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  • CLASSES

    5-Alpha Reductase Inhibitors
    Alpha-Blockers

    DEA CLASS

    Rx

    DESCRIPTION

    Combination 5-alpha-reductase inhibitor and alpha-blocker; used once-daily for BPH.

    COMMON BRAND NAMES

    Jalyn

    HOW SUPPLIED

    Dutasteride, Tamsulosin/Dutasteride, Tamsulosin Hydrochloride/Jalyn Oral Cap: 0.5-0.4mg

    DOSAGE & INDICATIONS

    For the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate.
    NOTE: Instruct patient to swallow capsules whole; do not chew or open since contact with the capsule contents may cause irritation of the oropharyngeal mucosa.
    Oral dosage
    Adult Males

    1 capsule (0.5 mg dutasteride and 0.4 mg tamsulosin) PO once daily; should be taken approximately 30 minutes after the same meal each day.

    MAXIMUM DOSAGE

    Adults

    One capsule (0.5 mg dutasteride/0.4 mg tamsulosin) per day PO.

    Elderly

    One capsule (0.5 mg dutasteride/0.4 mg tamsulosin) per day PO.

    Adolescents

    Dutasteride; tamsulosin is contraindicated.

    Children

    Dutasteride; tamsulosin is contraindicated.

    Infants

    Dutasteride; tamsulosin is contraindicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in moderate to severe hepatic impairment are not available; it appears that no dosage adjustments are needed. Since dutasteride; tamsulosin is extensively metabolized by the liver, use with caution in patients with severe hepatic impairment.

    Renal Impairment

    CrCl >= 10 mL/min: No dosage adjustment is necessary.
    CrCl < 10 mL/min: No specific guidelines for dosage adjustments are available; patients with CrCl < 10 mL/min have not been studied.

    ADMINISTRATION

    Oral Administration

    Swallow capsules whole; do not chew or open since contact with the capsule contents may cause irritation of the oropharyngeal mucosa. Administer approximately 30 minutes after the same meal each day.
    Do not administer capsules that are cracked or leaking; contact a pharmacist for replacements.
    Females who are pregnant or may become pregnant should not handle/administer dutasteride; tamsulosin capsules. If a woman who is pregnant gets enough dutasteride; tamsulosin through her skin after handling it, the drug could harm the unborn fetus. If skin contact with a leaking capsule occurs, the affected area should be washed with soap and water immediately.

    STORAGE

    Jalyn:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    NOTE: This monograph discusses the use of dutasteride; tamsulosin combination capsules for the treatment of symptomatic benign prostatic hyperplasia (BPH). Clinicians may wish to consult the individual drug monographs for more information.
     
    Dutasteride; tamsulosin is contraindicated in patients with a known hypersensitivity to dutasteride (e.g., angioedema) or any ingredient in the preparation. Cross-sensitivity with other 5-alpha-reductase inhibitors is possible.

    Pregnancy

    Dutasteride; tamsulosin is contraindicated for use in females of childbearing potential; it is pregnancy risk category X and is therefore contraindicated during pregnancy. Dutasteride and other 5-alpha-reductase inhibitors inhibit the conversion of testosterone to DHT that can cause abnormalities in the external genitalia of the male fetus. Pregnant women or women trying to conceive should not handle dutasteride capsules because dutasteride is absorbed through the skin and may result in fetal exposure. If skin contact with a leaking capsule occurs, the affected area should be washed with soap and water immediately. Dutasteride is secreted into male semen. The amount of dutasteride in semen that is available for vaginal absorption is estimated to be less than 100 times the concentrations that produces abnormalities in the genitalia of male offspring in animal studies. In addition, dutasteride is more than 96% protein bound in human semen, which may decrease vaginal absorption of the drug.

    Breast-feeding

    Dutasteride; tamsulosin is contraindicated for use in females of child-bearing potential, which would include females who are breast-feeding; it is not known whether dutasteride or tamsulosin is excreted in human milk.

    Children, infants, neonates

    Dutasteride; tamsulosin is contraindicated for use in neonates, infants, children, and adolescents under 18 years of age. Safety and effectiveness have not been established in this age group.

    Geriatric, orthostatic hypotension, renal disease, renal failure, renal impairment, syncope

    Dutasteride; tamsulosin should be used cautiously in patients with orthostatic hypotension, vertigo, or syncope. The signs and symptoms of orthostasis (postural hypotension, dizziness, and vertigo) were more frequently reported in tamsulosin-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 should syncope occur. Patients with renal impairment, renal failure or other renal disease and geriatric patients should also be monitored carefully for exaggerated hypotensive effects (e.g., first dose effect). Differences in safety and efficacy were not noted between patients > 65 years of age and younger patients.

    Prostate cancer, urinary tract obstruction

    Dutasteride reduces total serum prostate specific antigen (PSA) by about 40% after 3 months of treatment and 50% after 6, 12, and 24 months of treatment. This decrease is predictable over the entire range of PSA values, but may vary in individual patients. It is recommended that a new baseline PSA concentration be established after 3—6 months for interpretation of serial PSAs in men taking dutasteride; tamsulosin. This new baseline PSA should be used to assess potentially cancer-related changes in PSA. To interpret an isolated PSA value in a man treated with dutasteride for 6 months or more, the PSA value should be doubled for comparison with normal values in untreated men. The free-to-total PSA ratio (percent free PSA) remains constant at month 12, even under the influence of dutasteride. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men receiving dutasteride, no adjustment to its value appears necessary. Administration of dutasteride; tamsulosin results in similar changes to total PSA as dutasteride monotherapy. In June 2011, a review of two large, randomized controlled trials, the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial prompted the FDA to alert healthcare professionals of the potential risk of an increased incidence of high-grade prostate cancer in patients receiving finasteride or dutasteride treatment. Results from the REDUCE trial showed that men receiving dutasteride had a 23% decreased risk of being diagnosed with prostate cancer when compared to placebo (p < 0.0001); however, the risk reduction was limited to Gleason score (GS) <= 6 cancers. There was an increased incidence of GS 8—10 prostate cancers with dutasteride compared to placebo (1% vs. 0.5%, respectively). Therefore, in initiating or continuing treatment with dutasteride; tamsulosin, clinicians should weigh the known benefits of treatment against the potential risk and be aware that dutasteride may increase the risk of high-grade prostate cancer. Further, lower urinary tract symptoms of BPH can be indicative of other urological diseases, including prostate cancer. Patients should be assessed to rule out other urological diseases prior to treatment with dutasteride and periodically thereafter. Patients with a large residual urinary volume and/or severely diminished urinary flow may not be good candidates for 5-alpha-reductase inhibitor therapy and should be carefully monitored for urinary tract obstruction.

    Blood donation

    Males treated with dutasteride; tamsulosin should not undergo blood donation until at least 6 months have passed following their last dose. The purpose of this deferred period is to prevent administration of dutasteride to a pregnant female receiving a blood transfusion. Serum levels of dutasteride are detectable for 4—6 months following termination of therapy.

    Ocular surgery

    Patients receiving or who have previously received treatment with dutasteride; tamsulosin 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.

    Sulfonamide hypersensitivity

    Tamsulosin is a non-arylamine sulfonamide derivative. In patients with sulfonamide hypersensitivity, allergic reaction to tamsulosin has been rarely reported. If a patient reports a serious or life threatening sulfonamide allergy, the manufacturer advises caution when administering dutasteride; tamsulosin. However, tamsulosin is not contraindicated for use in patients with sulfonamide allergy. Based on clinical trials and post-marketing experience with tamsulosin, the potential for cross-reactivity in patients with sulfonamide allergy has not been established. In post-marketing experience, allergic-type reactions (such as skin rash, pruritus, urticaria, and angioedema of the tongue, lips, and face) have been reported in some cases, and, in very rare cases, in patients who had a history of sulfa allergy (manufacturer data on file). According to the manufacturer, clinical trials with tamsulosin did not screen for or exclude patients with a history of sulfonamide allergy; therefore, the actual potential for sulfonamide cross-reactivity with tamsulosin is unknown. Non-arylamine sulfonamide derivatives (e.g., tamsulosin) have been reported to be proposed to have a lower risk of allergic reactions in patients with sulfonamide allergy, presumably due to the lack of one of the proposed structural sites of action for sulfonamide allergy (arylamine group in the N4 position). One large retrospective cohort study has reported that in patients with the presence of an allergic reaction after exposure to a sulfonamide antibiotic, 9.9% had an allergic reaction after receiving a non-antibiotic sulfonamide derivative, and 1.6% of patients who lacked an allergic reaction after sulfonamide antibiotic exposure had an allergic reaction after administration of a non-antibiotic sulfonamide derivative (adjusted odds ratio 2.8; 95% CI, 2.1—3.7). A causal relationship between sulfonamide hypersensitivity and allergic reactions with non-arylamine sulfonamide derivatives has not been definitively established and remains controversial. In general, patients with a documented sulfonamide allergy are considered to be predisposed for development of allergic drug reactions. Until further data are available, caution is prudent when administering sulfonamide derivatives to patients with a documented sulfonamide hypersensitivity.

    Hepatic disease

    Dutasteride; tamsulosin should be used with caution in patients with hepatic disease; data are limited regarding the incidence of adverse effects or drug accumulation in these patients. Dutasteride is extensively metabolized by the liver and has a half-life of about 5 weeks at steady state. Patients with mild to moderate impairment do not require an adjustment in tamsulosin dosage. Tamsulosin has not been studied in patients with severe hepatic impairment and cautious use is warranted in this population.

    Priapism

    Rarely (probably less than 1 in 50,000), tamsulosin, 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

    heart failure / Delayed / 0-1.0
    atrial fibrillation / Early / Incidence not known
    teratogenesis / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    erythema multiforme / Delayed / Incidence not known

    Moderate

    ejaculation dysfunction / Delayed / 11.0-11.0
    impotence (erectile dysfunction) / Delayed / 5.4-5.4
    orthostatic hypotension / Delayed / 0-1.0
    priapism / Early / Incidence not known
    testicular swelling / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    palpitations / Early / Incidence not known
    dyspnea / Early / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    blurred vision / Early / Incidence not known
    floppy iris syndrome / Delayed / Incidence not known
    edema / Delayed / Incidence not known
    constipation / Delayed / Incidence not known
    depression / Delayed / Incidence not known

    Mild

    libido decrease / Delayed / 4.5-4.5
    dizziness / Early / 1.1-1.1
    vertigo / Early / 0-1.0
    syncope / Early / 0-1.0
    diarrhea / Early / 2.0
    sinusitis / Delayed / 2.0
    cough / Delayed / 2.0
    rhinitis / Early / 2.0
    back pain / Delayed / 2.0
    asthenia / Delayed / 2.0
    pharyngitis / Delayed / 2.0
    insomnia / Early / 2.0
    infection / Delayed / 2.0
    drowsiness / Early / 2.0
    testicular pain / Early / Incidence not known
    orgasm dysfunction / Delayed / Incidence not known
    decreased ejaculate volume / Delayed / Incidence not known
    breast enlargement / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known
    rash (unspecified) / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    vomiting / Early / Incidence not known
    xerostomia / Early / Incidence not known
    epistaxis / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Acetaminophen; Diphenhydramine: (Moderate) Use caution when administering tamsulosin with moderate CYP2D6 inhibitors. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4. Diphenhydramine is a CYP2D6 inhibitor; consider if another antihistamine would be appropriate to treat the patient's symptoms. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. Interactions with moderate CYP2D6 inhibitors have not been evaluated. The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin have also not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin is co-administered with a combination of both CYP3A4 and CYP2D6 inhibitors. If concomitant use in necessary, monitor patient closely for increased side effects.
    Acetaminophen; Propoxyphene: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of propoxyphene. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as propoxyphene, should be avoided.
    Aliskiren; Amlodipine: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Alpha-blockers: (Severe) Tamsulosin should not be adminsitered in combination with other alpha-blockers.
    Ambrisentan: (Minor) Because symptoms of orthostasis (e.g., postural hypotension, dizziness, vertigo) are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents.
    Amiodarone: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of amiodarone. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as amiodarone, should be avoided. (Moderate) Dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as amiodarone.
    Amlodipine: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Amlodipine; Atorvastatin: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Amlodipine; Benazepril: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Amlodipine; Olmesartan: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Amlodipine; Telmisartan: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Amlodipine; Valsartan: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Amobarbital: (Moderate) Concurrent use of amobarbital with antihypertensive agents may lead to hypotension. Monitor for decreases in blood pressure during times of coadministration.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of clarithromycin. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as clarithromycin, should be avoided.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of clarithromycin. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as clarithromycin, should be avoided.
    Amphetamine; Dextroamphetamine Salts: (Major) Amphetamines increase both systolic and diastolic blood pressure and may counteract the activity of some antihypertensive agents. Due to the risk of unopposed alpha-adrenergic activity, amphetamines should be used cautiously with beta-blockers. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. In particular, amphetamines can inhibit the antihypertensive response to guanadrel, an adrenergic antagonist that causes depletion of norepinephrine in the synapse. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed.
    Amprenavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Aprepitant, Fosaprepitant: (Moderate) Use caution if tamsulosin and aprepitant, fosaprepitant are used concurrently and monitor for an increase in tamsulosin-related adverse effects for several days after administration of a multi-day aprepitant regimen. Tamsulosin 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 tamsulosin. 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.
    Artemether; Lumefantrine: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as artemether; lumefantrine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects.
    Atazanavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Atazanavir; Cobicistat: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together. (Moderate) The plasma concentrations of dutasteride may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as impotence or libido decrease, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate. (Moderate) The plasma concentrations of tamsulosin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while tamsulosin is a CYP3A4 and CYP2D6 substrate.
    Atenolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Atenolol; Chlorthalidone: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Avanafil: (Major) Since the symptoms of orthostasis (e.g., postural hypotension, dizziness and vertigo) are reported more frequently in tamsulosin-treated vs. placebo patients, there is a theoretical risk of enhanced hypotensive effects in individual patients when tamsulosin co-administered with vasodilatory agents such as phosphodiesterase inhibitors. Concurrent use of PDE5 inhibitors and alpha-blockers may lead to symptomatic hypotension in some patients. When sildenafil (25 mg) was simultaneously administered with doxazosin (4 mg) to patients with BPH, mean additional reductions in supine blood pressure of 7 mmHg systolic and 7 mmHg diastolic were observed. When higher doses of sildenafil were administered with doxazosin (4 mg), symptomatic postural hypotension within 1 to 4 hours was reported in some patients. Sildenafil doses greater than 25 mg should not be taken within 4 hours of taking alpha-blockers. The manufacturers for tadalafil and vardenafil state that patients should be stabilized on alpha blocker therapy prior to starting either tadalafil or vardenafil, or if already receiving optimum dose of tadalafil or vardenafil, alpha blocker therapy should be started at the lowest possible dose.
    Bendroflumethiazide; Nadolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Beta-blockers: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Betaxolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Bisoprolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Boceprevir: (Severe) The concurrent use of tamsulosin and boceprevir is contraindicated due to the potential for serious/life-threatening reactions. Tamsulosin is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated tamsulosin plasma concentrations, which could cause adverse events such as hypotension and priapism. (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like boceprevir are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Brimonidine; Timolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Bupropion: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as bupropion. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects.
    Bupropion; Naltrexone: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as bupropion. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects.
    Calcium-channel blockers: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Carbetapentane; Chlorpheniramine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Use caution when administering tamsulosin with moderate CYP2D6 inhibitors. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4. Diphenhydramine is a CYP2D6 inhibitor; consider if another antihistamine would be appropriate to treat the patient's symptoms. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. Interactions with moderate CYP2D6 inhibitors have not been evaluated. The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin have also not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin is co-administered with a combination of both CYP3A4 and CYP2D6 inhibitors. If concomitant use in necessary, monitor patient closely for increased side effects.
    Carteolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Carvedilol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Ceritinib: (Moderate) Monitor for tamsulosin-related adverse reactions if coadministration with ceritinib is necessary; the risk may higher if the patient is also taking a CYP2D6 inhibitor. Ceritinib is a CYP3A4 inhibitor and tamsulosin is primarily metabolized by CYP3A4. Coadministration with a strong CYP3A4 inhibitor increased the Cmax and AUC of tamsulosin by 2.2-fold and 2.8-fold, respectively; the effects of concomitant administration of a moderate CYP3A4 inhibitor have not been evaluated. The degree of CYP3A4 inhibition by ceritinib is unknown.
    Chloramphenicol: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as chloramphenicol. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine; Codeine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine; Dextromethorphan: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine; Hydrocodone: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine; Phenylephrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpheniramine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Chlorpromazine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as chlorpromazine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Cimetidine: (Moderate) Cimetidine is a weak inhibitor of CYP2D6, one of the enzymes responsible for metabolism of tamsulosin. The manufacturer recommends that tamsulosin be used with caution in combination with cimetidine. A study involving 10 healthy volunteers (age range 21 to 40 years) showed that cimetidine administered at the highest recommended dose (400 mg q6h for 6 days) significantly (26%) decreased the clearance of a single tamsulosin 0.4 mg dose. This resulted in a moderate increase in tamsulosin AUC (44%). (Moderate) Dutasteride is metabolized by CYP3A4 enzyme. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as cimetidine.
    Cinacalcet: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as cinacalcet. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Citalopram: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as citalopram. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Clarithromycin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of clarithromycin. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as clarithromycin, should be avoided.
    Clevidipine: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Cobicistat: (Moderate) The plasma concentrations of dutasteride may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as impotence or libido decrease, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate. (Moderate) The plasma concentrations of tamsulosin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while tamsulosin is a CYP3A4 and CYP2D6 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of dutasteride may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as impotence or libido decrease, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate. (Moderate) The plasma concentrations of tamsulosin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while tamsulosin is a CYP3A4 and CYP2D6 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of dutasteride may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as impotence or libido decrease, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate. (Moderate) The plasma concentrations of tamsulosin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while tamsulosin is a CYP3A4 and CYP2D6 substrate.
    Codeine; Phenylephrine; Promethazine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as promethazine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Codeine; Promethazine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as promethazine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Conivaptan: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of conivaptan. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as conivaptan, should be avoided. (Moderate) According to the manufacturer, concomitant use of conivaptan (a strong CYP3A4 inhibitor) and CYP3A substrates (such as dutasteride) should be avoided. 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 dutasteride. Treatment with dutasteride may be initiated no sooner than 1 week after completion of conivaptan therapy.
    Crizotinib: (Moderate) Monitor for an increase in tamsulosin-related adverse reactions, including hypotension, if coadministration with crizotinib is necessary. Tamsulosin is a CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor. The effects of concomitant administration of a moderate CYP3A4 inhibitor on the pharmacokinetics of tamsulosin have not been evaluated, but tamsulosin exposure may increase based on the effects of strong CYP3A4 inhibition.
    Cyclosporine: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as cyclosporine. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Dalfopristin; Quinupristin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of dalfopristin; quinupristin. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as quinupristin, should be avoided.
    Danazol: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as danazol. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Darunavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Darunavir; Cobicistat: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together. (Moderate) The plasma concentrations of dutasteride may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as impotence or libido decrease, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate. (Moderate) The plasma concentrations of tamsulosin may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while tamsulosin is a CYP3A4 and CYP2D6 substrate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Delavirdine: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of delavirdine. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as delavirdine, should be avoided. (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like delavirdine are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Use caution when administering tamsulosin with moderate CYP2D6 inhibitors. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4. Diphenhydramine is a CYP2D6 inhibitor; consider if another antihistamine would be appropriate to treat the patient's symptoms. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. Interactions with moderate CYP2D6 inhibitors have not been evaluated. The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin have also not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin is co-administered with a combination of both CYP3A4 and CYP2D6 inhibitors. If concomitant use in necessary, monitor patient closely for increased side effects.
    Dextromethorphan; Promethazine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as promethazine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Dextromethorphan; Quinidine: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as quinidine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects.
    Diltiazem: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme and the clearance of dutasteride may be reduced when co-administered with the CYP3A4 inhibitor diltiazem. (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Diphenhydramine: (Moderate) Use caution when administering tamsulosin with moderate CYP2D6 inhibitors. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4. Diphenhydramine is a CYP2D6 inhibitor; consider if another antihistamine would be appropriate to treat the patient's symptoms. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. Interactions with moderate CYP2D6 inhibitors have not been evaluated. The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin have also not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin is co-administered with a combination of both CYP3A4 and CYP2D6 inhibitors. If concomitant use in necessary, monitor patient closely for increased side effects.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Use caution when administering tamsulosin with moderate CYP2D6 inhibitors. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4. Diphenhydramine is a CYP2D6 inhibitor; consider if another antihistamine would be appropriate to treat the patient's symptoms. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. Interactions with moderate CYP2D6 inhibitors have not been evaluated. The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin have also not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin is co-administered with a combination of both CYP3A4 and CYP2D6 inhibitors. If concomitant use in necessary, monitor patient closely for increased side effects.
    Diphenhydramine; Ibuprofen: (Moderate) Use caution when administering tamsulosin with moderate CYP2D6 inhibitors. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4. Diphenhydramine is a CYP2D6 inhibitor; consider if another antihistamine would be appropriate to treat the patient's symptoms. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. Interactions with moderate CYP2D6 inhibitors have not been evaluated. The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin have also not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin is co-administered with a combination of both CYP3A4 and CYP2D6 inhibitors. If concomitant use in necessary, monitor patient closely for increased side effects.
    Diphenhydramine; Naproxen: (Moderate) Use caution when administering tamsulosin with moderate CYP2D6 inhibitors. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4. Diphenhydramine is a CYP2D6 inhibitor; consider if another antihistamine would be appropriate to treat the patient's symptoms. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. Interactions with moderate CYP2D6 inhibitors have not been evaluated. The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin have also not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin is co-administered with a combination of both CYP3A4 and CYP2D6 inhibitors. If concomitant use in necessary, monitor patient closely for increased side effects.
    Diphenhydramine; Phenylephrine: (Moderate) Use caution when administering tamsulosin with moderate CYP2D6 inhibitors. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4. Diphenhydramine is a CYP2D6 inhibitor; consider if another antihistamine would be appropriate to treat the patient's symptoms. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. Interactions with moderate CYP2D6 inhibitors have not been evaluated. The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin have also not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin is co-administered with a combination of both CYP3A4 and CYP2D6 inhibitors. If concomitant use in necessary, monitor patient closely for increased side effects.
    Dorzolamide; Timolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Doxazosin: (Severe) Tamsulosin should not be adminsitered in combination with other alpha-blockers.
    Dronedarone: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of dronedarone. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as dronedarone, should be avoided.
    Drospirenone; Ethinyl Estradiol: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Duloxetine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as duloxetine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Elbasvir; Grazoprevir: (Moderate) Administering tamsulosin with elbasvir; grazoprevir may result in elevated tamsulosin plasma concentrations. Tamsulosin is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Eliglustat: (Moderate) Coadministration of tamsulosin and eliglustat may result in increased concentrations of tamsulosin. Use tamsulosin with caution in patients receiving eliglustat, particularly if the tamsulosin dose is greater than 0.4 mg, and monitor closely for tamsulosin-related adverse effects including hypotension, dizziness, and vertigo. Tamsulosin is a CYP2D6 and CYP3A4 substrate; eliglustat is a CYP2D6 inhibitor.
    Enalapril; Felodipine: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Erythromycin: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme and CYP3A5 isoenzymes. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as erythromycin. (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as erythromycin. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Erythromycin; Sulfisoxazole: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme and CYP3A5 isoenzymes. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as erythromycin. (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as erythromycin. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Escitalopram: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as escitalopram. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Esmolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Ethanol: (Moderate) Use caution when combining tamsulosin with alcohol-containing beverages. Alcohol-containing beverages may increase the effects of tamsulosin, which may lower the blood pressure. Tamsulosin 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 tamsulosin. Some experts advise that the patient to limit alcohol use while using this drug.
    Ethinyl Estradiol: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Desogestrel: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Etonogestrel: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Levonorgestrel: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Norelgestromin: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Norethindrone: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Norgestimate: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Ethinyl Estradiol; Norgestrel: (Moderate) Tamsulosin is metabolized by CYP3A4. Ethinyl Estradiol, which inhibits CYP3A4, may cause increases in tamsulosin plasma concentrations. Although no clinical studies have been done, tamsulosin should be used cautiously with ethinyl estradiol.
    Everolimus: (Moderate) Monitor for an increase in tamsulosin-related adverse reactions if coadministration with everolimus is necessary. Tamsulosin is a CYP3A4 and CYP2D6 substrate. Everolimus is a weak CYP3A4 inhibitor and a CYP2D6 inhibitor. The effects of coadministration of both a CYP3A4 and CYP2D6 inhibitor with tamsulosin have not been evaluated; however, there is a potential for significantly increased plasma concentrations of tamsulosin.
    Felodipine: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Fluconazole: (Moderate) Dutasteride is metabolized by the CYP3A4/5 hepatic enzyme. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors including fluconazole. (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as fluconazole. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Fluoxetine: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of fluoxetine. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as fluoxetine, should be avoided.
    Fluoxetine; Olanzapine: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of fluoxetine. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as fluoxetine, should be avoided.
    Fluvoxamine: (Moderate) Tamsulosin should be used with caution in combination with moderate inhibitors of CYP3A4 such as fluvoxamine. The cytochrome P450 enzymes CYP3A4 and CYP2D6 are responsible for the extensive metabolism of tamsulosin. Strong inhibitors of CYP3A4 are known to increase the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively. No studies have been performed with moderate CYP3A4 inhibitors. As with other alpha adrenergic blocking agents there is a potential risk of syncope with tamsulosin, particularly if serum concentrations are elevated. Monitor blood pressure and observe for symptoms of orthostasis.
    Fosamprenavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Gefitinib: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as gefitinib. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Grapefruit juice: (Moderate) Hepatic cytochrome P450 enzymes 2D6 and 3A4 are responsible for the extensive metabolism of tamsulosin. Although no clinical studies have been done, tamsulosin should be used with caution with inhibitors of CYP3A4 isoenzymes (e.g., grapefruit juice).
    Halofantrine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as halofantrine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Haloperidol: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as haloperidol. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Hydrochlorothiazide, HCTZ; Propranolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tamsulosin, a CYP3A substrate, as tamsulosin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like idelalisib are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Iloprost: (Minor) Iloprost can have additive effects when administered with other antihypertensive agents, including alpha-blockers. These effects can be used to therapeutic advantage, but dosage adjustments may be necessary.
    Imatinib: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of imatinib, STI-571. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as imatinib, STI-571, should be avoided. (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like imatinib are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Indinavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Isavuconazonium: (Moderate) The plasma concentrations of tamsulosin may be elevated when administered concurrently with isavuconazonium. Clinical monitoring for adverse effects, such as hypotension, is recommended during coadministration. Tamsulosin 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: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of isoniazid, INH. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as isoniazid, should be avoided.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of isoniazid, INH. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as isoniazid, should be avoided.
    Isoniazid, INH; Rifampin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of isoniazid, INH. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as isoniazid, should be avoided.
    Isradipine: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Itraconazole: (Major) Use of tamsulosin is not recommended during and for 2 weeks after itraconazole therapy due to the potential for elevated tamsulosin concentrations. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes, and strong inhibitors of CYP3A4 are expected to significantly raise tamsulosin concentrations. Concomitant treatment with another strong CYP3A4 inhibitor resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively. (Moderate) Monitor for increased dutasteride adverse effects if coadministration of itraconazole is necessary. No clinical drug interaction trials have been performed to evaluate the impact of CYP3A enzyme inhibitors on dutasteride pharmacokinetics. However, based on in vitro data, blood concentrations of dutasteride may increase in the presence of inhibitors of CYP3A4 such as itraconazole.
    Ivacaftor: (Moderate) Use caution when administering ivacaftor and dutasteride concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as dutasteride, can increase dutasteride exposure leading to increased or prolonged therapeutic effects and adverse events. (Minor) Use caution when administering ivacaftor and tamsulosin concurrently. Ivacaftor is an inhibitor of CYP3A and tamsulosin is partially metabolized by CYP3A. Co-administration can theoretically increase tamsulosin exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Ketoconazole: (Major) Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes, and strong inhibitors of CYP3A4 are expected to significantly raise tamsulosin concentrations. Plasma concentrations of tamsulosin are increased with concomitant use of ketoconazole, a strong inhibitor of CYP3A4. Concomitant treatment with ketoconazole resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as ketoconazole, itraconazole, posaconazole, or voriconazole should be avoided. (Moderate) Dutasteride is metabolized by CYP3A4 enzyme. CYP3A4 inhibitors, such as ketoconazole, may decrease the clearance of dutasteride.
    Labetalol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Levobetaxolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Levobunolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Lopinavir; Ritonavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and dutasteride concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as dutasteride, can increase dutasteride exposure leading to increased or prolonged therapeutic effects and adverse events. (Minor) Use caution when administering ivacaftor and tamsulosin concurrently. Ivacaftor is an inhibitor of CYP3A and tamsulosin is partially metabolized by CYP3A. Co-administration can theoretically increase tamsulosin exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
    Meperidine; Promethazine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as promethazine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Metoprolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Mifepristone, RU-486: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as mifepristone, RU-486. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Mirabegron: (Minor) The effect of mirabegron on tamsulosin pharmacokinetics was determined in drug interaction studies. Although no dose adjustment is recommended with tamsulosin treatment based on the lack of pharmacokinetic interaction, mirabegron should be administered with caution in patients taking other medications in the setting of urinary obstruction because of the risk of urinary retention.
    Mitotane: (Moderate) Use caution if mitotane and tamsulosin are used concomitantly, and monitor for decreased efficacy of tamsulosin and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and tamsulosin is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of tamsulosin.
    Nadolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Nebivolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Nebivolol; Valsartan: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Nefazodone: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of nefazodone. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as nefazodone, should be avoided. (Moderate) Dutasteride is metabolized by CYP3A4 enzyme. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors including nefazodone.
    Nelfinavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Nicardipine: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Nifedipine: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Nimodipine: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Nisoldipine: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Oritavancin: (Minor) Tamsulosin is metabolized by CYP3A4 and CYP2D6; oritavancin is a weak CYP3A4 and CYP2D6 inducer. Plasma concentrations and efficacy of tamsulosin may be reduced if these drugs are administered concurrently.
    Paroxetine: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as paroxetine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with paroxetine resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 1.3 and 1.6, respectively. If concomitant use in necessary, monitor patient closely for increased side effects.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and tamsulosin, a CYP3A4 substrate, may cause an increase in systemic concentrations of tamsulosin. Use caution when administering these drugs concomitantly.
    Peginterferon Alfa-2b: (Minor) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as peginterferon alfa-2b. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Penbutolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Perindopril; Amlodipine: (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Perphenazine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as perphenazine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Perphenazine; Amitriptyline: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as perphenazine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Phenoxybenzamine: (Severe) Tamsulosin should not be adminsitered in combination with other alpha-blockers.
    Phentolamine: (Severe) Tamsulosin should not be adminsitered in combination with other alpha-blockers.
    Phenylephrine; Promethazine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as promethazine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Phosphodiesterase inhibitors: (Major) Since the symptoms of orthostasis (e.g., postural hypotension, dizziness and vertigo) are reported more frequently in tamsulosin-treated vs. placebo patients, there is a theoretical risk of enhanced hypotensive effects in individual patients when tamsulosin co-administered with vasodilatory agents such as phosphodiesterase inhibitors. Concurrent use of PDE5 inhibitors and alpha-blockers may lead to symptomatic hypotension in some patients. When sildenafil (25 mg) was simultaneously administered with doxazosin (4 mg) to patients with BPH, mean additional reductions in supine blood pressure of 7 mmHg systolic and 7 mmHg diastolic were observed. When higher doses of sildenafil were administered with doxazosin (4 mg), symptomatic postural hypotension within 1 to 4 hours was reported in some patients. Sildenafil doses greater than 25 mg should not be taken within 4 hours of taking alpha-blockers. The manufacturers for tadalafil and vardenafil state that patients should be stabilized on alpha blocker therapy prior to starting either tadalafil or vardenafil, or if already receiving optimum dose of tadalafil or vardenafil, alpha blocker therapy should be started at the lowest possible dose.
    Pindolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Posaconazole: (Major) Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes, and strong inhibitors of CYP3A4 are expected to significantly raise tamsulosin concentrations. Plasma concentrations of tamsulosin are increased with concomitant use of ketoconazole, a strong inhibitor of CYP3A4. Concomitant treatment with ketoconazole resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as ketoconazole, itraconazole, posaconazole, or voriconazole should be avoided. (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like posaconazole are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Prazosin: (Severe) Tamsulosin should not be adminsitered in combination with other alpha-blockers.
    Promethazine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as promethazine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Propafenone: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as propafenone. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Propoxyphene: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of propoxyphene. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as propoxyphene, should be avoided.
    Propranolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Protease inhibitors: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Quinidine: (Moderate) Use caution when administering tamsulosin with a strong CYP2D6 inhibitor such as quinidine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure. If concomitant use in necessary, monitor patient closely for increased side effects.
    Quinine: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of quinine. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as quinine, should be avoided.
    Ranolazine: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of ranolazine. Tamsulosin is extensively metabolized by CYP2D6 and CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Therefore, concomitant use with drugs that inhibit both CYP2D6 and CYP3A4, such as ranolazine, should be avoided.
    Ribociclib: (Moderate) Use caution if coadministration of ribociclib with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increase in treatment-related adverse reactions including hypotension, dizziness, and vertigo. Ribociclib is a moderate CYP3A4 inhibitor and tamsulosin is a CYP3A4 substrate. The effect of concomitant use of a moderate CYP3A4 inhibitor with tamsulosin has not been evaluated; however, administration with a strong CYP3A4 inhibitor significantly increased the AUC and Cmax of tamsulosin.
    Ribociclib; Letrozole: (Moderate) Use caution if coadministration of ribociclib with tamsulosin is necessary, especially at a tamsulosin dose higher than 0.4 mg, as the systemic exposure of tamsulosin may be increased resulting in increase in treatment-related adverse reactions including hypotension, dizziness, and vertigo. Ribociclib is a moderate CYP3A4 inhibitor and tamsulosin is a CYP3A4 substrate. The effect of concomitant use of a moderate CYP3A4 inhibitor with tamsulosin has not been evaluated; however, administration with a strong CYP3A4 inhibitor significantly increased the AUC and Cmax of tamsulosin.
    Ritonavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Rolapitant: (Major) Use caution if tamsulosin and rolapitant are used concurrently, and monitor for tamsulosin-related adverse effects. Tamsulosin is a CYP2D6 substrate and rolapitant is a moderate CYP2D6 inhibitor; the inhibitory effect of rolapitant lasts for at least 7 days, and may last longer after single dose administration. The Cmax and AUC of another CYP2D6 substrate, dextromethorphan, were increased by 120% and 160%, respectively, on day 1 with rolapitant, and by 180% and 230%, respectively, on day 8 after rolapitant administration.
    Saquinavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Saw Palmetto, Serenoa repens: (Moderate) Saw palmetto may inhibit 5 alpha-reductase, preventing the conversion of testosterone to dihydrotestosterone. This action is similar to the action of 5-alpha reductase inhibitors, such as dutasteride and finasteride. Co-use is likely to be common by patients, but the effects of co-use are not known. In theory, the effects could be additive, but it is not known if the added effects would be beneficial or harmful. Clinicians should be alert for any unusual effects if patients ingest saw palmetto supplements while taking 5-alpha reductase inhibitors.
    Sertraline: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as sertraline. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Sildenafil: (Major) Since the symptoms of orthostasis (e.g., postural hypotension, dizziness and vertigo) are reported more frequently in tamsulosin-treated vs. placebo patients, there is a theoretical risk of enhanced hypotensive effects in individual patients when tamsulosin co-administered with vasodilatory agents such as phosphodiesterase inhibitors. Concurrent use of PDE5 inhibitors and alpha-blockers may lead to symptomatic hypotension in some patients. When sildenafil (25 mg) was simultaneously administered with doxazosin (4 mg) to patients with BPH, mean additional reductions in supine blood pressure of 7 mmHg systolic and 7 mmHg diastolic were observed. When higher doses of sildenafil were administered with doxazosin (4 mg), symptomatic postural hypotension within 1 to 4 hours was reported in some patients. Sildenafil doses greater than 25 mg should not be taken within 4 hours of taking alpha-blockers. The manufacturers for tadalafil and vardenafil state that patients should be stabilized on alpha blocker therapy prior to starting either tadalafil or vardenafil, or if already receiving optimum dose of tadalafil or vardenafil, alpha blocker therapy should be started at the lowest possible dose.
    Silodosin: (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.
    Simeprevir: (Moderate) Simeprevir, a mild intestinal CYP3A4 inhibitor, may increase the side effects of tamsulosin, which is a CYP3A4 substrate. Monitor patients for adverse effects of tamsulosin, such as hypotension, dizziness, syncope, and vertigo.
    Sotalol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Soy Isoflavones: (Minor) Theoretically, because the soy isoflavones appear to inhibit type II 5-alpha-reductase, the soy isoflavones may have additive effects with other 5-alpha reductase inhibitors.
    Streptogramins: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of dalfopristin; quinupristin. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as quinupristin, should be avoided.
    Tadalafil: (Major) Since the symptoms of orthostasis (e.g., postural hypotension, dizziness and vertigo) are reported more frequently in tamsulosin-treated vs. placebo patients, there is a theoretical risk of enhanced hypotensive effects in individual patients when tamsulosin co-administered with vasodilatory agents such as phosphodiesterase inhibitors. Concurrent use of PDE5 inhibitors and alpha-blockers may lead to symptomatic hypotension in some patients. When sildenafil (25 mg) was simultaneously administered with doxazosin (4 mg) to patients with BPH, mean additional reductions in supine blood pressure of 7 mmHg systolic and 7 mmHg diastolic were observed. When higher doses of sildenafil were administered with doxazosin (4 mg), symptomatic postural hypotension within 1 to 4 hours was reported in some patients. Sildenafil doses greater than 25 mg should not be taken within 4 hours of taking alpha-blockers. The manufacturers for tadalafil and vardenafil state that patients should be stabilized on alpha blocker therapy prior to starting either tadalafil or vardenafil, or if already receiving optimum dose of tadalafil or vardenafil, alpha blocker therapy should be started at the lowest possible dose.
    Telaprevir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of telaprevir. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as telaprevir, should be avoided.
    Telithromycin: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of telithromycin. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as telithromycin, should be avoided. (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like telithromycin are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and tamsulosin is necessary, as the systemic exposure of tamsulosin may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of tamsulosin; consider increasing the dose of tamsulosin if necessary. Tamsulosin 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.
    Terazosin: (Severe) Tamsulosin should not be adminsitered in combination with other alpha-blockers.
    Terbinafine: (Moderate) Use caution when administering tamsulosin with a moderate CYP2D6 inhibitor such as terbinafine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Thioridazine: (Moderate) Use caution when administering tamsulosin with a CYP2D6 inhibitor such as thioridazine. Tamsulosin is extensively metabolized by CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP2D6 inhibitor resulted in increases in tamsulosin exposure; interactions with moderate CYP2D6 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Timolol: (Minor) Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs. placebo patients, there is a potential risk of enhanced hypotensive effects when co-administered with antihypertensive agents
    Tipranavir: (Major) Plasma concentrations of tamsulosin may be increased with concomitant use of anti-retroviral protease inhibitors. Tamsulosin is extensively metabolized by CYP3A4 and CYP2D6 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use of tamsulosin with a strong CYP3A4 inhibitor, or an agent with both CYP3A4 and CYP2D6 inhibitor activity, should be avoided. (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Trandolapril; Verapamil: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme. The clearance of dutasteride may be reduced when co-administered with the CYP3A4 inhibitor verapamil. (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Vardenafil: (Major) Since the symptoms of orthostasis (e.g., postural hypotension, dizziness and vertigo) are reported more frequently in tamsulosin-treated vs. placebo patients, there is a theoretical risk of enhanced hypotensive effects in individual patients when tamsulosin co-administered with vasodilatory agents such as phosphodiesterase inhibitors. Concurrent use of PDE5 inhibitors and alpha-blockers may lead to symptomatic hypotension in some patients. When sildenafil (25 mg) was simultaneously administered with doxazosin (4 mg) to patients with BPH, mean additional reductions in supine blood pressure of 7 mmHg systolic and 7 mmHg diastolic were observed. When higher doses of sildenafil were administered with doxazosin (4 mg), symptomatic postural hypotension within 1 to 4 hours was reported in some patients. Sildenafil doses greater than 25 mg should not be taken within 4 hours of taking alpha-blockers. The manufacturers for tadalafil and vardenafil state that patients should be stabilized on alpha blocker therapy prior to starting either tadalafil or vardenafil, or if already receiving optimum dose of tadalafil or vardenafil, alpha blocker therapy should be started at the lowest possible dose.
    Vemurafenib: (Moderate) Vemurafenib is an inducer of CYP3A4 and decreased plasma concentrations of drugs metabolized by this enzyme, such as tamsulosin, could be expected with concurrent use. Use caution, and monitor therapeutic effects of tamsulosin when coadministered with vemurafenib.
    Verapamil: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme. The clearance of dutasteride may be reduced when co-administered with the CYP3A4 inhibitor verapamil. (Moderate) The concomitant administration of tamsulosin with other antihypertensive agents can cause additive hypotensive effects. In addition, diltiazem, nicardipine, and verapamil may increase tamsulosin plasma concentrations via CYP3A4 inhibition. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly.
    Voriconazole: (Major) Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes, and strong inhibitors of CYP3A4 are expected to significantly raise tamsulosin concentrations. Plasma concentrations of tamsulosin are increased with concomitant use of ketoconazole, a strong inhibitor of CYP3A4. Concomitant treatment with ketoconazole resulted in an increase in the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension. Therefore, concomitant use with a strong CYP3A4 inhibitor, such as ketoconazole, itraconazole, posaconazole, or voriconazole should be avoided. (Moderate) CYP3A4 inhibitors, such as voriconazole, may theoretically reduce the metabolism of dutasteride, which is metabolized by CYP3A4 enzyme. Reduced clearance of dutasteride may increase the risk of side effects.
    Warfarin: (Moderate) The manufacturer reports that results from limited in vitro and in vivo drug-drug interaction studies between tamsulosin and warfarin have been inconclusive; and therefore, tamsulosin should be used cautiously with warfarin.
    Zafirlukast: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as zafirlukast. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
    Zileuton: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as zileuton. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.

    PREGNANCY AND LACTATION

    Pregnancy

    Dutasteride; tamsulosin is contraindicated for use in females of childbearing potential; it is pregnancy risk category X and is therefore contraindicated during pregnancy. Dutasteride and other 5-alpha-reductase inhibitors inhibit the conversion of testosterone to DHT that can cause abnormalities in the external genitalia of the male fetus. Pregnant women or women trying to conceive should not handle dutasteride capsules because dutasteride is absorbed through the skin and may result in fetal exposure. If skin contact with a leaking capsule occurs, the affected area should be washed with soap and water immediately. Dutasteride is secreted into male semen. The amount of dutasteride in semen that is available for vaginal absorption is estimated to be less than 100 times the concentrations that produces abnormalities in the genitalia of male offspring in animal studies. In addition, dutasteride is more than 96% protein bound in human semen, which may decrease vaginal absorption of the drug.

    Dutasteride; tamsulosin is contraindicated for use in females of child-bearing potential, which would include females who are breast-feeding; it is not known whether dutasteride or tamsulosin is excreted in human milk.

    MECHANISM OF ACTION

    Dutasteride; tamsulosin is a combination of 2 drugs with different mechanisms of action to improve symptoms in patients with BPH: dutasteride, a 5-alpha-reductase inhibitor (5 ARI), and tamsulosin, an antagonist of alpha-1a-adrenoreceptors.
    Dutasteride: Dutasteride inhibits the conversion of testosterone to 5-alpha-dihydrotestosterone (DHT), the primary androgen that stimulates the development of prostate tissue. The intracellular enzyme 5-alpha-reductase is responsible for this conversion and exists in two isoforms, type I and II. The type II isoenzyme is primarily active in reproductive tissues (i.e., prostate, seminal vesicles, epididymides) and is responsible for two-thirds of circulating DHT. The type I isoenzyme is mostly active in the skin and liver. Dutasteride inhibits both the type I and type II isoforms. In the treatment of benign prostatic hyperplasia, dutasteride reduces circulating DHT, which leads to a reduction in prostate hypertrophy and improvement in urine flow. Dutasteride does not bind to androgen receptors in humans. In addition to reducing DHT, dutasteride increases total testosterone and thyroid-stimulating hormone (TSH) and decreases total serum prostate specific antigen (PSA). Dutasteride does not appear to alter circulating concentrations of sex hormone binding globulin, estradiol, luteinizing hormone, follicle-stimulating hormone, thyroxine (free T4), and dehydroepiandrosterone in healthy volunteers. Dutasteride does not affect the hypothalamic-pituitary-testicular-axis.
    Tamsulosin: Tamsulosin is a selective antagonist at alpha-1-receptors. Alpha-1-receptors are involved in contraction of smooth muscle and are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck. 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. Tamsulosin has 7—38-fold greater affinity for alpha-1a-receptors than for alpha-1b-receptors. Blockade of these receptors by tamsulosin can cause smooth muscles in the bladder neck and prostate to relax, thereby improving urine flow rate and reducing symptoms of BPH.

    PHARMACOKINETICS

    The combination product of dutasteride; tamsulosin (Jalyn) is administered orally. The pharmacokinetics of dutasteride and tamsulosin from Jalyn are comparable to the pharmacokinetics of dutasteride and tamsulosin when administered separately.
     
    Dutasteride: Once in the systemic circulation, approximately 99% of dutasteride is highly bound to albumin and alpha1-acid glycoprotein. Dutasteride is distributed widely throughout the body. Dutasteride is metabolized in the liver via CYP3A4 and CYP3A5 enzymes. Two minor mono-hydroxylated metabolites and 3 major metabolites have been identified. Of these metabolites, the 6-beta-hydroxydutasteride is the only one to have activity comparable to that of dutasteride. Dutasteride and its metabolites are primarily excreted in feces (5% unchanged drug and 40% as metabolites). Only trace amounts of unchanged drug are found in urine (<1%); the dose unaccounted for is approximately 55%. The terminal elimination half-life of dutasteride is about 5 weeks at steady state (average 40 ng/mL). Following daily dosing of 0.5 mg, steady-state concentration of 65% is achieved after 1 month and approximately 90% after 3 months. Steady-state serum and semen concentrations are achieved at about 6 months. On average, semen concentrations are 11.5% of serum dutasteride concentrations in healthy patients at 1 year. Because of the long half-life of dutasteride, serum concentrations remain detectable (> 0.1 ng/mL) for up to 4 to 6 months after stopping therapy. Of note, the reduction of serum DHT is dose dependent and is observed within 1 to 2 weeks.
    Tamsulosin: In the systemic circulation, tamsulosin is extensively bound to plasma proteins (94% to 99%), primarily to alpha1-acid glycoprotein (AAG). Tamsulosin is metabolized by the hepatic cytochrome P450 enzyme system, however, the specific enzymes have not been identified. The metabolites undergo extensive conjugation to glucuronide or sulfate prior to excretion in the urine. Less than 10% of the dose is excreted unchanged in the urine. The elimination half-life of tamsulosin in plasma ranges from 5 to 7 hours.

    Oral Route

    Dutasteride: After oral administration, dutasteride is absorbed rapidly with a short distribution phase. It's bioavailability is estimated to be about 60% (range 40% to 94%). Peak serum concentrations occur at a median of 3 hours.
    Tamsulosin: Following oral administration, tamsulosin is almost completely (> 90%) absorbed under fasting conditions. When administered with food, tamsulosin Cmax decreases by a mean of 30%. Taking tamsulosin on an empty stomach could potentially increase the risk of some side effects (i.e., orthostasis); therefore tamsulosin should be taken with food. The time to maximum concentration is roughly 6 hours under fed conditions.