muscle, causing additive vasodilation and profound hypotension.
Blood pressure and hypotension symptoms; haemodynamic status if chest pain occurs.
Syncope, severe dizziness, marked hypotension, chest pain — seek immediate care.
Absolute contraindication. Do not start tadalafil in patients taking nitrates; if a nitrate becomes necessary for angina, do so only after a prolonged interval and in a monitored setting.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895 ; approved Nitroglycerin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3c11c1c2-8e62-4f63-8293-2f8b8d845f7e ; PubMed — https://pubmed.ncbi.nlm.nih.gov/16884667/ ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining tadalafil with doxazosin can lower blood pressure too much, especially on standing, with dizziness and a risk of fainting.
In a controlled study, tadalafil augmented the hypotensive effects of doxazosin but had little haemodynamic interaction with tamsulosin. The combination should be started with caution: patient stable on the alpha-blocker, lowest tadalafil dose and warning about orthostatic hypotension.
PDE5 + alpha-blocker: tadalafil augmented doxazosin hypotensive effect in studies; stabilise the alpha-blocker and start the PDE5 at the lowest dose.
Additive vasodilator effect (PDE5 + alpha-1 antagonist).
Orthostatic blood pressure when starting the combination.
Dizziness on standing, syncope, symptomatic hypotension.
Stabilise the alpha-blocker; start tadalafil at the lowest dose; monitor orthostatic symptoms.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895 ; PubMed — https://pubmed.ncbi.nlm.nih.gov/15540759/ ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining tadalafil with tamsulosin can lower blood pressure and cause dizziness or fainting, especially on standing.
Combining tadalafil with alpha-blockers can cause symptomatic hypotension. The tadalafil label does not recommend combining with alpha-blockers for BPH treatment (efficacy not studied and risk of blood pressure lowering) and advises caution when used for erectile dysfunction. In a study, tadalafil had little haemodynamic interaction with tamsulosin, but caution remains.
PDE5 + tamsulosin: the tadalafil label advises against the combination for BPH and advises caution in erectile dysfunction; a study showed little haemodynamic interaction with tamsulosin.
Additive vasodilator effect (PDE5 + alpha-1 antagonist).
Orthostatic blood pressure when starting the combination.
Dizziness on standing, syncope.
Use with caution; consider a low starting dose; monitor orthostatic symptoms.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895 ; PubMed — https://pubmed.ncbi.nlm.nih.gov/15540759/ ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Ketoconazole can raise tadalafil blood levels (ketoconazole 400 mg/day can quadruple exposure), with a higher risk of side effects.
Tadalafil is mainly metabolised by CYP3A4. Ketoconazole (200 mg/day) increased tadalafil exposure (AUC) 2-fold; at 400 mg/day, 4-fold. This increases adverse reactions (headache, dyspepsia, myalgia, flushing, nasal congestion). Other strong CYP3A4 inhibitors (ritonavir, itraconazole, clarithromycin) are expected to have a similar effect.
CYP3A4: ketoconazole (strong inhibitor) increased tadalafil AUC 2–4-fold. Adjust the dose: as-needed tadalafil max. 10 mg every 72 h; daily use max. 2.5 mg.
CYP3A4 inhibition by ketoconazole, reducing tadalafil clearance.
Tadalafil adverse effects (headache, flushing, myalgia, dyspepsia).
Severe headache, symptomatic hypotension, priapism.
Adjust the dose per the label (as-needed: max. 10 mg/72 h; daily: max. 2.5 mg) and watch for adverse effects.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895 ; approved Ketoconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f162e616-21b4-49b1-b437-15e21001a6f0 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Clarithromycin can raise tadalafil blood levels, with a higher risk of side effects. Monitor and consider dose adjustment.
Tadalafil is metabolised by CYP3A4; inhibitors of this enzyme, such as clarithromycin, raise plasma concentrations and the incidence of adverse effects. The label recommends the same dose adjustments as for ketoconazole.
CYP3A4: clarithromycin (inhibitor) increases tadalafil exposure; adjust as with other strong inhibitors (as-needed max. 10 mg/72 h; daily max. 2.5 mg).
CYP3A4 inhibition by clarithromycin.
Tadalafil adverse effects.
Severe headache, symptomatic hypotension, priapism.
Adjust the tadalafil dose per the label during the clarithromycin course.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895 ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Rifampicin greatly reduces tadalafil blood levels (up to 88% reduction in exposure), which may reduce treatment effectiveness.
Rifampicin is a potent CYP3A4 inducer and reduced tadalafil exposure (AUC) by 88%. Other inducers (phenobarbital, phenytoin, carbamazepine) are expected to act similarly. Tadalafil efficacy may be compromised.
CYP3A4 inducer: rifampicin reduced tadalafil AUC by 88%; efficacy may decrease. Consider an alternative or adjustment.
CYP3A4 induction by rifampicin, accelerating tadalafil clearance.
Clinical response to tadalafil.
Lack of therapeutic effect.
Monitor clinical response; consider an alternative to tadalafil during the rifampicin course.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895 ; approved Rifampicin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Ritonavir increases Tadalafil exposure (up to 124% AUC), with a higher risk of hypotension and headache. For as-needed use, do not exceed 10 mg every 72 hours; for once-daily use, do not exceed 2.5 mg.
Tadalafil is predominantly metabolized by CYP3A4. Ritonavir, an inhibitor of CYP3A4 (and also of CYP2C9, CYP2C19 and CYP2D6), increases tadalafil exposure in a dose-dependent manner: with ritonavir 500–600 mg twice daily AUC increased by 32% (with a 30% reduction in Cmax), and with ritonavir 200 mg twice daily AUC increased by 124%. This increase potentiates the hypotensive effect of tadalafil and the risk of headache and flushing. The label recommends dose adjustment: for as-needed use, do not exceed 10 mg every 72 hours; for once-daily use, do not exceed 2.5 mg. The combination should be monitored, especially in patients with cardiovascular disease or on antihypertensive therapy.
Tadalafil + ritonavir: ritonavir increases tadalafil AUC (32–124%). For as-needed use, maximum 10 mg every 72 h; for once-daily use, maximum 2.5 mg.
Tadalafil is predominantly metabolized by CYP3A4; ritonavir, an inhibitor of this isoenzyme (and others), increases tadalafil exposure depending on the ritonavir dose (32% with 500–600 mg twice daily; 124% with 200 mg twice daily).
Monitor blood pressure, headache, dizziness and flushing.
Symptomatic hypotension, syncope or severe headache.
Adjust the tadalafil dose: as-needed use — maximum 10 mg every 72 hours; once-daily use — maximum 2.5 mg.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c3409762-3b2b-1cfc-e053-2995a90ab91b ; approved Ritonavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2849298e-de6e-47bb-8194-56e075b33fc3
Erythromycin, a CYP3A4 inhibitor, predictably increases Tadalafil exposure, with a higher risk of hypotension, flushing and headache.
Tadalafil is a substrate predominantly metabolized by CYP3A4, so inhibitors of this isoenzyme increase its exposure. Although no specific studies were conducted with erythromycin, the tadalafil label states that CYP3A4 inhibitors such as erythromycin would likely increase exposure to the drug, similar to ketoconazole (which increased AUC by 107–312% depending on the dose). The increased exposure potentiates hypotension, flushing and headache. Caution is recommended, considering a reduction in the tadalafil dose, and monitoring of vasodilatory effects, particularly in patients with cardiovascular disease.
Tadalafil + erythromycin: a CYP3A4 inhibitor predictably increases tadalafil exposure. Use with caution and consider dose reduction.
Tadalafil is a substrate predominantly metabolized by CYP3A4; inhibitors of this isoenzyme, such as erythromycin, increase its exposure (the label states that CYP3A4 inhibitors such as erythromycin would likely increase exposure).
Monitor blood pressure, headache, dizziness and flushing.
Symptomatic hypotension, dizziness or syncope.
Use with caution; consider reducing the tadalafil dose and monitor for adverse effects.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c3409762-3b2b-1cfc-e053-2995a90ab91b ; approved Erythromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c05e1f7-a3d4-8e69-e063-6394a90aecc3
Substantial alcohol intake (≥5 units) together with tadalafil can potentiate the blood pressure fall (additive vasodilator effect).
Avoid substantial alcohol intake during the tadalafil effect period; moderate intake has a limited effect.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895
Tadalafil may be taken with or without food; a high-fat meal does not significantly change its absorption.
Take with or without food, as preferred — no dietary restriction is needed.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895
Contraindicated in patients with myocardial infarction within the last 90 days, unstable angina, NYHA class ≥2 heart failure within the last 6 months, uncontrolled arrhythmias or stroke within the last 6 months.
Do not use; assess the cardiovascular risk associated with sexual activity beforehand.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Contraindicated in patients with uncontrolled hypotension (blood pressure <90/50 mmHg) due to the risk of worsening the blood pressure fall.
Do not use; correct hypotension before considering treatment.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895
Tadalafil is not recommended in patients with severe hepatic impairment (hepatic metabolism is compromised).
Do not use in severe hepatic impairment; in moderate impairment, adjust the dose per the label.
DailyMed/FDA (NIH/NLM) — approved Tadalafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bcd8f8ab-81a2-4891-83db-24a0b0e25895
MALE-ONLY drug (erectile dysfunction). No pregnancy studies exist because there is no clinical scenario of fetal exposure — the no_data category is honest and sufficient. Theoretical note: PDE5 inhibitors are not teratogenic in animals.
No indication in women; no fetal exposure expected.
No breastfeeding use scenario.
Not applicable (male-only drug).
Documented justification (audit 288): male-only use — EMC-UK SmPC 4.6 defines no pregnancy category.
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Long-acting PDE5 inhibitor used in erectile dysfunction and in benign prostatic hyperplasia symptoms. At therapeutic doses it produces no significant blood pressure change, but it potentiates the hypotensive effect of nitrates — the combination is contraindicated, with at least 48 hours to elapse after the last dose.
Selectively inhibits PDE5, increasing cGMP in the corpus cavernosum, prostate, bladder and their vascular supply; inhibition has no effect without sexual stimulation. It is more than 10,000-fold more potent for PDE5 than for PDE1, 2, 3, 4, 7, 8, 9 and 10, and 700-fold more potent than for PDE6.
After a single oral dose, Cmax is reached between 30 minutes and 6 hours (median 2 hours). The rate and extent of absorption are not influenced by food. The apparent volume of distribution is about 63 L and plasma protein binding is 94%.
Predominantly metabolised by CYP3A4 to a catechol metabolite, which undergoes extensive methylation and glucuronidation; the major circulating metabolite is methylcatechol glucuronide, without relevant pharmacological activity. Excreted mainly as metabolites, chiefly in faeces (about 61%) and, to a lesser extent, in urine (about 36%).
The mean terminal half-life is 17.5 hours in healthy subjects, allowing once-daily dosing.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
