Makena

MAKENA- hydroxyprogesterone caproate injection
Lumara Health Inc.

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

  • Administer intramuscularly at a dose of 250 mg (1 mL) once weekly (every 7 days) by a healthcare provider
  • Begin treatment between 16 weeks, 0 days and 20 weeks, 6 days of gestation
  • 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 1½ 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.

If the 5 mL multidose vial is used, 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 1 mL single dose vial contains 250 mg hydroxyprogesterone caproate. Each 5 mL multidose vial contains 1250 mg hydroxyprogesterone caproate.

4 CONTRAINDICATIONS

Do not use Makena 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

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).

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In a vehicle (placebo)-controlled clinical trial of 463 pregnant women at risk for spontaneous preterm delivery based on obstetrical history, 310 received 250 mg of Makena and 153 received a vehicle formulation containing no drug by a weekly intramuscular injection beginning at 16 to 20 weeks of gestation and continuing until 37 weeks of gestation or delivery, whichever occurred first.1 [See Clinical Studies (14.1).]

Certain pregnancy-related fetal and maternal complications or events were numerically increased in the Makena-treated subjects as compared to control subjects, including miscarriage and stillbirth, admission for preterm labor, preeclampsia or gestational hypertension, gestational diabetes, and oligohydramnios (Tables 1 and 2).

Table 1 Selected Fetal Complications
1 N = Total number of subjects enrolled prior to 20 weeks 0 days2 N = Total number of subjects at risk ≥ 20 weeks

Pregnancy Complication

Makena

Control

n/N

n/N

Miscarriage (< 20 weeks)1

5/209

0/107

Stillbirth (≥ 20 weeks)2

6/305

2/153

Table 2 Selected Maternal Complications
1 Other than delivery admission.

Pregnancy Complication

Makena N=310 %

Control N=153 %

Admission for preterm labor1

16.0

13.8

Preeclampsia or gestational hypertension

8.8

4.6

Gestational diabetes

5.6

4.6

Oligohydramnios

3.6

1.3

Common Adverse Reactions:

The most common adverse reaction was injection site pain, which was reported after at least one injection by 34.8% of the Makena group and 32.7% of the control group. Table 3 lists adverse reactions that occurred in ≥ 2% of subjects and at a higher rate in the Makena group than in the control group.

Table 3 Adverse Reactions Occurring in ≥ 2% of Makena-Treated Subjects and at a Higher Rate than Control Subjects

Preferred Term

Makena N=310 %

Control N=153 %

Injection site pain

34.8

32.7

Injection site swelling

17.1

7.8

Urticaria

12.3

11.1

Pruritus

7.7

5.9

Injection site pruritus

5.8

3.3

Nausea

5.8

4.6

Injection site nodule

4.5

2.0

Diarrhea

2.3

0.7

In the clinical trial, 2.2% of subjects receiving Makena were reported as discontinuing therapy due to adverse reactions compared to 2.6% of control subjects. The most common adverse reactions that led to discontinuation in both groups were urticaria and injection site pain/swelling (1% each).

Pulmonary embolus in one subject and injection site cellulitis in another subject were reported as serious adverse reactions in Makena-treated subjects.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.