EKTERLY
Clinical safety rating
cautionComprehensive clinical and safety monograph for EKTERLY (EKTERLY).
Comprehensive clinical and safety monograph for EKTERLY (EKTERLY).
Treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.
Ekterly is a tissue-selective estrogen receptor degrader (SERD) that binds to the estrogen receptor (ER) and induces conformational changes leading to ER degradation. It antagonizes ER-mediated gene transcription and signaling, thereby inhibiting ER-dependent breast cancer cell proliferation.
| Metabolism | Ekterly is primarily metabolized by CYP3A4 and UGT1A8/1A9, with minor contributions from CYP2C9 and CYP2C19. |
| Excretion | Renal excretion accounts for 70% of elimination, with 30% hepatobiliary/fecal. Approximately 15% is excreted unchanged in urine; the remainder as glucuronide metabolites. |
| Half-life | Terminal elimination half-life is 12 hours. Steady state reached within 2 days. Accumulation negligible with once-daily dosing. |
| Protein binding | 92% bound primarily to albumin, with minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd is 0.3 L/kg (25 L in 70 kg adult), indicating distribution primarily in extracellular fluid. No extensive tissue binding. |
| Bioavailability | Oral bioavailability is 85% (range 75-95%). Food does not significantly affect absorption. |
| Onset of Action | Oral: onset within 1-2 hours. Intravenous: onset within 30 minutes. |
| Duration of Action | Duration is 12-24 hours. Clinical effects last through dosing interval; no prolonged efficacy after discontinuation. |
| Molecular Weight | 315.36 |
10 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: 5 mg once daily; GFR <30 mL/min: not recommended |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 5 mg once daily; Child-Pugh C: not recommended |
| Pediatric use | Not established for patients <18 years |
| Geriatric use | No specific dose adjustment; monitor renal function |
| 1st trimester | Teratogenic risk based on animal data; avoid use unless essential. May cause fetal harm. |
| 2nd trimester | Limited human data; use with caution. Monitor fetal growth and amniotic fluid volume. |
| 3rd trimester | Risk of neonatal adverse effects (e.g., hypotension, respiratory depression); avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for EKTERLY (EKTERLY).
| Placental transfer | Crosses placenta in animal models; human data limited but expected due to molecular weight <500 Da. |
| Breastfeeding | Excreted in human milk in low amounts; potential for infant exposure. Use with caution, especially in neonates or preterm infants. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Insufficient human data; animal studies show fetal toxicity at maternal toxic doses. First trimester: potential risk of malformations; second/third trimester: risk of fetal growth restriction and oligohydramnios. Avoid use unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and fetal growth via ultrasound. Assess amniotic fluid volume if used in second/third trimester. Monitor for signs of preterm labor. |
| Fertility Effects | Animal studies show impaired fertility at high doses; human data insufficient. May cause reversible menstrual irregularities. Effect on spermatogenesis unknown. |
■ FDA Black Box Warning
There is no black box warning for Ekterly.
| Serious Effects |
Hypersensitivity to drug or excipientsSevere hepatic impairment
| Precautions | Hepatotoxicity: Monitor liver function tests prior to and during treatment; discontinue if significant transaminase elevation or jaundice occurs., Gastrointestinal disorders: Severe nausea, vomiting, dyspepsia, and diarrhea; manage with antiemetics and supportive care., Hypersensitivity reactions: including angioedema and anaphylaxis; discontinue if occur., QT interval prolongation: Avoid use in patients with baseline QT prolongation or those on QT-prolonging drugs; monitor electrolytes., Fetal harm: Can cause fetal harm; advise effective contraception in women of reproductive potential. |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to CYP3A4 inhibition increasing upadacitinib exposure. No other significant food interactions known. |
| Clinical Pearls | EKTERLY is a combination of upadacitinib and methotrexate for moderate-to-severe rheumatoid arthritis. Monitor for serious infections, thrombosis, and GI perforations. Check baseline and periodic lipids, LFTs, and CBC. Avoid use with strong CYP3A4 inhibitors or inducers. |
| Patient Advice | Take EKTERLY exactly as prescribed. Do not stop without consulting your doctor. · Report any signs of infection, such as fever, cough, or skin redness, immediately. · Avoid live vaccines while taking EKTERLY. Update vaccinations before starting treatment. · Inform your doctor if you have a history of blood clots, stomach ulcers, or diverticulitis. · Use effective contraception during treatment and for at least 4 weeks after stopping. · Avoid grapefruit and grapefruit juice as they may increase side effects. |
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