Lack of Clinically Meaningful Effect of Cariprazine on the Pharmacokinetics of a Combined Oral Contraceptive
Abstract Introduction Cariprazine (CAR) is a potent dopamine receptor partial agonist antipsychotic approved by the EMA and the FDA. To address the uncertainty regarding the effectiveness of hormonal contraceptives during CAR co-administration and whether a second barrier method is necessary, a drug...
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| Format: | Article |
| Language: | English |
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Adis, Springer Healthcare
2024-12-01
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| Series: | Neurology and Therapy |
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| Online Access: | https://doi.org/10.1007/s40120-024-00686-7 |
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| author | Márta Erzsébet Rosa Zoltán Juhász Gabriella Pásztor Mészáros Gabriella Magyar Judit Harsányi Balázs Szatmári Zoltán Hujber Máté Szabó Margit Kapás |
| author_facet | Márta Erzsébet Rosa Zoltán Juhász Gabriella Pásztor Mészáros Gabriella Magyar Judit Harsányi Balázs Szatmári Zoltán Hujber Máté Szabó Margit Kapás |
| author_sort | Márta Erzsébet Rosa |
| collection | DOAJ |
| description | Abstract Introduction Cariprazine (CAR) is a potent dopamine receptor partial agonist antipsychotic approved by the EMA and the FDA. To address the uncertainty regarding the effectiveness of hormonal contraceptives during CAR co-administration and whether a second barrier method is necessary, a drug–drug interaction study with an oral contraceptive was conducted post-approval. Methods The phase I, fixed-sequence multicenter study involved two periods with 24 patients with schizophrenia, aiming to evaluate the effect of CAR on the pharmacokinetics (PK) of a combined oral contraceptive (COC) containing 30 μg ethinylestradiol (EE) and 150 μg levonorgestrel (LNG). In period A, a single dose of COC alone was administered on day 1. In period B, the highest therapeutic dose of 6 mg CAR was administered once daily from day 4, and a second dose of COC was given concomitantly on day 31. Results Overall, CAR had no clinically meaningful effect on the PK of the COC. The terminal half-life and the time of maximum plasma concentration of EE and LNG were not altered by CAR co-administration. The highest difference observed was a decrease of 14% in the maximum plasma concentration of EE, with only slight deviation of the 90% confidence interval (CI) of the test/reference ratio (77.09–96.81) from the generally accepted bioequivalence range of 80–125%, which is not considered clinically relevant. Confidence intervals of all other exposure measures were within the 80–125% range for both EE and LNG. Conclusions According to these results, hormonal contraceptives can be considered effective during CAR treatment. Trial Registration Trial registration number (EudraCT) 2018-003722-80. |
| format | Article |
| id | doaj-art-7a878a0ec266491b8f3f5f0fa7e7d1b6 |
| institution | Kabale University |
| issn | 2193-8253 2193-6536 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Neurology and Therapy |
| spelling | doaj-art-7a878a0ec266491b8f3f5f0fa7e7d1b62025-01-26T12:58:30ZengAdis, Springer HealthcareNeurology and Therapy2193-82532193-65362024-12-0114129130110.1007/s40120-024-00686-7Lack of Clinically Meaningful Effect of Cariprazine on the Pharmacokinetics of a Combined Oral ContraceptiveMárta Erzsébet Rosa0Zoltán Juhász1Gabriella Pásztor Mészáros2Gabriella Magyar3Judit Harsányi4Balázs Szatmári5Zoltán Hujber6Máté Szabó7Margit Kapás8Gedeon Richter PlcGedeon Richter PlcGedeon Richter PlcGedeon Richter PlcGedeon Richter PlcGedeon Richter PlcGedeon Richter PlcGedeon Richter PlcGedeon Richter PlcAbstract Introduction Cariprazine (CAR) is a potent dopamine receptor partial agonist antipsychotic approved by the EMA and the FDA. To address the uncertainty regarding the effectiveness of hormonal contraceptives during CAR co-administration and whether a second barrier method is necessary, a drug–drug interaction study with an oral contraceptive was conducted post-approval. Methods The phase I, fixed-sequence multicenter study involved two periods with 24 patients with schizophrenia, aiming to evaluate the effect of CAR on the pharmacokinetics (PK) of a combined oral contraceptive (COC) containing 30 μg ethinylestradiol (EE) and 150 μg levonorgestrel (LNG). In period A, a single dose of COC alone was administered on day 1. In period B, the highest therapeutic dose of 6 mg CAR was administered once daily from day 4, and a second dose of COC was given concomitantly on day 31. Results Overall, CAR had no clinically meaningful effect on the PK of the COC. The terminal half-life and the time of maximum plasma concentration of EE and LNG were not altered by CAR co-administration. The highest difference observed was a decrease of 14% in the maximum plasma concentration of EE, with only slight deviation of the 90% confidence interval (CI) of the test/reference ratio (77.09–96.81) from the generally accepted bioequivalence range of 80–125%, which is not considered clinically relevant. Confidence intervals of all other exposure measures were within the 80–125% range for both EE and LNG. Conclusions According to these results, hormonal contraceptives can be considered effective during CAR treatment. Trial Registration Trial registration number (EudraCT) 2018-003722-80.https://doi.org/10.1007/s40120-024-00686-7CariprazineEthinylestradiolLevonorgestrelSchizophreniaContraceptive |
| spellingShingle | Márta Erzsébet Rosa Zoltán Juhász Gabriella Pásztor Mészáros Gabriella Magyar Judit Harsányi Balázs Szatmári Zoltán Hujber Máté Szabó Margit Kapás Lack of Clinically Meaningful Effect of Cariprazine on the Pharmacokinetics of a Combined Oral Contraceptive Neurology and Therapy Cariprazine Ethinylestradiol Levonorgestrel Schizophrenia Contraceptive |
| title | Lack of Clinically Meaningful Effect of Cariprazine on the Pharmacokinetics of a Combined Oral Contraceptive |
| title_full | Lack of Clinically Meaningful Effect of Cariprazine on the Pharmacokinetics of a Combined Oral Contraceptive |
| title_fullStr | Lack of Clinically Meaningful Effect of Cariprazine on the Pharmacokinetics of a Combined Oral Contraceptive |
| title_full_unstemmed | Lack of Clinically Meaningful Effect of Cariprazine on the Pharmacokinetics of a Combined Oral Contraceptive |
| title_short | Lack of Clinically Meaningful Effect of Cariprazine on the Pharmacokinetics of a Combined Oral Contraceptive |
| title_sort | lack of clinically meaningful effect of cariprazine on the pharmacokinetics of a combined oral contraceptive |
| topic | Cariprazine Ethinylestradiol Levonorgestrel Schizophrenia Contraceptive |
| url | https://doi.org/10.1007/s40120-024-00686-7 |
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