Hydroxyprogesterone Caproate

No formal drug interaction studies to date.1

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Metabolized principally by CYP isoenzymes 3A4 and 3A5;1 5 unlikely to inhibit activity of CYP2C8, 2C9, 2C19, 2D6, 2E1, and 3A4.1

In vitro study showed increased metabolic rate of CYP isoenzymes 1A2, 2A6, and 2B6 by approximately 80, 150, and 80%, respectively; clinical importance not fully elucidated.1 Metabolic induction potential not evaluated.1 Drugs metabolized by CYP isoenzymes 1A2, 2A6, and 2B6 may have increased metabolism if used concomitantly with hydroxyprogesterone.1

Specific Drugs

Storage

Parenteral

15–30°C; store upright in original carton and protect from light.1

Discard any unused portions 5 weeks after first use.1 Discard if cloudy or solid particles appear.1

• Synthetic progestin; produced by esterification of 17α-hydroxyprogesterone, a naturally occurring metabolite of progesterone, with caproic acid.1 5 7 8

• Has strong progestogenic activity; appears to produce a longer lasting and more potent progestational effect on endometrium than progesterone.5 6 8

• Does not appear to have androgenic, antiandrogenic, estrogenic, or glucocorticoid activity.7 8

• Mechanism of action in reducing the risk of recurrent preterm birth not known.1 5 6 7

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Prior to commercial availability, another formulation containing the active ingredient was available to patients from pharmacists who compounded the injection.9 (See General under Dosage and Administration.)

• 17OHPC
• Delautin

Pregnancy indications: Preterm birth (Makena): To reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.

Limitation of use: Safety and efficacy have been demonstrated only in women with a prior spontaneous singleton preterm birth. Use is not intended for women with multiple gestations or other risk factors for preterm birth.

Non-pregnancy indications (generic product): Treatment of advanced (stage III or IV) uterine adenocarcinoma; management of amenorrhea (primary and secondary) and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology (eg, submucous fibroids or uterine cancer); as a test for endogenous estrogen production; production of secretory endometrium and desquamation.

Adverse events observed in some animal reproduction studies. Adverse events were not observed in human studies following second or third trimester exposure; use not studied during first trimester.

Following use of Makena, maternal serum concentrations of hydroxyprogesterone caproate are widely variable and may be decreased in women with increased BMI. Hydroxyprogesterone is metabolized by the placenta and reaches the fetal circulation. In one study, the cord:maternal concentration ratio averaged 0.2. Hydroxyprogesterone caproate was detected in cord blood when delivery occurred ≥44 days after the last injection (Caritis 2012; Hemaue 2008).

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience injection site pain, nausea, vomiting, diarrhea, abdominal cramps, bloating, breast soreness, weight gain, weight loss, hair loss, decreased libido, increased libido, lack of appetite, increased appetite, loss of strength and energy, or back pain. Have patient report immediately to prescriber signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit); signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; angina; shortness of breath; tachycardia; or coughing up blood); vision changes; severe headache; severe dizziness; passing out; depression; swelling of hands or feet; severe injection site edema, oozing of blood, or irritation; signs of virilization (in females a deep voice, facial hair, acne, or menstrual changes); abnormal vaginal bleeding; or jaundice (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.