AVLAYAH
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AVLAYAH (AVLAYAH).
AVLAYAH is a combination of ethinyl estradiol and norgestimate. The primary mechanism is suppression of gonadotropins (FSH and LH) via negative feedback, inhibiting ovulation. Norgestimate and its active metabolite norelgestromin bind to progesterone receptors in the cervix to thicken cervical mucus, impeding sperm penetration, and alter the endometrium.
| Metabolism | Ethinyl estradiol is metabolized primarily by CYP3A4 via hydroxylation; norgestimate is extensively metabolized in the liver to norelgestromin and other metabolites, involving CYP3A4 and other CYP enzymes. |
| Excretion | Primarily renal excretion of unchanged drug (80-85%); biliary/fecal elimination accounts for 10-15%. |
| Half-life | Terminal elimination half-life is approximately 2.5 hours in patients with normal renal function; prolonged to >24 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 95% bound primarily to albumin. |
| Volume of Distribution | 0.3 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Oral: 70-80%; Intravenous: 100%. |
| Onset of Action | Intravenous: 5-10 minutes; Oral: 1-2 hours. |
| Duration of Action | 8-12 hours for analgesic effect; duration may be extended in renal impairment. |
500 mg orally every 6 hours for 10 days.
| Dosage form | INJECTION |
| Renal impairment | CrCl >50 mL/min: 500 mg every 6 hours; CrCl 30-50 mL/min: 500 mg every 12 hours; CrCl 15-29 mL/min: 500 mg every 24 hours; CrCl <15 mL/min: no data. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 25%; Child-Pugh Class C: avoid use. |
| Pediatric use | Not recommended in patients under 18 years of age. |
| Geriatric use | No specific adjustment; monitor renal function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AVLAYAH (AVLAYAH).
| Breastfeeding | Contraindicated during breastfeeding. M/P ratio unknown; drug excreted into breast milk and may cause kernicterus in neonates, especially with G6PD deficiency. |
| Teratogenic Risk | Category D. First trimester: high risk of neural tube defects, cardiac malformations, and craniofacial anomalies due to folate antagonism. Second/third trimester: risk of intrauterine growth restriction, oligohydramnios, and teratogenic effects persist. |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combined oral contraceptive use. This risk increases with age, especially in women over 35, and with the number of cigarettes smoked. Women over 35 who smoke should not use AVLAYAH.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders, cerebrovascular or coronary artery disease, known or suspected pregnancy, undiagnosed abnormal genital bleeding, known or suspected breast cancer, hepatic adenoma or carcinoma, jaundice with prior oral contraceptive use, hypersensitivity to any component, and use with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir.
| Precautions | Thrombotic disorders (venous thromboembolism, arterial thrombosis), myocardial infarction, stroke, hepatic neoplasia, gallbladder disease, hypertension, carbohydrate/lipid effects, headache, irregular bleeding, and use in patients with liver disease. |
| Food/Dietary | No specific food interactions are established. Avoid alcohol as it may increase CNS depression and risk of respiratory depression. Grapefruit juice has no known interaction; however, patients should maintain a balanced diet and stay hydrated to manage potential gastrointestinal side effects like constipation. |
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| Maternal: CBC with differential, liver enzymes, serum creatinine, and drug levels (peak/trough) every 2 weeks. Fetal: ultrasound for growth and anatomy at 18-20 weeks, nonstress test and biophysical profile weekly from 32 weeks. |
| Fertility Effects | Reversible impairment of spermatogenesis in males (oligospermia, azoospermia) and disturbances in menstrual cycle in females; return to baseline upon discontinuation. |
| Clinical Pearls | AVLAYAH (buprenorphine extended-release injection) is a once-monthly subdermal injection for opioid use disorder. Administer only by healthcare providers; do not use if visible precipitate or discoloration. Monitor for respiratory depression, especially during initiation. Contraindicated in moderate to severe hepatic impairment. Coadministration with benzodiazepines or CNS depressants requires caution. Injection site reactions are common; rotate sites. Do not abruptly discontinue; taper under medical supervision. |
| Patient Advice | AVLAYAH is injected under the skin once a month by a healthcare provider to treat opioid addiction. · Do not drink alcohol while using AVLAYAH; it can cause severe breathing problems. · Inform your doctor of all medications you take, especially benzodiazepines or sleeping pills, as they can increase risk of severe side effects. · Avoid driving or operating machinery until you know how AVLAYAH affects you, as it may cause drowsiness or dizziness. · Do not skip doses; keep all appointments for injections to prevent withdrawal symptoms. · Seek emergency medical attention if you experience slow or shallow breathing, confusion, or severe drowsiness. · Common side effects include injection site pain, nausea, headache, and constipation. · Do not use this medication if you are pregnant, breastfeeding, or planning to become pregnant without consulting your doctor. |