The lack of interaction between temafloxacin and combined oral contraceptive steroids

Back, DJ; Tjia, John; Martín, Carmen; Millar, E.; Mant, Tim; Morrison, Philippa K.; Orme, M.

doi:10.1016/0010-7824(91)90070-v

Cited by 21 publications

(11 citation statements)

References 10 publications

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“…The magnitude of increase in the systemic exposure of EE is similar to that observed with concomitant administration of other CYP3A4 inhibitors (e.g. voriconazole, clarithromycin, fluconazole) . A transient increase of EE concentrations exerted by concomitant administration of CYP3A4 inhibitors in the range observed with the strong CYP3A4 inhibitor ketoconazole is not considered to be of clinical relevance and does not necessitate dose adjustment.…”

Section: Discussionmentioning

confidence: 58%

Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol

Wiesinger

Berse

Klein

et al. 2015

Brit J Clinical Pharma

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AIMSThe present study was conducted to investigate the influence of the strong CYP3A4 inhibitor ketoconazole (KTZ) on the pharmacokinetics of drospirenone (DRSP) administered in combination with ethinylestradiol (EE) or estradiol (E2). METHODSThis was a randomized, multicentre, open label, one way crossover, fixed sequence study with two parallel treatment arms. A group sequential design allowed terminating the study for futility after first study cohort. About 50 healthy young women were randomized 1 : 1 to 'DRSP/EE' or 'DRSP/E2'. Subjects in the 'DRSP/EE' group received DRSP 3 mg/EE 0.02 mg (YAZ®, Bayer) once daily for 21 to 28 days followed by DRSP 3 mg/EE 0.02 mg once daily plus KTZ 200 mg twice daily for 10 days. Subjects in the 'DRSP/E2' group received DRSP 3 mg/E2 1.5 mg (research combination) once daily for 21 to 28 days followed by DRSP 3 mg/E2 1.5 mg once daily plus KTZ 200 mg twice daily for 10 days. RESULTSOral co-administration of DRSP/EE or DRSP/E2 and KTZ resulted in an increase in DRSP exposure (AUC(0,24 h)) in both treatment groups: DRSP/EE group: 2.68-fold DRSP increase (90% CI 2.44, 2.95); DRSP/E2 group: 2.30-fold DRSP increase (90% CI 2.08, 2.54). EE and estrone (metabolite of E2) exposures were increased~1.4-fold whereas E2 exposure was largely unaffected by KTZ co-administration. CONCLUSIONSA moderate pharmacokinetic drug-drug interaction between DRSP and KTZ was demonstrated in this study. No relevant changes of medical concern were detected in the safety data collected in this study. WHAT IS KNOWN ABOUT THIS SUBJECT• Prior data indicate that the major plasma metabolites of drospirenone are formed without CYP enzymes. Thus, no major CYPmediated drug interactions were expected.• However, in a recent study with a drospirenone-containing combination oral contraceptive, it was observed that coadministration of boceprevir, a CYP3A4 inhibitor, led to an increase in drospirenone exposure. WHAT THIS STUDY ADDS• In this study, a moderate pharmacokinetic interaction between drospirenone and ketoconazole, a strong CYP3A4 inhibitor, was observed (2 to 3-fold increase in DRSP exposure with ketoconazole coadministration).• Ketoconazole also slightly increased the systemic exposure of ethinylestradiol and estrone.• Overall, safety data indicated that these pharmacokinetic interactions are without clinical relevance.

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Section: Discussionmentioning

confidence: 58%

Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol

Wiesinger

Berse

Klein

et al. 2015

Brit J Clinical Pharma

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“…Other than the rifamycins, no antibiotics have been shown to alter the pharmacokinetics of ethinylestradiol in humans (Shenfield and Griffin, 1991). Soon after implicating antibiotics as a potential cause of OC failure, Back et al, (1991) allowed that the OC failure rate among antibiotic users may not be substantively greater than the natural failure rate of OCs.…”

Section: Downloaded Frommentioning

confidence: 99%

A Comprehensive in Vitro and in Silico Analysis of Antibiotics That Activate Pregnane X Receptor and Induce CYP3A4 in Liver and Intestine

Yasuda

Ranade²,

Venkataramanan³

et al. 2008

Drug Metab Dispos

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ABSTRACT:We have investigated several in silico and in vitro methods to improve our ability to predict potential drug interactions of antibiotics. Our focus was to identify those antibiotics that activate pregnane X receptor (PXR) and induce CYP3A4 in human hepatocytes and intestinal cells. Human PXR activation was screened using reporter assays in HepG2 cells, kinetic measurements of PXR activation were made in DPX-2 cells, and induction of CYP3A4 expression and activity was verified by quantitative polymerase chain reaction, immunoblotting, and testosterone 6␤-hydroxylation in primary human hepatocytes and LS180 cells. We found that in HepG2 cells CYP3A4 transcription was activated strongly (>10-fold) by rifampin and troleandomycin; moderately (>7-fold) by dicloxacillin, tetracycline, clindamycin, griseofulvin, and (>4-fold) erythromycin; and weakly (>2.4-fold) by nafcillin, cefaclor, sulfisoxazole, and (>2-fold) cefadroxil and penicillin V. Similar although not identical results were obtained in DPX-2 cells. CYP3A4 mRNA and protein expression were induced by these antibiotics to differing extents in both liver and intestinal cells. CYP3A4 activity was significantly increased by rifampin (9.7-fold), nafcillin and dicloxacillin (5.9-fold), and weakly induced (2-fold) by tetracycline, sufisoxazole, troleandomycin, and clindamycin. Multiple pharmacophore models and docking indicated a good fit for dicloxacillin and nafcillin in PXR. These results suggest that in vitro and in silico methods can help to prioritize and identify antibiotics that are most likely to reduce exposures of medications (such as oral contraceptive agents) which interact with enzymes and transporters regulated by PXR. In summary, nafcillin, dicloxacillin, cephradine, tetracycline, sulfixoxazole, erythromycin, clindamycin, and griseofulvin exhibit a clear propensity to induce CYP3A4 and warrant further clinical investigation.

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“…Thus, ofloxacin does not seem to interact with steroid metabolism in the same way as some other antibiotics [7][8][9][10][11][12]. Signs of ovarian activity in terms of high E2 levels up to 600 pmol/L in combination with ovarian follicles >~ 15 mm without any rise in P4 levels above 3 nmol/L were seen in four subjects.…”

Section: Discussionmentioning

confidence: 97%

Risk for ovulation in women taking a low-dose oral contraceptive (Microgynon) when receiving antibacterial treatment with a fluoroquinolone (ofloxacin)

Csemiczky

Alvendal

1996

Adv Contracept

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The possibility of escape ovulation in women using a fluoroquinolone ofloxacin for antibacterial treatment at a dose of 200 mg twice daily for 7 days when taking a combined oral contraceptive (Microgynon, 150 micrograms levonorgestrel and 30 micrograms ethinyl estradiol) was studied in 20 women. By using a placebo-controlled, randomized, cross-over design 6 contraceptive pill cycles were followed. Follicle-stimulating hormone and estradiol concentrations were measured on tablet days 5-8, 19-21; progesterone was assayed on days 19-21 during treatment with ofloxacin or placebo. Ultrasonographical investigations for measurements of the number and diameter of ovarian follicles were performed on one of days 5-10, 11-17, 18-24, 25-28. No indications of ovulation during ofloxacin medication were detected. It is concluded that alternative contraceptive precautions should not be needed when ofloxacin is prescribed for patients taking oral contraceptives.

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The lack of interaction between temafloxacin and combined oral contraceptive steroids

Cited by 21 publications

References 10 publications

Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol

Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol

A Comprehensive in Vitro and in Silico Analysis of Antibiotics That Activate Pregnane X Receptor and Induce CYP3A4 in Liver and Intestine

Risk for ovulation in women taking a low-dose oral contraceptive (Microgynon) when receiving antibacterial treatment with a fluoroquinolone (ofloxacin)

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