Avodart and SSRIs (Sertraline, Escitalopram) Interaction: What You Need to Know

What the Avodart label says about interactions

The Avodart label's drug interaction section addresses these items: potent, chronic CYP3A4 inhibitors such as ritonavir (use caution; their effect on dutasteride has not been studied), the alpha blockers tamsulosin and terazosin (dutasteride does not change their steady-state pharmacokinetics), the calcium channel blockers verapamil and diltiazem (they reduce dutasteride clearance and raise exposure, a change the label does not consider clinically significant and for which it recommends no dose adjustment), cholestyramine (no effect on dutasteride bioavailability), digoxin (no change in its pharmacokinetics) and warfarin (no change in its pharmacokinetics or in its effect on prothrombin time) [1].

Sertraline and escitalopram are not among them [1]. The label therefore gives no dutasteride dose change for either SSRI.

Does sertraline or escitalopram change dutasteride levels?

Dutasteride is extensively metabolized by CYP3A4 and CYP3A5, and it is not metabolized by CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6 or 2E1 [1].

The Zoloft label lists sertraline as a CYP2D6 inhibitor and says no dosage adjustment is required for diazepam, lithium, atenolol, tolbutamide, digoxin, or drugs metabolized by CYP3A4 when taken with sertraline [2]. Escitalopram's CYP2D6 effect has been measured: 20 mg a day for 21 days raised desipramine AUC by 100% and metoprolol AUC by 82% [3]. Those data describe exposure to desipramine and metoprolol, not to dutasteride, and dutasteride is not a CYP2D6 substrate [1].

Can the combination cause serotonin syndrome?

Serotonin syndrome can occur with sertraline alone. The Zoloft label says the risk is increased by other serotonergic drugs and by MAOIs, and dutasteride is not among those it names [2]. The drugs it names are triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines and St. John's wort [2]. Dutasteride's labeled mechanism is inhibition of type 1 and type 2 5-alpha-reductase, which blocks conversion of testosterone to dihydrotestosterone; it does not bind the androgen receptor [1].

The Zoloft label describes serotonin syndrome signs as mental status changes, autonomic instability, neuromuscular signs such as tremor and hyperreflexia, seizures, and gastrointestinal symptoms [2].

Sexual side effects: the overlap both labels describe

This is the part of the pairing that is documented, and it comes from each drug separately.

In the Avodart label's pooled 2-year BPH trials (2,167 men on dutasteride, 2,158 on placebo, mean age 66), the rates in the first six months were impotence 4.7% vs 1.7%, decreased libido 3.0% vs 1.4%, ejaculation disorders 1.4% vs 0.5%, and breast disorders 0.5% vs 0.2% [1]. Rates fell after six months except for breast disorders, which were 1.1% vs 0.3% at months 13 to 18 [1]. The label adds that these sexual adverse reactions may persist after the drug is stopped and that the role of dutasteride in that persistence is unknown [1].

In the Zoloft label's pooled trials, the male-only figures (1,316 on sertraline, 973 on placebo) were ejaculation failure 8% vs 1%, decreased libido 7% vs 2%, erectile dysfunction 4% vs 1%, ejaculation disorder 3% vs 0%, and male sexual dysfunction 2% vs 0% [2]. Every SSRI label warns of sexual dysfunction [2][3].

A 2009 meta-analysis that pooled studies using direct inquiry and specific questionnaires found treatment-emergent sexual dysfunction in 25.8% to 80.3% of patients depending on the antidepressant, ranked from sertraline at the high end down to fluvoxamine, with escitalopram near the lower end [4]. For hair-loss dosing, a 2019 meta-analysis of 15 randomized placebo-controlled trials (4,495 men) found a 1.57-fold relative risk of sexual dysfunction overall, 1.66 for finasteride 1 mg and 1.37 for dutasteride 0.5 mg (95% CI 0.81 to 2.32, not statistically significant, with few dutasteride trials) [5].

Reviews note that bupropion, mirtazapine, nefazodone and vilazodone are associated with less sexual dysfunction than SSRIs, and that some of these have been used to treat SSRI-induced sexual dysfunction [6].

Mood and depression

The Avodart label lists depressed mood among its postmarketing reports [1]. A Swedish register cohort of 2,236,876 men aged 50 to 90, of whom 8,774 started dutasteride, found an increased rate of depression (hazard ratio 1.68, 95% CI 1.43 to 1.96) and no association with suicide (hazard ratio 0.98, 95% CI 0.62 to 1.54) [7]. The cohort was observational and mostly older men treated for BPH, so it shows an association rather than a cause.

On the SSRI side, the Zoloft label carries the antidepressant boxed warning for suicidal thoughts and behaviors in pediatric and young adult patients. Its pooled placebo-controlled antidepressant trial data (not sertraline alone) show a drug-placebo difference per 1,000 treated of 14 additional cases under age 18, 5 additional at ages 18 to 24, 1 fewer at ages 25 to 64, and 6 fewer at 65 and older [2].

How long dutasteride stays in the body

Dutasteride has a terminal half-life of about 5 weeks at steady state, and serum levels can remain detectable above 0.1 ng/mL for up to 4 to 6 months after the last dose [1]. It reaches 65% of steady state after one month and about 90% after three months [1]. The Avodart label says men being treated with it should not donate blood until at least 6 months have passed since the last dose, to prevent giving dutasteride to a pregnant transfusion recipient [1].