Silodosin

G04C - Drugs used in benign prostatic hypertrophy ATC G04CA04 Small molecule approved 2008 Oral

JFDA label: SILDARIN 4

Mechanism of Action

Antagonist of Alpha-1A adrenergic receptor — Alpha-1a adrenergic receptor antagonist

Target	Action	Gene / class
Alpha-1A adrenergic receptor efficacy	ANTAGONIST	ADRA1A

Indications

Off-label

Ureteral calculi (distal)

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Concurrent use with other alpha-blockers (eg, prazosin, terazosin, doxazosin) Absolute
Hypersensitivity to silodosin or any component of the formulation, concurrent use with strong CYP3A4 inhibitors (eg, clarithromycin, itraconazole, ketoconazole, ritonavir) Absolute
severe renal impairment (CrCl Absolute

Adverse Reactions

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

Cardiac disorders (1)

Common Orthostatic hypotension

Nervous system disorders (3)

Common Dizziness · headache · insomnia

Renal and urinary disorders (1)

Common Prostate specific antigen increased

Gastrointestinal disorders (2)

Common abdominal pain · Diarrhea

Musculoskeletal and connective tissue disorders (1)

Common Weakness

Other (1)

Very Common Genitourinary: Retrograde ejaculation

Respiratory, thoracic and mediastinal disorders (3)

Common Nasal congestion · rhinorrhea · sinusitis

Dosing

Source: Lexicomp

BPH: Oral: 8 mg once daily with a meal Ureteral calculi (distal) expulsion (off-label use): Oral: 8 mg once daily, discontinue after successful expulsion (average time to expulsion was 3 to 18 days) (Dell’Atti 2015; Kumar 2015; Wang 2016). Note: Patients with stones >10 mm were excluded from studies.

Refer to adult dosing.

CrCl >50 mL/minute: No dosage adjustment necessary. CrCl 30-50 mL/minute: 4 mg once daily. CrCl

Mild-to-moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary. Severe impairment (Child-Pugh class C): Use is contraindicated (has not been studied).

Warnings & Precautions

Source: Lexicomp

Floppy iris syndrome

Intraoperative floppy iris syndrome has been observed in cataract surgery patients who were on or were previously treated with alpha1-blockers; causality has not been established and there appears to be no benefit in discontinuing alpha-blocker therapy prior to surgery.

Orthostatic hypotension/syncope

May cause significant orthostatic hypotension with or without syncope, especially with first dose; anticipate a similar effect if therapy is interrupted for a few days, if dosage is rapidly increased, or if another antihypertensive drug (particularly vasodilators) or a PDE-5 inhibitor (eg, sildenafil, tadalafil, vardenafil) is introduced although coadministration of sildenafil or tadalafil with silodosin was not associated with a clinically significant risk of orthostatic hypotension in one clinical trial (MacDiarmid 2010). “First-dose” orthostatic hypotension may occur 4 to 8 hours after dosing; may be dose related. Patients should be cautioned about performing hazardous tasks, driving, or operating heavy machinery when starting new therapy or adjusting dosage upward. Disease-related concerns:

Hepatic impairment

Use with caution in patients with mild-to-moderate hepatic impairment; contraindicated with severe impairment; not studied.

Prostate cancer

It is recommended to rule out prostatic carcinoma before beginning therapy.

Renal impairment

Use with caution in patients with moderate renal impairment; dosage adjustment recommended. Contraindicated in patients with severe impairment (CrCl Concurrent drug therapy issues:

High potential for interactions

Contraindicated in patients on strong CYP3A4 inhibitors. Special populations:

Elderly

Use with caution in the elderly; risk of orthostatic hypotension increases with increasing age. Patients ≥65 years of age experienced an incidence of up to 5% in clinical trials.

Females

Not indicated for use in women.

Pediatric

Not indicated for use in children. Other warnings/precautions:

Antihypertensive use

Not intended for use as an antihypertensive drug.

Pregnancy & Lactation

Pregnancy

FDA category B Teratogenic

Teratogenic effects were not observed in animal studies; however, silodosin is not approved for use in women.

Monitoring

Clinical pearl	Blood pressure; urinary symptoms

Chemistry & Properties

Formula	C25H32F3N3O4
Molecular weight	495.54 g/mol
IUPAC name	1-(3-hydroxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl]-2,3-dihydroindole-7-carboxamide
CAS	160970-54-7
PubChem CID	5312125
InChIKey	`PNCPYILNMDWPEY-QGZVFWFLSA-N`
logP	3.07 (XLogP 3.6)
Polar surface area	97.05 Å²
H-bond acceptors / donors	6 / 3
Drug-likeness (QED)	0.37
Lipinski violations	0

SMILES

C[C@H](Cc1cc2c(c(C(N)=O)c1)N(CCCO)CC2)NCCOc1ccccc1OCC(F)(F)F

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	1.451 h
Volume of distribution	0.618 L/kg
Protein binding	96.5%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Inhibitor	—
CYP2B6	Inhibitor	—
CYP2C8	Inhibitor	—
CYP2D6	Inhibitor	—
CYP2D6	Substrate	—
CYP3A4	Inhibitor	—
CYP3A4	Substrate	—

Transporters

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

Drug–drug interactions (96, DDInter)

Interacting drug	Severity	Management
Ceritinib	major
Clarithromycin	major
Cobicistat	major
Idelalisib	major
Ketoconazole	major
Alimemazine	moderate
Alpelisib	moderate
Amifostine	moderate
Aminoglutethimide	moderate
Apalutamide	moderate
Aprepitant	moderate
Bexarotene	moderate
Bicalutamide	moderate
Brigatinib	moderate
Brimonidine (ophthalmic)	moderate
Brimonidine (topical)	moderate
Bupropion	moderate
Cabozantinib	moderate
Canagliflozin	moderate
Chloramphenicol	moderate
Chlorphenesin	moderate
Cimetidine	moderate
Clotrimazole	moderate
Codeine	moderate
Crizotinib	moderate
Cyclosporine	moderate
Dabrafenib	moderate
Dapagliflozin	moderate
Dasatinib	moderate
Deferasirox	moderate
Dexamethasone	moderate
Diphenhydramine	moderate
Doxepin	moderate
Doxepin (topical)	moderate
Dronabinol	moderate
Eliglustat	moderate
Empagliflozin	moderate
Encorafenib	moderate
Entrectinib	moderate
Enzalutamide	moderate

Showing 40 of 96.

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
SILDARIN 4	Capsule 4 mg	30 cap	Reda Jardaneh Drug Store	8.860