Doxazosin is a medicine used for the symptoms of an enlarged prostate (benign prostatic hyperplasia) and for high blood pressure. It relaxes blood vessels and prostate muscles, but can cause dizziness, especially on standing.
Also known as: Cardura, Carduran
Combining sildenafil with doxazosin can lower blood pressure too much, especially on standing (orthostatic hypotension), with dizziness and a risk of fainting.
Both classes cause vasodilation; together they can produce symptomatic orthostatic hypotension, especially when the alpha-blocker is started or at high doses. In studies, sildenafil and tadalafil increased the hypotensive effect of doxazosin. The patient should be stabilised on the alpha-blocker before starting the PDE5, with a low starting dose and tolerability assessment.
PDE5 + alpha-blocker: additive vasodilator effect. Stabilise the alpha-blocker before starting the PDE5 and use the lowest starting dose; doxazosin has a greater haemodynamic interaction than tamsulosin.
Additive vasodilator effect between PDE5 and alpha-1 blocker.
Orthostatic blood pressure and symptoms when starting the combination.
Dizziness on standing, syncope, symptomatic hypotension.
Stabilise the alpha-blocker before starting the PDE5; start with the lowest PDE5 dose; advise standing up slowly.
DailyMed/FDA (NIH/NLM) — 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)
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 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 can raise doxazosin blood levels, with a higher risk of hypotension. Use with caution.
Doxazosin is metabolised by CYP3A4. Strong inhibitors of this enzyme (ketoconazole, itraconazole, clarithromycin, indinavir, ritonavir, saquinavir) raise plasma concentrations and the risk of postural hypotension.
CYP3A4: doxazosin is a CYP3A4 substrate; strong inhibitors (ketoconazole, itraconazole, clarithromycin) increase exposure and the risk of hypotension.
CYP3A4 inhibition, reducing doxazosin clearance.
Orthostatic blood pressure.
Dizziness on standing, symptomatic hypotension, syncope.
Use with caution and monitor blood pressure, especially at initiation.
DailyMed/FDA (NIH/NLM) — approved Doxazosin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e1f5e49-2da1-43ab-9795-228a8bcc5a82 ; approved Ketoconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f162e616-21b4-49b1-b437-15e21001a6f0 ; EMC-UK (MHRA) — approved Doxazosin SmPC: https://www.medicines.org.uk/emc/product/102410/smpc ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
No relevant food interactions are documented with doxazosin.
May be taken with or without food; keep the same dosing routine.
EMC-UK (MHRA) — approved Doxazosin SmPC: https://www.medicines.org.uk/emc/product/102410/smpc
Doxazosin is contraindicated in patients with a history of orthostatic hypotension, due to the risk of syncope with the first doses.
Do not use; at initiation, monitor blood pressure and advise standing up slowly.
EMC-UK (MHRA) — approved Doxazosin SmPC: https://www.medicines.org.uk/emc/product/102410/smpc ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Patients with left ventricular outflow obstruction may be sensitive to the vasodilator effect of doxazosin.
Use with caution; monitor blood pressure, especially at treatment initiation.
EMC-UK (MHRA) — approved Doxazosin SmPC: https://www.medicines.org.uk/emc/product/102410/smpc
No controlled studies in pregnant women are available; doxazosin should be used in pregnancy only if the expected benefit outweighs the risk.
Use only if benefit outweighs risk; insufficient data by trimester.
Milk excretion is very low (relative infant dose <1%), but human data are limited; use only if benefit outweighs risk.
No specific contraception needed.
EMC-UK (MHRA) — approved Doxazosin SmPC: https://www.medicines.org.uk/emc/product/102410/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Alpha-1 blocker used in hypertension and benign prostatic hyperplasia. In hypertension, maximum blood pressure reductions occur 2 to 6 hours after dosing, with a greater effect in the standing position. In BPH it significantly improves maximum urinary flow rate.
Selective blockade of alpha-1 (postjunctional) adrenergic receptors: reduces systemic vascular resistance (antihypertensive effect) and decreases smooth muscle tone in the prostate, prostatic capsule and bladder neck (improvement of BPH symptoms).
After oral administration, peak plasma concentrations occur at about 2 to 3 hours; bioavailability is approximately 65% (first-pass effect). Food slightly reduces Cmax and AUC without clinical significance. It is about 98% bound to plasma proteins.
Extensively metabolised in the liver, mainly by O-demethylation of the quinazoline nucleus and hydroxylation; the primary elimination pathway is CYP3A4, with a minor contribution from CYP2D6 and CYP2C9. Several metabolites are active.
Plasma elimination is biphasic, with a terminal half-life of about 22 hours.
