hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.rufinamideMinor (1)rufinamide will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.saquinavirSerious - Use Alternative (1)saquinavir increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.secobarbitalMinor (1)secobarbital will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)secobarbital will decrease the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.sertralineMonitor Closely (1)sertraline increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.sildenafilMonitor Closely (1)sildenafil, tamsulosin. Either increases effects of the other by additive vasodilation. Use Caution/Monitor. Risk of hypotension.silodosinSerious - Use Alternative (1)silodosin, tamsulosin. Either increases effects of the other by additive vasodilation. Avoid or Use Alternate Drug. Risk of hypotension.St John's WortMonitor Closely (1)St John's Wort will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.stiripentolMonitor Closely (1)stiripentol, tamsulosin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.tadalafilMonitor Closely (1)tadalafil, tamsulosin. Either increases effects of the other by additive vasodilation. Use Caution/Monitor. Risk of hypotension.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.terazosinSerious - Use Alternative (1)terazosin, tamsulosin. Either increases effects of the other by additive vasodilation. Avoid or Use Alternate Drug. Risk of hypotension.terbinafineMonitor Closely (1)terbinafine will increase the level or effect of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.thioridazineMonitor Closely (1)thioridazine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.ticlopidineMonitor Closely (1)ticlopidine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.tipranavirSerious - Use Alternative (1)tipranavir increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.topiramateMinor (1)topiramate will decrease the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.tranylcypromineMonitor Closely (1)tranylcypromine increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.trazodoneMonitor Closely (1)trazodone increases levels of tamsulosin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.vardenafilMonitor Closely (1)vardenafil, tamsulosin. Either increases effects of the other by additive vasodilation. Use Caution/Monitor. Risk of hypotension.verapamilMinor (1)verapamil will increase the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.voriconazoleMinor (1)voriconazole will increase the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)voriconazole increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.zafirlukastMinor (1)zafirlukast will increase the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. 1-10% Year 1 Ejaculation disorders (1.6-7.8%) Impotence (1.1-5.4%) Decreased libido (≤4.5%) Breast disorders (≤1.1%) Dizziness (≤1.1%) Year 2-4 Impotence (1.1-5.4%) Ejaculation disorders (≤1%) <1% Cardiac failure Year 2-4 Decreased libido Breast disorders Dizziness Postmarketing Reports Dutasteride Immune system disorders: Hypersensitivity reactions, including rash, pruritus, urticaria, localized edema, serious skin reactions, and angioedema Neoplasms: Male breast cancer Psychiatric disorders: Depressed mood Reproductive system and breast disorders: Testicular pain and testicular swelling Tamsulosin Immune system disorders: Hypersensitivity reactions, including rash, urticaria, pruritus, angioedema, and respiratory problems have been reported with positive rechallenge in some cases Cardiac disorders: Palpitations, dyspnea, atrial fibrillation, arrhythmia, and tachycardia Skin disorders: Skin desquamation, including Stevens-Johnson syndrome, erythema multiforme, dermatitis exfoliative Gastrointestinal disorders: Constipation, vomiting, dry mouth Reproductive system and breast disorders: Priapism Vascular disorders: Hypotension Ophthalmologic disorders: During cataract surgery, a variant of small pupil syndrome known as intraoperative floppy iris syndrome (IFIS) associated with alpha adrenergic antagonist therapy, blurred vision, visual impairment, glaucoma Respiratory: Epistaxis Contraindications Clinically significant hypersensitivity (eg, serious skin reactions, angioedema, urticaria, pruritus, respiratory symptoms) to dutasteride, other 5 alpha-reductase inhibitors, or tamsulosin Females who are pregnant Cautions Orthostatic hypotension and/or syncope can occur Reduces total serum prostate-specific antigen (PSA) concentration by ~50%, evaluate any confirmed increases in PSA levels from nadir, even if those values are within normal range, for the presence of prostate cancer Caution patients about the possibility and seriousness of priapism Advise patients to not donate blood until 6 months after their last dose Intraoperative floppy iris syndrome has been observed during cataract surgery after alpha-adrenergic antagonist exposure 5-ARIs and prostate cancer risk June 9, 2011: Recent data from 2 large, randomized, controlled trials, Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, observed an increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer) in trial participants taking 5-alpha reductase inhibitors (5-ARIs) Revised prescribing information recommends that before initiating 5-ARIs, rule out other urological conditions, including prostate cancer that might mimic benign prostatic hyperplasia (BPH) Drug interaction overview Tamsulosin: CYP3A4 and CYP2D6 substrate Dutasteride: CYP3A4 and CYP3A5 substrate Additive hypotensive effects Coadministration with PDE-5 inhibitors (eg, sildenafil) or other alpha-antagonists (eg, doxazosin, terazosin may increase risk of hypotension CYP3A4 and CYP2D6 inhibitors Strong CYP3A4 inhibitors (eg, ketoconazole): Avoid coadministration Less potent CYP3A4 inhibitors (eg, terbinafine), strong or moderate (eg, terbinafine, paroxetine) CYP2D6 inhibitors, a combination of both CYP3A4 and CYP2D6 inhibitors, or poor metabolizers of CYP2D6: Use caution Ketoconazole (strong CYP3A4 inhibitor) and paroxetine (strong CYP2D6 inhibitor) resulted in increased in plasma levels of tamsulosinEffects of CYP3A4 inhibitors on dutasteride has not been studied Calcium channel blockers No dosage adjustment recommended Coadministration of verapamil or diltiazem decreases clearance and increases effects of dutasteride Warfarin Use caution; monitor INR Limited studies showed inconclusive results regarding coadministration of tamsulosin with warfarin Pregnancy Not indicated for use in females; contraindicated for use in pregnancy because may cause harm to male fetus; dutasteride is a 5-alpha-reductase inhibitor that prevents conversion of testosterone to dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia Abnormalities in genitalia of male fetuses is an expected physiological consequence of inhibition of this conversion; these results are similar to observations in male infants with genetic 5-alpha-reductase deficiency Animal data In animal reproduction studies, dutasteride inhibited normal development of external genitalia in male offspring when given to rats or rabbits during organogenesis at less than maximum recommended human dose (MRHD) of 0.5 mg daily, in absence of maternal toxicity; at 15 times MRHD, prolonged pregnancy, decreased reproductive organ weights, and delayed puberty in male offspring were observed in rats, with no-effect levels less than the MRHD of 0.5 mg daily Increased placental weights in rabbits were also observed, with no-effect levels less than the MRHD of 0.5 mg daily Although dutasteride is secreted into human semen, drug concentration in human female partner is approximately 100 times less than concentrations producing abnormalities of male genitalia in animal studies In monkeys dosed during organogenesis at blood concentrations comparable to or above levels to which a human female partner is estimated to be exposed, male offspring external genitalia was not adversely affected No feminization occurred in male offspring of untreated female rats mated to treated male rats even though detectable blood levels of dutasteride were observed in the female rats No adverse developmental effects were observed in animal studies in which tamsulosin hydrochloride was administered to rats or rabbits during period of organogenesis Reproductive potential Effects of dutasteride 0.5 mg/day on semen characteristics were evaluated in normal volunteers aged 18 to 52 years (n = 27 dutasteride, n = 23 placebo) throughout 52 weeks of treatment and 24 weeks of post-treatment follow-up; at 52 weeks, mean percent reductions from baseline in total sperm count, semen volume, and sperm motility were 23%, 26%, and 18%, respectively, in the dutasteride group when adjusted for changes from baseline in placebo group; sperm concentration and morphology were unaffected After 24 weeks of follow-up, mean percent change in total sperm count in dutasteride group remained 23% lower than baseline, while mean values for all semen parameters at all timepoints remained within normal ranges and did not meet predefined criteria for a clinically significant change (30%), 2 subjects in the dutasteride group had decreases in sperm count of greater than 90% from baseline at 52 weeks, with partial recovery at 24-week follow-up; clinical significance of these effects on semen characteristics for an individual patient’s fertility is not known Lactation Therapy not indicated for use in femalesPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Dutasteride: Selective inhibitor of type 1 and type 2 isoforms of 5-alpha-reductase Tamsulosin: Alpha-adrenergic antagonist; blocks alpha-1a adrenergic receptor in smooth muscle of prostate, decreasing bladder neck & urethral resistance Absorption Bioavailability: 60% (dutasteride); 10% (tamsulosin) Peak Plasma Time: 2-3 hr (dutasteride); 4-5 hr fasting; 6-7 hr with food (tamsulosin) Onset: 1-2 weeks (dutasteride); 4-8 hr (tamsulosin) Distribution Protein Bound: 99% (dutasteride and tamsulosin) Vd: 300-500 L (dutasteride); 0.2 L (tamsulosin) Metabolism Dutasteride Metabolism: hepatic P450 enzyme CYP3A4 and CYP2D6 Metabolites, major: 4'-hydroxydutasteride, 6-hydroxydutasteride (as active as parent), 6,4'-dihydroxydutasteride Tamsulosin Metabolism: liver Metabolites: glucuronide and sulfate conjugates (inactive) Elimination Half-Life: 5 weeks at steady state (dutasteride); 14-15 hr (tamsulosin) Excretion: mainly feces (dutasteride); urine 76%, feces 21% (tamsulosin) Oral Administration Swallow capsules whole; do not chew, crush, or open High temperatures may deform and/or discolored capsules; discard if this occurs Missed dose Take later that same day, 30 min after a meal; do not take 2 capsules in the same day Missed doses for several days: Contact healthcare provider before restarting Storage Store at 25ºC (77ºF); excursions permitted 15-30ºC (59-86ºF) Capsules may become deformed and/or discolored if kept at high temperatures Dutasteride is absorbed through the skin Females who are pregnant or who could become pregnant should not be handling capsules No images available for this drug. 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