Dutasteride - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Orthostatic hypotension and/or syncope can occur.

Advise patients of symptoms related to postural hypotension and to avoid situations where injury could result if syncope occurs.

Do not use dutasteride and tamsulosin hydrochloride capsules with other alpha-adrenergic antagonists, as this may increase the risk of hypotension.

Dutasteride and tamsulosin hydrochloride capsules reduce serum prostate-specific antigen (PSA) concentration by approximately 50%.

However, any confirmed increase in PSA while on dutasteride and tamsulosin hydrochloride capsules may signal the presence of prostate cancer and should be evaluated, even if those values are still within the normal range for untreated men.

Do not use dutasteride and tamsulosin hydrochloride capsules with strong inhibitors of cytochrome P450 (CYP) 3A4 (e.g., ketoconazole).

Use caution in combination with moderate CYP3A4 inhibitors (e.g., erythromycin) or strong (e.g., paroxetine) or moderate CYP2D6 inhibitors, a combination of both CYP3A4 and CYP2D6 inhibitors, or known poor metabolizers of CYP2D6.

Concomitant use with known inhibitors can cause a marked increase in drug exposure. ( 5.2 , 7.1 , 12.3 ) Exercise caution with concomitant use of phosphodiesterase-5 (PDE-5) inhibitors, as this may increase the risk of hypotension.

Drugs that contain dutasteride, including dutasteride and tamsulosin hydrochloride capsules, may increase the risk of high-grade prostate cancer. ( 5.4 , 6.1 ) Prior to initiating treatment with dutasteride and tamsulosin hydrochloride capsules, consideration should be given to other urological conditions that may cause similar symptoms.

Females who are pregnant or may be pregnant should not handle dutasteride and tamsulosin hydrochloride capsules due to potential risk to a male fetus. ( 5.6 , 8.1 ) Advise patients about the possibility and seriousness of priapism.

Patients should not donate blood until 6 months after their last dose of dutasteride and tamsulosin hydrochloride capsules.

Intraoperative Floppy Iris Syndrome has been observed during cataract and glaucoma surgery after alpha-adrenergic antagonist exposure.

Advise patients considering cataract or glaucoma surgery to tell their ophthalmologist that they take or have taken dutasteride and tamsulosin hydrochloride capsules.

Exercise caution with concomitant use of warfarin. ( 5.2 , 7.2 , 12.3 ) 5.1 Orthostatic Hypotension As with other alpha-adrenergic antagonists, orthostatic hypotension (postural hypotension, dizziness, and vertigo) may occur in patients treated with tamsulosin-containing products, including dutasteride and tamsulosin hydrochloride capsules, and can result in syncope.

Patients starting treatment with dutasteride and tamsulosin hydrochloride capsules should be cautioned to avoid situations where syncope could result in an injury [see Adverse Reactions ] .

5.2 Drug-Drug Interactions Strong Inhibitors of Cytochrome P450 (CYP) 3A4 Tamsulosin-containing products, including dutasteride and tamsulosin hydrochloride capsules, should not be coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole) as this can significantly increase tamsulosin exposure [see Drug Interactions , Clinical Pharmacology ].

Moderate Inhibitors of CYP3A4, Inhibitors of CYP2D6, or a Combination of Both CYP3A4 and CYP2D6 Inhibitors Tamsulosin-containing products, including dutasteride and tamsulosin hydrochloride capsules, should be used with caution when coadministered with moderate inhibitors of CYP3A4 (e.g., erythromycin), strong (e.g., paroxetine) or moderate (e.g., terbinafine) inhibitors of CYP2D6, a combination of both CYP3A4 and CYP2D6 inhibitors, or in patients known to be poor metabolizers of CYP2D6, as there is a potential for significant increase in tamsulosin exposure [see Drug Interactions , Clinical Pharmacology ] .

Cimetidine Caution is advised when tamsulosin-containing products, including dutasteride and tamsulosin hydrochloride capsules, are coadministered with cimetidine [see Drug Interactions , Clinical Pharmacology ] .

Other Alpha-adrenergic Antagonists Tamsulosin-containing products, including dutasteride and tamsulosin hydrochloride capsules, should not be coadministered with other alpha-adrenergic antagonists because of the increased risk of symptomatic hypotension.

Phosphodiesterase-5 (PDE-5) Inhibitors Caution is advised when alpha-adrenergic-antagonist-containing products, including dutasteride and tamsulosin hydrochloride capsules, are coadministered with PDE-5 inhibitors.

Alpha-adrenergic antagonists and PDE-5 inhibitors are both vasodilators that can lower blood pressure.

Concomitant use of these 2 drug classes can potentially cause symptomatic hypotension.

Warfarin Caution should be exercised with concomitant administration of warfarin and tamsulosin-containing products, including dutasteride and tamsulosin hydrochloride capsules [see Drug Interactions , Clinical Pharmacology ] .

5.3 Effects on Prostate-Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection Coadministration of dutasteride with tamsulosin resulted in similar changes to serum PSA as with dutasteride monotherapy.

In clinical trials, dutasteride reduced serum PSA concentration by approximately 50% within 3 to 6 months of treatment.