Makena™ - also known as 17P

FDA has approved Makena (hydroxyprogesterone caproate injection), also known as 17P Makena

• The U.S. Food and Drug Administration (FDA) has approved Makena (hydroxyprogesterone caproate injection) – the first and only FDA-approved treatment indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.¹
• The effectiveness of Makena is based on improvement in the proportion of women who delivered at less than 37 weeks of gestation. There are no controlled trials demonstrating a direct clinical benefit, such as improvement in neonatal mortality and morbidity.¹
• Limitation of use: While there are many risk factors for preterm birth, safety and efficacy of Makena has been demonstrated only in women with a prior spontaneous singleton preterm birth. It is not intended for use in women with multiple gestations or other risk factors for preterm birth.¹
• Makena is administered by a healthcare provider as an intramuscular injection at a dose of 250mg (1 mL) once weekly (every 7 days). Makena treatment begins between 16 weeks, 0 days and 20 weeks, 6 days of pregnancy and continues once weekly until 37 completed weeks of pregnancy or delivery, whichever occurs first.¹
• Makena is commonly referred to as “17P.” Other references include HPC, 17 α-hydroxyprogesterone caproate,² 17 OHPC and hydroxyprogesterone caproate;¹ however, Makena is the only FDA-approved treatment indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.¹
• Makena is a prescription hormone medicine (progestin) used in women who are pregnant and who have delivered a baby too early (preterm) in the past. Makena is used to help lower the risk of having a preterm baby again.¹
• In partnership with the Society for Maternal-Fetal Medicine, a committee of the American College of Obstetricians and Gynecologists issued a written opinion in October 2008 stating that progesterone supplementation for the prevention of recurrent preterm birth should be offered to women with a singleton pregnancy and a prior spontaneous preterm birth.² Makena is indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth.
• Makena is marketed by Ther-Rx Corporation in the United States and is subject to all U.S. guidelines applicable to dispensing an FDA-approved prescription product. Makena is available by prescription only through specialty pharmacies and through specialty distributors. Makena is supplied in a multi-dose vial; each 5 mL, multi-dose vial contains five injections of Makena.¹

• The safety and efficacy of Makena in reducing the risk of preterm birth in women with a singleton pregnancy who have had a history of singleton spontaneous preterm birth was demonstrated in a multicenter, double-blind, placebo-controlled clinical trial sponsored by the National Institutes of Health¹ and published in the New England Journal of Medicine.
• The trial included 463 women (ranging from 16 to 43 years in age) with a singleton pregnancy and a documented history of a singleton spontaneous preterm birth (defined as delivery at less than 37 weeks of gestation following spontaneous preterm labor or premature rupture of membranes).¹
• Women in the study were randomized to receive either Makena (n=310) or placebo (n=153) at a dose of 250 mg administered weekly by intramuscular injection starting between 16 and 20 weeks (16 weeks, 0 days and 20 weeks, 6 days) of gestation, and continuing until 37 completed weeks of gestation or delivery, whichever comes first.¹
• Compared to controls, treatment with Makena reduced the proportion of women who delivered preterm at less than 37 weeks.¹
• After adjusting for time in the study, 7.5 percent of Makena-treated subjects delivered prior to 25 weeks compared to 4.7 percent of control subjects.¹

• Makena should not be used in women with any of the following conditions:

  -	Current or history of thrombosis or thromboembolic disorders
  -	Known or suspected breast cancer, other hormone-sensitive cancer or history of these conditions
  -	Undiagnosed abnormal vaginal bleeding unrelated to pregnancy
  -	Cholestatic jaundice of pregnancy
  -	Liver tumors, benign or malignant, or active liver disease
  -	Uncontrolled hypertension

• Makena should be discontinued if thrombosis or thromboembolism occurs
• Allergic reactions, including urticaria, pruritus and angioedema, have been reported with use of Makena or with other products containing castor oil
• Women receiving Makena should be monitored if they:

  -	Are prediabetic or diabetic
  -	Have conditions that may be affected by fluid retention, such as preeclampsia, epilepsy, cardiac or renal dysfunction
  -	Have a history of clinical depression; Makena should be discontinued if depression recurs
  -	Develop jaundice; consider whether benefit of use warrants continuation
  -	Develop hypertension

• Certain pregnancy-related fetal and maternal complications or events were numerically increased in Makena-treated subjects as compared to placebo subjects, including miscarriage (2.4% vs. 0%) and stillbirth (2% vs. 1.3%), admission for preterm labor (16% vs. 13.8%), preeclampsia or gestational hypertension (8.8% vs. 4.6%), gestational diabetes (5.6% vs. 4.6%), and oligohydramnios (3.6% vs. 1.3%)
• The most common adverse reactions reported in ≥2% of subjects and at a higher rate in the Makena group than in the control group were injection site reactions (pain [35% vs. 33%], swelling [17% vs. 8%], pruritus [6% vs. 3%], and nodule [5% vs. 2%]), urticaria (12% vs. 11%), pruritus (8% vs. 6%), nausea (6% vs. 5%), and diarrhea (2% vs. 1%)

• In conjunction with the approval of Makena, Ther-Rx launched the Makena Care Connection, a program for patients and healthcare providers that provides administrative, financial and treatment support for Makena
• After enrolling in the Makena Care Connection, patients and healthcare providers can access a range of support services including prescription processing, educational information, and a reminder program to facilitate compliance with weekly injections
• Visit www.makena.com to obtain more information about Makena and the prevention of preterm birth. To view the Makena Prescribing Information, please visit www.kvpharmaceutical.com/pdf/Makena_PI.pdf.