Jalyn (dutasteride/tamsulosin HCl)

The manufacturer states that safety and efficacy of tamsulosin in children younger than 18 years of age have not been established, and clinical experience in these patients is not available.

Although protein binding of tamsulosin may be altered in patients with mild to moderate (i.e., creatinine clearance of 30-70 mL/minute per 1.73 m2) or severe (i.e., creatinine clearance of 10 to less than 30 mL/minute per 1.73 m2) renal impairment and in patients with moderate hepatic impairment resulting in changes of overall plasma concentrations of the drug, alterations in intrinsic clearance and concentrations of unbound tamsulosin do not appear to be substantial. Therefore, the manufacturer states that dosage adjustment in such patients is not necessary. However, tamsulosin has not been studied in patients with end-stage (i.e., creatinine clearance of less than 10 mL/minute per 1.73 m2) renal disease.

Dutasteride is administered orally without regard to meals. Dutasteride capsules should be swallowed whole and not chewed or opened, since contact with the capsule contents may result in irritation of the oropharyngeal mucosa.

Tamsulosin is administered orally. Because food may decrease peak plasma concentrations of tamsulosin and lengthen the time to achievement of peak plasma concentrations and decrease oral bioavailability of the drug, the manufacturer recommends that tamsulosin be taken 30 minutes after a meal; it is recommended that the drug be taken after the same meal each day. Patients should be advised that the capsules must be swallowed intact and not be opened, chewed, or crushed.

There is no enhanced messaging for this drug.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Alfuzosin;Silodosin;Tamsulosin/Protease Inhibitors

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The protease inhibitors may inhibit the metabolism of alfuzosin,(1) silodosin,(2) and tamsulosin(3) by CYP3A4.

CLINICAL EFFECTS: Co-administration of a protease inhibitor may result in increased alfuzosin,(1) silodosin,(2) and tamsulosin(3) levels and serious effects such as hypotension.

PREDISPOSING FACTORS: In patients receiving tamsulosin, the interaction may be worse in patients who are CYP2D6 poor metabolizers because tamsulosin also undergoes metabolism by this pathway.(3)

PATIENT MANAGEMENT: The US manufacturers of alfuzosin(1) and silodosin(2) state that concurrent use of strong CYP3A4 inhibitors is contraindicated. The US manufacturer of tamsulosin states that tamsulosin should not be used with strong CYP3A4 inhibitors.(3) The US manufacturers of atazanavir,(4) darunavir,(5) ensitrelvir,(6) fosamprenavir,(7) indinavir,(8) lopinavir/ritonavir,(9) nelfinavir,(10), nirmatrelvir/ritonavir,(11) paritaprevir, (12) saquinavir,(13) and tipranavir(14) state that concurrent use of alfuzosin is contraindicated.

DISCUSSION: Administration of ketoconazole (400 mg daily), another inhibitor of CYP3A4, increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of alfuzosin (10 mg) by 2.3-fold and 3.2-fold, respectively.(1) Administration of ketoconazole (200 mg daily) increased the Cmax and AUC of a single dose of alfuzosin (10 mg) by 2.1-fold and 2.5-fold, respectively.(1) Administration of ketoconazole (200 mg daily for 4 days), increased the Cmax and AUC of a single dose of silodosin (4 mg) by 3.7-fold and 2.9-fold, respectively.(2) Administration of ketoconazole (400 mg daily for 4 days) increased the Cmax and AUC of a single dose of silodosin (8 mg) by 3.8-fold and 3.2-fold, respectively.(2) In a study in 24 healthy subjects, administration of ketoconazole (400 mg daily for 5 days) increased the Cmax and AUC of a single dose of tamsulosin (0.4 mg) by 2.2-fold and 2.8-fold, respectively.(3)

Alpha-Blockers/Iloperidone; Milsaperidone

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Concurrent use of iloperidone or milsaperidone and an alpha-blocker may result in additive or synergistic effects on blood pressure.(1,2)

CLINICAL EFFECTS: Concurrent use of iloperidone or milsaperidone and an alpha-blocker may result in symptomatic hypotension.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of iloperidone and milsaperidone state that concurrent use with alpha-blockers should be avoided.(1,2)

DISCUSSION: Iloperidone and milsaperidone have alpha-blocking properties.(1,2)

Silodosin; Tamsulosin/Strong Cyp3a4 Inhibitors

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Strong CYP3A4 inhibitors may inhibit the metabolism of silodosin and tamsulosin.(1,2)

CLINICAL EFFECTS: Coadministration of a strong CYP3A4 inhibitor may cause an increase in silodosin and tamsulosin levels and effects, including severe hypotension.(1,2)

PREDISPOSING FACTORS: In patients receiving tamsulosin, the interaction may be worse in patients who are CYP2D6 poor metabolizers because tamsulosin also undergoes metabolism by this pathway.(2)

PATIENT MANAGEMENT: The US manufacturer of silodosin states that concurrent use of strong CYP3A4 inhibitors is contraindicated.(1) The US manufacturer of tamsulosin states that tamsulosin should not be used with strong CYP3A4 inhibitors.(2) The US manufacturer of itraconazole states that silodosin or tamsulosin should not be administered until at least 2 weeks after itraconazole treatment.(3)

DISCUSSION: Administration of ketoconazole (200 mg daily for 4 days) increased the Cmax and AUC of a single dose of silodosin (4 mg) by 3.7-fold and 2.9-fold, respectively.(1) Administration of ketoconazole (400 mg daily for 4 days) increased the Cmax and AUC of a single dose of silodosin (8 mg) by 3.8-fold and 3.2-fold, respectively.(1) In a study in 24 healthy male subjects, administration of ketoconazole (400 mg daily for 5 days) increased the Cmax and AUC of a single dose of tamsulosin (0.4 mg) by 2.2-fold (90% CI 1.96, 2.45) and 2.8-fold (90% CI 2.56, 3.07), respectively. No serous adverse events were reported when subjects took tamsulosin with ketoconazole.(2,4) Strong inhibitors of CYP3A4 include: adagrasib, boceprevir, ceritinib, clarithromycin, cobicistat, idelalisib, itraconazole, josamycin, ketoconazole, lonafarnib, mibefradil, mifepristone, nefazodone, posaconazole, relacorilant, ribociclib, telaprevir, telithromycin, troleandomycin, tucatinib and voriconazole.(5,6)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Alpha-Blockers/Cgmp Specific Pde Type-5 Inhibitors

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Concurrent use of avanafil,(1) sildenafil,(2-5) tadalafil,(6-9) or vardenafil(10-14) and an alpha-blocker may result in additive or synergistic effects on blood pressure.

CLINICAL EFFECTS: Concurrent use of avanafil,(1) sildenafil,(2-5) tadalafil,(6-9) or vardenafil(10-14)) and an alpha-blocker may result in symptomatic hypotension.

PREDISPOSING FACTORS: Patients who have a history of hemodynamic instability on alpha-blocker therapy prior to initiating avanafil, sildenafil, tadalafil, or vardenafil may be at an increased risk of symptomatic hypotension during concurrent therapy.

PATIENT MANAGEMENT: The US manufacturer of avanafil states that patients taking alpha-blockers should be stabilized on their alpha-blocker prior to beginning avanafil therapy. Avanafil should be initiated at the 50 mg dosage. In patients stabilized on avanafil therapy, alpha-blocker therapy should be initiated at the lowest possible dosage.(1) The US, Australian, Canadian, and UK manufacturers of sildenafil state that patients taking alpha-blockers should be stabilized on their alpha-blocker prior to beginning sildenafil therapy. Sildenafil should be initiated at the lowest possible dosage. In patients stabilized on sildenafil therapy, alpha-blocker therapy should be initiated at the lowest possible dosage.(2-5) The US manufacturer of tadalafil states that patients taking tadalafil for erectile dysfunction (ED) and alpha-blockers should be stabilized on their alpha-blocker prior to beginning tadalafil therapy. Tadalafil should be initiated at the lowest possible dosage. In patients stabilized on tadalafil therapy, alpha-blocker therapy should be initiated at the lowest possible dose. The combination of tadalafil and an alpha-blocker for treatment of benign prostatic hyperplasia (BPH) is not recommended. Patients on alpha-blocker therapy for BPH should discontinue their alpha-blocker at least one day prior to starting tadalafil for once daily use for the treatment of BPH.(6) The Australian manufacturer of tadalafil states that tadalafil should be used with caution in patients taking alpha-blockers.(7) The Canadian manufacturer of tadalafil states that it may be used with tamsulosin and should be used with caution with other alpha-blockers.(8) The UK manufacturer of tadalafil states that concurrent use with alpha-blockers is not recommended.(9) The US, Canadian, and UK manufacturers of vardenafil state that patients taking alpha-blockers should be stabilized on their alpha-blocker prior to beginning vardenafil therapy. Vardenafil should be initiated at the lowest possible dosage. In patients stabilized on vardenafil therapy, alpha-blocker therapy should be initiated at the lowest possible dosage.(10-12) The UK manufacturer of vardenafil states that vardenafil may be give at any time in relation to tamsulosin; however, a dose separation period of 6 hour should be considered for other alpha-blockers.(12) The Australian manufacturer of vardenafil states that concurrent use with alpha-blockers is not recommended.(13) The US manufacturers of doxazosin,(14) prazosin(15) and terazosin(16) state that PDE-5 inhibitor therapy should be initiated at the lowest dose.

DISCUSSION: In a study in 24 subjects, concurrent use of avanafil (200 mg) with doxazosin (1 mg on Day 1, titrated to 8 mg for Days 8-18) resulted in 7 subjects experiencing potentially clinically significant changes in blood pressure.(1) In a study in 24 subjects, concurrent use of avanafil (200 mg) with tamsulosin (0.4 mg Days 1-11) resulted in 5 subjects experiencing potentially clinically significant changes in blood pressure.(1) Simultaneous administration of sildenafil (25 mg) and doxazosin (4 mg) resulted in mean additional reductions of supine blood pressure of 7 mmHg systolic and 7 mmHg diastolic. When doxazosin (4 mg) was simultaneously administered with higher doses of sildenafil, there were reports of symptomatic postural hypotension within one to four hours.(2) In a study, concurrent administration of a single dose of tadalafil (20 mg) to healthy subjects receiving alfuzosin (10 mg daily) resulted in mean maximum decreases in standing and supine systolic blood pressure by 2.2 mmHg and 4.4 mmHg, respectively. There were no subjects with a decrease from baseline standing systolic blood pressure greater than 30 mmHg.(6) In a study, concurrent administration of a single dose of tadalafil (20 mg) to 18 healthy subjects receiving doxazosin (8 mg daily) resulted in significant augmentation of the blood-pressure lowering effects of doxazosin (by 9.8 mmHg). The number of subjects with a standing blood pressure of less than 85 mmHg was greater after concurrent doxazosin and tadalafil than when compared to doxazosin with placebo (28% versus 6%). One subject reported vertigo and another reported dizziness. No syncope was reported.(5,14) In a second study, concurrent administration of a single dose of tadalafil (20 mg) to healthy subjects receiving doxazosin (4-8 mg daily) also resulted in augmentation of the blood-pressure lowering affects of doxazosin. One subject reported symptomatic hypotension and another reported dizziness with concurrent therapy.(6) In a study, concurrent administration of a single dose of tadalafil (20 mg) to healthy subjects receiving tamsulosin (0.4 mg daily) resulted in no significant decreases in blood pressure.(6,17) Hypotension has been reported with concurrent use of terazosin and phosphodiesterase-5 inhibitors.(16) With simultaneous administration of vardenafil (10 mg) and terazosin (10 mg), 6 of 8 healthy subjects experienced a standing systolic blood pressure of less than 85 mmHg. With simultaneous vardenafil (20 mg) and terazosin (10 mg), 2 of 9 subjects experienced a standing systolic blood pressure of less than 85 mmHg. When vardenafil (20 mg) was administered 6 hours apart from terazosin (10 mg), 7 of 28 subjects experienced a standing systolic blood pressure of less than 85 mmHg.(10) With simultaneous administration of vardenafil (10 mg) and tamsulosin (0.4 mg), two of 16 subjects experienced a standing systolic blood pressure of less than 85 mmHg. When vardenafil (20 mg) was administered six hours apart from tamsulosin (0.4 mg), one of 24 subjects experienced a standing systolic blood pressure of less than 85 mmHg.(10) In a study in subjects with benign prostatic hyperplasia (BPH) on stable tamsulosin or terazosin therapy, simultaneous vardenafil (5 mg) and tamsulosin resulted in no effects on blood pressure. Simultaneous vardenafil (5 mg) with terazosin resulted in hypotension in some subjects. This effect did not occur when vardenafil and terazosin were separated by 6 hours.(12) In a placebo controlled, crossover study in 22 subjects with benign prostatic hyperplasia receiving tamsulosin, subjects received single doses of vardenafil (10 mg and 20 mg). No patients exhibited symptomatic hypotension. Three patients receiving 20 mg of vardenafil reported dizziness, but none had a systolic blood pressure of less than 95 mmHg.(18) In a placebo-controlled study in 24 health male subjects, administration of sildenafil (100 mg) or tadalafil (20 mg) with silodosin resulted in an increase in positive orthostatic tests in the 12 hours after concurrent administration when compared with the administration of silodosin alone. There were no reports of symptomatic orthostasis or dizziness.(19)

Selected Antihypertensives/Tizanidine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Tizanidine is an alpha-2 agonist. Concurrent use with antihypertensive agents may result in additive effects on blood pressure.(1)

CLINICAL EFFECTS: Concurrent use of antihypertensives and tizanidine may result in hypotension.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving concurrent therapy should be monitored for hypotension. The risk of hypotension may be decreased by careful titration of tizanidine dosages and monitoring for hypotension prior to dose advancement. Counsel patients about the risk of orthostatic hypotension.(1)

DISCUSSION: Severe hypotension has been reported following the addition of tizanidine to existing lisinopril therapy.(2-4)

Tamsulosin/Diltiazem;Dronedarone;Verapamil

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Tamsulosin is primarily metabolized by CYP3A4 and CYP2D6. Diltiazem, dronedarone, and verapamil are both moderate inhibitors of CYP3A4 and weak inhibitors of CYP2D6(1,2) and so may delay tamsulosin metabolism via both major pathways. The pharmacodynamic effects of diltiazem and verapamil on blood pressure may further increase the risk for hypotension from tamsulosin.

CLINICAL EFFECTS: Co-administration of diltiazem, dronedarone, or verapamil may cause an increase in tamsulosin levels and effects, including symptomatic hypotension.

PREDISPOSING FACTORS: The interaction may be more severe in poor metabolizers of CYP2D6 or in patients receiving additional agents which inhibit CYP3A4 or CYP2D6.

PATIENT MANAGEMENT: The manufacturer of tamsulosin states there is a potential for a significant increase in exposure when tamsulosin is co-administered with both CYP3A4 and CYP2D6 inhibitors.(3) The risk for hypotension from tamsulosin is more likely after starting or increasing the dose of either drug.(3) Monitor for orthostatic hypotension prior to a dose increase and delay dose adjustment if needed. Monitor patients after a dose increase, particularly those with a history of hypotension, orthostasis or falls. Instruct patient to report episodes of dizziness, lightheadedness or feeling faint.(3)

DISCUSSION: An open label, multicenter, prospective trial evaluated the safety of tamsulosin 0.4 mg daily over 24 weeks in 1784 patients. The most commonly reported adverse effects were dizziness, headache, abnormal ejaculation and hypotension. Patients receiving verapamil had an approximately 3-fold (odds ratio 3.166, 95% confidence interval 1.513, 6.58) increase in the risk for adverse events.(4)

*Pregnancy.

*Known hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride, other 5alpha-reductase inhibitors, or any ingredient in the formulation.

Known hypersensitivity to tamsulosin or any ingredient in the formulation.

• Lactation
• Pregnancy

• CYp2d6 poor metabolizer
• CYp3a4 poor metabolizer
• Intraoperative floppy iris syndrome
• Orthostatic hypotension
• Priapism

• Cataract surgery
• Disease of liver
• High-grade prostate cancer

Adverse effects reported in at least 1% of patients receiving dutasteride and more frequently than with placebo include impotence, decreased libido, ejaculation disorder, and breast disorders (including breast tenderness and enlargement). Ejaculation disorders have been reported more frequently with combined therapy with dutasteride and tamsulosin than with either drug alone.

Headache, infection, asthenia, back pain, chest pain, dizziness, somnolence, insomnia, decreased libido, rhinitis, pharyngitis, increased cough, sinusitis, diarrhea, nausea, tooth disorder, abnormal ejaculation, blurred vision.

Less Frequent

• High-grade prostate cancer

Rare or Very Rare

• Angioedema
• Angioedema
• Atrial fibrillation
• Cardiac arrhythmia
• Erythema multiforme
• Exfoliative dermatitis
• Gynecomastia
• Hypersensitivity drug reaction
• Hypersensitivity drug reaction
• Intraoperative floppy iris syndrome
• Localized edema
• Malignant tumor of male breast
• Priapism
• Skin rash
• Skin rash
• Stevens-johnson syndrome
• Syncope
• Urticaria

More Frequent

• Back pain
• Diarrhea
• Disorder of ejaculation
• Disorder of ejaculation
• Dizziness
• Erectile dysfunction
• General weakness
• Headache disorder
• Libido changes
• Rhinitis

Less Frequent

• Asthenozoospermia
• Blurred vision
• Chest pain
• Cough
• Drowsy
• Infection
• Insomnia
• Libido changes
• Nausea
• Oligospermia
• Pharyngitis
• Sinusitis
• Tooth disorder
• Vertigo

Rare or Very Rare

• Accidental fall
• Constipation
• Decrease ejaculate volume
• Depression
• Dizziness
• Dyspnea
• Epistaxis
• Hypotension
• Mastalgia
• Orthostatic hypotension
• Palpitations
• Pruritus of skin
• Pruritus of skin
• Testicular pain
• Testicular swelling
• Urticaria
• Visual changes
• Vomiting
• Xerostomia

No enhanced messaging available.

Safety and efficacy not established in children; the drug is not indicatedfor use in children.

Not indicated for use in children.

Dutasteride is not indicated for use in women and is contraindicated in women who are pregnant. If used during pregnancy or if pregnancy occurs, apprise the pregnant woman of potential fetal hazard to a male fetus.

Because 5alpha-reductase inhibitors inhibit the conversion of testosterone to DHT, dutasteride may cause abnormalities of the external genitalia of male fetuses exposed to the drug during pregnancy. In animal reproduction studies, dutasteride inhibited normal development of externalgenitalia in male offspring when given to rats or rabbits during organogenesis at doses lessthan the maximum recommended human dose (MRHD) of 0.5 mg daily, in the absenceof maternal toxicity.

Because of the possibility of absorption through the skin and subsequent risk to a male fetus, women who are pregnant or who potentially may be pregnant should not handle dutasteride capsules; if contact with a leaking dutasteride capsuleoccurs during pregnancy, the affected area should be washed immediately with soap and water.

Category B. Not indicated for use in women.

Not known whether dutasteride is distributed into milk in humans or if the drug has any effects on the breastfed infant or on milk production. Dutasteride is not indicated for use in women.

Not indicated for use in women.

No substantial differences in safety and efficacy relative to younger men in clinical studies or experience to date, but increased sensitivity cannot be ruled out.

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.