The sections below provide information on substances for which data on drug interactions with COCs are available. There is little information available about the clinical effect of most drug interactions that may affect COCs. However, based on the known pharmacokinetic effects of these drugs, clinical strategies to minimize any potential adverse effect on contraceptive effectiveness or safety are suggested.
Consult the approved product labeling of all concurrently used drugs to obtain further information about interactions with COCs or the potential for metabolic enzyme or transporter system alterations.
No drug-drug interaction studies were conducted with Ayuna.
4.1 Effects of Other Drugs on Combined Oral Contraceptives
Substances Decreasing the Plasma Concentrations of COCs and Potentially Diminishing the Efficacy of COCs:
Table 1 includes substances that demonstrated an important drug interaction with Ayuna.
Table 1: Significant Drug Interactions Involving Substances That Affect COCs
|Metabolic Enzyme Inducers|
|Clinical effect|| |
|Prevention or management|| |
|Examples||Aprepitant, barbiturates, bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, rifabutin, rufinamide, topiramate, products containing St. John’s worta , and certain protease inhibitors (see separate section on protease inhibitors below).|
|Clinical effect|| |
|Prevention or management||Administer 4 or more hours apart to attenuate this drug interaction.|
a Induction potency of St. John’s wort may vary widely based on preparation.
Substances increasing the systemic exposure of COCs:
Co-administration of atorvastatin or rosuvastatin and COCs containing ethinyl estradiol increase systemic exposure of ethinyl estradiol by approximately 20 to 25 percent. Ascorbic acid and acetaminophen may increase systemic exposure of ethinyl estradiol, possibly by inhibition of conjugation. CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice,7 or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of COCs.
Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors:
Significant decreases in systemic exposure of the estrogen and/or progestin have been noted when COCs are co-administered with some HIV protease inhibitors (e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some HCV protease inhibitors (e.g., boceprevir and telaprevir), and some non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine).
In contrast, significant increases in systemic exposure of the estrogen and/or progestin have been noted when COCs are co-administered with certain other HIV protease inhibitors (e.g., indinavir and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (e.g., etravirine).
4.2 Effects of Combined Oral Contraceptives on Other Drugs
Table 2 provides significant drug interaction information for drugs co-administered with Ayuna.
Table 2: Significant Drug Interaction Information for Drugs Co-Administered With COCs
|Clinical effect|| |
|Prevention or management||Dose adjustment may be necessary. Consult the approved product labeling for lamotrigine.|
|Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy|
|Clinical effect||Concomitant use of COCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid-binding and cortisol-binding globulin (see Warnings, EFFECT ON BINDING GLOBULINS).|
|Prevention or management||The dose of replacement thyroid hormone or cortisol therapy may need to be increased. Consult the approved product labeling for the therapy in use (see Warnings, EFFECT ON BINDING GLOBULINS).|
|Clinical effect||Concomitant use of COCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. Concomitant use with ethinyl estradiol-containing COCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole).|
|Prevention or management||The dosage of drugs that can be affected by this interaction may need to be increased. Consult the approved product labeling for the concomitantly used drug.|
4.3 Concomitant Use with Hepatitis C Virus (HCV) Combination Therapy –Liver Enzyme Elevation
Do not co-administer Ayuna with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, [see Warnings (5)], and glecaprevir/pibrentasvir due to potential for ALT elevations.
4.4 Effect on Laboratory Tests
The use of COCs may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.
See WARNINGS (11).
Discontinue Ayuna if pregnancy occurs because there is no reason to use COCs in pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to COCs before conception or during early pregnancy. Animal studies to evaluate embryo/fetal toxicity were not conducted.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.
Contraceptive hormones and/or metabolites are present in human milk. COCs can reduce milk production in breast-feeding females. This reduction can occur at any time but is less likely to occur once breast-feeding is well-established. When possible, advise the nursing female to use other methods of contraception until she discontinues breast-feeding. (see DOSAGE AND ADMINISTRATION). The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for Ayuna and any potential adverse effects on the breast-fed child from Ayuna or from the underlying maternal condition.
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