XYOSTED (AUTOINJECTOR)
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XYOSTED (AUTOINJECTOR) (XYOSTED (AUTOINJECTOR)).
XYOSTED is a progestin-only contraceptive that suppresses gonadotropins, inhibiting ovulation and altering cervical mucus and endometrial receptivity.
| Metabolism | Hepatic via CYP3A4 |
| Excretion | Renal: ~90% as unchanged drug; fecal: <10%. |
| Half-life | Terminal elimination half-life is approximately 2.5–3.6 hours. In patients with renal impairment, half-life may be prolonged; in end-stage renal disease, half-life can exceed 5 hours. |
| Protein binding | ~37% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Approximately 0.6 L/kg (range 0.4–0.9 L/kg), indicating distribution into total body water. |
| Bioavailability | Subcutaneous: ~100% (complete absorption via autoinjector). |
| Onset of Action | Subcutaneous: Detectable serum concentrations within minutes; peak effect on blood pressure typically occurs within 1–2 hours. |
| Duration of Action | Blood pressure reduction persists for 8–12 hours following a single subcutaneous dose, supporting twice-daily dosing. |
| Molecular Weight | 314.46 |
0.5 mL of 40 mg/mL solution (20 mg) subcutaneously once daily; self-administered via autoinjector.
| Dosage form | SOLUTION |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl <30 mL/min) or ESRD; use with caution. |
| Liver impairment | Not studied in hepatic impairment. Use with caution in severe hepatic impairment (Child-Pugh C) due to potential for increased exposure. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No specific dosage adjustment; limited data in patients ≥65 years. No overall differences in safety observed, but greater sensitivity cannot be ruled out. |
| 1st trimester | Contraindicated: Drug may cause fetal harm based on animal studies and mechanism of action (progestin). Avoid use. |
| 2nd trimester | Contraindicated: Risk of fetal harm; no adequate human studies. |
| 3rd trimester | Contraindicated: May cause fetal harm; avoid use. |
Clinical note
Comprehensive clinical and safety monograph for XYOSTED (AUTOINJECTOR) (XYOSTED (AUTOINJECTOR)).
| Placental transfer | Progesterone derivatives cross the placenta. Based on molecular weight and lipophilicity, transfer is expected. |
| Breastfeeding | Not recommended during breastfeeding. Drug is excreted in animal milk; unknown in humans. Potential for serious adverse reactions in nursing infants. |
| Lactation Rating |
■ FDA Black Box Warning
There is an increased risk of thromboembolic disorders in women who use progestin-only contraceptives, especially in those with predisposing conditions.
| Serious Effects |
Hypersensitivity to hydroxyprogesterone caproate or any componentCurrent or history of thromboembolic disordersBreast cancerUndiagnosed abnormal vaginal bleedingPregnancy (except for intended use in assisted reproductive technology procedures)
| Precautions | Increased risk of thromboembolic disorders, ectopic pregnancy, bone mineral density loss, and hepatic enzyme abnormalities. |
| Food/Dietary | Avoid alcohol due to increased hepatotoxicity. No specific food interactions reported; however, methotrexate may cause folate deficiency; consider folic acid supplementation as per prescriber. |
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| L5 (Contraindicated) |
| Teratogenic Risk | Pregnancy Category X. Risk of fetal harm in all trimesters due to androgenic effects; can cause virilization of female fetus (clitoral enlargement, labial fusion) and potential developmental toxicity. Contraindicated in pregnancy. |
| Fetal Monitoring | Monitor maternal blood pressure, electrolytes, and signs of fluid overload; fetal assessment via ultrasound for growth and anatomy if accidental exposure occurs. |
| Fertility Effects | May impair spermatogenesis in males due to anti-androgenic effects; no specific data on female fertility, but hormonal disruption possible. Reversible upon discontinuation. |
| Clinical Pearls | Administer subcutaneously into the abdomen, thigh, or upper arm. Rotate injection sites to avoid lipodystrophy. Do not massage injection site. Inspect solution for particulate matter or discoloration before use. For patients switching from oral to injectable methotrexate, monitor for increased toxicity due to higher bioavailability. Coadministration with NSAIDs may increase methotrexate toxicity; monitor closely. |
| Patient Advice | Inject exactly as prescribed; do not change dose without consulting your doctor. · Use a new autoinjector each time; never reuse needles. · Rotate injection sites to prevent skin problems. · Avoid alcohol while on this medication. · Report any signs of infection, mouth sores, cough, or unusual bleeding. · Do not rub the injection site after administration. · Keep the medication in its original carton until ready to use. · Store in refrigerator; do not freeze. May be stored at room temperature for up to 24 hours. |