MAKENA- hydroxyprogesterone caproate injection
Ther-Rx Corporation
1 INDICATIONS AND USAGE
Makena is a progestin indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of singleton spontaneous preterm birth. The effectiveness of Makena is based on improvement in the proportion of women who delivered <37 weeks of gestation. There are no controlled trials demonstrating a direct clinical benefit, such as improvement in neonatal mortality and morbidity.
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.
2 DOSAGE AND ADMINISTRATION
2.1 Dosing
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Administer intramuscularly at a dose of 250 mg (1 mL) once weekly (every 7 days) by a healthcare provider
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Begin treatment between 16 weeks, 0 days and 20 weeks, 6 days of gestation
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Continue administration once weekly until week 37 (through 36 weeks, 6 days) of gestation or delivery, whichever occurs first
2.2 Preparation and Administration
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Makena is a clear, yellow solution. Do not use if solid particles appear or if the solution is cloudy.
Instructions for administration:
1.
Clean the vial top with an alcohol swab before use.
2.
Draw up 1 mL of drug into a 3 mL syringe with an 18 gauge needle.
3.
Change the needle to a 21 gauge 1 1/2 inch needle.
4.
After preparing the skin, inject in the upper outer quadrant of the gluteus maximus. The solution is viscous and oily. Slow injection (over one minute or longer) is recommended.
5.
Applying pressure to the injection site may minimize bruising and swelling.
Discard any unused product 5 weeks after first use.
3 DOSAGE FORMS AND STRENGTHS
Makena (250 mg/mL) is a sterile solution of hydroxyprogesterone caproate in castor oil for injection. Each 5 mL multidose vial contains 1250 mg hydroxyprogesterone caproate.
4 CONTRAINDICATIONS
Do not use Makena in women with any of the following conditions:
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Current or history of thrombosis or thromboembolic disorders
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Known or suspected breast cancer, other hormone-sensitive cancer, or history of these conditions
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Undiagnosed abnormal vaginal bleeding unrelated to pregnancy
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Cholestatic jaundice of pregnancy
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Liver tumors, benign or malignant, or active liver disease
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Uncontrolled hypertension
5 WARNINGS AND PRECAUTIONS
5.1 Thromboembolic Disorders
Discontinue Makena if an arterial or deep venous thrombotic or thromboembolic event occurs.
5.2 Allergic Reactions
Allergic reactions, including urticaria, pruritus and angioedema, have been reported with use of Makena or with other products containing castor oil. Consider discontinuing the drug if such reactions occur.
5.3 Decrease in Glucose Tolerance
A decrease in glucose tolerance has been observed in some patients on progestin treatment. The mechanism of this decrease is not known. Carefully monitor prediabetic and diabetic women while they are receiving Makena.
5.4 Fluid Retention
Because progestational drugs may cause some degree of fluid retention, carefully monitor women with conditions that might be influenced by this effect (e.g., preeclampsia, epilepsy, migraine, asthma, cardiac or renal dysfunction).
5.5 Depression
Monitor women who have a history of clinical depression and discontinue Makena if clinical depression recurs.
5.6 Jaundice
Carefully monitor women who develop jaundice while receiving Makena and consider whether the benefit of use warrants continuation.
5.7 Hypertension
Carefully monitor women who develop hypertension while receiving Makena and consider whether the benefit of use warrants continuation.
6 ADVERSE REACTIONS
For the most serious adverse reactions to the use of progestins, see Warnings and Precautions (5). 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 C27 H40 O4 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. 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).
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Hydroxyprogesterone caproate is a synthetic progestin. The mechanism by which hydroxyprogesterone caproate reduces the risk recurrent preterm birth is not known. HOW SUPPLIED/STORAGE AND HANDLING
Makena (NDC 64011-243-01) is supplied as 5 mL of a sterile solution in a multidose glass vial.
Each 5 mL 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).
Single unit carton: Contains one 5 mL multidose vial of Makena (250 mg/mL) containing 1250 mg of hydroxyprogesterone caproate.
Store at controlled room temperature [15�-30�C (59�-86�F)]. Use within 5 weeks after first use.
Caution: Protect vial from light. Store vial in its box. Store upright.