Brand names: Safyral
FDA Black Box Warning
WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs should not be used by women who are over 35 years of age and smoke [ see Contraindications ( 4 ) ]. WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS See full prescribing information for complete boxed warning. • Women over 35 years old who smoke should not use Safyral. ( 4 ) • Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. ( 4 )
Contraindications
4 CONTRAINDICATIONS Safyral is contraindicated in females who are known to have or develop the following conditions: • Renal impairment • Adrenal insufficiency • A high risk of arterial or venous thrombotic diseases. Examples include women who are known to: • Smoke, if over age 35 [see Boxed Warning and Warnings and Precautions ( 5.1 )] • Have deep vein thrombosis or pulmonary embolism, now or in the past [see Warnings and Precautions ( 5.1 ) ] • Have cerebrovascular disease [see Warnings and Precautions ( 5.1 )] • Have coronary artery disease [see Warnings and Precautions ( 5.1 )] • Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see Warnings and Precautions ( 5.1 )] • Have inherited or acquired hypercoagulopathies [see Warnings and Precautions ( 5.1 )] • Have uncontrolled hypertension [see Warnings and Precautions ( 5.6 )] • Have diabetes mellitus with vascular disease [see Warnings and Precautions ( 5.8 )] • Have headaches with focal neurological symptoms or have migraine headaches with or without aura if over age 35 [see Warnings and Precautions ( 5.9 )] • Undiagnosed abnormal uterine bleeding [see Warnings and Precautions ( 5.10 )] • Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions ( 5.3 )] • Liver tumor (benign or malignant) or liver disease [see Warnings and Precautions ( 5.4 ) and Use in Specific Populations ( 8.7 )] • Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir due to the potential for ALT elevations [see Warnings and Precautions ( 5.5 ) and Drug Interactions ( 7.3 )]. • Renal impairment ( 4 ) • Adrenal insufficiency ( 4 ) • A high risk of arterial or venous thrombotic diseases ( 4 ) • Undiagnosed abnormal uterine bleeding ( 4 ) • Breast cancer ( 4 ) • Liver tumors or liver disease ( 4 ) • Co-administration with He
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary There is no use for contraception in pregnancy; therefore, Safyral should be discontinued during pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy. 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. Data Human Data A retrospective database study of women in Norway, that included 44,734 pregnancies of which 368 were women who inadvertently took drospirenone/ethinyl estradiol during the first trimester of a pregnancy, found there were no adverse effects on pre-term birth, small for gestational age, or birth weight Z-scores. Post-marketing adverse event data on the use of Safyral in pregnant women suggest that frequencies of miscarriage and congenital anomalies were not higher than the estimated background risk in the general population.
31 interactions on record
May increase plasma ethinyl estradiol concentrations possibly by inhibition of conjugation.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
May increase plasma ethinyl estradiol concentrations possibly by inhibition of conjugation.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Co-administration increases AUC values for ethinyl estradiol by approximately 20%.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Enzyme inducers that may decrease effectiveness of COCs or increase breakthrough bleeding. Use back-up contraception.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Enzyme inducer that may decrease effectiveness of COCs or increase breakthrough bleeding. Use back-up contraception.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Enzyme inducer that may decrease effectiveness of COCs or increase breakthrough bleeding. Use back-up contraception.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Concomitant administration of moderate or strong CYP3A4 inhibitors such as azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g., clarithromycin, erythromycin), diltiazem, and grapefruit juice can increase the plasma concentrations of the estrogen or the progestin or both.
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Moderate CYP3A4 inhibitor that can increase plasma concentrations of estrogen or progestin.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Concomitant administration of moderate or strong CYP3A4 inhibitors such as azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g., clarithromycin, erythromycin), diltiazem, and grapefruit juice can increase the plasma concentrations of the estrogen or the progestin or both.
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Enzyme inducer that may decrease effectiveness of COCs or increase breakthrough bleeding. Use back-up contraception.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Concomitant administration of moderate or strong CYP3A4 inhibitors such as azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g., clarithromycin, erythromycin), diltiazem, and grapefruit juice can increase the plasma concentrations of the estrogen or the progestin or both.
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Can increase plasma concentrations of estrogen or progestin through CYP3A4 inhibition.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Enzyme inducer that may decrease effectiveness of COCs or increase breakthrough bleeding. Use back-up contraception.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Concomitant administration of moderate or strong CYP3A4 inhibitors such as azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g., clarithromycin, erythromycin), diltiazem, and grapefruit juice can increase the plasma concentrations of the estrogen or the progestin or both.
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Concomitant administration of moderate or strong CYP3A4 inhibitors such as azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g., clarithromycin, erythromycin), diltiazem, and grapefruit juice can increase the plasma concentrations of the estrogen or the progestin or both. In a clinical drug-drug interaction study conducted in premenopausal women, once daily co-administration of DRSP 3 mg/EE 0.02 mg containing tablets with strong CYP3A4 inhibitor, ketoconazole 200 mg twice daily for 10 days resulted in a moderate increase of DRSP systemic exposure.
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
May cause significant changes (increase or decrease) in plasma concentrations of estrogen and progestin.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
COCs Increasing the Plasma Concentrations of CYP450 Enzymes: In clinical studies, administration of a hormonal contraceptive containing EE did not lead to any increase or only to a weak increase in plasma concentrations of CYP3A4 substrates (e.g., midazolam) while plasma concentrations of CYP2C19 substrates (e.g., omeprazole and voriconazole) and CYP1A2 substrates (e.g., theophylline and tizanidine) can have a weak or moderate increase.
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
COCs Increasing the Plasma Concentrations of CYP450 Enzymes: In clinical studies, administration of a hormonal contraceptive containing EE did not lead to any increase or only to a weak increase in plasma concentrations of CYP3A4 substrates (e.g., midazolam) while plasma concentrations of CYP2C19 substrates (e.g., omeprazole and voriconazole) and CYP1A2 substrates (e.g., theophylline and tizanidine) can have a weak or moderate increase.
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Enzyme inducer that may decrease effectiveness of COCs or increase breakthrough bleeding. Use back-up contraception.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Enzyme inducer that may decrease effectiveness of COCs or increase breakthrough bleeding. Use back-up contraception.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
May cause significant changes (increase or decrease) in plasma concentrations of estrogen and progestin.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Enzyme inducer that may decrease effectiveness of COCs or increase breakthrough bleeding. Use back-up contraception.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Herbal product that may decrease effectiveness of COCs or increase breakthrough bleeding. Use back-up contraception.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Enzyme inducer that may decrease effectiveness of COCs or increase breakthrough bleeding. Use back-up contraception.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Moderate to strong CYP3A4 inhibitor that can increase plasma concentrations of estrogen or progestin.
Source: NLP:drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
Concomitant administration of moderate or strong CYP3A4 inhibitors such as azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (e.g., clarithromycin, erythromycin), diltiazem, and grapefruit juice can increase the plasma concentrations of the estrogen or the progestin or both. COCs Increasing the Plasma Concentrations of CYP450 Enzymes: In clinical studies, administration of a hormonal contraceptive containing EE did not lead to any increase or only to a weak increase in plasma concentrations of CYP3A4 substrates (e.g., midazolam) while plasma concentrations of CYP2C19 substrates (e.g., omeprazole and voriconazole) and CYP1A2 substrates (e.g., theophylline and tizanidine) can have a weak or moderate increase.
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
DRSP causes an increase in plasma renin activity and plasma aldosterone induced by its mild anti-mineralocorticoid activity.
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
7.3 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer Beyaz with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions ( 5.5 )] .
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
7.3 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer Beyaz with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions ( 5.5 )] .
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
7.3 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer Beyaz with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions ( 5.5 )] .
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium
7.3 Concomitant Use with HCV Combination Therapy – Liver Enzyme Elevation Do not co-administer Beyaz with HCV drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to potential for ALT elevations [see Warnings and Precautions ( 5.5 )] .
Source: FDA drug label - drospirenone/ethinyl estradiol/levomefolate calcium and levomefolate calcium