QOLIANA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for QOLIANA (QOLIANA).
QOLIANA (elagolix) is a nonpeptide, orally active gonadotropin-releasing hormone (GnRH) receptor antagonist that competitively binds to GnRH receptors in the pituitary gland, thereby reducing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This leads to decreased ovarian production of estrogen and progesterone, resulting in a hypoestrogenic state.
| Metabolism | Primarily metabolized by CYP3A4 and, to a lesser extent, CYP3A5. Elagolix is a weak inducer of CYP3A4 and a weak inhibitor of CYP2C19, CYP2C8, and CYP2C9. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 30% of elimination; biliary/fecal excretion accounts for 60% (including metabolites); 10% is metabolized with negligible pulmonary elimination. |
| Half-life | Terminal elimination half-life is 12 hours (range 10–15 hours) in healthy adults; may extend to 18–24 hours in patients with moderate hepatic impairment (Child-Pugh B). |
| Protein binding | 98% bound primarily to albumin and alpha-1 acid glycoprotein. |
| Volume of Distribution | 0.8 L/kg (range 0.6–1.0 L/kg), indicating extensive extravascular distribution (e.g., tissues, including cardiac and vascular endothelium). |
| Bioavailability | Oral: 45% (range 40–50%) due to first-pass metabolism; Sublingual: 60% (avoidance of partial first-pass). |
| Onset of Action | Oral: 1–2 hours; Intravenous: 10–15 minutes (immediate onset for pressor effect). |
| Duration of Action | Oral: 8–12 hours; Intravenous: 4–6 hours with sustained release formulation extending up to 18 hours. Note that dose-dependent effects on heart rate may persist longer than pressor effects. |
| Molecular Weight | 446.4 |
Initiate at 5 mg orally once daily, increase as tolerated to 10 mg once daily. Maximum dose 20 mg once daily.
| Dosage form | SOLUTION/DROPS |
| Renal impairment | No dosage adjustment required for mild-to-moderate renal impairment (eGFR ≥30 mL/min). Not recommended in severe renal impairment (eGFR <30 mL/min) due to lack of data. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 5 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy have not been established in pediatric patients below 18 years of age. |
| Geriatric use | No specific dose adjustment recommended; however, consider starting at 5 mg once daily due to potential age-related decreased renal function and increased sensitivity. |
| 1st trimester | Insufficient human data; animal studies show risk. Avoid use unless benefit outweighs risk. |
| 2nd trimester | Insufficient human data; use only if clearly needed. |
| 3rd trimester | Insufficient human data; consider risk of neonatal adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for QOLIANA (QOLIANA).
| Placental transfer | Predicted to cross placenta based on molecular weight (<500 Da) and lipophilicity; no specific data. |
| Breastfeeding | No data on excretion in breast milk; due to potential for serious adverse effects, breastfeeding is not recommended during treatment and for 5 half-lives after last dose. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to active substance or excipientsConcurrent use with strong CYP3A4 inducersSevere hepatic impairment
| Precautions | Bone loss: Dose-dependent decreases in bone mineral density (BMD) occur, which may not be fully reversible. Use beyond 2 years is not recommended., Sustained hypoestrogenic state: May increase the risk of osteoporosis and fractures., Hepatic impairment: Not recommended in patients with moderate to severe hepatic impairment., Mood changes: Depression and mood swings have been reported., Suicidal ideation: Advise patients to seek medical attention if mood changes or suicidal thoughts occur., Alterations in menstrual bleeding pattern: Irregular bleeding or amenorrhea is expected during treatment., Contraception: Non-hormonal contraception is recommended due to potential fetal risk; elagolix may reduce efficacy of hormonal contraceptives. |
| Food/Dietary | Grapefruit and grapefruit juice may increase elagolix concentrations and should be avoided. No other food interactions are clinically significant. Concomitant administration with a high-fat meal does not meaningfully alter elagolix absorption. |
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| L5 |
| Teratogenic Risk | Pregnancy Category X. First trimester: High risk of major congenital malformations including neural tube defects, craniofacial anomalies, and cardiovascular defects. Second and third trimesters: Increased risk of spontaneous abortion, fetal growth restriction, and oligohydramnios. Avoid in pregnancy. |
| Fetal Monitoring | Monitor liver function tests, complete blood count, and renal function monthly. Assess fetal growth via ultrasound every 4 weeks. Perform fetal echocardiography at 20-22 weeks gestation if exposure occurs. |
| Fertility Effects | May impair female fertility through disruption of ovarian folliculogenesis and ovulation. Reversible upon discontinuation. No data on male fertility. |
| Clinical Pearls | QOLIANA (elagolix) is an oral GnRH antagonist indicated for endometriosis-associated pain. It suppresses ovarian estradiol production, reducing endometrial lesion growth. Monitor bone mineral density with long-term use due to hypoestrogenic state. Avoid concomitant use with strong CYP3A4 inducers (e.g., rifampin) or inhibitors (e.g., ketoconazole) as they significantly alter elagolix exposure. Assess pregnancy status before initiation; use effective contraception. May reduce efficacy of hormonal contraceptives containing estrogen. |
| Patient Advice | Take QOLIANA at the same time each day, with or without food. · Do not take QOLIANA if you are pregnant or planning to become pregnant; use effective non-hormonal contraception. · Avoid grapefruit juice or grapefruit products during treatment as they may increase drug levels. · Inform your doctor if you have a history of osteoporosis or bone loss. · Report any new or worsening mood changes, suicidal thoughts, or unusual bleeding. · QOLIANA may cause hot flashes, night sweats, headache, or nausea; these are common. · Do not breastfeed while taking QOLIANA. · Store at room temperature, away from moisture and light. |