Alfuzosin

G04C - Drugs used in benign prostatic hypertrophy ATC G04CA01 Small molecule approved 2003 Oral Natural product

JFDA label: XATRAL 10mg XL tablet

Mechanism of Action

An antagonist of alpha1-adrenoreceptors in the lower urinary tract. Smooth muscle tone is mediated by the sympathetic nervous stimulation of alpha1-adrenoreceptors, which are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck. Blockade of these adrenoreceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in BPH symptoms.

Indications

Approved

Benign prostatic hyperplasia

Off-label

Facilitation of expulsion of ureteral stones

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Concurrent use with other alpha1-blockers Absolute
Hypersensitivity to alfuzosin or any component of the formulation Absolute
concurrent use with potent CYP3A4 inhibitors (eg, itraconazole, ketoconazole, ritonavir) Absolute
moderate or severe hepatic impairment (Child-Pugh class B and C) Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (4)

Common Dizziness · fatigue · headache · pain

Renal and urinary disorders (1)

Common Impotence

Gastrointestinal disorders (4)

Common Abdominal pain · constipation · dyspepsia · nausea

Respiratory, thoracic and mediastinal disorders (4)

Common bronchitis · pharyngitis · sinusitis · Upper respiratory tract infection

Dosing

Source: Lexicomp

Benign prostatic hyperplasia (BPH): Oral: 10 mg once daily Ureteral stones, expulsion (off-label use): Oral: 10 mg once daily, discontinue after successful expulsion (average time to expulsion 1-2 weeks) (Agrawal, 2009; Ahmed, 2010; Gurbuz, 2011). Note: Patients with stones >10 mm were excluded from studies.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution in severe renal impairment (CrCl

Mild hepatic impairment (Child-Pugh class A): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution. Moderate or severe hepatic impairment (Child-Pugh class B or C): Use is contraindicated.

Warnings & Precautions

Source: Lexicomp

Angina

Discontinue if symptoms of angina occur or worsen.

CNS depression

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

Floppy iris syndrome

Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; there appears to be no benefit in discontinuing alpha1-blocker therapy prior to surgery. May require modifications to surgical technique.

Orthostatic hypotension/syncope

May cause orthostatic hypotension and syncope within a few hours following administration; anticipate a similar effect if therapy is interrupted for a few days, if dosage is rapidly increased, or if another antihypertensive drug, PDE-5 inhibitors, or nitrates is introduced. Use with caution in patients with symptomatic orthostatic hypotension.

Priapism

Priapism has been associated with use (rarely); seek immediate medical assistance for erections lasting longer than 4 hours. Disease-related concerns:

Cardiovascular disease

Use with caution in patients with histories of tachyarrhythmia or with certain cardiovascular conditions, such as myocardial ischemia.

Hepatic impairment

Use with caution in patients with mild hepatic impairment; contraindicated in moderate-to-severe impairment.

Prostate cancer

Rule out prostatic carcinoma before beginning therapy (many symptoms of BPH and prostate cancer are similar).

QT prolongation

Alfuzosin has been shown to prolong the QT interval alone (minimal) and with other drugs with comparable effects on the QT interval (additive). Use with caution in patients with known QT prolongation (congenital or acquired).

Renal impairment

Use with caution in patients with severe renal impairment (CrCl Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warning/precautions:

Limitation of use

Not intended for use as an antihypertensive drug.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events have not been observed in animal reproduction studies.

Lactation

It is not known if alfuzosin is excreted in breast milk.

Monitoring

Clinical pearl	Urine flow, blood pressure, PSA

Chemistry & Properties

Formula	C19H27N5O4
Molecular weight	389.46 g/mol
IUPAC name	N-[3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)-methylamino]propyl]oxolane-2-carboxamide
CAS	81403-80-7
PubChem CID	2092
InChIKey	`WNMJYKCGWZFFKR-UHFFFAOYSA-N`
logP	1.35 (XLogP 1.7)
Polar surface area	111.83 Å²
H-bond acceptors / donors	8 / 2
Drug-likeness (QED)	0.65
Lipinski violations	0

SMILES

COc1cc2nc(N(C)CCCNC(=O)C3CCCO3)nc(N)c2cc1OC

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2B6	Substrate	—
CYP2C19	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MDR1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Anagrelide	major
Arsenic trioxide	major
Cabozantinib	major
Ceritinib	major
Chloroquine	major
Cisapride	major
Clarithromycin	major
Cobicistat	major
Crizotinib	major
Dolasetron	major
Erythromycin	major
Fingolimod	major
Halofantrine	major
Hydroxychloroquine	major
Idelalisib	major
Ivosidenib	major
Ketoconazole	major
Lumefantrine	major
Macimorelin	major
Nilotinib	major
Osimertinib	major
Ozanimod	major
Panobinostat	major
Papaverine	major
Pasireotide	major
Ribociclib	major
Siponimod	major
Toremifene	major
Vandetanib	major
Vemurafenib	major
Abarelix	moderate
Abiraterone	moderate
Alimemazine	moderate
Amifostine	moderate
Apalutamide	moderate
Aprepitant	moderate
Astemizole	moderate
Bicalutamide	moderate
Bisacodyl	moderate
Bosutinib	moderate

Showing 40 of 100+.

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Proflow XL	Tablet 10 mg	30 tab	Dar Al Dawa Development and Investment Co Ltd/Jordan	8.380
XATRAL 10mg XL tablet	Tablet 10 mg	30 tab	Ulfa Pharma Co.	10.140