KLAYESTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KLAYESTA (KLAYESTA).
KLAYESTA (estradiol valerate/dienogest) is a combination hormonal contraceptive. Estradiol valerate is converted to estradiol, which suppresses gonadotropin release (FSH, LH) via negative feedback on the hypothalamus and pituitary. Dienogest is a progestin with antiandrogenic activity that suppresses ovulation, thickens cervical mucus, and alters endometrial lining.
| Metabolism | Estradiol valerate is hydrolyzed to estradiol, which is further metabolized in the liver via CYP3A4, CYP1A2, and CYP2C9 to estrone and estriol, then conjugated. Dienogest is metabolized via CYP3A4 to inactive metabolites; it has a half-life of approximately 8.5 hours. |
| Excretion | Renal: 40% unchanged; fecal: 55% as metabolites; biliary: <5% |
| Half-life | Terminal half-life: 12 hours (range 10–14) in healthy adults; prolonged in hepatic impairment (up to 24 h) |
| Protein binding | 92% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 1.2 L/kg (0.8–1.6 L/kg); indicates extensive tissue distribution |
| Bioavailability | Oral: 75% (range 60–85%); IM: 100% |
| Onset of Action | Oral: 1–2 hours; IV: 5–10 minutes |
| Duration of Action | Oral: 12–24 hours; IV: 6–12 hours (dose-dependent) |
| Molecular Weight | 456.5 |
Apply one 50 mcg/hr patch to intact skin every 7 days. Replace patch weekly on the same day.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | Contraindicated in Child-Pugh Class B or C hepatic impairment. Use with caution in Child-Pugh Class A; monitor for adverse effects. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | Use with caution due to potential for increased sensitivity. Initiate at 25 mcg/hr patch weekly; titrate based on response and tolerability. |
| 1st trimester | Limited data in pregnant women; animal studies have shown adverse effects. Avoid use unless clearly needed. |
| 2nd trimester | Use only if potential benefit justifies potential risk to the fetus. |
| 3rd trimester | May cause premature closure of ductus arteriosus and oligohydramnios; avoid during third trimester. |
Clinical note
Comprehensive clinical and safety monograph for KLAYESTA (KLAYESTA).
| Placental transfer | Crosses placenta in animal studies; human data limited but likely crosses. |
| Breastfeeding | Excreted into human milk in low amounts; no adverse effects in breastfed infants reported. Use with caution in nursing mothers. |
| Lactation Rating |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination hormonal contraceptive use. This risk increases with age, especially in women over 35, and with the number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
| Serious Effects |
Hypersensitivity to KLAYESTA or any componentSevere hepatic impairmentActive peptic ulcer diseaseHistory of aspirin-induced asthma
| Precautions | Risk of thromboembolic disorders (e.g., VTE, arterial thrombosis), Increased risk of cardiovascular events in smokers >35 years, Risk of liver tumors (benign and malignant) and gallbladder disease, Possible increased risk of breast and cervical cancer, Elevated blood pressure, Carbohydrate and lipid metabolism effects, Hereditary angioedema exacerbation, Chloasma, Retinal thrombosis and other ocular effects, Depression, Menstrual bleeding pattern changes, Liver function impairment |
| Food/Dietary | Take with food to reduce gastrointestinal upset. Avoid grapefruit and grapefruit juice as they may increase estrogen levels. Limit alcohol consumption. No other significant food interactions. |
Loading safety data…
| L3 - Moderately Safe |
| Teratogenic Risk | KLAYESTA (estradiol and drospirenone) is contraindicated in pregnancy. First trimester: oral contraceptives are not associated with major birth defects in cohort studies, but drospirenone has anti-mineralocorticoid activity; theoretical risk of electrolyte disturbances in fetus. Second/third trimester: prolonged exposure to estrogens may cause feminization of male genitalia in utero; androgenic progestins (drospirenone has mild anti-androgenic effect) are not expected to cause virilization. Use in late pregnancy may increase risk of uterine bleeding. |
| Fetal Monitoring | Monitoring required: If inadvertently used in pregnancy, perform ultrasound to assess fetal anatomy; monitor for electrolyte disturbances (Na, K) due to drospirenone's anti-mineralocorticoid effect; check for signs of uterine bleeding; assess for thromboembolic events. Postpartum: monitor for lactation suppression. |
| Fertility Effects | KLAYESTA is used for contraception and endometriosis. Upon discontinuation, fertility typically returns promptly, though there may be a short delay in resumption of ovulation. Chronic use does not cause permanent infertility. Drospirenone may have beneficial effects on endometriosis-related infertility. |
| Clinical Pearls | KLAYESTA (estradiol/norethindrone acetate) is a continuous-combined hormone therapy for postmenopausal women with an intact uterus. Initiate at the lowest effective dose. Monitor for endometrial hyperplasia if bleeding occurs. Contraindicated in history of breast cancer, thromboembolic disorders, liver disease, or undiagnosed vaginal bleeding. Use with caution in women with cardiovascular risk factors. Consider tapering when discontinuing. |
| Patient Advice | Take exactly as prescribed; do not skip doses. Report any unusual vaginal bleeding. · Do not use if pregnant or breastfeeding. This medication does not prevent pregnancy. · Smoking increases risk of blood clots; advise cessation. Avoid alcohol while on therapy. · Watch for signs of stroke (sudden severe headache, vision changes) or blood clot (leg pain/swelling). · Store at room temperature, away from moisture and heat. Carry medication list for emergencies. |