NEXTSTELLIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NEXTSTELLIS (NEXTSTELLIS).
Combination oral contraceptive: estrogen (estetrol) and progestin (drospirenone) suppress gonadotropin release, inhibiting ovulation; increase cervical mucus viscosity, impeding sperm penetration; alter endometrial lining, reducing implantation likelihood.
| Metabolism | Estetrol: primarily glucuronidation (UGT2B7, UGT1A1, UGT1A3) and to a lesser extent sulfation; Drospirenone: extensively metabolized via cytochrome P450 3A4 (CYP3A4) with subsequent conjugation. |
| Excretion | Urine (60%) and feces (35%); drospirenone and metabolites, with enterohepatic recirculation. |
| Half-life | Drospirenone: 30 hours; ethinyl estradiol: 12 hours. The long half-life allows once-daily dosing and stable serum concentrations. |
| Protein binding | Drospirenone: 97% bound to serum albumin, not to SHBG or CBG; ethinyl estradiol: 98% bound to albumin, induces SHBG synthesis. |
| Volume of Distribution | Drospirenone: 4 L/kg; ethinyl estradiol: 4.5 L/kg. Indicates extensive tissue distribution beyond plasma volume. |
| Bioavailability | Drospirenone: 76%; ethinyl estradiol: 40% (due to first-pass metabolism). |
| Onset of Action | 7 days of continuous dosing to achieve contraceptive effect; follicular suppression begins within 2-3 days. |
| Duration of Action | Contraceptive protection persists for 7 days after last dose if no pill-free interval exceeds 7 days; longer intervals increase ovulation risk. |
One tablet orally once daily, each tablet containing drospirenone 3 mg and estetrol 14.2 mg, taken continuously without a break.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in patients with renal impairment (GFR <60 mL/min/1.73 m²). No dose adjustment recommended for mild impairment (GFR 60-89 mL/min/1.73 m²); use with caution. |
| Liver impairment | Contraindicated in patients with Child-Pugh Class B or C hepatic impairment. Use with caution in Child-Pugh Class A; monitor liver function. |
| Pediatric use | Not indicated for use in pediatric patients before menarche. Post-menarche: same as adult dosing (one tablet daily) for females aged 12-17 years. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific geriatric dose adjustment; contraindicated if renal or hepatic impairment present. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEXTSTELLIS (NEXTSTELLIS).
| Breastfeeding | Small amounts of contraceptive steroids and/or metabolites are excreted in breast milk. Drospirenone has been detected in breast milk; the M/P ratio is not established. Estetrol is likely excreted. Use in breastfeeding women is not recommended until weaning, as it may reduce milk production and affect infant hormonal balance. |
| Teratogenic Risk | NEXTSTELLIS (drospirenone and estetrol) is contraindicated in pregnancy. There is no indication for use during pregnancy; however, inadvertent exposure during early pregnancy does not appear to increase the risk of birth defects based on limited data from observational studies with drospirenone-containing COCs. Estetrol has no human pregnancy data. Due to the hormonal milieu, continuation post-conception is not recommended. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use. Risk increases with age (especially >35 years) and with number of cigarettes smoked. Women >35 years who smoke should not use this product.
| Serious Effects |
Known or suspected pregnancy; breastfeeding; current or history of venous thrombotic events (deep vein thrombosis, pulmonary embolism); arterial thrombotic events (stroke, myocardial infarction); cerebrovascular disease; coronary artery disease; prothrombotic conditions (e.g., factor V Leiden, antiphospholipid syndrome); hypertension (uncontrolled); diabetes with vascular disease; headaches with focal neurological symptoms (e.g., migraine with aura over age 35); smoking >15 cigarettes/day and age ≥35; liver tumors (benign or malignant); active liver disease or impaired hepatic function; history of cholestatic jaundice or jaundice with prior oral contraceptive use; renal impairment (creatinine clearance <50 mL/min); adrenal insufficiency; known or suspected sex hormone-sensitive tumors (e.g., breast cancer); undiagnosed abnormal uterine bleeding; hypersensitivity to any component; use with hepatitis C regimens containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir.
| Precautions | Thrombotic disorders (venous thromboembolism, arterial thromboembolism), cerebrovascular disease, myocardial infarction; smoking; hypertension; gallbladder disease; hepatic impairment; carbohydrate/lipid effects; headache; bleeding irregularities; depression; malignancy (breast cancer); hereditary angioedema; hyperkalemia (due to drospirenone's antimineralocorticoid activity); hepatic neoplasia; somatostatin/tumor necrosis; ureteral/renal effects; reduced efficacy with enzyme-inducing drugs; exacerbation of autoimmune disorders. |
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| Fetal Monitoring | If unintentional use during pregnancy occurs, no specific fetal monitoring is indicated beyond routine prenatal care. Pregnancy testing should be performed if pregnancy is suspected. No routine maternal monitoring beyond standard prenatal care is required. |
| Fertility Effects | NEXTSTELLIS is a hormonal contraceptive that suppresses ovulation, thereby preventing pregnancy. Fertility returns to baseline upon discontinuation, with no long-term impairment. There is no evidence of adverse effects on future fertility. |