Makena is the brand name of an injection that contains the active drug hydroxyprogesterone caproate. Hydroxyprogesterone is an artificial progesterone-like hormone in a class of drugs called progestins.
Makena is indicated for use to reduce the risk of premature birth in pregnant women. Premature birth is when the baby arrives early before the scheduled due date, usually before 37 weeks of pregnancy. Premature birth has a higher prevalence in women who have had a previous premature birth.
Makena is only available with a doctor’s prescription. Makena is not intended for women with multiple pregnancies (twins or triplets). Likewise, Makena will not help if premature labor has already started.
How Is Makena Supplied and Used?
Makena comes in the following forms and strengths:
- 1.1 ml single-use auto-injector containing 275 mg of hydroxyprogesterone caproate for subcutaneous (SC) use. A healthcare provider injects the drug into the area beneath the skin, usually in the back of your upper arm.
- 1 ml single-dose vial for intramuscular (IM) injection containing 250 mg of active drug.
- 5 ml multi-dose vial for IM administration containing 1,250 mg of active drug.
A healthcare professional will inject Makena subcutaneously or intramuscularly based on the dosage. The IM formulation is usually injected into the buttock muscle.
How Does Makena Work?
It is understood that Makena and its active ingredient, which is hydroxyprogesterone caproate, help to get the pregnancy to full term in women pregnant with one baby and those who have had a previous premature birth.
According to the manufacturer, a lower proportion of Makena-treated women delivered before 37 weeks compared to those who received a placebo.
Researchers believe that progesterone supplementation may help prevent preterm birth by [1]:
- Altering hormones and other substances that regulate uterine contraction and the timing of labor.
- Reducing inflammation and premature rupture of the membranes.
What Are the Side Effects of Makena?
Common Side Effects
While side effects are rare, the most common side effects of the injection include:
- Pain, swelling, itching, and irritation at the injection site
- Nausea
- Diarrhea
These effects typically go away without any specific treatment. However, if they persist or worsen, talk to your doctor immediately.
Serious Side Effects
Makena may cause severe side effects, such as:
- Blood clots. Common symptoms include leg swelling, pain, and redness.
- Depression
- Headaches
- Jaundice (yellowish skin and eyes)
- High blood pressure
- Allergic reactions, which may cause hives, itching, swelling of the face, and breathing difficulty
Talk with your doctor immediately if you experience any of the symptoms above during treatment.
Other Side Effects
In clinical trials, Makena use was associated with a higher occurrence of the following conditions:
- Miscarriage (pregnancy loss before the 20th week)
- Stillbirth (fetal death during or after the 20th week)
- Hospital admission for preterm labor
- Preeclampsia (high blood pressure and elevated protein levels in the urine)
- Gestational hypertension (high blood pressure during pregnancy)
- Gestational diabetes (diabetes first diagnosed during pregnancy)
Postmarketing Experience
Once a medicine reaches the market following approval, users may voluntarily report side effects to the manufacturer or the FDA. This practice is known as postmarketing surveillance (PMS).
Users have reported the following adverse effects:
- Fever
- Hot flashes
- Flushes
- Vomiting
- Urinary tract infection
- Headache
- Dizziness
- Premature rupture of membranes
- Weak cervical tissues
- Shortened cervix
- Shortness of breath
- Chest discomfort
- Skin rashes
Can Makena Harm an Unborn Baby?
Only a few studies have looked into the effects of Makena on an unborn baby (fetus). For instance, one infant follow-up study failed to find evidence of fetal abnormalities in infants born to pregnant women who used Makena. Likewise, animal studies have found no evidence of harm to the mother or fetus.
Makena Dosage
Subcutaneous (SC) route: 275 mg (1.1 ml) once weekly using auto-injector.
Intramuscular (IM) route: 250 mg (1 ml) once weekly.
Treatment begins between the 16th and 20th week of gestation and is continued until the 37th week of gestation or delivery (whichever occurs first).
What Should You Know Before Taking Makena?
You should not start Makena if you have:
- An allergy to hydroxyprogesterone or castor oil
- Abnormal vaginal bleeding unrelated to your pregnancy
- Severe or uncontrolled high blood pressure
- Liver disease or liver cancer
- Jaundice associated with pregnancy
- A history of cancer of the breast, uterus/cervix, or vagina
- A history of a stroke, blood clot, or circulatory system diseases
The US FDA has not approved Makena for use in individuals younger than 16 years old.
Your doctor should know if you have a history of:
- Preeclampsia
- Kidney disease
- High blood pressure
- Heart disease
- Migraine
- Diabetes
- Seizures
- Asthma
- Depression
How Much Does Makena Cost?
The cost of treatment may vary depending on your insurance plan, geographical location, and pharmacy. Contact your insurance provider to find out if your plan covers Makena or if you need prior authorization.
The manufacturer offers financial assistance of up to $5,000 or until therapy is complete. Click here to learn more.
Is a Generic Version Available?
Yes. You can get generic versions of Makena. Talk to your doctor, pharmacist, or other healthcare professionals for more information.
Is Makena Still FDA Approved?
Yes, Makena is still approved in the United States.
However, a federal advisory panel has been seeking to revoke the medicine’s approval since 2020, citing that its effectiveness remains doubtful.
The FDA granted Makena an accelerated approval in 2011 after a small trial showed the drug to be beneficial [2]. Nonetheless, the drug failed to replicate the benefits in a large 2019 study [3].
Following the controversial findings, the FDA’s Obstetrics, Reproductive and Urologic Drugs Advisory Committee reviewed the available evidence and voted on whether the drug should remain on the market. The vote was 14-1 against the drug’s effectiveness.
The panel members fear that keeping an apparently “ineffective” medicine in the market may expose women to potentially life-threatening risks, such as blood clots, allergic reactions, and depression.
On the other hand, the maker of Makena stresses that since Makena is the only FDA-approved drug in the U.S. to prevent preterm births, revoking its approval may lead to unwanted consequences.
Furthermore, the maker has proposed to the panel to continue approval while they conduct another trial to demonstrate the drug’s effectiveness. Likewise, they have also proposed a partial withdrawal, meaning only women at the highest risk of premature birth will have access to the drug.
It remains to be seen whether the drug will stay on the market.
REFERENCES:
- Norwitz, Errol R, and Aaron B Caughey. “Progesterone supplementation and the prevention of preterm birth.” Reviews in obstetrics & gynecology vol. 4,2 (2011): 60-72.
- Meis, Paul J et al. “Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.” The New England journal of medicine vol. 348,24 (2003): 2379-85. doi:10.1056/NEJMoa035140
- Blackwell, Sean C et al. “17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial.” American journal of perinatology vol. 37,2 (2020): 127-136. doi:10.1055/s-0039-3400227
