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)
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
Vardenafil is not indicated for use in women; no studies in pregnant women are available.
Not indicated in women; no data in pregnancy.
Not indicated in women; no data on milk excretion.
Not applicable (male-only drug).
EMC-UK (MHRA) — approved Vardenafil SmPC: https://www.medicines.org.uk/emc/product/11394/smpc
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.
