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  • CLASSES

    Alpha-Blockers

    DEA CLASS

    Rx

    DESCRIPTION

    Highly selective, oral alpha-1 blocker
    Used for benign prostatic hyperplasia (BPH) in men; as effective as tamsulosin for improving BPH symptoms
    Abnormal ejaculation is more common with silodosin than tamsulosin

    COMMON BRAND NAMES

    Rapaflo

    HOW SUPPLIED

    Rapaflo/Silodosin Oral Cap: 4mg, 8mg

    DOSAGE & INDICATIONS

    For the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH).
    Oral dosage
    Adults

    8 mg PO once daily with a meal.

    MAXIMUM DOSAGE

    Adults

    8 mg/day PO.

    Geriatric

    8 mg/day PO.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Mild to moderate hepatic impairment (Child Pugh A and B): No dosage adjustment is needed.
    Severe hepatic impairment (Child-Pugh C, score 10 or higher): Contraindicated.

    Renal Impairment

    CrCl 50 mL/minute or more: No dosage adjustment is needed.
    CrCl 30 to 49 mL/minute: 4 mg PO once daily.
    CrCl less than 30 mL/minute: Contraindicated.

    ADMINISTRATION

    Oral Administration

    Administer silodosin with a meal, at about the same time every day.

    Oral Solid Formulations

    Swallow the capsule intact; do not chew or crush.
    Alternatively, the capsule may be opened and the entire contents sprinkled over 1 tablespoonful (15 mL) of applesauce; do NOT sprinkle contents over hot applesauce or any other food or beverage. Do not subdivide capsule contents. The dose should be swallowed immediately (within 5 minutes) without chewing and followed by an 8 ounce (240 mL) glass of cool water.

    STORAGE

    Rapaflo:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Silodosin is contraindicated in patients with a hypersensitivity to the drug or any of the formulation ingredients.

    Prostate cancer

    Prostate cancer and benign prostatic hyperplasia (BPH) cause many of the same symptoms, and frequently, they coexist. Patients should be evaluated prior to starting silodosin therapy to rule out the presence of prostate cancer.

    Hypotension, orthostatic hypotension, syncope

    Postural hypotension, with or without symptoms (e.g., dizziness) may develop when beginning silodosin treatment. As with other alpha-blockers, there is potential for syncope. Silodosin should be used cautiously in patients with a history of orthostatic hypotension. Patients with a history of low blood pressure, renal dysfunction, taking antihypertensive medicines, and the elderly should be monitored carefully for exaggerated hypotensive effects (e.g., first-dose effect).

    Driving or operating machinery

    Symptoms of orthostasis may occur during treatment with silodosin, particularly during initiation of therapy. Advise patients about the possible occurrence of symptoms related to postural hypotension (such as dizziness), and caution patients about driving or operating machinery, or performing other hazardous tasks until they know how silodosin will affect them. This is especially important for those with low blood pressure or who are taking antihypertensive medications.

    Renal failure, renal impairment

    Silodosin is contraindicated in patients with severe renal impairment with a creatinine clearance (CrCl) less than 30 mL/minute, including renal failure. No dosage adjustment is needed for those with mild impairment (50 to 80 mL/minute). Dosage reduction is recommended for patients with moderate renal impairment (CrCl 30 to 49 mL/minute). Patients with moderate renal impairment should also be monitored carefully for exaggerated hypotensive effects (e.g., first-dose effect). During clinical trials, the incidences of orthostatic hypotension and dizziness were greater in those with moderate renal impairment than those with mild impairment or normal renal function.

    Hepatic disease

    Silodosin is contraindicated for use in patients with severe hepatic disease (Child-Pugh score 10 or more), due to lack of testing in this population. No dosage adjustments are needed in those with mild to moderate hepatic disease.

    Ocular surgery

    Patients planning cataract ocular surgery should be told to inform their ophthalmologist that they are taking silodosin. Intraoperative Floppy Iris Syndrome has been observed during cataract surgery in some patients on alpha-1 blockers or previously treated with alpha-1 blockers. This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents; progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs; and potential prolapse of the iris toward the phacoemulsification incisions.

    Priapism

    Rarely, silodosin, like other alpha-1 blockers, has been associated with priapism (persistent painful penile erection unrelated to sexual activity) in men. Priapism, if not treated promptly, can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention.

    Infertility

    Counsel patients that the most common side effect seen with silodosin use in men is an orgasm with reduced or no semen. This side effect does not pose a safety concern and is reversible with discontinuation of the product; however, this side effect may affect fertility. Based on data from animal studies, treatment with silodosin may be associated with male infertility. Male rats receiving silodosin for 15 days at doses approximately 2-times the maximum recommended human dose (MRHD) experienced a reduction in fertility. This decrease in fertility was reversible after a 2-week recovery period. Additionally, decreased sperm viability and sperm counts were observed in rats who received doses 65-times the MRHD for 1 month. A histopathological examination of infertile male rats showed changes to the testes and epididymides at doses approximately 30-times the MRHD. The clinical relevance of these findings is unknown.

    Geriatric

    The risk for orthostatic hypotension appears to be higher in geriatric patients receiving silodosin compared to younger adult men. During clinical trials, geriatric adults experienced a higher incidence of orthostatic hypotension compared to patients under 65 years of age. The older adult should be monitored carefully for exaggerated hypotensive effects (e.g., first-dose effect). The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to the OBRA guidelines, assessment of the underlying causes and identification of the type/category of urinary incontinence needs to be documented prior to or soon after the time of initiating treatment with a urinary incontinence medication. Silodosin is rarely used for urinary incontinence. These medications have specific and limited indications based on the cause and categorization of incontinence. Patients should be assessed periodically for medication effects on urinary incontinence as well as lower urinary tract symptoms and treatment tolerability.

    Females, pregnancy

    Silodosin is indicated for the treatment of benign prostatic hyperplasia in men; the drug is not indicated for any use in females and therefore would not be used during pregnancy.

    Breast-feeding

    Silodosin is indicated for the treatment of benign prostatic hyperplasia in men; the drug is not indicated for any use in females and therefore would not be used during breast-feeding.

    Children, infants

    Silodosin is not indicated for use in pediatric patients less than 18 years of age; safety and efficacy have not been established in adolescents, children or infants.

    ADVERSE REACTIONS

    Severe

    angioedema / Rapid / Incidence not known

    Moderate

    ejaculation dysfunction / Delayed / 22.3-28.1
    urinary incontinence / Early / 0-6.3
    orthostatic hypotension / Delayed / 2.6-2.6
    priapism / Early / Incidence not known
    jaundice / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    floppy iris syndrome / Delayed / Incidence not known

    Mild

    dizziness / Early / 3.2-3.2
    diarrhea / Early / 2.6-2.6
    headache / Early / 2.4-2.4
    pharyngitis / Delayed / 2.4-2.4
    nasal congestion / Early / 2.1-2.1
    abdominal pain / Early / 1.0-2.0
    insomnia / Early / 1.0-2.0
    asthenia / Delayed / 1.0-2.0
    rhinorrhea / Early / 1.0-2.0
    sinusitis / Delayed / 1.0-2.0
    syncope / Early / Incidence not known
    rash / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    purpura / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Alfuzosin: (Contraindicated) The pharmacokinetic and pharmacodynamic interactions between alfuzosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects, therefore, alfuzosin should not be administered in combination with other alpha-blockers.
    Aliskiren: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Aliskiren; Amlodipine: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Aliskiren; Valsartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Alpha-blockers: (Major) Silodosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between silodosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
    Ambrisentan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Amiloride: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Amlodipine: (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Amlodipine; Atorvastatin: (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Amlodipine; Benazepril: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Amlodipine; Celecoxib: (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Amlodipine; Olmesartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Amlodipine; Valsartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. Clarithromycin inhibits CYP3A4 and may cause significant increases in silodosin plasma concentrations. Concurrent use is contraindicated.
    Amprenavir: (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
    Angiotensin II receptor antagonists: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Angiotensin-converting enzyme inhibitors: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Aprepitant, Fosaprepitant: (Moderate) Use caution if silodosin and aprepitant, fosaprepitant are used concurrently and monitor for an increase in silodosin-related adverse effects for several days after administration of a multi-day aprepitant regimen. Silodosin is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of silodosin. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Atazanavir: (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
    Atazanavir; Cobicistat: (Contraindicated) Concurrent use of silodosin and cobicistat is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Cobicistat is a strong inhibitor of CYP3A4 and a P-glycoprotein (P-gp) inhibitor. Silodosin is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold. (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
    Atenolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Atenolol; Chlorthalidone: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Avanafil: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on silodosin therapy before initiating therapy with the lowest dose of avanafil. Conversely, patients already receiving an optimized dose of avanafil should be started on the lowest dose of silodosin; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of avanafil and silodosin.
    Azilsartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Azilsartan; Chlorthalidone: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Benazepril: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Bendroflumethiazide; Nadolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Berotralstat: (Major) Coadministration of silodosin and berotralstat is not recommended due to the potential for increased silodosin exposure. Silodosin is a CYP3A4 and P-gp substrate; berotralstat is a P-gp and moderate CYP3A4 inhibitor.
    Beta-adrenergic blockers: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Betaxolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Bisoprolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Boceprevir: (Contraindicated) The concurrent use of silodosin and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Silodosin is a substrate of the drug efflux transporter P-glycoprotein (P-gp) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated silodosin plasma concentrations, which could cause adverse events such as hypotension and priapism.
    Bosentan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Brigatinib: (Moderate) Monitor for an increase in silodosin-related adverse reactions if coadministration with brigatinib is necessary. Silodosin is a substrate of P-glycoprotein (P-gp). Brigatinib inhibits P-gp in vitro and may have the potential to increase concentrations of P-gp substrates.
    Brimonidine; Timolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Bumetanide: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Cabozantinib: (Minor) Monitor for an increase in silodosin-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of silodosin may be necessary. Silodosin is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
    Candesartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Cannabidiol: (Major) Avoid coadministration of silodosin and cannabidiol due to the potential for increased silodosin exposure. In vitro data indicate that silodosin is a P-glycoprotein substrate; cannabidiol is a P-gp inhibitor.
    Capmatinib: (Moderate) Monitor for an increase in silodosin-related adverse reactions if coadministration with capmatinib is necessary. Silodosin is a P-glycoprotein (P-gp) substrate and capmatinib is a P-gp inhibitor. Concomitant use may increase silodosin exposure.
    Captopril: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Carteolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Carvedilol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Central-acting adrenergic agents: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Ceritinib: (Contraindicated) Concurrent use of silodosin and ceritinib is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Silodosin is extensively metabolized by CYP3A4 and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold.
    Chloramphenicol: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as chloramphenicol may cause significant increases in silodosin plasma concentrations.
    Chlorothiazide: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Chlorthalidone: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Chlorthalidone; Clonidine: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Clarithromycin: (Contraindicated) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. Clarithromycin inhibits CYP3A4 and may cause significant increases in silodosin plasma concentrations. Concurrent use is contraindicated.
    Clonidine: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Cobicistat: (Contraindicated) Concurrent use of silodosin and cobicistat is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Cobicistat is a strong inhibitor of CYP3A4 and a P-glycoprotein (P-gp) inhibitor. Silodosin is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold.
    Conivaptan: (Major) Avoid coadministration of silodosin and conivaptan due to the potential for increased silodosin exposure. Silodosin is a CYP3A and P-gp substrate; conivaptan is a moderate CYP3A and P-gp inhibitor.
    Crizotinib: (Moderate) Monitor for silodosin-related adverse reactions if coadministration with crizotinib is necessary. Silodosin is a substrate of CYP3A4. Crizotinib is a moderate CYP3A inhibitor. The effect of moderate CYP3A4 inhibitors has not been evaluated; however, plasma concentrations of silodosin may increase based on its interaction with strong CYP3A4 inhibitors.
    Cyclosporine: (Major) In vitro data indicate that silodosin is a P-glycoprotein substrate. The manufacturer of silodosin recommends against concurrent use of silodosin and potent P-gp inhibitors such as cyclosporine.
    Daclatasvir: (Moderate) Systemic exposure of silodosin, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of silodosin; monitor patients for potential adverse effects.
    Danazol: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4, such as danazol, may cause significant increases in silodosin plasma concentrations.
    Darunavir: (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
    Darunavir; Cobicistat: (Contraindicated) Concurrent use of silodosin and cobicistat is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Cobicistat is a strong inhibitor of CYP3A4 and a P-glycoprotein (P-gp) inhibitor. Silodosin is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold. (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Concurrent use of silodosin and cobicistat is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Cobicistat is a strong inhibitor of CYP3A4 and a P-glycoprotein (P-gp) inhibitor. Silodosin is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold. (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) Coadministration of silodosin and ombitasvir; paritaprevir; ritonavir or dasabuvir; ombitasvir; paritaprevir; ritonavir is contraindicated. Silodosin is extensively metabolized by CYP3A4 and the manufacturer contraindicates concurrent use with potent CYP3A4 inhibitors, including ritonavir. Also of note, silodosin is a P-glycoprotein (P-gp) substrate and ritonavir and paritaprevir are P-gp inhibitors. Coadministration would be expected to cause significant increases in silodosin plasma concentrations. (Contraindicated) Concurrent use of silodosin and ritonavir is contraindicated. Silodosin is extensively metabolized by CYP3A4; ritonavir is a potent inhibitor of this enzyme. Also of note, silodosin is a P-glycoprotein (P-gp) substrate and ritonavir is a P-gp inhibitor. Coadministration may cause significant increases in silodosin plasma concentrations, potentially resulting in adverse events.
    Delavirdine: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as delavirdine may cause significant increases in silodosin plasma concentrations.
    Diazoxide: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Diltiazem: (Moderate) Monitor for silodosin-related adverse effects if coadministered with diltiazem; silodosin exposure may be increased. In addition the incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials. Diltiazem is a moderate CYP3A4 inhibitor; silodosin is a CYP3A4 substrate. Although the effect of moderate CYP3A4 inhibitors on silodosin exposure has not been studied, coadministration of a strong inhibitor increased the silodosin AUC by 2.9-fold to 3.2-fold.
    Dorzolamide; Timolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Doxazosin: (Major) Silodosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between silodosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
    Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A; dronedarone also inhibits P-gp. Silodosin is a substrate for CYP3A4 and P-gp. The concomitant administration of dronedarone with CYP3A4 and P-gp substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
    Dutasteride; Tamsulosin: (Major) The pharmacodynamic effects of coadministration of silodosin and other alpha-blockers has not been studied. Additive effects on blood pressure or an increased incidence of adverse reactions common to alpha-blocker treatment is possible. Therefore, combined use of silodosin and other alpha-blockers is not recommended.
    Duvelisib: (Moderate) Monitor for silodosin-related adverse reactions if coadministration with duvelisib is necessary. Coadministration may increase the exposure of silodosin. Silodosin is a substrate of CYP3A4 and duvelisib is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibitors has not been evaluated; however, plasma concentrations of silodosin may increase based on its interaction with strong CYP3A4 inhibitors.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Concurrent use of silodosin and cobicistat is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Cobicistat is a strong inhibitor of CYP3A4 and a P-glycoprotein (P-gp) inhibitor. Silodosin is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Concurrent use of silodosin and cobicistat is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Cobicistat is a strong inhibitor of CYP3A4 and a P-glycoprotein (P-gp) inhibitor. Silodosin is a CYP3A4 and P-gp substrate. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold.
    Enalapril, Enalaprilat: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Enalapril; Felodipine: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) Monitor for adverse effects if silodosin is coadministered with felodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Enasidenib: (Major) Avoid coadministration of silodosin and enasidenib due to the potential for increased silodosin exposure. In vitro data indicate that silodosin is a P-glycoprotein substrate; enasidenib is a P-gp inhibitor.
    Eplerenone: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Epoprostenol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Eprosartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Erythromycin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, drugs that inhibit CYP3A4 and P-gp such as erythromycin may cause significant increases in silodosin plasma concentrations.
    Erythromycin; Sulfisoxazole: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, drugs that inhibit CYP3A4 and P-gp such as erythromycin may cause significant increases in silodosin plasma concentrations.
    Esmolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Ethacrynic Acid: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Ethanol: (Moderate) Use caution when combining silodosin with alcohol-containing beverages. Alcohol-containing beverages may increase the effects of silodosin, which may lower the blood pressure. Silodosin ordinarily does not have much effect on blood pressure and the manufacturer does not make any formal advice on alcohol use, However, published literature suggests that ethanol potentiates antihypertensive effects of alpha blockers, including selective ones like silodosin. Some experts advise that the patient to limit alcohol use while using this drug.
    Etravirine: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and silodosin is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
    Fedratinib: (Moderate) Monitor for silodosin-related adverse reactions if coadministration with fedratinib is necessary. Silodosin is a substrate of CYP3A4. Fedratinib is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibitors has not been evaluated; however, plasma concentrations of silodosin may increase based on its interaction with strong CYP3A4 inhibitors.
    Felodipine: (Moderate) Monitor for adverse effects if silodosin is coadministered with felodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Fenoldopam: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Fluconazole: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as fluconazole may cause significant increases in silodosin plasma concentrations. KMD-3213G, the primary metabolite of silodosin, is formed from direct conjugation of silodosin by UDP-glucuronosyltransferase 2B7 (UBT2B7). In theory, coadministration of silodosin with UBT2B7 inhibitors such as fluconazole may increase silodosin plasma concentrations.
    Fluvoxamine: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as fluvoxamine may cause significant increases in silodosin plasma concentrations.
    Fosamprenavir: (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
    Fosinopril: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Furosemide: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and silodosin as coadministration may increase serum concentrations of silodosin and increase the risk of adverse effects. Silodosin is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and silodosin as coadministration may increase serum concentrations of silodosin and increase the risk of adverse effects. Silodosin is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
    Grapefruit juice: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. Grapefruit juice contains compounds that inhibit the activity of P-450 enzymes in cells lining the intestinal wall. In theory, grapefruit juice may cause significant increases in silodosin plasma concentrations.
    Guanabenz: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Guanfacine: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Hydralazine: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Idelalisib: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with silodosin, a CYP3A substrate, as silodosin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Iloprost: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Imatinib: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as imatinib, STI-571 may cause significant increases in silodosin plasma concentrations.
    Indapamide: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Indinavir: (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
    Irbesartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Isavuconazonium: (Moderate) The plasma concentrations of silodosin may be elevated when administered concurrently with isavuconazonium. Clinical monitoring for adverse effects, such as hypotension or dizziness, is recommended during coadministration. Silodosin is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp.
    Isradipine: (Moderate) Monitor for adverse effects if silodosin is coadministered with isradipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Istradefylline: (Moderate) Monitor for silodosin-related adverse reactions if coadministration with istradefylline is necessary as concurrent use may increase silodosin exposure. Silodosin is a P-gp substrate; istradefylline is a P-gp inhibitor.
    Itraconazole: (Contraindicated) Silodosin is contraindicated for use during itraconazole therapy and is not recommended for 2 weeks after completion of itraconazole therapy. Concurrent use may significantly increase silodosin plasma concentrations. Silodosin is extensively metabolized by CYP3A4; itraconazole is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of silodosin by 3.8-fold and 3.2-fold, respectively.
    Ketoconazole: (Contraindicated) Concurrent use of silodosin and ketoconazole is contraindicated. Silodosin is extensively metabolized by CYP3A4 and is a P-glycoprotein (P-gp) substrate; ketoconazole inhibits CYP3A4 and P-gp. Coadministration may cause significant increases in silodosin plasma concentrations. In one study, coadministration resulted in a 3.8-fold increase in maximum plasma silodosin concentrations and a 3.2-fold increase in silodosin AUC.
    Labetalol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. Clarithromycin inhibits CYP3A4 and may cause significant increases in silodosin plasma concentrations. Concurrent use is contraindicated.
    Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of silodosin-associated adverse reactions is advised with concomitant administration of ledipasvir. Silodosin is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase silodosin plasma concentrations.
    Lefamulin: (Moderate) Monitor for silodosin-related adverse reactions if coadministration with oral lefamulin is necessary. Silodosin is a substrate of CYP3A4. Oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. The effect of moderate CYP3A4 inhibitors has not been evaluated; however, plasma concentrations of silodosin may increase based on its interaction with strong CYP3A4 inhibitors.
    Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of silodosin; monitor for potential reduction in efficacy. Silodosin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of silodosin; monitor for potential reduction in efficacy. Silodosin is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
    Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of silodosin may occur if given with letermovir; exercise caution and monitor patients for adverse events if these drugs are given together. Coadministration is contraindicated in patients who are also receiving treatment with cyclosporine, because the magnitude of this interaction may be amplified. Silodosin is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent administration with a strong CYP3A4 inhibitor caused a 3.8-fold increase in the maximum plasma silodosin concentration (Cmax) and 3.2-fold increase in silodosin exposure (AUC). The effect of moderate CYP3A4 inhibitors on the pharmacokinetics of silodosin has not been evaluated.
    Levamlodipine: (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Levobetaxolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Levobunolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Lisinopril: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Lonafarnib: (Contraindicated) Concurrent use of silodosin and lonafarnib is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Silodosin is extensively metabolized by CYP3A4 and is a P-gp substrate; lonafarnib is a strong CYP3A4 inhibitor and a P-gp inhibitor. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold.
    Loop diuretics: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Lopinavir; Ritonavir: (Contraindicated) Concurrent use of silodosin and ritonavir is contraindicated. Silodosin is extensively metabolized by CYP3A4; ritonavir is a potent inhibitor of this enzyme. Also of note, silodosin is a P-glycoprotein (P-gp) substrate and ritonavir is a P-gp inhibitor. Coadministration may cause significant increases in silodosin plasma concentrations, potentially resulting in adverse events.
    Losartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Losartan; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Mecamylamine: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Methyclothiazide: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Methyldopa: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Metolazone: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Metoprolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Mifepristone: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4 and is a P-glycoprotein (P-gp) substrate. In theory, drugs that inhibit CYP3A4 and P-gp such as mifepristone may cause significant increases in silodosin plasma concentrations.
    Minoxidil: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Mitotane: (Major) Use caution if mitotane and silodosin are used concomitantly, and monitor for decreased efficacy of silodosin and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and silodosin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of silodosin.
    Moexipril: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Nadolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Nebivolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Nebivolol; Valsartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Nefazodone: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as nefazodone may cause significant increases in silodosin plasma concentrations.
    Nelfinavir: (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
    Nicardipine: (Moderate) Monitor for adverse effects if silodosin is coadministered with nicardipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Nifedipine: (Moderate) Monitor for adverse effects if silodosin is coadministered with nifedipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Nimodipine: (Moderate) Monitor for adverse effects if silodosin is coadministered with nimodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Nisoldipine: (Moderate) Monitor for adverse effects if silodosin is coadministered with nisoldipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Nitroprusside: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Olmesartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Ombitasvir; Paritaprevir; Ritonavir: (Contraindicated) Coadministration of silodosin and ombitasvir; paritaprevir; ritonavir or dasabuvir; ombitasvir; paritaprevir; ritonavir is contraindicated. Silodosin is extensively metabolized by CYP3A4 and the manufacturer contraindicates concurrent use with potent CYP3A4 inhibitors, including ritonavir. Also of note, silodosin is a P-glycoprotein (P-gp) substrate and ritonavir and paritaprevir are P-gp inhibitors. Coadministration would be expected to cause significant increases in silodosin plasma concentrations. (Contraindicated) Concurrent use of silodosin and ritonavir is contraindicated. Silodosin is extensively metabolized by CYP3A4; ritonavir is a potent inhibitor of this enzyme. Also of note, silodosin is a P-glycoprotein (P-gp) substrate and ritonavir is a P-gp inhibitor. Coadministration may cause significant increases in silodosin plasma concentrations, potentially resulting in adverse events.
    Oritavancin: (Moderate) Silodosin is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of silodosin may be reduced if these drugs are administered concurrently.
    Penbutolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Perindopril: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Perindopril; Amlodipine: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Phenoxybenzamine: (Major) Silodosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between silodosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
    Phentolamine: (Major) Silodosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between silodosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
    Pindolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Posaconazole: (Major) Posaconazole and silodosin should be coadministered with caution due to an increased potential for adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of silodosin. Further, both silodosin and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may cause alterations in the plasma concentrations of both posaconazole and silodosin, ultimately resulting in an increased risk of adverse events.
    Potassium-sparing diuretics: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Prazosin: (Major) Silodosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between silodosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
    Probenecid: (Major) KMD-3213G, the primary metabolite of silodosin, is formed from direct conjugation of silodosin by UDP-glucuronosyltransferase 2B7 (UBT2B7). In theory, coadministration of silodosin with UBT2B7 inhibitors such as probenecid may increase silodosin plasma concentrations.
    Probenecid; Colchicine: (Major) KMD-3213G, the primary metabolite of silodosin, is formed from direct conjugation of silodosin by UDP-glucuronosyltransferase 2B7 (UBT2B7). In theory, coadministration of silodosin with UBT2B7 inhibitors such as probenecid may increase silodosin plasma concentrations.
    Propranolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Quinapril: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Ramipril: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Reserpine: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Ribociclib: (Contraindicated) Concurrent use of silodosin and ribociclib is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Silodosin is extensively metabolized by CYP3A4 and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold.
    Ribociclib; Letrozole: (Contraindicated) Concurrent use of silodosin and ribociclib is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Silodosin is extensively metabolized by CYP3A4 and ribociclib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold.
    Ritonavir: (Contraindicated) Concurrent use of silodosin and ritonavir is contraindicated. Silodosin is extensively metabolized by CYP3A4; ritonavir is a potent inhibitor of this enzyme. Also of note, silodosin is a P-glycoprotein (P-gp) substrate and ritonavir is a P-gp inhibitor. Coadministration may cause significant increases in silodosin plasma concentrations, potentially resulting in adverse events.
    Sacubitril; Valsartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Saquinavir: (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
    Sildenafil: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on silodosin therapy before initiating therapy with the lowest dose of sildenafil. Conversely, patients already receiving an optimized dose of sildenafil should be started on the lowest dose of silodosin; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of sildenafil and silodosin.
    Simeprevir: (Moderate) Simeprevir, a P-glycoprotein (P-gp) inhibitor and a mild intestinal CYP3A4 inhibitor, may increase the side effects of silodosin, which is a P-gp and CYP3A4 substrate. Monitor patients for adverse effects of silodosin, such as dizziness and hypotension.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of silodosin, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently.
    Sotorasib: (Major) Avoid coadministration of silodosin and sotorasib due to the potential for increased silodosin exposure. In vitro data indicate that silodosin is a P-glycoprotein substrate; sotorasib is a P-gp inhibitor.
    Spironolactone: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Tadalafil: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on silodosin therapy before initiating therapy with the lowest recommended dose of tadalafil. Conversely, patients already receiving an optimized dose of tadalafil should be started on the lowest dose of silodosin; increases in the alpha-blocker dose should be done in a stepwise fashion. When tadalafil is used for benign prostatic hypertrophy (BPH), discontinue silodosin therapy at least 1 day prior to initiating tadalafil therapy. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of tadalafil and silodosin.
    Tamsulosin: (Major) The pharmacodynamic effects of coadministration of silodosin and other alpha-blockers has not been studied. Additive effects on blood pressure or an increased incidence of adverse reactions common to alpha-blocker treatment is possible. Therefore, combined use of silodosin and other alpha-blockers is not recommended.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering silodosin with telaprevir due to an increased potential for silodosin-related adverse events. If silodosin dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of silodosin. Silodosin is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; telaprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated silodosin plasma concentrations.
    Telithromycin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as telithromycin may cause significant increases in silodosin plasma concentrations.
    Telmisartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Telmisartan; Amlodipine: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) Monitor for adverse effects if silodosin is coadministered with amlodipine. The incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials.
    Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Temsirolimus: (Moderate) Monitor for an increase in silodosin-related adverse reactions if coadministration with temsirolimus is necessary. Silodosin is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of silodosin.
    Tepotinib: (Major) Avoid coadministration of silodosin and tepotinib due to the potential for increased silodosin exposure. In vitro data indicate that silodosin is a P-glycoprotein substrate; tepotinib is a P-gp inhibitor.
    Terazosin: (Major) Silodosin should not be administered in combination with other alpha-blockers. The pharmacokinetic and pharmacodynamic interactions between silodosin and other alpha-blockers (used for high blood pressure or for benign prostatic hyperplasia) have not been determined. However, interactions or side effects (dizziness, hypotension, syncope, etc.) may be expected from the duplication of pharmacologic effects.
    Thiazide diuretics: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Timolol: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. In addition, increased concentrations of silodosin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and silodosin is a P-gp substrate.
    Tipranavir: (Major) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as anti-retroviral protease inhibitors may cause significant increases in silodosin plasma concentrations.
    Torsemide: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Trandolapril: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Trandolapril; Verapamil: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) Monitor for silodosin-related adverse effects if coadministered with verapamil; silodosin exposure may be increased. In addition the incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials. Verapamil is a moderate CYP3A4 inhibitor and P-gp inhibitor; silodosin is a CYP3A4 and P-gp substrate. Although the effect of moderate CYP3A4 inhibitors on silodosin exposure has not been studied, coadministration of a combined P-gp/strong CYP3A4 inhibitor increased the silodosin AUC by 2.9-fold to 3.2-fold.
    Treprostinil: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Triamterene: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Tucatinib: (Contraindicated) Concurrent use of silodosin and tucatinib is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Silodosin is extensively metabolized by CYP3A4 and is a P-glycoprotein (P-gp) substrate; tucatinib is a strong CYP3A4 inhibitor and P-gp inhibitor. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold.
    Valproic Acid, Divalproex Sodium: (Major) KMD-3213G, the primary metabolite of silodosin, is formed from direct conjugation of silodosin by UDP-glucuronosyltransferase 2B7 (UBT2B7). In theory, coadministration of silodosin with UBT2B7 inhibitors such as valproic acid may increase silodosin plasma concentrations.
    Valsartan: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents. (Moderate) During clinical trials with silodosin, the incidence of dizziness and orthostatic hypotension was higher in patients receiving concomitant antihypertensive treatment. Thus, caution is advisable when silodosin is administered with antihypertensive agents.
    Vardenafil: (Moderate) Due to the potential for symptomatic hypotension, patients should be stable on silodosin therapy before initiating therapy with the lowest dose of vardenafil. Conversely, patients already receiving an optimized dose of vardenafil should be started on the lowest dose of silodosin; increases in the alpha-blocker dose should be done in a stepwise fashion. Other variables, such as intravascular volume depletion, concurrent antihypertensive therapy, or evidence of hemodynamic instability with alpha-blocker monotherapy, may affect the safety of concomitant use of vardenafil and silodosin.
    Vemurafenib: (Moderate) Concomitant use of vemurafenib and silodosin may result in altered concentrations of silodosin. Vemurafenib is an inhibitor of P-glycoprotein (PGP) and an inducer of CYP3A4. Silodosin is a substrate of PGP and CYP3A4. Use caution and monitor patients for toxicity and efficacy.
    Verapamil: (Moderate) Monitor for silodosin-related adverse effects if coadministered with verapamil; silodosin exposure may be increased. In addition the incidence of dizziness and orthostatic hypotension were increased in patients also receiving antihypertensive medications in clinical trials. Verapamil is a moderate CYP3A4 inhibitor and P-gp inhibitor; silodosin is a CYP3A4 and P-gp substrate. Although the effect of moderate CYP3A4 inhibitors on silodosin exposure has not been studied, coadministration of a combined P-gp/strong CYP3A4 inhibitor increased the silodosin AUC by 2.9-fold to 3.2-fold.
    Voclosporin: (Major) Avoid coadministration of silodosin and voclosporin due to the potential for increased silodosin exposure. In vitro data indicate that silodosin is a P-glycoprotein substrate; voclosporin is a P-gp inhibitor.
    Voriconazole: (Contraindicated) Concurrent use of silodosin and voriconazole is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Silodosin is extensively metabolized by CYP3A4 and voriconazole is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold.
    Zafirlukast: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as zafirlukast may cause significant increases in silodosin plasma concentrations.
    Zileuton: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as zileuton may cause significant increases in silodosin plasma concentrations.

    PREGNANCY AND LACTATION

    Pregnancy

    Silodosin is indicated for the treatment of benign prostatic hyperplasia in men; the drug is not indicated for any use in females and therefore would not be used during breast-feeding.

    MECHANISM OF ACTION

    Silodosin is a selective antagonist at post-synaptic alpha-1a receptors. Three subtypes of alpha-1 receptors have been identified: alpha-1A, alpha-1B, and alpha-1D. Alpha-1A receptors mediate human prostatic smooth muscle contraction whereas alpha-1B and alpha-1D receptors are involved in vascular smooth muscle contraction. Both alpha-1A and alpha-1B receptors exist in the prostate; however, approximately 70% of the alpha receptors in the human prostate are of the alpha-1A subtype. Blockade of these receptors by silodosin causes smooth muscles in the bladder base, bladder neck, prostate capsule, and prostatic urethra to relax thereby improving urine flow rate and reducing symptoms of BPH. The affinity of silodosin for alpha-1A receptors is 583-fold greater than for alpha-1B receptors and is 56-fold greater than for alpha-1D receptors. Because the binding affinity for alpha-1B receptors is significantly lower, there is a decreased potential for vascular effects such as hypotension. Compared to tamsulosin, silodosin is 38-times more selective for alpha-1A versus alpha-1B receptors.

    PHARMACOKINETICS

    Silodosin is administered orally. The volume of distribution is 49.5 L; the drug is approximately 97% protein bound. Silodosin undergoes extensive metabolism through glucuronidation, alcohol and aldehyde dehydrogenase, and CYP3A4 pathways. The primary metabolite is KMD-3213G, which is formed from direct conjugation of silodosin by UDP-glucuronosyltransferase 2B7 (UBT2B7). In vitro data indicate that KMD-3213G is an active metabolite with a half-life of approximately 24 hours. Plasma levels of KMD-3213G are 4-times greater than those of silodosin. The second major metabolite, KMD-3293, reaches similar plasma levels as silodosin, although KMD-3293 is not thought to significantly contribute to the pharmacologic actions of the drug. The elimination half-life of silodosin is 13.3 +/- 8.07 hours. After 10 days, about 33.5% and 54.9% of a dose are recovered in the urine and feces, respectively.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)
    Silodosin is extensively metabolized by CYP3A4 and is a P-gp substrate. In a clinical metabolic inhibition study, a 3.8-fold increase in silodosin maximum plasma concentrations and 3.2-fold increase in silodosin exposure were observed with concurrent administration of a strong CYP3A4 inhibitor; the concurrent use of silodosin with strong CYP3A4 inhibitors is contraindicated. The concurrent use of P-gp inhibitors should be avoided, and moderate CYP3A4 inhibitors should be used with caution. In vitro data indicate that it does not inhibit CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4 and does not induce CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4, or P-gp.

    Oral Route

    Following oral administration, the absolute bioavailability of silodosin is approximately 32%; the mean time to maximum plasma concentration is roughly 2.6 hours. The maximum effect of food (i.e., co-administration with a high fat, high calorie meal) on silodosin pharmacokinetics was not evaluated. The effect of a moderate fat, moderate calorie meal was variable and decreased silodosin Cmax by approximately 18 to 43% and AUC by 4 to 49% across three different studies. In a separate study, the relative bioavailability of the contents of an 8 mg silodosin capsule sprinkled over cool applesauce was compared to the contents administered as an intact capsule. Based on AUC and Cmax, administration over the applesauce was bioequivalent to the intact capsule. To minimize variability, silodosin should be administered with a meal.