- Drugs and Lactation Database (LactMed): Contraceptives, Oral, Combined [BOOK]Drugs and Lactation Database (LactMed). National Library of Medicine (US): Bethesda (MD)BOOK
- The weight of current evidence seems to indicate that combination oral contraceptives probably do not affect the composition of milk substantially in healthy, well-nourished mothers and do not adversely affect long-term infant growth and development. Combined oral contraceptives might transiently affect growth negatively during the first month after introduction. The magnitude of the effect on la…
The weight of current evidence seems to indicate that combination oral contraceptives probably do not affect the composition of milk substantially in healthy, well-nourished mothers and do not adversely affect long-term infant growth and development. Combined oral contraceptives might transiently affect growth negatively during the first month after introduction. The magnitude of the effect on lactation likely depends on the dose and the time of introduction postpartum. A treatment scheme has been reported for mothers with hypergalactia that uses low-dose, combined oral contraceptives to decrease milk supply. Ethinyl estradiol in doses greater than 30 mcg daily can suppress lactation and lead to more supplementation and possibly earlier discontinuation of breastfeeding than nonhormonal or progestin-only contraception. Additionally, introduction of an estrogen before 3 weeks postpartum may increase the risk of thromboembolism in postpartum women. Rare cases of reversible breast enlargement in breastfed infants have been reported, mostly with estrogen doses higher than are currently used. Based on the available evidence, expert opinion in the United States states that postpartum women who are breastfeeding should not use combined hormonal contraceptives during the first 3 weeks after delivery because of concerns about increased risk for venous thromboembolism and generally should not use combined hormonal contraceptives during the fourth week postpartum because of concerns about potential effects on breastfeeding performance. Postpartum breastfeeding women with other risk factors for venous thromboembolism generally should not use combined hormonal contraceptives 4 to 6 weeks after delivery. World Health Organization guidelines are more restrictive, stating that combined oral contraceptives should not be used in nursing mothers before 42 days postpartum and the disadvantages of using the method generally outweigh the advantages between 6 weeks and 6 months postpartum.
- Risk of sexual dysfunction with progestin-based contraceptives in women of child-bearing age. [Journal Article]Eur J Clin Pharmacol. 2021 Jan; 77(1):133-140.EJ
- CONCLUSIONS: Our study found an increase in the use of levonorgestrel (COC and IUD), drospirenone, and medroxyprogesterone in subjects with SD. The risk of contraceptives did not differ when compared with oral levonorgestrel. The small association size and lack of difference between drug formulations suggest a minimal impact of progestin-based contraceptives on sexual dysfunction.
- The effect of laquinimod, a novel immuno-modulator in development to treat Huntington disease, on the pharmacokinetics of ethinylestradiol and levonorgestrel in healthy young women. [Randomized Controlled Trial]Eur J Clin Pharmacol. 2019 Jan; 75(1):41-49.EJ
- CONCLUSIONS: The combination of COC and laquinimod treatment was found to be safe, tolerable, and devoid of any noticeable pharmacokinetic interaction.
- Combined oral contraceptive interference with the ability of ulipristal acetate to delay ovulation: A prospective cohort study. [Journal Article]Contraception. 2018 12; 98(6):463-466.C
- CONCLUSIONS: UPA's effectiveness is significantly reduced by administering COCs 2 days later.
- Effect of Extended 30 μg Ethinyl Estradiol with Continuous Low-Dose Ethinyl Estradiol and Cyclic 20 μg Ethinyl Estradiol Oral Contraception on Adolescent Bone Density: A Randomized Trial. [Randomized Controlled Trial]J Pediatr Adolesc Gynecol. 2016 Dec; 29(6):635-642.JP
- CONCLUSIONS: Compared with the reference group, bone accrual was statistically significantly lower among LNG/EE 21/7 users but not among LNG/EE 30-μg extended regimen users. Additional research is needed to clarify the clinical relevance of these findings.
- Pharmacokinetic drug-drug interaction assessment of LCZ696 (an angiotensin receptor neprilysin inhibitor) with omeprazole, metformin or levonorgestrel-ethinyl estradiol in healthy subjects. [Controlled Clinical Trial]Clin Pharmacol Drug Dev. 2016 Jan; 5(1):27-39.CP
- LCZ696 is a novel angiotensin receptor neprilysin inhibitor in development for the treatment of cardiovascular diseases. Here, we assessed the potential for pharmacokinetic drug-drug interaction of LCZ696 (400 mg, single dose or once daily [q.d.]) when co-administered with omeprazole 40 mg q.d. (n = 28) or metformin 1000 mg q.d. (n = 27) or levonorgestrel-ethinyl estradiol 150/30 μg single dose (…
LCZ696 is a novel angiotensin receptor neprilysin inhibitor in development for the treatment of cardiovascular diseases. Here, we assessed the potential for pharmacokinetic drug-drug interaction of LCZ696 (400 mg, single dose or once daily [q.d.]) when co-administered with omeprazole 40 mg q.d. (n = 28) or metformin 1000 mg q.d. (n = 27) or levonorgestrel-ethinyl estradiol 150/30 μg single dose (n = 24) in three separate open-label, single-sequence studies in healthy subjects. Pharmacokinetic parameters of LCZ696 analytes (sacubitril, LBQ657, and valsartan), metformin, and levonorgestrel-ethinyl estradiol were assessed. Omeprazole did not alter the AUCinf of sacubitril and pharmacokinetics of LBQ657; however, 7% decrease in the Cmax of sacubitril, and 11% and 13% decreases in AUCinf and Cmax of valsartan were observed. Co-administration of LCZ696 with metformin had no significant effect on the pharmacokinetics of LBQ657 and valsartan; however, AUCtau,ss and Cmax,ss of metformin were decreased by 23%. Co-administration of LCZ696 with levonorgestrel-ethinyl estradiol had no effect on the pharmacokinetics of ethinyl estradiol and LBQ657 or AUCinf of levonorgestrel. The Cmax of levonorgestrel decreased by 15%, and AUCtau,ss and Cmax,ss of valsartan decreased by 14% and 16%, respectively. Co-administration of LCZ696 with omeprazole, metformin, or levonorgestrel-ethinyl estradiol was not associated with any clinically relevant pharmacokinetic drug interactions.
- Extended-Cycle Levonorgestrel/Ethinylestradiol and Low-Dose Ethinylestradiol (Seasonique(®)): A Review of Its Use as an Oral Contraceptive. [Review]Drugs. 2015 Jun; 75(9):1019-26.D
- A 91-day extended-cycle oral contraceptive (OC) consisting of levonorgestrel/ethinylestradiol 150/30 µg for 84 days and ethinylestradiol 10 µg for 7 days (Seasonique(®)) has recently been approved for the prevention of pregnancy in adult women in the EU. This regimen allows for a reduction in the number of withdrawal bleeding episodes to four per year, compared with 13 episodes per year with conv…
A 91-day extended-cycle oral contraceptive (OC) consisting of levonorgestrel/ethinylestradiol 150/30 µg for 84 days and ethinylestradiol 10 µg for 7 days (Seasonique(®)) has recently been approved for the prevention of pregnancy in adult women in the EU. This regimen allows for a reduction in the number of withdrawal bleeding episodes to four per year, compared with 13 episodes per year with conventional 28-day regimens. Seasonique(®) was effective in preventing pregnancy in a large (n = 1006), noncomparative trial of healthy, sexually active women. In this trial, the overall Pearl index (pregnancies per 100 woman-years of use) in women aged 18-35 years (n = 621) was 0.76 and the Pearl index for method-failure (compliant use) was 0.26. Scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with a mean of 2 days of bleeding and 1 day of spotting per each 91-day cycle. Unscheduled bleeding and unscheduled spotting was highest during the first few cycles of use and decreased thereafter. Seasonique(®) was generally well tolerated, with a tolerability profile in line with that expected for OCs. Seasonique(®) extends the contraceptive options currently available to women, particularly in those who desire fewer withdrawal bleeding episodes.
- Ovulatory effects of three oral contraceptive regimens: a randomized, open-label, descriptive trial. [Randomized Controlled Trial]Contraception. 2015 Jun; 91(6):495-502.C
- CONCLUSIONS: The 21/7-active low-dose COC regimen (DSG/EE+7 days EE) showed ovarian activity suppression that was similar to the 24/4 (DRSP/EE+4 days PBO) and 21/7 (LNG/EE+7days PBO) regimens.
- Effect of pradigastat, a diacylglycerol acyltransferase 1 inhibitor, on the pharmacokinetics of a combination oral contraceptive in healthy female subjects. [Controlled Clinical Trial]Int J Clin Pharmacol Ther. 2015 Apr; 53(4):317-24.IJ
- CONCLUSIONS: Pradigastat did not elicit clinically relevant changes in the magnitude of Levora-28® exposure. Therefore, dose adjustment is not required for Levora-28® when co-administered with pradigastat.
- A phase 1, multicentre, open-label study to evaluate ovarian follicular activity and hormone levels with an extended-regimen combined oral contraceptive with low-dose ethinyl estradiol supplementation. [Clinical Trial, Phase I]Eur J Contracept Reprod Health Care. 2015; 20(4):249-58.EJ
- CONCLUSIONS: The 91-day extended-regimen COC with low-dose EE supplementation was found to be effective in suppressing ovarian activity and inhibiting ovulation and was well tolerated. Return to ovulation was rapid, occurring within approximately one month after discontinuation of COC.
- Bleeding pattern and cycle control of a low-dose transdermal contraceptive patch compared with a combined oral contraceptive: a randomized study. [Randomized Controlled Trial]Contraception. 2015 Feb; 91(2):113-20.C
- CONCLUSIONS: Bleeding pattern and cycle control with the EE/GSD patch was comparable to an EE/LNG-containing COC.
- No interacting influence of lavender oil preparation silexan on oral contraception using an ethinyl estradiol/levonorgestrel combination. [Randomized Controlled Trial]Drugs R D. 2014 Dec; 14(4):265-72.DR
- CONCLUSIONS: Co-administration of Silexan did not affect the efficacy of a combination oral contraceptive containing EE and LNG and was well tolerated.
- Estradiol valerate plus dienogest versus ethinylestradiol plus levonorgestrel for the treatment of primary dysmenorrhea. [Randomized Controlled Trial]Int J Gynaecol Obstet. 2014 Jun; 125(3):270-4.IJ
- CONCLUSIONS: Both E(2)V/DNG and EE/LNG led to considerable relief of dysmenorrheic complaints among women with primary dysmenorrhea, decreasing the number of days with dysmenorrheic pain from baseline to a similar extent. ClinicalTrials.gov:NCT00909857.
- Effect of brivaracetam (400 mg/day) on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive in healthy women. [Randomized Controlled Trial]J Clin Pharmacol. 2013 Dec; 53(12):1313-21.JC
- Brivaracetam is a high-affinity synaptic vesicle protein 2A ligand, in Phase III clinical development for epilepsy. This study assessed the effect of brivaracetam 400 mg/day on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive (OC) containing 30 µg ethinylestradiol and 150 µg levonorgestrel, in healthy pre-menopausal women. This open-label, single-center, randomized, t…
Brivaracetam is a high-affinity synaptic vesicle protein 2A ligand, in Phase III clinical development for epilepsy. This study assessed the effect of brivaracetam 400 mg/day on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive (OC) containing 30 µg ethinylestradiol and 150 µg levonorgestrel, in healthy pre-menopausal women. This open-label, single-center, randomized, two-way crossover, multiple oral dose study (N01080) included two consecutive 28-day cycles without (control) or with brivaracetam (test), and a 28-day follow-up. OC was taken on Days 1–21 of every cycle and brivaracetam 200 mg twice daily was administered on Days 1–20 of the test cycle. Ethinylestradiol and levonorgestrel pharmacokinetics were determined on Day 20 and endogenous hormones were measured frequently during both control and test cycles. Overall, 23/24 participants (age: 19–39 years) completed the study. AUC ratio (90% confidence interval) for brivaracetam versus control was 0.73 (0.69, 0.78) for ethinylestradiol and 0.78 (0.72, 0.83) for levonorgestrel, outside pre-defined bioequivalence limits (0.80–1.25). Levels of endogenous hormones were similar and normal during brivaracetam and control cycles. Brivaracetam in combination with OC was well tolerated. Brivaracetam 400 mg/day co-administered with a combination OC in healthy women reduced ethinylestradiol and levonorgestrel plasma levels but did not result in ovulation.
- Women's experiences with tailored use of a combined oral contraceptive: a qualitative study. [Journal Article]Hum Reprod. 2013 Jun; 28(6):1620-5.HR
- CONCLUSIONS: Some women reported very positive experiences with tailored use of COCPs, others did not like the unpredictability about when they would bleed and some women reported increased anxiety about possible pregnancy.The sample comprised mainly young, nulliparous women. The majority of women were using COCPs at the start of the study.Clinicians discussing extended-use regimes with patients should mention that women may need time to adjust to an extended-use regime. Future research should attempt to identify predictors of response to extended use of COCPs.
- Pharmacokinetics of fingolimod (FTY720) and a combined oral contraceptive coadministered in healthy women: drug-drug interaction study results. [Journal Article]Int J Clin Pharmacol Ther. 2012 Aug; 50(8):540-4.IJ
- CONCLUSIONS: Fingolimod therapy does not alter the pharmacokinetics of the combined OC ethinylestradiol/ levonorgestrel to a clinically significant degree. Ethinylestradiol/levonorgestrel does not alter the pharmacokinetics of fingolimod. Women receiving fingolimod therapy are able to use a combined OC as a means of effective birth control.
- A randomized controlled trial of subantimicrobial-dose doxycycline to prevent unscheduled bleeding with continuous oral contraceptive pill use. [Randomized Controlled Trial]Contraception. 2012 Apr; 85(4):351-8.C
- CONCLUSIONS: The coadministration of subantimicrobial-dose doxycycline during initiation of continuous OCPs results in a significant reduction in the length of time needed to achieve amenorrhea.
- Assessment of the activity of an oral contraceptive on the levels of oxidative stress and changes in oxidative stress after co-treatment with two different types of physiological modulators with antioxidant action. [Clinical Trial]Contraception. 2011 Oct; 84(4):418-22.C
- CONCLUSIONS: We conclude that to control the OS generated by OC, specific types of physiological modulators are needed.
- Metabolic and haemostatic effects of estradiol valerate/dienogest, a novel oral contraceptive: a randomized, open-label, single-centre study. [Randomized Controlled Trial]Clin Drug Investig. 2011; 31(8):573-584.CD
- CONCLUSIONS: E(2)V/DNG had a minimal impact on metabolic and haemostatic parameters, and a more favourable effect than EE/LNG on lipid markers.
- An open-label, comparative study of the effects of a dose-reduced oral contraceptive containing 0.02 mg ethinylestradiol/2 mg chlormadinone acetate on hemostatic parameters and lipid and carbohydrate metabolism variables. [Randomized Controlled Trial]Contraception. 2010 May; 81(5):391-400.C
- CONCLUSIONS: The changes observed were typical of those seen across low-dose COCs that differ according to commonly-used progestogens.