Drug Interaction Between Dienogest and Aripiprazole
There is a documented interaction between dienogest (when combined with ethinyl estradiol in oral contraceptives) and aripiprazole, though the clinical significance appears modest and primarily involves potential reduction in contraceptive efficacy rather than aripiprazole effectiveness. 1
Evidence from Guidelines
The 2016 Journal of the American Academy of Dermatology guidelines explicitly list aripiprazole among medications that interact with combined oral contraceptives containing ethinyl estradiol and progestins (including dienogest-containing formulations). 1 This interaction is documented in the context of:
- Ethinyl estradiol/norethindrone acetate combinations - where aripiprazole is listed as an interacting medication 1
- Ethinyl estradiol/drospirenone combinations - where similar interactions are noted 1
The mechanism likely involves aripiprazole's effects on hepatic enzyme systems or drug transporters, potentially reducing contraceptive hormone levels and thereby decreasing contraceptive efficacy. 1
Clinical Implications
For Contraceptive Efficacy
- The primary concern is reduced contraceptive effectiveness when dienogest is used in combination oral contraceptive formulations alongside aripiprazole 1
- Patients taking both medications should be counseled about potential breakthrough bleeding and the need for backup contraception 1
For Dienogest Monotherapy (Endometriosis Treatment)
- No specific interaction data exists for dienogest 2 mg/day monotherapy (used for endometriosis) with aripiprazole 2, 3
- Dienogest monotherapy has different pharmacokinetics than combined oral contraceptives, with high oral bioavailability (>90%) and minimal hepatic metabolism 2
- The interaction risk may be lower with dienogest monotherapy since it lacks the ethinyl estradiol component that typically drives contraceptive-drug interactions 2
Monitoring Recommendations
When prescribing these medications together:
- Monitor for breakthrough bleeding or spotting, which may indicate reduced hormonal efficacy 1
- Counsel patients using dienogest for contraception to employ backup methods (barrier contraception) 1
- Be vigilant for mood changes, as dienogest itself carries risk of depression (including severe cases with suicidal ideation), and aripiprazole is used for psychiatric conditions 4
- Watch for additive central nervous system effects, as both medications can cause headache, dizziness, and mood alterations 5, 4, 6
Important Caveats
The interaction is primarily relevant for combined hormonal contraceptives rather than dienogest monotherapy for endometriosis treatment. 1, 2 The guideline evidence specifically addresses ethinyl estradiol-containing products, and dienogest monotherapy has distinct pharmacological properties including lack of SHBG binding and minimal hepatic first-pass metabolism. 2
Psychiatric monitoring is essential given dienogest's documented association with major depressive disorder (even in patients without psychiatric history) and aripiprazole's use in psychiatric conditions. 4 This represents a more clinically significant concern than the pharmacokinetic interaction itself.