Vardenafil is a medicine used to treat erectile dysfunction. Its effect starts about 30 to 60 minutes after taking it. It must not be taken with nitrates (such as nitroglycerin).
Also known as: Levitra
Never take vardenafil with nitrates (such as nitroglycerin). The combination can cause a sudden, dangerous drop in blood pressure, with a risk of fainting or heart attack.
Vardenafil potentiates the vasodilator action of nitrates through the same nitric oxide/cGMP pathway. The combination, with any nitrate form (including intermittent use for angina or NO donors), causes additive vasodilation with profound hypotension, syncope and a risk of ischaemic events. It is absolutely contraindicated. If a nitrate becomes clinically essential, wait at least 24 hours after the last vardenafil dose; patients with chest pain should seek immediate medical care.
PDE5 + nitrate: absolute contraindication. Additive GMPc-mediated vasodilation with potentially fatal profound hypotension; 24 h safety window after the last vardenafil dose.
Additive GMPc-mediated vasodilation (nitrate + PDE5), with a marked fall in blood pressure.
Blood pressure and hypotension symptoms.
Syncope, severe dizziness, marked hypotension, chest pain — seek immediate care.
Absolute contraindication; do not start vardenafil in patients on nitrates. If needed, at least 24 h after the last dose, in a monitored setting.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6 ; 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 vardenafil with doxazosin can lower blood pressure too much, especially on standing, with dizziness and a risk of fainting.
Co-administration of vardenafil with alpha-blockers (doxazosin) can cause symptomatic hypotension through additive vasodilation. In patients stable on an alpha-blocker, the label recommends starting vardenafil at 5 mg and monitoring tolerability.
PDE5 + alpha-blocker: documented additive hypotensive effect; stabilise the alpha-blocker and start vardenafil at 5 mg.
Additive vasodilator effect (PDE5 + alpha-1 antagonist).
Orthostatic blood pressure when starting the combination.
Dizziness on standing, syncope.
Stabilise the alpha-blocker; start vardenafil 5 mg; monitor orthostatic symptoms.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6 ; approved Doxazosin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e1f5e49-2da1-43ab-9795-228a8bcc5a82 ; PubMed — https://pubmed.ncbi.nlm.nih.gov/16387566/ ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Ketoconazole greatly raises vardenafil blood levels (up to 10-fold), with a high risk of side effects. The combination should be avoided, especially in men over 75.
Vardenafil is metabolised by CYP3A4. Ketoconazole (200 mg) increased vardenafil AUC about 10-fold and Cmax 4-fold. Concomitant use with ketoconazole or itraconazole (oral) should be avoided; it is contraindicated in men over 75. It increases the risk of headache, flushing, dyspepsia, nasal congestion and hypotension.
CYP3A4: ketoconazole increased vardenafil AUC ~10-fold. Avoid the combination; if unavoidable, max vardenafil 2.5 mg/24 h (or 5 mg with ketoconazole 200 mg); contraindicated over 75 years.
CYP3A4 inhibition, reducing vardenafil clearance.
Vardenafil adverse effects and hypotension symptoms.
Severe headache, symptomatic hypotension, priapism.
Avoid the combination; if unavoidable, reduce the vardenafil dose per the label.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6 ; approved Ketoconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f162e616-21b4-49b1-b437-15e21001a6f0 ; EMC-UK (MHRA) — approved Vardenafil SmPC: https://www.medicines.org.uk/emc/product/11394/smpc ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Clarithromycin can raise vardenafil blood levels, with a higher risk of side effects. Adjust the dose (max. 2.5 mg/24 h during the course).
Clarithromycin inhibits CYP3A4, increasing vardenafil exposure. The vardenafil label sets, for inhibitors such as clarithromycin and ketoconazole, a maximum dose of 2.5 mg in 24 hours during co-administration.
CYP3A4: clarithromycin is a moderate/strong CYP3A4 inhibitor; the label limits vardenafil to 2.5 mg/24 h with clarithromycin.
CYP3A4 inhibition by clarithromycin.
Vardenafil adverse effects.
Severe headache, symptomatic hypotension.
Limit vardenafil to 2.5 mg/24 h during the clarithromycin course.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6 ; 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 reduces vardenafil blood levels, which may reduce treatment effectiveness.
Vardenafil is predominantly metabolised by CYP3A4; rifampicin, a potent inducer of this enzyme, reduces plasma concentrations and may compromise efficacy.
CYP3A4 inducer: rifampicin accelerates vardenafil clearance (CYP3A4 substrate); monitor clinical response.
CYP3A4 induction by rifampicin.
Clinical response to vardenafil.
Lack of therapeutic effect.
Monitor clinical response; consider an alternative during the rifampicin course.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6 ; 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 greatly increases exposure to Vardenafil (up to 49-fold AUC), with a risk of severe hypotension, syncope and priapism. Do not exceed a single 2.5 mg dose of Vardenafil within 72 hours during concomitant use.
Ritonavir is a potent inhibitor of CYP3A4 and CYP2C9, the enzymes responsible for the hepatic metabolism of vardenafil. In a clinical study, coadministration of ritonavir 600 mg twice daily with vardenafil 5 mg increased vardenafil AUC 49-fold and Cmax 13-fold, prolonging the half-life to about 26 hours. This marked increase in vardenafil exposure raises the risk of severe hypotension, syncope and prolonged erection. Therefore, the label recommends not exceeding a single 2.5 mg dose of vardenafil within a 72-hour period when used with ritonavir. In patients who need both therapies, the lowest effective dose should be chosen, blood pressure monitored, and the patient instructed to seek immediate help in case of prolonged erection or symptoms of hypotension.
Vardenafil + ritonavir: ritonavir, a potent CYP3A4/CYP2C9 inhibitor, increases vardenafil AUC up to 49-fold. Do not exceed vardenafil 2.5 mg within a 72-hour period.
Ritonavir is a potent CYP3A4 inhibitor (and also inhibits CYP2C9) and blocks the hepatic metabolism of vardenafil, prolonging its half-life to about 26 hours and markedly raising its plasma concentration.
Monitor blood pressure, dizziness, headache and signs of prolonged erection.
Severe hypotension, syncope, prolonged erection or priapism.
Avoid the combination whenever possible. If unavoidable, do not exceed a single 2.5 mg dose of vardenafil within a 72-hour period and monitor for symptoms of hypotension.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6 ; approved Ritonavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2849298e-de6e-47bb-8194-56e075b33fc3
Erythromycin, a moderate CYP3A4 inhibitor, may reduce Vardenafil clearance and increase its exposure, potentiating adverse effects such as hypotension and headache.
Vardenafil is metabolized primarily by the CYP3A4/5 isoenzymes and, to a lesser extent, by CYP2C9 of the cytochrome P450 system. Erythromycin, a moderate CYP3A4 inhibitor, reduces vardenafil clearance, increasing its plasma concentrations and potentiating vasodilatory and adverse effects. The vardenafil label states that inhibitors of these enzymes reduce drug clearance, so an increase in exposure is expected. The combination should be used with caution, considering initiation at the lowest vardenafil dose and monitoring for hypotension, dizziness and headache. With strong CYP3A4 inhibitors (ketoconazole, ritonavir), the maximum permitted dose is substantially lower.
Vardenafil + erythromycin: erythromycin, a moderate CYP3A4 inhibitor, reduces vardenafil clearance and increases exposure. Use with caution and consider the lowest dose.
Vardenafil is metabolized primarily by CYP3A4/5 isoforms (and to a lesser extent by CYP2C9); inhibitors of these enzymes, such as erythromycin, reduce its clearance and increase plasma concentrations.
Monitor blood pressure, dizziness and headache after dosing.
Orthostatic hypotension, severe dizziness or syncope.
Use with caution; consider starting with the lowest vardenafil dose and monitor for adverse effects. With strong CYP3A4 inhibitors the maximum dose is lower.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6 ; approved Erythromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0c05e1f7-a3d4-8e69-e063-6394a90aecc3
A high-fat meal may delay the onset of vardenafil effect (slower absorption).
If rapid onset is desired, take vardenafil on an empty stomach or away from high-fat meals.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6
Contraindicated in patients with unstable angina, severe heart failure (NYHA III–IV), recent (6 months) history of stroke or myocardial infarction and hypotension (<90/50 mmHg).
Do not use in these patients; assess the cardiovascular risk associated with sexual activity.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Vardenafil is contraindicated in severe hepatic impairment (Child-Pugh C); in moderate impairment, the maximum dose is 10 mg.
Do not use in Child-Pugh C; in Child-Pugh B, start at 5 mg and do not exceed 10 mg.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6
Vardenafil prolongs the QT interval; it should be avoided in patients with congenital QT syndrome or taking class IA or III antiarrhythmics.
Avoid vardenafil in these patients; consider an alternative PDE5 without relevant QT effect.
DailyMed/FDA (NIH/NLM) — approved Vardenafil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2782efed-6198-47b9-81ac-3e255e2ab7f6
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.
PDE5 inhibitor used in erectile dysfunction. It produces a slight blood pressure reduction (mean maximum decrease of 7/8 mmHg) and a small increase in heart rate; it potentiates the hypotensive effect of nitrates, so the combination is contraindicated. At supratherapeutic doses it slightly prolongs the QT interval.
Selectively inhibits PDE5 (more than 15-fold more selective for PDE5 than for PDE6), increasing cGMP in the corpus cavernosum and promoting smooth muscle relaxation during sexual stimulation; without stimulation it has no effect.
Rapidly absorbed, with absolute bioavailability of about 15%; peak plasma concentrations are reached 30 minutes to 2 hours after dosing (median 60 minutes when fasted). High-fat meals reduce Cmax by 18 to 50%. It is about 95% bound to plasma proteins and the volume of distribution is 208 L.
Predominantly metabolised in the liver by CYP3A4, with contribution from CYP3A5 and the CYP2C isoforms; the main circulating metabolite, M1 (desethylation), has about 28% of the in vitro inhibitory potency and accounts for about 7% of total pharmacological activity. Excreted as metabolites mainly in faeces (91 to 95%) and, to a lesser extent, in urine (2 to 6%).
The terminal half-life of vardenafil and its main metabolite is approximately 4 to 5 hours.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
