Drospirenone and estetrol
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combined hormonal contraceptive (CHC) use. This risk increases with age, particularly in females over 35 years of age, and with the number of cigarettes smoked. For this reason, CHCs, including NEXTSTELLIS, are contraindicated in females who are over 35 years of age and smoke. [See Contraindications (4) and Warnings and Precautions (5.1) ] WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS See full prescribing information for complete boxed warning .
Females over 35 years old who smoke should not use NEXTSTELLIS ( 4 ) Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. ( 4 )
Dosing in kidney impairment
Renal Impairment NEXTSTELLIS is contraindicated in females with renal impairment [see Contraindications , Warnings and Precautions ]. In subjects with creatinine clearance (CLcr) of 50–79 mL/min, serum DRSP levels were comparable to those in a control group with CLcr ≥ 80 mL/min. In subjects with CLcr of 30–49 mL/min, serum DRSP concentrations were on average 37% higher than those in the control group.
In addition, there is a potential to develop hyperkalemia in subjects with renal impairment whose serum potassium is in the upper reference range, and who are concomitantly using potassium sparing drugs [see Warnings and Precautions , Drug Interactions and Clinical Pharmacology ] .
Dosing in liver impairment
Hepatic Impairment NEXTSTELLIS is contraindicated in females with hepatic impairment [see Contraindications , Warnings and Precautions (5.1 , 5.3) ] . The mean exposure to drospirenone (DRSP) in females with moderate liver impairment is approximately three times higher than the exposure in females with normal liver function.
NEXTSTELLIS has not been studied in females with severe hepatic impairment [see Clinical Pharmacology ].
Preparation and administration
Recommended Dosage and Administration Start NEXTSTELLIS using a Day 1 start. Take one tablet by mouth at the same time every day with or without food.
Additional Administration Information To achieve maximum contraceptive effectiveness, take one tablet every day at about the same time each day. The recommended dosage of NEXTSTELLIS is one tablet daily for 28 consecutive days: one pink active tablet daily during the first 24 days followed by one white inactive tablet daily during the 4 following days (see Table 1 ). [See table below.] Starting NEXTSTELLIS after Abortion or Miscarriage ≤14 weeks gestation Within the first 7 days of complete first trimester abortion or miscarriage, use additional nonhormonal contraception for the next 7 days.
After the first 7 days, follow instructions for "Starting NEXTSTELLIS in females with no current use of hormonal contraception". > 14 weeks but ≤ 20 weeks gestation After 4 weeks following second trimester abortion or miscarriage. Consider duration of pregnancy and increased risk of thromboembolism [see Warnings and Precautions ] If menstrual cycles have returned, follow instructions for "Starting NEXTSTELLIS in females with no current use of hormonal contraception." If menstrual cycles have not resumed, consider the possibility of ovulation and pregnancy.
If not pregnant, use additional nonhormonal contraception for the first 7 days of NEXTSTELLIS use.
Administration Recommendations after Vomiting or Acute Diarrhea If vomiting or acute diarrhea occurs within 3 to 4 hours after taking an active tablet, take the new active tablet (scheduled for the next day) as soon as possible. Take the new tablet within 12 hours of the usual time of tablet-taking if possible. If more than two tablets are missed, follow the advice concerning missed tablets, including using backup non-hormonal contraception.
For additional recommendations, refer to the table above [see Dosage and Administration ].
Drug interactions
Check drospirenone and estetrol against a medication listLabel text (9 paragraphs)
7 DRUG INTERACTIONS CYP3A Inducers: May lead to contraceptive failure and/or increase breakthrough bleeding. Avoid concomitant use. If concomitant use is unavoidable, use an alternative or back-up contraceptive method during co-administration and up to 28 days after discontinuation of the CYP3A inducer. ( 7.1 ) See Full Prescribing Information for additional clinically significant drug interactions ( 7 ).
7.1 Effects of Other Drugs on Hormonal Contraceptives Clinically significant drug interactions with other drugs that affect NEXTSTELLIS are presented in Table 5. Table 5. Clinically Significant Drug Interactions With Other Drugs that Affect NEXTSTELLIS CYP3A Inducers Clinical Effect DRSP is a CYP3A4 substrate. Concomitant use with strong CYP3A inducers or certain moderate or weak CYP3A inducers may decrease DRSP exposure [see Clinical Pharmacology (12.3) ] , which may lead to contraceptive failure. Prevention or Management Strong CYP3A Inducers Avoid concomitant use.
If concomitant use is unavoidable, use an alternative contraceptive method (e.g., intrauterine system) or backup non-hormonal contraceptive method during coadministration and up to 28 days after discontinuation of the strong CYP3A inducer. Moderate and Weak CYP3A Inducers Use an alternative or backup contraceptive method during coadministration and up to 28 days after discontinuation of the CYP3A inducer, unless the Prescribing Information of the specific moderate or weak CYP3A inducer indicates there is no clinically significant interaction with NEXTSTELLIS. Strong CYP3A Inhibitors Clinical Effect DRSP is a CYP3A4 substrate.
Concomitant use with a strong CYP3A inhibitor may increase DRSP exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions of NEXTSTELLIS, including hyperkalemia [see Warnings and Precautions (5.2) ] . Prevention or Management Consider monitoring serum potassium concentration in patients who take a strong CYP3A4 inhibitor long-term and concomitantly with NEXTSTELLIS. Drugs that May Reduce the Absorption of NEXTSTELLIS Clinical Effect Concomitant use with drugs such as bile acid sequestrants may decrease the E4 and DRSP exposure, which may lead to contraceptive failure and/or an increase in breakthrough bleeding.
Prevention or Management Separate time of administration of NEXTSTELLIS and the concomitant drug. Refer to the concomitant drug's Prescribing Information for additional information.
7.2 Effects of NEXTSTELLIS on Other Drugs Table 6 includes clinically significant drug interactions with NEXTSTELLIS that affect other drugs. Table 6. Clinically Significant Drug Interactions of NEXTSTELLIS on Other Drugs Anti-Diabetic Drugs Clinical Effect Concomitant use of NEXTSTELLIS may reduce the blood glucose lowering effect of anti-diabetic drugs [see Warnings and Precautions (5.8) and Clinical Pharmacology (12.2) . Prevention or Management Increase frequency of glucose monitoring and increase anti-diabetic drug dosage, as needed, based on glucose levels.
Drugs that may increase serum potassium concentration Clinical Effect There is a potential for an increase in serum potassium concentration in females taking NEXTSTELLIS with other drugs that may increase serum potassium concentration [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2) ]. Prevention or Management Monitor serum potassium concentration in females at increased risk for hyperkalemia. Lamotrigine Clinical Effect Concomitant use of NEXTSTELLIS may decrease lamotrigine exposure [see Clinical Pharmacology (12.3) ] , which may reduce efficacy of lamotrigine.
Prevention or Management Adjust lamotrigine dosage as recommended in its Prescribing Information based on NEXTSTELLIS initiation or discontinuation. Systemic Corticosteroids Clinical Effect Concomitant use of NEXTSTELLIS may increase the exposure of certain systemic corticosteroids, which may increase the risk of corticosteroid-related adverse reactions [ see Clinical Pharmacology (12.2) . Prevention or Management Follow the recommendation for the corticosteroid in accordance with its Prescribing Information. Consider more frequent monitoring for corticosteroid adverse reactions when used concomitantly with NEXTSTELLIS.
Thyroid Hormone Replacement Therapy Clinical Effect Concomitant use of NEXTSTELLIS may increase thyroid-binding globulin concentration [see Warnings and Precautions (5.10) and Clinical Pharmacology (12.2) ]. Prevention or Management Monitor thyroid-stimulating hormone (TSH) level and follow the recommendation for thyroid hormone replacement in accordance with its Prescribing Information.
Contraindications
4 CONTRAINDICATIONS NEXTSTELLIS is contraindicated in females who are known to have or develop the following conditions: A history of, increased risk for, or current arterial or venous thrombotic/thromboembolic diseases.
Examples include females who are known to: - Smoke, if 35 years of age and older [see Boxed Warning and Warnings and Precautions (5.1) ] - Have current or history of deep vein thrombosis or pulmonary embolism [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 or hypertension with vascular disease [see Warnings and Precautions (5.1) ] - Have diabetes mellitus with hypertension or end-organ damage; or diabetes mellitus of > 20 years duration [see Warnings and Precautions (5.9) ] - Have migraine headaches with aura [see Warnings and Precautions (5.4) ] Current diagnosis of, or history of, breast cancer, which may be hormone-sensitive [see Warnings and Precautions (5.5) ] Hepatic adenoma, hepatocellular carcinoma, acute hepatitis, or severe (decompensated) cirrhosis [see Warnings and Precautions (5.6) ] 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 (5.7) ] Abnormal uterine bleeding that has an undiagnosed etiology [see Warnings and Precautions (5.5) ] Renal Impairment [see Warnings and Precautions (5.2) ] Adrenal insufficiency [see Warnings and Precautions (5.2) ] A high risk of arterial or venous thrombotic diseases ( 4 ) Breast cancer or history of breast cancer ( 4 ) Hepatic adenoma, hepatocellular carcinoma, acute hepatitis or decompensated cirrhosis ( 4 ) Co-administration with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without…
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Discontinue NEXTSTELLIS if pregnancy occurs, because there is no reason to use hormonal contraceptives during pregnancy [see Contraindications (4) ] . 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. Reproductive toxicity studies performed with E4 alone have shown expected pharmacologic effects in animals, which are considered consistent with estrogen exposure. 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.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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