Usage
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Hydroxyprogesterone caproate is prescribed to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. It is not intended for use in women with multiple gestations or other risk factors for preterm birth. Off-label uses include the management of amenorrhea, abnormal uterine bleeding due to hormonal imbalance, and advanced endometrial cancer. It can also be used to test for endogenous estrogen production.
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Pharmacological classification: Progestin (a synthetic form of progesterone, a female hormone).
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Mechanism of action: Although the exact mechanism for preventing preterm birth is not fully understood, hydroxyprogesterone likely works by quieting uterine contractions and suppressing the maternal immune response against the fetus. It also helps in thickening and maintaining the uterine lining (endometrium).
Alternate Names
How It Works
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Pharmacodynamics: Hydroxyprogesterone binds to progesterone receptors, mimicking the effects of endogenous progesterone. This leads to decreased myometrial activity and quieting of uterine contractions. Also modifies the maternal immune response, reducing the chances of fetal rejection.
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Pharmacokinetics:
- Absorption: After intramuscular injection, peak serum levels are reached in 3 to 7 days. Subcutaneous absorption is similar but may be slightly slower.
- Metabolism: Hydroxyprogesterone caproate is extensively metabolized in the liver, primarily by CYP3A4 and CYP3A5 enzymes. Metabolites include sulfated and glucuronidated products.
- Elimination: Both conjugated metabolites and free steroids are excreted in the urine and feces, predominantly as conjugated metabolites.
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Mode of action: Hydroxyprogesterone acts as a progesterone receptor agonist. Upon binding, it modulates gene expression, influencing various physiological processes related to pregnancy maintenance.
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Receptor binding: Primarily binds to progesterone receptors. Exhibits minimal binding to other steroid hormone receptors.
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Enzyme inhibition/modulation: Minimal potential for CYP1A2, CYP2A6, CYP2B6 inhibition at clinically relevant concentrations. Not likely to inhibit CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 at therapeutic concentrations.
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Elimination pathways: Primarily hepatic metabolism followed by renal and fecal excretion of conjugated metabolites.
Dosage
Standard Dosage
Adults:
- Intramuscular (IM): 250 mg IM once weekly (every 7 days) injected slowly (over 1 minute) into the upper outer quadrant of the gluteus maximus.
- Subcutaneous (SC): 275 mg SC once weekly via auto-injector into the back of either upper arm.
- Initiate treatment between 16 weeks, 0 days and 20 weeks, 6 days of gestation.
- Continue weekly administration until 37 weeks of gestation or delivery, whichever occurs first.
Children:
- Not indicated for use in patients younger than 16 years of age.
Special Cases:
- Elderly Patients: Not intended for use in postmenopausal women.
- Patients with Renal Impairment: No specific dosage adjustments are available. Use with caution.
- Patients with Hepatic Dysfunction: Contraindicated in patients with active liver disease.
- Patients with Comorbid Conditions: Use with caution in patients with diabetes, hypertension, epilepsy, cardiac dysfunction, renal dysfunction, and history of depression. Monitor closely for disease exacerbation.
Clinical Use Cases
Hydroxyprogesterone caproate is not indicated for use in the following clinical settings:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
Adjustments may be necessary based on patient tolerance and comorbidities. Close monitoring for adverse effects is crucial, particularly in patients with renal impairment, diabetes, hypertension, epilepsy, and depression.
Side Effects
Common Side Effects
- Injection site reactions (pain, swelling, itching, nodule)
- Hives (urticaria)
- Pruritus (itching)
- Nausea
- Diarrhea
Rare but Serious Side Effects
- Blood clots (thromboembolism)
- Allergic reactions (angioedema, anaphylaxis)
- Jaundice
- Depression (worsening of pre-existing depression)
- Preeclampsia (high blood pressure in pregnancy)
- Migraine
- Hypertension
Long-Term Effects
Limited data are available on long-term side effects.
Adverse Drug Reactions (ADR)
- Severe allergic reactions
- Thromboembolic events (pulmonary embolism, deep vein thrombosis)
- Liver dysfunction
- Worsening of depression
Contraindications
- Current or history of thromboembolic disorders
- Known or suspected breast cancer or other hormone-sensitive cancers
- Undiagnosed abnormal vaginal bleeding unrelated to pregnancy
- Cholestatic jaundice of pregnancy
- Active liver disease or liver tumors
- Uncontrolled hypertension
- Hypersensitivity to hydroxyprogesterone caproate or castor oil (IM formulation)
Drug Interactions
- Hydroxyprogesterone is primarily metabolized by CYP3A4 and may interact with drugs that induce or inhibit this enzyme.
- Concurrent use with enzyme inducers (e.g., rifampin, carbamazepine, St. John’s Wort) may decrease hydroxyprogesterone levels.
- Concurrent use with enzyme inhibitors (e.g., ketoconazole, itraconazole, grapefruit juice) may increase hydroxyprogesterone levels.
- May interact with anticoagulants, potentially decreasing their efficacy.
- Refer to a comprehensive drug interaction database for a complete list of interactions.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B (Animal studies show no risk, but human studies are inadequate; or animal studies show adverse effects, but human studies do not.)
- Fetal risks: No increased risk of congenital anomalies has been observed in controlled studies.
- Drug excretion in breast milk: Detectable amounts of progestins are present in breast milk. Discontinue at 37 weeks of gestation or delivery, whichever occurs first.
- Neonatal side effects: No significant adverse effects on nursing infants have been reported.
Drug Profile Summary
- Mechanism of Action: Progesterone receptor agonist; reduces myometrial activity.
- Side Effects: Injection site reactions, hives, itching, nausea, diarrhea, thromboembolic events.
- Contraindications: Thromboembolic disorders, hormone-sensitive cancers, undiagnosed vaginal bleeding, liver disease, uncontrolled hypertension.
- Drug Interactions: CYP3A4 inducers and inhibitors, anticoagulants.
- Pregnancy & Breastfeeding: Pregnancy category B; detectable in breast milk, discontinue at 37 weeks.
- Dosage: IM: 250 mg weekly; SC: 275 mg weekly; initiate at 16-20 weeks, continue until 37 weeks.
- Monitoring Parameters: Monitor for signs of thromboembolism, allergic reactions, liver dysfunction, worsening depression, and preeclampsia.
Popular Combinations
No regularly used drug combinations exist for this specific indication.
Precautions
- Screen for contraindications and risk factors prior to initiating therapy.
- Monitor blood glucose in diabetic patients.
- Monitor blood pressure and signs of fluid retention.
- Assess for signs of depression.
- Observe for signs of thromboembolic events.
- Advise patient about potential injection site reactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hydroxyprogesterone?
A: For the prevention of preterm birth, 250 mg IM or 275 mg SC once weekly, starting between 16 and 20 weeks of gestation and continuing until 37 weeks of gestation or delivery.
Q2: What are the common side effects?
A: Common side effects include injection site reactions, hives, itching, nausea, and diarrhea.
Q3: Who should not take Hydroxyprogesterone?
A: Patients with a history of thromboembolic disorders, breast or other hormone-sensitive cancers, undiagnosed vaginal bleeding, liver disease, or uncontrolled hypertension should not take this medication.
Q4: How does Hydroxyprogesterone work?
A: It works by mimicking the effects of progesterone, reducing uterine contractions and suppressing the maternal immune response against the fetus.
Q5: Can Hydroxyprogesterone be used to stop active preterm labor?
A: No, it is not intended to stop active preterm labor. Its efficacy is in preventing preterm birth in women with a prior history.
Q6: Are there any drug interactions I should be aware of?
A: Yes, it can interact with drugs that affect CYP3A4 enzyme activity, such as certain antifungals and antibiotics. It may also interact with anticoagulants.
Q7: Is Hydroxyprogesterone safe during pregnancy?
A: It is considered relatively safe during pregnancy when used as indicated for preventing preterm birth, but it should be used under close medical supervision.
Q8: What should I monitor in patients receiving Hydroxyprogesterone?
A: Monitor for signs of thromboembolic events, allergic reactions, liver dysfunction, worsening depression, preeclampsia, and injection site reactions.
Q9: How is Hydroxyprogesterone administered?
A: It can be administered via IM injection into the gluteus maximus or SC injection into the back of the upper arm using an auto-injector.
