HYDROXYPROGESTERONE CAPROATE
Clinical safety rating: avoid
CYP3A4 inducers can decrease efficacy Can cause thromboembolic disorders.
Hydroxyprogesterone caproate is a synthetic progestin that acts as an agonist of the progesterone receptor. Its mechanism in preventing preterm birth is not fully understood but may involve suppression of uterine contractility, maintenance of cervical integrity, and modulation of the inflammatory response.
| Metabolism | Metabolized primarily in the liver via reduction, hydroxylation, and conjugation; CYP3A4 is involved in oxidative metabolism. Excreted mainly in urine as glucuronide and sulfate conjugates. |
| Excretion | Primarily renal as metabolites; approximately 50-60% of a dose is excreted in urine within 96 hours, with less than 5% as unchanged drug. Biliary/fecal excretion accounts for approximately 30-40%. |
| Half-life | Terminal elimination half-life is approximately 7-8 days (range 5-14 days) due to slow release from the intramuscular depot, supporting weekly or biweekly dosing. |
| Protein binding | Highly protein bound (approximately 99%) primarily to albumin and corticosteroid-binding globulin (CBG). |
| Volume of Distribution | Volume of distribution is approximately 1.5 L/kg (range 1-2 L/kg) indicating extensive distribution into tissues, including maternal and fetal compartments. |
| Bioavailability | Intramuscular: Bioavailability is essentially 100% due to the route of administration. Oral bioavailability is negligible (<5%) due to extensive first-pass metabolism. |
| Onset of Action | Intramuscular: Onset occurs within 1-2 days, with peak plasma concentrations achieved in 5-7 days after a single injection. |
| Duration of Action | Intramuscular: Duration is approximately 7-14 days following a single injection, allowing weekly or biweekly dosing for prevention of preterm birth. |
250-500 mg intramuscularly once weekly. For recurrent preterm birth prevention: 250 mg intramuscularly weekly starting at 16-20 weeks gestation until 36 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No specific guidelines; use with caution in severe renal impairment due to potential accumulation of excipients. GFR <30 mL/min: consider reducing dose or extending interval. |
| Liver impairment | Child-Pugh Class A: no adjustment. Class B: reduce dose by 50% or extend interval. Class C: avoid use due to risk of hepatic encephalopathy. |
| Pediatric use | Not typically used in pediatric populations. No established weight-based dosing. Contraindicated for use in children except for approved indications (e.g., recurrent preterm birth prevention in adolescents aged 16-17 years: same adult dosing). |
| Geriatric use | No specific dosing adjustments. Use with caution due to potential coexisting conditions (e.g., hepatic/renal impairment) and increased sensitivity to adverse effects (e.g., thromboembolic events). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CYP3A4 inducers can decrease efficacy Can cause thromboembolic disorders.
| FDA category | Positive |
| Breastfeeding | Hydroxyprogesterone caproate is excreted into breast milk in low amounts. The milk-to-plasma ratio is not well established. It is considered compatible with breastfeeding, but caution is advised due to potential effects on the infant. Monitor the infant for signs of hormonal effects, such as jaundice or breast enlargement. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | abnormal uterine bleeding |
| Serious Effects |
["Known hypersensitivity to hydroxyprogesterone caproate or castor oil (vehicle)","Current or history of thromboembolic disorders (e.g., deep vein thrombosis, pulmonary embolism)","Known or suspected breast cancer or other progesterone-sensitive cancer","Undiagnosed abnormal vaginal bleeding","Intrauterine fetal death (pregnancy not viable)","Severe uncontrolled hypertension","Acute porphyria"]
| Precautions | ["Thromboembolic disorders: Use with caution in patients with history of thromboembolism or thrombotic risk factors.","Retinal vascular lesions: Discontinue if unexplained sudden partial or complete loss of vision occurs.","Fluid retention: Monitor patients with conditions that may be aggravated by fluid retention (e.g., cardiac or renal dysfunction, epilepsy, migraine).","Depression: Use with caution in patients with history of depression; discontinue if serious depression recurs.","Hepatic impairment: Use with caution in patients with impaired hepatic function.","Glucose tolerance: May decrease glucose tolerance; monitor diabetic patients."] |
Loading safety data…
| Hydroxyprogesterone caproate is not associated with an increased risk of major birth defects when used during the first trimester based on available data. However, as a progestin, theoretical risks include potential virilization of female fetuses if used in later stages of pregnancy. Current evidence does not demonstrate teratogenicity, but use in pregnancy should be limited to indicated conditions (e.g., prevention of preterm birth). |
| Fetal Monitoring | Monitor maternal blood pressure, blood glucose (especially in women with gestational diabetes), and signs of thromboembolic events. Fetal monitoring includes ultrasound for fetal growth and assessment of amniotic fluid volume. Perform glucose tolerance testing as clinically indicated. |
| Fertility Effects | Hydroxyprogesterone caproate is used in assisted reproductive technology to support luteal phase and early pregnancy. It does not impair fertility; rather, it is used to enhance fertility outcomes. Long-term use may cause menstrual irregularities, but effects on fertility are reversible upon discontinuation. |