Chemical formula: C₂₇H₃₀F₆N₂O₂ Molecular mass: 528.53 g/mol PubChem compound: 6918296
Dutasteride interacts in the following cases:
Dutasteride is mainly eliminated via metabolism. In vitro studies indicate that this metabolism is catalysed by CYP3A4 and CYP3A5. No formal interaction studies have been performed with potent CYP3A4 inhibitors. However, in a population pharmacokinetic study, dutasteride serum concentrations were on average 1.6 to 1.8 times greater, respectively, in a small number of patients treated concurrently with verapamil or diltiazem (moderate inhibitors of CYP3A4 and inhibitors of P-glycoprotein) than in other patients.
Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 (e.g. ritonavir, indinavir, nefazodone, itraconazole, ketoconazole administered orally) may increase serum concentrations of dutasteride. Further inhibition of 5-alpha reductase at increased dutasteride exposure, is not likely. However, a reduction of the dutasteride dosing frequency can be considered if side effects are noted. It should be noted that in the case of enzyme inhibition, the long half-life may be further prolonged and it can take more than 6 months of concurrent therapy before a new steady state is reached.
Dutasteride has been reported to affect semen characteristics (reduction in sperm count, semen volume, and sperm motility) in healthy men. The possibility of reduced male fertility cannot be excluded.
Dutasteride capsule is contraindicated for use by women.
As with other 5 alpha reductase inhibitors, dutasteride inhibits the conversion of testosterone to dihydrotestosterone and may, if administered to a woman carrying a male foetus, inhibit the development of the external genitalia of the foetus. Small amounts of dutasteride have been recovered from the semen in subjects receiving dutasteride 0.5 mg a day. It is not known whether a male foetus may be adversely affected if his mother is exposed to the semen of a patient being treated with dutasteride (the risk of which is greatest during the first 16 weeks of pregnancy).
As with all 5 alpha reductase inhibitors, when the patient’s partner is or may potentially be pregnant it is recommended that the patient avoids exposure of his partner to semen by use of a condom.
Dutasteride capsule is contraindicated for use by women.
It is not known whether dutasteride is excreted in human milk.
Dutasteride capsule is contraindicated for use by women.
Dutasteride has been reported to affect semen characteristics (reduction in sperm count, semen volume, and sperm motility) in healthy men. The possibility of reduced male fertility cannot be excluded.
Based on the pharmacodynamic properties of dutasteride, treatment with dutasteride would not be expected to interfere with the ability to drive or operate machinery.
Approximately 19% of the 2167 patients who received dutasteride in the 2 year Phase III placebo-controlled trials developed adverse reactions during the first year of treatment. The majority of events were mild to moderate and occurred in the reproductive system. No change to the adverse event profile was apparent over a further 2 years in open-label extension studies.
The following table shows adverse reactions from controlled clinical trials and post-marketing experience. The listed adverse events from clinical trials are investigator-judged drug-related events (with incidence more than or equal to 1%) reported with a higher incidence in patients treated with dutasteride compared with placebo during the first year of treatment. Adverse events from post-marketing experience were identified from spontaneous post-marketing reports; therefore the true incidence is not known: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to, <1/1,000); Very rare (<1/10,000); not known (cannot be estimated from the available data).
| Organ system | Adverse reaction | Incidence from clinical trial data | |
|---|---|---|---|
| Incidence during year 1 of treatment (n=2167) | Incidence during year 2 of treatment (n=1744) | ||
| Reproductive system and breast disorders | Impotence* | 6.0% | 1.7% |
| Altered (decreased) libido* | 3.7% | 0.6% | |
| Ejaculation disorders* | 1.8% | 0.5% | |
| Breast disorders+ | 1.3% | 1.3% | |
| Immune system disorders | Allergic reactions including rash, pruritus, urticaria, localised oedema, and angioedema | Incidence estimated from post-marketing data | |
| Not known | |||
| Psychiatric disorders | Depressed mood | Not known | |
| Skin and subcutaneous tissue diosrders | Alopecia (primarily body hair loss), hypertrichosis | Uncommon | |
| Reproductive system and breast disorders | Testicular pain and swelling | Not known | |
* These sexual adverse events are associated with dutasteride treatment (including monotherapy and combination with tamsulosin). These adverse events may persist after treatment discontinuation. The role of dutasteride in this persistence is unknown.
+ includes breast tenderness and breast enlargement
Data from the 4 year CombAT Study, comparing dutasteride 0.5mg (n=1623) and tamsulosin 0.4mg (n=1611) once daily alone and in combination (n=1610) have shown that the incidence of any investigator-judged drug-related adverse event during the first, second, third and fourth years of treatment respectively was 22%, 6%, 4% and 2% for dutasteride/tamsulosin combination therapy, 15%, 6%, 3% and 2% for dutasteride monotherapy and 13%, 5%, 2% and 2% for tamsulosin monotherapy. The higher incidence of adverse events in the combination therapy group in the first year of treatment was due to a higher incidence of reproductive disorders, specifically ejaculation disorders, observed in this group.
The following investigator-judged drug-related adverse events have been reported with an incidence of greater than or equal to 1% during the first year of treatment in the CombAT Study; the incidence of these events during the four years of treatment is shown in the table below:
| System Organ Class | Adverse Reaction | Incidence during treatment period | |||
|---|---|---|---|---|---|
| Year 1 | Year 2 | Year 3 | Year 4 | ||
| Combinationa (n) | (n=1610) | (n=1428) | (n=1283) | (n=1200) | |
| Dutasteride | (n=1623) | (n=1464) | (n=1325) | (n=1200) | |
| Tamsulosin | (n=1611) | (n=1468) | (n=1281) | (n=1112) | |
| Nervous system disorders | Dizziness | ||||
| Combinationa | 1.4% | 0.1% | <0.1% | 0.2% | |
| Dutasteride | 0.7% | 0.1% | <0.1% | <0.1% | |
| Tamsulosin | 1.3% | 0.4% | <0.1% | 0% | |
| Cardiac disorders | Cardiac failure (composite termb) | ||||
| Combinationa | 0.2% | 0.4% | 0.2% | 0.2% | |
| Dutasteride | <0.1% | 0.1% | <0.1% | 0% | |
| Tamsulosin | 0.1% | <0.1% | 0.4% | 0.2% | |
| Reproductive system and breast disorders, Psychiatric disorders, Investigations | Impotencec | ||||
| Combinationa | 6.3% | 1.8% | 0.9% | 0.4% | |
| Dutasteride | 5.1% | 1.6% | 0.6% | 0.3% | |
| Tamsulosin | 3.3% | 1.0% | 0.6% | 1.1% | |
| Altered (decreased) libidoc | |||||
| Combinationa | 5.3% | 0.8% | 0.2% | 0% | |
| Dutasteride | 3.8% | 1.0% | 0.2% | 0% | |
| Tamsulosin | 2.5% | 0.7% | 0.2% | <0.1% | |
| Ejaculation disordersc | |||||
| Combinationa | 9.0% | 1.0% | 0.5% | <0.1% | |
| Dutasteride | 1.5% | 0.5% | 0.2% | 0.3% | |
| Tamsulosin | 2.7% | 0.5% | 0.2% | 0.3% | |
| Breast disordersd | |||||
| Combinationa | 2.1% | 0.8% | 0.9% | 0.6% | |
| Dutasteride | 1.7% | 1.2% | 0.5% | 0.7% | |
| Tamsulosin | 0.8% | 0.4% | 0.2% | 0% | |
a Combination = dutasteride 0.5 mg once daily plus tamsulosin 0.4 mg once daily.
b Cardiac failure composite term comprised of Cardiac failure congestive, cardiac failure, left ventricular failure, cardiac failure acute, cardiogenic shock, left ventricular failure acute, right ventricular failure, right ventricular failure acute, ventricular failure, cardiopulmonary failure, congestive cardiomyopathy.
c These sexual adverse events are associated with dutasteride treatment (including monotherapy and combination with tamsulosin). These adverse events may persist after treatment discontinuation. The role of dutasteride in this persistence is unknown.
d Includes breast tenderness and breast enlargement.
The REDUCE study revealed a higher incidence of Gleason 8-10 prostate cancers in dutasteride treated men compared to placebo. Whether the effect of dutasteride to reduce prostate volume, or study related factors, impacted the results of this study has not been established.
The following has been reported in clinical trials and post-marketing use: male breast cancer.
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