Dosing and uses of Makena (hydroxyprogesterone caproate)
Adult dosage forms and strengths
solution for IM injection
- 5mL multidose vial: 250mg/mL in castor oil USP (28.6% v/v) and benzyl benzoate USP (46% v/v) with the preservative benzyl alcohol NF (2% v/v)
- 1mL single-dose vial: 250mg/mL (25% w/v), in castor oil USP (30.6% v/v) and benzyl benzoate USP (46% v/v)
Preterm Labor
Indicated for prevention of preterm labor in a singleton pregnancy for patients aged 16 years or older who have a history of spontaneous preterm birth
250 mg IM qWeek
Initiate between the 16th and 20th week of gestation and ending at the 37th week of gestation or birth (whichever is first)
Renal Impairment
Not studied in patients with renal impairment
Hepatic Impairment
Not studied; product is extensively metabolized in liver; potential for reduce elimination
Pediatric dosage forms and strengths
Safety and efficacy not established
Makena (hydroxyprogesterone caproate) adverse (side) effects
>10%
Injection site pain (34.8%)
Injection site swelling (17.1%)
Urticaria (12.3%)
1-10%
Pruritus (7.7%)
Injection site pruritus (5.8%)
Nausea (5.8%)
Injection site nodule (4.5%)
Diarrhea (2.3%)
Frequency not defined
Thromboembolic events
Angioedema
Depression
Decreased glucose tolerance
Fluid retention
Jaundice
Hypertension
Vaginal bleeding
Postmarketing Reports
Body as a whole: Local injection site reactions (including erythema, urticaria, rash, irritation, hypersensitivity, warmth); fatigue; fever; hot flashes/flushes
Digestive disorders: Vomiting
Infections: Urinary tract infection
Nervous system disorders: Headache, dizziness
Pregnancy, puerperium and perinatal conditions: Cervical incompetence, premature rupture of membranes
Reproductive system and breast disorders: Cervical dilation, shortened cervix
Respiratory disorders: Dyspnea, chest discomfort
Skin: Rash
Warnings
Contraindications
Thromboembolism or history of thromboembolism
Breast cancer or history of breast cancer
Hormone sensitive cancer or history of hormone sensitive cancer
Undiagnosed abnormal vaginal bleeding unrelated to pregnancy
Liver tumors or active liver disease
Uncontrolled hypertension
Hypersensitivity to castor oil or hydroxyprogesterone caproate
Cautions
Not intended for use in women with multiple gestations or other risk factors for preterm birth
Discontinue use if an arterial or deep venous thrombotic or thromboembolic event occurs
Consider discontinuing if allergic reaction develops Monitor for the development of prediabetes, diabetes, or worsening diabetes
Carefully monitor patients that have conditions sensitive to fluid retention (eg, preeclampsia, epilepsy, migraine, asthma, cardiac or renal dysfunction)
Monitor women with history of depression and discontinue if depression recurs
Carefully monitor women who develop jaundice and consider the risks and benefits of continuation
Carefully monitor women who develop hypertension and consider the risks and benefits of continuation
Pregnancy and lactation
Pregnancy category: B
No adequate or well-controlled studies in women during first trimester
Data from controlled studies of 310 women who received hydroxyprogesterone during in their second and third trimesters show no increase in congenital anomalies, including genital abnormalities in male or female infants, from exposure during pregnancy to hydroxyprogesterone caproate
Lactation: Excreted into breast milk, avoid
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Makena (hydroxyprogesterone caproate)
Mechanism of action
Synthetic progestin
Mechanism in risk reduction of preterm labor is unknown.
Absorption
Note: Pharmacokinetic data based on single 1000 mg IM injection; data for 250 mg dose has not been evaluated
Peak Plasma Concentration: 3-7 days (after a single IM injection)
Peak Plasma Time: 4.6 (± 1.7) days
Distribution
Protein Bound: binds extensively to plasma proteins (including albumin and corticosteroid binding globulins
Metabolism
Half-Life: 7.8 (± 3.0) days
Metabolism: hepatic (primarily CYP3A4 and CYP3A5)
Elimination
Excretion: feces (50%), urine (30%); both conjugated and free drug
Administration
IM Administration
Inject IM over 1 minute in upper outer quadrant of the gluteus maximus
Inject IM over 1 minute in upper outer quadrant of the gluteus maximus The solution if viscous and oilyThe solution if viscous and oily
1-mL vial does not contain preservatives and is for single dose use
Once opened, the 5-mL multidose vial must be used within 5 weeks
Discard any unused drug remaining in the opened vial after 5 weeks
Storage
Store at controlled room temperature 15-30°C (59-86°F)
