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  • CLASSES

    Alpha-Blockers

    DEA CLASS

    Rx

    DESCRIPTION

    Highly selective, oral alpha-1 blocker for BPH; as effective as tamsulosin for improving BPH symptoms; abnormal ejaculation is more common with silodosin.

    COMMON BRAND NAMES

    Rapaflo

    HOW SUPPLIED

    Rapaflo Oral Cap: 4mg, 8mg

    DOSAGE & INDICATIONS

    For the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH).
    NOTE: Silodosin is not indicated for the treatment of hypertension.
    Oral dosage
    Adults

    8 mg PO once daily with a meal.

    Geriatric

    See adult dosage. Elderly patients may be more sensitive to the effects of silodosin. Adjust dosage based on clinical response.

    MAXIMUM DOSAGE

    Adults

    8 mg/day PO.

    Elderly

    8 mg/day PO.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is needed in patients with mild to moderate hepatic impairment. Silodosin is not recommended in those with severe hepatic impairment (Child-Pugh score >= 10).

    Renal Impairment

    CrCl >= 50 ml/min: No dosage adjustment is needed.
    CrCl 30—49 ml/min: 4 mg PO once daily.
    CrCl < 30 ml/min: Not recommended.

    ADMINISTRATION

    Oral Administration

    Administer with a meal.

    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 water.

    STORAGE

    Rapaflo:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

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

    Driving or operating machinery

    Symptoms of orthostasis may occur during treatment with silodosin, particularly during initiation of therapy. Therefore, patients should use caution when driving or operating machinery until they are aware of the effects of the medication.

    Hypotension, orthostatic hypotension, syncope

    Silodosin should be used cautiously in patients with hypotension, orthostatic hypotension, vertigo, or syncope. During clinical trials, the signs and symptoms of orthostasis (postural hypotension, dizziness, and vertigo) were more frequently reported in silodosin-treated patients than those receiving placebo. As with other alpha-adrenergic blocking agents, there is a potential risk of syncope and patients should be cautioned to avoid situations where injury could result if syncope occur. Patients with renal dysfunction and older patients should also be monitored carefully for exaggerated hypotensive effects (e.g., first dose effect).

    Renal disease, renal failure, renal impairment

    During therapy with silodosin, patients with mild to moderate renal impairment or renal disease should be monitored carefully for exaggerated hypotensive effects (e.g., first dose effect); silodosin is contraindicated in patients with severe renal impairment or severe renal disease (CrCl < 30 ml/min), including renal failure. During clinical trials, the incidences of orthostatic hypotension and dizziness were greater in those with moderate renal impairment than those with mild renal impairment or normal renal function. A dosage reduction is recommended for those with moderate renal impairment (CrCl 30—50 ml/min) (see Dosage).

    Geriatric

    The risk for orthostatic hypotension appears to be higher in geriatric patients receiving silodosin compared to younger adults. During clinical trials, elderly patients experienced a higher incidence of orthostatic hypotension compared to those 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.

    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.

    Hepatic disease

    Silodosin is extensively metabolized in the liver. Silodosin has not been studied in patients with severe hepatic disease (Child-Pugh score >= 10) and is therefore contraindicated in this patient population. Cautious initiation is advisable in patients with mild to moderate hepatic disease, although no dosage adjustments are needed.

    Females, pregnancy

    Silodosin is classified as FDA pregnancy risk category B. Teratogenicity was not observed in animal studies. In addition, no physical or behavioral effects in animal offspring were noted. Decreased fertility, sperm viability, and sperm count was noted in male rats; however no effect on fertility was observed in females. The clinical relevance of these findings is unknown. Human data pertaining to the risk during pregnancy is not available. It should be noted that silodosin is indicated for the treatment of benign prostatic hyperplasia in men and is not indicated for use in females.

    Children, infants, neonates

    Silodosin is not indicated for use in neonates, infants, children, or adolescents; the drug has not been evaluated in patients less than 18 years of age.

    Ocular surgery

    Patients receiving or who have previously received treatment with silodosin or other alpha-1 blockers may be at risk for intraoperative floppy iris syndrome during surgery for cataracts (ocular surgery). Intraoperative floppy iris syndrome is a small pupil syndrome variant that is characterized by 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. There does not appear to be a benefit of stopping alpha-1 blocker therapy prior to cataract surgery, but ophthalmologists should be prepared for possible modifications to their surgical technique such as the use of iris hooks, iris dilator rings, or viscoelastic substances.

    Breast-feeding

    Silodosin is indicated for the treatment of benign prostatic hyperplasia in men; the drug is not indicated for any use females and therefore would not be used during breast-feeding. No effects on the physical or behavioral development of offspring were noted when the drug was given to lactating rats at doses of up to 300 mg/kg/day; it is not known if the drug is excreted in human milk.

    Priapism

    Rarely, silodosin, like other alpha adrenergic antagonists, has been associated with priapism (persistent painful penile erection unrelated to sexual activity). 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.

    ADVERSE REACTIONS

    Severe

    angioedema / Rapid / Incidence not known

    Moderate

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

    Mild

    polydipsia / Early / 10.3-10.3
    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
    asthenia / Delayed / 1.0-2.0
    insomnia / Early / 1.0-2.0
    rhinorrhea / Early / 1.0-2.0
    sinusitis / Delayed / 1.0-2.0
    syncope / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    purpura / Delayed / Incidence not known
    rash (unspecified) / Early / 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: (Severe) 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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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) 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.
    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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    Amlodipine; Atorvastatin: (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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    Amlodipine; Hydrochlorothiazide, HCTZ; 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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    Amlodipine; Hydrochlorothiazide, HCTZ; 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. (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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    Amlodipine; 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. (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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    Amoxicillin; Clarithromycin; Lansoprazole: (Severe) 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.
    Amoxicillin; Clarithromycin; Omeprazole: (Severe) 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: (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. (Moderate) The plasma concentrations of silodosin may be significantly elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension or dizziness, is recommended during coadministration. Cobicistat is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while silodosin is a CYP3A4 and P-gp substrate.
    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.
    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.
    Azithromycin: (Moderate) Silodosin is a substrate of P-glycoprotein (P-gp) and azithromycin is a P-gp inhibitor; therefore, silodosin concentrations could be increased with coadministration. Monitor patients for increased side effects if these drugs are given together.
    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.
    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: (Severe) 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.
    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: (Moderate) Monitor for an increase in silodosin-related adverse events if concomitant use with cabozantinib is necessary, as plasma concentrations of silodosin may be increased. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and silodosin is a substrate of P-gp in vitro; the clinical relevance of this finding is unknown.
    Calcium-channel 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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.
    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: (Moderate) Monitor for an increase in silodosin-related adverse reactions if coadministration with ceritinib is necessary. Ceritinib is a CYP3A4 inhibitor and silodosin is primarily metabolized by CYP3A4. Coadministration with a strong CYP3A4 inhibitor increased the Cmax and AUC of silodosin by 3.8-fold and 3.2-fold, respectively; strong CYP3A4 inhibitors are contraindicated for use with silodosin. The effect of moderate CYP3A4 inhibitors on the pharmacokinetics of silodosin has not been evaluated. The degree of CYP3A4 inhibition by ceritinib is unknown.
    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: (Severe) 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.
    Clevidipine: (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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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: (Moderate) The plasma concentrations of silodosin may be significantly elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension or dizziness, is recommended during coadministration. Cobicistat is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while silodosin is a CYP3A4 and P-gp substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of silodosin may be significantly elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension or dizziness, is recommended during coadministration. Cobicistat is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while silodosin is a CYP3A4 and P-gp substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of silodosin may be significantly elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension or dizziness, is recommended during coadministration. Cobicistat is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while silodosin is a CYP3A4 and P-gp substrate.
    Conivaptan: (Major) Avoid coadministration of conivaptan, a CYP3A4/P-glycoprotein (P-gp) inhibitor and silodosin, a CYP3A4/P-gp substrate. Concurrent use may result in increased serum concentrations of silodosin. According to the manufacturer of conivaptan, concomitant use of conivaptan and CYP3A substrates should be avoided. Subsequent treatment with CYP3A substrates may be initiated no sooner than 1 week after completion of conivaptan therapy. Coadministration of conivaptan with other CYP3A substrates (midazolam, simvastatin, amlodipine) has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with silodosin.
    Crizotinib: (Moderate) Monitor for silodosin-related adverse reactions if coadministration with crizotinib is necessary. Silodosin is a substrate of CYP3A4 and P-glycoprotein (P-gp). Crizotinib is a moderate CYP3A4 inhibitor, and also inhibits P-gp and clinically relevant concentrations. 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. The risk of interaction is increased if the medication also inhibits P-gp.
    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.
    Dalfopristin; Quinupristin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as dalfopristin; quinupristin may cause significant increases in silodosin plasma concentrations.
    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: (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. (Moderate) The plasma concentrations of silodosin may be significantly elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension or dizziness, is recommended during coadministration. Cobicistat is a CYP3A4 and P-glycoprotein (P-gp) inhibitor, while silodosin is a CYP3A4 and P-gp substrate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Severe) 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. (Severe) 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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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) 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.
    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.
    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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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.
    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.
    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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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; 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. (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; 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. (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; 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. (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; 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. (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.
    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.
    Hydrochlorothiazide, HCTZ; 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) 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; 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. (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.
    Hydrochlorothiazide, HCTZ; 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. (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; 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. (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; 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. (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; 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. (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; 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.
    Idelalisib: (Severe) 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.
    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.
    Isoniazid, INH: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as isoniazid, INH may cause significant increases in silodosin plasma concentrations.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as isoniazid, INH may cause significant increases in silodosin plasma concentrations.
    Isoniazid, INH; Rifampin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as isoniazid, INH may cause significant increases in silodosin plasma concentrations.
    Isradipine: (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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    Itraconazole: (Severe) 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.
    Ivacaftor: (Moderate) Use caution when administering ivacaftor and silodosin concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as silodosin, can increase silodosin exposure leading to increased or prolonged therapeutic effects and adverse events.
    Ketoconazole: (Severe) 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.
    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.
    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.
    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.
    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: (Severe) 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. (Severe) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. Drugs that inhibit CYP3A4 may cause significant increases in silodosin plasma concentrations. According to the manufacturer, concurrent use of silodosin and potent inhibitors of CYP3A4, such as the ritonavir component of lopinavir; ritonavir, is contraindicated.
    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.
    Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and silodosin concurrently. Ivacaftor is an inhibitor of CYP3A and P-glycoprotein (Pgp). Co-administration of ivacaftor with CYP3A and Pgp substrates, such as silodosin, can increase silodosin exposure leading to increased or prolonged therapeutic effects and adverse events.
    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.
    Mifepristone, RU-486: (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, RU-486 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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    Nifedipine: (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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    Nimodipine: (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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    Nisoldipine: (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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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.
    Ombitasvir; Paritaprevir; Ritonavir: (Severe) 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. (Severe) 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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    Phenoxybenzamine: (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.
    Phentolamine: (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.
    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) 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.
    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.
    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.
    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.
    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: (Moderate) Use caution if coadministration of ribociclib with silodosin is necessary, as the systemic exposure of silodosin may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and silodosin is a CYP3A4 substrate. The effect of moderate CYP3A4 inhibitors on the pharmacokinetics of silodosin has not been evaluated. However, administration with strong CYP3A4 inhibitors is contraindicated due to a significant increase in exposure to silodosin. Moderate 3A4 inhibitors may also increase the exposure to silodosin and should therefore be used with caution and close monitoring for adverse events.
    Ribociclib; Letrozole: (Moderate) Use caution if coadministration of ribociclib with silodosin is necessary, as the systemic exposure of silodosin may be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a moderate CYP3A4 inhibitor and silodosin is a CYP3A4 substrate. The effect of moderate CYP3A4 inhibitors on the pharmacokinetics of silodosin has not been evaluated. However, administration with strong CYP3A4 inhibitors is contraindicated due to a significant increase in exposure to silodosin. Moderate 3A4 inhibitors may also increase the exposure to silodosin and should therefore be used with caution and close monitoring for adverse events.
    Ritonavir: (Severe) 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.
    Sapropterin: (Moderate) Caution is advised with the concomitant use of sapropterin and silodosin as coadministration may result in increased systemic exposure of silodosin. Silodosin is a substrate for the drug transporter P-glycoprotein (P-gp); in vitro data show that sapropterin may inhibit P-gp. If these drugs are used together, closely monitor for increased side effects of silodosin.
    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: (Major) Patients should be stable on alpha-blocker therapy before initiating therapy with sildenafil. Conversely, patients already receiving an optimized dose of a PDE5 inhibitor should be started on the lowest dose of an alpha-blocker; increases in the alpha-blocker dose should be done in a stepwise fashion. Using sildenafil and alpha-blockers together may reduce blood pressure significantly in some patients and may lead to symptomatic hypotension. Sildenafil doses greater than 25 mg should not be taken within 4 hours of taking alpha-blockers.
    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.
    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.
    Streptogramins: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as dalfopristin; quinupristin may cause significant increases in silodosin plasma concentrations.
    Tadalafil: (Major) Symptoms of orthostasis (e.g., postural hypotension, dizziness and vertigo) may occur during treatment with alpha-blockers such as silodosin. Enhanced hypotensive effects are possible when alpha-blockers are coadministered with vasodilatory agents such as tadalafil. Patients should be stabilized on alpha blocker therapy prior to starting tadalafil, or if already receiving an optimum dose of tadalafil, alpha blocker therapy should be started at the lowest possible dose.
    Tamoxifen: (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 tamoxifen may cause significant increases in silodosin plasma concentrations.
    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.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and silodosin is necessary, as the systemic exposure of silodosin may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of silodosin; consider increasing the dose of silodosin if necessary. Silodosin is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Temsirolimus: (Moderate) Use caution if coadministration of temsirolimus with silodosin is necessary, and monitor for an increase in silodosin-related adverse reactions. Temsirolimus is a P-glycoprotein (P-gp) inhibitor in vitro, and silodosin is an in vitro P-gp substrate. Pharmacokinetic data are not available for concomitant use of temsirolimus with P-gp substrates, but exposure to silodosin is likely to increase.
    Terazosin: (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.
    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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    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.
    Ulipristal: (Minor) In vitro data indicate that ulipristal may be an inhibitor of P-glycoprotein (P-gp) at clinically relevant concentrations. Thus, co-administration of ulipristal and P-gp substrates such as silodosin may increase silodosin concentrations. With single doses of ulipristal for emergency contraception it is not clear this interaction will have clinical consequence. In the absence of clinical data, co-administration of ulipristal (when given daily) and P-gp substrates is not recommended.
    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.
    Vandetanib: (Moderate) Use caution if coadministration of vandetanib with silodosin is necessary, due to a possible increase in silodosin-related adverse reactions. Silodosin is extensively metabolized by CYP3A4 and P-glycoprotein (P-gp) in vitro. Coadministration with vandetanib increased the Cmax and AUC of digoxin, another P-gp substrate, by 29% and 23%, respectively. Silodosin is not recommended for use in patients taking strong P-gp inhibitors, but recommendations are not available for moderate inhibitors.
    Vardenafil: (Major) Symptoms of orthostasis (e.g., postural hypotension, dizziness and vertigo) may occur during treatment with alpha-blockers such as silodosin. Enhanced hypotensive effects are possible when alpha-blockers are coadministered with vasodilatory agents such as vardenafil. Patients should be stabilized on alpha blocker therapy prior to starting vardenafil, or if already receiving an optimum dose of vardenafil, alpha blocker therapy should be started at the lowest possible dose.
    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) 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. Silodosin is extensively metabolized by CYP450 3A4 and is a substrate for P-glycoprotein (P-gp). In theory, antihypertensive drugs that inhibit CYP3A4 such as diltiazem, verapamil, and nicardipine may cause significant increases in silodosin plasma concentrations. Verapamil may also interact with silodosin through its effects as a P-gp inhibitor.
    Voriconazole: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4 such as voriconazole may cause significant increases in silodosin plasma concentrations.
    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 females and therefore would not be used during breast-feeding. No effects on the physical or behavioral development of offspring were noted when the drug was given to lactating rats at doses of up to 300 mg/kg/day; it is not known if the drug is excreted in human milk.

    MECHANISM OF ACTION

    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, and it is approximately 97% protein bound. The mean time to maximum concentration is roughly 2.6 hours. Silodosin is metabolized by the hepatic cytochrome P450 enzyme system, specifically CYP3A4, as well as through glucuronidation and alcohol and aldehyde dehydrogenase. In vitro data indicate that silodosin does not inhibit CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4 and does not induce CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4, or P-gp. The primary metabolite is KMD-3213G, which is formed from direct conjugation of silodosin by UDP-glucuronosyltransferase 2B7 (UBT2B7). In theory, co-administration of silodosin with UBT2B7 inhibitors may increase silodosin plasma concentrations. 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 four 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-gp
    Silodosin is extensively metabolized by CYP3A4 hepatic enzymes and is a P-glycoprotein (P-gp) substrate. 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. In pharmacokinetic study, coadministration with a moderate fat, moderate caloric meal resulted in a decrease in Cmax by 18% to 43% and decrease in AUC by 4% to 49%. 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.