Source: Marketing Authorisation Holder Revision Year: 2013
Prior to initiating treatment with URIMAX D tablets, consideration should be given to other urological conditions that may cause similar symptoms. In addition, BPH and prostate cancer may coexist.
The signs and symptoms of orthostasis (postural hypotension, dizziness and vertigo) were detected more frequently in tamsulosin hydrochloride treated patients than in placebo recipients. As with other alpha-adrenergic blocking agents, there is a potential risk of syncope. Patients beginning treatment with URIMAX D tablets should be cautioned to avoid situations in which injury could result should syncope occur.
Rarely (probably less than 1 in 50,000 patients), tamsulosin hydrochloride, like other alpha1-antagonists, has been associated with priapism (persistent painful penile erection unrelated to sexual activity). Because this condition can lead to permanent impotence if not properly treated, patients must be advised about the seriousness of the condition.
Intraoperative floppy iris syndrome (IFIS) has been observed during cataract surgery in some patients treated with alpha adrenergic antagonists, including tamsulosin hydrochloride.
Most reports were in patients taking the alpha1-blocker when IFIS occurred, but in some cases, the alpha adrenergic antagonist had been stopped prior to surgery. In most of these cases, the alpha adrenergic antagonist had been stopped recently prior to surgery (2-14 days), but in a few cases, IFIS was reported after the patient had been off the alpha1-blocker for a longer period (5 weeks-9 months). IFIS is a variant of small-pupil syndrome and is characterized by the combination of 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. The patient’s ophthalmologist should be prepared for possible modifications to their surgical technique, such as the utilization of iris hooks, iris dilator rings or viscoelastic substances.
IFIS may increase the risk of eye complications during and after the operation. The benefit of stopping alpha adrenergic antagonist therapy prior to cataract surgery has not been established. The initiation of therapy with tamsulosin hydrochloride in patients for whom cataract surgery is scheduled is not recommended.
In patients with sulpha allergy, allergic reaction to tamsulosin hydrochloride has been rarely reported. If a patient reports a serious or life-threatening sulpha allergy, caution is warranted when administering URIMAX D tablets.
Women who are pregnant or may be pregnant should not handle URIMAX D tablets because of the possibility of the absorption of dutasteride through the skin, which could result in unintended foetal exposure. If a woman who is pregnant or who could become pregnant comes in contact with leaking broken URIMAX D tablets, the contact area should be washed immediately with soap and water.
Men being treated with URIMAX D tablets should not donate blood until at least 6 months have passed following their last dose, so as to prevent pregnant women from receiving dutasteride through blood transfusion.
In clinical studies, dutasteride reduced serum prostate-specific antigen (PSA) concentration by approximately 50% within 3-6 months of treatment. This decrease was predictable over the entire range of PSA values in patients with symptomatic BPH, although it may vary in individuals. Dutasteride may also cause decreases in serum PSA in the presence of prostate cancer. To interpret serial PSAs in men taking dutasteride, a new PSA baseline should be established at least 3 months after starting treatment and the PSA monitored periodically thereafter. Any confirmed increase from the lowest PSA value while on dutasteride may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5 alpha-reductase inhibitor. Non-compliance with dutasteride may also affect PSA test results.
To interpret an isolated PSA value in a man treated with dutasteride for 3 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, 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. Co-administration of dutasteride and tamsulosin hydrochloride resulted in similar changes to serum PSA as with dutasteride monotherapy.
In men aged 50 to 75 years, with a prior negative biopsy for prostate cancer and a baseline PSA between 2.5 ng/mL and 10.0 ng/mL, who were taking dutasteride in the 4-year Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, there was an increased incidence of Gleason score 8-10 prostate cancer compared with men taking placebo (dutasteride 1.0% versus placebo 0.5%). In a 7-year, placebo-controlled clinical trial with another 5 alpha-reductase inhibitor (finasteride 5 mg), similar results for Gleason score 8-10 prostate cancer were observed (finasteride 1.8% versus placebo 1.1%). The 5 alpha-reductase inhibitors may increase the risk of development of high-grade prostate cancer. It has not been established as to whether the effect of 5 alpha-reductase inhibitors to reduce prostate volume, or study-related factors, impacted the results of these studies.
The 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, the mean percent reduction 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 the placebo group. Sperm concentration and sperm morphology were unaffected. After 24 weeks of follow-up, the mean percent change in total sperm count in the dutasteride group remained 23% lower than baseline. While mean values for all semen parameters at all time points remained within the 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 the 24-week follow-up. The clinical significance of dutasteride’s effect on semen characteristics for an individual patient’s fertility is not known. The effects of tamsulosin hydrochloride on sperm counts or sperm function have not been evaluated.
Patients should be told about the possible occurrence of symptoms related to postural hypotension such as dizziness and syncope when taking URIMAX D tablets, and they should be cautioned about driving, operating machinery or performing hazardous tasks.
Patients should be advised about the possibility of priapism as a result of treatment with URIMAX D tablets. Patients should be informed that this reaction is extremely rare, but if not brought to immediate medical attention, can lead to permanent erectile dysfunction (impotence).
Prostate cancer and BPH frequently co-exist; therefore, patients should be screened for the presence of prostate cancer prior to treatment with URIMAX D tablets and at regular intervals afterwards.
Patients considering cataract surgery should be advised to tell their ophthalmologist that they have taken URIMAX D tablets.
Physicians should inform patients that dutasteride reduces serum PSA levels by approximately 50% within 3-6 months of therapy, although it may vary for each individual. For patients undergoing PSA screening, increases in PSA levels while on treatment with dutasteride may signal the presence of prostate cancer and should be evaluated.
Physicians should inform patients that there was an increase in high-grade prostate cancer in men treated with 5 alpha-reductase inhibitors (which are indicated for BPH treatment), including dutasteride, compared with those treated with placebo, in studies looking at the use of these drugs to reduce the risk of prostate cancer.
Physicians should inform patients that URIMAX D tablets should not be handled by a woman who is pregnant or who could become pregnant because of the potential for absorption of dutasteride and the subsequent potential risk to a developing male foetus. Dutasteride is absorbed through the skin and could result in unintended foetal exposure. If a pregnant woman or woman of childbearing potential comes in contact with broken URIMAX D tablets, the contact area should be washed immediately with soap and water.
Physicians should inform men treated with URIMAX D tablets that they should not donate blood until at least 6 months following their last dose, so as to prevent pregnant women from receiving dutasteride through blood transfusion. Serum levels of dutasteride are detectable for 4-6 months after treatment ends.
Patients should be advised not to crush or chew the URIMAX D tablets.
Patients with renal impairment do not require any dosage adjustment in tamsulosin hydrochloride dosage. However, patients with end-stage renal disease (CLcr <10 mL/min/1.73 m²) have not been studied.
No dose adjustment is necessary for dutasteride in patients with renal impairment
Patients with moderate hepatic impairement do not require any dosage adjustment in tamsulosin hydrochloride dosage. Tamsulosin hydrochloride has not been studied in patients with severe hepatic impairment.
The effect of hepatic impairment on dutasteride pharmacokinetics has not been studied. Because dutasteride is extensively metabolized, exposure could be higher in hepatically impaired patients. However, in a clinical study where 60 subjects received 5 mg (10 times the therapeutic dose) daily for 24 weeks, no additional adverse events were observed compared with those observed at the therapeutic dose of 0.5 mg.
URIMAX D tablets are not indicated for use in the paediatric population.
Of 1,610 male subjects treated with coadministered dutasteride and tamsulosin in the Combat trial, 58% of enrolled subjects were aged 65 years and older and 13% of enrolled subjects were aged 75 years and older. No overall difference in the safety or effectiveness were observed between these subjects and younger subjects, and the reported clinical experience has not been identified differences in responses between the elderly and younger patients, but the greater sensitivity of some older patients cannot be ruled out. No dose adjustment is necessary in the elderly.
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 CYP3A4/5 such as ritonavir, ketoconazole, verapamil, diltiazem, cimetidine, troleandomycin, and ciprofloxacin.
Dutasteride does not inhibit the in vitro metabolism of model substrates for the major human cytochrome P450 isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) at a concentration of 1,000 ng/mL, 25 times greater than steady-state serum concentrations in humans.
The effects of ketoconazole (a strong inhibitor of CYP3A4) at 400 mg once daily for 5 days on the pharmacokinetics of a single tamsulosin hydrochloride capsule 0.4 mg dose was investigated in 24 healthy volunteers (age range: 23 to 47 years). Concomitant treatment with ketoconazole resulted in increases in the Cmax and AUC of tamsulosin by factors of 2.2 and 2.8, respectively. The effects of concomitant administration of a moderate CYP3A4 inhibitor (e.g., erythromycin) on the pharmacokinetics of tamsulosin have not been evaluated.
The effects of paroxetine (a strong inhibitor of CYP2D6) at 20 mg once daily for 9 days on the pharmacokinetics of a single tamsulosin capsule 0.4 mg dose was investigated in 24 healthy volunteers (age range: 23 to 47 years). Concomitant treatment with paroxetine resulted in increases in the Cmax and AUC of tamsulosin by factors of 1.3 and 1.6, respectively. A similar increase in exposure is expected in poor metabolizers (PM) of CYP2D6 as compared to extensive metabolizers (EM). A fraction of the population (about 7% of Caucasians and 2% of African-Americans) are CYP2D6 PMs. Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in tamsulosin exposure exists when tamsulosin 0.4 mg is coadministered with strong CYP3A4 inhibitors in CYP2D6 PMs, tamsulosin 0.4 mg capsules should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole).The effects of concomitant administration of a moderate CYP2D6 inhibitor (e.g., terbinafine) on the pharmacokinetics of tamsulosin have not been evaluated.
The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with tamsulosin capsules have not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when tamsulosin 0.4 mg is coadministered with a combination of both CYP3A4 and CYP2D6 inhibitors.
The pharmacokinetic and pharmacodynamic interactions between tamsulosin hydrochloride and other alpha-adrenergic blocking agents have not been determined. However, interactions may be expected and URIMAX D tablets should not be used in combination with other alpha-adrenergic blocking agents.
In a single-sequence, crossover trial in healthy volunteers, the administration of tamsulosin or terazosin in combination with dutasteride had no effect on the steady-state pharmacokinetics of either alpha-adrenergic antagonist. Although the effect of administration of tamsulosin or terazosin on dutasteride pharmacokinetic parameters was not evaluated, the percent change in DHT concentrations was similar for dutasteride, alone or in combination with tamsulosin or terazosin.
The effects of cimetidine at the highest recommended dose (400 mg every 6 hours for 6 days) on the pharmacokinetics of tamsulosin hydrochloride 0.4 mg dose was investigated in 10 healthy volunteers (age range: 21 to 38 years). Treatment with cimetidine resulted in a significant decrease (26%) in the clearance of tamsulosin hydrochloride, which resulted in a moderate increase in the tamsulosin hydrochloride AUC (44%). Therefore, URIMAX D tablets should be used with caution in combination with cimetidine.
Caution is advised when alpha-adrenergic blocking agent including tamsulosin hydrochloride is co-administered with PDE5 inhibitors. Alpha-adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension.
A definitive drug-drug interaction study between tamsulosin hydrochloride and warfarin was not conducted. Results from limited in vitro and in vivo drug-drug interaction studies between tamsulosin hydrochloride and warfarin are inconclusive. Concomitant administration of dutasteride 0.5 mg/day for 3 weeks with warfarin does not alter the steady-state pharmacokinetics of the S- or R-warfarin isomers or alter the effect of warfarin on prothrombin time. Therefore, caution should be exercised with concomitant administration of warfarin and URIMAX D tablets.
In 3 trials in hypertensive subjects (age range: 47 to 79 years) whose blood pressure was controlled with stable doses of nifedipine extended-release, atenolol, or enalapril for at least 3 months, tamsulosin hydrochloride capsules 0.4 mg for 7 days followed by tamsulosin hydrochloride capsules 0.8 mg for another 7 days (n = 8 per trial) resulted in no clinically significant effects on blood pressure and pulse rate compared with placebo (n = 4 per trial). Therefore, dosage adjustments are not necessary when tamsulosin is administered concomitantly with nifedipine extended-release, atenolol, or enalapril.
Dosage adjustments are not necessary when tamsulosin hydrochloride is administered concomitantly with digoxin or theophylline. Dutasteride does not alter the steady-state pharmacokinetics of digoxin when administered concomitantly at a dose of 0.5 mg/day for 3 weeks.
The pharmacokinetic and pharmacodynamic interaction between tamsulosin hydrochloride 0.8 mg/day (steady-state) and furosemide 20 mg intravenously (single dose) was evaluated in 10 healthy volunteers (age range: 21 to 40 years). Tamsulosin hydrochloride had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11-12% reduction in tamsulosin hydrochloride Cmax and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the tamsulosin hydrochloride dosage.
In a population pharmacokinetics analysis, a decrease in clearance of dutasteride was noted when coadministered with the CYP3A4 inhibitors verapamil (-37%, n=6) and diltiazem (-44%, n=5). In contrast, no decrease in clearance was seen when amlodipine, another calcium channel antagonist that is not a CYP3A4 inhibitor, was coadministered with dutasteride (+7%, n=4). The decrease in clearance and subsequent increase in exposure to dutasteride in the presence of verapamil and diltiazem is not considered to be clinically significant. The change in dutasteride exposure is not considered to be clinically significant. No dosage adjustment of dutasteride is recommended.
Administration of a single 5 mg dose of dutasteride followed 1 hour later by a 12 g dose of cholestyramine does not affect the relative bioavailability of dutasteride.
Pregnancy Category X.
URIMAX D tablets are not indicated for use in women.
Dutasteride is contraindicated for use in women of childbearing potential and during pregnancy. Dutasteride is a 5 alpha-reductase inhibitor that prevents conversion of testosterone to dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. In animal reproduction and developmental toxicity studies, dutasteride inhibited normal development of external genitalia in male fetuses. Therefore, dutasteride may cause fetal harm when administered to a pregnant woman. If dutasteride is used during pregnancy or if the patient becomes pregnant while taking dutasteride, the patient should be apprised of the potential hazard to the fetus.
Abnormalities in the genitalia of male fetuses is an expected physiological consequence of inhibition of the conversion of testosterone to DHT by 5 alpha-reductase inhibitors. These results are similar to observations in male infants with genetic 5 alpha-reductase deficiency. Dutasteride is absorbed through the skin. To avoid potential fetal exposure, women who are pregnant or could become pregnant should not handle dutasteride-containing URIMAX D tablets. If contact is made with leaking tablets, the contact area should be washed immediately with soap and water. Dutasteride is secreted into semen. The highest measured semen concentration of dutasteride in treated men was 14 ng/mL. Assuming exposure of a 50-kg woman to 5 mL of semen and 100% absorption, the woman’s dutasteride concentration would be about 0.0175 ng/mL. This concentration is more than 100 times less than concentrations producing abnormalities of male genitalia in animal studies. Dutasteride is highly protein bound in human semen (greater than 96%), which may reduce the amount of dutasteride available for vaginal absorption.
URIMAX D tablets are not indicated for use in nursing mothers. It is not known whether dutasteride or tamsulosin is excreted in human milk.
The clinical efficacy and safety of coadministered dutasteride and tamsulosin, have been evaluated in a multicenter, randomized, double-blind, parallel group trial (the Combination with Alpha-Blocker Therapy, or Combat, trial). Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trial of another drug and may not reflect the rates observed in practice.
The most common adverse reactions reported in subjects receiving coadministered dutasteride and tamsulosin were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), ejaculation disorders, and dizziness. Ejaculation disorders occurred significantly more in subjects receiving coadministration therapy (11%) compared with those receiving dutasteride (2%) or tamsulosin (4%) as monotherapy.
Trial withdrawal due to adverse reactions occurred in 6% of subjects receiving coadministered dutasteride and tamsulosin and in 4% of subjects receiving dutasteride or tamsulosin as monotherapy. The most common adverse reaction in all treatment arms leading to trial withdrawal was erectile dysfunction (1% to 1.5%).
The clinical efficacy and safety of co-administered dutasteride and tamsulosin hydrochloride have been evaluated in 4,800 male subjects with BPH who were randomly assigned to receive 0.5 mg dutasteride, 0.4 mg tamsulosin hydrochloride or co-administration therapy (0.5 mg dutasteride and 0.4 mg tamsulosin hydrochloride) administered once daily in a 4-year, double-blind study. Table 1 summarizes adverse reactions reported in at least 1% of subjects receiving co-administration therapy and at a higher incidence than subjects receiving either dutasteride or tamsulosin hydrochloride as monotherapy.
Table 1. Adverse Reactions Reported Over a 48-Month Period in ≥1% of Subjects and More Frequently in the Co-administration Therapy Group than the Dutasteride or Tamsulosin Monotherapy Group (Combat) by Time of Onset:
| Adverse Reaction | Adverse Reaction Time of Onset | ||||
|---|---|---|---|---|---|
| Year 1 | Year 2 | Year 3 | Year 4 | ||
| Months 0-6 | Months 7-12 | ||||
| Co-administrationa | (n=1,610) | (n=1,527) | (n=1,428) | (n=1,283) | (n=1,200) |
| Dutasteride | (n=1,623) | (n=1,548) | (n=1,464) | (n=1,325) | (n=1,200) |
| Tamsulosin | (n=1,611) | (n=1,545) | (n=1,468) | (n=1,281) | (n=1,112) |
| Ejaculation disordersb,c | |||||
| Co-administration | 7.8% | 1.6% | 1.0% | 0.5% | <0.1% |
| Dutasteride | 1.0% | 0.5% | 0.5% | 0.2% | 0.3% |
| Tamsulosin | 2.2% | 0.5% | 0.5% | 0.2% | 0.3% |
| Impotencec,d | |||||
| Co-administration | 5.4% | 1.1% | 1.8% | 0.9% | 0.4% |
| Dutasteride | 4.0% | 1.1% | 1.6% | 0.6% | 0.3% |
| Tamsulosin | 2.6% | 0.8% | 1.0% | 0.6% | 0.1% |
| Decreased libidoc,e | |||||
| Co-administration | 4.5% | 0.9% | 0.8% | 0.2% | 0.0% |
| Dutasteride | 3.1% | 0.7% | 1.0% | 0.2% | 0.0% |
| Tamsulosin | 2.0% | 0.6% | 0.7% | 0.2% | 0.1% |
| Breast disordersf | |||||
| Co-administration | 1.1% | 1.1% | 0.8% | 0.9% | 0.6% |
| Dutasteride | 0.9% | 0.9% | 1.2% | 0.5% | 0.7% |
| Tamsulosin | 0.4% | 0.4% | 0.4% | 0.2% | 0.0% |
| Dizziness | |||||
| Co-administration | 1.1% | 0.4% | 0.1% | <0.1% | 0.2% |
| Dutasteride | 0.5% | 0.3% | 0.1% | <0.1% | <0.1% |
| Tamsulosin | 0.9% | 0.5% | 0.4% | <0.1% | 0.0% |
a Co-administration = Dutasteride 0.5 mg once daily plus tamsulosin hydrochloride 0.4 mg once daily.
b Includes anorgasmia, retrograde ejaculation, semen volume decreased, orgasmic sensation decreased, orgasm abnormal, ejaculation delayed, ejaculation disorder, ejaculation failure and premature ejaculation.
c These sexual adverse reactions are associated with dutasteride treatment (including monotherapy and combination with tamsulosin). These adverse reactions may persist after treatment discontinuation. The role of dutasteride in this persistence is unknown.
d Includes erectile dysfunction and disturbance in sexual arousal.
e Includes libido decreased, libido disorder, loss of libido, sexual dysfunction and male sexual dysfunction.
f Includes breast enlargement, gynaecomastia, breast swelling, breast pain, breast tenderness, nipple pain and nipple swelling.
In Combat, after 4 years of treatment, the incidence of the composite term, cardiac, failure in the co-administration group (12/1,610; 0.7%) was higher than in either monotherapy group: dutasteride, 2/1,623 (0.1%) and tamsulosin hydrochloride, 9/1,611 (0.6%). Composite cardiac failure was also examined in a separate 4-year, placebo-controlled trial evaluating dutasteride in men at risk for development of prostate cancer. The incidence of cardiac failure in subjects taking dutasteride was 0.6% (26/4,105) compared with 0.4% (15/4,126) in subjects on placebo. A majority of subjects with cardiac failure in both studies had co-morbidities associated with an increased risk of cardiac failure. Therefore, the clinical significance of the numerical imbalances in cardiac failure is unknown. No causal relationship between dutasteride, alone or co-administered with tamsulosin hydrochloride, and cardiac failure has been established. No imbalance was observed in the incidence of overall cardiovascular adverse events in either study.
Additional information regarding adverse reactions in placebo-controlled trials with dutasteride or tamsulosin hydrochloride monotherapy was as follows:
In two 13-week treatment trials with tamsulosin hydrochloride monotherapy, adverse reactions occurring in at least 2% of subjects receiving 0.4 mg tamsulosin hydrochloride and at an incidence higher than in subjects receiving placebo were as follows: infection, asthenia, back pain, chest pain, somnolence, insomnia, rhinitis, pharyngitis, cough increased, sinusitis, and diarrhoea.
According to the tamsulosin hydrochloride prescribing information, in clinical studies with tamsulosin hydrochloride monotherapy, a positive orthostatic test result was observed in 16% (81/502) of subjects receiving 0.4 mg tamsulosin vs. 11% (54/493) of subjects receiving placebo. Because orthostasis was detected more frequently in the tamsulosin hydrochloride treated subjects than in placebo recipients, there is a potential risk of syncope.
High-grade Prostate Cancer: The REDUCE trial was a randomized, double-blind, placebo-controlled trial that enrolled 8,231 men aged 50 to 75 years, with a serum PSA of 2.5 ng/mL to 10 ng/mL and a negative prostate biopsy within the previous 6 months. Subjects were randomized to receive placebo (n=4,126) or 0.5 mg daily doses of dutasteride (n=4,105) for up to 4 years. The mean age was 63 years and 91% were Caucasian. Subjects underwent protocol-mandated scheduled prostate biopsies at 2 and 4 years of treatment or had “for-cause biopsies” at non-scheduled times if clinically indicated. There was a higher incidence of Gleason score 8-10 prostate cancer in men receiving dutasteride (1.0%) compared with men on placebo (0.5%). In a 7-year placebo-controlled clinical trial with another 5 alpha-reductase inhibitor (finasteride 5 mg), similar results for Gleason score 8-10 prostate cancer were observed (finasteride 1.8% versus placebo 1.1%). No clinical benefit has been demonstrated in patients with prostate cancer treated with dutasteride.
Reproductive and Breast Disorders: In the three pivotal placebo-controlled BPH trials with dutasteride, each of 4 years in duration, there was no evidence of increased sexual adverse reactions (impotence, decreased libido and ejaculation disorder) or breast disorders with increased duration of treatment. Among these three trials, there was one case of breast cancer in the dutasteride group and one case in the placebo group. No cases of breast cancer were reported in any treatment group in the 4-year Combat trial or the 4-year REDUCE trial. The relationship between the long-term use of dutasteride and male breast neoplasia is currently unknown.
The following adverse reactions have been identified during post-approval use of the tamsulosin hydrochloride and dutasteride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting or potential causal connection to drug exposure.
Immune system disorders: Hypersensitivity reactions, including rash, urticaria, pruritus, angioedema, and respiratory problems.
Cardiac disorders: Palpitations, dyspnoea, atrial fibrillation, arrhythmia, and tachycardia.
Skin disorders: Skin desquamation, including Stevens-Johnson syndrome.
Gastrointestinal disorders: Constipation, vomiting.
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), which is associated with alpha-adrenergic antagonist therapy.
Immune system disorders: Hypersensitivity reactions, including rash, urticaria, pruritus, angioedema, and respiratory problems.
Cardiac disorders: Palpitations, dyspnoea, atrial fibrillation, arrhythmia, and tachycardia.
Skin disorders: Skin desquamation, including Stevens-Johnson syndrome.
Gastrointestinal disorders: Constipation, vomiting.
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), which is > associated with alpha-adrenergic antagonist therapy.
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