First drug to prevent premature births

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First drug to prevent premature births
First drug to prevent premature births

Product: Makena

Company: Ther-Rx

Pharmacologic class: Progestin

Active ingredient: Hydroxyprogesterone caproate 250 mg/mL; for deep intramuscular (IM) injection; contains castor oil, benzyl benzoate, benzyl alcohol.

Indication: To reduce risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. Not intended for use in patients with multiple gestations or other risk factors for preterm birth.

Pharmacology: Hydroxyprogesterone caproate is a synthetic progestin that is indicated to reduce the risk of preterm birth in certain at-risk women. After IM administration, hydroxyprogesterone caproate reaches peak levels in about three to seven days in nonpregnant women. It is highly bound to plasma proteins and is extensively metabolized in the liver by several metabolic pathways. Both conjugated metabolites and free steroids are eliminated via urinary and fecal routes.

Clinical trials: A multicenter, randomized, double-blind, vehicle-controlled trial involving 463 pregnant women was conducted to assess the safety and efficacy of hydroxyprogesterone caproate in reducing the risk of spontaneous preterm birth. The study enrolled women aged 16 to 43 years with a history of singleton spontaneous preterm birth who were between 16 weeks 0 days and 20 weeks 6 days gestation with a singleton pregnancy. At the time of randomization, ultrasound was used to confirm gestational age and the absence of any known fetal abnormality. Women with prior progesterone treatment or heparin use were excluded, as were those with a history of thrombotic disease or maternal/obstetrical complications.

Compared with treatment with the vehicle control, treatment with hydroxyprogesterone caproate reduced the proportion of women who delivered preterm at <37 weeks (-17.8%). The proportions of women who delivered at <35 weeks and <32 weeks were also lower in the group given the study drug (-9.4% and -7.7%, respectively). There was no overall survival advantage to treatment with the study drug due to a higher rate of stillbirth and miscarriage; studies are continuing.

Adults: Begin treatment between 16 weeks 0 days and 20 weeks 6 days gestation. Inject slowly (over one minute or longer) into upper outer quadrant of gluteus maximus. 250 mg IM once weekly. Continue until Week 37 (through 36 weeks, 6 days) of gestation or delivery, whichever comes first.

Children: Not applicable.

Contraindications: Current or history of thrombosis or thrombo­embolic disorders. Breast or other hormone-sensitive cancers. Undiagnosed abnormal genital bleeding. Cholestatic jaundice of pregnancy. Hepatic adenoma or carcinoma. Uncontrolled hypertension.

Warnings/Precautions: Conditions aggravated by fluid retention (e.g., pre-eclampsia, migraine, asthma, seizures, cardiac or renal dysfunction). Monitor diabetics and for depression. Hepatic impairment. Discontinue if depression, thrombo­embolic events, or allergic reactions occur. Reevaluate if jaundice or hypertension occurs. Not for use in stopping active preterm labor. Pregnancy (Cat. B) (limited data on first-trimester use). Nursing mothers: not recommended; discontinue upon delivery.

Interactions: May affect metabolism of drugs metabolized by CYP1A2, CYP2A6, or CYP2B6 (e.g., theophylline, tizanidine, clozapine, nicotine, acetaminophen, efavirenz, bupropion, methadone).

Adverse reactions: Injection site reactions (pain, swelling, pruritus, nodule), urticaria, pruritus, GI upset; pregnancy-related fetal and maternal complications.

How supplied: Multidose vial (5 mL)—1

For more information, call 877.567.7676 or visit www.Makena.com.

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