f gestation. There were no teratogenic effects in either species.
Makena is not intended for use to stop active preterm labor. The effect of Makena in active labor is unknown.
Discontinue Makena at 37 weeks of gestation or upon delivery. Detectable amounts of progestins have been identified in the milk of mothers receiving progestin treatment. Many studies have found no adverse effects of progestins on breastfeeding performance, or on the health, growth, or development of the infant.
Makena is not indicated for use in children. Safety and effectiveness in pediatric patients less than 16 years of age have not been established. A small number of women under age 18 years were studied; safety and efficacy are expected to be the same in women aged 16 years and above as for users 18 years and older. [See Clinical Studies (14).]
Makena is not intended for use in postmenopausal women. Safety and effectiveness in postmenopausal women have not been established.
No studies have been conducted to examine the pharmacokinetics of Makena in patients with renal impairment.
No studies have been conducted to examine the pharmacokinetics of Makena in patients with hepatic impairment. Makena is extensively metabolized and hepatic impairment may reduce the elimination of Makena.
There have been no reports of adverse events associated with overdosage of Makena in clinical trials. In the case of overdosage, the patient should be treated symptomatically.
The active pharmaceutical ingredient in Makena is hydroxyprogesterone caproate.
The chemical name for hydroxyprogesterone caproate is pregn-4-ene-3,20-dione, 17[(1-oxohexyl)oxy]. It has an empirical formula of CHO and a molecular weight of 428.60. Hydroxyprogesterone caproate exists as white to practically white crystals or powder with a melting point of 120°-124°C.
The structural formula is:
Makena is a clear, yellow, sterile, non-pyrogenic solution for intramuscular injection. Each 5 mL multidose vial contains hydroxyprogesterone caproate USP, 250 mg/mL (25% w/v), in castor oil USP (28.6% v/v) and benzyl benzoate USP (46% v/v) with the preservative benzyl alcohol NF (2% v/v).
Hydroxyprogesterone caproate is a synthetic progestin. The mechanism by which hydroxyprogesterone caproate reduces the risk recurrent preterm birth is not known.
No specific pharmacodynamic studies were conducted with Makena.
Absorption: Peak serum levels of hydroxyprogesterone caproate appeared after 3-7 days in non-pregnant female subjects following a single intramuscular injection of 1000 mg hydroxyprogesterone caproate. Based on pharmacokinetic analysis of five non-pregnant female subjects who received a single intramuscular administration of 1000 mg hydroxyprogesterone caproate, the mean (±SD) C is estimated to be 27.8 (±5.3) ng/mL, and the T is estimated to be 4.6 (±1.7) days. The elimination half-life of hydroxyprogesterone caproate was 7.8 (±3.0) days. Once-weekly intramuscular administration of 1000 mg hydroxyprogesterone caproate to non-pregnant women resulted in trough concentration of 60.0 (±14) ng/mL after 13 weeks. The pharmacokinetics of the 250 mg dose of hydroxyprogesterone caproate has not been eva luated.
Distribution: Hydroxyprogesterone caproate binds extensively to plasma proteins including albumin and corticosteroid binding globulins.
Metabolism: In vitro studies have shown that hydroxyprogesterone caproate can be met |
